US20210380703A1 - Acvr2a-specific antibody and method of use thereof - Google Patents

Acvr2a-specific antibody and method of use thereof Download PDF

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US20210380703A1
US20210380703A1 US17/394,228 US202117394228A US2021380703A1 US 20210380703 A1 US20210380703 A1 US 20210380703A1 US 202117394228 A US202117394228 A US 202117394228A US 2021380703 A1 US2021380703 A1 US 2021380703A1
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sequence
antibody
region
variable domain
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Todd M. Kinsella
Ramesh Bhatt
Kristen BALTGALVIS
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Rigel Pharmaceuticals Inc
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Rigel Pharmaceuticals Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/06—Anabolic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/543—Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Definitions

  • ACVR2A The activin receptor, type II A
  • ACVR2A is a high affinity receptor for the activin proteins as well as other members of the TGF-beta superfamily.
  • ACVR2A is generally thought to transduce signals that lead to the phosphorylation of one or more SMAD transcription factors, particularly SMADs 1, 2, 3 and 5.
  • SMADs 1, 2, 3 and 5 SMADs 1, 2, 3 and 5.
  • ACVR2A has been implicated in the regulation of a wide range of biological processes, including bone formation, muscle formation, red blood cell formation, tumor growth, immune function and the production of reproductive hormones.
  • an antibody may comprise: (a) a variable domain comprising: i. heavy chain CDR1, CDR2 and CDR3 regions that are identical the heavy chain CDR1, CDR2 and CDR3 regions of an antibody selected from any of Tables 2A-2F; and ii.
  • an antibody may comprise: (a) a heavy chain variable domain comprising a heavy chain framework, a CDR1 region, a CDR2 region, and a CDR3 region of sequence ARSATWHDTXLD (SEQ ID NO:6538) or a variant of ARSATWHDTXLD (SEQ ID NO:6538) that comprises up to three amino acid substitutions, and (b) a light chain variable domain comprising a light chain framework, a CDR1 region, a CDR2 region, and a CDR3 region.
  • antibodies and immunoglobulin include antibodies or immunoglobulins of any isotype, fragments of antibodies which retain specific binding to antigen, including, but not limited to, Fab, Fv, scFv, and Fd fragments, chimeric antibodies, humanized antibodies, single-chain antibodies, and fusion proteins comprising an antigen-binding portion of an antibody and a non-antibody protein.
  • the antibodies may be detectably labeled, e.g., with a radioisotope, an enzyme which generates a detectable product, a fluorescent protein, and the like.
  • the antibodies may be further conjugated to other moieties, such as members of specific binding pairs, e.g., biotin (member of biotin-avidin specific binding pair), and the like.
  • the antibodies may also be bound to a solid support, including, but not limited to, polystyrene plates or beads, and the like.
  • Fab′, Fv, F(ab′) 2 are also encompassed by the term.
  • An antibody may be monovalent or bivalent.
  • Antibody fragments comprise a portion of an intact antibody, for example, the antigen binding or variable region of the intact antibody.
  • antibody fragments include Fab, Fab′, F(ab′) 2 , and Fv fragments; diabodies; linear antibodies (Zapata et al., Protein Eng. 8(10): 1057-1062 (1995)); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.
  • Papain digestion of antibodies produces two identical antigen-binding fragments, called “Fab” fragments, each with a single antigen-binding site, and a residual “Fc” fragment, a designation reflecting the ability to crystallize readily.
  • Pepsin treatment yields an F(ab′) 2 fragment that has two antigen combining sites and is still capable of cross-linking antigen.
  • “Fv” is the minimum antibody fragment which contains a complete antigen-recognition and -binding site. This region consists of a dimer of one heavy- and one light-chain variable domain in tight, non-covalent association. It is in this configuration that the three CDRS of each variable domain interact to define an antigen-binding site on the surface of the V H -V L dimer. Collectively, the six CDRs confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.
  • the “Fab” fragment also contains the constant domain of the light chain and the first constant domain (CH 1 ) of the heavy chain.
  • Fab fragments differ from Fab′ fragments by the addition of a few residues at the carboxyl terminus of the heavy chain CH 1 domain including one or more cysteines from the antibody hinge region.
  • Fab′-SH is the designation herein for Fab′ in which the cysteine residue(s) of the constant domains bear a free thiol group.
  • F(ab′) 2 antibody fragments originally were produced as pairs of Fab′ fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.
  • immunoglobulins The “light chains” of antibodies (immunoglobulins) from any vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda, based on the amino acid sequences of their constant domains. Depending on the amino acid sequence of the constant domain of their heavy chains, immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA, and IgA2.
  • immunoglobulins There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG
  • Single-chain Fv or “sFv” antibody fragments comprise the V H and V L domains of antibody, wherein these domains are present in a single polypeptide chain.
  • the Fv polypeptide further comprises a polypeptide linker between the V H and V L domains, which enables the sFv to form the desired structure for antigen binding.
  • diabodies refers to small antibody fragments with two antigen-binding sites, which fragments comprise a heavy-chain variable domain (V H ) connected to a light-chain variable domain (V L ) in the same polypeptide chain (V H —V L ).
  • V H heavy-chain variable domain
  • V L light-chain variable domain
  • the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites.
  • Diabodies are described more fully in, for example, EP 404,097; WO 93/11161; and Hollinger et al., Proc. Natl. Acad. Sci . USA, 90:6444-6448 (1993).
  • affinity refers to the equilibrium constant for the reversible binding of two agents and is expressed as a dissociation constant (Kd).
  • Kd dissociation constant
  • Affinity can be at least 1-fold greater, at least 2-fold greater, at least 3-fold greater, at least 4-fold greater, at least 5-fold greater, at least 6-fold greater, at least 7-fold greater, at least 8-fold greater, at least 9-fold greater, at least 10-fold greater, at least 20-fold greater, at least 30-fold greater, at least 40-fold greater, at least 50-fold greater, at least 60-fold greater, at least 70-fold greater, at least 80-fold greater, at least 90-fold greater, at least 100-fold greater, or at least 1000-fold greater, or more, than the affinity of an antibody for unrelated amino acid sequences.
  • Affinity of an antibody to a target protein can be, for example, from about 100 nanomolar (nM) to about 0.1 nM, from about 100 nM to about 1 picomolar (pM), or from about 100 nM to about 1 femtomolar (fM) or more.
  • nM nanomolar
  • pM picomolar
  • fM femtomolar
  • the term “avidity” refers to the resistance of a complex of two or more agents to dissociation after dilution.
  • the terms “immunoreactive” and “preferentially binds” are used interchangeably herein with respect to antibodies and/or antigen-binding fragments.
  • binding refers to a direct association between two molecules, due to, for example, covalent, electrostatic, hydrophobic, and ionic and/or hydrogen-bond interactions, including interactions such as salt bridges and water bridges.
  • An ACVR2A-specific antibody antibodies binds specifically to an epitope within a ACVR2A polypeptide. Non-specific binding would refer to binding with an affinity of less than about 10 ⁇ 7 M, e.g., binding with an affinity of 10 ⁇ 6 M, 10 ⁇ 5 M, 10 ⁇ 4 M, etc.
  • CDR complementarity determining region
  • CDRs have been described by Kabat et al., J. Biol. Chem. 252:6609-6616 (1977); Kabat et al., U.S. Dept. of Health and Human Services, “Sequences of proteins of immunological interest” (1991); by Chothia et al., J. Mol. Biol. 196:901-917 (1987); and MacCallum et al., J. Mol. Biol.
  • variable region when used in reference to an antibody variable region is intended to mean all amino acid residues outside the CDR regions within the variable region of an antibody.
  • a variable region framework is generally a discontinuous amino acid sequence between about 100-120 amino acids in length but is intended to reference only those amino acids outside of the CDRs.
  • framework region is intended to mean each domain of the framework that is separated by the CDRs.
  • an “isolated” antibody is one that has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would interfere with diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes.
  • the antibody will be purified (1) to greater than 90%, greater than 95%, or greater than 98%, by weight of antibody as determined by the Lowry method, for example, more than 99% by weight, (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing or nonreducing conditions using Coomassie blue or silver stain.
  • Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present. In some instances, isolated antibody will be prepared by at least one purification step.
  • treatment refers to obtaining a desired pharmacologic and/or physiologic effect.
  • the effect may be prophylactic in terms of completely or partially preventing a disease or symptom thereof and/or may be therapeutic in terms of a partial or complete cure for a disease and/or adverse effect attributable to the disease.
  • Treatment covers any treatment of a disease in a mammal, particularly in a human, and includes: (a) preventing the disease from occurring in a subject which may be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting the disease, i.e., arresting its development; and (c) relieving the disease, i.e., causing regression of the disease.
  • the terms “individual,” “subject,” “host,” and “patient,” used interchangeably herein, refer to a mammal, including, but not limited to, murines (rats, mice), non-human primates, humans, canines, felines, ungulates (e.g., equines, bovines, ovines, porcines, caprines), etc.
  • a “therapeutically effective amount” or “efficacious amount” refers to the amount of an ACVR2A-specific antibody that, when administered to a mammal or other subject for treating a disease, is sufficient to effect such treatment for the disease.
  • the “therapeutically effective amount” will vary depending on the ACVR2A-specific antibody, the disease and its severity and the age, weight, etc., of the subject to be treated.
  • a “biological sample” encompasses a variety of sample types obtained from an individual and can be used in a diagnostic or monitoring assay.
  • the definition encompasses blood and other liquid samples of biological origin, solid tissue samples such as a biopsy specimen or tissue cultures or cells derived therefrom and the progeny thereof.
  • the definition also includes samples that have been manipulated in any way after their procurement, such as by treatment with reagents, solubilization, or enrichment for certain components, such as polynucleotides.
  • the term “biological sample” encompasses a clinical sample, and also includes cells in culture, cell supernatants, cell lysates, serum, plasma, biological fluid, and tissue samples.
  • the present disclosure may make use of consensus sequences. If an amino acid sequence is indicated as being “of sequence Y”, where Y is a consensus sequence, the amino acid sequence falls within the consensus sequence. In a consensus sequence, the amino acid “X” can be any amino acid.
  • the present disclosure provides antibodies that specifically bind to and block signaling by ACVR2A, i.e., ACVR2A but not ACVR2B.
  • the antibody may comprise (a) a variable domain comprising: i. heavy chain CDR1, CDR2 and CDR3 regions that are identical the heavy chain CDR1, CDR2 and CDR3 regions of an antibody selected from any of Tables 2A-2F; and ii.
  • the antibody may comprise: a heavy chain variable domain comprising: a heavy chain framework, a CDR1 region, a CDR2 region, and a CDR3 region of sequence AxxAxWHDTxLD; and a light chain variable domain comprising: a light chain framework, a CDR1 region, a CDR2 region, and a CDR3 region.
  • the heavy chain variable domain of the antibody may comprise a CDR3 region of sequence ARSATWHDTxLD (SEQ ID NO: 6538) (e.g., ARAANWHDTA/HLD (SEQ ID NO: 6539)), ARAATWHDTxLD (SEQ ID NO: 6540) (e.g., ARAATWHDTH/ALD (SEQ ID NO: 6541)), ARGANWHDTxLD (SEQ ID NO: 6542) (e.g., ARGANWHDTA/HLD (SEQ ID NO: 6543)), ARGATWHDTxLD (SEQ ID NO: 6544) (e.g., ARGATWHDTH/ALD (SEQ ID NO: 6545)), ARSANWHDTxLD (SEQ ID NO: 6546) (e.g., AR/KSANWHDTA/HLD (SEQ ID NO: 6547)) or ARSATWHDTxLD (SEQ ID NO: 6548) (e.g., ARSATWHDTxLD (SEQ ID
  • the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of D/SS/DYG/SMH/N (SEQ ID NO: 6550), ii. a CDR2 region that has a sequence of WVA/SS/G/NINYNG/SGYT/KS/G (SEQ ID NO: 6551), and iii. a CDR3 region that has a sequence of ARAANWHDTA/HLD (SEQ ID NO: 6552); and a light chain variable domain comprising: i.
  • a CDR1 region that has a sequence of XXYL/VNWY (SEQ ID NO: 6553) (e.g., L/V/I/SS/T/RYL/VNWY (SEQ ID NO: 6554)), ii. a CDR2 region that has a sequence of LV/LIYXXXS/NR/LX (SEQ ID NO: 6555)(e.g., LV/LIYA/Y/VA/V/TT/S/NS/NR/LA/H/Q/P (SEQ ID NO: 6556)), and iii.
  • a CDR3 region that has a sequence of QQ/HSY/DXXPL (SEQ ID NO: 6557) (e.g., QQ/HSY/DD/E/S/NL/N/S/TPL (SEQ ID NO: 6558)).
  • the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of D/SS/DYG/SMH/N (SEQ ID NO: 6550), ii. a CDR2 region that has a sequence of WVA/SS/G/NINYNG/SGYT/KS/G (SEQ ID NO: 6551), and iii. a CDR3 region that has a sequence of ARAATWHDTH/ALD (SEQ ID NO: 6559); and a light chain variable domain comprising: i.
  • a CDR1 region that has a sequence of XS/TYL/VNWY (SEQ ID NO: 6560) (e.g., L/V/I/SS/TYL/VNWY (SEQ ID NO: 6561)), ii. a CDR2 region that has a sequence of LL/VIYA/YXXS/NR/LX (SEQ ID NO: 6562)(e.g., LL/VIYA/YA/T/VT/S/NS/NR/LA/P/Q (SEQ ID NO: 6563)), and iii.
  • a CDR3 region that has a sequence of QQSY/D/NXXPL (SEQ ID NO: 6564) (e.g., QQSY/D/ND/E/S/NL/S/T/NPL (SEQ ID NO: 6565)).
  • the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of S/DS/DYS/GMN/H (SEQ ID NO: 6566), ii. a CDR2 region that has a sequence of WVS/AG/S/NINYNG/SGYT/KS/G (SEQ ID NO: 6567), and iii. a CDR3 region that has a sequence of ARGANWHDTA/HLD (SEQ ID NO: 6543); and a light chain variable domain comprising: i.
  • a CDR1 region that has a sequence of XS/TYL/VNWY (SEQ ID NO: 6568) (e.g., L/V/S/IS/TYL/VNWY (SEQ ID NO: 6569)), ii. a CDR2 region that has a sequence of LL/VIYAXT/SSR/LX (SEQ ID NO: 6570) (e.g., LL/VIYAA/V/TT/SSR/LA/H/Q (SEQ ID NO: 6571)), and iii.
  • a CDR3 region that has a sequence of QQSY/DXXPL (SEQ ID NO: 6572) (e.g., QQSY/DD/E/S/NS/T/N/LPL (SEQ ID NO: 6573)).
  • the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of S/DS/DYS/GMN/H (SEQ ID NO: 6574), ii. a CDR2 region that has a sequence of WVA/SG/N/SINYNG/SGYT/KS/G (SEQ ID NO: 6575), and iii. a CDR3 region that has a sequence of ARGATWHDTH/ALD (SEQ ID NO: 6544); and a light chain variable domain comprising: i.
  • a CDR1 region that has a sequence of XS/TYL/VNWY (SEQ ID NO: 6568) (e.g., L/I/V/SS/TYL/VNWY (SEQ ID NO: 6576)), ii. a CDR2 region that has a sequence of LL/VIYAXT/SSR/LX (SEQ ID NO: 6570) (e.g., LL/VIYAA/V/TT/SSR/LA/H/Q (SEQ ID NO: 6571)), and iii.
  • a CDR3 region that has a sequence of QQSY/DXXPL (SEQ ID NO: 6572) (e.g., QQSY/DD/E/S/NT/S/N/LPL (SEQ ID NO: 6577)).
  • the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of S/DS/DYG/SMN/H (SEQ ID NO: 6578), ii. a CDR2 region that has a sequence of WVS/AG/N/SINYNG/SGYT/KS/G (SEQ ID NO: 6579), and iii. a CDR3 region that has a sequence of AR/KSANWHDTA/HLD (SEQ ID NO: 6580); and a light chain variable domain comprising: i.
  • a CDR1 region that has a sequence of XS/TYL/VNWY (SEQ ID NO: 6568) (e.g., L/V/I/SS/TYL/VNWY (SEQ ID NO: 6561)), ii. a CDR2 region that has a sequence of LL/VIYA/YXT/SS/NR/LX (SEQ ID NO: 6581) (e.g., LL/VIYA/YA/V/TT/SS/NR/LA/H/Q (SEQ ID NO: 6582)), and iii.
  • a CDR3 region that has a sequence of QQSY/DXXPL (SEQ ID NO: 6572) (e.g., QQSY/DD/E/N/S S/T/L/NPL (SEQ ID NO: 6583)).
  • the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of D/SS/DYS/GMN/H (SEQ ID NO: 6584), ii. a CDR2 region that has a sequence of WVA/SG/N/SINYNG/SGYT/KS/G (SEQ ID NO: 6585), and iii. a CDR3 region that has a sequence of ARSATWHDTH/ALD (SEQ ID NO: 6586); and a light chain variable domain comprising: i.
  • a CDR1 region that has a sequence of XXYL/VNWY (SEQ ID NO: 6587) (e.g., L/V/I/SS/T/RYL/VNWY (SEQ ID NO: 6588)), ii. a CDR2 region that has a sequence of LL/VIYA/YXT/SS/NR/LX (SEQ ID NO: 6589) (e.g., LL/VIYA/YA/V/TT/SS/NR/LA/H/Q (SEQ ID NO: 6590)), and iii.
  • a CDR3 region that has a sequence of QQSY/DXXPL (SEQ ID NO: 6572) (e.g., QQSY/DD/E/S/NL/N/T/SPL (SEQ ID NO: 6591)).
  • the antibody may comprise: a heavy chain variable domain comprising an amino acid sequence that is at least 80% identical to (e.g., at least 90%, at least 95%, at least 98%, at least 99%, or 100% identical to) the amino acid sequence of the heavy chain variable domain of an antibody selected from any of Tables 2A-2F; and a light chain variable domain comprising an amino acid sequence that is at least 80% identical to (e.g., at least 90%, at least 95%, at least 98%, at least 99%, or 100% identical to) the light chain variable domain of the antibody selected from any of Tables 2A-2F.
  • Tables 2A-2F provides the amino acid sequences of the heavy and light variable domains of some examples of the present antibody.
  • Table 3A provides the amino acid sequences of the CDRs of the antibodies shown in Table 2A.
  • HCDR1 (SEQ ID NO: 6550) D/SS/DYG/SMH/N HCDR2: (SEQ ID NO: 6551) WVA/SS/G/NINYNG/SGYT/KS/G HCDR3: (SEQ ID NO: 6552) ARAANWHDTA/HLD LCDR1: (SEQ ID NO: 6554) L/V/I/SS/T/RYL/VNWY LCDR2: (SEQ ID NO: 6592) LV/LIYA/Y/VA/V/TT/S/NS/NR/LA/H/Q/P LCDR3 (SEQ ID NO: 6593) QQ/HSY/DD/E/S/NL/N/S/TPL
  • Table 3B provides the amino acid sequences of the CDRs of the antibodies shown in Table 2B.
  • HCDR1 (SEQ ID NO: 6550) D/SS/DYG/SMH/N HCDR2: (SEQ ID NO: 6551) WVA/SS/G/NINYNG/SGYT/KS/G HCDR3: (SEQ ID NO: 6559) ARAATWHDTH/ALD LCDR1: (SEQ ID NO: 6561) L/V/I/SS/TYL/VNWY LCDR2: (SEQ ID NO: 6563) LL/VIYA/YA/T/VT/S/NS/NR/LA/P/Q LCDR3: (SEQ ID NO: 6565) QQSY/D/ND/E/S/NL/S/T/NPL
  • Table 3C provides the amino acid sequences of the CDRs of the antibodies shown in Table 2C.
  • HCDR1 (SEQ ID NO: 6566) S/DS/DYS/GMN/H HCDR2: (SEQ ID NO: 6594) WVS/AG/S/NINYNG/SGYT/KS/G HCDR3: (SEQ ID NO: 6543) ARGANWHDTA/HLD LCDR1: (SEQ ID NO: 6569) L/V/S/IS/TYL/VNWY LCDR2: (SEQ ID NO:) LL/VIYAA/V/TT/SSR/LA/H/Q LCDR3: (SEQ ID NO: 6571) QQSY/DD/E/S/NS/T/N/LPL
  • Table 3D provides the amino acid sequences of the CDRs of the antibodies shown in Table 2D.
  • HCDR1 (SEQ ID NO: 6574) S/DS/DYS/GMN/H HCDR2: (SEQ ID NO: 6575) WVA/SG/N/SINYNG/SGYT/KS/G HCDR3: (SEQ ID NO: 6595) ARGATWHDTH/ALD LCDR1: (SEQ ID NO: 6596) L/I/V/SS/TYL/VNWY LCDR2: (SEQ ID NO: 6571) LL/VIYAA/V/TT/SSR/LA/H/Q LCDR3: (SEQ ID NO: 6577) QQSY/DD/E/S/NT/S/N/LPL
  • Table 3E provides the amino acid sequences of the CDRs of the antibodies shown in Table 2E.
  • HCDR1 (SEQ ID NO: 6578) S/DS/DYG/SMN/H HCDR2: (SEQ ID NO: 6579) WVS/AG/N/SINYNG/SGYT/KS/G HCDR3: (SEQ ID NO: 6597) AR/KSANWHDTA/HLD LCDR1: (SEQ ID NO: 6561) L/V/I/SS/TYLNNWY LCDR2: (SEQ ID NO: 6582) LL/VIYA/YA/V/TT/SS/NR/LA/H/Q LCDR3: (SEQ ID NO: 6598) QQSY/DD/E/N/SS/T/L/NPL
  • Table 3F provides the amino acid sequences of the CDRs of the antibodies shown in Table 2F.
  • HCDR1 (SEQ ID NO: 6584) D/SS/DYS/GMN/H HCDR2: (SEQ ID NO: 6585) WVA/SG/N/SINYNG/SGYT/KS/G HCDR3: (SEQ ID NO: 6586) ARSATWHDTH/ALD LCDR1: (SEQ ID NO: 6588) L/V/I/SS/T/RYL/VNWY LCDR2: (SEQ ID NO: 6590) LL/VIYA/YA/V/TT/SS/NR/LA/H/Q LCDR3: (SEQ ID NO: 6591) QQSY/DD/E/S/NL/N/T/SPL
  • the present antibody may exhibit high affinity binding to ACVR2A.
  • the antibody may binds to ACVR2 with an affinity of at least about 10 ⁇ 7 M, at least about 10 ⁇ 8 M, at least about 10 ⁇ 9 M, at least about 10 ⁇ 10 M, at least about 10 ⁇ 11 M, or at least about 10 ⁇ 12 M, or greater than 10 ⁇ 12 M.
  • the present antibody binds to ACVR2A with a substantially lower affinity, e.g., at least 10 fold, 50 fold, 100 fold, 500 fold, 1000 fold, 5000 fold, 10,000 fold, 50,000 fold 100,000, or 500,000 fold lower affinity.
  • the present antibody may reduce binding of ACVR2A to GDF8 and/or other activins.
  • the antibody may reduce binding of ACVR2A to GDF8 and/or other activins by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more, compared to the degree of binding between ACVR2A and GDF8 and/or other activins in the absence of the antibody.
  • an antibody comprises one or more (e.g., one or two) heavy chain variable regions (VH) and/or one or more (e.g., one or two) light chain variable regions (VL), or subfragments thereof capable of binding an epitope.
  • VH and VL regions can be further subdivided into regions of hypervariability, termed “complementarity determining regions (CDR)”, interspersed with regions that are more conserved, termed “framework regions (FR)”.
  • CDR complementarity determining regions
  • FR framework regions
  • a VH can comprise three CDRs and four FRs arranged from N-terminus to C-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
  • a VL can comprise three CDRs and four FRs arranged from N-terminus to C-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
  • the VH or VL chain of an antibody can further include all or part of a heavy or light chain constant region, to thereby form a heavy or light immunoglobulin chain, respectively.
  • the antibody is a tetramer of two heavy and two light chains, wherein the heavy and light chains are interconnected by, for example, disulphide bonds.
  • the heavy chain constant region is comprised of three domains, CH1, CH2 and CH3.
  • the light chain constant region is comprised of one domain, CL.
  • the variable regions of the heavy and light chains comprise binding regions that interact with antigen.
  • the constant regions of the antibodies typically mediate the binding of the antibody to host tissues and factors, including various cells of the immune system and the first component of the complement system.
  • the term “antibody” includes intact immunoglobulins of types IgA, IgG, IgE, IgD, IgM and subtypes thereof.
  • a subject antibody is an IgG isotype.
  • immunoglobulin refers to a protein consisting of one or more polypeptides substantially encoded by immunoglobulin genes.
  • the recognized human immunoglobulin genes include the kappa, lambda, alpha (IgA1 and IgA2), gamma (IgG1, IgG2, IgG3, IgG4), delta, epsilon and mu constant region genes; and numerous immunoglobulin variable region genes.
  • Full-length immunoglobulin light chains (about 25 kD or 214 amino acids) are encoded by a variable region gene at the N-terminus (about 110 amino acids) and a kappa or lambda constant region at the C-terminus.
  • Full-length immunoglobulin heavy chains (about 50 kD or 446 amino acids) are encoded by a variable region gene at the N-terminus (about 116 amino acids) and one of the other aforementioned constant region genes at the C-terminus, e.g. gamma (encoding about 330 amino acids).
  • a subject antibody comprises full-length immunoglobulin heavy chain and a full-length immunoglobulin light chain.
  • a subject antibody does not comprise a full-length immunoglobulin heavy chain and a full-length immunoglobulin light chain, and instead comprises antigen-binding fragments of a full-length immunoglobulin heavy chain and a full-length immunoglobulin light chain.
  • the antigen-binding fragments are contained on separate polypeptide chains; in other embodiments, the antigen-binding fragments are contained within a single polypeptide chain.
  • the term “antigen-binding fragment” refers to one or more fragments of a full-length antibody that are capable of specifically binding to ACVR2A as described above.
  • binding fragments include (i) a Fab fragment (a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab′) 2 fragment (a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment (consisting of the VH and CH1 domains); (iv) a Fv fragment (consisting of the VH and VL domains of a single arm of an antibody); (v) a dAb fragment (consisting of the VH domain); (vi) an isolated CDR; (vii) a single chain Fv (scFv) (consisting of the VH and VL domains of a single arm of an antibody joined by a synthetic linker using recombinant means such that the VH and VL domains pair to form a monovalent molecule); (viii) diabodies (consisting of two scFvs in which the VH and VL
  • a subject antibody is a recombinant or modified antibody, e.g., a chimeric, humanized, deimmunized or an in vitro generated antibody.
  • the term “recombinant” or “modified” antibody as used herein is intended to include all antibodies that are prepared, expressed, created, or isolated by recombinant means, such as (i) antibodies expressed using a recombinant expression vector transfected into a host cell; (ii) antibodies isolated from a recombinant, combinatorial antibody library; (iii) antibodies isolated from an animal (e.g.
  • Such recombinant antibodies include humanized, CDR grafted, chimeric, deimmunized, and in vitro generated antibodies; and can optionally include constant regions derived from human germline immunoglobulin sequences.
  • a subject antibody comprises, in order from N-terminus to C-terminus: a light chain FR1 region; a CDR1; a light chain FR2 region; a CDR2; a light chain FR3 region; a CDR3; optionally a light chain FR4 region; a linker region; optionally a heavy chain FR1 region; a CDR1; a heavy chain FR2 region; a CDR2; a heavy chain FR3 region; a CDR3; and a heavy chain FR4 region.
  • each of the FR regions is a human FR region.
  • the linker region can be from about 5 amino acids to about 50 amino acids in length, e.g., from about 5 aa to about 10 aa, from about 10 aa to about 15 aa, from about 15 aa to about 20 aa, from about 20 aa to about 25 aa, from about 25 aa to about 30 aa, from about 30 aa to about 35 aa, from about 35 aa to about 40 aa, from about 40 aa to about 45 aa, or from about 45 aa to about 50 aa in length.
  • Linkers suitable for use a subject antibody include “flexible linkers”. If present, the linker molecules are generally of sufficient length to permit some flexible movement between linked regions. The linker molecules are generally about 6-50 atoms long. The linker molecules may also be, for example, aryl acetylene, ethylene glycol oligomers containing 2-10 monomer units, diamines, diacids, amino acids, or combinations thereof. Other linker molecules which can bind to polypeptides may be used in light of this disclosure.
  • Suitable linkers can be readily selected and can be of any of a suitable of different lengths, such as from 1 amino acid (e.g., Gly) to 20 amino acids, from 2 amino acids to 15 amino acids, from 3 amino acids to 12 amino acids, including 4 amino acids to 10 amino acids, 5 amino acids to 9 amino acids, 6 amino acids to 8 amino acids, or 7 amino acids to 8 amino acids, and may be 1, 2, 3, 4, 5, 6, or 7 amino acids.
  • Exemplary flexible linkers include glycine polymers (G) n , glycine-serine polymers (including, for example, (GS) n , GSGGS n (SEQ ID NO: 6599) and GGGS n (SEQ ID NO: 6600), where n is an integer of at least one), glycine-alanine polymers, alanine-serine polymers, and other flexible linkers known in the art. Glycine and glycine-serine polymers are of interest since both of these amino acids are relatively unstructured, and therefore may serve as a neutral tether between components.
  • Glycine polymers are of particular interest since glycine accesses significantly more phi-psi space than even alanine, and is much less restricted than residues with longer side chains (see Scheraga, Rev. Computational Chem. 11173-142 (1992)).
  • Exemplary flexible linkers include, but are not limited GGSG (SEQ ID NO:6601), GGSGG (SEQ ID NO:6602), GSGSG (SEQ ID NO: 6603), GSGGG (SEQ ID NO:6604), GGGSG (SEQ ID NO: 6605), GSSSG (SEQ ID NO: 6606), and the like.
  • the ordinarily skilled artisan will recognize that design of a peptide conjugated to any elements described above can include linkers that are all or partially flexible, such that the linker can include a flexible linker as well as one or more portions that confer less flexible structure.
  • a subject antibody is “humanized”
  • the term “humanized antibody” refers to an antibody comprising at least one chain comprising variable region framework residues substantially from a human antibody chain (referred to as the acceptor immunoglobulin or antibody) and at least one CDR substantially from a mouse antibody, (referred to as the donor immunoglobulin or antibody). See, Queen et al., Proc. Natl. Acad. Sci. USA 86:10029 10033 (1989), U.S. Pat. Nos. 5,530,101, 5,585,089, 5,693,761, WO 90/07861, and U.S. Pat. No. 5,225,539.
  • the constant region(s), if present, can also be substantially or entirely from a human immunoglobulin.
  • a subject antibody may comprise one or more CDRs and one or more FR regions from a human antibody.
  • Methods of making humanized antibodies are known in the art. See, e.g., U.S. Pat. No. 7,256,273.
  • the substitution of mouse CDRs into a human variable domain framework can result in retention of their correct spatial orientation where, e.g., the human variable domain framework adopts the same or similar conformation to the mouse variable framework from which the CDRs originated.
  • This can be achieved by obtaining the human variable domains from human antibodies whose framework sequences exhibit a high degree of sequence identity with the murine variable framework domains from which the CDRs were derived.
  • the heavy and light chain variable framework regions can be derived from the same or different human antibody sequences.
  • the human antibody sequences can be the sequences of naturally occurring human antibodies or can be consensus sequences of several human antibodies. See Kettleborough et al., Protein Engineering 4:773 (1991); Kolbinger et al., Protein Engineering 6:971 (1993).
  • the next step is to determine which, if any, residues from these components should be substituted to optimize the properties of the resulting humanized antibody.
  • substitution of human amino acid residues with murine should be minimized, because introduction of murine residues increases the risk of the antibody eliciting a human-anti-mouse-antibody (HAMA) response in humans.
  • HAMA human-anti-mouse-antibody
  • Art-recognized methods of determining immune response can be performed to monitor a HAMA response in a particular patient or during clinical trials. Patients administered humanized antibodies can be given an immunogenicity assessment at the beginning and throughout the administration of the therapy.
  • the HAMA response is measured, for example, by detecting antibodies to the humanized therapeutic reagent, in serum samples from the patient using a method known to one in the art, including surface plasmon resonance technology (BIACORE) and/or solid-phase ELISA analysis.
  • BIACORE surface plasmon resonance technology
  • a subject humanized antibody does not substantially elicit a HAMA response in a human subject.
  • Certain amino acids from the human variable region framework residues are selected for substitution based on their possible influence on CDR conformation and/or binding to antigen.
  • the unnatural juxtaposition of murine CDR regions with human variable framework region can result in unnatural conformational restraints, which, unless corrected by substitution of certain amino acid residues, lead to loss of binding affinity.
  • the selection of amino acid residues for substitution can be determined, in part, by computer modeling.
  • Computer hardware and software for producing three-dimensional images of immunoglobulin molecules are known in the art.
  • molecular models are produced starting from solved structures for immunoglobulin chains or domains thereof.
  • the chains to be modeled are compared for amino acid sequence similarity with chains or domains of solved three-dimensional structures, and the chains or domains showing the greatest sequence similarity is/are selected as starting points for construction of the molecular model.
  • Chains or domains sharing at least 50% sequence identity are selected for modeling, and preferably those sharing at least 60%, 70%, 80%, 90% sequence identity or more are selected for modeling.
  • the solved starting structures are modified to allow for differences between the actual amino acids in the immunoglobulin chains or domains being modeled, and those in the starting structure.
  • the modified structures are then assembled into a composite immunoglobulin.
  • the model is refined by energy minimization and by verifying that all atoms are within appropriate distances from one another and that bond lengths and angles are within chemically acceptable limits.
  • CDR and framework regions are as defined by Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md., 1987 and 1991).
  • An alternative structural definition has been proposed by Chothia et al., J. Mol. Biol. 196:901 (1987); Nature 342:878 (1989); and J. Mol. Biol. 186:651 (1989) (collectively referred to as “Chothia”).
  • Chothia When framework residues, as defined by Kabat, supra, constitute structural loop residues as defined by Chothia, supra, the amino acids present in the mouse antibody may be selected for substitution into the humanized antibody.
  • Residues which are “adjacent to a CDR region” include amino acid residues in positions immediately adjacent to one or more of the CDRs in the primary sequence of the humanized immunoglobulin chain, for example, in positions immediately adjacent to a CDR as defined by Kabat, or a CDR as defined by Chothia (See e.g., Chothia and Lesk JMB 196:901 (1987)). These amino acids are particularly likely to interact with the amino acids in the CDRs and, if chosen from the acceptor, to distort the donor CDRs and reduce affinity. Moreover, the adjacent amino acids may interact directly with the antigen (Amit et al., Science, 233:747 (1986)) and selecting these amino acids from the donor may be desirable to keep all the antigen contacts that provide affinity in the original antibody.
  • a subject antibody comprises scFv multimers.
  • a subject antibody is an scFv dimer (e.g., comprises two tandem scFv (scFv 2 )), an scFv trimer (e.g., comprises three tandem scFv (scFv 3 )), an scFv tetramer (e.g., comprises four tandem scFv (scFv 4 )), or is a multimer of more than four scFv (e.g., in tandem).
  • the scFv monomers can be linked in tandem via linkers of from about 2 amino acids to about 10 amino acids in length, e.g., 2 aa, 3 aa, 4 aa, 5 aa, 6 aa, 7 aa, 8 aa, 9 aa, or 10 aa in length.
  • Suitable linkers include, e.g., (Gly) x , where x is an integer from 2 to 10. Other suitable linkers are those discussed above.
  • each of the scFv monomers in a subject scFV multimer is humanized, as described above.
  • a subject antibody comprises a constant region of an immunoglobulin (e.g., an Fc region).
  • the Fc region if present, can be a human Fc region.
  • the antibody can contain both light chain and heavy chain constant regions.
  • Suitable heavy chain constant region include CH1, hinge, CH2, CH3, and CH4 regions.
  • the antibodies described herein include antibodies having all types of constant regions, including IgM, IgG, IgD, IgA and IgE, and any isotype, including IgG1, IgG2, IgG3 and IgG4.
  • An example of a suitable heavy chain Fc region is a human isotype IgG1 Fc.
  • Light chain constant regions can be lambda or kappa.
  • a subject antibody (e.g., a subject humanized antibody) can comprise sequences from more than one class or isotype.
  • Antibodies can be expressed as tetramers containing two light and two heavy chains, as separate heavy chains, light chains, as Fab, Fab′ F(ab′)2, and Fv, or as single chain antibodies in which heavy and light chain variable domains are linked through a spacer.
  • a subject antibody comprises a free thiol (—SH) group at the carboxyl terminus, where the free thiol group can be used to attach the antibody to a second polypeptide (e.g., another antibody, including a subject antibody), a scaffold, a carrier, etc.
  • a second polypeptide e.g., another antibody, including a subject antibody
  • a subject antibody comprises one or more non-naturally occurring amino acids.
  • the non-naturally encoded amino acid comprises a carbonyl group, an acetyl group, an aminooxy group, a hydrazine group, a hydrazide group, a semicarbazide group, an azide group, or an alkyne group. See, e.g., U.S. Pat. No. 7,632,924 for suitable non-naturally occurring amino acids. Inclusion of a non-naturally occurring amino acid can provide for linkage to a polymer, a second polypeptide, a scaffold, etc.
  • a subject antibody linked to a water-soluble polymer can be made by reacting a water-soluble polymer (e.g., PEG) that comprises a carbonyl group to an the subject antibody that comprises a non-naturally encoded amino acid that comprises an aminooxy, hydrazine, hydrazide or semicarbazide group.
  • a subject antibody linked to a water-soluble polymer can be made by reacting a subject antibody that comprises an alkyne-containing amino acid with a water-soluble polymer (e.g., PEG) that comprises an azide moiety; in some embodiments, the azide or alkyne group is linked to the PEG molecule through an amide linkage.
  • non-naturally encoded amino acid refers to an amino acid that is not one of the 20 common amino acids or pyrolysine or selenocysteine.
  • Other terms that may be used synonymously with the term “non-naturally encoded amino acid” are “non-natural amino acid,” “unnatural amino acid,” “non-naturally-occurring amino acid,” and variously hyphenated and non-hyphenated versions thereof.
  • the term “non-naturally encoded amino acid” also includes, but is not limited to, amino acids that occur by modification (e.g.
  • a naturally encoded amino acid including but not limited to, the 20 common amino acids or pyrolysine and selenocysteine
  • non-naturally-occurring amino acids include, but are not limited to, N-acetylglucosaminyl-L-serine, N-acetylglucosaminyl-L-threonine, and O-phosphotyrosine.
  • a subject antibody is linked (e.g., covalently linked) to a polymer (e.g., a polymer other than a polypeptide).
  • a polymer e.g., a polymer other than a polypeptide.
  • Suitable polymers include, e.g., biocompatible polymers, and water-soluble biocompatible polymers.
  • Suitable polymers include synthetic polymers and naturally-occurring polymers.
  • Suitable polymers include, e.g., substituted or unsubstituted straight or branched chain polyalkylene, polyalkenylene or polyoxyalkylene polymers or branched or unbranched polysaccharides, e.g. a homo- or hetero-polysaccharide.
  • Suitable polymers include, e.g., ethylene vinyl alcohol copolymer (commonly known by the generic name EVOH or by the trade name EVAL); polybutylmethacrylate; poly(hydroxyvalerate); poly(L-lactic acid); polycaprolactone; poly(lactide-co-glycolide); poly(hydroxybutyrate); poly(hydroxybutyrate-co-valerate); polydioxanone; polyorthoester; polyanhydride; poly(glycolic acid); poly(D,L-lactic acid); poly(glycolic acid-co-trimethylene carbonate); polyphosphoester; polyphosphoester urethane; poly(amino acids); cyanoacrylates; poly(trimethylene carbonate); poly(iminocarbonate); copoly(ether-esters) (e.g., poly(ethylene oxide)-poly(lactic acid) (PEO/PLA) co-polymers); polyalkylene oxalates; polyphosphazene
  • Suitable synthetic polymers include unsubstituted and substituted straight or branched chain poly(ethyleneglycol), poly(propyleneglycol) poly(vinylalcohol), and derivatives thereof, e.g., substituted poly(ethyleneglycol) such as methoxypoly(ethyleneglycol), and derivatives thereof.
  • Suitable naturally-occurring polymers include, e.g., albumin, amylose, dextran, glycogen, and derivatives thereof.
  • Suitable polymers can have an average molecular weight in a range of from 500 Da to 50000 Da, e.g., from 5000 Da to 40000 Da, or from 25000 to 40000 Da.
  • a subject antibody comprises a poly(ethylene glycol) (PEG) or methoxypoly(ethyleneglycol) polymer
  • the PEG or methoxypoly(ethyleneglycol) polymer can have a molecular weight in a range of from about 0.5 kiloDaltons (kDa) to 1 kDa, from about 1 kDa to 5 kDa, from 5 kDa to 10 kDa, from 10 kDa to 25 kDa, from 25 kDa to 40 kDa, or from 40 kDa to 60 kDa.
  • kDa kiloDaltons
  • a subject antibody is covalently linked to a PEG polymer.
  • a subject scFv multimer is covalently linked to a PEG polymer. See, e.g., Albrecht et al. (2006) J. Immunol. Methods 310:100. Methods and reagents suitable for PEGylation of a protein are well known in the art and may be found in, e.g., U.S. Pat. No. 5,849,860.
  • PEG suitable for conjugation to a protein is generally soluble in water at room temperature, and has the general formula R(O—CH 2 —CH 2 ) n O—R, where R is hydrogen or a protective group such as an alkyl or an alkanol group, and where n is an integer from 1 to 1000. Where R is a protective group, it generally has from 1 to 8 carbons.
  • the PEG conjugated to the subject antibody can be linear.
  • the PEG conjugated to the subject protein may also be branched. Branched PEG derivatives such as those described in U.S. Pat. No. 5,643,575, “star-PEG's” and multi-armed PEG's such as those described in Shearwater Polymers, Inc. catalog “Polyethylene Glycol Derivatives 1997-1998.” Star PEGs are described in the art including, e.g., in U.S. Pat. No. 6,046,305.
  • a subject antibody can be glycosylated, e.g., comprise a covalently linked carbohydrate or polysaccharide moiety.
  • Glycosylation of antibodies 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 tripeptide 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.
  • the presence of either of these tripeptide 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 may also be used.
  • glycosylation sites to an antibody is conveniently accomplished by altering the amino acid sequence such that it contains one or more of the above-described tripeptide sequences (for N-linked glycosylation sites).
  • the alteration may also be made by the addition of, or substitution by, one or more serine or threonine residues to the sequence of the original antibody (for O-linked glycosylation sites).
  • removal of glycosylation sites can be accomplished by amino acid alteration within the native glycosylation sites of an antibody.
  • a subject antibody will in some embodiments comprise a “radiopaque” label, e.g. a label that can be easily visualized using for example x-rays.
  • Radiopaque materials are well known to those of skill in the art. The most common radiopaque materials include iodide, bromide or barium salts. Other radiopaque materials are also known and include, but are not limited to organic bismuth derivatives (see, e.g., U.S. Pat. No. 5,939,045), radiopaque multiurethanes (see U.S. Pat. No. 5,346,981), organobismuth composites (see, e.g., U.S. Pat. No. 5,256,334), radiopaque barium multimer complexes (see, e.g., U.S. Pat. No. 4,866,132), and the like.
  • a subject antibody can be covalently linked to a second moiety (e.g., a lipid, a polypeptide other than a subject antibody, a synthetic polymer, a carbohydrate, and the like) using for example, glutaraldehyde, a homobifunctional cross-linker, or a heterobifunctional cross-linker.
  • Glutaraldehyde cross-links polypeptides via their amino moieties.
  • Homobifunctional cross-linkers e.g., a homobifunctional imidoester, a homobifunctional N-hydroxysuccinimidyl (NHS) ester, or a homobifunctional sulfhydryl reactive cross-linker
  • a homobifunctional imidoester e.g., a homobifunctional N-hydroxysuccinimidyl (NHS) ester, or a homobifunctional sulfhydryl reactive cross-linker
  • a homobifunctional imidoester e.g., a homobifunctional N-hydroxysuccinimidyl (NHS) ester, or a homobifunctional sulfhydryl reactive cross-linker
  • Homobifunctional NHS ester and imido esters cross-link amine containing polypeptides. In a mild alkaline pH, imido esters react only with primary amines to form imidoamides, and overall charge of the cross-linked
  • Homobifunctional sulfhydryl reactive cross-linkers includes bismaleimidhexane (BMH), 1,5-difluoro-2,4-dinitrobenzene (DFDNB), and 1,4-di-(3′,2′-pyridyldithio) propinoamido butane (DPDPB).
  • BMH bismaleimidhexane
  • DFDNB 1,5-difluoro-2,4-dinitrobenzene
  • DPDPB 1,4-di-(3′,2′-pyridyldithio) propinoamido butane
  • Heterobifunctional cross-linkers have two or more different reactive moieties (e.g., amine reactive moiety and a sulfhydryl-reactive moiety) and are cross-linked with one of the polypeptides via the amine or sulfhydryl reactive moiety, then reacted with the other polypeptide via the non-reacted moiety.
  • Multiple heterobifunctional haloacetyl cross-linkers are available, as are pyridyl disulfide cross-linkers.
  • Carbodiimides are a classic example of heterobifunctional cross-linking reagents for coupling carboxyls to amines, which results in an amide bond.
  • a subject antibody can be immobilized on a solid support.
  • Suitable supports are well known in the art and comprise, inter alia, commercially available column materials, polystyrene beads, latex beads, magnetic beads, colloid metal particles, glass and/or silicon chips and surfaces, nitrocellulose strips, nylon membranes, sheets, duracytes, wells of reaction trays (e.g., multi-well plates), plastic tubes, etc.
  • a solid support can comprise any of a variety of substances, including, e.g., glass, polystyrene, polyvinyl chloride, polypropylene, polyethylene, polycarbonate, dextran, nylon, amylose, natural and modified celluloses, polyacrylamides, agaroses, and magnetite.
  • Solid supports can be soluble or insoluble, e.g., in aqueous solution.
  • a suitable solid support is generally insoluble in an aqueous solution.
  • a subject antibody will in some embodiments comprise a detectable label.
  • Suitable detectable labels include any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. Suitable include, but are not limited to, magnetic beads (e.g.
  • DynabeadsTM fluorescent dyes (e.g., fluorescein isothiocyanate, texas red, rhodamine, a green fluorescent protein, a red fluorescent protein, a yellow fluorescent protein, and the like), radiolabels (e.g., 3 H, 125 I 35 S, 14 C, or 32 P), enzymes (e.g., horse radish peroxidase, alkaline phosphatase, luciferase, and others commonly used in an enzyme-linked immunosorbent assay (ELISA)), and colorimetric labels such as colloidal gold or colored glass or plastic (e.g. polystyrene, polypropylene, latex, etc.) beads.
  • fluorescent dyes e.g., fluorescein isothiocyanate, texas red, rhodamine, a green fluorescent protein, a red fluorescent protein, a yellow fluorescent protein, and the like
  • radiolabels e.g., 3 H, 125 I
  • a subject antibody comprises a contrast agent or a radioisotope, where the contrast agent or radioisotope is one that is suitable for use in imaging, e.g., imaging procedures carried out on humans.
  • labels include radioisotope such as 1231 I (iodine), 18 F (fluorine), 99 Tc (technetium), 111 In (indium), and 67 Ga (gallium), and contrast agent such as gadolinium (Gd), dysprosium, and iron.
  • Radioactive Gd isotopes ( 153 Gd) also are available and suitable for imaging procedures in non-human mammals.
  • a subject antibody can be labeled using standard techniques.
  • a subject antibody can be iodinated using chloramine T or 1,3,4,6-tetrachloro-3 ⁇ ,6 ⁇ -dephenylglycouril.
  • fluorination fluorine is added to a subject antibody during the synthesis by a fluoride ion displacement reaction. See, Muller-Gartner, H., TIB Tech., 16:122-130 (1998) and Saji, H., Crit. Rev. Ther. Drug Carrier Syst., 16(2):209-244 (1999) for a review of synthesis of proteins with such radioisotopes.
  • a subject antibody can also be labeled with a contrast agent through standard techniques.
  • a subject antibody can be labeled with Gd by conjugating low molecular Gd chelates such as Gd diethylene triamine pentaacetic acid (GdDTPA) or Gd tetraazacyclododecanetetraacetic (GdDOTA) to the antibody.
  • GdDTPA Gd diethylene triamine pentaacetic acid
  • GdDOTA Gd tetraazacyclododecanetetraacetic
  • a subject antibody can be labeled with Gd by, for example, conjugating polylysine-Gd chelates to the antibody. See, for example, Curtet et al., Invest. Radiol., 33(10):752-761 (1998).
  • a subject antibody can be labeled with Gd by incubating paramagnetic polymerized liposomes that include Gd chelator lipid with avidin and biotinylated antibody. See, for example, Sipkins et al., Nature Med., 4:623-626 (1998).
  • Suitable fluorescent proteins that can be linked to a subject antibody include, but are not limited to, a green fluorescent protein from Aequoria victoria or a mutant or derivative thereof e.g., as described in U.S. Pat. Nos. 6,066,476; 6,020,192; 5,985,577; 5,976,796; 5,968,750; 5,968,738; 5,958,713; 5,919,445; 5,874,304; e.g., Enhanced GFP, many such GFP which are available commercially, e.g., from Clontech, Inc.; a red fluorescent protein; a yellow fluorescent protein; any of a variety of fluorescent and colored proteins from Anthozoan species, as described in, e.g., Matz et al. (1999) Nature Biotechnol. 17:969-973; and the like.
  • a subject antibody will in some embodiments be linked to (e.g., covalently or non-covalently linked) a fusion partner, e.g., a ligand; an epitope tag; a peptide; a protein other than an antibody; and the like.
  • a fusion partner e.g., a ligand; an epitope tag; a peptide; a protein other than an antibody; and the like.
  • Suitable fusion partners include peptides and polypeptides that confer enhanced stability in vivo (e.g., enhanced serum half-life); provide ease of purification, e.g., (His) n , e.g., 6His, and the like; provide for secretion of the fusion protein from a cell; provide an epitope tag, e.g., GST, hemagglutinin (HA; e.g., CYPYDVPDYA; SEQ ID NO:6607), FLAG (e.g., DYKDDDDK; SEQ ID NO:6608), c-myc (e.g., CEQKLISEEDL; SEQ ID NO:6609), and the like; provide a detectable signal, e.g., an enzyme that generates a detectable product (e.g., ⁇ -galactosidase, luciferase), or a protein that is itself detectable, e.g., a green fluorescent protein,
  • the fusion may also include an affinity domain, including peptide sequences that can interact with a binding partner, e.g., such as one immobilized on a solid support, useful for identification or purification.
  • a binding partner e.g., such as one immobilized on a solid support
  • Consecutive single amino acids, such as histidine when fused to a protein, can be used for one-step purification of the fusion protein by high affinity binding to a resin column, such as nickel sepharose.
  • affinity domains include His5 (HHHHH) (SEQ ID NO:6610), HisX6 (HHHHHH) (SEQ ID NO:6611), C-myc (EQKLISEEDL) (SEQ ID NO:6612), Flag (DYKDDDDK) (SEQ ID NO:6608), StrepTag (WSHPQFEK) (SEQ ID NO:6613), hemagglutinin, e.g., HA Tag (YPYDVPDYA; SEQ ID NO:6614), glutathinone-S-transferase (GST), thioredoxin, cellulose binding domain, RYIRS (SEQ ID NO:6615), Phe-His-His-Thr (SEQ ID NO:6616), chitin binding domain, S-peptide, T7 peptide, SH2 domain, C-end RNA tag, WEAAAREACCRECCARA (SEQ ID NO:6617), metal binding domains, e.g., zinc binding domains or calcium binding domains such
  • a subject antibody will in some embodiments be fused to a polypeptide that binds to an endogenous blood brain barrier (BBB) receptor
  • BBB blood brain barrier
  • Linking a subject antibody to a polypeptide that binds to an endogenous BBB receptor facilitates crossing the BBB, e.g., in a subject treatment method (see below) involving administration of a subject antibody to an individual in need thereof.
  • Suitable polypeptides that bind to an endogenous BBB include antibodies, e.g., monoclonal antibodies, or antigen-binding fragments thereof, that specifically bind to an endogenous BBB receptor.
  • Suitable endogenous BBB receptors include, but are not limited to, an insulin receptor, a transferrin receptor, a leptin receptor, a lipoprotein receptor, and an insulin-like growth factor receptor. See, e.g., U.S. Patent Publication No. 2009/0156498.
  • a subject antibody comprises a polyamine modification.
  • Polyamine modification of a subject antibody enhances permeability of the modified antibody at the BBB.
  • a subject antibody can be modified with polyamines that are either naturally occurring or synthetic. See, for example, U.S. Pat. No. 5,670,477.
  • Useful naturally occurring polyamines include putrescine, spermidine, spermine, 1,3-deaminopropane, norspermidine, syn-homospermidine, thermine, thermospermine, caldopentamine, homocaldopentamine, and canavalmine. Putrescine, spermidine and spermine are particularly useful.
  • Synthetic polyamines are composed of the empirical formula C x H y N z , can be cyclic or acyclic, branched or unbranched, hydrocarbon chains of 3-12 carbon atoms that further include 1-6 NR or N(R) 2 moieties, wherein R is H, (C 1 -C 4 ) alkyl, phenyl, or benzyl.
  • Polyamines can be linked to an antibody using any standard crosslinking method.
  • a subject antibody is modified to include a carbohydrate moiety, where the carbohydrate moiety can be covalently linked to the antibody.
  • a subject antibody is modified to include a lipid moiety, where the lipid moiety can be covalently linked to the antibody.
  • Suitable lipid moieties include, e.g., an N-fatty acyl group such as N-lauroyl, N-oleoyl, etc.; a fatty amine such as dodecyl amine, oleoyl amine, etc.; a C3-C16 long-chain aliphatic lipid; and the like. See, e.g., U.S. Pat. No. 6,638,513).
  • a subject antibody is incorporated into a liposome.
  • the present antibody can be produced by any known method, e.g., conventional synthetic methods for protein synthesis; recombinant DNA methods; etc.
  • a subject antibody is a single chain polypeptide
  • it can synthesized using standard chemical peptide synthesis techniques.
  • the synthesis may proceed via liquid-phase or solid-phase.
  • Solid phase polypeptide synthesis SPPS
  • Fmoc and Boc Various forms of SPPS, such as Fmoc and Boc, are available for synthesizing a subject antibody.
  • Techniques for solid phase synthesis are described by Barany and Merrifield, Solid-Phase Peptide Synthesis; pp. 3-284 in The Peptides: Analysis, Synthesis, Biology.
  • Standard recombinant methods can be used for production of a subject antibody.
  • nucleic acids encoding light and heavy chain variable regions, optionally linked to constant regions are inserted into expression vectors.
  • the light and heavy chains can be cloned in the same or different expression vectors.
  • the DNA segments encoding immunoglobulin chains are operably linked to control sequences in the expression vector(s) that ensure the expression of immunoglobulin polypeptides.
  • Expression control sequences include, but are not limited to, promoters (e.g., naturally-associated or heterologous promoters), signal sequences, enhancer elements, and transcription termination sequences.
  • the expression control sequences can be eukaryotic promoter systems in vectors capable of transforming or transfecting eukaryotic host cells (e.g., COS or CHO cells). Once the vector has been incorporated into the appropriate host, the host is maintained under conditions suitable for high level expression of the nucleotide sequences, and the collection and purification of the antibodies.
  • eukaryotic host cells e.g., COS or CHO cells.
  • nucleic acid sequences can encode each immunoglobulin amino acid sequence.
  • the desired nucleic acid sequences can be produced by de novo solid-phase DNA synthesis or by polymerase chain reaction (PCR) mutagenesis of an earlier prepared variant of the desired polynucleotide.
  • Oligonucleotide-mediated mutagenesis is an example of a suitable method for preparing substitution, deletion and insertion variants of target polypeptide DNA. See Adelman et al., DNA 2:183 (1983). Briefly, the target polypeptide DNA is altered by hybridizing an oligonucleotide encoding the desired mutation to a single-stranded DNA template. After hybridization, a DNA polymerase is used to synthesize an entire second complementary strand of the template that incorporates the oligonucleotide primer, and encodes the selected alteration in the target polypeptide DNA.
  • Suitable expression vectors are typically replicable in the host organisms either as episomes or as an integral part of the host chromosomal DNA. Commonly, expression vectors contain selection markers (e.g., ampicillin-resistance, hygromycin-resistance, tetracycline resistance, kanamycin resistance or neomycin resistance) to permit detection of those cells transformed with the desired DNA sequences.
  • selection markers e.g., ampicillin-resistance, hygromycin-resistance, tetracycline resistance, kanamycin resistance or neomycin resistance
  • Escherichia coli is an example of a prokaryotic host cell that can be used for cloning a subject antibody-encoding polynucleotide.
  • Other microbial hosts suitable for use include bacilli, such as Bacillus subtilis , and other enterobacteriaceae, such as Salmonella, Serratia , and various Pseudomonas species.
  • bacilli such as Bacillus subtilis
  • enterobacteriaceae such as Salmonella, Serratia
  • various Pseudomonas species include Salmonella, Serratia , and various Pseudomonas species.
  • expression vectors which will typically contain expression control sequences compatible with the host cell (e.g., an origin of replication).
  • any number of a variety of well-known promoters will be present, such as the lactose promoter system, a tryptophan (trp) promoter system, a beta-lactamase promoter system, or a promoter system from phage lambda.
  • the promoters will typically control expression, optionally with an operator sequence, and have ribosome binding site sequences and the like, for initiating and completing transcription and translation.
  • yeast Other microbes, such as yeast, are also useful for expression.
  • Saccharomyces e.g., S. cerevisiae
  • Pichia are examples of suitable yeast host cells, with suitable vectors having expression control sequences (e.g., promoters), an origin of replication, termination sequences and the like as desired.
  • Typical promoters include 3-phosphoglycerate kinase and other glycolytic enzymes.
  • Inducible yeast promoters include, among others, promoters from alcohol dehydrogenase, isocytochrome C, and enzymes responsible for maltose and galactose utilization.
  • mammalian cells e.g., mammalian cells grown in in vitro cell culture
  • the polypeptides of the present invention e.g., polynucleotides encoding immunoglobulins or fragments thereof. See Winnacker, From Genes to Clones, VCH Publishers, N.Y., N.Y. (1987).
  • Suitable mammalian host cells include CHO cell lines, various Cos cell lines, HeLa cells, myeloma cell lines, and transformed B-cells or hybridomas.
  • Expression vectors for these cells can include expression control sequences, such as an origin of replication, a promoter, and an enhancer (Queen et al., Immunol. Rev. 89:49 (1986)), and necessary processing information sites, such as ribosome binding sites, RNA splice sites, polyadenylation sites, and transcriptional terminator sequences.
  • suitable expression control sequences are promoters derived from immunoglobulin genes, SV40, adenovirus, bovine papilloma virus, cytomegalovirus and the like. See Co et al., J. Immunol. 148:1149 (1992).
  • the whole antibodies, their dimers, individual light and heavy chains, or other forms of a subject antibody can be purified according to standard procedures of the art, including ammonium sulfate precipitation, affinity columns, column chromatography, high performance liquid chromatography (HPLC) purification, gel electrophoresis, and the like (see generally Scopes, Protein Purification (Springer-Verlag, N.Y., (1982)).
  • a subject antibody can be substantially pure, e.g., at least about 80% to 85% pure, at least about 85% to 90% pure, at least about 90% to 95% pure, or 98% to 99%, or more, pure, e.g., free from contaminants such as cell debris, macromolecules other than a subject antibody, etc.
  • a subject antibody composition can comprise, in addition to a subject antibody, one or more of: a salt, e.g., NaCl, MgCl 2 , KCl, MgSO 4 , etc.; a buffering agent, e.g., a Tris buffer, N-(2-Hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid) (HEPES), 2-(N-Morpholino)ethanesulfonic acid (MES), 2-(N-Morpholino)ethanesulfonic acid sodium salt (MES), 3-(N-Morpholino)propanesulfonic acid (MOPS), N-tris[Hydroxymethyl]methyl-3-aminopropanesulfonic acid (TAPS), etc.; a solubilizing agent; a detergent, e.g., a non-ionic detergent such as Tween-20,
  • nucleic acids comprising nucleotide sequences encoding a subject antibody.
  • a nucleotide sequence encoding a subject antibody can be operably linked to one or more regulatory elements, such as a promoter and enhancer, that allow expression of the nucleotide sequence in the intended target cells (e.g., a cell that is genetically modified to synthesize the encoded antibody).
  • Suitable promoter and enhancer elements are known in the art.
  • suitable promoters include, but are not limited to, lad, lacZ, T3, T7, gpt, lambda P and trc.
  • suitable promoters include, but are not limited to, light and/or heavy chain immunoglobulin gene promoter and enhancer elements; cytomegalovirus immediate early promoter; herpes simplex virus thymidine kinase promoter; early and late SV40 promoters; promoter present in long terminal repeats from a retrovirus; mouse metallothionein-I promoter; and various art-known tissue specific promoters.
  • a suitable promoter is a constitutive promoter such as an ADH1 promoter, a PGK1 promoter, an ENO promoter, a PYK1 promoter and the like; or a regulatable promoter such as a GAL1 promoter, a GAL10 promoter, an ADH2 promoter, a PHO5 promoter, a CUP1 promoter, a GAL7 promoter, a MET25 promoter, a MET3 promoter, a CYC1 promoter, a HIS3 promoter, an ADH1 promoter, a PGK promoter, a GAPDH promoter, an ADC1 promoter, a TRP1 promoter, a URA3 promoter, a LEU2 promoter, an ENO promoter, a TP1 promoter, and AOX1 (e.g., for use in Pichia ). Selection of the appropriate vector and promoter is well within the appropriate vector and promoter is well within the appropriate vector and promoter.
  • Suitable promoters for use in prokaryotic host cells include, but are not limited to, a bacteriophage T7 RNA polymerase promoter; a trp promoter; a lac operon promoter; a hybrid promoter, e.g., a lac/tac hybrid promoter, a tac/trc hybrid promoter, a trp/lac promoter, a T7/lac promoter; a trc promoter; a tac promoter, and the like; an araBAD promoter; in vivo regulated promoters, such as an ssaG promoter or a related promoter (see, e.g., U.S. Patent Publication No.
  • a pagC promoter (Pulkkinen and Miller, J. Bacteriol., 1991: 173(1): 86-93; Alpuche-Aranda et al., PNAS, 1992; 89(21): 10079-83), a nirB promoter (Harborne et al. (1992) Mol. Micro. 6:2805-2813), and the like (see, e.g., Dunstan et al. (1999) Infect. Immun. 67:5133-5141; McKelvie et al. (2004) Vaccine 22:3243-3255; and Chatfield et al. (1992) Biotechnol.
  • sigma70 promoter e.g., a consensus sigma70 promoter (see, e.g., GenBank Accession Nos. AX798980, AX798961, and AX798183); a stationary phase promoter, e.g., a dps promoter, an spy promoter, and the like; a promoter derived from the pathogenicity island SPI-2 (see, e.g., WO96/17951); an actA promoter (see, e.g., Shetron-Rama et al. (2002) Infect. Immun.
  • Suitable strong promoters for use in prokaryotes such as Escherichia coli include, but are not limited to Trc, Tac, T5, T7, and P Lambda .
  • operators for use in bacterial host cells include a lactose promoter operator (Lad repressor protein changes conformation when contacted with lactose, thereby preventing the Lad repressor protein from binding to the operator), a tryptophan promoter operator (when complexed with tryptophan, TrpR repressor protein has a conformation that binds the operator; in the absence of tryptophan, the TrpR repressor protein has a conformation that does not bind to the operator), and a tac promoter operator (see, for example, deBoer et al. (1983) Proc. Natl. Acad. Sci. U.S.A. 80:21-25).
  • a nucleotide sequence encoding a subject antibody can be present in an expression vector and/or a cloning vector. Where a subject antibody comprises two separate polypeptides, nucleotide sequences encoding the two polypeptides can be cloned in the same or separate vectors.
  • An expression vector can include a selectable marker, an origin of replication, and other features that provide for replication and/or maintenance of the vector.
  • Bacterial pBs, phagescript, PsiX174, pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene, La Jolla, Calif., USA); pTrc99A, pKK223-3, pKK233-3, pDR540, and pRIT5 (Pharmacia, Uppsala, Sweden).
  • Eukaryotic pWLneo, pSV2cat, pOG44, PXR1, pSG (Stratagene) pSVK3, pBPV, pMSG and pSVL (Pharmacia).
  • Expression vectors generally have convenient restriction sites located near the promoter sequence to provide for the insertion of nucleic acid sequences encoding heterologous proteins.
  • a selectable marker operative in the expression host may be present.
  • Suitable expression vectors include, but are not limited to, viral vectors (e.g.
  • viral vectors based on vaccinia virus; poliovirus; adenovirus see, e.g., Li et al., Invest Opthalmol Vis Sci 35:2543 2549, 1994; Borras et al., Gene Ther 6:515 524, 1999; Li and Davidson, PNAS 92:7700 7704, 1995; Sakamoto et al., H Gene Ther 5:1088 1097, 1999; WO 94/12649, WO 93/03769; WO 93/19191; WO 94/28938; WO 95/11984 and WO 95/00655); adeno-associated virus (see, e.g., Ali et al., Hum Gene Ther 9:81 86, 1998, Flannery et al., PNAS 94:6916 6921, 1997; Bennett et al., Invest Opthalmol Vis Sci 38:2857 2863, 1997; Jomary et al., Gene Ther
  • SV40 herpes simplex virus
  • human immunodeficiency virus see, e.g., Miyoshi et al., PNAS 94:10319 23, 1997; Takahashi et al., J Virol 73:7812 7816, 1999
  • a retroviral vector e.g., Murine Leukemia Virus, spleen necrosis virus, and vectors derived from retroviruses such as Rous Sarcoma Virus, Harvey Sarcoma Virus, avian leukosis virus, human immunodeficiency virus, myeloproliferative sarcoma virus, and mammary tumor virus
  • retroviral vector e.g., Murine Leukemia Virus, spleen necrosis virus, and vectors derived from retroviruses such as Rous Sarcoma Virus, Harvey Sarcoma Virus, avian leukosis virus, human immunodeficiency virus, myeloproliferative sarcoma virus, and mamm
  • a subject nucleic acid comprises a nucleotide sequence encoding a subject antibody.
  • a subject nucleic acid can comprise a nucleotide sequence encoding heavy- and light-chain CDRs.
  • a subject nucleic acid comprises a nucleotide sequence encoding heavy- and light-chain CDRs, where the CDR-encoding sequences are interspersed with FR-encoding nucleotide sequences.
  • the FR-encoding nucleotide sequences are human FR-encoding nucleotide sequences.
  • a subject nucleic acid comprises a nucleotide sequence having at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100%, nucleotide sequence identity to the nucleotide sequence set forth in herein. In some embodiments, a subject nucleic acid comprises a nucleotide sequence having at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100%, nucleotide sequence identity to the nucleotide sequence set forth in herein.
  • the present disclosure provides isolated genetically modified host cells (e.g., in vitro cells) that are genetically modified with a subject nucleic acid.
  • a subject isolated genetically modified host cell can produce a subject antibody.
  • Suitable host cells include eukaryotic host cells, such as a mammalian cell, an insect host cell, a yeast cell; and prokaryotic cells, such as a bacterial cell.
  • eukaryotic host cells such as a mammalian cell, an insect host cell, a yeast cell
  • prokaryotic cells such as a bacterial cell.
  • Introduction of a subject nucleic acid into the host cell can be effected, for example by calcium phosphate precipitation, DEAE dextran mediated transfection, liposome-mediated transfection, electroporation, or other known method.
  • Suitable mammalian cells include primary cells and immortalized cell lines.
  • Suitable mammalian cell lines include human cell lines, non-human primate cell lines, rodent (e.g., mouse, rat) cell lines, and the like.
  • Suitable mammalian cell lines include, but are not limited to, HeLa cells (e.g., American Type Culture Collection (ATCC) No. CCL-2), CHO cells (e.g., ATCC Nos. CRL9618, CCL61, CRL9096), 293 cells (e.g., ATCC No. CRL-1573), Vero cells, NIH 3T3 cells (e.g., ATCC No. CRL-1658), Huh-7 cells, BHK cells (e.g., ATCC No.
  • ATCC American Type Culture Collection
  • CCL10 PC12 cells
  • COS cells COS-7 cells
  • RAT1 cells mouse L cells
  • HEK cells ATCC No. CRL1573
  • HLHepG2 cells HLHepG2 cells, and the like.
  • Suitable yeast cells include, but are not limited to, Pichia pastoris, Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia sp., Saccharomyces cerevisiae, Saccharomyces sp., Hansenula polymorpha, Kluyveromyces sp., Kluyveromyces lactis, Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium sp., Fusarium gramineum, Fusarium
  • Suitable prokaryotic cells include, but are not limited to, any of a variety of laboratory strains of Escherichia coli, Lactobacillus sp., Salmonella sp., Shigella sp., and the like. See, e.g., Carrier et al. (1992) J. Immunol. 148:1176-1181; U.S. Pat. No. 6,447,784; and Sizemore et al. (1995) Science 270:299-302.
  • Salmonella strains which can be employed in the present invention include, but are not limited to, Salmonella typhi and S. typhimurium .
  • Suitable Shigella strains include, but are not limited to, Shigella flexneri, Shigella sonnei , and Shigella disenteriae.
  • the laboratory strain is one that is non-pathogenic.
  • suitable bacteria include, but are not limited to, Bacillus subtilis, Pseudomonas pudita, Pseudomonas aeruginosa, Pseudomonas mevalonii, Rhodobacter sphaeroides, Rhodobacter capsulatus, Rhodospirillum rubrum, Rhodococcus sp., and the like.
  • the host cell is Escherichia coli.
  • compositions comprising a subject antibody.
  • a formulation comprises an effective amount of a subject antibody.
  • An “effective amount” means a dosage sufficient to produce a desired result, e.g., an increase of muscle mass or amelioration of a symptom of a disease.
  • the desired result is at least a reduction in a symptom of an ACVR2A-associated conditino, as compared to a control.
  • a subject antibody can be delivered in such a manner as to avoid the blood-brain barrier, as described in more detail below.
  • a subject antibody can be formulated and/or modified to enable the antibody to cross the blood-brain barrier.
  • a subject antibody in the subject methods, can be administered to the host using any convenient means capable of resulting in the desired therapeutic effect or diagnostic effect.
  • the agent can be incorporated into a variety of formulations for therapeutic administration.
  • a subject antibody can be formulated into pharmaceutical compositions by combination with appropriate, pharmaceutically acceptable carriers or diluents, and may be formulated into preparations in solid, semi-solid, liquid or gaseous forms, such as tablets, capsules, powders, granules, ointments, solutions, suppositories, injections, inhalants and aerosols.
  • a subject antibody in pharmaceutical dosage forms, can be administered in the form of their pharmaceutically acceptable salts, or they may also be used alone or in appropriate association, as well as in combination, with other pharmaceutically active compounds.
  • the following methods and excipients are merely exemplary and are in no way limiting.
  • a subject antibody can be used alone or in combination with appropriate additives to make tablets, powders, granules or capsules, for example, with conventional additives, such as lactose, mannitol, corn starch or potato starch; with binders, such as crystalline cellulose, cellulose derivatives, acacia, corn starch or gelatins; with disintegrators, such as corn starch, potato starch or sodium carboxymethylcellulose; with lubricants, such as talc or magnesium stearate; and if desired, with diluents, buffering agents, moistening agents, preservatives and flavoring agents.
  • conventional additives such as lactose, mannitol, corn starch or potato starch
  • binders such as crystalline cellulose, cellulose derivatives, acacia, corn starch or gelatins
  • disintegrators such as corn starch, potato starch or sodium carboxymethylcellulose
  • lubricants such as talc or magnesium stearate
  • a subject antibody can be formulated into preparations for injection by dissolving, suspending or emulsifying them in an aqueous or nonaqueous solvent, such as vegetable or other similar oils, synthetic aliphatic acid glycerides, esters of higher aliphatic acids or propylene glycol; and if desired, with conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifying agents, stabilizers and preservatives.
  • compositions comprising a subject antibody are prepared by mixing the antibody having the desired degree of purity with optional physiologically acceptable carriers, excipients, stabilizers, surfactants, buffers and/or tonicity agents.
  • Acceptable carriers, excipients and/or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid, glutathione, cysteine, methionine and citric acid; preservatives (such as ethanol, benzyl alcohol, phenol, m-cresol, p-chlor-m-cresol, methyl or propyl parabens, benzalkonium chloride, or combinations thereof); amino acids such as arginine, glycine, ornithine, lysine, histidine, glutamic acid, aspartic acid, isoleucine, leucine, alanine, phenylalanine, tyrosine, tryptophan
  • the pharmaceutical composition may be in a liquid form, a lyophilized form or a liquid form reconstituted from a lyophilized form, wherein the lyophilized preparation is to be reconstituted with a sterile solution prior to administration.
  • the standard procedure for reconstituting a lyophilized composition is to add back a volume of pure water (typically equivalent to the volume removed during lyophilization); however solutions comprising antibacterial agents may be used for the production of pharmaceutical compositions for parenteral administration; see also Chen (1992) Drug Dev Ind Pharm 18, 1311-54.
  • Exemplary antibody concentrations in a subject pharmaceutical composition may range from about 1 mg/mL to about 200 mg/ml or from about 50 mg/mL to about 200 mg/mL, or from about 150 mg/mL to about 200 mg/mL.
  • An aqueous formulation of the antibody may be prepared in a pH-buffered solution, e.g., at pH ranging from about 4.0 to about 7.0, or from about 5.0 to about 6.0, or alternatively about 5.5.
  • buffers that are suitable for a pH within this range include phosphate-, histidine-, citrate-, succinate-, acetate-buffers and other organic acid buffers.
  • the buffer concentration can be from about 1 mM to about 100 mM, or from about 5 mM to about 50 mM, depending, e.g., on the buffer and the desired tonicity of the formulation.
  • a tonicity agent may be included in the antibody formulation to modulate the tonicity of the formulation.
  • exemplary tonicity agents include sodium chloride, potassium chloride, glycerin and any component from the group of amino acids, sugars as well as combinations thereof.
  • the aqueous formulation is isotonic, although hypertonic or hypotonic solutions may be suitable.
  • isotonic denotes a solution having the same tonicity as some other solution with which it is compared, such as physiological salt solution or serum.
  • Tonicity agents may be used in an amount of about 5 mM to about 350 mM, e.g., in an amount of 100 mM to 350 nM.
  • a surfactant may also be added to the antibody formulation to reduce aggregation of the formulated antibody and/or minimize the formation of particulates in the formulation and/or reduce adsorption.
  • exemplary surfactants include polyoxyethylensorbitan fatty acid esters (Tween), polyoxyethylene alkyl ethers (Brij), alkylphenylpolyoxyethylene ethers (Triton-X), polyoxyethylene-polyoxypropylene copolymer (Poloxamer, Pluronic), and sodium dodecyl sulfate (SDS).
  • Suitable polyoxyethylenesorbitan-fatty acid esters are polysorbate 20, (sold under the trademark Tween 20TM) and polysorbate 80 (sold under the trademark Tween 80TM).
  • suitable polyethylene-polypropylene copolymers are those sold under the names Pluronic® F68 or Poloxamer 188TM.
  • suitable Polyoxyethylene alkyl ethers are those sold under the trademark BrijTM.
  • Exemplary concentrations of surfactant may range from about 0.001% to about 1% w/v.
  • a lyoprotectant may also be added in order to protect the labile active ingredient (e.g. a protein) against destabilizing conditions during the lyophilization process.
  • lyoprotectants include sugars (including glucose and sucrose); polyols (including mannitol, sorbitol and glycerol); and amino acids (including alanine, glycine and glutamic acid). Lyoprotectants can be included in an amount of about 10 mM to 500 nM.
  • a subject formulation includes a subject antibody, and one or more of the above-identified agents (e.g., a surfactant, a buffer, a stabilizer, a tonicity agent) and is essentially free of one or more preservatives, such as ethanol, benzyl alcohol, phenol, m-cresol, p-chlor-m-cresol, methyl or propyl parabens, benzalkonium chloride, and combinations thereof.
  • a preservative is included in the formulation, e.g., at concentrations ranging from about 0.001 to about 2% (w/v).
  • a subject formulation can be a liquid or lyophilized formulation suitable for parenteral administration, and can comprise: about 1 mg/mL to about 200 mg/mL of a subject antibody; about 0.001% to about 1% of at least one surfactant; about 1 mM to about 100 mM of a buffer; optionally about 10 mM to about 500 mM of a stabilizer; and about 5 mM to about 305 mM of a tonicity agent; and has a pH of about 4.0 to about 7.0.
  • a subject parenteral formulation is a liquid or lyophilized formulation comprising: about 1 mg/mL to about 200 mg/mL of a subject antibody; 0.04% Tween 20 w/v; 20 mM L-histidine; and 250 mM Sucrose; and has a pH of 5.5.
  • a subject parenteral formulation comprises a lyophilized formulation comprising: 1) 15 mg/mL of a subject antibody; 0.04% Tween 20 w/v; 20 mM L-histidine; and 250 mM sucrose; and has a pH of 5.5; or 2) 75 mg/mL of a subject antibody; 0.04% Tween 20 w/v; 20 mM L-histidine; and 250 mM sucrose; and has a pH of 5.5; or 3) 75 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 20 mM L-histidine; and 250 mM Sucrose; and has a pH of 5.5; or 4) 75 mg/mL of a subject antibody; 0.04% Tween 20 w/v; 20 mM L-histidine; and 250 mM trehalose; and has a pH of 5.5; or 6) 75 mg/mL of a subject antibody; 0.02% Tween 20 w/
  • a subject parenteral formulation is a liquid formulation comprising: 1) 7.5 mg/mL of a subject antibody; 0.022% Tween 20 w/v; 120 mM L-histidine; and 250 125 mM sucrose; and has a pH of 5.5; or 2) 37.5 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 10 mM L-histidine; and 125 mM sucrose; and has a pH of 5.5; or 3) 37.5 mg/mL of a subject antibody; 0.01% Tween 20 w/v; 10 mM L-histidine; and 125 mM sucrose; and has a pH of 5.5; or 4) 37.5 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 10 mM L-histidine; 125 mM trehalose; and has a pH of 5.5; or 5) 37.5 mg/mL of a subject antibody; 0.0
  • a subject antibody can be utilized in aerosol formulation to be administered via inhalation.
  • a subject antibody can be formulated into pressurized acceptable propellants such as dichlorodifluoromethane, propane, nitrogen and the like.
  • a subject antibody can be made into suppositories by mixing with a variety of bases such as emulsifying bases or water-soluble bases.
  • bases such as emulsifying bases or water-soluble bases.
  • a subject antibody can be administered rectally via a suppository.
  • the suppository can include vehicles such as cocoa butter, carbowaxes and polyethylene glycols, which melt at body temperature, yet are solidified at room temperature.
  • Unit dosage forms for oral or rectal administration such as syrups, elixirs, and suspensions may be provided wherein each dosage unit, for example, teaspoonful, tablespoonful, tablet or suppository, contains a predetermined amount of the composition containing one or more inhibitors.
  • unit dosage forms for injection or intravenous administration may comprise a subject antibody in a composition as a solution in sterile water, normal saline or another pharmaceutically acceptable carrier.
  • unit dosage form refers to physically discrete units suitable as unitary dosages for human and animal subjects, each unit containing a predetermined quantity of compounds of the present invention calculated in an amount sufficient to produce the desired effect in association with a pharmaceutically acceptable diluent, carrier or vehicle.
  • the specifications for a subject antibody may depend on the particular antibody employed and the effect to be achieved, and the pharmacodynamics associated with each antibody in the host.
  • a subject antibody can be formulated in suppositories and, in some cases, aerosol and intranasal compositions.
  • the vehicle composition will include traditional binders and carriers such as, polyalkylene glycols, or triglycerides.
  • suppositories may be formed from mixtures containing the active ingredient in the range of about 0.5% to about 10% (w/w), e.g., about 1% to about 2%.
  • Intranasal formulations will usually include vehicles that neither cause irritation to the nasal mucosa nor significantly disturb ciliary function.
  • Diluents such as water, aqueous saline or other known substances can be employed with the subject invention.
  • the nasal formulations may also contain preservatives such as, but not limited to, chlorobutanol and benzalkonium chloride.
  • a surfactant may be present to enhance absorption of the subject proteins by the nasal mucosa.
  • a subject antibody can be administered as an injectable formulation.
  • injectable compositions are prepared as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection may also be prepared.
  • the preparation may also be emulsified or the antibody encapsulated in liposome vehicles.
  • Suitable excipient vehicles are, for example, water, saline, dextrose, glycerol, ethanol, or the like, and combinations thereof.
  • the vehicle may contain minor amounts of auxiliary substances such as wetting or emulsifying agents or pH buffering agents.
  • auxiliary substances such as wetting or emulsifying agents or pH buffering agents.
  • Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in the art. See, e.g., Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa., 17th edition, 1985.
  • the composition or formulation to be administered will, in any event, contain a quantity of a subject antibody adequate to achieve the desired state in the subject being treated.
  • the pharmaceutically acceptable excipients such as vehicles, adjuvants, carriers or diluents, are readily available to the public.
  • pharmaceutically acceptable auxiliary substances such as pH adjusting and buffering agents, tonicity adjusting agents, stabilizers, wetting agents and the like, are readily available to the public.
  • a subject antibody is formulated in a controlled release formulation.
  • Sustained-release preparations may be prepared using methods well known in the art. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody in which the matrices are in the form of shaped articles, e.g. films or microcapsules. Examples of sustained-release matrices include polyesters, copolymers of L-glutamic acid and ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, hydrogels, polylactides, degradable lactic acid-glycolic acid copolymers and poly-D-( ⁇ )-3-hydroxybutyric acid. Possible loss of biological activity and possible changes in immunogenicity of antibodies comprised in sustained-release preparations may be prevented by using appropriate additives, by controlling moisture content and by developing specific polymer matrix compositions.
  • Controlled release within the scope of this invention can be taken to mean any one of a number of extended release dosage forms.
  • the following terms may be considered to be substantially equivalent to controlled release, for the purposes of the present invention: continuous release, controlled release, delayed release, depot, gradual release, long-term release, programmed release, prolonged release, proportionate release, protracted release, repository, retard, slow release, spaced release, sustained release, time coat, timed release, delayed action, extended action, layered-time action, long acting, prolonged action, repeated action, slowing acting, sustained action, sustained-action medications, and extended release. Further discussions of these terms may be found in Lesczek Krowczynski, Extended - Release Dosage Forms, 1987 (CRC Press, Inc.).
  • Controlled release technologies cover a very broad spectrum of drug dosage forms. Controlled release technologies include, but are not limited to physical systems and chemical systems.
  • Physical systems include, but are not limited to, reservoir systems with rate-controlling membranes, such as microencapsulation, macroencapsulation, and membrane systems; reservoir systems without rate-controlling membranes, such as hollow fibers, ultra microporous cellulose triacetate, and porous polymeric substrates and foams; monolithic systems, including those systems physically dissolved in non-porous, polymeric, or elastomeric matrices (e.g., nonerodible, erodible, environmental agent ingression, and degradable), and materials physically dispersed in non-porous, polymeric, or elastomeric matrices (e.g., nonerodible, erodible, environmental agent ingression, and degradable); laminated structures, including reservoir layers chemically similar or dissimilar to outer control layers; and other physical methods, such as osmotic pumps, or adsorption onto ion-exchange resins.
  • rate-controlling membranes such as microencapsulation, macroencapsulation, and membrane systems
  • Chemical systems include, but are not limited to, chemical erosion of polymer matrices (e.g., heterogeneous, or homogeneous erosion), or biological erosion of a polymer matrix (e.g., heterogeneous, or homogeneous). Additional discussion of categories of systems for controlled release may be found in Agis F. Kydonieus, Controlled Release Technologies: Methods, Theory and Applications, 1980 (CRC Press, Inc.).
  • controlled release drug formulations that are developed for oral administration. These include, but are not limited to, osmotic pressure-controlled gastrointestinal delivery systems; hydrodynamic pressure-controlled gastrointestinal delivery systems; membrane permeation-controlled gastrointestinal delivery systems, which include microporous membrane permeation-controlled gastrointestinal delivery devices; gastric fluid-resistant intestine targeted controlled-release gastrointestinal delivery devices; gel diffusion-controlled gastrointestinal delivery systems; and ion-exchange-controlled gastrointestinal delivery systems, which include cationic and anionic drugs. Additional information regarding controlled release drug delivery systems may be found in Yie W. Chien, Novel Drug Delivery Systems, 1992 (Marcel Dekker, Inc.).
  • a suitable dosage can be determined by an attending physician or other qualified medical personnel, based on various clinical factors. As is well known in the medical arts, dosages for any one patient depend upon many factors, including the patient's size, body surface area, age, the particular compound to be administered, sex of the patient, time, and route of administration, general health, and other drugs being administered concurrently.
  • a subject antibody may be administered in amounts between 1 ng/kg body weight and 20 mg/kg body weight per dose, e.g. between 0.1 mg/kg body weight to 10 mg/kg body weight, e.g. between 0.5 mg/kg body weight to 5 mg/kg body weight; however, doses below or above this exemplary range are envisioned, especially considering the aforementioned factors. If the regimen is a continuous infusion, it can also be in the range of 1 ⁇ g to 10 mg per kilogram of body weight per minute.
  • dose levels can vary as a function of the specific antibody, the severity of the symptoms and the susceptibility of the subject to side effects.
  • Preferred dosages for a given compound are readily determinable by those of skill in the art by a variety of means.
  • a subject antibody is administered to an individual using any available method and route suitable for drug delivery, including in vivo and ex vivo methods, as well as systemic and localized routes of administration.
  • a subject antibody composition can be administered in a single dose or in multiple doses.
  • a subject antibody composition is administered orally.
  • a subject antibody composition is administered via an inhalational route.
  • a subject antibody composition is administered intranasally.
  • a subject antibody composition is administered locally.
  • a subject antibody composition is administered intracranially.
  • a subject antibody composition is administered intravenously.
  • the agent can be administered to a host using any available conventional methods and routes suitable for delivery of conventional drugs, including systemic or localized routes.
  • routes of administration contemplated by the invention include, but are not necessarily limited to, enteral, parenteral, or inhalational routes.
  • Parenteral routes of administration other than inhalation administration include, but are not necessarily limited to, topical, transdermal, subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, and intravenous routes, i.e., any route of administration other than through the alimentary canal.
  • Parenteral administration can be carried to effect systemic or local delivery of a subject antibody. Where systemic delivery is desired, administration typically involves invasive or systemically absorbed topical or mucosal administration of pharmaceutical preparations.
  • a subject antibody can also be delivered to the subject by enteral administration.
  • Enteral routes of administration include, but are not necessarily limited to, oral and rectal (e.g., using a suppository) delivery.
  • treatment is meant at least an amelioration of the symptoms associated with the pathological condition afflicting the host, where amelioration is used in a broad sense to refer to at least a reduction in the magnitude of a parameter, e.g. symptom, associated with the pathological condition being treated, such as muscle atrophy.
  • amelioration also includes situations where the pathological condition, or at least symptoms associated therewith, are completely inhibited, e.g. prevented from happening, or stopped, e.g. terminated, such that the host no longer suffers from the pathological condition, or at least the symptoms that characterize the pathological condition.
  • a subject antibody is administered by injection and/or delivery, e.g., to a site in a brain artery or directly into brain tissue.
  • a subject antibody can also be administered directly to a target site e.g., by biolistic delivery to the target site.
  • hosts are treatable according to the subject methods.
  • hosts are “mammals” or “mammalian,” where these terms are used broadly to describe organisms which are within the class mammalia, including the orders carnivore (e.g., dogs and cats), rodentia (e.g., mice, guinea pigs, and rats), and primates (e.g., humans, chimpanzees, and monkeys).
  • the hosts will be humans.
  • Kits with unit doses of a subject antibody e.g. in oral or injectable doses, are provided.
  • kits in addition to the containers containing the unit doses will be an informational package insert describing the use and attendant benefits of the antibody in treating pathological condition of interest.
  • Preferred compounds and unit doses are those described herein above.
  • the present disclosure provides methods of treating an ACVR2A-associated condition, the methods generally involving administering to an individual in need thereof (e.g., an individual having a ACVR2A-associated condition) an effective amount of a subject antibody, alone (e.g., in monotherapy) or in combination (e.g., in combination therapy) with one or more additional therapeutic agents.
  • an ACVR2A-specific antibody can be used for treating or preventing a disease or condition that can be treated by decreasing ACVR2A signaling.
  • the present invention provides methods of treating or preventing a disease, disorder, or condition in an individual in need thereof through administering to the individual a therapeutically effective amount of an ACVR2A-specific antibody as described above. These methods are particularly aimed at therapeutic and prophylactic treatments of animals, and more particularly, humans.
  • mice genetically deficient in the inhibin- ⁇ subunit are deficient in inhibin A and inhibin B, have gonadal tumors that overexpress activins A and B (Matzuk et al., 1992, Nature 360:313-319; Matzuk et al., 1994, Proc Natl Acad Sci USA 91:8817-8821). All such mice develop these tumors and eventually die of a cancer cachexia-like syndrome mediated by high levels of tumor-derived activin acting through ACVR2A (Coerver et al., 1996, Mol Endocrinol 10:534-543).
  • an antibody that specifically blocks binding of a ligand to ACVR2A may be useful for treating a variety of conditions that are related to muscle atrophy.
  • an ACVR2A-specific antibody may be used to reduce the effects of activin-producing tumors, alleviating activin-mediated cachexia, and prolonging patient survival.
  • the subject may have a muscle-wasting disorder such as insufficient lean body mass, a decrease in muscle mass or muscle function, cachexia or sarcopenia.
  • ACVR2A and ACVR2A-ligand complexes play essential roles in tissue growth as well as early developmental processes such as the correct formation of various structures or in one or more post-developmental capacities including sexual development, pituitary hormone production, and creation of bone and cartilage.
  • ACVR2A-associated conditions include abnormal tissue growth and developmental defects.
  • ACVR2A-associated conditions include, but are not limited to, disorders of cell growth and differentiation such as inflammation, allergy, autoimmune diseases, infectious diseases, and tumors.
  • Exemplary ACVR2A-associated conditions include neuromuscular disorders (e.g., muscular dystrophy and muscle atrophy), congestive obstructive pulmonary disease or pulmonary emphysema (and associated muscle wasting), muscle wasting syndrome, sarcopenia, cachexia, adipose tissue disorders (e.g., obesity), type 2 diabetes, and bone degenerative disease (e.g., osteoporosis).
  • neuromuscular disorders e.g., muscular dystrophy and muscle atrophy
  • muscle wasting syndrome e.g., sarcopenia
  • cachexia e.g., adipose tissue disorders
  • type 2 diabetes e.g., type 2 diabetes
  • bone degenerative disease e.g., osteoporosis
  • ACVR2A-associated conditions include musculodegenerative and neuromuscular disorders, tissue repair (e.g., wound healing), neurodegenerative diseases (e.g., amyotrophic lateral sclerosis), immunologic disorders (e.g., disorders related to abnormal proliferation or function of lymphocytes), and obesity or disorders related to abnormal proliferation of adipocytes.
  • tissue repair e.g., wound healing
  • neurodegenerative diseases e.g., amyotrophic lateral sclerosis
  • immunologic disorders e.g., disorders related to abnormal proliferation or function of lymphocytes
  • obesity or disorders related to abnormal proliferation of adipocytes e.g., obesity or disorders related to abnormal proliferation of adipocytes.
  • an ACVR2A-specific antibody may be used as part of a treatment for a muscular dystrophy.
  • muscle dystrophy refers to a group of degenerative muscle diseases characterized by gradual weakening and deterioration of skeletal muscles and sometimes the heart and respiratory muscles. Muscular dystrophies are genetic disorders characterized by progressive muscle wasting and weakness that begin with microscopic changes in the muscle. As muscles degenerate over time, the person's muscle strength declines.
  • Exemplary muscular dystrophies that can be treated with a regimen including the subject ACVR2A-specific antibodies include: Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), fascioscapulohumeral muscular dystrophy (FSH or FSHD) (also known as Landouzy-Dejerine), myotonic muscular dystrophy (MMD) (also known as Steinert's Disease), oculopharyngeal muscular dystrophy (OPMD), distal muscular dystrophy (DD), congenital muscular dystrophy (CMD), and scapulohumeral muscular dystrophy (SMD).
  • DMD Duchenne muscular dystrophy
  • BMD Becker muscular dystrophy
  • EDMD Emery-Dreifuss muscular dystrophy
  • LGMD limb-girdle muscular dystrophy
  • FSH or FSHD fascioscapulohumer
  • DMD Duchenne muscular dystrophy
  • BMD Becker muscular dystrophy
  • DMD is one of the most frequent inherited diseases in males, affecting one in 3,500 boys.
  • DMD occurs when the dystrophin gene, located on the short arm of the X chromosome, is broken. Since males only carry one copy of the X chromosome, they only have one copy of the dystrophin gene. Without the dystrophin protein, muscle is easily damaged during cycles of contraction and relaxation. While early in the disease muscle compensates by regeneration, later on muscle progenitor cells cannot keep up with the ongoing damage and healthy muscle is replaced by non-functional fibro-fatty tissue.
  • ACVR2A-specific antibodies may also be used to treat or prevent muscular atrophy due to myopathies, examples of which include inflammatory myopathy, metabolic myopathy, and myotonia.
  • Subject ACVR2A-specific antibodies have application in treating congenital myopathies such as myotubular myopathy, nemalene myopathy, and mitochondrial myopathy.
  • the subject ACVR2A-specific antibodies may be used to treat inclusion body myositis, myoglobinurias, rhabdomyolysis, myositis ossificans, polymyositis, or dermatomyositis.
  • ACVR2A-specific antibodies may treat or prevent muscle atrophy arising from glucocorticoid treatment, sarcopenia, prolonged bed rest, skeletal immobilization, sepsis, or congestive heart failure.
  • An ACVR2A-specific antibody may provide an effective means to increase muscle mass in other neuromuscular diseases or conditions that are in need of muscle growth.
  • amyotrophic lateral sclerosis also known as Lou Gehrig's disease or motor neuron disease
  • ALS amyotrophic lateral sclerosis
  • Lou Gehrig's disease or motor neuron disease is a chronic, incurable, and unstoppable CNS disorder that attacks the motor neurons, components of the CNS that connect the brain to the skeletal muscles.
  • the motor neurons deteriorate and eventually die, and though a person's brain normally remains fully functioning and alert, the command to move cannot reach the muscles, Most people who develop ALS are between 40 and 70 years old.
  • the first motor neurons that weaken are those leading to the arms or legs.
  • ACVR2A-specific antibodies may be useful include paralysis due to spinal cord injury or stroke; denervation due to trauma or degenerative, metabolic, or inflammatory neuropathy; adult motor neuron disease; autoimmune motor neuropathy with multifocal conductor block; and infantile or juvenile spinal muscular atrophy.
  • the cancer anorexia-cachexia syndrome is among the most debilitating and life-threatening aspects of cancer. Progressive weight loss in cancer anorexia-cachexia syndrome is a common feature of many types of cancer and is responsible not only for a poor quality of life and poor response to chemotherapy, but also a shorter survival time than is found in patients with comparable tumors without weight loss. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. It is one of the most common causes of death among cancer patients and is present in 80% at death. It is a complex example of metabolic chaos effecting protein, carbohydrate, and fat metabolism.
  • Tumors produce both direct and indirect abnormalities, resulting in anorexia and weight loss.
  • Cancer anorexia-cachexia syndrome affects cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism.
  • anorexia is common, a decreased food intake alone is unable to account for the changes in body composition seen in cancer patients, and increasing nutrient intake is unable to reverse the wasting syndrome.
  • Cachexia is generally suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a six-month period.
  • ACVR2A-specific antibodies can be, beneficially used to prevent, treat, or alleviate the symptoms of the cachexia syndrome, where muscle growth is desired. This would include cachexia associated with cancer as well as cachexia associated with rheumatoid arthritis.
  • a subject treatment method involves administering a subject antibody and one or more additional therapeutic agents.
  • additional therapeutic agents include, but are not limited to, anabolic steroids, deacetylase inhibitors and selective adrenergic receptor modulators (SARMs).
  • Suitable subjects include any individual, e.g., a human, who has an ACVR2A-associated condition, who has been diagnosed with an ACVR2A-associated condition, who is at risk for developing an ACVR2A-associated condition, who has had an ACVR2A-associated condition and is at risk for recurrence of the an ACVR2A-associated condition, or who is recovering from an ACVR2A-associated condition.
  • Standard abbreviations may be used, e.g., bp, base pair(s); kb, kilobase(s); pl, picoliter(s); s or sec, second(s); min, minute(s); h or hr, hour(s); aa, amino acid(s); kb, kilobase(s); bp, base pair(s); nt, nucleotide(s); i.m., intramuscular(ly); i.p., intraperitoneal(ly); s.c., subcutaneous(ly); and the like.
  • Phagemid expression of diversified monovalent Fab libraries was accomplished by standard methods. TG-1 cells transformed with expression plasmids were grown to mid log (O.D. 600.about.0.3) in 2-YT media supplemented with 100 mcg/ml ampicillin and 2% glucose repression and then infected with m13K07 helper phage and grown overnight in 2-YT media supplemented with 100 mcg ampicillin, 70 mcg/ml kanamycin, and 200 micromolar IPTG. Phage containing supernatants were precipitated using polyethylene glycol and PBS resuspended phage were used to pan on immobilized ACVR2.
  • Panning of the libraries was performed by using recombinant soluble extracellular domains of ACVR2 (Peprotech or R&D Systems) immobilized on the wells of a microtiter dish or biotinylated ACVR2 immobilized on streptavidin derivatized magnetic beads (Dynal-Life Technologies).
  • ACVR2A-specific monoclonal antibodies to human ACVR2A, mouse ACVR2A, biotinylated goat anti-human kappa light chain (positive control) and human Fc (negative control) were determined by ELISA.
  • Table 4 The results of this assay are shown in Table 4 below. The values shown are optical densities.
  • the data in this table shows that the antibodies listed I specifically bind to ACVR2A.
  • the sequences of the heavy and light chains of the antibodies listed in Table 4 are shown above in FIGS. 2A-2F.
  • Example 2 The ability of several of the antibodies identified in Example 2 to block Activin A and GDF8 binding to ACVR2A or ACVR2B was assessed by ELISA.
  • Activin A R&D systems
  • GDF8 R&D systems
  • Activin A and GDF8 were coated on 384-well Immunolon plates in 1 ⁇ coating buffer (SurModics) at 0.5 ⁇ g/mL.
  • Antibodies were serially diluted in a 10-point curve starting at 1 ⁇ M in 3-fold steps.
  • ACVR2A and ACVR2B proteins were purchased from R&D Systems and biotinylated using the EZ-Link NHS-PEG4-biotin kit (Thermo Fisher).
  • the antibodies were pre-incubated with biotinylated human ACVR2A-Fc, mouse ACVR2A-Fc, human ACVR2B-Fc, or mouse ACVR2B-Fc at a concentration of 500 ng/mL in 1% BSA in PBST for 1 hour.
  • the mixtures of antibodies and biotinylated receptors were added to the Activin A/GDF8-coated plates for 1 hour.
  • the inhibition of ligand-receptor interaction was detected with streptavidin-HRP (Jackson ImmunoResearch) at a concentration of 10 ng/mL and TMB.
  • Example 2 The ability of several of the antibodies identified in Example 2 to specifically block GDF8-induced dimerization between ACVR2A and ALK5 in U2OS cells was assessed using the DiscoverX receptor dimerization assay.
  • two receptors are tagged with ProLinkTM (PK) or Enzyme Acceptor (EA).
  • PK ProLinkTM
  • EA Enzyme Acceptor
  • the receptors dimerize forcing the two ⁇ -gal components to complement and create an active enzyme. Active ⁇ -gal generates a chemiluminescent signal in the presence of substrate.
  • Example 2 The binding of several of the antibodies identified in Example 2 to human ACVR2A, mouse ACVR2A, human ACVR2B, and mouse ACVR2B were quantified by ELISA. His-tagged recombinant proteins (Sino Biological, Inc.) were His-tagged Human ACVR2A, Mouse ACVR2A, Human ACVR2B, or Mouse ACVR2B were coated on Immunolon 384-well plates at a concentration of 0.5 ⁇ g/mL in 1 ⁇ coating buffer (SurModics). Antibodies were diluted to 1 ⁇ M in PBS buffer containing 1% BSA and diluted 3-fold in a 10-point curve.
  • His-tagged recombinant proteins (Sino Biological, Inc.) were His-tagged Human ACVR2A, Mouse ACVR2A, Human ACVR2B, or Mouse ACVR2B were coated on Immunolon 384-well plates at a concentration of 0.5 ⁇ g/mL in 1 ⁇ coating buffer (SurModics). Antibodies were
  • Detection of the antibody binding to the antigen was performed using biotinylated goat anti-human kappa light chain (Bethyl Laboratories). Detection of the secondary antibody was determined using streptavidin-HRP and TMB reagent. All assays were performed at room temperature. Curve-fitting software was used to determine the EC50 for each antibody (MatLab).
  • Example 2 The ability of several of the antibodies identified in Example 2 to alter SMAD3 activity in muscle cells was tested.
  • Myoblasts were differentiated in DMEM/F-12K (50:50) supplemented with 2% horse serum (Corning) and 1% Penicillin/Streptomycin. After 4 days of differentiation, myotubes were pre-treated with antibodies for 1 hour at a starting concentration of 1 ⁇ M and diluted serially 3-fold in a 10-point curve.
  • GDF8 R&D was added for 1 hour at 100 ng/mL.
  • Phospho-SMAD3 Ser423/425
  • AlphaLisa Perkin-Elmer
  • Example 2 The ability of several of the antibodies identified in Example 2 to specifically inhibit GDF8-induced SMAD activation in HEK293 was tested cells using a smad2/3 luciferase reporter construct.
  • a smad2/3 luciferase reporter (SBI #TR203VA-P) was introduced into HEK293 cells. Endogenous ACVR2A and ACVR2B function was knocked out using custom made CRISPR/CAS9 targeting sequences. Finally, individual reporter lines were generated by reintroduction of ACVR2A or ACVR2B expression vectors.
  • This method involved dispensing 30,000 cells into each well in total volume of 80 ul, dispensing antibody into each well in total volume of 10 ul, incubating the treated cells for 1 hr at 37° C., dispensing GDF8 into wells in total volume of 10 ul (final conc. 100 ng/ml), incubating the stimulated cells for 24 hr at 37° C., adding 100 ul of 1X ONE-Glo detection reagent to each well, incubate the plate for 5 min at room temperature and then reading luminescence using a plate reader.
  • Example 2 The ability of several of the antibodies identified in Example 2 to specifically inhibit GDF8-induced SMAD activation was tested cells using the following protocol.
  • HEK293 cells were infected with a lentiviral SMAD2/3/4 reporter (pGF-SMAD2/3/4-mCMV-EF1-Puro System Biosciences).
  • the lentiviral based reporter expresses both GFP and luciferase under the control of a Smad3-responsive element (CAGA) 12 .
  • Cells were sorted for their responsiveness to GDF8 based on their GFP expression. Single cell clones were expanded and transcriptional activation was tested by GDF8-induced luciferase activity.
  • Clone 4E1 was unresponsive to GDF8 or Activin A. This clone was further transfected with Human or Mouse ACVR2A or ACVR2B plasmids. The ability of the antibodies to inhibit luciferase induction by GDF8 or Activin A in these cell lines was tested.

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Abstract

The present disclosure provides antibodies that specifically bind to and block signaling by ACVR2A, i.e., ACVR2A but not ACVR2B, as well as methods for using the same. The antibodies may be used for the treatment of a number of conditions associated with muscle atrophy, as well as other conditions.

Description

    CROSS-REFERENCING
  • This application claims the benefit of U.S. provisional application Ser. No. 62/477,911, filed on Mar. 28, 2017, which application is incorporated herein in its entirety.
    • BACKGROUND
  • The activin receptor, type II A (ACVR2A) is a high affinity receptor for the activin proteins as well as other members of the TGF-beta superfamily. ACVR2A is generally thought to transduce signals that lead to the phosphorylation of one or more SMAD transcription factors, particularly SMADs 1, 2, 3 and 5. ACVR2A has been implicated in the regulation of a wide range of biological processes, including bone formation, muscle formation, red blood cell formation, tumor growth, immune function and the production of reproductive hormones.
  • There is a need for reagents, e.g., antibodies, that specifically bind to ACVR2A and inhibit ACVR2A signaling.
    • SUMMARY OF THE INVENTION
  • The present disclosure provides antibodies that specifically bind to and block signaling by ACVR2A, i.e., ACVR2A but not ACVR2B. The antibodies are useful in various treatment, diagnostic, and monitoring applications. In some embodiments, an antibody may comprise: (a) a variable domain comprising: i. heavy chain CDR1, CDR2 and CDR3 regions that are identical the heavy chain CDR1, CDR2 and CDR3 regions of an antibody selected from any of Tables 2A-2F; and ii. light chain CDR1, CDR2 and CDR3 regions that are identical the light chain CDR1, CDR2 and CDR3 regions of the antibody selected from any of Tables 2A-2F; or (b) a variant of said variable domain of (a) that is otherwise identical to said antibody variable domain except for up to 15 amino acid substitutions in said CDR regions.
  • In some embodiments, an antibody may comprise: (a) a heavy chain variable domain comprising a heavy chain framework, a CDR1 region, a CDR2 region, and a CDR3 region of sequence ARSATWHDTXLD (SEQ ID NO:6538) or a variant of ARSATWHDTXLD (SEQ ID NO:6538) that comprises up to three amino acid substitutions, and (b) a light chain variable domain comprising a light chain framework, a CDR1 region, a CDR2 region, and a CDR3 region.
    • Definitions
  • The terms “antibodies” and “immunoglobulin” include antibodies or immunoglobulins of any isotype, fragments of antibodies which retain specific binding to antigen, including, but not limited to, Fab, Fv, scFv, and Fd fragments, chimeric antibodies, humanized antibodies, single-chain antibodies, and fusion proteins comprising an antigen-binding portion of an antibody and a non-antibody protein. The antibodies may be detectably labeled, e.g., with a radioisotope, an enzyme which generates a detectable product, a fluorescent protein, and the like. The antibodies may be further conjugated to other moieties, such as members of specific binding pairs, e.g., biotin (member of biotin-avidin specific binding pair), and the like. The antibodies may also be bound to a solid support, including, but not limited to, polystyrene plates or beads, and the like. Also encompassed by the term are Fab′, Fv, F(ab′)2, and or other antibody fragments that retain specific binding to antigen, and monoclonal antibodies. An antibody may be monovalent or bivalent.
  • “Antibody fragments” comprise a portion of an intact antibody, for example, the antigen binding or variable region of the intact antibody. Examples of antibody fragments include Fab, Fab′, F(ab′)2, and Fv fragments; diabodies; linear antibodies (Zapata et al., Protein Eng. 8(10): 1057-1062 (1995)); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments. Papain digestion of antibodies produces two identical antigen-binding fragments, called “Fab” fragments, each with a single antigen-binding site, and a residual “Fc” fragment, a designation reflecting the ability to crystallize readily. Pepsin treatment yields an F(ab′)2 fragment that has two antigen combining sites and is still capable of cross-linking antigen.
  • “Fv” is the minimum antibody fragment which contains a complete antigen-recognition and -binding site. This region consists of a dimer of one heavy- and one light-chain variable domain in tight, non-covalent association. It is in this configuration that the three CDRS of each variable domain interact to define an antigen-binding site on the surface of the VH-VL dimer. Collectively, the six CDRs confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.
  • The “Fab” fragment also contains the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Fab fragments differ from Fab′ fragments by the addition of a few residues at the carboxyl terminus of the heavy chain CH1 domain including one or more cysteines from the antibody hinge region. Fab′-SH is the designation herein for Fab′ in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab′)2 antibody fragments originally were produced as pairs of Fab′ fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.
  • The “light chains” of antibodies (immunoglobulins) from any vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda, based on the amino acid sequences of their constant domains. Depending on the amino acid sequence of the constant domain of their heavy chains, immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA, and IgA2.
  • “Single-chain Fv” or “sFv” antibody fragments comprise the VH and VL domains of antibody, wherein these domains are present in a single polypeptide chain. In some embodiments, the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains, which enables the sFv to form the desired structure for antigen binding. For a review of sFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).
  • The term “diabodies” refers to small antibody fragments with two antigen-binding sites, which fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (VL) in the same polypeptide chain (VH—VL). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. Diabodies are described more fully in, for example, EP 404,097; WO 93/11161; and Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).
  • As used herein, the term “affinity” refers to the equilibrium constant for the reversible binding of two agents and is expressed as a dissociation constant (Kd). Affinity can be at least 1-fold greater, at least 2-fold greater, at least 3-fold greater, at least 4-fold greater, at least 5-fold greater, at least 6-fold greater, at least 7-fold greater, at least 8-fold greater, at least 9-fold greater, at least 10-fold greater, at least 20-fold greater, at least 30-fold greater, at least 40-fold greater, at least 50-fold greater, at least 60-fold greater, at least 70-fold greater, at least 80-fold greater, at least 90-fold greater, at least 100-fold greater, or at least 1000-fold greater, or more, than the affinity of an antibody for unrelated amino acid sequences. Affinity of an antibody to a target protein can be, for example, from about 100 nanomolar (nM) to about 0.1 nM, from about 100 nM to about 1 picomolar (pM), or from about 100 nM to about 1 femtomolar (fM) or more. As used herein, the term “avidity” refers to the resistance of a complex of two or more agents to dissociation after dilution. The terms “immunoreactive” and “preferentially binds” are used interchangeably herein with respect to antibodies and/or antigen-binding fragments.
  • The term “binding” refers to a direct association between two molecules, due to, for example, covalent, electrostatic, hydrophobic, and ionic and/or hydrogen-bond interactions, including interactions such as salt bridges and water bridges. An ACVR2A-specific antibody antibodies binds specifically to an epitope within a ACVR2A polypeptide. Non-specific binding would refer to binding with an affinity of less than about 10−7 M, e.g., binding with an affinity of 10−6 M, 10−5 M, 10−4 M, etc.
  • As used herein, the term “CDR” or “complementarity determining region” is intended to mean the non-contiguous antigen combining sites found within the variable region of both heavy and light chain polypeptides. CDRs have been described by Kabat et al., J. Biol. Chem. 252:6609-6616 (1977); Kabat et al., U.S. Dept. of Health and Human Services, “Sequences of proteins of immunological interest” (1991); by Chothia et al., J. Mol. Biol. 196:901-917 (1987); and MacCallum et al., J. Mol. Biol. 262:732-745 (1996), where the definitions include overlapping or subsets of amino acid residues when compared against each other. Nevertheless, application of either definition to refer to a CDR of an antibody or grafted antibodies or variants thereof is intended to be within the scope of the term as defined and used herein. The amino acid residues which encompass the CDRs as defined by each of the above cited references are set forth below in Table 1 as a comparison.
  • TABLE 1
    CDR Definitions
    Kabat1 Chothia2 MacCallum3
    VH CDR1 31-35 26-32 30-35
    VH CDR2 50-65 53-55 47-58
    VH CDR3  95-102  96-101  93-101
    VL CDR1 24-34 26-32 30-36
    VL CDR2 50-56 50-52 46-55
    VL CDR3 89-97 91-96 89-96
    1Residue numbering follows the nomenclature of Kabat et al., supra
    2Residue numbering follows the nomenclature of Chothia et al., supra
    3Residue numbering follows the nomenclature of MacCallum et al., supra
  • As used herein, the term “framework” when used in reference to an antibody variable region is intended to mean all amino acid residues outside the CDR regions within the variable region of an antibody. A variable region framework is generally a discontinuous amino acid sequence between about 100-120 amino acids in length but is intended to reference only those amino acids outside of the CDRs. As used herein, the term “framework region” is intended to mean each domain of the framework that is separated by the CDRs.
  • An “isolated” antibody is one that has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would interfere with diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes. In some embodiments, the antibody will be purified (1) to greater than 90%, greater than 95%, or greater than 98%, by weight of antibody as determined by the Lowry method, for example, more than 99% by weight, (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing or nonreducing conditions using Coomassie blue or silver stain. Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present. In some instances, isolated antibody will be prepared by at least one purification step.
  • As used herein, the terms “treatment,” “treating,” and the like, refer to obtaining a desired pharmacologic and/or physiologic effect. The effect may be prophylactic in terms of completely or partially preventing a disease or symptom thereof and/or may be therapeutic in terms of a partial or complete cure for a disease and/or adverse effect attributable to the disease. “Treatment,” as used herein, covers any treatment of a disease in a mammal, particularly in a human, and includes: (a) preventing the disease from occurring in a subject which may be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting the disease, i.e., arresting its development; and (c) relieving the disease, i.e., causing regression of the disease.
  • The terms “individual,” “subject,” “host,” and “patient,” used interchangeably herein, refer to a mammal, including, but not limited to, murines (rats, mice), non-human primates, humans, canines, felines, ungulates (e.g., equines, bovines, ovines, porcines, caprines), etc.
  • A “therapeutically effective amount” or “efficacious amount” refers to the amount of an ACVR2A-specific antibody that, when administered to a mammal or other subject for treating a disease, is sufficient to effect such treatment for the disease. The “therapeutically effective amount” will vary depending on the ACVR2A-specific antibody, the disease and its severity and the age, weight, etc., of the subject to be treated.
  • A “biological sample” encompasses a variety of sample types obtained from an individual and can be used in a diagnostic or monitoring assay. The definition encompasses blood and other liquid samples of biological origin, solid tissue samples such as a biopsy specimen or tissue cultures or cells derived therefrom and the progeny thereof. The definition also includes samples that have been manipulated in any way after their procurement, such as by treatment with reagents, solubilization, or enrichment for certain components, such as polynucleotides. The term “biological sample” encompasses a clinical sample, and also includes cells in culture, cell supernatants, cell lysates, serum, plasma, biological fluid, and tissue samples.
  • The present disclosure may make use of consensus sequences. If an amino acid sequence is indicated as being “of sequence Y”, where Y is a consensus sequence, the amino acid sequence falls within the consensus sequence. In a consensus sequence, the amino acid “X” can be any amino acid.
  • Before the present invention is further described, it is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.
  • Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.
  • Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, the preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited.
  • It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “an antibody” includes a plurality of such antibodies and reference to “the ACVR2A-specific antibody” includes reference to one or more ACVR2A-specific antibodies and equivalents thereof known to those skilled in the art, and so forth. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation.
  • The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.
    • DETAILED DESCRIPTION
  • The present disclosure provides antibodies that specifically bind to and block signaling by ACVR2A, i.e., ACVR2A but not ACVR2B. In some embodiments, the antibody may comprise (a) a variable domain comprising: i. heavy chain CDR1, CDR2 and CDR3 regions that are identical the heavy chain CDR1, CDR2 and CDR3 regions of an antibody selected from any of Tables 2A-2F; and ii. light chain CDR1, CDR2 and CDR3 regions that are identical the light chain CDR1, CDR2 and CDR3 regions of the antibody selected from any of Tables 2A-2F; or (b) a variant of the variable domain of (a) that is otherwise identical to the antibody variable domain of (a) except for up to 15 amino acid substitutions in the CDR regions, e.g., up to 15, up to 14, up to 13, up to 12, up to 11, up to 10, up to 9, up to 8, up to 7, up to 6, up to 5, up to 4, up to 3, up to 2 amino acid substitutions in the CDR regions.
  • In some embodiments, the antibody may comprise: a heavy chain variable domain comprising: a heavy chain framework, a CDR1 region, a CDR2 region, and a CDR3 region of sequence AxxAxWHDTxLD; and a light chain variable domain comprising: a light chain framework, a CDR1 region, a CDR2 region, and a CDR3 region. For example, in some embodiments, the heavy chain variable domain of the antibody may comprise a CDR3 region of sequence ARSATWHDTxLD (SEQ ID NO: 6538) (e.g., ARAANWHDTA/HLD (SEQ ID NO: 6539)), ARAATWHDTxLD (SEQ ID NO: 6540) (e.g., ARAATWHDTH/ALD (SEQ ID NO: 6541)), ARGANWHDTxLD (SEQ ID NO: 6542) (e.g., ARGANWHDTA/HLD (SEQ ID NO: 6543)), ARGATWHDTxLD (SEQ ID NO: 6544) (e.g., ARGATWHDTH/ALD (SEQ ID NO: 6545)), ARSANWHDTxLD (SEQ ID NO: 6546) (e.g., AR/KSANWHDTA/HLD (SEQ ID NO: 6547)) or ARSATWHDTxLD (SEQ ID NO: 6548) (e.g., ARSATWHDTH/ALD (SEQ ID NO: 6549)).
  • As will be shown below, there is considerable diversity in the heavy chain CDR1, heavy chain CDR2, light chain CDR1, light chain CDR2 and light chain CDR3 regions in the present antibodies. Therefore, consistent with Barrios et al (Mol. Recognit. 2004 17: 332-8) and Bowers et al (J. Biol. Chem. 2013 288: 7688-96) the heavy chain CDR3 is believed primarily responsible for antigen binding in the present antibody.
  • In some embodiments, the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of D/SS/DYG/SMH/N (SEQ ID NO: 6550), ii. a CDR2 region that has a sequence of WVA/SS/G/NINYNG/SGYT/KS/G (SEQ ID NO: 6551), and iii. a CDR3 region that has a sequence of ARAANWHDTA/HLD (SEQ ID NO: 6552); and a light chain variable domain comprising: i. a CDR1 region that has a sequence of XXYL/VNWY (SEQ ID NO: 6553) (e.g., L/V/I/SS/T/RYL/VNWY (SEQ ID NO: 6554)), ii. a CDR2 region that has a sequence of LV/LIYXXXS/NR/LX (SEQ ID NO: 6555)(e.g., LV/LIYA/Y/VA/V/TT/S/NS/NR/LA/H/Q/P (SEQ ID NO: 6556)), and iii. a CDR3 region that has a sequence of QQ/HSY/DXXPL (SEQ ID NO: 6557) (e.g., QQ/HSY/DD/E/S/NL/N/S/TPL (SEQ ID NO: 6558)).
  • In some embodiments, the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of D/SS/DYG/SMH/N (SEQ ID NO: 6550), ii. a CDR2 region that has a sequence of WVA/SS/G/NINYNG/SGYT/KS/G (SEQ ID NO: 6551), and iii. a CDR3 region that has a sequence of ARAATWHDTH/ALD (SEQ ID NO: 6559); and a light chain variable domain comprising: i. a CDR1 region that has a sequence of XS/TYL/VNWY (SEQ ID NO: 6560) (e.g., L/V/I/SS/TYL/VNWY (SEQ ID NO: 6561)), ii. a CDR2 region that has a sequence of LL/VIYA/YXXS/NR/LX (SEQ ID NO: 6562)(e.g., LL/VIYA/YA/T/VT/S/NS/NR/LA/P/Q (SEQ ID NO: 6563)), and iii. a CDR3 region that has a sequence of QQSY/D/NXXPL (SEQ ID NO: 6564) (e.g., QQSY/D/ND/E/S/NL/S/T/NPL (SEQ ID NO: 6565)).
  • In some embodiments, the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of S/DS/DYS/GMN/H (SEQ ID NO: 6566), ii. a CDR2 region that has a sequence of WVS/AG/S/NINYNG/SGYT/KS/G (SEQ ID NO: 6567), and iii. a CDR3 region that has a sequence of ARGANWHDTA/HLD (SEQ ID NO: 6543); and a light chain variable domain comprising: i. a CDR1 region that has a sequence of XS/TYL/VNWY (SEQ ID NO: 6568) (e.g., L/V/S/IS/TYL/VNWY (SEQ ID NO: 6569)), ii. a CDR2 region that has a sequence of LL/VIYAXT/SSR/LX (SEQ ID NO: 6570) (e.g., LL/VIYAA/V/TT/SSR/LA/H/Q (SEQ ID NO: 6571)), and iii. a CDR3 region that has a sequence of QQSY/DXXPL (SEQ ID NO: 6572) (e.g., QQSY/DD/E/S/NS/T/N/LPL (SEQ ID NO: 6573)).
  • In some embodiments, the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of S/DS/DYS/GMN/H (SEQ ID NO: 6574), ii. a CDR2 region that has a sequence of WVA/SG/N/SINYNG/SGYT/KS/G (SEQ ID NO: 6575), and iii. a CDR3 region that has a sequence of ARGATWHDTH/ALD (SEQ ID NO: 6544); and a light chain variable domain comprising: i. a CDR1 region that has a sequence of XS/TYL/VNWY (SEQ ID NO: 6568) (e.g., L/I/V/SS/TYL/VNWY (SEQ ID NO: 6576)), ii. a CDR2 region that has a sequence of LL/VIYAXT/SSR/LX (SEQ ID NO: 6570) (e.g., LL/VIYAA/V/TT/SSR/LA/H/Q (SEQ ID NO: 6571)), and iii. a CDR3 region that has a sequence of QQSY/DXXPL (SEQ ID NO: 6572) (e.g., QQSY/DD/E/S/NT/S/N/LPL (SEQ ID NO: 6577)).
  • In some embodiments, the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of S/DS/DYG/SMN/H (SEQ ID NO: 6578), ii. a CDR2 region that has a sequence of WVS/AG/N/SINYNG/SGYT/KS/G (SEQ ID NO: 6579), and iii. a CDR3 region that has a sequence of AR/KSANWHDTA/HLD (SEQ ID NO: 6580); and a light chain variable domain comprising: i. a CDR1 region that has a sequence of XS/TYL/VNWY (SEQ ID NO: 6568) (e.g., L/V/I/SS/TYL/VNWY (SEQ ID NO: 6561)), ii. a CDR2 region that has a sequence of LL/VIYA/YXT/SS/NR/LX (SEQ ID NO: 6581) (e.g., LL/VIYA/YA/V/TT/SS/NR/LA/H/Q (SEQ ID NO: 6582)), and iii. a CDR3 region that has a sequence of QQSY/DXXPL (SEQ ID NO: 6572) (e.g., QQSY/DD/E/N/S S/T/L/NPL (SEQ ID NO: 6583)).
  • In some embodiments, the antibody may comprise a heavy chain variable domain comprising: i. a CDR1 region that has a sequence of D/SS/DYS/GMN/H (SEQ ID NO: 6584), ii. a CDR2 region that has a sequence of WVA/SG/N/SINYNG/SGYT/KS/G (SEQ ID NO: 6585), and iii. a CDR3 region that has a sequence of ARSATWHDTH/ALD (SEQ ID NO: 6586); and a light chain variable domain comprising: i. a CDR1 region that has a sequence of XXYL/VNWY (SEQ ID NO: 6587) (e.g., L/V/I/SS/T/RYL/VNWY (SEQ ID NO: 6588)), ii. a CDR2 region that has a sequence of LL/VIYA/YXT/SS/NR/LX (SEQ ID NO: 6589) (e.g., LL/VIYA/YA/V/TT/SS/NR/LA/H/Q (SEQ ID NO: 6590)), and iii. a CDR3 region that has a sequence of QQSY/DXXPL (SEQ ID NO: 6572) (e.g., QQSY/DD/E/S/NL/N/T/SPL (SEQ ID NO: 6591)).
  • In some embodiments the antibody may comprise: a heavy chain variable domain comprising an amino acid sequence that is at least 80% identical to (e.g., at least 90%, at least 95%, at least 98%, at least 99%, or 100% identical to) the amino acid sequence of the heavy chain variable domain of an antibody selected from any of Tables 2A-2F; and a light chain variable domain comprising an amino acid sequence that is at least 80% identical to (e.g., at least 90%, at least 95%, at least 98%, at least 99%, or 100% identical to) the light chain variable domain of the antibody selected from any of Tables 2A-2F.
  • Tables 2A-2F provides the amino acid sequences of the heavy and light variable domains of some examples of the present antibody.
  • TABLE 2A
    Group I Antibody Sequences
    Ab VH sequence VL sequence
    365_B04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQK
    GMHWVRQAPGKGLEWVASINYNSGYTSYADSV PGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSDESPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 58)
    NO: 1)
    365_B10 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSILRYLNWYQQK
    SMHWVRQAPGKGLEWVASINYNSGYKGYADSV PGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSDNLPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 59)
    NO: 2)
    365_C03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQK
    GMHWVRQAPGKGLEWVAGINYNSGYKGYADSV PGKAPKLVIYATTSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYNTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 60)
    NO: 3)
    365_C06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSISTYVNWYQQK
    GMHWVRQAPGKGLEWVSGINYNGGYTSYADSV PGKAPKLLIYAVTSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 61)
    NO: 4)
    365_D04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQK
    GMHWVRQAPGKGLEWVAGINYNGGYKSYADSV PGKAPKLVIYAVTSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 62)
    NO: 5)
    365_E04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQK
    GMHWVRQAPGKGLEWVASINYNGGYKSYADSV PGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 63)
    NO: 6)
    365_F11 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYVNWYQQK
    SMNWVRQAPGKGLEWVSGINYNSGYKGYADSV PGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYNTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 64)
    NO: 7)
    365_G07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQK
    GMHWVRQAPGKGLEWVSSINYNGGYTSYADSV PGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 65)
    NO: 8)
    365_H08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQK
    GMHWVRQAPGKGLEWVASINYNGGYKSYADSV PGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 66)
    NO: 9)
    366_A02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQK
    GMNWVRQAPGKGLEWVASINYNSGYKGYADSV PGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 67)
    NO: 10)
    366_A04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQK
    GMNWVRQAPGKGLEWVAGINYNGGYTSYADSV PGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSDDSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 68)
    NO: 11)
    366_D01 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQK
    GMHWVRQAPGKGLEWVSSINYNGGYTGYADSV PGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 69)
    NO: 12)
    366 D03 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQK
    GMHWVRQAPGKGLEWVSSINYNGGYTGYADSV PGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 70)
    NO: 13)
    366_F10 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQK
    SMNWVRQAPGKGLEWVAGINYNGGYTGYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 71)
    NO: 14)
    366_G06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQK
    GMHWVRQAPGKGLEWVASINYNGGYTGYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 72)
    NO: 15)
    367_B09 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQK
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 73)
    NO: 16)
    367_B11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQK
    SMHWVRQAPGKGLEWVANINYNSGYTSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 74)
    NO: 17)
    367_C09 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQK
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV PGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYNTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 75)
    NO: 18)
    367_D11 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQK
    GMHWVRQAPGKGLEWVSNINYNGGYKSYADSV PGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 76)
    NO: 19)
    367_F06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYVNWYQQK
    GMNWVRQAPGKGLEWVSSINYNSGYTSYADSV PGKAPKLLIYAVTSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 77)
    NO: 20)
    367_H01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQK
    GMNWVRQAPGKGLEWVSGINYNGGYKSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 78)
    NO: 21)
    368_A02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYVNWYQQK
    GMNWVRQAPGKGLEWVAGINYNGGYKSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 79)
    NO: 22)
    368_A06 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQK
    SMHWVRQAPGKGLEWVAGINYNSGYKGYADSV PGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 80)
    NO: 23)
    368_A12 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQK
    SMHWVRQAPGKGLEWVSSINYNSGYKGYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 81)
    NO: 24)
    368_B03 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQK
    GMNWVRQAPGKGLEWVSGINYNGGYTSYADSV PGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQHSYENPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 82)
    NO: 25)
    368_B08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQK
    GMNWVRQAPGKGLEWVSSINYNGGYTSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 83)
    NO: 26)
    368_B10 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQK
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSDELPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 84)
    NO: 27)
    368_B11 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQK
    GMHWVRQAPGKGLEWVSGINYNGGYKSYADSV PGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 85)
    NO: 28)
    368_C09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQK
    SMHWVRQAPGKGLEWVSNINYNGGYTGYADSV PGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 86)
    NO: 29)
    368 D09 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQK
    GMHWVRQAPGKGLEWVAGINYNSGYKSYADSV PGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 87)
    NO: 30)
    368_F02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQK
    GMNWVRQAPGKGLEWVASINYNSGYTSYADSV PGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYSLPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 88)
    NO: 31)
    368_F10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQK
    GMNWVRQAPGKGLEWVAGINYNSGYTSYADSV PGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 89)
    NO: 32)
    369_B03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQK
    GMHWVRQAPGKGLEWVAGINYNGGYTSYADSV PGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 90)
    NO: 33)
    369_G10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQK
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 91)
    NO: 34)
    369_H03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQK
    SMHWVRQAPGKGLEWVASINYNSGYKSYADSV PGKAPKLLIYATTSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 92)
    NO: 35)
    370_B01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQK
    GMHWVRQAPGKGLEWVSGINYNGGYKSYADSV PGKAPKLLIYVASSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYSLPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 93)
    NO: 36)
    370_D06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQK
    GMNWVRQAPGKGLEWVASINYNGGYTSYADSV PGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYSSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 94)
    NO: 37)
    370_G04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQK
    GMHWVRQAPGKGLEWVSGINYNGGYTGYADSV PGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 95)
    NO: 38)
    370_H08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQK
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV PGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYSLPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 96)
    NO: 39)
    371_A04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQK
    GMNWVRQAPGKGLEWVSSINYNSGYTGYADSV PGKAPKLLIYAVTSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 97)
    NO: 40)
    371_A09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYVNWYQQK
    GMNWVRQAPGKGLEWVSGINYNGGYKSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 98)
    NO: 41)
    371_D07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQK
    GMNWVRQAPGKGLEWVANINYNGGYKGYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 99)
    NO: 42)
    371_D12 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQK
    GMNWVRQAPGKGLEWVSGINYNGGYKSYADSV PGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 100)
    NO: 43)
    371_H02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQK
    SMNWVRQAPGKGLEWVSGINYNGGYKSYADSV PGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 101)
    NO: 44)
    372_A09 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQK
    GMNWVRQAPGKGLEWVSGINYNGGYTSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 102)
    NO: 45)
    372_B11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQK
    SMHWVRQAPGKGLEWVAGINYNSGYTSYADSV PGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 103)
    NO: 46)
    372_E02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYVNWYQQK
    GMNWVRQAPGKGLEWVASINYNGGYTSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 104)
    NO: 47)
    373_E11 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQK
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 105)
    NO: 48)
    373_H02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQK
    GMHWVRQAPGKGLEWVAGINYNSGYTSYADSV PGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYXNPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 106)
    NO: 49)
    374_B02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQK
    SMHWVRQAPGKGLEWVAGINYNSGYTSYADSV PGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 107)
    NO: 50)
    374_F03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYVNWYQQK
    GMNWVRQAPGKGLEWVASINYNGGYTSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 108)
    NO: 51)
    375_A04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQK
    GMNWVRQAPGKGLEWVAGINYNGGYKSYADSV PGKAPKLVIYYVNNLPSGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 109)
    NO: 52)
    375_A11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQK
    GMHWVRQAPGKGLEWVSSINYNSGYKSYADSV PGKAPKLLIYYVTNLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 110)
    NO: 53)
    375_C10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQK
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV PGKAPKLVIYAASSLQSGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 111)
    NO: 54)
    375_F12 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQK
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV PGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSDELPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 112)
    NO: 55)
    375_H01 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQK
    SMNWVRQAPGKGLEWVAGINYNSGYTSYADSV PGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYSNPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTHLDYWGQGTLVTVSS (SEQ ID NO: 113)
    NO: 56)
    376_G02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSISRYLNWYQQK
    GMNWVRQAPGKGLEWVSGINYNGGYTSYADSV PGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTISSL
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC QPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ ID
    ARAANWHDTALDYWGQGTLVTVSS (SEQ ID NO: 114)
    NO: 57)
  • Table 3A provides the amino acid sequences of the CDRs of the antibodies shown in Table 2A.
  • TABLE 3A
    CDR sequences for Group I antibodies
    Ab HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3
    365_B04 SSYGMH WVASINYNSGYTS ARAANWHDTALD LTYLNWY LLIYAATSRH QQSDESPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 172) 229) NO: NO: 343) NO: 400)
    115) 286)
    365_B10 DDYSMH WVASINYNSGYKG ARAANWHDTALD LRYLNWY LLIYAATSRA QQSDNLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 173) 230) NO: NO: 344) NO: 401)
    116) 287)
    365_C03 SSYGMH WVAGINYNSGYKG ARAANWHDTHLD LTYVNWY LVIYATTSLA QQSYNTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 174) 231) NO: NO: 345) NO: 402)
    117) 288)
    365_C06 SDYGMH WVSGINYNGGYTS ARAANWHDTALD STYVNWY LLIYAVTSLA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 175) 232) NO: NO: 346) NO: 403)
    118) 289)
    365_D04 SDYGMH WVAGINYNGGYKS ARAANWHDTALD SSYLNWY LVIYAVTSRA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 176) 233) NO: NO: 347) NO: 404)
    119) 290)
    365_E04 DSYGMH WVASINYNGGYKS ARAANWHDTALD LSYVNWY LLIYAATSLA QQSYELPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 177) 234) NO: NO: 348) NO: 405)
    120) 291)
    365_F11 DSYSMN WVSGINYNSGYKG ARAANWHDTHLD ISYVNWY LLIYAATSRA QQSYNTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 178) 235) NO: NO: 349) NO: 406)
    121) 292)
    365_G07 DSYGMH WVSSINYNGGYTS ARAANWHDTALD VSYLNWY LLIYAATSRA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 179) 236) NO: NO: 350) NO: 407)
    122) 293)
    365_H08 SSYGMH WVASINYNGGYKS ARAANWHDTALD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 180) 237) NO: NO: 351) NO: 408)
    123) 294)
    366_A02 DSYGMN WVASINYNSGYKG ARAANWHDTHLD VSYVNWY LLIYAATSRA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 181) 238) NO: NO: 352) NO: 409)
    124) 295)
    366_A04 SSYGMN WVAGINYNGGYTS ARAANWHDTALD LTYLNWY LVIYAATSLA QQSDDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 182) 239) NO: NO: 353) NO: 410)
    125) 296)
    366_D01 SSYGMH WVSSINYNGGYTG ARAANWHDTHLD LTYVNWY LLIYAATSRA QQSYENPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 183) 240) NO: NO: 354) NO: 411)
    126) 297)
    366_D03 DSYGMH WVSSINYNGGYTG ARAANWHDTHLD LSYVNWY LLIYAATSRA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 184) 241) NO: NO: 355) NO: 412)
    127) 298)
    366_F10 DSYSMN WVAGINYNGGYTG ARAANWHDTHLD VSYLNWY LVIYAATSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 185) 242) NO: NO: 356) NO: 413)
    128) 299)
    366_G06 SSYGMH WVASINYNGGYTG ARAANWHDTHLD VSYVNWY LVIYAATSRA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 186) 243) NO: NO: 357) NO: 414)
    129) 300)
    367_B09 DSYGMH WVASINYNGGYTS ARAANWHDTALD LSYVNWY LVIYAATSRA QQSYENPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 187) 244) NO: NO: 358) NO: 415)
    130) 301)
    367_B11 SDYSMH WVANINYNSGYTS ARAANWHDTALD LSYLNWY LVIYAATSRA QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 188) 245) NO: NO: 359) NO: 416)
    131) 302)
    367_C09 DSYGMH WVASINYNGGYTS ARAANWHDTHLD LVIYAATSRH LSYVNWY QQSYNTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 189) 246) NO: NO: 360) NO: 417)
    132) 303)
    367_D11 DSYGMH WVSNINYNGGYKS ARAANWHDTALD ISYLNWY LLIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 190) 247) NO: NO: 361) NO: 418)
    133) 304)
    367_F06 SSYGMN WVSSINYNSGYTS ARAANWHDTALD SSYVNWY LLIYAVTSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 191) 248) NO: NO: 362) NO: 419)
    134) 305)
    367_H01 DSYGMN WVSGINYNGGYKS ARAANWHDTALD LTYLNWY LVIYAATSRA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 192) 249) NO: NO: 363) NO: 420)
    135) 306)
    368_A02 DSYGMN WVAGINYNGGYKS ARAANWHDTHLD ISYVNWY LVIYAATSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 193) 250) NO: NO: 364) NO: 421)
    136) 307)
    368_A06 DSYSMH WVAGINYNSGYKG ARAANWHDTHLD LSYVNWY LLIYAATSRH QQSYNSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 194) 251) NO: NO: 365) NO: 422)
    137) 308)
    368_Al2 DSYSMH WVSSINYNSGYKG ARAANWHDTALD LTYLNWY LVIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 195) 252) NO: NO: 366) NO: 423)
    138) 309)
    368_B03 DDYGMN WVSGINYNGGYTS ARAANWHDTALD LTYLNWY LVIYAATSLA QHSYENPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 196) 253) NO: NO: 367) NO: 424)
    139) 310)
    368_B08 DSYGMN WVSSINYNGGYTS ARAANWHDTHLD LTYVNWY LVIYAATSRA QQSYENPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 197) 254) NO: NO: 368) NO: 425)
    140) 311)
    368_B10 DSYGMH WVASINYNGGYTS ARAANWHDTALD LTYLNWY LVIYAATSRA QQSDELPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 198) 255) NO: NO: 369) NO: 426)
    141) 312)
    368_B11 DSYGMH WVSGINYNGGYKS ARAANWHDTHLD LSYLNWY LLIYAASSLQ QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 199) 256) NO: NO: 370) NO: 427)
    142) 313)
    368_C09 SSYSMH WVSNINYNGGYTG ARAANWHDTHLD LTYVNWY LLIYAATSLA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 200) 257) NO: NO: 371) NO: 428)
    143) 314)
    368_D09 DSYGMH WVAGINYNSGYKS ARAANWHDTHLD VSYVNWY LLIYAATSLA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 201) 258) NO: NO: 372) NO: 429)
    144) 315)
    368_F02 SSYGMN WVASINYNSGYTS ARAANWHDTHLD LSYLNWY LLIYAASSLQ QQSYSLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 202) 259) NO: NO: 373) NO: 430)
    145) 316)
    368_F10 SSYGMN WVAGINYNSGYTS ARAANWHDTHLD VSYVNWY LLIYAATSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 203) 260) NO: NO: 374) NO: 431)
    146) 317)
    369_B03 SSYGMH WVAGINYNGGYTS ARAANWHDTALD LTYVNWY LVIYAATSLA QQSYELPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 204) 261) NO: NO: 375) NO: 432)
    147) 318)
    369_G10 SSYGMH WVASINYNGGYTS ARAANWHDTALD LSYLNWY LVIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 205) 262) NO: NO: 376) NO: 433)
    148) 319)
    369_H03 SSYSMH WVASINYNSGYKS ARAANWHDTALD VSYLNWY LLIYATTSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 206) 263) NO: NO: 377) NO: 434)
    149) 320)
    370_B01 DDYGMH WVSGINYNGGYKS ARAANWHDTALD LSYVNWY LLIYVASSRA QQSYSLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 207) 264) NO: NO: 378) NO: 435)
    150) 321)
    370_D06 SSYGMN WVASINYNGGYTS ARAANWHDTHLD ISYLNWY LVIYAATSLA QQSYSSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 208) 265) NO: NO: 379) NO: 436)
    151) 322)
    370_G04 SSYGMH WVSGINYNGGYTG ARAANWHDTALD LSYVNWY LLIYAATSRA QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 209) 266) NO: NO: 380) NO: 437)
    152) 323)
    370_H08 SSYGMH WVASINYNGGYTS ARAANWHDTHLD LSYVNWY LLIYAATSRH QQSYSLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 210) 267) NO: NO: 381) NO: 438)
    153) 324)
    371_A04 D SYGMN WVSSINYNSGYTG ARAANWHDTALD LTYLNWY LLIYAVTSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 211) 268) NO: NO: 382) NO: 439)
    154) 325)
    371_A09 SSYGMN WVSGINYNGGYKS ARAANWHDTALD VTYVNWY LVIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 212) 269) NO: NO: 383) NO: 440)
    155) 326)
    371_D07 DDYGMN WVANINYNGGYKG ARAANWHDTHLD LTYLNWY LVIYAATSRA QQSYELPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 213) 270) NO: NO: 384) NO: 441)
    156) 327)
    371_D12 DSYGMN WVSGINYNGGYKS ARAANWHDTALD LSYLNWY LLIYAATSRA QQSYELPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 214) 271) NO: NO: 385) NO: 442)
    157) 328)
    371_H02 DDYSMN WVSGINYNGGYKS ARAANWHDTHLD ISYLNWY LVIYAATSLA QQSYENPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 215) 272) NO: NO: 386) NO: 443)
    158) 329)
    372_A09 DSYGMN WVSGINYNGGYTS ARAANWHDTALD LSYLNWY LVIYAATSRA QQSYNSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 216) 273) NO: NO: 387) NO: 444)
    159) 330)
    372_B11 SSYSMH WVAGINYNSGYTS ARAANWHDTHLD LTYVNWY LVIYAATSLA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 217) 274) NO: NO: 388) NO: 445)
    160) 331)
    372_E02 SSYGMN WVASINYNGGYTS ARAANWHDTALD ISYVNWY LVIYAATSRA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 218) 275) NO: NO: 389) NO: 446)
    161) 332)
    373_E11 DSYGMH WVASINYNGGYTS ARAANWHDTALD VSYLNWY LVIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 219) 276) NO: NO: 390) NO: 447)
    162) 333)
    373_H02 SSYGMH WVAGINYNSGYTS ARAANWHDTALD VSYVNWY LLIYAATSRH QQSYXNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO:  220) 277) NO: NO: 391) NO: 448)
    163) 334)
    374_B02 DSYSMH WVAGINYNSGYTS ARAANWHDTHLD ISYLNWY LLIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 221) 278) NO: NO: 392) NO: 449)
    164) 335)
    374_F03 SSYGMN WVASINYNGGYTS ARAANWHDTHLD ISYVNWY LVIYAATSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 222) 279) NO: NO: 393) NO: 450)
    165) 336)
    375_A04 DSYGMN WVAGINYNGGYKS ARAANWHDTALD LTYLNWY LVIYYVNNLP QQSYNSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 223) 280) NO: NO: 394) NO: 451)
    166) 337)
    375_A11 SDYGMH WVSSINYNSGYKS ARAANWHDTALD VSYLNWY LLIYYVTNLA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 224) 281) NO: NO: 395) NO: 452)
    167) 338)
    375_C10 SSYGMH WVASINYNGGYTS ARAANWHDTALD STYLNWY LVIYAASSLQ QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 225) 282) NO: NO: 396) NO: 453)
    168) 339)
    375_F12 DSYGMH WVASINYNGGYTS ARAANWHDTALD LTYLNWY LVIYAATSRA QQSDELPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 226) 283) NO: NO: 397) NO: 454)
    169) 340)
    375_H01 SDYSMN WVAGINYNSGYTS ARAANWHDTHLD LTYLNWY LLIYAATSRH QQSYSNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 227) 284) NO: NO: 398) NO: 455)
    170) 341)
    376_G02 SDYGMN WVSGINYNGGYTS ARAANWHDTALD SRYLNWY LVIYAATSLA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 228) 285) NO: NO: 399) NO: 456)
    171) 342)
  • The consensus sequences for each of these CDRs shown in FIG. 3A are as follows:
  • HCDR1:
    (SEQ ID NO: 6550)
    D/SS/DYG/SMH/N
    HCDR2:
    (SEQ ID NO: 6551)
    WVA/SS/G/NINYNG/SGYT/KS/G
    HCDR3:
    (SEQ ID NO: 6552)
    ARAANWHDTA/HLD
    LCDR1:
    (SEQ ID NO: 6554)
    L/V/I/SS/T/RYL/VNWY
    LCDR2:
    (SEQ ID NO: 6592)
    LV/LIYA/Y/VA/V/TT/S/NS/NR/LA/H/Q/P
    LCDR3
    (SEQ ID NO: 6593)
    QQ/HSY/DD/E/S/NL/N/S/TPL
  • TABLE 2B
    Group II Antibody Sequences
    Ab VH sequence VL sequence
    365_A05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    GMHWVRQAPGKGLEWVSSINYNGGYTSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 528)
    NO: 457)
    365_B08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    GMNWVRQAPGKGLEWVSNINYNSGYKGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSSPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 529)
    NO: 458)
    365_B12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSISTYVNWYQQ
    GMHWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAVTSLHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 530)
    NO: 459)
    365_D03 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    SMHWVRQAPGKGLEWVASINYNGGYKSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 531)
    NO: 460)
    365_D08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIITYVNWYQQ
    SMHWVRQAPGKGLEWVSSINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 532)
    NO: 461)
    365_E06 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 533)
    NO: 462)
    365_F10 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYVNWYQQ
    GMHWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 534)
    NO: 463)
    365_G06 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMHWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDSTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 535)
    NO: 464)
    365_G08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 536)
    NO: 465)
    366_B09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMHWVRQAPGKGLEWVSSINYNSGYKSYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 537)
    NO: 466)
    366_C05 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQ
    GMHWVRQAPGKGLEWVSSINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 538)
    NO: 467)
    366_E07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMHWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDNSPLTFGGGTKVEIK (SEQ
    ARAATWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 539)
    NO: 468)
    366_G02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMHWVRQAPGKGLEWVSSINYNGGYTSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDDNPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 540)
    NO: 469)
    366_H01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMHWVRQAPGKGLEWVANINYNGGYTSYADSV KPGKAPKLVIYATTSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 541)
    NO: 470)
    367_C06 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMHWVRQAPGKGLEWVASINYNGGYKSYADSV KPGKAPKLVIYAATSLHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 542)
    NO: 471)
    367_C12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYATTSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 543)
    NO: 472)
    367_E08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMNWVRQAPGKGLEWVASINYNGGYTSYADSV KPGKAPKLLIYATTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 544)
    NO: 473)
    367_E10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVSSINYNGGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 545)
    NO: 474)
    367_F08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVSSINYNSGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSNELPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 546)
    NO: 475)
    367_F10 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNSGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 547)
    NO: 476)
    367_G03 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    SMHWVRQAPGKGLEWVANINYNGGYTSYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 548)
    NO: 477)
    367_G11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDDSPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 549)
    NO: 478)
    367_H08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    GMNWVRQAPGKGLEWVSSINYNGGYTSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 550)
    NO: 479)
    368_B04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    GMHWVRQAPGKGLEWVSSINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 551)
    NO: 480)
    368_B12 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    GMHWVRQAPGKGLEWVSGINYNSGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 552)
    NO: 481)
    368_C04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVSNINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 553)
    NO: 482)
    368_C07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    GMHWVRQAPGKGLEWVAGINYNSGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 554)
    NO: 483)
    368_C12 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDSNPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 555)
    NO: 484)
    368_D03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSIITYVNWYQQ
    SMHWVRQAPGKGLEWVASINYNGGYTSYADSV KPGKAPKLLIYATTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 556)
    NO: 485)
    368_D06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMNWVRQAPGKGLEWVSNINYNGGYTGYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 557)
    NO: 486)
    368 D07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    GMHWVRQAPGKGLEWVASINYNGGYTGYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 558)
    NO: 487)
    368_E05 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMHWVRQAPGKGLEWVSSINYNGGYKSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSSPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 559)
    NO: 488)
    368_E08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVANINYNSGYTGYADSV KPGKAPKLVIYAATSLHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 560)
    NO: 489)
    368_G11 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMHWVRQAPGKGLEWVSGINYNSGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDNTPLTFGGGTKVEIK (SEQ
    ARAATWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 561)
    NO: 490)
    368_H03 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMHWVRQAPGKGLEWVASINYNGGYTGYADSV KPGKAPKLVIYAVTSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSNPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 562)
    NO: 491)
    369_A04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    GMHWVRQAPGKGLEWVASINYNGGYKSYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 563)
    NO: 492)
    369_A12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMHWVRQAPGKGLEWVASINYNSGYTGYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 564)
    NO: 493)
    369_B07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    GMHWVRQAPGKGLEWVANINYNGGYKSYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 565)
    NO: 494)
    369_B08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVSSINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 566)
    NO: 495)
    369_C06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMHWVRQAPGKGLEWVSSINYNGGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 567)
    NO: 496)
    369_C09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    GMHWVRQAPGKGLEWVSSINYNGGYTGYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 568)
    NO: 497)
    369_C11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMHWVRQAPGKGLEWVAGINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 569)
    NO: 498)
    369_E03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 570)
    NO: 499)
    370_B06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    GMHWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 571)
    NO: 500)
    370_B07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    GMHWVRQAPGKGLEWVANINYNSGYKSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSSPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 572)
    NO: 501)
    370_E12 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 573)
    NO: 502)
    370_H05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMHWVRQAPGKGLEWVSNINYNGGYTSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDSLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 574)
    NO: 503)
    371_A05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMHWVRQAPGKGLEWVSNINYNGGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDNLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 575)
    NO: 504)
    371_B02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    GMNWVRQAPGKGLEWVSNINYNGGYTSYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNNPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 576)
    NO: 505)
    371_B11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMHWVRQAPGKGLEWVASINYNSGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 577)
    NO: 506)
    371_C02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    GMHWVRQAPGKGLEWVAGINYNSGYTGYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 578)
    NO: 507)
    371_D05 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMHWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 579)
    NO: 508)
    371_F07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMHWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDSNPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 580)
    NO: 509)
    371_G07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    GMHWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 581)
    NO: 510)
    372_D07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 582)
    NO: 511)
    373_B01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVSGINYNGGYKSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 583)
    NO: 512)
    373_D11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    GMHWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 584)
    NO: 513)
    373_G06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVASINYNSGYTGYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNLPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 585)
    NO: 514)
    374_A10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 586)
    NO: 515)
    374_A12 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMHWVRQAPGKGLEWVSSINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDSNPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 587)
    NO: 516)
    374_B01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMHWVRQAPGKGLEWVAGINYNSGYTSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 588)
    NO: 517)
    374_B07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQ
    GMHWVRQAPGKGLEWVSSINYNGGYKSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 589)
    NO: 518)
    374_H02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 590)
    NO: 519)
    375_C03 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMHWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 591)
    NO: 520)
    375_C05 EVQLLESGGGLVQPGGSLRLSCAASGFTFXSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMNWVRQAPGKGLEWVASINYNGGYKGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 592)
    NO: 521)
    375_D02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSNINYNGGYTSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 593)
    NO: 522)
    375_G08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYVNWYQQ
    GMHWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 594)
    NO: 523)
    375_H04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMHWVRQAPGKGLEWVAGINYNSGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSNPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 595)
    NO: 524)
    376_D08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVANINYNSGYKSYADSV KPGKAPKLVIYYANNRPSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSNPLTFGGGTKVEIK (SEQ
    ARAATWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 596)
    NO: 525)
    376_F09 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMHWVRQAPGKGLEWVSSINYNGGYKSYADSV KPGKAPKLLIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 597)
    NO: 526)
    376_H12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSIITYLNWYQQ
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARAATWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 598)
    NO: 527)
  • Table 3B provides the amino acid sequences of the CDRs of the antibodies shown in Table 2B.
  • TABLE 3B
    CDR sequences for Group II antibodies
    Ab HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3
    365_A05 SSYGMH WVSSINYNGGYTS ARAATWHDTHLD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID  (SEQ ID NO: 670) (SEQ ID NO: 742) (SEQ ID NO: 813) (SEQ ID NO: 884) (SEQ ID NO: 955)
    NO: 599)
    365_B08 DSYGMN WVSNINYNSGYKG ARAATWHDTHLD VTYLNWY LLIYAATSRA QQSYSSPL
    (SEQ ID  (SEQ ID NO: 671) (SEQ ID NO: 743) (SEQ ID NO: 814) (SEQ ID NO: 885) (SEQ ID NO: 956)
    NO: 600)
    365_B12 SDYGMH WVSGINYNGGYTS ARAATWHDTHLD STYVNWY LLIYAVTSLH QQSYDNPL
    (SEQ ID  (SEQ ID NO: 672) (SEQ ID NO: 744) (SEQ ID NO: 815) (SEQ ID NO: 886) (SEQ ID NO: 957)
    NO: 601)
    365_D03 DDYSMH WVASINYNGGYKS ARAATWHDTHLD VSYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 673) (SEQ ID NO: 745) (SEQ ID NO: 816) (SEQ ID NO: 887) (SEQ ID NO: 958)
    NO: 602)
    365_D08 DSYSMH WVSSINYNGGYTS ARAATWHDTHLD ITYVNWY LLIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 674) (SEQ ID NO: 746) (SEQ ID NO: 817) (SEQ ID NO: 888) (SEQ ID NO: 959)
    NO: 603)
    365_E06 DSYGMN WVSGINYNGGYTG ARAATWHDTHLD LTYLNWY LVIYAATSRA QQSYNTPL
    (SEQ ID  (SEQ ID NO: 675) (SEQ ID NO: 747) (SEQ ID NO: 818) (SEQ ID NO: 889) (SEQ ID NO: 960)
    NO: 604)
    365_F10 DDYGMH WVSGINYNGGYTS ARAATWHDTHLD VTYVNWY LLIYAATSRA QQSYELPL
    (SEQ ID  (SEQ ID NO: 676) (SEQ ID NO: 748) (SEQ ID NO: 819) (SEQ ID NO: 890) (SEQ ID NO: 961)
    NO: 605)
    365_G06 DSYGMH WVAGINYNGGYTS ARAATWHDTHLD LSYLNWY LLIYAATSLA QQSDSTPL
    (SEQ ID  (SEQ ID NO: 677) (SEQ ID NO: 749) (SEQ ID NO: 820) (SEQ ID NO: 891) (SEQ ID NO: 962)
    NO: 606)
    365_G08 SSYGMH WVASINYNGGYTS ARAATWHDTHLD SSYLNWY LLIYAASSLQ QQSYETPL
    (SEQ ID  (SEQ ID NO: 678) (SEQ ID NO: 750) (SEQ ID NO: 821) (SEQ ID NO: 892) (SEQ ID NO: 963)
    NO: 607)
    366_B09 SDYGMH WVSSINYNSGYKS ARAATWHDTHLD LTYLNWY LVIYAATSRH QQSYDSPL
    (SEQ ID  (SEQ ID NO: 679) (SEQ ID NO: 751) (SEQ ID NO: 822) (SEQ ID NO: 893) (SEQ ID NO: 964)
    NO: 608)
    366_C05 DDYGMH WVSSINYNGGYTG ARAATWHDTHLD ISYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 680) (SEQ ID NO: 752) (SEQ ID NO: 823) (SEQ ID NO: 894) (SEQ ID NO: 965)
    NO: 609)
    366_E07 DSYGMH WVAGINYNGGYTS ARAATWHDTALD LTYLNWY LVIYAATSRH QQSDNSPL
    (SEQ ID  (SEQ ID NO: 681) (SEQ ID NO: 753) (SEQ ID NO: 824) (SEQ ID NO: 895) (SEQ ID NO: 966)
    NO: 610)
    366_G02 DSYGMH WVSSINYNGGYTS ARAATWHDTHLD LTYLNWY LLIYAATSRH QQSDDNPL
    (SEQ ID  (SEQ ID NO: 682) (SEQ ID NO: 754) (SEQ ID NO: 825) (SEQ ID NO: 896) (SEQ ID NO: 967)
    NO: 611)
    366_H01 DDYSMH WVANINYNGGYTS ARAATWHDTHLD LTYLNWY LVIYATTSRH QQSYESPL
    (SEQ ID  (SEQ ID NO: 683) (SEQ ID NO: 755) (SEQ ID NO: 826) (SEQ ID NO: 897) (SEQ ID NO: 968)
    NO: 612)
    367_C06 DSYSMH WVASINYNGGYKS ARAATWHDTHLD LTYLNWY LVIYAATSLH QQSYDTPL
    (SEQ ID  (SEQ ID NO: 684) (SEQ ID NO: 756) (SEQ ID NO: 827) (SEQ ID NO: 898) (SEQ ID NO: 969)
    NO: 613)
    367_C12 SSYGMH WVSGINYNGGYTS ARAATWHDTHLD LSYVNWY LLIYATTSRH QQSYESPL
    (SEQ ID  (SEQ ID NO: 685) (SEQ ID NO: 757) (SEQ ID NO: 828) (SEQ ID NO: 899) (SEQ ID NO: 970)
    NO: 614)
    367_E08 SDYGMN WVASINYNGGYTS ARAATWHDTHLD LSYLNWY LLIYATTSRA QQSYDNPL
    (SEQ ID  (SEQ ID NO: 686) (SEQ ID NO: 758) (SEQ ID NO: 829) (SEQ ID NO: 900) (SEQ ID NO: 971)
    NO: 615)
    367_E10 SSYGMH WVSSINYNGGYTG ARAATWHDTHLD LSYVNWY LLIYAATSRA QQSYELPL
    (SEQ ID  (SEQ ID NO: 687) (SEQ ID NO: 759) (SEQ ID NO: 830) (SEQ ID NO: 901) (SEQ ID NO: 972)
    NO: 616)
    367_F08 SSYGMH WVSSINYNSGYTS ARAATWHDTHLD LSYVNWY LVIYAATSRA QQSNELPL
    (SEQ ID  (SEQ ID NO: 688) (SEQ ID NO: 760) (SEQ ID NO: 831) (SEQ ID NO: 902) (SEQ ID NO: 973)
    NO: 617)
    367_F10 DSYGMN WVSGINYNSGYTS ARAATWHDTHLD LTYLNWY LLIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 689) (SEQ ID NO: 761) (SEQ ID NO: 832) (SEQ ID NO: 903) (SEQ ID NO: 974)
    NO: 618)
    367_G03 DSYSMH WVANINYNGGYTS ARAATWHDTHLD VSYVNWY LVIYAATSRH QQSYDLPL
    (SEQ ID  (SEQ ID NO: 690) (SEQ ID NO: 762) (SEQ ID NO: 833) (SEQ ID NO: 904) (SEQ ID NO: 975)
    NO: 619)
    367_G11 SSYGMH WVASINYNGGYTS ARAATWHDTHLD LTYLNWY LLIYAATSRH QQSDDSPL
    (SEQ ID  (SEQ ID NO: 691) (SEQ ID NO: 763) (SEQ ID NO: 834) (SEQ ID NO: 905) (SEQ ID NO: 976)
    NO: 620)
    367_H08 DSYGMN WVSSINYNGGYTS ARAATWHDTHLD LTYVNWY LLIYAATSRH QQSYNLPL
    (SEQ ID  (SEQ ID NO: 692) (SEQ ID NO: 764) (SEQ ID NO: 835) (SEQ ID NO: 906) (SEQ ID NO: 977)
    NO: 621)
    368_B04 DSYGMH WVSSINYNGGYTS ARAATWHDTHLD VSYLNWY LVIYAATSRA QQSYENPL
    (SEQ ID  (SEQ ID NO: 693) (SEQ ID NO: 765) (SEQ ID NO: 836) (SEQ ID NO: 907) (SEQ ID NO: 978)
    NO: 622)
    368_B12 DSYGMH WVSGINYNSGYTS ARAATWHDTHLD VSYVNWY LLIYAATSRA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 694) (SEQ ID NO: 766) (SEQ ID NO: 837) (SEQ ID NO: 908) (SEQ ID NO: 979)
    NO: 623)
    368_C04 DSYGMH WVSNINYNGGYTS ARAATWHDTHLD LSYVNWY LLIYAATSRA QQSYSTPL
    (SEQ ID  (SEQ ID NO: 695) (SEQ ID NO: 767) (SEQ ID NO: 838) (SEQ ID NO: 909) (SEQ ID NO: 980)
    NO: 624)
    368_C07 SSYGMH WVAGINYNSGYTS ARAATWHDTHLD VSYVNWY LVIYAATSRA QQSYENPL
    (SEQ ID  (SEQ ID NO: 696) (SEQ ID NO: 768) (SEQ ID NO: 839) (SEQ ID NO: 910) (SEQ ID NO: 981)
    NO: 625)
    368_C12 DSYGMH WVASINYNGGYTS ARAATWHDTHLD LTYLNWY LLIYAATSRA QQSDSNPL
    (SEQ ID  (SEQ ID NO: 697) (SEQ ID NO: 769) (SEQ ID NO: 840) (SEQ ID NO: 911) (SEQ ID NO: 982)
    NO: 626)
    368_D03 SDYSMH WVASINYNGGYTS ARAATWHDTHLD ITYVNWY LLIYATTSRA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 698) (SEQ ID NO: 770) (SEQ ID NO: 841) (SEQ ID NO: 912) (SEQ ID NO: 983)
    NO: 627)
    368_D06 SSYGMN WVSNINYNGGYTG ARAATWHDTHLD LSYVNWY LVIYAATSRH QQSYENPL
    (SEQ ID  (SEQ ID NO: 699) (SEQ ID NO: 771) (SEQ ID NO: 842) (SEQ ID NO: 913) (SEQ ID NO: 984)
    NO: 628)
    368_D07 DSYGMH WVASINYNGGYTG ARAATWHDTHLD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID  (SEQ ID NO: 700) (SEQ ID NO: 772) (SEQ ID NO: 843) (SEQ ID NO: 914) (SEQ ID NO: 985)
    NO: 629)
    368_E05 DSYSMH WVSSINYNGGYKS ARAATWHDTHLD LSYLNWY LVIYAATSRA QQSYSSPL
    (SEQ ID  (SEQ ID NO: 701) (SEQ ID NO: 773) (SEQ ID NO: 844) (SEQ ID NO: 915) (SEQ ID NO: 986)
    NO: 630)
    368_E08 DSYGMH WVANINYNSGYTG ARAATWHDTHLD LSYVNWY LVIYAATSLH QQSYETPL
    (SEQ ID  (SEQ ID NO: 702) (SEQ ID NO: 774) (SEQ ID NO: 845) (SEQ ID NO: 916) (SEQ ID NO: 987)
    NO: 631)
    368_G11 DSYGMH WVSGINYNSGYKS ARAATWHDTALD LTYLNWY LLIYAATSRA QQSDNTPL
    (SEQ ID  (SEQ ID NO: 703) (SEQ ID NO: 775) (SEQ ID NO: 846) (SEQ ID NO: 917) (SEQ ID NO: 988)
    NO: 632)
    368_H03 DDYSMH WVASINYNGGYTG ARAATWHDTHLD LSYVNWY LVIYAVTSRH QQSYSNPL
    (SEQ ID  (SEQ ID NO: 704) (SEQ ID NO: 776) (SEQ ID NO: 847) (SEQ ID NO: 918) (SEQ ID NO: 989)
    NO: 633)
    369_A04 DSYGMH WVASINYNGGYKS ARAATWHDTHLD VSYVNWY LVIYAATSLA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 705) (SEQ ID NO: 777) (SEQ ID NO: 848) (SEQ ID NO: 919) (SEQ ID NO: 990)
    NO: 634)
    369_A12 SSYSMH WVASINYNSGYTG ARAATWHDTHLD LTYLNWY LLIYAATSRH QQSYDLPL
    (SEQ ID  (SEQ ID NO: 706) (SEQ ID NO: 778) (SEQ ID NO: 849) (SEQ ID NO: 920) (SEQ ID NO: 991)
    NO: 635)
    369_B07 DSYGMH WVANINYNGGYKS ARAATWHDTHLD VSYVNWY LVIYAATSLA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 707) (SEQ ID NO: 779) (SEQ ID NO: 850) (SEQ ID NO: 921) (SEQ ID NO: 992)
    NO: 636)
    369_B08 DSYGMH WVSSINYNGGYTS ARAATWHDTHLD LSYVNWY LLIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 708) (SEQ ID NO: 780) (SEQ ID NO: 851) (SEQ ID NO: 922) (SEQ ID NO: 993)
    NO: 637)
    369_C06 SSYSMH WVSSINYNGGYKS ARAATWHDTHLD LSYVNWY LLIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 709) (SEQ ID NO: 781) (SEQ ID NO: 852) (SEQ ID NO: 923) (SEQ ID NO: 994)
    NO: 638)
    369_C09 SSYGMH WVSSINYNGGYTG ARAATWHDTHLD VSYLNWY LVIYAATSRH QQSYDLPL
    (SEQ ID  (SEQ ID NO: 710) (SEQ ID NO: 782) (SEQ ID NO: 853) (SEQ ID NO: 924) (SEQ ID NO: 995)
    NO: 639)
    369_C11 SDYGMH WVAGINYNGGYTG ARAATWHDTHLD LSYLNWY LVIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 711) (SEQ ID NO: 783) (SEQ ID NO: 854) (SEQ ID NO: 925) (SEQ ID NO: 996)
    NO: 640)
    369_E03 SSYGMH WVAGINYNGGYTS ARAATWHDTHLD LSYVNWY LLIYAATSLA QQSYENPL
    (SEQ ID  (SEQ ID NO: 712) (SEQ ID NO: 784) (SEQ ID NO: 855) (SEQ ID NO: 926) (SEQ ID NO: 997)
    NO: 641)
    370_B06 SSYGMH WVAGINYNGGYTS ARAATWHDTHLD VSYVNWY LVIYAATSRA QQSYETPL
    (SEQ ID  (SEQ ID NO: 713) (SEQ ID NO: 785) (SEQ ID NO: 856) (SEQ ID NO: 927) (SEQ ID NO: 998)
    NO: 642)
    370_B07 SSYGMH WVANINYNSGYKS ARAATWHDTHLD LTYVNWY LLIYAATSRH QQSYSSPL
    (SEQ ID  (SEQ ID NO: 714) (SEQ ID NO: 786) (SEQ ID NO: 857) (SEQ ID NO: 928) (SEQ ID NO: 999)
    NO: 643)
    370_E12 DSYGMH WVAGINYNGGYTS ARAATWHDTHLD LSYVNWY LLIYAATSRA QQSYENPL
    (SEQ ID  (SEQ ID NO: 715) (SEQ ID NO: 787) (SEQ ID NO: 858) (SEQ ID NO: 929) (SEQ ID NO: 1000)
    NO: 644)
    370_H05 SSYGMH WVSNINYNGGYTS ARAATWHDTHLD LSYLNWY LLIYAASSLQ QQSDSLPL
    (SEQ ID  (SEQ ID NO: 716) (SEQ ID NO: 788) (SEQ ID NO: 859) (SEQ ID NO: 930) (SEQ ID NO: 1001)
    NO: 645)
    371_A05 SSYGMH WVSNINYNGGYKS ARAATWHDTHLD LTYLNWY LLIYAATSRA QQSDNLPL
    (SEQ ID  (SEQ ID NO: 717) (SEQ ID NO: 789) (SEQ ID NO: 860) (SEQ ID NO: 931) (SEQ ID NO: 1002)
    NO: 646)
    371_B02 DSYGMN WVSNINYNGGYTS ARAATWHDTHLD LTYVNWY LVIYAATSLA QQSYNNPL
    (SEQ ID  (SEQ ID NO: 718) (SEQ ID NO: 790) (SEQ ID NO: 861) (SEQ ID NO: 932) (SEQ ID NO: 1003)
    NO: 647)
    371_B11 SSYSMH WVASINYNSGYTS ARAATWHDTHLD LTYLNWY LLIYAATSRA QQSYELPL
    (SEQ ID  (SEQ ID NO: 719) (SEQ ID NO: 791) (SEQ ID NO: 862) (SEQ ID NO: 933) (SEQ ID NO: 1004)
    NO: 648)
    371_C02 DSYGMH WVAGINYNSGYTG ARAATWHDTHLD LTYVNWY LLIYAASSLQ QQSYDTPL
    (SEQ ID  (SEQ ID NO: 720) (SEQ ID NO: 792) (SEQ ID NO: 863) (SEQ ID NO: 934) (SEQ ID NO: 1005)
    NO: 649)
    371_D05 DDYGMH WVSGINYNGGYTS ARAATWHDTHLD LTYLNWY LLIYAASSLQ QQSYDSPL
    (SEQ ID  (SEQ ID NO: 721) (SEQ ID NO: 793) (SEQ ID NO: 864) (SEQ ID NO: 935) (SEQ ID NO: 1006)
    NO: 650)
    371_F07 SSYGMH WVAGINYNGGYTS ARAATWHDTHLD LTYLNWY LLIYAATSLA QQSDSNPL
    (SEQ ID  (SEQ ID NO: 722) (SEQ ID NO: 794) (SEQ ID NO: 865) (SEQ ID NO: 936) (SEQ ID NO: 1007)
    NO: 651)
    371_G07 SDYGMH WVAGINYNGGYTS ARAATWHDTHLD VSYVNWY LVIYAATSRA QQSYSLPL
    (SEQ ID  (SEQ ID NO: 723) (SEQ ID NO: 795) (SEQ ID NO: 866) (SEQ ID NO: 937) (SEQ ID NO: 1008)
    NO: 652)
    372_D07 SSYGMN WVAGINYNGGYTS ARAATWHDTHLD LSYLNWY LLIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 724) (SEQ ID NO: 796) (SEQ ID NO: 867) (SEQ ID NO: 938) (SEQ ID NO: 1009)
    NO: 653)
    373_B01 DSYGMH WVSGINYNGGYKS ARAATWHDTHLD LSYVNWY LVIYAATSRA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 725) (SEQ ID NO: 797) (SEQ ID NO: 868) (SEQ ID NO: 939) (SEQ ID NO: 1010)
    NO: 654)
    373_D11 SSYGMH WVAGINYNGGYTS ARAATWHDTHLD LTYVNWY LLIYAATSRA QQSYDNPL
    (SEQ ID  (SEQ ID NO: 726) (SEQ ID NO: 798) (SEQ ID NO: 869) (SEQ ID NO: 940) (SEQ ID NO: 1011)
    NO: 655)
    373_G06 SSYGMH WVASINYNSGYTG ARAATWHDTHLD LSYVNWY LLIYAATSLA QQSYNLPL
    (SEQ ID  (SEQ ID NO: 727) (SEQ ID NO: 799) (SEQ ID NO: 870) (SEQ ID NO: 941) (SEQ ID NO: 1012)
    NO: 656)
    374_A10 SSYGMH WVSGINYNGGYTS ARAATWHDTHLD LSYVNWY LLIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 728) (SEQ ID NO: 800) (SEQ ID NO: 871) (SEQ ID NO: 942) (SEQ ID NO: 1013)
    NO: 657)
    374_A12 DSYGMH WVSSINYNGGYTS ARAATWHDTHLD LTYLNWY LLIYAATSRA QQSDSNPL
    (SEQ ID  (SEQ ID NO: 729) (SEQ ID NO: 801) (SEQ ID NO: 872) (SEQ ID NO: 943) (SEQ ID NO: 1014)
    NO: 658)
    374_B01 DSYGMH WVAGINYNSGYTS ARAATWHDTHLD LSYLNWY LLIYAASSLQ QQSYDSPL
    (SEQ ID  (SEQ ID NO: 730) (SEQ ID NO: 802) (SEQ ID NO: 873) (SEQ ID NO: 944) (SEQ ID NO: 1015)
    NO: 659)
    374_B07 SSYGMH WVSSINYNGGYKS ARAATWHDTHLD ISYLNWY LLIYAATSLA QQSYESPL
    (SEQ ID  (SEQ ID NO: 731) (SEQ ID NO: 803) (SEQ ID NO: 874) (SEQ ID NO: 945) (SEQ ID NO: 1016)
    NO: 660)
    374_H02 SSYGMH WVASINYNGGYTS ARAATWHDTHLD LSYVNWY LLIYAATSLA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 732) (SEQ ID NO: 804) (SEQ ID NO: 875) (SEQ ID NO: 946) (SEQ ID NO: 1017)
    NO: 661)
    375_C03 DSYSMH WVSGINYNGGYTS ARAATWHDTHLD LSYVNWY LVIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 733) (SEQ ID NO: 805) (SEQ ID NO: 876) (SEQ ID NO: 947) (SEQ ID NO: 1018)
    NO: 662)
    375_C05 XSYGMN WVASINYNGGYKG ARAATWHDTHLD LSYLNWY LLIYAATSRA QQSYELPL
    (SEQ ID  (SEQ ID NO: 734) (SEQ ID NO: 806) (SEQ ID NO: 877) (SEQ ID NO: 948) (SEQ ID NO: 1019)
    NO: 663)
    375_D02 SSYSMN WVSNINYNGGYTS ARAATWHDTHLD LTYLNWY LLIYAASSLQ QQSYELPL
    (SEQ ID  (SEQ ID NO: 735) (SEQ ID NO: 807) (SEQ ID NO: 878) (SEQ ID NO: 949) (SEQ ID NO: 1020)
    NO: 664)
    375_G08 SSYGMH WVSGINYNGGYTS ARAATWHDTHLD SSYVNWY LLIYAVTSRA QQSYSTPL
    (SEQ ID  (SEQ ID NO: 736) (SEQ ID NO: 808) (SEQ ID NO: 879) (SEQ ID NO: 950) (SEQ ID NO: 1021)
    NO: 665)
    375_H04 SSYGMH WVAGINYNSGYTG ARAATWHDTHLD LSYLNWY LVIYAATSRA QQSYSNPL
    (SEQ ID  (SEQ ID NO: 737) (SEQ ID NO: 809) (SEQ ID NO: 880) (SEQ ID NO: 951) (SEQ ID NO: 1022)
    NO: 666)
    376_D08 DSYGMN WVANINYNSGYKS ARAATWHDTALD LTYLNWY LVIYYANNRP QQSYSNPL
    (SEQ ID  (SEQ ID NO: 738) (SEQ ID NO: 810) (SEQ ID NO: 881) (SEQ ID NO: 952) (SEQ ID NO: 1023)
    NO: 667)
    376_F09 DSYSMH WVSSINYNGGYKS ARAATWHDTHLD LTYVNWY LLIYAVTSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 739) (SEQ ID NO: 811) (SEQ ID NO: 882) (SEQ ID NO: 953) (SEQ ID NO: 1024)
    NO: 668)
    376_H12 SDYGMH WVASINYNGGYTS ARAATWHDTHLD ITYLNWY LVIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 740) (SEQ ID NO: 812) (SEQ ID NO: 883) (SEQ ID NO: 954) (SEQ ID NO: 1025)
    NO: 669)
  • The consensus sequences for each of these CDRs shown in FIG. 3B are as follows:
  • HCDR1:
    (SEQ ID NO: 6550)
    D/SS/DYG/SMH/N
    HCDR2:
    (SEQ ID NO: 6551)
    WVA/SS/G/NINYNG/SGYT/KS/G
    HCDR3:
    (SEQ ID NO: 6559)
    ARAATWHDTH/ALD
    LCDR1:
    (SEQ ID NO: 6561)
    L/V/I/SS/TYL/VNWY
    LCDR2:
    (SEQ ID NO: 6563)
    LL/VIYA/YA/T/VT/S/NS/NR/LA/P/Q
    LCDR3:
    (SEQ ID NO: 6565)
    QQSY/D/ND/E/S/NL/S/T/NPL
  • TABLE 2C
    Group III Antibody Sequences
    Ab VH sequence VL sequence
    365_C05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKGYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1205)
    NO: 1026)
    365_E10 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    SMNWVRQAPGKGLEWVSSINYNSGYKGYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1206)
    NO: 1027)
    365_E12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVSNINYNGGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1207)
    NO: 1028)
    365_F02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKGYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1208)
    NO: 1029)
    365_F03 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSSINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1209)
    NO: 1030)
    365_G03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    GMNWVRQAPGKGLEWVAGINYNSGYKGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1210)
    NO: 1031)
    365_G04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTGYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1211)
    NO: 1032)
    365_G05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNGGYKGYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1212)
    NO: 1033)
    365_G09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIITYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1213)
    NO: 1034)
    365_H07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISTYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1214)
    NO: 1035)
    366_A06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    SMNWVRQAPGKGLEWVASINYNGGYKSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1215)
    NO: 1036)
    366_A08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYKGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1216)
    NO: 1037)
    366_B05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYKSYADSV KPGKAPKLVIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1217)
    NO: 1038)
    366_B07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYATTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1218)
    NO: 1039)
    366_E01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVSNINYNGGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1219)
    NO: 1040)
    366_E08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    SMNWVRQAPGKGLEWVSNINYNGGYTSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSNPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1220)
    NO: 1041)
    366_F02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNSGYTGYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1221)
    NO: 1042)
    366_G12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMHWVRQAPGKGLEWVSGINYNSGYKGYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1222)
    NO: 1043)
    366_H04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVSNINYNGGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1223)
    NO: 1044)
    367_A03 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    GMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYATTSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1224)
    NO: 1045)
    367_A06 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMNWVRQAPGKGLEWVASINYNGGYKGYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1225)
    NO: 1046)
    367_A08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1226)
    NO: 1047)
    367_A10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIITYVNWYQQ
    GMNWVRQAPGKGLEWVAGINYNSGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1227)
    NO: 1048)
    367_A12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNSGYTSYADSV KPGKAPKLLIYAATSLHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNNPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1228)
    NO: 1049)
    367_B01 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1229)
    NO: 1050)
    367_B04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1230)
    NO: 1051)
    367_B12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVASINYNGGYKSYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1231)
    NO: 1052)
    367_C07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVSSINYNSGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNLPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1232)
    NO: 1053)
    367_C10 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1233)
    NO: 1054)
    367_D03 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIITYLNWYQQ
    SMNWVRQAPGKGLEWVSSINYNGGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1234)
    NO: 1055)
    367_D06 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1235)
    NO: 1056)
    367_D08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1236)
    NO: 1057)
    367_D12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    SMNWVRQAPGKGLEWVSSINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1237)
    NO: 1058)
    367_E05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1238)
    NO: 1059)
    367_F01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQ
    SMNWVRQAPGKGLEWVSNINYNGGYKSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1239)
    NO: 1060)
    367_G01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    GMNWVRQAPGKGLEWVASINYNSGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1240)
    NO: 1061)
    367_G04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNSGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1241)
    NO: 1062)
    367_H02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    GMNWVRQAPGKGLEWVSSINYNGGYTGYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1242)
    NO: 1063)
    367_H03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIITYVNWYQQ
    GMNWVRQAPGKGLEWVAGINYNSGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1243)
    NO: 1064)
    368_A03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTGYADSV KPGKAPKLLIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1244)
    NO: 1065)
    368_A04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKSYADSV KPGKAPKLVIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1245)
    NO: 1066)
    368_B09 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMNWVRQAPGKGLEWVSNINYNGGYKGYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1246)
    NO: 1067)
    368_C02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSISTYVNWYQQ
    SMNWVRQAPGKGLEWVANINYNGGYKGYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1247)
    NO: 1068)
    368_C08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1248)
    NO: 1069)
    368_E12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    GMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1249)
    NO: 1070)
    368_F09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNSGYTSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1250)
    NO: 1071)
    368_H02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    GMNWVRQAPGKGLEWVAGINYNSGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1251)
    NO: 1072)
    368_H05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    SMNWVRQAPGKGLEWVANINYNGGYKSYADSV KPGKAPKLVIYATTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1252)
    NO: 1073)
    369_A07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1253)
    NO: 1074)
    369_B05 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1254)
    NO: 1075)
    369_C05 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYATTSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1255)
    NO: 1076)
    369_D03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1256)
    NO: 1077)
    369_D07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNGGYKSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1257)
    NO: 1078)
    369_D09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVSNINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1258)
    NO: 1079)
    369_E06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1259)
    NO: 1080)
    369_F08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMHWVRQAPGKGLEWVSGINYNSGYTSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1260)
    NO: 1081)
    369_G08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSSINYNGGYKGYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1261)
    NO: 1082)
    370_A02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    GMNWVRQAPGKGLEWVAGINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1262)
    NO: 1083)
    370_B03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVANINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNNPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1263)
    NO: 1084)
    370_B11 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYTSYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQGYDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1264)
    NO: 1085)
    370_B12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKGYADSV KPGKAPKLVIYATTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1265)
    NO: 1086)
    370_D01 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSSINYNGGYTGYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1266)
    NO: 1087)
    370_D05 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSIITYLNWYQQ
    SMNWVRQAPGKGLEWVSNINYNGGYKGYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1267)
    NO: 1088)
    370_F03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMNWVRQAPGKGLEWVSSINYNSGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1268)
    NO: 1089)
    370_H02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1269)
    NO: 1090)
    370_H07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDSSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1270)
    NO: 1091)
    371_A10 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1271)
    NO: 1092)
    371_B03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV KPGKAPKLLIYATTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1272)
    NO: 1093)
    371_B04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKSYADSV KPGKAPKLVIYAVTSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1273)
    NO: 1094)
    371_B09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNSGYTGYADSV KPGKAPKLVIYATTSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1274)
    NO: 1095)
    371_B12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNSGYTSYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNNPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1275)
    NO: 1096)
    371_C01 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    GMHWVRQAPGKGLEWVSSINYNGGYTGYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1276)
    NO: 1097)
    371_C04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNSGYKGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1277)
    NO: 1098)
    371_C05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMHWVRQAPGKGLEWVANINYNGGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1278)
    NO: 1099)
    371_C12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNSGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1279)
    NO: 1100)
    371_D02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1280)
    NO: 1101)
    371_D04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTGYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1281)
    NO: 1102)
    371_E06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAVTSLHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1282)
    NO: 1103)
    371_E07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1283)
    NO: 1104)
    371_E10 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1284)
    NO: 1105)
    371_F10 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNSGYTSYADSV KPGKAPKLVIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1285)
    NO: 1106)
    371_F11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1286)
    NO: 1107)
    371_G02 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMNWVRQAPGKGLEWVASINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1287)
    NO: 1108)
    371_G04 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKSYADSV KPGKAPKLLIYAATSLHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1288)
    NO: 1109)
    371_G09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVANINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1289)
    NO: 1110)
    371_G11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMNWVRQAPGKGLEWVSNINYNSGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1290)
    NO: 1111)
    371_H04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVSNINYNGGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1291)
    NO: 1112)
    371_H05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNSGYKSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSLPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1292)
    NO: 1113)
    371_H06 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1293)
    NO: 1114)
    371_H08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYVNWYQQ
    GMNWVRQAPGKGLEWVASINYNGGYKGYADSV KPGKAPKLVIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1294)
    NO: 1115)
    371_H10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNSGYKSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1295)
    NO: 1116)
    372_B02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYTSYADSV KPGKAPKLLIYAVTSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1296)
    NO: 1117)
    372_C06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1297)
    NO: 1118)
    372_D03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNSGYKSYADSV KPGKAPKLVIYAVTSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1298)
    NO: 1119)
    372_E01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKGYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1299)
    NO: 1120)
    372_G12 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTGYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1300)
    NO: 1121)
    373_A01 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    GMNWVRQAPGKGLEWVSNINYNGGYTGYADSV KPGKAPKLVIYATTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNLPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1301)
    NO: 1122)
    373_A03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVANINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1302)
    NO: 1123)
    373_A05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYKSYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1303)
    NO: 1124)
    373_A09 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1304)
    NO: 1125)
    373_A11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSNY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVANINYNGGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1305)
    NO: 1126)
    373_A12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSSINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1306)
    NO: 1127)
    373_B05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    SMNWVRQAPGKGLEWVSNINYNGGYKSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSNPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1307)
    NO: 1128)
    373_B07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1308)
    NO: 1129)
    373_C03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1309)
    NO: 1130)
    373_C07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNSGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1310)
    NO: 1131)
    373_C10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1311)
    NO: 1132)
    373_D03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1312)
    NO: 1133)
    373_D12 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMNWVRQAPGKGLEWVSSINYNSGYKGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSLPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1313)
    NO: 1134)
    373_E10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1314)
    NO: 1135)
    373_F08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1315)
    NO: 1136)
    373_F11 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    GMHWVRQAPGKGLEWVSGINYNSGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNLPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1316)
    NO: 1137)
    373_F12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQ
    SMNWVRQAPGKGLEWVSNINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1317)
    NO: 1138)
    373_G08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSNINYNGGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1318)
    NO: 1139)
    373_H03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYKSYADSV KPGKAPKLLIYATTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1319)
    NO: 1140)
    373_H07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1320)
    NO: 1141)
    373_H09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIITYLNWYQQ
    GMNWVRQAPGKGLEWVASINYNSGYKSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1321)
    NO: 1142)
    374_A06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSSINYNSGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1322)
    NO: 1143)
    374_A09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVSSINYNGGYKGYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1323)
    NO: 1144)
    374_B03 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1324)
    NO: 1145)
    374_B05 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYTSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1325)
    NO: 1146)
    374_B08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1326)
    NO: 1147)
    374_B10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVSSINYNSGYTSYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1327)
    NO: 1148)
    374_C01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVSGINYNSGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1328)
    NO: 1149)
    374_C09 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    GMNWVRQAPGKGLEWVSSINYNGGYKGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1329)
    NO: 1150)
    374_C12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDNSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1330)
    NO: 1151)
    374_D03 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1331)
    NO: 1152)
    374_D05 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1332)
    NO: 1153)
    374_D06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1333)
    NO: 1154)
    374_D07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYKSYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1334)
    NO: 1155)
    374_D10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    GMHWVRQAPGKGLEWVASINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1335)
    NO: 1156)
    374_E10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1336)
    NO: 1157)
    374_E12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1337)
    NO: 1158)
    374_F06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSLHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1338)
    NO: 1159)
    374_F07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVASINYNGGYTGYADSV KPGKAPKLVIYAVTSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1339)
    NO: 1160)
    374_F08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKSYADSV KPGKAPKLVIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1340)
    NO: 1161)
    374_G03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1341)
    NO: 1162)
    374_G08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1342)
    NO: 1163)
    374_G09 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVRYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKGYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1343)
    NO: 1164)
    374_G10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    SMNWVRQAPGKGLEWVSSINYNSGYTSYADSV KPGKAPKLVIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1344)
    NO: 1165)
    374_G11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSIISYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1345)
    NO: 1166)
    374_H01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYENPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1346)
    NO: 1167)
    374_H11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSLHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSNPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1347)
    NO: 1168)
    375_A01 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1348)
    NO: 1169)
    375_A07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSSINYNSGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1349)
    NO: 1170)
    375_A08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1350)
    NO: 1171)
    375_A12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNSGYKSYADSV KPGKAPKLVIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1351)
    NO: 1172)
    375_B12 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1352)
    NO: 1173)
    375_C04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1353)
    NO: 1174)
    375_D01 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1354)
    NO: 1175)
    375_D10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1355)
    NO: 1176)
    375_E02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1356)
    NO: 1177)
    375_E03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVANINYNGGYTGYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1357)
    NO: 1178)
    375_E05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1358)
    NO: 1179)
    375_E06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYKSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1359)
    NO: 1180)
    375_E10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1360)
    NO: 1181)
    375_F02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVASINYNSGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1361)
    NO: 1182)
    375_F07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVSNINYNGGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1362)
    NO: 1183)
    375_F08 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    GMNWVRQAPGKGLEWVSSINYNSGYKSYADSV KPGKAPKLLIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1363)
    NO: 1184)
    375_G04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    GMNWVRQAPGKGLEWVASINYNSGYTGYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1364)
    NO: 1185)
    375_G05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAVTSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID No: 1365)
    NO: 1186)
    375_H05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMNWVRQAPGKGLEWVSNINYNGGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1366)
    NO: 1187)
    375_H07 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1367)
    NO: 1188)
    376_A03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    GMNWVRQAPGKGLEWVAGINYNGGYTGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1368)
    NO: 1189)
    376_B03 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNSGYKSYADSV KPGKAPKLVIYAVTSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDSPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1369)
    NO: 1190)
    376_B10 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKGYADSV KPGKAPKLVIYAATSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1370)
    NO: 1191)
    376_C04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMNWVRQAPGKGLEWVSNINYNGGYTGYADSV KPGKAPKLLIYAVTSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDNPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1371)
    NO: 1192)
    376_C08 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNSGYTGYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1372)
    NO: 1193)
    376_D07 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1373)
    NO: 1194)
    376_E02 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKGYADSV KPGKAPKLVIYAATSRHSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSDNTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1374)
    NO: 1195)
    376_E11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVSGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYELPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1375)
    NO: 1196)
    376_F01 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKSYADSV KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1376)
    NO: 1197)
    376_F06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    GMNWVRQAPGKGLEWVSGINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYETPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1377)
    NO: 1198)
    376_G05 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIISYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1378)
    NO: 1199)
    376_G06 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVNWYQQ
    GMNWVRQAPGKGLEWVAGINYNGGYTGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYNSPLTFGGGTKVEIK (SEQ
    ARGANWHDTHLDYWGQGTLVTVSS (SEQ ID ID NO: 1379)
    NO: 1200)
    376_G10 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSILSYVNWYQQ
    GMNWVRQAPGKGLEWVAGINYNGGYTSYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1380)
    NO: 1201)
    376_H01 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDY DIQMTQSPSSLSASVGDRVTITCRASQSILTYLNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKGYADSV KPGKAPKLLIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1381)
    NO: 1202)
    376_H04 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSY DIQMTQSPSSLSASVGDRVTITCRASQSILTYVNWYQQ
    SMNWVRQAPGKGLEWVAGINYNGGYKGYADSV KPGKAPKLVIYAATSRASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYDLPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1382)
    NO: 1203)
    376_H11 EVQLLESGGGLVQPGGSLRLSCAASGFTFDSY DIQMTQSPSSLSASVGDRVTITCRASQSISRYLNWYQQ
    SMNWVRQAPGKGLEWVSNINYNGGYTGYADSV KPGKAPKLLIYAVTSLASGVPSRFSGSGSGTDFTLTIS
    KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC SLQPEDFATYYCQQSYESPLTFGGGTKVEIK (SEQ
    ARGANWHDTALDYWGQGTLVTVSS (SEQ ID ID NO: 1383)
    NO: 1204)
  • Table 3C provides the amino acid sequences of the CDRs of the antibodies shown in Table 2C.
  • TABLE 3C
    CDR sequences for Group III antibodies
    Ab HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3
    365_C05 SDYSMN WVSGINYNGGYKG ARGANWHDTHLD LTYLNWY LLIYAATSRH QQSYNSPL
    (SEQ ID  (SEQ ID NO: 5643) (SEQ ID NO: 5822) (SEQ ID NO: 6001) (SEQ ID NO: 6180) (SEQ ID NO: 6359)
    NO: 5464)
    365_E10 DSYSMN WVSSINYNSGYKG ARGANWHDTHLD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5644) (SEQ ID NO: 5823) (SEQ ID NO: 6002) (SEQ ID NO: 6181) (SEQ ID NO: 6360)
    NO: 5465)
    365_E12 SDYGMN WVSNINYNGGYTG ARGANWHDTALD LTYLNWY LLIYAATSRA QQSYETPL
    (SEQ ID  (SEQ ID NO: 5645) (SEQ ID NO: 5824) (SEQ ID NO: 6003) (SEQ ID NO: 6182) (SEQ ID NO: 6361)
    NO: 5466)
    365_F02 SSYSMN WVSGINYNGGYKG ARGANWHDTHLD LTYVNWY LLIYAATSRH QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5646) (SEQ ID NO: 5825) (SEQ ID NO: 6004) (SEQ ID NO: 6183) (SEQ ID NO: 6362)
    NO: 5467)
    365_F03 DSYSMN WVSSINYNGGYTS ARGANWHDTHLD LSYLNWY LLIYAATSRA QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5647) (SEQ ID NO: 5826) (SEQ ID NO: 6005) (SEQ ID NO: 6184) (SEQ ID NO: 6363)
    NO: 5468)
    365_G03 SSYGMN WVAGINYNSGYKG ARGANWHDTHLD VSYLNWY LLIYAATSRA QQSYNTPL
    (SEQ ID  (SEQ ID NO: 5648) (SEQ ID NO: 5827) (SEQ ID NO: 6006) (SEQ ID NO: 6185) (SEQ ID NO: 6364)
    NO: 5469)
    365_G04 DSYSMN WVAGINYNGGYTG ARGANWHDTHLD VSYVNWY LVIYAATSLA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5649) (SEQ ID NO: 5828) (SEQ ID NO: 6007) (SEQ ID NO: 6186) (SEQ ID NO: 6365)
    NO: 5470)
    365_G05 SSYGMN WVSGINYNGGYKG ARGANWHDTALD LSYLNWY LVIYAATSLA QQSYENPL
    (SEQ ID  (SEQ ID NO: 5650) (SEQ ID NO: 5829) (SEQ ID NO: 6008) (SEQ ID NO: 6187) (SEQ ID NO: 6366)
    NO: 5471)
    365_G09 SSYSMN WVSGINYNGGYKS ARGANWHDTHLD ITYLNWY LVIYAATSRA QQSYNSPL
    (SEQ ID  (SEQ ID NO: 5651) (SEQ ID NO: 5830) (SEQ ID NO: 6009) (SEQ ID NO: 6188) (SEQ ID NO: 6367)
    NO: 5472)
    365_H07 DSYSMN WVSGINYNGGYTS ARGANWHDTHLD STYVNWY LLIYAATSRH QQSYENPL
    (SEQ ID  (SEQ ID NO: 5652) (SEQ ID NO: 5831) (SEQ ID NO: 6010) (SEQ ID NO: 6189) (SEQ ID NO: 6368)
    NO: 5473)
    366_A06 SDYSMN WVASINYNGGYKS ARGANWHDTHLD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5653) (SEQ ID NO: 5832) (SEQ ID NO: 6011) (SEQ ID NO: 6190) (SEQ ID NO: 6369)
    NO: 5474)
    366_A08 DDYSMN WVSGINYNSGYKG ARGANWHDTHLD VSYVNWY LVIYAATSRA QQSYNSPL
    (SEQ ID  (SEQ ID NO: 5654) (SEQ ID NO: 5833) (SEQ ID NO: 6012) (SEQ ID NO: 6191) (SEQ ID NO: 6370)
    NO: 5475)
    366_B05 SDYSMN WVSGINYNSGYKS ARGANWHDTALD SSYLNWY LVIYAVTSRA QQSYELPL
    (SEQ ID  (SEQ ID NO: 5655) (SEQ ID NO: 5834) (SEQ ID NO: 6013) (SEQ ID NO: 6192) (SEQ ID NO: 6371)
    NO: 5476)
    366_B07 SDYGMN WVSGINYNGGYTS ARGANWHDTHLD VSYLNWY LVIYATTSRA QQSYNSPL
    (SEQ ID  (SEQ ID NO: 5656) (SEQ ID NO: 5835) (SEQ ID NO: 6014) (SEQ ID NO: 6193) (SEQ ID NO: 6372)
    NO: 5477)
    366_E01 DSYGMN WVSNINYNGGYKS ARGANWHDTHLD LTYLNWY LLIYAATSRA QQSYSSPL
    (SEQ ID  (SEQ ID NO: 5657) (SEQ ID NO: 5836) (SEQ ID NO: 6015) (SEQ ID NO: 6194) (SEQ ID NO: 6373)
    NO: 5478)
    366_E08 SDYSMN WVSNINYNGGYTS ARGANWHDTHLD VTYLNWY LLIYAATSRH QQSYSNPL
    (SEQ ID  (SEQ ID NO: 5658) (SEQ ID NO: 5837) (SEQ ID NO: 6016) (SEQ ID NO: 6195) (SEQ ID NO: 6374)
    NO: 5479)
    366_F02 SSYGMN WVSGINYNSGYTG ARGANWHDTHLD LTYLNWY LVIYAATSRH QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5659) (SEQ ID NO: 5838) (SEQ ID NO: 6017) (SEQ ID NO: 6196) (SEQ ID NO: 6375)
    NO: 5480)
    366_G12 SSYGMH WVSGINYNSGYKG ARGANWHDTHLD LSYLNWY LLIYAATSRH QQSYNTPL
    (SEQ ID  (SEQ ID NO: 5660) (SEQ ID NO: 5839) (SEQ ID NO: 6018) (SEQ ID NO: 6197) (SEQ ID NO: 6376)
    NO: 5481)
    366_H04 DSYGMN WVSNINYNGGYKS ARGANWHDTHLD LTYLNWY LLIYAATSRA QQSYSSPL
    (SEQ ID  (SEQ ID NO: 5661) (SEQ ID NO: 5840) (SEQ ID NO: 6019) (SEQ ID NO: 6198) (SEQ ID NO: 6377)
    NO: 5482)
    367_A03 DSYGMN WVAGINYNGGYTS ARGANWHDTALD LTYVNWY LLIYATTSRH QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5662) (SEQ ID NO: 5841) (SEQ ID NO: 6020) (SEQ ID NO: 6199) (SEQ ID NO: 6378)
    NO: 5483)
    367_A06 DSYGMN WVASINYNGGYKG ARGANWHDTHLD LSYVNWY LLIYAATSRH QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5663) (SEQ ID NO: 5842) (SEQ ID NO: 6021) (SEQ ID NO: 6200) (SEQ ID NO: 6379)
    NO: 5484)
    367_A08 DSYGMN WVAGINYNGGYTS ARGANWHDTHLD LTYLNWY LLIYAVTSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5664) (SEQ ID NO: 5843) (SEQ ID NO: 6022) (SEQ ID NO: 6201) (SEQ ID NO: 6380)
    NO: 5485)
    367_A10 SSYGMN WVAGINYNSGYTS ARGANWHDTHLD ITYVNWY LLIYAATSLA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 5665) (SEQ ID NO: 5844) (SEQ ID NO: 6023) (SEQ ID NO: 6202) (SEQ ID NO: 6381)
    NO: 5486)
    367_A12 SSYGMN WVSGINYNSGYTS ARGANWHDTHLD LSYLNWY LLIYAATSLH QQSYNNPL
    (SEQ ID  (SEQ ID NO: 5666) (SEQ ID NO: 5845) (SEQ ID NO: 6024) (SEQ ID NO: 6203) (SEQ ID NO: 6382)
    NO: 5487)
    367_B01 SSYSMN WVAGINYNGGYKG ARGANWHDTALD SSYVNWY LVIYAATSRA QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5667) (SEQ ID NO: 5846) (SEQ ID NO: 6025) (SEQ ID NO: 6204) (SEQ ID NO: 6383)
    NO: 5488)
    367_B04 DSYSMN WVSGINYNSGYKS ARGANWHDTHLD LSYLNWY LLIYAATSRA QQSYELPL
    (SEQ ID  (SEQ ID NO: 5668) (SEQ ID NO: 5847) (SEQ ID NO: 6026) (SEQ ID NO: 6205) (SEQ ID NO: 6384)
    NO: 5489)
    367_B12 SSYGMH WVASINYNGGYKS ARGANWHDTHLD LSYVNWY LVIYAATSLA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5669) (SEQ ID NO: 5848) (SEQ ID NO: 6027) (SEQ ID NO: 6206) (SEQ ID NO: 6385)
    NO: 5490)
    367_C07 SSYSMN WVSSINYNSGYTG ARGANWHDTHLD LTYVNWY LLIYAATSRA QQSYNLPL
    (SEQ ID  (SEQ ID NO: 5670) (SEQ ID NO: 5849) (SEQ ID NO: 6028) (SEQ ID NO: 6207) (SEQ ID NO: 6386)
    NO: 5491)
    367_C10 DSYSMN WVSGINYNGGYTS ARGANWHDTALD VSYVNWY LLIYAVTSRA QQSYETPL
    (SEQ ID  (SEQ ID NO: 5671) (SEQ ID NO: 5850) (SEQ ID NO: 6029) (SEQ ID NO: 6208) (SEQ ID NO: 6387)
    NO: 5492)
    367_D03 DSYSMN WVSSINYNGGYTG ARGANWHDTHLD ITYLNWY LLIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5672) (SEQ ID NO: 5851) (SEQ ID NO: 6030) (SEQ ID NO: 6209) (SEQ ID NO: 6388)
    NO: 5493)
    367_D06 DSYSMN WVAGINYNGGYTS ARGANWHDTHLD STYLNWY LVIYAATSLA QQSYNSPL
    (SEQ ID  (SEQ ID NO: 5673) (SEQ ID NO: 5852) (SEQ ID NO: 6031) (SEQ ID NO: 6210) (SEQ ID NO: 6389)
    NO: 5494)
    367_D08 SDYSMN WVAGINYNGGYTS ARGANWHDTHLD LSYLNWY LVIYAATSRH QQSDDLPL
    (SEQ ID  (SEQ ID NO: 5674) (SEQ ID NO: 5853) (SEQ ID NO: 6032) (SEQ ID NO: 6211) (SEQ ID NO: 6390)
    NO: 5495)
    367_D12 SSYSMN WVSSINYNGGYTG ARGANWHDTHLD VSYVNWY LVIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5675) (SEQ ID NO: 5854) (SEQ ID NO: 6033) (SEQ ID NO: 6212) (SEQ ID NO: 6391)
    NO: 5496)
    367_E05 SSYGMN WVAGINYNGGYTS ARGANWHDTHLD LSYLNWY LLIYAATSRH QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5676) (SEQ ID NO: 5855) (SEQ ID NO: 6034) (SEQ ID NO: 6213) (SEQ ID NO: 6392)
    NO: 5497)
    367_F01 DSYSMN WVSNINYNGGYKS ARGANWHDTHLD ISYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5677) (SEQ ID NO: 5856) (SEQ ID NO: 6035) (SEQ ID NO: 6214) (SEQ ID NO: 6393)
    NO: 5498)
    367_G01 DSYGMN WVASINYNSGYTG ARGANWHDTHLD SSYLNWY LVIYAATSRA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 5678) (SEQ ID NO: 5857) (SEQ ID NO: 6036) (SEQ ID NO: 6215) (SEQ ID NO: 6394)
    NO: 5499)
    367_G04 SSYSMN WVAGINYNSGYTS ARGANWHDTHLD LSYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5679) (SEQ ID NO: 5858) (SEQ ID NO: 6037) (SEQ ID NO: 6216) (SEQ ID NO: 6395)
    NO: 5500)
    367_H02 DSYGMN WVSSINYNGGYTG ARGANWHDTHLD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5680) (SEQ ID NO: 5859) (SEQ ID NO: 6038) (SEQ ID NO: 6217) (SEQ ID NO: 6396)
    NO: 5501)
    367_H03 SSYGMN WVAGINYNSGYTS ARGANWHDTHLD ITYVNWY LLIYAATSLA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 5681) (SEQ ID NO: 5860) (SEQ ID NO: 6039) (SEQ ID NO: 6218) (SEQ ID NO: 6397)
    NO: 5502)
    368_A03 SSYSMN WVSGINYNGGYTG ARGANWHDTHLD ISYLNWY LLIYAVTSRA QQSYENPL
    (SEQ ID  (SEQ ID NO: 5682) (SEQ ID NO: 5861) (SEQ ID NO: 6040) (SEQ ID NO: 6219) (SEQ ID NO: 6398)
    NO: 5503)
    368_A04 DDYSMN WVAGINYNGGYKS ARGANWHDTHLD LTYLNWY LVIYAVTSRA QQSYELPL
    (SEQ ID  (SEQ ID NO: 5683) (SEQ ID NO: 5862) (SEQ ID NO: 6041) (SEQ ID NO: 6220) (SEQ ID NO: 6399)
    NO: 5504)
    368_B09 DSYGMN WVSNINYNGGYKG ARGANWHDTHLD LSYLNWY LLIYAATSRH QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5684) (SEQ ID NO: 5863) (SEQ ID NO: 6042) (SEQ ID NO: 6221) (SEQ ID NO: 6400)
    NO: 5505)
    368_C02 DDYSMN WVANINYNGGYKG ARGANWHDTHLD STYVNWY LLIYAATSLA QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5685) (SEQ ID NO: 5864) (SEQ ID NO: 6043) (SEQ ID NO: 6222) (SEQ ID NO: 6401)
    NO: 5506)
    368_C08 SDYSMN WVSGINYNGGYTS ARGANWHDTHLD LTYVNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5686) (SEQ ID NO: 5865) (SEQ ID NO: 6044) (SEQ ID NO: 6223) (SEQ ID NO: 6402)
    NO: 5507)
    368_E12 SDYGMN WVAGINYNGGYTS ARGANWHDTHLD VSYVNWY LVIYAVTSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5687) (SEQ ID NO: 5866) (SEQ ID NO: 6045) (SEQ ID NO: 6224) (SEQ ID NO: 6403)
    NO: 5508)
    368_F09 SSYGMN WVSGINYNSGYTS ARGANWHDTHLD LTYLNWY LLIYAASSLQ QQSYETPL
    (SEQ ID  (SEQ ID NO: 5688) (SEQ ID NO: 5867) (SEQ ID NO: 6046) (SEQ ID NO: 6225) (SEQ ID NO: 6404)
    NO: 5509)
    368_H02 SSYGMN WVAGINYNSGYTS ARGANWHDTALD VTYLNWY LVIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5689) (SEQ ID NO: 5868) (SEQ ID NO: 6047) (SEQ ID NO: 6226) (SEQ ID NO: 6405)
    NO: 5510)
    368_H05 SSYSMN WVANINYNGGYKS ARGANWHDTHLD VSYVNWY LVIYATTSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5690) (SEQ ID NO: 5869) (SEQ ID NO: 6048) (SEQ ID NO: 6227) (SEQ ID NO: 6406)
    NO: 5511)
    369_A07 SSYSMN WVAGINYNGGYKG ARGANWHDTALD LSYLNWY LVIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5691) (SEQ ID NO: 5870) (SEQ ID NO: 6049) (SEQ ID NO: 6228) (SEQ ID NO: 6407)
    NO: 5512)
    369_B05 DSYSMN WVSGINYNGGYKS ARGANWHDTHLD ISYLNWY LLIYAATSLA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5692) (SEQ ID NO: 5871) (SEQ ID NO: 6050) (SEQ ID NO: 6229) (SEQ ID NO: 6408)
    NO: 5513)
    369_C05 DSYSMN WVAGINYNGGYTS ARGANWHDTALD SSYVNWY LVIYATTSRH QQSYNSPL
    (SEQ ID  (SEQ ID NO: 5693) (SEQ ID NO: 5872) (SEQ ID NO: 6051) (SEQ ID NO: 6230) (SEQ ID NO: 6409)
    NO: 5514)
    369_D03 SSYSMN WVSGINYNGGYTS ARGANWHDTHLD LTYLNWY LVIYAATSRA QQSYENPL
    (SEQ ID  (SEQ ID NO: 5694) (SEQ ID NO: 5873) (SEQ ID NO: 6052) (SEQ ID NO: 6231) (SEQ ID NO: 6410)
    NO: 5515)
    369_D07 SSYGMN WVSGINYNGGYKS ARGANWHDTHLD VSYLNWY LVIYAATSRA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 5695) (SEQ ID NO: 5874) (SEQ ID NO: 6053) (SEQ ID NO: 6232) (SEQ ID NO: 6411)
    NO: 5516)
    369_D09 SDYGMN WVSNINYNGGYTS ARGANWHDTALD LTYLNWY LLIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5696) (SEQ ID NO: 5875) (SEQ ID NO: 6054) (SEQ ID NO: 6233) (SEQ ID NO: 6412)
    NO: 5517)
    369_E06 SSYGMN WVSGINYNGGYTS ARGANWHDTALD ISYLNWY LVIYAATSRH QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5697) (SEQ ID NO: 5876) (SEQ ID NO: 6055) (SEQ ID NO: 6234) (SEQ ID NO: 6413)
    NO: 5518)
    369_F08 SDYGMH WVSGINYNSGYTS ARGANWHDTALD LSYLNWY LLIYAASSLQ QQSYDLPL
    (SEQ ID  (SEQ ID NO: 5698) (SEQ ID NO: 5877) (SEQ ID NO: 6056) (SEQ ID NO: 6235) (SEQ ID NO: 6414)
    NO: 5519)
    369_G08 DSYSMN WVSSINYNGGYKG ARGANWHDTHLD LTYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5699) (SEQ ID NO: 5878) (SEQ ID NO: 6057) (SEQ ID NO: 6236) (SEQ ID NO: 6415)
    NO: 5520)
    370_A02 DSYGMN WVAGINYNGGYTG ARGANWHDTALD VTYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5700) (SEQ ID NO: 5879) (SEQ ID NO: 6058) (SEQ ID NO: 6237) (SEQ ID NO: 6416)
    NO: 5521)
    370_B03 SSYSMN WVANINYNGGYTG ARGANWHDTALD LSYLNWY LVIYAATSRA QQSYNNPL
    (SEQ ID  (SEQ ID NO: 5701) (SEQ ID NO: 5880) (SEQ ID NO: 6059) (SEQ ID NO: 6238) (SEQ ID NO: 6417)
    NO: 5522)
    370_B11 DSYSMN WVSGINYNSGYTS ARGANWHDTHLD LSYLNWY LVIYAATSRH QQGYDLPL
    (SEQ ID  (SEQ ID NO: 5702) (SEQ ID NO: 5881) (SEQ ID NO: 6060) (SEQ ID NO: 6239) (SEQ ID NO: 6418)
    NO: 5523)
    370_B12 SDYSMN WVSGINYNGGYKG ARGANWHDTALD LSYVNWY LVIYATTSRA QQSYETPL
    (SEQ ID  (SEQ ID NO: 5703) (SEQ ID NO: 5882) (SEQ ID NO: 6061) (SEQ ID NO: 6240) (SEQ ID NO: 6419)
    NO: 5524)
    370_D01 SSYSMN WVSSINYNGGYTG ARGANWHDTALD LSYLNWY LLIYAATSRH QQSYNTPL
    (SEQ ID  (SEQ ID NO: 5704) (SEQ ID NO: 5883) (SEQ ID NO: 6062) (SEQ ID NO: 6241) (SEQ ID NO: 6420)
    NO: 5525)
    370_D05 DDYSMN WVSNINYNGGYKG ARGANWHDTALD ITYLNWY LVIYAATSRH QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5705) (SEQ ID NO: 5884) (SEQ ID NO: 6063) (SEQ ID NO: 6242) (SEQ ID NO: 6421)
    NO: 5526)
    370_F03 SSYGMN WVSSINYNSGYKS ARGANWHDTALD LSYVNWY LLIYAATSRA QQSYENPL
    (SEQ ID  (SEQ ID NO: 5706) (SEQ ID NO: 5885) (SEQ ID NO: 6064) (SEQ ID NO: 6243) (SEQ ID NO: 6422)
    NO: 5527)
    370_H02 DSYSMN WVSGINYNSGYTS ARGANWHDTHLD LTYLNWY LLIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5707) (SEQ ID NO: 5886) (SEQ ID NO: 6065) (SEQ ID NO: 6244) (SEQ ID NO: 6423)
    NO: 5528)
    370_H07 SSYSMN WVAGINYNGGYKS ARGANWHDTALD LSYLNWY LLIYAATSLA QQSDSSPL
    (SEQ ID  (SEQ ID NO: 5708) (SEQ ID NO: 5887) (SEQ ID NO: 6066) (SEQ ID NO: 6245) (SEQ ID NO: 6424)
    NO: 5529)
    371_A10 DDYSMN WVSGINYNGGYKG ARGANWHDTALD VSYLNWY LVIYAATSRA QQSYENPL
    (SEQ ID  (SEQ ID NO: 5709) (SEQ ID NO: 5888) (SEQ ID NO: 6067) (SEQ ID NO: 6246) (SEQ ID NO: 6425)
    NO: 5530)
    371_B03 SSYGMH WVASINYNGGYTS ARGANWHDTHLD LSYVNWY LLIYATTSRA QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5710) (SEQ ID NO: 5889) (SEQ ID NO: 6068) (SEQ ID NO: 6247) (SEQ ID NO: 6426)
    NO: 5531)
    371_B04 SSYSMN WVSGINYNGGYKS ARGANWHDTALD LSYLNWY LVIYAVTSRH QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5711) (SEQ ID NO: 5890) (SEQ ID NO: 6069) (SEQ ID NO: 6248) (SEQ ID NO: 6427)
    NO: 5532)
    371_B09 SSYSMN WVAGINYNSGYTG ARGANWHDTHLD LSYVNWY LVIYATTSLA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5712) (SEQ ID NO: 5891) (SEQ ID NO: 6070) (SEQ ID NO: 6249) (SEQ ID NO: 6428)
    NO: 5533)
    371_B12 SDYSMN WVAGINYNSGYTS ARGANWHDTALD VTYLNWY LVIYAATSRH QQSYNNPL
    (SEQ ID  (SEQ ID NO: 5713) (SEQ ID NO: 5892) (SEQ ID NO: 6071) (SEQ ID NO: 6250) (SEQ ID NO: 6429)
    NO: 5534)
    371_C01 SSYGMH WVSSINYNGGYTG ARGANWHDTHLD VSYLNWY LLIYAATSRH QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5714) (SEQ ID NO: 5893) (SEQ ID NO: 6072) (SEQ ID NO: 6251) (SEQ ID NO: 6430)
    NO: 5535)
    371_C04 DSYGMN WVSGINYNSGYKG ARGANWHDTALD LSYLNWY LLIYAATSRA QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5715) (SEQ ID NO: 5894) (SEQ ID NO: 6073) (SEQ ID NO: 6252) (SEQ ID NO: 6431)
    NO: 5536)
    371_C05 SDYGMH WVANINYNGGYTG ARGANWHDTALD LSYLNWY LLIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5716) (SEQ ID NO: 5895) (SEQ ID NO: 6074) (SEQ ID NO: 6253) (SEQ ID NO: 6432)
    NO: 5537)
    371_C12 SSYSMN WVAGINYNSGYKS ARGANWHDTHLD VSYVNWY LLIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5717) (SEQ ID NO: 5896) (SEQ ID NO: 6075) (SEQ ID NO: 6254) (SEQ ID NO: 6433)
    NO: 5538)
    371_D02 DDYSMN WVAGINYNGGYKS ARGANWHDTALD VTYLNWY LLIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5718) (SEQ ID NO: 5897) (SEQ ID NO: 6076) (SEQ ID NO: 6255) (SEQ ID NO: 6434)
    NO: 5539)
    371_D04 DDYSMN WVAGINYNGGYTG ARGANWHDTHLD VSYVNWY LLIYAATSLA QQSYENPL
    (SEQ ID  (SEQ ID NO: 5719) (SEQ ID NO: 5898) (SEQ ID NO: 6077) (SEQ ID NO: 6256) (SEQ ID NO: 6435)
    NO: 5540)
    371_E06 SSYSMN WVSGINYNGGYTS ARGANWHDTALD STYLNWY LLIYAVTSLH QQSYESPL
    (SEQ ID  (SEQ ID NO: 5720) (SEQ ID NO: 5899) (SEQ ID NO: 6078) (SEQ ID NO: 6257) (SEQ ID NO: 6436)
    NO: 5541)
    371_E07 DSYSMN WVAGINYNGGYTS ARGANWHDTALD ISYLNWY LLIYAATSLA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5721) (SEQ ID NO: 5900) (SEQ ID NO: 6079) (SEQ ID NO: 6258) (SEQ ID NO: 6437)
    NO: 5542)
    371_E10 DSYSMN WVAGINYNGGYTS ARGANWHDTALD STYLNWY LLIYAVTSRA QQSYNSPL
    (SEQ ID  (SEQ ID NO: 5722) (SEQ ID NO: 5901) (SEQ ID NO: 6080) (SEQ ID NO: 6259) (SEQ ID NO: 6438)
    NO: 5543)
    371_F10 DSYGMN WVSGINYNSGYTS ARGANWHDTALD SSYLNWY LVIYAVTSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5723) (SEQ ID NO: 5902) (SEQ ID NO: 6081) (SEQ ID NO: 6260) (SEQ ID NO: 6439)
    NO: 5544)
    371_F11 SSYSMN WVSGINYNGGYTS ARGANWHDTALD ISYVNWY LLIYAVTSRA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 5724) (SEQ ID NO: 5903) (SEQ ID NO: 6082) (SEQ ID NO: 6261) (SEQ ID NO: 6440)
    NO: 5545)
    371_G02 DSYGMN WVASINYNGGYTS ARGANWHDTHLD LSYLNWY LLIYAATSRA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 5725) (SEQ ID NO: 5904) (SEQ ID NO: 6083) (SEQ ID NO: 6262) (SEQ ID NO: 6441)
    NO: 5546)
    371_G04 DSYSMN WVSGINYNGGYKS ARGANWHDTALD LSYLNWY LLIYAATSLH QQSYESPL
    (SEQ ID  (SEQ ID NO: 5726) (SEQ ID NO: 5905) (SEQ ID NO: 6084) (SEQ ID NO: 6263) (SEQ ID NO: 6442)
    NO: 5547)
    371_G09 SSYSMN WVANINYNGGYTG ARGANWHDTALD LSYLNWY LVIYAATSRA QQSDSTPL
    (SEQ ID  (SEQ ID NO: 5727) (SEQ ID NO: 5906) (SEQ ID NO: 6085) (SEQ ID NO: 6264) (SEQ ID NO: 6443)
    NO: 5548)
    371_G11 SSYGMN WVSNINYNSGYTS ARGANWHDTALD LSYVNWY LLIYAATSLA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5728) (SEQ ID NO: 5907) (SEQ ID NO: 6086) (SEQ ID NO: 6265) (SEQ ID NO: 6444)
    NO: 5549)
    371_H04 SSYGMN WVSNINYNGGYTG ARGANWHDTALD LTYLNWY LLIYAATSRA QQSYNSPL
    (SEQ ID  (SEQ ID NO: 5729) (SEQ ID NO: 5908) (SEQ ID NO: 6087) (SEQ ID NO: 6266) (SEQ ID NO: 6445)
    NO: 5550)
    371_H05 SSYGMN WVSGINYNSGYKS ARGANWHDTALD ISYLNWY LLIYAATSLA QQSYSLPL
    (SEQ ID  (SEQ ID NO: 5730) (SEQ ID NO: 5909) (SEQ ID NO: 6088) (SEQ ID NO: 6267) (SEQ ID NO: 6446)
    NO: 5551)
    371_H06 DSYGMN WVSGINYNGGYTS ARGANWHDTALD SSYLNWY LVIYAVTSRA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 5731) (SEQ ID NO: 5910) (SEQ ID NO: 6089) (SEQ ID NO: 6268) (SEQ ID NO: 6447)
    NO: 5552)
    371_H08 SSYGMN WVASINYNGGYKG ARGANWHDTHLD ISYVNWY LVIYAVTSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5732) (SEQ ID NO: 5911) (SEQ ID NO: 6090) (SEQ ID NO: 6269) (SEQ ID NO: 6448)
    NO: 5553)
    371_H10 SSYSMN WVAGINYNSGYKS ARGANWHDTHLD STYLNWY LLIYAATSRH QQSYENPL
    (SEQ ID  (SEQ ID NO: 5733) (SEQ ID NO: 5912) (SEQ ID NO: 6091) (SEQ ID NO: 6270) (SEQ ID NO: 6449)
    NO: 5554)
    372_B02 SSYSMN WVSGINYNSGYTS ARGANWHDTALD LSYVNWY LLIYAVTSLA QQSYETPL
    (SEQ ID  (SEQ ID NO: 5734) (SEQ ID NO: 5913) (SEQ ID NO: 6092) (SEQ ID NO: 6271) (SEQ ID NO: 6450)
    NO: 5555)
    372_C06 SDYSMN WVSGINYNGGYTS ARGANWHDTALD VSYVNWY LLIYAATSRA QQSYSSPL
    (SEQ ID  (SEQ ID NO: 5735) (SEQ ID NO: 5914) (SEQ ID NO: 6093) (SEQ ID NO: 6272) (SEQ ID NO: 6451)
    NO: 5556)
    372_D03 SSYSMN WVAGINYNSGYKS ARGANWHDTALD LSYVNWY LVIYAVTSRH QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5736) (SEQ ID NO: 5915) (SEQ ID NO: 6094) (SEQ ID NO: 6273) (SEQ ID NO: 6452)
    NO: 5557)
    372_E01 DDYSMN WVSGINYNGGYKG ARGANWHDTALD VSYLNWY LVIYAATSRH QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5737) (SEQ ID NO: 5916) (SEQ ID NO: 6095) (SEQ ID NO: 6274) (SEQ ID NO: 6453)
    NO: 5558)
    372_G12 DSYSMN WVAGINYNGGYTG ARGANWHDTHLD LTYLNWY LVIYAATSRH QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5738) (SEQ ID NO: 5917) (SEQ ID NO: 6096) (SEQ ID NO: 6275) (SEQ ID NO: 6454)
    NO: 5559)
    373_A01 SSYGMN WVSNINYNGGYTG ARGANWHDTHLD VTYLNWY LVIYATTSRA QQSYNLPL
    (SEQ ID  (SEQ ID NO: 5739) (SEQ ID NO: 5918) (SEQ ID NO: 6097) (SEQ ID NO: 6276) (SEQ ID NO: 6455)
    NO: 5560)
    373_A03 SDYSMN WVANINYNGGYTG ARGANWHDTALD LSYLNWY LVIYAATSRA QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5740) (SEQ ID NO: 5919) (SEQ ID NO: 6098) (SEQ ID NO: 6277) (SEQ ID NO: 6456)
    NO: 5561)
    373_A05 SDYSMN WVSGINYNSGYKS ARGANWHDTHLD LSYVNWY LVIYAATSRH QQSYESPL
    (SEQ ID  (SEQ ID NO: 5741) (SEQ ID NO: 5920) (SEQ ID NO: 6099) (SEQ ID NO: 6278) (SEQ ID NO: 6457)
    NO: 5562)
    373_A09 DSYSMN WVAGINYNGGYTS ARGANWHDTALD LTYLNWY LLIYAATSLA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5742) (SEQ ID NO: 5921) (SEQ ID NO: 6100) (SEQ ID NO: 6279) (SEQ ID NO: 6458)
    NO: 5563)
    373_A11 SNYGMN WVANINYNGGYTG ARGANWHDTALD LTYLNWY LLIYAATSRA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 5743) (SEQ ID NO: 5922) (SEQ ID NO: 6101) (SEQ ID NO: 6280) (SEQ ID NO: 6459)
    NO: 5564)
    373_A12 SSYSMN WVSSINYNGGYTS ARGANWHDTALD LTYLNWY LVIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5744) (SEQ ID NO: 5923) (SEQ ID NO: 6102) (SEQ ID NO: 6281) (SEQ ID NO: 6460)
    NO: 5565)
    373_B05 SDYSMN WVSNINYNGGYKS ARGANWHDTALD VTYLNWY LVIYAATSRA QQSYSNPL
    (SEQ ID  (SEQ ID NO: 5745) (SEQ ID NO: 5924) (SEQ ID NO: 6103) (SEQ ID NO: 6282) (SEQ ID NO: 6461)
    NO: 5566)
    373_B07 DSYSMN WVSGINYNGGYTS ARGANWHDTALD LTYVNWY LVIYAATSRA QQSYELPL
    (SEQ ID  (SEQ ID NO: 5746) (SEQ ID NO: 5925) (SEQ ID NO: 6104) (SEQ ID NO: 6283) (SEQ ID NO: 6462)
    NO: 5567)
    373_C03 SSYSMN WVSGINYNGGYKS ARGANWHDTALD VTYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5747) (SEQ ID NO: 5926) (SEQ ID NO: 6105) (SEQ ID NO: 6284) (SEQ ID NO: 6463)
    NO: 5568)
    373_C07 DSYSMN WVAGINYNSGYTS ARGANWHDTHLD LTYLNWY LVIYAATSRA QQSYETPL
    (SEQ ID  (SEQ ID NO: 5748) (SEQ ID NO: 5927) (SEQ ID NO: 6106) (SEQ ID NO: 6285) (SEQ ID NO: 6464)
    NO: 5569)
    373_C10 SSYSMN WVAGINYNGGYTS ARGANWHDTALD LTYVNWY LLIYAATSRA QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5749) (SEQ ID NO: 5928) (SEQ ID NO: 6107) (SEQ ID NO: 6286) (SEQ ID NO: 6465)
    NO: 5570)
    373_D03 SSYSMN WVSGINYNGGYTS ARGANWHDTALD VSYLNWY LLIYAATSLA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5750) (SEQ ID NO: 5929) (SEQ ID NO: 6108) (SEQ ID NO: 6287) (SEQ ID NO: 6466)
    NO: 5571)
    373_D12 DSYSMN WVSSINYNSGYKG ARGANWHDTHLD LSYVNWY LLIYAATSRA QQSYSLPL
    (SEQ ID  (SEQ ID NO: 5751) (SEQ ID NO: 5930) (SEQ ID NO: 6109) (SEQ ID NO: 6288) (SEQ ID NO: 6467)
    NO: 5572)
    373_E10 SDYSMN WVSGINYNGGYTS ARGANWHDTALD LTYVNWY LVIYAATSRH QQSYETPL
    (SEQ ID  (SEQ ID NO: 5752) (SEQ ID NO: 5931) (SEQ ID NO: 6110) (SEQ ID NO: 6289) (SEQ ID NO: 6468)
    NO: 5573)
    373_F08 SSYSMN WVSGINYNGGYTS ARGANWHDTALD LTYLNWY LLIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5753) (SEQ ID NO: 5932) (SEQ ID NO: 6111) (SEQ ID NO: 6290) (SEQ ID NO: 6469)
    NO: 5574)
    373_F11 DSYGMH WVSGINYNSGYTS ARGANWHDTHLD VSYVNWY LLIYAATSRA QQSYNLPL
    (SEQ ID  (SEQ ID NO: 5754) (SEQ ID NO: 5933) (SEQ ID NO: 6112) (SEQ ID NO: 6291) (SEQ ID NO: 6470)
    NO: 5575)
    373_F12 SSYSMN WVSNINYNGGYTG ARGANWHDTALD STYLNWY LVIYAATSRA QQSYETPL
    (SEQ ID  (SEQ ID NO: 5755) (SEQ ID NO: 5934) (SEQ ID NO: 6113) (SEQ ID NO: 6292) (SEQ ID NO: 6471)
    NO: 5576)
    373_G08 DSYSMN WVSNINYNGGYTS ARGANWHDTALD LTYLNWY LLIYAATSLA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5756) (SEQ ID NO: 5935) (SEQ ID NO: 6114) (SEQ ID NO: 6293) (SEQ ID NO: 6472)
    NO: 5577)
    373_H03 SSYSMN WVSGINYNSGYKS ARGANWHDTALD LSYLNWY LLIYATTSRA QQSYENPL
    (SEQ ID  (SEQ ID NO: 5757) (SEQ ID NO: 5936) (SEQ ID NO: 6115) (SEQ ID NO: 6294) (SEQ ID NO: 6473)
    NO: 5578)
    373_H07 SSYSMN WVAGINYNGGYTS ARGANWHDTHLD VTYLNWY LLIYAASSLQ QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5758) (SEQ ID NO: 5937) (SEQ ID NO: 6116) (SEQ ID NO: 6295) (SEQ ID NO: 6474)
    NO: 5579)
    373_H09 SSYGMN WVASINYNSGYKS ARGANWHDTHLD ITYLNWY LVIYAATSRA QQSDDSPL
    (SEQ ID  (SEQ ID NO: 5759) (SEQ ID NO: 5938) (SEQ ID NO: 6117) (SEQ ID NO: 6296) (SEQ ID NO: 6475)
    NO: 5580)
    374_A06 SSYSMN WVSSINYNSGYTS ARGANWHDTHLD LSYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5760) (SEQ ID NO: 5939) (SEQ ID NO: 6118) (SEQ ID NO: 6297) (SEQ ID NO: 6476)
    NO: 5581)
    374_A09 SSYSMN WVSSINYNGGYKG ARGANWHDTHLD LTYVNWY LLIYAATSLA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5761) (SEQ ID NO: 5940) (SEQ ID NO: 6119) (SEQ ID NO: 6298) (SEQ ID NO: 6477)
    NO: 5582)
    374_B03 DSYSMN WVSGINYNGGYTS ARGANWHDTALD LTYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5762) (SEQ ID NO: 5941) (SEQ ID NO: 6120) (SEQ ID NO: 6299) (SEQ ID NO: 6478)
    NO: 5583)
    374_B05 DSYSMN WVSGINYNSGYTS ARGANWHDTALD VSYLNWY LLIYAATSRH QQSYESPL
    (SEQ ID  (SEQ ID NO: 5763) (SEQ ID NO: 5942) (SEQ ID NO: 6121) (SEQ ID NO: 6300) (SEQ ID NO: 6479)
    NO: 5584)
    374_B08 DSYSMN WVAGINYNGGYTS ARGANWHDTALD VSYVNWY LLIYAATSRH QQSYELPL
    (SEQ ID  (SEQ ID NO: 5764) (SEQ ID NO: 5943) (SEQ ID NO: 6122) (SEQ ID NO: 6301) (SEQ ID NO: 6480)
    NO: 5585)
    374_B10 SSYSMN WVSSINYNSGYTS ARGANWHDTHLD LTYVNWY LVIYAATSLA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5765) (SEQ ID NO: 5944) (SEQ ID NO: 6123) (SEQ ID NO: 6302) (SEQ ID NO: 6481)
    NO: 5586)
    374_C01 DSYGMN WVSGINYNSGYKS ARGANWHDTALD LTYLNWY LLIYAATSRA QQSYETPL
    (SEQ ID  (SEQ ID NO: 5766) (SEQ ID NO: 5945) (SEQ ID NO: 6124) (SEQ ID NO: 6303) (SEQ ID NO: 6482)
    NO: 5587)
    374_C09 DSYGMN WVSSINYNGGYKG ARGANWHDTHLD VSYLNWY LVIYAATSRA QQSYELPL
    (SEQ ID  (SEQ ID NO: 5767) (SEQ ID NO: 5946) (SEQ ID NO: 6125) (SEQ ID NO: 6304) (SEQ ID NO: 6483)
    NO: 5588)
    374_C12 SSYSMN WVAGINYNGGYKS ARGANWHDTALD LTYLNWY LVIYAATSRA QQSDNSPL
    (SEQ ID  (SEQ ID NO: 5768) (SEQ ID NO: 5947) (SEQ ID NO: 6126) (SEQ ID NO: 6305) (SEQ ID NO: 6484)
    NO: 5589)
    374_D03 DSYSMN WVAGINYNGGYKS ARGANWHDTHLD VTYLNWY LLIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5769) (SEQ ID NO: 5948) (SEQ ID NO: 6127) (SEQ ID NO: 6306) (SEQ ID NO: 6485)
    NO: 5590)
    374_D05 DSYSMN WVSGINYNSGYTG ARGANWHDTHLD LTYLNWY LLIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5770) (SEQ ID NO: 5949) (SEQ ID NO: 6128) (SEQ ID NO: 6307) (SEQ ID NO: 6486)
    NO: 5591)
    374_D06 SSYSMN WVSGINYNGGYTS ARGANWHDTALD LSYVNWY LVIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5771) (SEQ ID NO: 5950) (SEQ ID NO: 6129) (SEQ ID NO: 6308) (SEQ ID NO: 6487)
    NO: 5592)
    374_D07 DSYSMN WVSGINYNSGYKS ARGANWHDTALD VSYLNWY LVIYAATSLA QQSYNSPL
    (SEQ ID  (SEQ ID NO: 5772) (SEQ ID NO: 5951) (SEQ ID NO: 6130) (SEQ ID NO: 6309) (SEQ ID NO: 6488)
    NO: 5593)
    374_D10 SSYGMH WVASINYNGGYTS ARGANWHDTHLD LTYVNWY LLIYAATSRA QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5773) (SEQ ID NO: 5952) (SEQ ID NO: 6131) (SEQ ID NO: 6310) (SEQ ID NO: 6489)
    NO: 5594)
    374_E10 SSYSMN WVSGINYNGGYKS ARGANWHDTALD LSYLNWY LLIYAATSRH QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5774) (SEQ ID NO: 5953) (SEQ ID NO: 6132) (SEQ ID NO: 6311) (SEQ ID NO: 6490)
    NO: 5595)
    374_E12 SSYSMN WVSGINYNGGYKS ARGANWHDTALD LSYLNWY LVIYAATSRA QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5775) (SEQ ID NO: 5954) (SEQ ID NO: 6133) (SEQ ID NO: 6312) (SEQ ID NO: 6491)
    NO: 5596)
    374_F06 SSYSMN WVSGINYNGGYTS ARGANWHDTALD ISYVNWY LVIYAATSLH QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5776) (SEQ ID NO: 5955) (SEQ ID NO: 6134) (SEQ ID NO: 6313) (SEQ ID NO: 6492)
    NO: 5597)
    374_F07 DSYSMN WVASINYNGGYTG ARGANWHDTHLD LSYLNWY LVIYAVTSLA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5777) (SEQ ID NO: 5956) (SEQ ID NO: 6135) (SEQ ID NO: 6314) (SEQ ID NO: 6493)
    NO: 5598)
    374_F08 DSYSMN WVSGINYNGGYKS ARGANWHDTALD LTYVNWY LVIYAVTSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5778) (SEQ ID NO: 5957) (SEQ ID NO: 6136) (SEQ ID NO: 6315) (SEQ ID NO: 6494)
    NO: 5599)
    374_G03 SDYSMN WVSGINYNGGYTS ARGANWHDTALD SSYLNWY LVIYAATSRA QQSDDTPL
    (SEQ ID  (SEQ ID NO: 5779) (SEQ ID NO: 5958) (SEQ ID NO: 6137) (SEQ ID NO: 6316) (SEQ ID NO: 6495)
    NO: 5600)
    374_G08 DSYSMN WVSGINYNGGYTS ARGANWHDTALD LTYVNWY LVIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5780) (SEQ ID NO: 5959) (SEQ ID NO: 6138) (SEQ ID NO: 6317) (SEQ ID NO: 6496)
    NO: 5601)
    374_G09 SSYSMN WVAGINYNGGYKG ARGANWHDTHLD VRYLNWY LVIYAATSLA QQSYELPL
    (SEQ ID  (SEQ ID NO: 5781) (SEQ ID NO: 5960) (SEQ ID NO: 6139) (SEQ ID NO: 6318) (SEQ ID NO: 6497)
    NO: 5602)
    374_G10 SSYSMN WVSSINYNSGYTS ARGANWHDTHLD VSYLNWY LVIYAVTSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5782) (SEQ ID NO: 5961) (SEQ ID NO: 6140) (SEQ ID NO: 6319) (SEQ ID NO: 6498)
    NO: 5603)
    374_G11 SDYSMN WVSGINYNGGYTS ARGANWHDTALD ISYVNWY LVIYAATSLA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5783) (SEQ ID NO: 5962) (SEQ ID NO: 6141) (SEQ ID NO: 6320) (SEQ ID NO: 6499)
    NO: 5604)
    374_H01 DSYSMN WVAGINYNGGYTS ARGANWHDTHLD LSYLNWY LVIYAATSLA QQSYENPL
    (SEQ ID  (SEQ ID NO: 5784) (SEQ ID NO: 5963) (SEQ ID NO: 6142) (SEQ ID NO: 6321) (SEQ ID NO: 6500)
    NO: 5605)
    374_H11 SSYSMN WVSGINYNGGYTS ARGANWHDTALD ISYVNWY LVIYAATSLH QQSYSNPL
    (SEQ ID  (SEQ ID NO: 5785) (SEQ ID NO: 5964) (SEQ ID NO: 6143) (SEQ ID NO: 6322) (SEQ ID NO: 6501)
    NO: 5606)
    375_A01 DSYSMN WVAGINYNGGYTS ARGANWHDTALD LSYLNWY LVIYAATSRA QQSYNTPL
    (SEQ ID  (SEQ ID NO: 5786) (SEQ ID NO: 5965) (SEQ ID NO: 6144) (SEQ ID NO: 6323) (SEQ ID NO: 6502)
    NO: 5607)
    375_A07 DSYSMN WVSSINYNSGYTG ARGANWHDTHLD LTYLNWY LLIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5787) (SEQ ID NO: 5966) (SEQ ID NO: 6145) (SEQ ID NO: 6324) (SEQ ID NO: 6503)
    NO: 5608)
    375_A08 SSYSMN WVAGINYNGGYTG ARGANWHDTALD VTYLNWY LLIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5788) (SEQ ID NO: 5967) (SEQ ID NO: 6146) (SEQ ID NO: 6325) (SEQ ID NO: 6504)
    NO: 5609)
    375_A12 SSYSMN WVSGINYNSGYKS ARGANWHDTALD LSYLNWY LVIYAVTSRA QQSYETPL
    (SEQ ID  (SEQ ID NO: 5789) (SEQ ID NO: 5968) (SEQ ID NO: 6147) (SEQ ID NO: 6326) (SEQ ID NO: 6505)
    NO: 5610)
    375_B12 DSYSMN WVAGINYNGGYKS ARGANWHDTALD VTYLNWY LLIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5790) (SEQ ID NO: 5969) (SEQ ID NO: 6148) (SEQ ID NO: 6327) (SEQ ID NO: 6506)
    NO: 5611)
    375_C04 SDYSMN WVAGINYNGGYTS ARGANWHDTALD LTYLNWY LVIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5791) (SEQ ID NO: 5970) (SEQ ID NO: 6149) (SEQ ID NO: 6328) (SEQ ID NO: 6507)
    NO: 5612)
    375_D01 SSYSMN WVSGINYNGGYTG ARGANWHDTALD LTYLNWY LVIYAATSRA QQSYETPL
    (SEQ ID  (SEQ ID NO: 5792) (SEQ ID NO: 5971) (SEQ ID NO: 6150) (SEQ ID NO: 6329) (SEQ ID NO: 6508)
    NO: 5613)
    375_D10 SSYSMN WVAGINYNGGYTS ARGANWHDTALD LTYVNWY LLIYAATSRA QQSDDSPL
    (SEQ ID  (SEQ ID NO: 5793) (SEQ ID NO: 5972) (SEQ ID NO: 6151) (SEQ ID NO: 6330) (SEQ ID NO: 6509)
    NO: 5614)
    375_E02 SDYSMN WVAGINYNGGYTS ARGANWHDTALD LTYLNWY LLIYAATSRA QQSYSSPL
    (SEQ ID  (SEQ ID NO: 5794) (SEQ ID NO: 5973) (SEQ ID NO: 6152) (SEQ ID NO: 6331) (SEQ ID NO: 6510)
    NO: 5615)
    375_E03 SDYSMN WVANINYNGGYTG ARGANWHDTHLD LTYLNWY LVIYAATSLA QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5795) (SEQ ID NO: 5974) (SEQ ID NO: 6153) (SEQ ID NO: 6332) (SEQ ID NO: 6511)
    NO: 5616)
    375_E05 SSYSMN WVAGINYNGGYTS ARGANWHDTALD LSYLNWY LVIYAATSLA QQSYSSPL
    (SEQ ID  (SEQ ID NO: 5796) (SEQ ID NO: 5975) (SEQ ID NO: 6154) (SEQ ID NO: 6333) (SEQ ID NO: 6512)
    NO: 5617)
    375_E06 SSYSMN WVSGINYNGGYKS ARGANWHDTALD LSYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5797) (SEQ ID NO: 5976) (SEQ ID NO: 6155) (SEQ ID NO: 6334) (SEQ ID NO: 6513)
    NO: 5618)
    375_E10 SSYSMN WVSGINYNGGYTS ARGANWHDTALD LSYLNWY LVIYAATSRA QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5798) (SEQ ID NO: 5977) (SEQ ID NO: 6156) (SEQ ID NO: 6335) (SEQ ID NO: 6514)
    NO: 5619)
    375_F02 SSYSMN WVASINYNSGYTS ARGANWHDTHLD LSYLNWY LLIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5799) (SEQ ID NO: 5978) (SEQ ID NO: 6157) (SEQ ID NO: 6336) (SEQ ID NO: 6515)
    NO: 5620)
    375_F07 SDYSMN WVSNINYNGGYTG ARGANWHDTALD LSYLNWY LLIYAATSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5800) (SEQ ID NO: 5979) (SEQ ID NO: 6158) (SEQ ID NO: 6337) (SEQ ID NO: 6516)
    NO: 5621)
    375_F08 SSYGMN WVSSINYNSGYKS ARGANWHDTHLD LSYLNWY LLIYAATSRH QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5801) (SEQ ID NO: 5980) (SEQ ID NO: 6159) (SEQ ID NO: 6338) (SEQ ID NO: 6517)
    NO: 5622)
    375_G04 SSYGMN WVASINYNSGYTG ARGANWHDTHLD VSYVNWY LLIYAATSLA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5802) (SEQ ID NO: 5981) (SEQ ID NO: 6160) (SEQ ID NO: 6339) (SEQ ID NO: 6518)
    NO: 5623)
    375_G05 SSYSMN WVAGINYNGGYTS ARGANWHDTALD VSYLNWY LLIYAVTSRA QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5803) (SEQ ID NO: 5982) (SEQ ID NO: 6161) (SEQ ID NO: 6340) (SEQ ID NO: 6519)
    NO: 5624)
    375_H05 SSYSMN WVSNINYNGGYTG ARGANWHDTALD LSYVNWY LLIYAATSRA QQSYDTPL
    (SEQ ID  (SEQ ID NO: 5804) (SEQ ID NO: 5983) (SEQ ID NO: 6162) (SEQ ID NO: 6341) (SEQ ID NO: 6520)
    NO: 5625)
    375_H07 SSYSMN WVAGINYNGGYTS ARGANWHDTALD LSYLNWY LLIYAATSLA QQSYSSPL
    (SEQ ID  (SEQ ID NO: 5805) (SEQ ID NO: 5984) (SEQ ID NO: 6163) (SEQ ID NO: 6342) (SEQ ID NO: 6521)
    NO: 5626)
    376_A03 SSYGMN WVAGINYNGGYTG ARGANWHDTALD LTYLNWY LLIYAATSRA QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5806) (SEQ ID NO: 5985) (SEQ ID NO: 6164) (SEQ ID NO: 6343) (SEQ ID NO: 6522)
    NO: 5627)
    376_B03 SSYSMN WVAGINYNSGYKS ARGANWHDTALD LSYVNWY LVIYAVTSRH QQSYDSPL
    (SEQ ID  (SEQ ID NO: 5807) (SEQ ID NO: 5986) (SEQ ID NO: 6165) (SEQ ID NO: 6344) (SEQ ID NO: 6523)
    NO: 5628)
    376_B10 SDYSMN WVAGINYNGGYKG ARGANWHDTALD LSYLNWY LVIYAATSLA QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5808) (SEQ ID NO: 5987) (SEQ ID NO: 6166) (SEQ ID NO: 6345) (SEQ ID NO: 6524)
    NO: 5629)
    376_C04 SSYGMN WVSNINYNGGYTG ARGANWHDTALD LSYVNWY LLIYAVTSRH QQSYDNPL
    (SEQ ID  (SEQ ID NO: 5809) (SEQ ID NO: 5988) (SEQ ID NO: 6167) (SEQ ID NO: 6346) (SEQ ID NO: 6525)
    NO: 5630)
    376_C08 DSYSMN WVAGINYNSGYTG ARGANWHDTHLD LSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5810) (SEQ ID NO: 5989) (SEQ ID NO: 6168) (SEQ ID NO: 6347) (SEQ ID NO: 6526)
    NO: 5631)
    376_D07 DSYSMN WVSGINYNGGYTS ARGANWHDTHLD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5811) (SEQ ID NO: 5990) (SEQ ID NO: 6169) (SEQ ID NO: 6348) (SEQ ID NO: 6527)
    NO: 5632)
    376_E02 SSYSMN WVAGINYNGGYKG ARGANWHDTALD LSYVNWY LVIYAATSRH QQSDNTPL
    (SEQ ID  (SEQ ID NO: 5812) (SEQ ID NO: 5991) (SEQ ID NO: 6170) (SEQ ID NO: 6349) (SEQ ID NO: 6528)
    NO: 5633)
    376_E11 SSYSMN WVSGINYNGGYTS ARGANWHDTALD LTYVNWY LVIYAATSRA QQSYELPL
    (SEQ ID  (SEQ ID NO: 5813) (SEQ ID NO: 5992) (SEQ ID NO: 6171) (SEQ ID NO: 6350) (SEQ ID NO: 6529)
    NO: 5634)
    376_F01 SDYSMN WVAGINYNGGYKS ARGANWHDTALD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5814) (SEQ ID NO: 5993) (SEQ ID NO: 6172) (SEQ ID NO: 6351) (SEQ ID NO: 6530)
    NO: 5635)
    376_F06 SSYGMN WVSGINYNGGYTG ARGANWHDTHLD LTYVNWY LVIYAATSRA QQSYETPL
    (SEQ ID  (SEQ ID NO: 5815) (SEQ ID NO: 5994) (SEQ ID NO: 6173) (SEQ ID NO: 6352) (SEQ ID NO: 6531)
    NO: 5636)
    376_G05 SSYSMN WVAGINYNGGYTS ARGANWHDTALD ISYVNWY LVIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5816) (SEQ ID NO: 5995) (SEQ ID NO: 6174) (SEQ ID NO: 6353) (SEQ ID NO: 6532)
    NO: 5637)
    376_G06 SSYGMN WVAGINYNGGYTG ARGANWHDTHLD VSYVNWY LVIYAATSRA QQSYNSPL
    (SEQ ID  (SEQ ID NO: 5817) (SEQ ID NO: 5996) (SEQ ID NO: 6175) (SEQ ID NO: 6354) (SEQ ID NO: 6533)
    NO: 5638)
    376_G10 DSYGMN WVAGINYNGGYTS ARGANWHDTALD LSYVNWY LLIYAATSRA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5818) (SEQ ID NO: 5997) (SEQ ID NO: 6176) (SEQ ID NO: 6355) (SEQ ID NO: 6534)
    NO: 5639)
    376_H01 SDYSMN WVAGINYNGGYKG ARGANWHDTALD LTYLNWY LLIYAATSRA QQSYSTPL
    (SEQ ID  (SEQ ID NO: 5819) (SEQ ID NO: 5998) (SEQ ID NO: 6177) (SEQ ID NO: 6356) (SEQ ID NO: 6535)
    NO: 5640)
    376_H04 SSYSMN WVAGINYNGGYKG ARGANWHDTALD LTYVNWY LVIYAATSRA QQSYDLPL
    (SEQ ID  (SEQ ID NO: 5820) (SEQ ID NO: 5999) (SEQ ID NO: 6178) (SEQ ID NO: 6357) (SEQ ID NO: 6536)
    NO: 5641)
    376_H11 DSYSMN WVSNINYNGGYTG ARGANWHDTALD SRYLNWY LLIYAVTSLA QQSYESPL
    (SEQ ID  (SEQ ID NO: 5821) (SEQ ID NO: 6000) (SEQ ID NO: 6179) (SEQ ID NO: 6358) (SEQ ID NO: 6537)
    NO: 5642)
  • The consensus sequences for each of these CDRs shown in FIG. 3C are as follows:
  • HCDR1:
    (SEQ ID NO: 6566)
    S/DS/DYS/GMN/H
    HCDR2:
    (SEQ ID NO: 6594)
    WVS/AG/S/NINYNG/SGYT/KS/G
    HCDR3:
    (SEQ ID NO: 6543)
    ARGANWHDTA/HLD
    LCDR1:
    (SEQ ID NO: 6569)
    L/V/S/IS/TYL/VNWY
    LCDR2:
    (SEQ ID NO:)
    LL/VIYAA/V/TT/SSR/LA/H/Q
    LCDR3:
    (SEQ ID NO: 6571)
    QQSY/DD/E/S/NS/T/N/LPL
  • TABLE 2D
    Group IV Antibody Sequences
    Ab VH sequence VL sequence
    365_A08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    SSYSMNWVRQAPGKGLEWVASINYNGGYK WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSDNTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1477)
    TVSS (SEQ ID NO: 1384)
    365_A09 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    SSYGMHWVRQAPGKGLEWVASINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1478)
    TVSS (SEQ ID NO: 1385)
    365_C02 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSISTYLN
    DSYSMNWVRQAPGKGLEWVSNINYNGGYK WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1479)
    TVSS (SEQ ID NO: 1386)
    365_C04 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    DSYSMNWVRQAPGKGLEWVANINYNGGYK WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1480)
    TVSS (SEQ ID NO: 1387)
    365_D02 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    SSYSMHWVRQAPGKGLEWVASINYNGGYT WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1481)
    TVSS (SEQ ID NO: 1388)
    365_D07 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    SSYGMNWVRQAPGKGLEWVSSINYNSGYK WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1482)
    TVSS (SEQ ID NO: 1389)
    365_D10 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSISTYLN
    SSYSMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1483)
    TVSS (SEQ ID NO: 1390)
    365_E11 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    DDYSMNWVRQAPGKGLEWVSSINYNGGYK WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1484)
    TVSS (SEQ ID NO: 1391)
    365_F05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVTYVN
    SSYGMNWVRQAPGKGLEWVASINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1485)
    TVSS (SEQ ID NO: 1392)
    365_H05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    SSYGMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLLIYAATSLHSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1486)
    TVSS (SEQ ID NO: 1393)
    366_D08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    SSYGMHWVRQAPGKGLEWVSNINYNGGYK WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1487)
    TVSS (SEQ ID NO: 1394)
    366_F08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    SSYGMNWVRQAPGKGLEWVSSINYNGGYT WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1488)
    TVSS (SEQ ID NO: 1395)
    366_G09 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    DDYSMNWVRQAPGKGLEWVASINYNSGYT WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1489)
    TVSS (SEQ ID NO: 1396)
    367_A02 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    DSYGMNWVRQAPGKGLEWVSSINYNSGYK WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1490)
    TVSS (SEQ ID NO: 1397)
    367_B06 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    SSYSMNWVRQAPGKGLEWVANINYNGGYT WYQQKPGKAPKLVIYAATSLHSGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1491)
    TVSS (SEQ ID NO: 1398)
    367_C08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    DSYSMHWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSDSNPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1492)
    TVSS (SEQ ID NO: 1399)
    367_D05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    SDYSMNWVRQAPGKGLEWVSSINYNGGYK WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1493)
    TVSS (SEQ ID NO: 1400)
    367_D09 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    DSYGMNWVRQAPGKGLEWVASINYNGGYK WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1494)
    TVSS (SEQ ID NO: 1401)
    367_E07 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    SDYSMNWVRQAPGKGLEWVSSINYNGGYK WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1495)
    TVSS (SEQ ID NO: 1402)
    367_E12 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    SSYGMHWVRQAPGKGLEWVASINYNGGYT WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1496)
    TVSS (SEQ ID NO: 1403)
    367_F09 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    DSYSMHWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSDSNPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1497)
    TVSS (SEQ ID NO: 1404)
    367_H05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    SSYGMHWVRQAPGKGLEWVASINYNSGYK WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1498)
    TVSS (SEQ ID NO: 1405)
    367_H10 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    SSYGMNWVRQAPGKGLEWVASINYNGGYT WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1499)
    TVSS (SEQ ID NO: 1406)
    368_B02 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    SSYGMNWVRQAPGKGLEWVSGINYNSGYK WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1500)
    TVSS (SEQ ID NO: 1407)
    368_C11 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    SDYSMNWVRQAPGKGLEWVSSINYNSGYK WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1501)
    TVSS (SEQ ID NO: 1408)
    368_D02 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSISTYLN
    DDYGMNWVRQAPGKGLEWVSNINYNGGYT WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1502)
    TVSS (SEQ ID NO: 1409)
    368_D12 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    SSYGMNWVRQAPGKGLEWVSSINYNGGYT WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1503)
    TVSS (SEQ ID NO: 1410)
    368_F06 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    DDYSMHWVRQAPGKGLEWVANINYNSGYT WYQQKPGKAPKLVIYATTSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1504)
    TVSS (SEQ ID NO: 1411)
    368_G03 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    SSYSMNWVRQAPGKGLEWVSGINYNSGYT WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTALDYWGQGTLV KVEIK (SEQ ID NO: 1505)
    TVSS (SEQ ID NO: 1412)
    368_G10 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    SSYSMHWVRQAPGKGLEWVSSINYNGGYT WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1506)
    TVSS (SEQ ID NO: 1413)
    368_H06 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    DSYGMHWVRQAPGKGLEWVANINYNGGYK WYQQKPGKAPKLLIYATTSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1507)
    TVSS (SEQ ID NO: 1414)
    368_H11 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    DSYGMHWVRQAPGKGLEWVASINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSDDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1508)
    TVSS (SEQ ID NO: 1415)
    369_A11 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    DSYGMNWVRQAPGKGLEWVANINYNGGYK WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1509)
    TVSS (SEQ ID NO: 1416)
    369_C12 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYGMNWVRQAPGKGLEWVANINYNGGYK WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1510)
    TVSS (SEQ ID NO: 1417)
    369_D08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SDYSMNWVRQAPGKGLEWVASINYNGGYK WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1511)
    TVSS (SEQ ID NO: 1418)
    369_E05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SDYGMNWVRQAPGKGLEWVANINYNGGYK WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1512)
    TVSS (SEQ ID NO: 1419)
    369_E08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    SSYSMNWVRQAPGKGLEWVASINYNSGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1513)
    TVSS (SEQ ID NO: 1420)
    369_F05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    SSYSMNWVRQAPGKGLEWVSGINYNGGYK WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQGYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1514)
    TVSS (SEQ ID NO: 1421)
    369_F09 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    SSYGMHWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1515)
    TVSS (SEQ ID NO: 1422)
    369_G05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    SSYSMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1516)
    TVSS (SEQ ID NO: 1423)
    369_H02 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    DDYSMNWVRQAPGKGLEWVSNINYNGGYK WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1517)
    TVSS (SEQ ID NO: 1424)
    369_H08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    SSYSMNWVRQAPGKGLEWVAGINYNSGYK WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1518)
    TVSS (SEQ ID NO: 1425)
    369_H12 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVTYVN
    SSYSMNWVRQAPGKGLEWVAGINYNGGYK WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1519)
    TVSS (SEQ ID NO: 1426)
    370_B08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    SDYSMNWVRQAPGKGLEWVANINYNGGYT WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1520)
    TVSS (SEQ ID NO: 1427)
    370_C06 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    SSYSMNWVRQAPGKGLEWVANINYNGGYK WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1521)
    TVSS (SEQ ID NO: 1428)
    370_C07 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    SSYSMNWVRQAPGKGLEWVANINYNGGYK WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1522)
    TVSS (SEQ ID NO: 1429)
    370_C10 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    DSYSMNWVRQAPGKGLEWVSNINYNSGYK WYQQKPGKAPKLLIYATTSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1523)
    TVSS (SEQ ID NO: 1430)
    370_D03 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    SSYSMNWVRQAPGKGLEWVASINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1524)
    TVSS (SEQ ID NO: 1431)
    370_D09 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    SDYSMNWVRQAPGKGLEWVSGINYNSGYT WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1525)
    TVSS (SEQ ID NO: 1432)
    370_E04 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYSMNWVRQAPGKGLEWVANINYNGGYK WYQQKPGKAPKLLIYAVTSLHSGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1526)
    TVSS (SEQ ID NO: 1433)
    370_E05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSISTYLN
    SSYGMNWVRQAPGKGLEWVSNINYNGGYK WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1527)
    TVSS (SEQ ID NO: 1434)
    370_F01 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    SSYGMNWVRQAPGKGLEWVSNINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1528)
    TVSS (SEQ ID NO: 1435)
    370_F02 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    DSYGMNWVRQAPGKGLEWVANINYNGGYT WYQQKPGKAPKLLIYAVTSRHSGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1529)
    TVSS (SEQ ID NO: 1436)
    370_F12 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    SDYSMNWVRQAPGKGLEWVANINYNGGYT WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1530)
    TVSS (SEQ ID NO: 1437)
    370_G08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SDYSMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1531)
    TVSS (SEQ ID NO: 1438)
    370_H04 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    SSYSMNWVRQAPGKGLEWVSNINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1532)
    TVSS (SEQ ID NO: 1439)
    370_H06 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    DDYSMNWVRQAPGKGLEWVANINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1533)
    TVSS (SEQ ID NO: 1440)
    371_B01 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    DSYSMNWVRQAPGKGLEWVSNINYNSGYT WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1534)
    TVSS (SEQ ID NO: 1441)
    371_C06 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    SSYSMNWVRQAPGKGLEWVSSINYNGGYT WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1535)
    TVSS (SEQ ID NO: 1442)
    371_C07 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    DSYGMNWVRQAPGKGLEWVSNINYNGGYT WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTALDYWGQGTLV KVEIK (SEQ ID NO: 1536)
    TVSS (SEQ ID NO: 1443)
    371_E05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    SSYSMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1537)
    TVSS (SEQ ID NO: 1444)
    371_E08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    SSYSMNWVRQAPGKGLEWVSNINYNSGYK WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1538)
    TVSS (SEQ ID NO: 1445)
    371_E09 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SDYSMNWVRQAPGKGLEWVSGINYNSGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1539)
    TVSS (SEQ ID NO: 1446)
    371_E12 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    DSYSMNWVRQAPGKGLEWVSGINYNSGYK WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1540)
    TVSS (SEQ ID NO: 1447)
    371_F03 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    SSYSMNWVRQAPGKGLEWVSGINYNGGYT WYQQKPGKAPKLLIYAATSLHSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1541)
    TVSS (SEQ ID NO: 1448)
    371_F09 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYSMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1542)
    TVSS (SEQ ID NO: 1449)
    371_G01 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SDYSMNWVRQAPGKGLEWVSNINYNGGYT WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1543)
    TVSS (SEQ ID NO: 1450)
    371_H11 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYSMNWVRQAPGKGLEWVSGINYNGGYK WYQQKPGKAPKLLIYATTSRHSGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1544)
    TVSS (SEQ ID NO: 1451)
    372_B09 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYSMNWVRQAPGKGLEWVSSINYNSGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1545)
    TVSS (SEQ ID NO: 1452)
    372_E08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    SDYSMNWVRQAPGKGLEWVSNINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1546)
    TVSS (SEQ ID NO: 1453)
    372_F02 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYGMHWVRQAPGKGLEWVASINYNGGYT WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1547)
    TVSS (SEQ ID NO: 1454)
    372_H11 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    SSYGMHWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1548)
    TVSS (SEQ ID NO: 1455)
    373_A06 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    SSYSMNWVRQAPGKGLEWVSGINYNGGYK WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1549)
    TVSS (SEQ ID NO: 1456)
    373_B09 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    DSYSMNWVRQAPGKGLEWVSGINYNGGYK WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1550)
    TVSS (SEQ ID NO: 1457)
    373_D06 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    SSYSMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1551)
    TVSS (SEQ ID NO: 1458)
    373_F07 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    SSYSMNWVRQAPGKGLEWVSGINYNSGYK WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1552)
    TVSS (SEQ ID NO: 1459)
    373_G02 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    SSYSMNWVRQAPGKGLEWVSGINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1553)
    TVSS (SEQ ID NO: 1460)
    374_A04 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYSMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1554)
    TVSS (SEQ ID NO: 1461)
    374_A05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVRYLN
    SDYGMNWVRQAPGKGLEWVANINYNGGYK WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1555)
    TVSS (SEQ ID NO: 1462)
    374_C10 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    SSYSMNWVRQAPGKGLEWVSSINYNGGYK WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1556)
    TVSS (SEQ ID NO: 1463)
    374_D04 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    SSYSMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1557)
    TVSS (SEQ ID NO: 1464)
    374_D09 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    DSYGMNWVRQAPGKGLEWVANINYNGGYK WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1558)
    TVSS (SEQ ID NO: 1465)
    374_G05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    SSYSMNWVRQAPGKGLEWVSNINYNSGYK WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1559)
    TVSS (SEQ ID NO: 1466)
    374_H05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    SSYSMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1560)
    TVSS (SEQ ID NO: 1467)
    375_A03 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    DSYSMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1561)
    TVSS (SEQ ID NO: 1468)
    375_B03 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYSMNWVRQAPGKGLEWVAGINYNGGYT WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1562)
    TVSS (SEQ ID NO: 1469)
    375 C01 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    SSYGMNWVRQAPGKGLEWVSSINYNGGYK WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1563)
    TVSS (SEQ ID NO: 1470)
    375_C11 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    SSYSMNWVRQAPGKGLEWVSSINYNGGYT WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1564)
    TVSS (SEQ ID NO: 1471)
    375_F10 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYSMNWVRQAPGKGLEWVSGINYNGGYT WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1565)
    TVSS (SEQ ID NO: 1472)
    375_H08 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYSMNWVRQAPGKGLEWVSGINYNGGYT WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1566)
    TVSS (SEQ ID NO: 1473)
    376_A02 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    SSYSMNWVRQAPGKGLEWVAGINYNGGYK WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1567)
    TVSS (SEQ ID NO: 1474)
    376_A05 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYSMNWVRQAPGKGLEWVAGINYNSGYK WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    GYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1568)
    TVSS (SEQ ID NO: 1475)
    376_A07 EVQLLESGGGLVQPGGSLRLSCAASGFTF DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    SSYSMNWVRQAPGKGLEWVSGINYNGGYK WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    SYADSVKGRFTISRDNSKNTLYLQMNSLR TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    AEDTAVYYCARGATWHDTHLDYWGQGTLV KVEIK (SEQ ID NO: 1569)
    TVSS (SEQ ID NO: 1476)
  • Table 3D provides the amino acid sequences of the CDRs of the antibodies shown in Table 2D.
  • TABLE 3D
    CDR sequences for Group IV antibodies
    Ab HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3
    365_A08 SSYSMN WVASINYNGGYKS ARGATWHDTHLD ITYLNWY LVIYAATSRA QQSDNTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1663) 1756) NO: NO: 1942) NO:
    1570) 1849) 2035)
    365_A09 SSYGMH WVASINYNGGYTS ARGATWHDTHLD LSYVNWY LLIYAATSRA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1664) 1757) NO: NO: 1943) NO:
    1571) 1850) 2036)
    365_C02 DSYSMN WVSNINYNGGYKG ARGATWHDTHLD STYLNWY LVIYAATSRH QQSYENPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1665) 1758) NO: NO: 1944) NO:
    1572) 1851) 2037)
    365_C04 DSYSMN WVANINYNGGYKG ARGATWHDTHLD LTYLNWY LVIYAATSLA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1666) 1759) NO: NO: 1945) NO:
    1573) 1852) 2038)
    365_D02 SSYSMH WVASINYNGGYTS ARGATWHDTHLD VTYLNWY LLIYAATSLA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1667) 1760) NO: NO: 1946) NO:
    1574) 1853) 2039)
    365_D07 SSYGMN WVSSINYNSGYKS ARGATWHDTHLD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1668) 1761) NO: NO: 1947) NO:
    1575) 1854) 2040)
    365_D10 SSYSMN WVAGINYNGGYTG ARGATWHDTHLD STYLNWY LLIYAATSRA QQSYESPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1669) 1762) NO: NO: 1948) NO:
    1576) 1855) 2041)
    365_E11 DDYSMN WVSSINYNGGYKS ARGATWHDTHLD SSYLNWY LLIYAASSLQ QQSYNTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1670) 1763) NO: NO: 1949) NO:
    1577) 1856) 2042)
    365_F05 SSYGMN WVASINYNGGYTS ARGATWHDTHLD VTYVNWY LLIYAATSRA QQSYETPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1671) 1764) NO: NO: 1950) NO:
    1578) 1857) 2043)
    365_H05 SSYGMN WVAGINYNGGYTS ARGATWHDTHLD LTYVNWY LLIYAATSLH QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1672) 1765) NO: NO: 1951) NO:
    1579) 1858) 2044)
    366_D08 SSYGMH WVSNINYNGGYKS ARGATWHDTHLD LSYVNWY LVIYAATSLA QQSYENPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1673) 1766) NO: NO: 1952) NO:
    1580) 1859) 2045)
    366_F08 SSYGMN WVSSINYNGGYTS ARGATWHDTHLD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1674) 1767) NO: NO: 1953) NO:
    1581) 1860) 2046)
    366_G09 DDYSMN WVASINYNSGYTG ARGATWHDTHLD LSYVNWY LVIYAATSRA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1675) 1768) NO: NO: 1954) NO:
    1582) 1861) 2047)
    367_A02 DSYGMN WVSSINYNSGYKG ARGATWHDTHLD ISYLNWY LLIYAVTSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1676) 1769) NO: NO: 1955) NO:
    1583) 1862) 2048)
    367_B06 SSYSMN WVANINYNGGYTG ARGATWHDTHLD ISYVNWY LVIYAATSLH QQSYNSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1677) 1770) NO: NO: 1956) NO:
    1584) 1863) 2049)
    367_C08 DSYSMH WVAGINYNGGYTS ARGATWHDTHLD LTYLNWY LLIYAATSLA QQSDSNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1678) 1771) NO: NO: 1957) NO:
    1585) 1864) 2050)
    367_D05 SDYSMN WVSSINYNGGYKS ARGATWHDTHLD ISYVNWY LVIYAATSLA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1679) 1772) NO: NO: 1958) NO:
    1586) 1865) 2051)
    367_D09 DSYGMN WVASINYNGGYKS ARGATWHDTHLD LTYLNWY LLIYAATSLA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1680) 1773) NO: NO: 1959) NO:
    1587) 1866) 2052)
    367_E07 SDYSMN WVSSINYNGGYKG ARGATWHDTHLD LSYVNWY LVIYAATSRA QQSYENPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1681) 1774) NO: NO: 1960) NO:
    1588) 1867) 2053)
    367_E12 SSYGMH WVASINYNGGYTS ARGATWHDTHLD LTYVNWY LLIYAASSLQ QQSYNSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1682) 1775) NO: NO: 1961) NO:
    1589) 1868) 2054)
    367_F09 DSYSMH WVAGINYNGGYTS ARGATWHDTHLD LTYLNWY LLIYAATSLA QQSDSNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1683) 1776) NO: NO: 1962) NO:
    1590) 1869) 2055)
    367 H05 SSYGMH WVASINYNSGYKS ARGATWHDTHLD LSYVNWY LLIYAASSLQ QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: NO: NO: 1870) NO: 1963) 2056)
    1591) 1684) 1777)
    367_H10 SSYGMN WVASINYNGGYTG ARGATWHDTHLD LSYVNWY LVIYAATSRA QQSYELPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1685) 1778) NO: NO: 1964) NO:
    1592) 1871) 2057)
    368_B02 SSYGMN WVSGINYNSGYKS ARGATWHDTHLD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1686) 1779) NO: NO: 1965) NO:
    1593) 1872) 2058)
    368_C11 SDYSMN WVSSINYNSGYKS ARGATWHDTHLD ISYLNWY LLIYAATSRA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1687) 1780) NO: NO: 1966) NO:
    1594) 1873) 2059)
    368_D02 DDYGMN WVSNINYNGGYTG ARGATWHDTHLD STYLNWY LVIYAATSRH QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1688) 1781) NO: NO: 1967) NO:
    1595) 1874) 2060)
    368_D12 SSYGMN WVSSINYNGGYTS ARGATWHDTHLD LSYVNWY LVIYAATSRA QQSYNNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1689) 1782) NO: NO: 1968) NO:
    1596) 1875) 2061)
    368_F06 DDYSMH WVANINYNSGYTG ARGATWHDTHLD LSYLNWY LVIYATTSRA QQSYENPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1690) 1783) NO: NO: 1969) NO:
    1597) 1876) 2062)
    368_G03 SSYSMN WVSGINYNSGYTS ARGATWHDTALD LSYLNWY LVIYAATSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1691) 1784) NO: NO: 1970) NO:
    1598) 1877) 2063)
    368_G10 SSYSMH WVSSINYNGGYTS ARGATWHDTHLD VSYVNWY LVIYAATSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1692) 1785) NO: NO: 1971) NO:
    1599) 1878) 2064)
    368_H06 DSYGMH WVANINYNGGYKS ARGATWHDTHLD LTYVNWY LLIYATTSRA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1693) 1786) NO: NO: 1972) NO:
    1600) 1879) 2065)
    368_H11 DSYGMH WVASINYNGGYTS ARGATWHDTHLD LSYLNWY LLIYAATSRA QQSDDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1694) 1787) NO: NO: 1973) NO:
    1601) 1880) 2066)
    369_A11 DSYGMN WVANINYNGGYKG ARGATWHDTHLD ITYLNWY LVIYAATSRH QQSYESPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1695) 1788) NO: NO: 1974) NO:
    1602) 1881) 2067)
    369_C12 SSYGMN WVANINYNGGYKG ARGATWHDTHLD LTYLNWY LLIYAATSRH QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1696) 1789) NO: NO: 1975) NO:
    1603) 1882) 2068)
    369_D08 SDYSMN WVASINYNGGYKG ARGATWHDTHLD LTYLNWY LLIYAATSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1697) 1790) NO: NO: 1976) NO:
    1604) 1883) 2069)
    369_E05 SDYGMN WVANINYNGGYKS ARGATWHDTHLD LTYLNWY LLIYAATSLA QQSYETPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1698) 1791) NO: NO: 1977) NO:
    1605) 1884) 2070)
    369_E08 SSYSMN WVASINYNSGYTG ARGATWHDTHLD LTYVNWY LLIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1699) 1792) NO: NO: 1978) NO:
    1606) 1885) 2071)
    369_F05 SSYSMN WVSGINYNGGYKS ARGATWHDTHLD SSYLNWY LLIYAASSLQ QQGYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1700) 1793) NO: NO: 1979) NO:
    1607) 1886) 2072)
    369_F09 SSYGMH WVAGINYNGGYTS ARGATWHDTHLD LTYVNWY LLIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1701) 1794) NO: NO: 1980) NO:
    1608) 1887) 2073)
    369_G05 SSYSMN WVAGINYNGGYTS ARGATWHDTHLD VSYLNWY LLIYAATSRH QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1702) 1795) NO: NO: 1981) NO:
    1609) 1888) 2074)
    369_H02 DDYSMN WVSNINYNGGYKS ARGATWHDTHLD ISYLNWY LLIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1703) 1796) NO: NO: 1982) NO:
    1610) 1889) 2075)
    369_H08 SSYSMN WVAGINYNSGYKS ARGATWHDTHLD LSYVNWY LVIYAATSLA QQSYESPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1704) 1797) NO: NO: 1983) NO:
    1611) 1890) 2076)
    369_H12 SSYSMN WVAGINYNGGYKS ARGATWHDTHLD VTYVNWY LVIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1705) 1798) NO: NO: 1984) NO:
    1612) 1891) 2077)
    370_B08 SDYSMN WVANINYNGGYTG ARGATWHDTHLD LSYLNWY LLIYAASSLQ QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1706) 1799) NO: NO: 1985) NO:
    1613) 1892) 2078)
    370_C06 SSYSMN WVANINYNGGYKS ARGATWHDTHLD LTYVNWY LLIYAASSLQ QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1707) 1800) NO: NO: 1986) NO:
    1614) 1893) 2079)
    370_C07 SSYSMN WVANINYNGGYKS ARGATWHDTHLD LSYLNWY LLIYAATSRH QQSYESPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1708) 1801) NO: NO: 1987) NO:
    1615) 1894) 2080)
    370_C10 DSYSMN WVSNINYNSGYKG ARGATWHDTHLD VSYVNWY LLIYATTSRA QQSYSSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1709) 1802) NO: NO: 1988) NO:
    1616) 1895) 2081)
    370_D03 SSYSMN WVASINYNGGYTS ARGATWHDTHLD ITYLNWY LLIYAATSRA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1710) 1803) NO: NO: 1989) NO:
    1617) 1896) 2082)
    370_D09 SDYSMN WVSGINYNSGYTS ARGATWHDTHLD VTYLNWY LVIYAATSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1711) 1804) NO: NO: 1990) NO:
    1618) 1897) 2083)
    370_E04 SSYSMN WVANINYNGGYKG ARGATWHDTHLD LTYLNWY LLIYAVTSLH QQSYETPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1712) 1805) NO: NO: 1991) NO:
    1619) 1898) 2084)
    370_E05 SSYGMN WVSNINYNGGYKG ARGATWHDTHLD STYLNWY LVIYAVTSRA QQSYNSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1713) 1806) NO: NO: 1992) NO:
    1620) 1899) 2085)
    370_F01 SSYGMN WVSNINYNGGYTS ARGATWHDTHLD VSYLNWY LLIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1714) 1807) NO: NO: 1993) NO:
    1621) 1900) 2086)
    370_F02 DSYGMN WVANINYNGGYTG ARGATWHDTHLD LSYLNWY LLIYAVTSRH QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1715) 1808) NO: NO: 1994) NO:
    1622) 1901) 2087)
    370_F12 SDYSMN WVANINYNGGYTG ARGATWHDTHLD LSYLNWY LLIYAASSLQ QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1716) 1809) NO: NO: 1995) NO:
    1623) 1902) 2088)
    370_G08 SDYSMN WVAGINYNGGYTG ARGATWHDTHLD LTYLNWY LVIYAATSRA QQSYESPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1717) 1810) NO: NO: 1996) NO:
    1624) 1903) 2089)
    370_H04 SSYSMN WVSNINYNGGYTG ARGATWHDTHLD LSYVNWY LLIYAATSRA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1718) 1811) NO: NO: 1997) NO:
    1625) 1904) 2090)
    370_H06 DDYSMN WVANINYNGGYTG ARGATWHDTHLD LTYLNWY LLIYAATSRA QQSYETPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1719) 1812) NO: NO: 1998) NO:
    1626) 1905) 2091)
    371_B01 DSYSMN WVSNINYNSGYTG ARGATWHDTHLD LSYVNWY LLIYAATSLA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1720) 1813) NO: NO: 1999) NO:
    1627) 1906) 2092)
    371_C06 SSYSMN WVSSINYNGGYTS ARGATWHDTHLD SSYLNWY LLIYAVTSRA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1721) 1814) NO: NO: 2000) NO:
    1628) 1907) 2093)
    371_C07 DSYGMN WVSNINYNGGYTG ARGATWHDTALD LSYLNWY LLIYAATSLA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1722) 1815) NO: NO: 2001) NO:
    1629) 1908) 2094)
    371_E05 SSYSMN WVAGINYNGGYTS ARGATWHDTHLD ISYLNWY LVIYAATSRA QQSYSSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1723) 1816) NO: NO: 2002) NO:
    1630) 1909) 2095)
    371_E08 SSYSMN WVSNINYNSGYKS ARGATWHDTHLD VSYVNWY LVIYAATSRH QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1724) 1817) NO: NO: 2003) NO:
    1631) 1910) 2096)
    371_E09 SDYSMN WVSGINYNSGYTS ARGATWHDTHLD LTYLNWY LLIYAATSRA QQSYNSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1725) 1818) NO: NO: 2004) NO:
    1632) 1911) 2097)
    371_E12 DSYSMN WVSGINYNSGYKS ARGATWHDTHLD LSYLNWY LLIYAATSLA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1726) 1819) NO: NO: 2005) NO:
    1633) 1912) 2098)
    371_F03 SSYSMN WVSGINYNGGYTS ARGATWHDTHLD ITYLNWY LLIYAATSLH QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1727) 1820) NO: NO: 2006) NO:
    1634) 1913) 2099)
    371_F09 SSYSMN WVAGINYNGGYTS ARGATWHDTHLD LTYLNWY LLIYAATSRA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1728) 1821) NO: NO: 2007) NO:
    1635) 1914) 2100)
    371_G01 SDYSMN WVSNINYNGGYTS ARGATWHDTHLD LTYLNWY LLIYAATSLA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1729) 1822) NO: NO: 2008) NO:
    1636) 1915) 2101)
    371_H11 SSYSMN WVSGINYNGGYKG ARGATWHDTHLD LTYLNWY LLIYATTSRH QQSYESPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1730) 1823) NO: NO: 2009) NO:
    1637) 1916) 2102)
    372_B09 SSYSMN WVSSINYNSGYTS ARGATWHDTHLD LTYLNWY LLIYAATSRA QQSYETPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1731) 1824) NO: NO: 2010) NO:
    1638) 1917) 2103)
    372_E08 SDYSMN WVSNINYNGGYTS ARGATWHDTHLD ITYLNWY LLIYAATSRA QQSYNLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1732) 1825) NO: NO: 2011) NO:
    1639) 1918) 2104)
    372_F02 SSYGMH WVASINYNGGYTS ARGATWHDTHLD LTYLNWY LVIYAATSRH QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1733) 1826) NO: NO: 2012) NO:
    1640) 1919) 2105)
    372_H11 SSYGMH WVAGINYNGGYTS ARGATWHDTHLD LSYVNWY LLIYAATSRA QQSYENPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1734) 1827) NO: NO: 2013) NO:
    1641) 1920) 2106)
    373_A06 SSYSMN WVSGINYNGGYKS ARGATWHDTHLD VTYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1735) 1828) NO: NO: 2014) NO:
    1642) 1921) 2107)
    373_B09 DSYSMN WVSGINYNGGYKS ARGATWHDTHLD LSYLNWY LVIYAATSLA QQSYETPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1736) 1829) NO: NO: 2015) NO:
    1643) 1922) 2108)
    373_D06 SSYSMN WVAGINYNGGYTS ARGATWHDTHLD VTYLNWY LLIYAATSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1737) 1830) NO: NO: 2016) NO:
    1644) 1923) 2109)
    373_F07 SSYSMN WVSGINYNSGYKS ARGATWHDTHLD LSYLNWY LLIYAATSLA QQSYETPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1738) 1831) NO: NO: 2017) NO:
    1645) 1924) 2110)
    373_G02 SSYSMN WVSGINYNGGYTS ARGATWHDTHLD ITYLNWY LLIYAATSRA QQSYSSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1739) 1832) NO: NO: 2018) NO:
    1646) 1925) 2111)
    374_A04 SSYSMN WVAGINYNGGYTS ARGATWHDTHLD LTYLNWY LVIYAATSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1740) 1833) NO: NO: 2019) NO:
    1647) 1926) 2112)
    374_A05 SDYGMN WVANINYNGGYKG ARGATWHDTHLD VRYLNWY LVIYAATSLA QQSYELPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1741) 1834) NO: NO: 2020) NO:
    1648) 1927) 2113)
    374_C10 SSYSMN WVSSINYNGGYKG ARGATWHDTHLD VTYLNWY LLIYAATSLA QQSYNTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1742) 1835) NO: NO: 2021) NO:
    1649) 1928) 2114)
    374_D04 SSYSMN WVAGINYNGGYTS ARGATWHDTHLD LSYLNWY LVIYAATSRH QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1743) 1836) NO: NO: 2022) NO:
    1650) 1929) 2115)
    374_D09 DSYGMN WVANINYNGGYKG ARGATWHDTHLD ISYVNWY LLIYAATSLA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1744) 1837) NO: NO: 2023) NO:
    1651) 1930) 2116)
    374_G05 SSYSMN WVSNINYNSGYKG ARGATWHDTHLD ISYLNWY LLIYAATSRA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1745) 1838) NO: NO: 2024) NO:
    1652) 1931) 2117)
    374_H05 SSYSMN WVAGINYNGGYTS ARGATWHDTHLD LSYVNWY LVIYAATSRA QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1746) 1839) NO: NO: 2025) NO:
    1653) 1932) 2118)
    375_A03 DSYSMN WVAGINYNGGYTS ARGATWHDTHLD LTYLNWY LLIYAATSRH QQSYDNPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1747) 1840) NO: NO: 2026) NO:
    1654) 1933) 2119)
    375_B03 SSYSMN WVAGINYNGGYTS ARGATWHDTHLD LTYLNWY LLIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1748) 1841) NO: NO: 2027) NO:
    1655) 1934) 2120)
    375_C01 SSYGMN WVSSINYNGGYKG ARGATWHDTHLD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1749) 1842) NO: NO: 2028) NO:
    1656) 1935) 2121)
    375_C11 SSYSMN WVSSINYNGGYTS ARGATWHDTHLD LSYVNWY LLIYAATSRH QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1750) 1843) NO: NO: 2029) NO:
    1657) 1936) 2122)
    375_F10 SSYSMN WVSGINYNGGYTG ARGATWHDTHLD LTYLNWY LVIYAATSRA QQSYDTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1751) 1844) NO: NO: 2030) NO:
    1658) 1937) 2123)
    375_H08 SSYSMN WVSGINYNGGYTS ARGATWHDTHLD LTYLNWY LLIYAATSLA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1752) 1845) NO: NO: 2031) NO:
    1659) 1938) 2124)
    376_A02 SSYSMN WVAGINYNGGYKS ARGATWHDTHLD LSYLNWY LLIYAATSRA QQSYDLPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1753) 1846) NO: NO: 2032) NO:
    1660) 1939) 2125)
    376_A05 SSYSMN WVAGINYNSGYKG ARGATWHDTHLD LTYLNWY LLIYAATSRA QQSYNTPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1754) 1847) NO: NO: 2033) NO:
    1661) 1940) 2126)
    376_A07 SSYSMN WVSGINYNGGYKS ARGATWHDTHLD LTYLNWY LLIYAATSRA QQSYDSPL
    (SEQ (SEQ ID NO: (SEQ ID NO: (SEQ ID (SEQ ID (SEQ ID
    ID NO: 1755) 1848) NO: NO: 2034) NO:
    1662) 1941) 2127)
  • The consensus sequences for each of these CDRs shown in FIG. 3D are as follows:
  • HCDR1:
    (SEQ ID NO: 6574)
    S/DS/DYS/GMN/H
    HCDR2:
    (SEQ ID NO: 6575)
    WVA/SG/N/SINYNG/SGYT/KS/G
    HCDR3:
    (SEQ ID NO: 6595)
    ARGATWHDTH/ALD
    LCDR1:
    (SEQ ID NO: 6596)
    L/I/V/SS/TYL/VNWY
    LCDR2:
    (SEQ ID NO: 6571)
    LL/VIYAA/V/TT/SSR/LA/H/Q
    LCDR3:
    (SEQ ID NO: 6577)
    QQSY/DD/E/S/NT/S/N/LPL
  • TABLE 2E
    Group V Antibody Sequences
    Ab VH sequence VL sequence
    365_A03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2376)
    GTLVTVSS (SEQ ID NO: 2128)
    365_A11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDDYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2377)
    GTLVTVSS (SEQ ID NO: 2129)
    365_A12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYGMHWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCAKSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2378)
    GTLVTVSS (SEQ ID NO: 2130)
    365_B01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYVN
    FDSYGMHWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2379)
    GTLVTVSS (SEQ ID NO: 2131)
    365_B06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYGMHWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYATTSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2380)
    GTLVTVSS (SEQ ID NO: 2132)
    365_B07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMHWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2381)
    GTLVTVSS (SEQ ID NO: 2133)
    365_B11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FSSYGMHWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYATTSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2382)
    GTLVTVSS (SEQ ID NO: 2134)
    365_C01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FDSYGMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2383)
    GTLVTVSS (SEQ ID NO: 2135)
    365_C10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYGMHWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2384)
    GTLVTVSS (SEQ ID NO: 2136)
    365_C11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2385)
    GTLVTVSS (SEQ ID NO: 2137)
    365_C12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYGMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAVTSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2386)
    GTLVTVSS (SEQ ID NO: 2138)
    365_D09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMHWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2387)
    GTLVTVSS (SEQ ID NO: 2139)
    365_D11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2388)
    GTLVTVSS (SEQ ID NO: 2140)
    365_D12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2389)
    GTLVTVSS (SEQ ID NO: 2141)
    365_E01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FSDYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2390)
    GTLVTVSS (SEQ ID NO: 2142)
    365_E05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYGMHWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2391)
    GTLVTVSS (SEQ ID NO: 2143)
    365_E07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYGMHWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCAKSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2392)
    GTLVTVSS (SEQ ID NO: 2144)
    365_E09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYGMHWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2393)
    GTLVTVSS (SEQ ID NO: 2145)
    365_F01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2394)
    GTLVTVSS (SEQ ID NO: 2146)
    365_F06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYGMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDNLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2395)
    GTLVTVSS (SEQ ID NO: 2147)
    365_F12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSDYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2396)
    GTLVTVSS (SEQ ID NO: 2148)
    365_G01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYGMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYATTSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2397)
    GTLVTVSS (SEQ ID NO: 2149)
    365_G11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYVN
    FSSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAVTSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2398)
    GTLVTVSS (SEQ ID NO: 2150)
    365_H02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSDYGMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2399)
    GTLVTVSS (SEQ ID NO: 2151)
    365_H03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDDYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSLHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2400)
    GTLVTVSS (SEQ ID NO: 2152)
    365_H06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYVN
    FSSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2401)
    GTLVTVSS (SEQ ID NO: 2153)
    365_H10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYVN
    FDSYGMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2402)
    GTLVTVSS (SEQ ID NO: 2154)
    365_H11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2403)
    GTLVTVSS (SEQ ID NO: 2155)
    365_H12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYVN
    FSSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2404)
    GTLVTVSS (SEQ ID NO: 2156)
    366_A07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYGMHWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2405)
    GTLVTVSS (SEQ ID NO: 2157)
    366_B08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2406)
    GTLVTVSS (SEQ ID NO: 2158)
    366_B10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FSSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2407)
    GTLVTVSS (SEQ ID NO: 2159)
    366_B12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2408)
    GTLVTVSS (SEQ ID NO: 2160)
    366_D04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYVN
    FSSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYATTSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2409)
    GTLVTVSS (SEQ ID NO: 2161)
    366_E10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2410)
    GTLVTVSS (SEQ ID NO: 2162)
    366_F04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSDYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYATTSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2411)
    GTLVTVSS (SEQ ID NO: 2163)
    366_F05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDNTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2412)
    GTLVTVSS (SEQ ID NO: 2164)
    366_F07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    FSDYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2413)
    GTLVTVSS (SEQ ID NO: 2165)
    EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    366_G04 FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2414)
    GTLVTVSS (SEQ ID NO: 2166)
    EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    366_G05 FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2415)
    GTLVTVSS (SEQ ID NO: 2167)
    366_H06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLLIYATTSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2416)
    GTLVTVSS (SEQ ID NO: 2168)
    366_H07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FSSYGMHWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2417)
    GTLVTVSS (SEQ ID NO: 2169)
    366_H08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSDYGMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2418)
    GTLVTVSS (SEQ ID NO: 2170)
    366_H09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDSYGMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLVIYATTSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2419)
    GTLVTVSS (SEQ ID NO: 2171)
    367_A04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    FSSYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2420)
    GTLVTVSS (SEQ ID NO: 2172)
    367_A05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSDYGMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2421)
    GTLVTVSS (SEQ ID NO: 2173)
    367_B02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FDSYGMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2422)
    GTLVTVSS (SEQ ID NO: 2174)
    367_B03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2423)
    GTLVTVSS (SEQ ID NO: 2175)
    367_B07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FSDYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2424)
    GTLVTVSS (SEQ ID NO: 2176)
    367_B08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSDYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2425)
    GTLVTVSS (SEQ ID NO: 2177)
    367_C01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDDYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYATTSLHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2426)
    GTLVTVSS (SEQ ID NO: 2178)
    367_C05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDDYGMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2427)
    GTLVTVSS (SEQ ID NO: 2179)
    367_C11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2428)
    GTLVTVSS (SEQ ID NO: 2180)
    367_D10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2429)
    GTLVTVSS (SEQ ID NO: 2181)
    367_E01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYATTSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2430)
    GTLVTVSS (SEQ ID NO: 2182)
    367_E04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSDYSMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2431)
    GTLVTVSS (SEQ ID NO: 2183)
    367_E06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FDSYSMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2432)
    GTLVTVSS (SEQ ID NO: 2184)
    367_E09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSDYGMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLVIYATTSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2433)
    GTLVTVSS (SEQ ID NO: 2185)
    367_E11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDSYGMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2434)
    GTLVTVSS (SEQ ID NO: 2186)
    367_F03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2435)
    GTLVTVSS (SEQ ID NO: 2187)
    367_F07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FDSYGMHWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2436)
    GTLVTVSS (SEQ ID NO: 2188)
    367_F11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2437)
    GTLVTVSS (SEQ ID NO: 2189)
    367_G05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSDYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2438)
    GTLVTVSS (SEQ ID NO: 2190)
    367_G06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYATTSLHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2439)
    GTLVTVSS (SEQ ID NO: 2191)
    367_G10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FDDYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2440)
    GTLVTVSS (SEQ ID NO: 2192)
    367_H06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    FSSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2441)
    GTLVTVSS (SEQ ID NO: 2193)
    367_H11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2442)
    GTLVTVSS (SEQ ID NO: 2194)
    368_A01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FSSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2443)
    GTLVTVSS (SEQ ID NO: 2195)
    368_A05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2444)
    GTLVTVSS (SEQ ID NO: 2196)
    368_A07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYATTSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSNELPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2445)
    GTLVTVSS (SEQ ID NO: 2197)
    368_A09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2446)
    GTLVTVSS (SEQ ID NO: 2198)
    368_B01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FSSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2447)
    GTLVTVSS (SEQ ID NO: 2199)
    368_B06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FDSYGMHWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2448)
    GTLVTVSS (SEQ ID NO: 2200)
    368_B07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSDYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2449)
    GTLVTVSS (SEQ ID NO: 2201)
    368_C05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDSNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2450)
    GTLVTVSS (SEQ ID NO: 2202)
    368_D01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMHWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2451)
    GTLVTVSS (SEQ ID NO: 2203)
    368_D04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISTYVN
    FSSYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAVTSRHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2452)
    GTLVTVSS (SEQ ID NO: 2204)
    368_D05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2453)
    GTLVTVSS (SEQ ID NO: 2205)
    368_D11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDDYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2454)
    GTLVTVSS (SEQ ID NO: 2206)
    368_E01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLLIYAVTSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2455)
    GTLVTVSS (SEQ ID NO: 2207)
    368_E02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2456)
    GTLVTVSS (SEQ ID NO: 2208)
    368_E04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2457)
    GTLVTVSS (SEQ ID NO: 2209)
    368_E06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSDYGMHWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYGATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2458)
    GTLVTVSS (SEQ ID NO: 2210)
    368_E07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCAKSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2459)
    GTLVTVSS (SEQ ID NO: 2211)
    368_F03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCAKSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2460)
    GTLVTVSS (SEQ ID NO: 2212)
    368_F11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSDYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2461)
    GTLVTVSS (SEQ ID NO: 2213)
    368_G01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSDYGMHWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2462)
    GTLVTVSS (SEQ ID NO: 2214)
    368_G12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYVN
    FSSYGMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2463)
    GTLVTVSS (SEQ ID NO: 2215)
    368_H04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCAKSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2464)
    GTLVTVSS (SEQ ID NO: 2216)
    369_A02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2465)
    GTLVTVSS (SEQ ID NO: 2217)
    369_A03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAVTSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQGYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2466)
    GTLVTVSS (SEQ ID NO: 2218)
    369_B01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2467)
    GTLVTVSS (SEQ ID NO: 2219)
    369_C02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2468)
    GTLVTVSS (SEQ ID NO: 2220)
    369_C03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2469)
    GTLVTVSS (SEQ ID NO: 2221)
    369_C04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYTTTSLHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2470)
    GTLVTVSS (SEQ ID NO: 2222)
    369_D01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSDYGMNWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2471)
    GTLVTVSS (SEQ ID NO: 2223)
    369_D02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSDYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2472)
    GTLVTVSS (SEQ ID NO: 2224)
    369_D04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2473)
    GTLVTVSS (SEQ ID NO: 2225)
    369_D12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2474)
    GTLVTVSS (SEQ ID NO: 2226)
    369_E02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYATTSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2475)
    GTLVTVSS (SEQ ID NO: 2227)
    369_E11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FSSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2476)
    GTLVTVSS (SEQ ID NO: 2228)
    369_E12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FSSYGMHWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2477)
    GTLVTVSS (SEQ ID NO: 2229)
    369_F01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2478)
    GTLVTVSS (SEQ ID NO: 2230)
    369_F02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSSYGMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2479)
    GTLVTVSS (SEQ ID NO: 2231)
    369_F03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSDYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2480)
    GTLVTVSS (SEQ ID NO: 2232)
    369_F06 EVQLLESGGGLVQPGGSLRLSCAASGFT
    FDDYSMNWVRQAPGKGLEWVAGINYNGG DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    YKGYADSVKGRFTISRDNSKNTLYLQMN WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    SLRAEDTAVYYCARSANWHDTALDYWGQ TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    GTLVTVSS (SEQ ID NO: 2233) KVEIK (SEQ ID NO: 2481)
    369_F10 EVQLLESGGGLVQPGGSLRLSCAASGFT
    FDSYGMNWVRQAPGKGLEWVSNINYNSG DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    YKSYADSVKGRFTISRDNSKNTLYLQMN WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    SLRAEDTAVYYCARSANWHDTALDYWGQ TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    GTLVTVSS (SEQ ID NO: 2234) KVEIK (SEQ ID NO: 2482)
    369_F11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2483)
    GTLVTVSS (SEQ ID NO: 2235)
    369_G01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2484)
    GTLVTVSS (SEQ ID NO: 2236)
    369_G04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYATTSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2485)
    GTLVTVSS (SEQ ID NO: 2237)
    369_G06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2486)
    GTLVTVSS (SEQ ID NO: 2238)
    369_G11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2487)
    GTLVTVSS (SEQ ID NO: 2239)
    369_G12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDNTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2488)
    GTLVTVSS (SEQ ID NO: 2240)
    369_H05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2489)
    GTLVTVSS (SEQ ID NO: 2241)
    369_H06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2490)
    GTLVTVSS (SEQ ID NO: 2242)
    369_H09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDDYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAVTSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2491)
    GTLVTVSS (SEQ ID NO: 2243)
    370_A01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISTYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2492)
    GTLVTVSS (SEQ ID NO: 2244)
    370_A03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2493)
    GTLVTVSS (SEQ ID NO: 2245)
    370_A04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2494)
    GTLVTVSS (SEQ ID NO: 2246)
    370_A12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2495)
    GTLVTVSS (SEQ ID NO: 2247)
    370_C01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2496)
    GTLVTVSS (SEQ ID NO: 2248)
    370_C03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYYVTNRQSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2497)
    GTLVTVSS (SEQ ID NO: 2249)
    370_C05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2498)
    GTLVTVSS (SEQ ID NO: 2250)
    370_C08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISNYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2499)
    GTLVTVSS (SEQ ID NO: 2251)
    370_C09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FDSYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2500)
    GTLVTVSS (SEQ ID NO: 2252)
    370_D04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2501)
    GTLVTVSS (SEQ ID NO: 2253)
    370_D11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2502)
    GTLVTVSS (SEQ ID NO: 2254)
    370_E03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLVIYYASNRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2503)
    GTLVTVSS (SEQ ID NO: 2255)
    370_E06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYATTSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2504)
    GTLVTVSS (SEQ ID NO: 2256)
    370_E09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDDSSMHWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCAKSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2505)
    GTLVTVSS (SEQ ID NO: 2257)
    370_F05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2506)
    GTLVTVSS (SEQ ID NO: 2258)
    370_F07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2507)
    GTLVTVSS (SEQ ID NO: 2259)
    370_F10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2508)
    GTLVTVSS (SEQ ID NO: 2260)
    370_G02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSDYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2509)
    GTLVTVSS (SEQ ID NO: 2261)
    370_G03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYATTSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2510)
    GTLVTVSS (SEQ ID NO: 2262)
    370_G06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSDYGMHWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDNTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2511)
    GTLVTVSS (SEQ ID NO: 2263)
    370_G09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2512)
    GTLVTVSS (SEQ ID NO: 2264)
    370_G10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FSDYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYVVNNRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2513)
    GTLVTVSS (SEQ ID NO: 2265)
    370_G11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSSYSMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2514)
    GTLVTVSS (SEQ ID NO: 2266)
    370_H01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2515)
    GTLVTVSS (SEQ ID NO: 2267)
    370_H09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2516)
    GTLVTVSS (SEQ ID NO: 2268)
    371_A03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSDYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYATTSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2517)
    GTLVTVSS (SEQ ID NO: 2269)
    371_A06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2518)
    GTLVTVSS (SEQ ID NO: 2270)
    371_A07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSDYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYATTSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2519)
    GTLVTVSS (SEQ ID NO: 2271)
    371_A08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMHWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2520)
    GTLVTVSS (SEQ ID NO: 2272)
    371_A12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2521)
    GTLVTVSS (SEQ ID NO: 2273)
    371_B06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2522)
    GTLVTVSS (SEQ ID NO: 2274)
    371_B07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2523)
    GTLVTVSS (SEQ ID NO: 2275)
    371_C03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYATTSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2524)
    GTLVTVSS (SEQ ID NO: 2276)
    371_D06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FDDYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2525)
    GTLVTVSS (SEQ ID NO: 2277)
    371_D09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2526)
    GTLVTVSS (SEQ ID NO: 2278)
    371_F01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2527)
    GTLVTVSS (SEQ ID NO: 2279)
    371_F04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2528)
    GTLVTVSS (SEQ ID NO: 2280)
    371_F06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FDSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2529)
    GTLVTVSS (SEQ ID NO: 2281)
    371_F08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDDYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2530)
    GTLVTVSS (SEQ ID NO: 2282)
    371_G05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2531)
    GTLVTVSS (SEQ ID NO: 2283)
    371_G10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYVN
    FSSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2532)
    GTLVTVSS (SEQ ID NO: 2284)
    371_H09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2533)
    GTLVTVSS (SEQ ID NO: 2285)
    372_A04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2534)
    GTLVTVSS (SEQ ID NO: 2286)
    372_B04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2535)
    GTLVTVSS (SEQ ID NO: 2287)
    372_C07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSDYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDNTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2536)
    GTLVTVSS (SEQ ID NO: 2288)
    372_D02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMHWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2537)
    GTLVTVSS (SEQ ID NO: 2289)
    372_F03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2538)
    GTLVTVSS (SEQ ID NO: 2290)
    372_F06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSDYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2539)
    GTLVTVSS (SEQ ID NO: 2291)
    372_F08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSDYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2540)
    GTLVTVSS (SEQ ID NO: 2292)
    372_F09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2541)
    GTLVTVSS (SEQ ID NO: 2293)
    373_A02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYATTSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2542)
    GTLVTVSS (SEQ ID NO: 2294)
    373_A08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2543)
    GTLVTVSS (SEQ ID NO: 2295)
    373_A10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2544)
    GTLVTVSS (SEQ ID NO: 2296)
    373_B04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2545)
    GTLVTVSS (SEQ ID NO: 2297)
    373_B06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSDYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2546)
    GTLVTVSS (SEQ ID NO: 2298)
    373_B10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2547)
    GTLVTVSS (SEQ ID NO: 2299)
    373_B12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDSYGMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2548)
    GTLVTVSS (SEQ ID NO: 2300)
    373_C02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDDYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2549)
    GTLVTVSS (SEQ ID NO: 2301)
    373_C04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FSSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2550)
    GTLVTVSS (SEQ ID NO: 2302)
    373_C06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2551)
    GTLVTVSS (SEQ ID NO: 2303)
    373_C08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FSSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2552)
    GTLVTVSS (SEQ ID NO: 2304)
    373_C11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2553)
    GTLVTVSS (SEQ ID NO: 2305)
    373_D01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2554)
    GTLVTVSS (SEQ ID NO: 2306)
    373_D04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2555)
    GTLVTVSS (SEQ ID NO: 2307)
    373_D05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2556)
    GTLVTVSS (SEQ ID NO: 2308)
    373_D08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2557)
    GTLVTVSS (SEQ ID NO: 2309)
    373_D10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2558)
    GTLVTVSS (SEQ ID NO: 2310)
    373_E01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2559)
    GTLVTVSS (SEQ ID NO: 2311)
    373_B05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2560)
    GTLVTVSS (SEQ ID NO: 2312)
    373_E07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2561)
    GTLVTVSS (SEQ ID NO: 2313)
    373_E12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2562)
    GTLVTVSS (SEQ ID NO: 2314)
    373_G10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSDYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2563)
    GTLVTVSS (SEQ ID NO: 2315)
    373_G12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYATTSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2564)
    GTLVTVSS (SEQ ID NO: 2316)
    373_H01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2565)
    GTLVTVSS (SEQ ID NO: 2317)
    373_H05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSDYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2566)
    GTLVTVSS (SEQ ID NO: 2318)
    374_A07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2567)
    GTLVTVSS (SEQ ID NO: 2319)
    374_B04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSSYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2568)
    GTLVTVSS (SEQ ID NO: 2320)
    374_B06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2569)
    GTLVTVSS (SEQ ID NO: 2321)
    374_B12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2570)
    GTLVTVSS (SEQ ID NO: 2322)
    374_C03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2571)
    GTLVTVSS (SEQ ID NO: 2323)
    374_C06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDDYSMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2572)
    GTLVTVSS (SEQ ID NO: 2324)
    374_D01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYVN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2573)
    GTLVTVSS (SEQ ID NO: 2325)
    374_D08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2574)
    GTLVTVSS (SEQ ID NO: 2326)
    374_E01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYVN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2575)
    GTLVTVSS (SEQ ID NO: 2327)
    374_E02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2576)
    GTLVTVSS (SEQ ID NO: 2328)
    374_E05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSFVN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2577)
    GTLVTVSS (SEQ ID NO: 2329)
    374_E07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYVN
    FSDYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2578)
    GTLVTVSS (SEQ ID NO: 2330)
    374_E08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2579)
    GTLVTVSS (SEQ ID NO: 2331)
    374_E11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FSSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2580)
    GTLVTVSS (SEQ ID NO: 2332)
    374_F01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2581)
    GTLVTVSS (SEQ ID NO: 2333)
    374_F02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FDSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2582)
    GTLVTVSS (SEQ ID NO: 2334)
    374_F04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2583)
    GTLVTVSS (SEQ ID NO: 2335)
    374_F10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2584)
    GTLVTVSS (SEQ ID NO: 2336)
    374_F11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAVTSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2585)
    GTLVTVSS (SEQ ID NO: 2337)
    374_G04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2586)
    GTLVTVSS (SEQ ID NO: 2338)
    374_G06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMHWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2587)
    GTLVTVSS (SEQ ID NO: 2339)
    374_G07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2588)
    GTLVTVSS (SEQ ID NO: 2340)
    374_H03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2589)
    GTLVTVSS (SEQ ID NO: 2341)
    374_H04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2590)
    GTLVTVSS (SEQ ID NO: 2342)
    374_H06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2591)
    GTLVTVSS (SEQ ID NO: 2343)
    374_H07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2592)
    GTLVTVSS (SEQ ID NO: 2344)
    374_H09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLVIYAVTSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2593)
    GTLVTVSS (SEQ ID NO: 2345)
    375_A05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2594)
    GTLVTVSS (SEQ ID NO: 2346)
    375_C06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDDYGMHWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLVIYATTSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2595)
    GTLVTVSS (SEQ ID NO: 2347)
    375_D04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDDSSMHWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCAKSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2596)
    GTLVTVSS (SEQ ID NO: 2348)
    375_D05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSSYSMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLLIYAATSLHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTHLDYWGQ KVEIK (SEQ ID NO: 2597)
    GTLVTVSS (SEQ ID NO: 2349)
    375_D07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    FSSYGMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2598)
    GTLVTVSS (SEQ ID NO: 2350)
    375_D08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    FSDYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2599)
    GTLVTVSS (SEQ ID NO: 2351)
    375_D12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYGMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2600)
    GTLVTVSS (SEQ ID NO: 2352)
    375_E01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2601)
    GTLVTVSS (SEQ ID NO: 2353)
    375_E07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FSDYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYVVTNRESGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2602)
    GTLVTVSS (SEQ ID NO: 2354)
    375_H12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYYVTNRQSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSIPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2603)
    GTLVTVSS (SEQ ID NO: 2355)
    376_A04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2604)
    GTLVTVSS (SEQ ID NO: 2356)
    376_A10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSDYGMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2605)
    GTLVTVSS (SEQ ID NO: 2357)
    376_A12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2606)
    GTLVTVSS (SEQ ID NO: 2358)
    376_B04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDSYGMHWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2607)
    GTLVTVSS (SEQ ID NO: 2359)
    376_B05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FSSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2608)
    GTLVTVSS (SEQ ID NO: 2360)
    376_B09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2609)
    GTLVTVSS (SEQ ID NO: 2361)
    376_B11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2610)
    GTLVTVSS (SEQ ID NO: 2362)
    376_C01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2611)
    GTLVTVSS (SEQ ID NO: 2363)
    376_C02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FDSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2612)
    GTLVTVSS (SEQ ID NO: 2364)
    376_C12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2613)
    GTLVTVSS (SEQ ID NO: 2365)
    376_D05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2614)
    GTLVTVSS (SEQ ID NO: 2366)
    376_D11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2615)
    GTLVTVSS (SEQ ID NO: 2367)
    376_E03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2616)
    GTLVTVSS (SEQ ID NO: 2368)
    376_E08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSDYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2617)
    GTLVTVSS (SEQ ID NO: 2369)
    376_F03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYVN
    FDSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYATTSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2618)
    GTLVTVSS (SEQ ID NO: 2370)
    376_F04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FDSYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2619)
    GTLVTVSS (SEQ ID NO: 2371)
    376_G08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2620)
    GTLVTVSS (SEQ ID NO: 2372)
    376_G09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISYYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2621)
    GTLVTVSS (SEQ ID NO: 2373)
    376_H09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    FSDYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYYVSNLPSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2622)
    GTLVTVSS (SEQ ID NO: 2374)
    376_H10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSANWHDTALDYWGQ KVEIK (SEQ ID NO: 2623)
    GTLVTVSS (SEQ ID NO: 2375)
  • Table 3E provides the amino acid sequences of the CDRs of the antibodies shown in Table 2E.
  • TABLE 3E
    CDR sequences for Group V antibodies
    Ab HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3
    365_A03 SSYSMN WVAGINYNSGYKG ARSANWHDTALD LSYLNWY LVIYAVTSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2624) NO: 2872) NO: 3120) NO: 3368) NO: 3616) NO: 3864)
    365_A11 DDYGMN WVSGINYNSGYTS ARSANWHDTALD LSYLNWY LVIYAATSLA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2625) NO: 2873) NO: 3121) NO: 3369) NO: 3617) NO: 3865)
    365_A12 SSYGMH WVAGINYNGGYTS AKSANWHDTHLD LTYVNWY LLIYAATSRH QQSYENPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2626) NO: 2874) NO: 3122) NO: 3370) NO: 3618) NO: 3866)
    365_B01 DSYGMH WVASINYNSGYTS ARSANWHDTALD SSYVNWY LVIYAATSRA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2627) NO: 2875) NO: 3123) NO: 3371) NO: 3619) NO: 3867)
    365_B06 DSYGMH WVSNINYNGGYKS ARSANWHDTALD LTYVNWY LLIYATTSLA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2628) NO: 2876) NO: 3124) NO: 3372) NO: 3620) NO: 3868)
    365_B07 SSYGMH WVASINYNSGYTS ARSANWHDTALD LTYLNWY LLIYAATSRA QQSYENPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2629) NO: 2877) NO: 3125) NO: 3373) NO: 3621) NO: 3869)
    365_B11 SSYGMH WVAGINYNGGYTS ARSABWGDTALD ISYLNWY LVIYATTSRH QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2630) NO: 2878) NO: 3126) NO: 3374) NO: 3622) NO: 3870)
    365_C01 DSYGMN WVSSINYNSGYKS ARSANWHDTHLD VSYLNWY LVIYAVTSRA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2631) NO: 2879) NO: 3127) NO: 3375) NO: 3623) NO: 3871)
    365_C10 SSYGMH WVASINYNGGYTS ARSANWHDTALD LSYVNWY LLIYAATSLA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2632) NO: 2880) NO: 3128) NO: 3376) NO: 3624) NO: 3872)
    365_C11 SSYSMN WVAGINYNGGYKS ARSANWHDTHLD ITYLNWY LVIYAVTSRA QQSYSLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2633) NO: 2881) NO: 3129) NO: 3377) NO: 3625) NO: 3873)
    365_C12 SSYGMN WVAGINYNSGYKS ARSANWHDTALD VSYVNWY LVIYAVTSLA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2634) NO: 2882) NO: 3130) NO: 3378) NO: 2626) NO: 3874)
    365_D09 SSYGMH WVSGINYNSGYTS ARSANWHDTALD LSYLNWY LLIYAATSRA QQSDESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2635) NO: 2883) NO: 3131) NO: 3379) NO: 3627) NO: 3875)
    365_D11 DSYGMN WVSNINYNSGYTS ARSANWHDTALD VSYLNWY LVIYAATSRA QQSYSSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2636) NO: 2884) NO: 3132) NO: 3380) NO: 3628) NO: 3876)
    365_D12 DSYGMN WVSNINYNGGYTG ARSANWHDTALD VTYLNWY LVIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2637) NO: 2885) NO: 3133) NO: 3381) NO: 3629) NO: 3877)
    365_E01 SDYSMN WVSGINYNSGYKG ARSANWHDTALD ISYLNWY LLIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2638) NO: 2886) NO: 3134) NO: 3382) NO: 3630) NO: 3878)
    365_E05 SSYGMH WVAGINYNGGYTS ARSANWHDTALD VSYVNWY LLIYAATSLA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2639) NO: 2887) NO: 3135) NO: 3383) NO: 3631) NO: 3879)
    365_E07 DSYGMH WVSGINYNSGYTS AKSANWHDTHLD LSYLNWY LLIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2640) NO: 2888) NO: 3136) NO: 3384) NO: 3632) NO: 3880)
    365_E09 SSYGMH WVASINYNSGYKS ARSANWHDTALD LTYVNWY LVIYAATSRA QQSDDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2641) NO: 2889) NO: 3137) NO: 3385) NO: 3633) NO: 3881)
    365_F01 DSYSMN WVSGINYNSGYKG ARSANWHDTHLD VSYLNWY LVIYAATSLA QQSYELPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2642) NO: 2890) NO: 3138) NO: 3386) NO: 3634) NO: 3882)
    365_F06 SSYGMN WVAGINYNSGYKS ARSANWHDTALD LSYVNWY LLIYAATSRA QQSDNLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2643) NO: 2891) NO: 3139) NO: 3387) NO: 3635) NO: 3883)
    365_F12 SDYSMN WVSGINYNGGYTS ARSANWHDTHLD LTYVNWY LVIYAATSRH QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2644) NO: 2892) NO: 3140) NO: 3388) NO: 3636) NO: 3884)
    365_G01 DSYGMN WVAGINYNSGYKS ARSANWHDTALD LTYVNWY LLIYATTSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2645) NO: 2893) NO: 3141) NO: 3389) NO: 3637) NO: 3885)
    365_G11 SSYGMN WVANINYNGGYTG ARSANWHDTALD ITYVNWY LLIYAVTSRH QQSYNSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2646) NO: 2894) NO: 3142) NO: 3390) NO: 3638) NO: 3886)
    365_H02 SDYGMN WVSSINYNGGYTG ARSANWHDTHLD LTYLNWY LLIYAATSRA QQSYENPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2647) NO: 2895) NO: 3143) NO: 3391) NO: 3639) NO: 3887)
    365_H03 DDYGMN WVAGINYNGGYKS ARSANWHDTALD LSYVNWY LVIYAATSLH QQSYNNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2648) NO: 2896) NO: 3144) NO: 3392) NO: 3640) NO: 3888)
    365_H06 SSYGMN WVSGINYNSGYTG ARSANWHDTALD SSYVNWY LLIYAATSRA QQSYSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2649) NO: 2897) NO: 3145) NO: 3393) NO: 3641) NO: 3889)
    365_H10 DSYGMN WVAGINYNSGYKS ARSANWHDTHLD VTYVNWY LVIYAATSLA QQSYNTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2650) NO: 2898) NO: 3146) NO: 3394) NO: 3642) NO: 3890)
    365_H11 SSYSMN WVSGINYNSGYTG ARSANWHDTALD LTYLNWY LLIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2651) NO: 2899) NO: 3147) NO: 3395) NO: 3643) NO: 3891)
    365_H12 SSYSMN WVSNINYNGGYKS ARSANWHDTHLD ITYVNWY LLIYAATSRA QQSYSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2652) NO: 2900) NO: 3148) NO: 3396) NO: 3644) NO: 3892)
    366_A07 SSYGMH WVASINYNGGYTG ARSANWHDTALD VSYVNWY LVIYAATSRH QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2653) NO: 2901) NO: 3149) NO: 3397) NO: 3645) NO: 3893)
    366_B08 DSYGMN WVSNINYNGGYKG ARSANWHDTHLD VSYLNWY LLIYAATSRH QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2654) NO: 2902) NO: 3150) NO: 3398) NO: 3646) NO: 3894)
    366_B10 SSYGMN WVSGINYNSGYTS ARSANWHDTALD ISYLNWY LLIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2655) NO: 2903) NO: 3151) NO: 3399) NO: 3647) NO: 3895)
    366_B12 SSYSMN WVAGINYNSGYKG ARSANWHDTALD LTYVNWY LLIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2656) NO: 2904) NO: 3152) NO: 3400) NO: 3648) NO: 3896)
    366_D04 SSYSMN WVSGINYNGGYTS ARSANWHDTALD SSYVNWY LLIYATTSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2657) NO: 2905) NO: 3153) NO: 3401) NO: 3649) NO: 3897)
    366_E10 DSYGMN WVSGINYNGGYKG ARSANWHDTHLD LSYVNWY LVIYAATSRH QQSYSLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2658) NO: 2906) NO: 3154) NO: 3402) NO: 3650) NO: 3898)
    366_F04 SDYGMN WVSGINYNGGYTS ARSANWHDTALD LSYVNWY LVIYATTSRH QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2659) NO: 2907) NO: 3155) NO: 3403) NO: 3651) NO: 3899)
    366_F05 SSYSMN WVANINYNSGYKS ARSANWHDTHLD LTYLNWY LLIYAATSRA QQSDNTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2660) NO: 2908) NO: 3156) NO: 3404) NO: 3652) NO: 3900)
    366_F07 SDYSMN WVAGINYNSGYTS ARSANWHDTHLD ITYLNWY LLIYAATSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2661) NO: 2909) NO: 3157) NO: 3405) NO: 3653) NO: 3901)
    366_G04 SSYSMN WVSGINYNSGYTS ARSANWHDTALD ITYLNWY LLIYAATSRA QQSDDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2662) NO: 2910) NO: 3158) NO: 3406) NO: 3654) NO: 3902)
    366_G05 DSYGMN WVSNINYNGGYTS ARSANWHDTALD ISYVNWY LVIYAATSRA QQSYENPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2663) NO: 2911) NO: 3159) NO: 3407) NO: 3655) NO: 3903)
    366_H06 SSYGMN WVSSINYNGGYTG ARSANWHDTALD LSYLNWY LLIYATTSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2664) NO: 2912) NO: 3160) NO: 3408) NO: 3656) NO: 3904)
    366_H07 SSYGMH WVSGINYNGGYTS ARSANWHDTALD ISYVNWY LVIYAVTSRA QQSYENPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2665) NO: 2913) NO: 3161) NO: 3409) NO: 3657) NO: 3905)
    366_H08 SDYGMN WVASINYNSGYTS ARSANWHDTHLD LSYVNWY LLIYAATSRH QQSYNNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2666) NO: 2914) NO: 3162) NO: 3410) NO: 3658) NO: 3906)
    366_H09 DSYGMN WVSNINYNSGYKG ARSANWHDTALD VSYVNWY LVIYATTSRA QQSYSSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2667) NO: 2915) NO: 3163) NO: 3411) NO: 3659) NO: 3907)
    367_A04 SSYSMN WVSNINYNSGYKS ARSANWHDTALD ITYLNWY LLIYAATSRA QQSDDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2668) NO: 2916) NO: 3164) NO: 3412) NO: 3660) NO: 3908)
    367_A05 SDYGMN WVSSINYNGGYKG ARSANWHDTALD LSYLNWY LVIYAVTSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2669) NO: 2917) NO: 3165) NO: 3413) NO: 3661) NO: 3909)
    367_B02 DSYGMN WVSSINYNGGYTS ARSANWHDTALD VTYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2670) NO: 2918) NO: 3166) NO: 3414) NO: 3662) NO: 3910)
    367_B03 SSYGMN WVAGINYNGGYKS ARSANWHDTALD LTYLNWY LLIYAATSLA QQSYNLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2671) NO: 2919) NO: 3167) NO: 3415) NO: 3663) NO: 3911)
    367_B07 SDYSMN WVAGINYNSGYTG ARSANWHDTHLD ISYVNWY LLIYAATSLA QQSYNLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2672) NO: 2920) NO: 3168) NO: 3416) NO: 3664) NO: 3912)
    367_B08 SDYGMN WVSGINYNGGYKG ARSANWHDTALD LTYLNWY LVIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2673) NO: 2921) NO: 3169) NO: 3417) NO: 3665) NO: 3913)
    367_C01 DDYSMN WVSGINYNGGYKS ARSANWHDTHLD LTYLNWY LVIYATTSLH QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2674) NO: 2922) NO: 3170) NO: 3418) NO: 3666) NO: 3914)
    367_C05 DDYGMN WVSSINYNGGYTG ARSANWHDTHLD LSYVNWY LVIYAATSRH QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2675) NO: 2923) NO: 3171) NO: 3419) NO: 3667) NO: 3915)
    367_C11 DSYSMN WVSSINYNSGYTG ARSANWHDTHLD LSYLNWY LVIYAATSRH QQSYNTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2676) NO: 2924) NO: 3172) NO: 3420) NO: 3668) NO: 3916)
    367_D10 DSYGMN WVSNINYNGGYTS ARSANWHDTALD ISYLNWY LVIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2677) NO: 2925) NO: 3173) NO: 3421) NO: 3669) NO: 3917)
    367_E01 SSYGMN WVAGINYNGGYKS ARSANWHDTALD LSYVNWY LLIYTTSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2678) NO: 2926) NO: 3174) NO: 3422) NO: 3670) NO: 3918)
    367_E04 SDYSMN WVSSINYNGGYKG ARSANWHDTHLD LSYLNWY LLIYAATSRA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2679) NO: 2927) NO: 3175) NO: 3423) NO: 3671) NO: 3919)
    367_E06 DSYSMN WVSSINYNSGYKG ARSANWHDTHLD SYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2680) NO: 2928) NO: 3176) NO: 3424) NO: 3672) NO: 3920)
    367_E09 SDYGMN WVASINYNSGYKG ARSANWHDTALD LSYLNWY LVIYATTSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2681) NO: 2929) NO: 3177) NO: 3425) NO: 3673) NO: 3921)
    367_E11 DSYGMN WVSSINYNSGYKG ARSANWHDTHLD VSYVNWY LVIYAATSRH QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2682) NO: 2930) NO: 3178) NO: 3426) NO: 3674) NO: 3922)
    367_F03 SSYSMN WVAGINYNSGYKS ARSANWHDTALD LSYVNWY LVIYAATSLA QQSDDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2683) NO: 2931) NO: 3179) NO: 3427) NO: 3675) NO: 3923)
    367_F07 DSYGMH WVANINYNGGYTG ARSANWHDTALD ISYVNWY LLIYAATSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2684) NO: 2932) NO: 3180) NO: 3428) NO: 3676) NO: 3924)
    367_F11 SSYSMN WVAGINYNSGYTG ARSANWHDTHLD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2685) NO: 2933) NO: 3181) NO: 3429) NO: 3677) NO: 3925)
    367_G05 SDYGMN WVANINYNGGYTS ARSANWHDTALD VSYLNWY LVIYAATSLA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2686) NO: 2934) NO: 3182) NO: 3430) NO: 3678) NO: 3926)
    367_G06 SSYGMN WVSGINYNSGYKS ARSANWHDTHLD LTYVNWY LLIYATTSLH QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2687) NO: 2935) NO: 3183) NO: 3431) NO: 3679) NO: 3927)
    367_G10 DDYGMN WVSGINYNGGYTS ARSANWHDTALD ISYVNWY LLIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2688) NO: 2936) NO: 3184) NO: 3432) NO: 3680) NO: 3928)
    367_H06 SSYGMN WVSNINYNGGYTG ARSANWHDTHLD ITYLNWY LLIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2689) NO: 2937) NO: 3185) NO: 3433) NO: 3681) NO: 3929)
    367_H11 SSYGMN WVAINYNGGYKG ARSANWHDTALD ISYVNWY LVIYAATSRA QQSYNSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2690) NO: 2938) NO: 3186) NO: 3434) NO: 3682) NO: 3930)
    368_A01 SSYGMN WVSNINYNGGYTS ARSANWHDTALD ISYLNWY LLIYAATSRH QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2691) NO: 2939) NO: 3187) NO: 3435) NO: 3683) NO: 3931)
    368_A05 SSYSMN WVAGINYNSGYTG ARSANWHDTALD VSYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2692) NO: 2940) NO: 3188) NO: 3436) NO: 3684) NO: 3932)
    368_A07 SSYSMN WVAGINYNSGYTS ARSANWHDTHLD LTYLNWY LVIYATTSRA QQSNELPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2693) NO: 2941) NO: 3189) NO: 3437) NO: 3685) NO: 3933)
    368_A09 DSYSMN WVSGINYNGGYTS ARSANWHDTHLD LSYVNWY LLIYAVTSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2694) NO: 2942) NO: 3190) NO: 3438) NO: 3686) NO: 3934)
    368_B01 SSYGMN WVSGINYNSGYKS ARSANWHDTALD SSYLNWY LLIYAATSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2695) NO: 2943) NO: 3191) NO: 3439) NO: 3687) NO: 3935)
    368_B06 DSYGMH WVSGINYNSGYTS ARSANWHDTALD ISYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2696) NO: 2944) NO: 3192) NO: 3440) NO: 3688) NO: 3936)
    368_B07 SDYSMN WVSNINYNGGYKS ARSANWHDTALD VSYLNWY LLIYAATSLA QQSYSSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2697) NO: 2945) NO: 3193) NO: 3441) NO: 3689) NO: 3937)
    368_C05 DSYGMN WVSGINYNSGYTS ARSANWHDTALD LSYLNWY LVIYAATSRA QQSDSNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2698) NO: 2946) NO: 3194) NO: 3442) NO: 3690) NO: 3938)
    368_D01 SSYGMH WVANINYNGGYTS ARSANWHDTALD LSYLNWY LVIYAATSRA QQSDSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2699) NO: 2947) NO: 3195) NO: 3443) NO: 3691) NO: 3939)
    368_D04 SSYGMN WVSGINYNGGYKS ARSANWHDTALD STYVNWY LVIYAVTSRH QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2700) NO: 2948) NO: 3196) NO: 3444) NO: 3692) NO: 3940)
    368_D05 SSYSMN WVSGINYNGGYTS ARSANWHDTALD LTYLNWY LVIYAATSRA QQSDDPSL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2701) NO: 2949) NO: 3197) NO: 3445) NO: 3693) NO: 3941)
    368_D11 SSYGMN WVSNINYNGGYKS ARSANWHDTALD LTYLNWY LVIYAATSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2702) NO: 2950) NO: 3198) NO: 3446) NO: 3694) NO: 3942)
    368_E01 SSYSMN WVASINYNSGYTG ARSANWHDTHLD LSYLNWY LVIYAVTSRH QQSYSLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2703) NO: 2951) NO: 3199) NO: 3447) NO: 3695) NO: 3943)
    368_E02 DSYSMN WVAGINYNSGYTS ARSANWHDTHLD LTYLNWY LLIYAATSRA QQSYSSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2704) NO: 2952) NO: 3200) NO: 3448) NO: 3696) NO: 3944)
    368_E04 SSYSMN WVANINYNSGYTG ARSANWHDTALD LSYVNWY LLIYAATSRH QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2705) NO: 2953) NO: 3201) NO: 3449) NO: 3697) NO: 3945)
    368_E06 SDYGMH WVSGINYNGGYTG ARSANWHDTALD LSYLNWY LVIYGATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2706) NO: 2954) NO: 3202) NO: 3450) NO: 3698) NO: 3946)
    368_E07 SSYGMN WVAGINYNGGYTS AKSANWHDTALD LSYLNWY LLIYAVTSRA QQSYENPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2707) NO: 2955) NO: 3203) NO: 3451) NO: 3699) NO: 3947)
    368_F03 DSYSMN WVAGINYNSGYTG AKSANWHDTALD ISYLNWY LVIYAATSRH QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2708) NO: 2956) NO: 3204) NO: 3452) NO: 3700) NO: 3948)
    368_F11 SDYGMN WVSGINYNGGYTS ARSANWHDTHLD VWYVNWY LVIYAATSRA QQSYNNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2709) NO: 2957) NO: 3205) NO: 3453) NO: 3701) NO: 3949)
    368_G01 SDYGMH WVASINYNSGYTS ARSANWHDTALD LTYLNWY LVIYAATSRA QQSYNLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2710) NO: 2959) NO: 3206) NO: 3454) NO: 3702) NO: 3950)
    368_G12 SSYGMN WVASINYNSGYTG ARSANWHDTALD SSYVNWY LVIYAVTSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2711) NO: 2959) NO: 3207) NO: 3455) NO: 3703) NO: 3951)
    368_H04 SSYSMN WVAGINYNSGYKG AKSANWHDTHLD VSYVNWY LLIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2712) NO: 2960) NO: 3208) NO: 3456) NO: 3704) NO: 3952)
    369_A02 SSYSMN WVAGINYNSGYTG ARSANWHDTHLD LSYVNWY LLIYAATSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2713) NO: 2961) NO: 3209) NO: 3457) NO: 3705) NO: 3953)
    369_A03 SSYGMN WVSNINYNGGYTG ARSANWHDTALD LTYLNWY LLIYAVTSRH QQGYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2714) NO: 2962) NO: 3210) NO: 3458) NO: 3706) NO: 3954)
    369_B01 SSYSMN WVSGINYNGGYTS ARSANWHDTALD LSYLNWY LLIYAVTSRA QQSYENPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2715) NO: 2963) NO: 3211) NO: 3459) NO: 3707) NO: 3955)
    369_B01 DSYSMN WVSNINYNGGYKS ARSANWHDTALD LTYLNWY LVIYAATSRA QQSYELPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2716) NO: 2964) NO: 3212) NO: 3460) NO: 3708) NO: 3956)
    369_C03 SSYGMN WVSNINYNGGYKS ARSANWHDTALD LTYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2717) NO: 2965) NO: 3213) NO: 3461) NO: 3709) NO: 3957)
    369_C04 SSYSMN WVSNINYNGGYTG ARSANWHDTALD LTYVNWY LLIYTTTSLH QQSYNNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2718) NO: 2966) NO: 3214) NO: 3462) NO: 3710) NO: 3958)
    369_D01 SDYGMN WVASINYNGGYTG ARSANWHDTALD LTYLNWY LLIYAATSRA QQSYSNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2719) NO: 2967) NO: 3215) NO: 3463) NO: 3711) NO: 3959)
    369_D02 SDYSMN WVSNINYNSGYTG ARSANWHDTALD LSYLNWY LVIYAVTSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2720) NO: 2968) NO: 3216) NO: 3464) NO: 3712) NO: 3960)
    369_D04 DSYGMN WVSGINYNGGYTS ARSANWHDTALD LSYVNWY LVIYAATSRA QQSYNLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2721) NO: 2969) NO: 3217) NO: 3465) NO: 3713) NO: 3961)
    369_D12 DSYSMN WVAGINYNSGYTS ARSANWHDTALD LSYLNWY LLIYAATSLA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2722) NO: 2970) NO: 3218) NO: 3466) NO: 3714) NO: 3962)
    369_E02 DSYGMN WVSNINYNGGYTG ARSANWHDTALD VSYVNWY LLIYATTSRH QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2723) NO: 2971) NO: 3219) NO: 3467) NO: 3715) NO: 3963)
    369_E11 SSYGMN WVSNINYNGGYTS ARSANWHDTALD ISYLNWY LLIYAATSLA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2724) NO: 2972) NO: 3220) NO: 3468) NO: 3716) NO: 3964)
    369_E12 SSYGMH WVASINYNSGYTS ARSANWHDTALD ISYLNWY LLIYAATSRA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2725) NO: 2973) NO: 3221) NO: 3469) NO: 3717) NO: 3965)
    369_F01 SSYGMN WVSGINYNGGYKS ARSANWHDTALD LTYVNWY LLIYAATSRA QQSYELPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2726) NO: 2974) NO: 3222) NO: 3470) NO: 3718) NO: 3966)
    369_F02 SSYGMN WVASINYNSGYKS ARSANWHDTALD VSYLNWY LVIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2727) NO: 2975) NO: 3223) NO: 3471) NO: 3719) NO: 3967)
    369_F03 SSYGMN WVSGINYNSGYTS ARSANWHDTALD VSYVNWY LVIYAATSLA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2728) NO: 2976) NO: 3224) NO: 3472) NO: 3720) NO: 3968)
    369_F06 DDYSMN WVAGINYNGGYKG ARSANWHDTALD VSYVNWY LVIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2729) NO: 2977) NO: 3225) NO: 3473) NO: 3721) NO: 3969)
    369_F10 DSYGMN WVSNINYNSGYKS ARSANWHDTALD VTYLNWY LLIYAVTSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2730) NO: 2978) NO: 3226) NO: 3474) NO: 3722) NO: 3970)
    369_F11 DSYGMN WVSNINYNSGYKS ARSANWHDTALD ISYLNWY LLIYAATSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2731) NO: 2979) NO: 3227) NO: 3475) NO: 3723) NO: 3971)
    369_G01 SSYSMN WVSNINYNSGYKS ARSANWHDTALD LSYVNWY LLIYAATSRA QQSYSSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2732) NO: 2980) NO: 3228) NO: 3476) NO: 3724) NO: 3972)
    369_G04 DSYSMN WVSGINYNGGYTS ARSANWHDTALD LTYVNWY LLIYATTSRH QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2733) NO: 2981) NO: 3229) NO: 3477) NO: 3725) NO: 3973)
    369_G06 DSYGMN WVAGINYNGGYTS ARSANWHDTALD LYSVNWY LVIYAATSRA QQSYENPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2734) NO: 2982) NO: 3230) NO: 3478) NO: 3726) NO: 3974)
    369_G11 SSYSMN WVANINYNSGYKG ARSANWHDTALD LTYLNWY LLIYAATSLA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2735) NO: 2983) NO: 3231) NO: 3479) NO: 3727) NO: 3975)
    369_G12 SSYSMN WVANINYNGGYTG ARSANWHDTALD LTYVNWY LVIYAATSRH QQSDNTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2736) NO: 2984) NO: 3232) NO: 3480) NO: 3728) NO: 3976)
    369_H05 SSYGMN WVANINYNGGYTG ARSANWHDTALD VSYVNWY LLIYAATSRA QQSYSNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2737) NO: 2985) NO: 3233) NO: 3481) NO: 3729) NO: 3977)
    369_H06 SSYGMN WVANINYNGGYKS ARSANWHDTALD VSYVNWY LLIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2738) NO: 2986) NO: 3234) NO: 3482) NO: 3730) NO: 3978)
    369_H09 DDYSMN WVSGINYNGGYTS ARSANWHDTALD LSYVNWY LLIYAVTSLA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2739) NO: 2987) NO: 3235) NO: 3483) NO: 3731) NO: 3979)
    370_A01 SSYSMN WVSGINYNSGYKS ARSANWHDTALD STYLNWY LVIYAATSRA QQSYNLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2740) NO: 2988) NO: 3236) NO: 3484) NO: 3732) NO: 3980)
    370_A03 SSYSMN WVSNINYNGGYTS ARSANWHDTALD LSYLNWY LLIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2741) NO: 2989) NO: 3237) NO: 3485) NO: 3733) NO: 3981)
    370_A04 DSYSMN WVSGINYNGGYTS ARSANWHDTALD ITYLNWY LLIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2742) NO: 2990) NO: 3238) NO: 3486) NO: 3734) NO: 3982)
    370_A12 SSYGMN WVAGINYNGGYTS ARSANWHDTALD LTYLNWY LLIYAATSLA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2743) NO: 2991) NO: 3239) NO: 3487) NO: 3735) NO: 3983)
    370_C01 DSYSMN WVSGINYNSGYTG ARSANWHDTALD LTYLNWY LVIYAATSLA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2744) NO: 2992) NO: 3240) NO: 3488) NO: 3736) NO: 3984)
    370_C03 SSYGMN WVAGINYNGGYKG ARSANWHDTALD LTYLNWY LLIYYVTNRQ QQSYSSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2745) NO: 2993) NO: 3241) NO: 3489) NO: 3737) NO: 3985)
    370_C05 SSYSMN WVAGINYNSGYTG ARSANWHDTALD LSYVNWY LVIYAATSRA QQSYNSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2746) NO: 2994) NO: 3242) NO: 3490) NO: 3738) NO: 3986)
    370_C08 SSYGMN WVAGINYNGGYKG ARSANWHDTALD SNYLNWY LLIYAVTSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2747) NO: 2995) NO: 3243) NO: 3491) NO: 3739) NO: 3987)
    370_C09 DSYGMN WVSGINYNGGYTS ARSANWHDTALD ISYLNWY LVIYAATSLA QQSYSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2748) NO: 2996) NO: 3244) NO: 3492) NO: 3740) NO: 3988)
    370_D04 DSYSMN WVANINYNSGYKG ARSANWHDTALD LTYLNWY LVIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2749) NO: 2997) NO: 3245) NO: 3493) NO: 3741) NO: 3989)
    370_D11 DSYSMN WVSGINYNGGYTG ARSANWHDTALD VSYLNWY LLIYAASTRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2750) NO: 2998) NO: 3246) NO: 3494) NO: 3742) NO: 3990)
    370_E03 SSYGMN WVSSINYNGGYKG ARSANWHDTALD LTYLNWY LVIYYASNRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2751) NO: 2999) NO: 3247) NO: 3495) NO: 3743) NO: 3991)
    370_E06 SSYGMN WVSGINYNSGYKS ARSANWHDTALD LSYLNWY LVIYATTSLA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2752) NO: 3000) NO: 3248) NO: 3496) NO: 3744) NO: 3992)
    370_E09 DDSSMH WVSNINYNGGYTG AKSANWHDTALD LSYVNWY LVIYAATSRA QQSYELPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2753) NO: 3001) NO: 3249) NO: 3497) NO: 3745) NO: 3993)
    370_F05 SSYGMN WVSGINYNSGYTS ARSANWHDTALD VSYVNWY LVIYAATSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2754) NO: 3002) NO: 3250) NO: 3498) NO: 3746) NO: 3994)
    370_F07 DSYSMN WVSNINYNGGYKG ARSANWHDTALD LSYLNWY LLIYAATSRA QQSYNLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2755) NO: 3003) NO: 3251) NO: 3499) NO: 3747) NO: 3995)
    370_F10 SSYSMN WVAGINYNGGYTS ARSANWHDTALD VSYLNWY LVIYAATSRA QQSYNSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2756) NO: 3004) NO: 3252) NO: 3500) NO: 3748) NO: 3996)
    370_G02 SDYSMN WVANINYNGGYKG ARSANWHDTALD VSYLNWY LLIYAATSRH QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2757) NO: 3005) NO: 3253) NO: 3501) NO: 3749) NO: 3997)
    370_G03 SSYSMN WVANINYNGGYTG ARSANWHDTALD LTYVNWY LVIYATTSRA QQSYNNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2758) NO: 3006) NO: 3254) NO: 3502) NO: 3750) NO: 3998)
    370_G06 SDYGMH WVSSINYNGGYTS ARSANWHDTALD LSYVNWY LVIYAATSRA QQSDNTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2759) NO: 3007) NO: 3255) NO: 3503) NO: 3751) NO: 3999)
    370_G09 SSYGMN WVAGINYNGGYKS ARSANWHDTALD LSYVNWY LVIYAATSRA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2760) NO: 3008) NO: 3256) NO: 3504) NO: 3752) NO: 4000)
    370_G10 SDYGMN WVSGINYNSGYTS ARSANWHDTALD SSYLNWY LLIYVVNNRA QQSYENPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2761) NO: 3009) NO: 3257) NO: 3505) NO: 3753) NO: 4001)
    370_G11 SSYSMN WVASINYNSGYTS ARSANWHDTHLD VSYLNWY LVIYAATSRA QQSYSLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2762) NO: 3010) NO: 3258) NO: 3506) NO: 3754) NO: 4002)
    370_H01 SSYSMN WVSGINYNSGYKG ARSANWHDTALD ISYLNWY LLIYAVTSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2763) NO: 3011) NO: 3259) NO: 3607) NO: 3755) NO: 4003)
    370_H09 SSYGMN WVANINYNGGYTS ARSANWHDTALD VSYVNWY LLIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2764) NO: 3012) NO: 3260) NO: 3508) NO: 3756) NO: 4004)
    371_A03 SDYGMN WVANINYNGGYTG ARSANWHDTALD LSYLNWY LVIYATTSRA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2765) NO: 3013) NO: 3261) NO: 3509) NO: 3757) NO: 4005)
    371_A06 SSYGMN WVAGINYNGGYTS ARSANWHDTALD LTYLNWY LVIYAATSRH QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2766) NO: 3014) NO: 3262) NO: 3510) NO: 3758) NO: 4006)
    371_A07 SDYSMN WVSNINYNGGYKS ARSANWHDTALD LSYLNWY LVIYATTSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2767) NO: 3015) NO: 3263) NO: 3511) NO: 3759) NO: 4007)
    371_A08 SSYGMH WVSSINYNGGYTS ARSANWHDTALD LSYLNWY LVIYAATSRA QQSYELPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2768) NO: 3016) NO: 3264) NO: 3512) NO: 3760) NO: 4008)
    371_A12 DSYSMN WVAGINYNSGYTS ARSANWHDTALD LSYVNWTY LVIYAATSLA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2769) NO: 3017) NO: 3265) NO: 3513) NO: 3761) NO: 4009)
    371_B06 DSYSMN WVAGINYNGGYKS ARSANWHDTALD LTYVNWY LVIYAATSRH QQSYNLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2770) NO: 3018) NO: 3266) NO: 3514) NO: 3762) NO: 4010)
    371_B07 DSYSMN WVAGINYNGGYTS ARSANWHDTALD LTYVNWY LLIYAATSRA QQSYELPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2771) NO: 3019) NO: 3267) NO: 3515) NO: 3763) NO: 4011)
    371_C03 SSYSMN WVSNINYNGGYKG ARSANWHDTALD LSYLNWY LVIYATTSRA QQSTSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2772) NO: 3020) NO: 3268) NO: 3516) NO: 3764) NO: 4012)
    371_D06 DDYSMN WVAGINYNGGYTS ARSANWHDTALD ISYVNWY LLIYAATSRA QQSYSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2773) NO: 3021) NO: 3269) NO: 3517) NO: 3765) NO: 4013)
    371_D09 SSYSMN WVSNINYNSGYTG ARSANWHDTALD LTYLNWY LVIYAATSRA QQSYNNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2774) NO: 3022) NO: 3270) NO: 3518) NO: 3766) NO: 4014)
    371_F01 SSYSMN WVAGINYNGGYTG ARSANWHDTALD LTYVNWY LVIYAATSLA QQSYNNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2775) NO: 3023) NO: 3271) NO: 3519) NO: 3767) NO: 4015)
    371_F04 DSYSMN WVAGINYNSGYKG ARSANWHDTALD LSYLNWY LLIYAATSRH QQSYNNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2776) NO: 3024) NO: 3272) NO: 3520) NO: 3768) NO: 4016)
    371_F06 DSYSMN WVANINYNGGYTS ARSANWHDTALD VSYLNWY LVIYAATSRH QQSYNSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2777) NO: 3025) NO: 3273) NO: 3521) NO: 3769) NO: 4017)
    371_F08 DDSYMN WVSGINYNGGYTG ARSANWHDTALD VSYVNWY LVIYAATSRH QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2778) NO: 3026) NO: 3274) NO: 3522) NO: 3770) NO: 4018)
    371_G05 DSYSMN WVSGINYNSGYTG ARSANWHDTALD SSYLNWY LLIYAVTSRA QQSYSSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2779) NO: 3027) NO: 3275) NO: 3523) NO: 3771) NO: 4019)
    371_G10 SSYSMN WVSGINYNGGYKS ARSANWHDTALD SSYVNWY LLIYAATSRH QQDDDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2780) NO: 3028) NO: 3276) NO: 3524) NO: 3772) NO: 4020)
    371_H09 DSYSMN WVSNINYNGGYTS ARSANWHDTALD LTYVNWY LVIYAATSLA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2781) NO: 3029) NO: 3277) NO: 3525) NO: 3773) NO: 4021)
    372_A04 DSYSMN WVSGINYNSGYTS ARSANWHDTALD LTYLNWY LVIYAATSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2782) NO: 3030) NO: 3278) NO: 3526) NO: 3774) NO: 4022)
    372_B04 DSYGMN WVANINYNGGYTS ARSANWHDTALD LSYVNWY LVIYAATSLA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2783) NO: 3031) NO: 3279) NO: 3527) NO: 3775) NO: 4023)
    272_C07 SDYSMN WVSNINYNSGYTS ARSANWHDTHLD LSYLNWY LVIYAATSRH QQSDNTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2784) NO: 3032) NO: 3280) NO: 3528) NO: 3776) NO: 4024)
    372_D02 SSYGMN WVAGINYNGGYTG ARSANWHDTALD LTYLNWY LVIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2785) NO: 3033) NO: 3281) NO: 3529) NO: 3777) NO: 4025)
    372_F03 SSYGMN WVAGINYNGGYTS ARSANWHDTALD LSYLNWY LVIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2786) NO: 3034) NO: 3282) NO: 3530) NO: 3778) NO: 4026)
    372_F06 SDYGMN WVAGINYNGGYKS ARSANWHDTALD LSYVNWY LLIYAATSLA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2787) NO: 3035) NO: 3283) NO: 3531) NO: 3779) NO: 4027)
    372_F08 SDYSMN WVSNINYNSGYTG ARSANWHDTALD LTYVNWY LVIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2788) NO: 3036) NO: 3284) NO: 3532) NO: 3780) NO: 4028)
    372_F09 DSYSMN WVANINYNSGYKG ARSANWHDTALD LTYLNWY LVIYAATSLA QQSYSSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2789) NO: 3037) NO: 3285) NO: 3533) NO: 3781) NO: 4029)
    373_A02 DSYGMN WVSGINYNGGYKG ARSANWHDTALD LSYVNWY LVIYATTSLA QQSYNTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2790 NO: 3038) NO: 3286) NO: 3534) NO: 3782) NO: 4030)
    373_A08 DSYGMN WVSNINYNGGYTG ARSANWHDTALD VSYVNWY LLIYAATSLA QQSYSLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2791) NO: 3039) NO: 3287) NO: 3535) NO: 3783) NO: 4031)
    373_A10 SSYGMN WVSGINYNSGYTS ARSANWHDTALD LSYLNWY LVIYAATSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2792) NO: 3040) NO: 3288) NO: 3536) NO: 3784) NO: 3032)
    373_B04 SSYGMN WVAGINYNSGYKG ARSANWHDTALD LTYLNWY LLIYAATSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2793) NO: 3041) NO: 3289) NO: 3537) NO: 3785) NO: 4033)
    373_B06 SDYSMN WVAGINYNGGYTG ARSANWHDTALD LTYVNWY LVIYAATSRH QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2794) NO: 3042) NO: 3290) NO: 3538) NO: 3786) NO: 4034)
    373_B10 DSYGMN WVSNINYNGGYTS ARSANWHDTALD LSYLNWY LLIYAATSRA QQSTDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2795) NO: 3043) NO: 3292) NO: 3539) NO: 3787) NO: 4035)
    373_B12 DSYGMN WVSSINYNSGYTS ARSANWHDTALD VSYVNWY LLIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2796) NO: 3044) NO: 3292) NO: 3540) NO: 3788) NO: 4036)
    373_C02 DDYSMN WVSGINYNSGYKG ARSANWHDTALD LSYVNWY LLIYAATSRA QQSYNTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2797) NO: 3045) NO: 3293) NO: 3541) NO: 3789) NO: 4037)
    373_C04 SSYSMN WVANINYNSGYTG ARSANWHTALD ISYVNWY LVIYAVTSRA QQSYNSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2798) NO: 3046) NO: 3294) NO: 3542) NO: 3790) NO: 4038)
    373_C06 SSYSMN WVAGINYNGGYTG ARSANWHDTALD VSYVNWY LVIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2799) NO: 3047) NO: 3295) NO: 3543) NO: 3791) NO: 4039)
    373_C08 SSYSMN WVANINYNGGYTS ARSANWHDTALD ISYLNWY LLIYAASSLQ QQSYNNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2800) NO: 3048) NO: 3296) NO: 3544) NO: 3792) NO: 4040)
    373_C11 SSYSMN WVSGINYNSGYTG ARSANWHDTALD LTYVNWY LVIYAVTSRA QSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2801) NO: 3049) NO: 3297) NO: 3545) NO: 3793) NO: 4041)
    373_D01 DSYSMN WVSGINYNSGYKS ARSANWHDTHLD LSYVNWY LVIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2802) NO: 3050) NO: 3298) NO: 3546) NO: 3794) NO: 4042)
    373_D04 DSYSMN WVSGINYNSGYKG ARSANWHDTALD LSYLNWY LLIYAATSRH QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2803) NO: 3051) NO: 3299) NO: 3547) NO: 3795) NO: 4043)
    373_D05 SSYSMN WVSGINYNSGYKG ARSANWHDTALD LSYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2804) NO: 3052) NO: 3300) NO: 3548) NO: 3796) NO: 4044)
    373_D08 DDYSMN WVSGINYNGGYKS ARSANWHDTALD LSYVNWY LLIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2805) NO: 3053) NO: 3301) NO: 3549) NO: 3797) NO: 4045)
    373_D10 DSYSMN WVSNINYNSGYKG ARSANWHDTALD LSYVNWY LLIYAATSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2806) NO: 3054) NO: 3302) NO: 3550) NO: 3798) NO: 4046)
    373_E01 SSYGMN WVSGINYNGGYKG ARSANWHDTALD VYSVNWY LLIYAATSRH QQSYNNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2807) NO: 3055) NO: 3303) NO: 3551) NO: 3799) NO: 4047)
    373_E05 DSYGMN WVSNINYNGGYTS ARSANWHDTALD LSYVNWY LLIYAVTSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2808) NO: 3056) NO: 3304) NO: 3552) NO: 3800) NO: 4048)
    373_E07 SSYGMN WVANINYNGGYTS ARSANWHDTALD LTYVNWY LLIYAATSLA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2809) NO: 3057) NO: 3305) NO: 3553) NO: 3801) NO: 4049)
    373_E12 SSYSMN WVANINYNGGYTG ARSANWHDTALD LSYVNWY LVIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 3810) NO: 3058) NO: 3306) NO: 3554) NO: 3802) NO: 4050)
    373_G10 SDYGMN WVSNINYNGGYKS ARSANWHDTALD VSYVNWY LLIYAATSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2811) NO: 3059) NO: 3307) NO: 3555) NO: 3803) NO: 4051)
    373_G12 SSYSMN WVSNINYNGGYTS ARSANWHDTALD LSYLNWY LLIYATTSLA QQSYNSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2812) NO: 3060) NO: 3308) NO: 3556) NO: 3804) NO: 4052)
    373_H01 DSYSMN WVANINYNGGYTG ARSANWHDTALD LSYLNWY LVIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2813) NO: 3061) NO: 3309) NO: 3557) NO: 3805) NO: 4053)
    373_H05 SDYSMN WVANINYNGGYKG ARSANWHDTALD LTYVNWY LVIYAATSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2814) NO: 3062) NO: 3310) NO: 3558) NO: 3806) NO: 4054)
    374_A07 SSYSMN WVSGINYNSGYKG ARSANWHDTALD LSYVNWY LLIYAVTSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2815) NO: 3063) NO: 3311) NO: 3559) NO: 3807) NO: 4055)
    374_B04 SSYSMN WVSNINYNSGYTG ARSANWHDTALD VSYLNWY LLIYAVTSRA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2816) NO: 3064) NO: 3312) NO: 3560) NO: 3808) NO: 4056)
    374_B06 DSYSMN WVAGINYNSGYKG ARSANEHDTHLD LTYVNWY LLIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2817) NO: 3065) NO: 3313) NO: 3561) NO: 3809) NO: 4057)
    374_B12 DSYSMN WVAGINYNGGYTG ARSANWHDTHLD SSYLNWY LVIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2818) NO: 3066) NO: 3314) NO: 3562) NO: 3810) NO: 4058)
    374_C03 DSYSMN WVSGINYNSGYTS ARSANWHDTALD LTYLNWY LLIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2819) NO: 3067) NO: 3315) NO: 3563) NO: 3811) NO: 4059)
    374_C06 DDYSMN WVSSINYNSGYKG ARSANWHDTALD LTYVNWY LLIYAATSRA QQSYNSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2820) NO: 3068) NO: 3316) NO: 3564) NO: 3812) NO: 4060)
    374_D01 DSYSMN WVSGINYNSGYKG ARSANWHDTALD ITYVNWY LLIYAATSLA QQSYSSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2821) NO: 3069) NO: 3317) NO: 3565) NO: 3813) NO: 4061)
    374_D08 DSYGMN WVSGINYNSGYTG ARSANWHDTHLD LTYLNWY LLIYAATSRH QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2822) NO: 3070) NO: 3318) NO: 3566) NO: 3814) NO: 4062)
    374_E01 SSYGMN WVAGINYNGGYTS ARSANWHDTALD SSYVNWY LLIYAATSRA QQSYSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2823) NO: 3071) NO: 3319) NO: 3567) NO: 3815) NO: 4063)
    374_E02 SSYSMN WVSGINYNGGYTS ARSANWHDTALD LSYLNWY LLIYAATSLA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2824) NO: 3072) NO: 3320) NO: 3568) NO: 3816) NO: 4064)
    374_E05 SSYSMN WVAGINYNGGYTS ARSANWHDTALD LSFVNWY LVIYAATSRA QQSYNLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2825) NO: 3073) NO: 3321) NO: 3569) NO: 3817) NO: 4065)
    374_E07 SDYSMN WVAGINYNGGYTS ARSANWHDTALD ITYVNWY LVIYAATSRA QQSYNTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2826) NO: 3074) NO: 3322) NO: 3570) NO: 3818) NO: 4066)
    374_E08 SSYGMN WVAGINYNGGYKS ARSANEHDTALD LSYLNWY LLIYAATSRH QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2827) NO: 3075) NO: 3323) NO: 3571) NO: 3819) NO: 4067)
    374_E11 SSYGMN WVSNINYNGGYTS ARSANWHDTALD VTYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2828) NO: 3076) NO: 3324) NO: 3572) NO: 3820) NO: 4068)
    374_F01 DSYSMN WVSNINYNGGYTG ARSANWHDTALD LSYVNWY LVIYAATSRH QQSYENPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2829) NO: 3077) NO: 3325) NO: 3573) NO: 3821) NO: 4069)
    374_F02 DSYSMN WVANINYNSGYTS ARSANWHDTALD VSYLNWY LLIYAASSLQ QQSYELPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2830 NO: 3078) NO: 3326) NO: 3574) NO: 3822) NO: 4070)
    374_F04 SSYGMN WVSGINYNSGYKS ARSANWHDTALD LTYVNWY LLIYAATSRA QQSYNSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2831) NO: 3079) NO: 3327) NO: 3575) NO: 3823) NO: 4071)
    374_F10 SSYSMN WVSGINYNGGYTS ARSANWHDTALD LSYLNWY LVIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2832) NO: 3080) NO: 3328) NO: 3576) NO: 3824) NO: 4072)
    374_F11 DSYSMN WVSNINYNGGYTG ARSANWHDTALD LSYLNWY LLIYAVTSLA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2933) NO: 3081) NO: 3329) NO: 3577) NO: 3825) NO: 4073)
    374_G04 SSYSMN WVAGINYNGGYTG ARSANWHDTALD LTYLNWY LVIYAATSLA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2834) NO: 3082) NO: 3330) NO: 3578) NO: 3826) NO: 4074)
    374_G06 SSYGMH WVASINYNGGYTS ARSANWHDTALD LSYLNWY LLIYAVTSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2835) NO: 3083) NO: 3331) NO: 3579) NO: 3827) NO: 4075)
    374_G07 SSYSMN WVSGINYNSGYKS ARSANWHDTALD ISYLNWY LLIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2836) NO: 3084) NO: 3332) NO: 3580) NO: 3828) NO: 4076)
    374_H03 SSYGMN WVSGINYNSGYKS ARSANWHDTALD LSYVNWY LVIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2837 NO: 3085) NO: 3333) NO: 3581) NO: 3829) NO: 4077)
    374_H04 DSYSMN WVSGINYNSGYTS ARSANWHDTALD LTYLNWY LLIYAATSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2838 NO: 3086) NO: 3334) NO: 3582) NO: 3830) NO: 4078)
    374_H06 SSYGMN WVSNINYNGGYTG ARSANWHDTALD VSYVNWY LVIYAATSRA QQSYNLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2839) NO: 3087) NO: 3335) NO: 3583) NO: 3831) NO: 4079)
    374_H07 DSYGMN WVANINYNGGYTG ARSANWHDTALD LTYLNWY LLIYAATSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2840) NO: 3088) NO: 3336) NO: 3584) NO: 3832) NO: 4080)
    374_H09 SSYSMN WVANINYNSGYKS ARSANWHDTALD LSYLNWY LVIYAVTSLA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2841) NO: 3089) NO: 3337) NO: 3585) NO: 3833) NO: 4081)
    375_A05 SSYGMN WVANINYNGGYKG ARSANWHDTALD LSYLNWY LLIYAATSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2842) NO: 3090) NO: 3338) NO: 3586) NO: 3834) NO: 4082)
    375_C06 DDYGMH WVASINYNSGYTS ARSANWHDTALD LTYVNWY LVIYATTSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2843) NO: 3091) NO: 3339) NO: 3587) NO: 3835) NO: 4083)
    375_D04 DDSSMH WVSNINYNGGYTG AKSANWHDTALD LSYVNWY LVIYAATSRA QQSYELPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2844) NO: 3092) NO: 3340) NO: 3588) NO: 3836) NO: 4084)
    375_D05 SSYSMN WVASINYNSGYTS ARSANWHDTHLD VSYLNWY LLIYAATSLH QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2845) NO: 3093) NO: 3341) NO: 3589) NO: 3837) NO: 4085)
    375_D07 SSYGMN WVANINYNSGYTG ARSANWHDTALD ITYLNWY LLIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2846) NO: 3094) NO: 3342) NO: 3590) NO: 3838) NO: 4086)
    375_D08 SDYGMN WVSGINYNSGYKG ARSANWHDTALD ITYLNWY LLIYAATSRA QQSYSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2847) NO: 3095) NO: 3343) NO: 3591) NO: 3839) NO: 4087)
    375_D12 DSYGMN WVSSINYNSGYTS ARSANWHDTALD LTYVNWY LVIYAATSRA QQSYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2848) NO: 3096) NO: 3344) NO: 3592) NO: 3840) NO: 4088)
    375_E01 SSYSMN WVSGINYNSGYKS ARSANWHDTLAD LTYLNWY LVIYAATSRA QQSDDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2849) NO: 3097) NO: 3345) NO: 3593) NO: 3841) NO: 4089)
    375_E07 SDYSMN WVAGINYNSGYKG ARSANWHDTALD VTYLNWY LLIYVVTNRE AASYETPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2850) NO: 3098) NO: 3346) NO: 3594) NO: 3842) NO: 4090)
    375_H12 SSYGMN WVAGINYNGGYKG ARSANWHDTALD LTYLNWY LLIYYVTNRQ QQSYSIPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2851) NO: 3099) NO: 3347) NO: 3595) NO: 3843) NO: 4091)
    376_A04 DSYSMN WVSNINYNGGYTS ARSANWHDTALD VTYLNWY LVIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2852) NO: 3100) NO: 3348) NO: 3596) NO: 3844) NO: 4092)
    376_A10 SDYGMN WVSNINYNSGYKG ARSANWHDTALD LSYLNWY LLIYAATSRA QQSYESPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2853) NO: 3101) NO: 3349) NO: 3597) NO: 3845) NO: 4093)
    376_A12 SSYSMN WVANINYNSGYKG ARSANWHDTALD LSYVNWY LVIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2854) NO: 3102) NO: 3350) NO: 3598) NO: 3846) NO: 4094)
    376_B04 DSYGMH WVASINYNGGYTG ARSANWHDTALD VSYVNWY LVIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2855) NO: 3103) NO: 3351) NO: 3599) NO: 3847) NO: 4095)
    376_B05 SSYSMN WVANINYNGGYTG ARSANWHDTALD ISYVNWY LLIYAATSRA QQSYELPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2856) NO: 3104) NO: 3352) NO: 3600) NO: 3848) NO: 4096)
    376_B09 DSYSMN WVANINYNSGYKG ARSANWHDTALD LTYVNWY LVIYAATSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2857) NO: 3105) NO: 3353) NO: 3601) NO: 3849) NO: 4097)
    376_B11 SSYSMN WVSGINYNGGYTS ARSANWHDTALD LSYVNWY LVIYAATSRA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2858) NO: 3106) NO: 3354) NO: 3602) NO: 3850) NO: 4098)
    376_C01 DSYSMN WVAGINYNGGYTS ARSANWHDTALD LTYLNWY LLIYAATSLA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2859) NO: 3107) NO: 3355) NO: 3603) NO: 3851) NO: 4099)
    376_C02 DSYGMN WVSGINYNSGYTS ARSANWHDTALD VSYLNWY LVIYAVTSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2860) NO: 3108) NO: 3356) NO: 3604) NO: 3852) NO: 4100)
    376_C12 SSYSMN WVAGINYNGGYTG ARSANWHDTALD LTYVNWY LLIYAATSRA QQDYSDPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2861) NO: 3109) NO: 3357) NO: 3605) NO: 3853) NO: 4101)
    376_D05 SSYSMN WVSNINYNGGYKG ARSANWHDTALD VSYVNWY LLIYAATSLA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2862) NO: 3110) NO: 3358) NO: 3606) NO: 3854) NO: 4102)
    376_D11 SSYGMN WVANINYNGGYTG ARSANWHDTALD LSYLNWY LVIYAATSRA QQSYNNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2863) NO: 3111) NO: 3359) NO: 3607) NO: 3855) NO: 4103)
    376_E03 SSYGMN WVANINYNGGYTG ARSANWHDTALD LSYVNWY LVIYAATSLA QQSYDLPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2864) NO: 3112) NO: 3360) NO: 3608) NO: 3856) NO: 4101)
    376_E08 SDYGMN WVAGININGGYTS ARSANWHDTALD VSYVNWY LVIYAATSRA QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2865) NO: 3113) NO: 3361) NO: 3609) NO: 3857) NO: 4105)
    376_F03 DSYGMN WVANINYNGGYTG ARSANWHDTALD ITYVNWY LVIYATTLSA QQSYSSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2866) NO: 3114) NO: 3362) NO: 3610) NO: 3858) NO: 4106)
    376_F04 DSYSMN WVSNINYNSGYTG ARSANWHDTALD SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2867) NO: 3115) NO: 3363) NO: 3611) NO: 3859) NO: 4107)
    376_G08 DSYGMN WVANINYNGGYTS ARSANWHDTALD LSYVNWY LVIYAATSRA QQSYDTPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2868) NO: 3116) NO: 3364) NO: 3612) NO: 3860) NO: 4108)
    376_G09 DAYSMN WVSGINYNSGYKG ARSANWHDTALD SYYLNWY LLIYAVTSRA QQSYDNPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2869) NO: 3117) NO: 3365) NO: 3613) NO: 3861) NO: 4109)
    376_H09 SDYSMN WVANINYNGGYTG ARSANWHDTALD ITYLNWY LVIYYVSNLP QQSYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2870) NO: 3118) NO: 3366) NO: 3614) NO: 3862) NO: 4110)
    376_H10 DSYSMN WVSGINYNSGYKS ARSANWHDTALD LTYLNWY LVIYAATSRH QQDYDSPL
    (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID
    NO: 2871) NO: 3119) NO: 3367) NO: 3615) NO: 3863) NO: 4111)
  • The consensus sequences for each of these CDRs shown in FIG. 3E are as follows:
  • HCDR1:
    (SEQ ID NO: 6578)
    S/DS/DYG/SMN/H
    HCDR2:
    (SEQ ID NO: 6579)
    WVS/AG/N/SINYNG/SGYT/KS/G
    HCDR3:
    (SEQ ID NO: 6597)
    AR/KSANWHDTA/HLD
    LCDR1:
    (SEQ ID NO: 6561)
    L/V/I/SS/TYLNNWY
    LCDR2:
    (SEQ ID NO: 6582)
    LL/VIYA/YA/V/TT/SS/NR/LA/H/Q
    LCDR3:
    (SEQ ID NO: 6598)
    QQSY/DD/E/N/SS/T/L/NPL
  • TABLE 2F
    Group IV Antibody Sequences
    Ab VH sequence VL sequence
    365_E02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FSSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCAKSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4281)
    GTLVTVSS (SEQ ID NO: 4112)
    370_G12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDESPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4282)
    GTLVTVSS (SEQ ID NO: 4113)
    368_C01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    FDSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4283)
    GTLVTVSS (SEQ ID NO: 4114)
    376_C06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4284)
    GTLVTVSS (SEQ ID NO: 4115)
    368_D10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYGMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4285)
    GTLVTVSS (SEQ ID NO: 4116)
    365_G12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYGMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4286)
    GTLVTVSS (SEQ ID NO: 4117)
    367_C03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYATTSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4287)
    GTLVTVSS (SEQ ID NO: 4118)
    367_H07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYATTSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4288)
    GTLVTVSS (SEQ ID NO: 4119)
    371_D03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4289)
    GTLVTVSS (SEQ ID NO: 4120)
    369_C10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FSSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSLHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDSLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4290)
    GTLVTVSS (SEQ ID NO: 4121)
    367_F05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYGMNWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4291)
    GTLVTVSS (SEQ ID NO: 4122)
    365_C07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSDYGMNWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4292)
    GTLVTVSS (SEQ ID NO: 4123)
    374_C08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4293)
    GTLVTVSS (SEQ ID NO: 4124)
    376_A06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYYVSNRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4294)
    GTLVTVSS (SEQ ID NO: 4125)
    376_B07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYYVSNRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4295)
    GTLVTVSS (SEQ ID NO: 4126)
    365_F07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4296)
    GTLVTVSS (SEQ ID NO: 4127)
    369_E10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4297)
    GTLVTVSS (SEQ ID NO: 4128)
    373_E03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTALDYWGQ KVEIK (SEQ ID NO: 4298)
    GTLVTVSS (SEQ ID NO: 4129)
    366_B04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4299)
    GTLVTVSS (SEQ ID NO: 4130)
    376_F12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FDDYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4300)
    GTLVTVSS (SEQ ID NO: 4131)
    369_F07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4301)
    GTLVTVSS (SEQ ID NO: 4132) DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    368_C06 EVQLLESGGGLVQPGGSLRLSCAASGFT WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    FDSYSMNWVRQAPGKGLEWVAGINYNGG TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    YKSYADSVKGRFTISRDNSKNTLYLQMN KVEIK (SEQ ID NO: 4302)
    SLRAEDTAVYYCARSATWHDTHLDYWGQ
    GTLVTVSS (SEQ ID NO: 4133)
    376_E12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4303)
    GTLVTVSS (SEQ ID NO: 4134)
    371_H01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4304)
    GTLVTVSS (SEQ ID NO: 4135)
    367_E02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4305)
    GTLVTVSS (SEQ ID NO: 4136)
    365_F04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYVN
    FSSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4306)
    GTLVTVSS (SEQ ID NO: 4137)
    370_A09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4307)
    GTLVTVSS (SEQ ID NO: 4138)
    365_B03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4308)
    GTLVTVSS (SEQ ID NO: 4139)
    369_A05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4309)
    GTLVTVSS (SEQ ID NO: 4140)
    373_H10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4310)
    GTLVTVSS (SEQ ID NO: 4141)
    367_A09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4311)
    GTLVTVSS (SEQ ID NO: 4142)
    370_F08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4312)
    GTLVTVSS (SEQ ID NO: 4143)
    376_B01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4313)
    GTLVTVSS (SEQ ID NO: 4144)
    365_D05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4314)
    GTLVTVSS (SEQ ID NO: 4145)
    373_E04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4315)
    GTLVTVSS (SEQ ID NO: 4146)
    368_G05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSLHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4316)
    GTLVTVSS (SEQ ID NO: 4147)
    365_A01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSDYGMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYATTSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4317)
    GTLVTVSS (SEQ ID NO: 4148)
    373_H06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FSSYGMHWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4318)
    GTLVTVSS (SEQ ID NO: 4149)
    369_G07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4319)
    GTLVTVSS (SEQ ID NO: 4150)
    373_G05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4320)
    GTLVTVSS (SEQ ID NO: 4151)
    372_F07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDDYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4321)
    GTLVTVSS (SEQ ID NO: 4152)
    370_H03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4322)
    GTLVTVSS (SEQ ID NO: 4153)
    366_A03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4323)
    GTLVTVSS (SEQ ID NO: 4154)
    365_A07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSSYGMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4324)
    GTLVTVSS (SEQ ID NO: 4155)
    376_B06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4325)
    GTLVTVSS (SEQ ID NO: 4156)
    374_C11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4326)
    GTLVTVSS (SEQ ID NO: 4157)
    375_A06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4327)
    GTLVTVSS (SEQ ID NO: 4158)
    365_B09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILRYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSLHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4328)
    GTLVTVSS (SEQ ID NO: 4159)
    373_E06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILRYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSLHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4329)
    GTLVTVSS (SEQ ID NO: 4160)
    374_C05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIIRYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4330)
    GTLVTVSS (SEQ ID NO: 4161)
    376_C11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4331)
    GTLVTVSS (SEQ ID NO: 4162)
    373_C09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4332)
    GTLVTVSS (SEQ ID NO: 4163)
    368_H01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYATTSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4333)
    GTLVTVSS (SEQ ID NO: 4164)
    373_B03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4334)
    GTLVTVSS (SEQ ID NO: 4165)
    374_C04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4335)
    GTLVTVSS (SEQ ID NO: 4166)
    371_F05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4336)
    GTLVTVSS (SEQ ID NO: 4167)
    369_A10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4337)
    GTLVTVSS (SEQ ID NO: 4168)
    366_A05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4338)
    GTLVTVSS (SEQ ID NO: 4169)
    375_G07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4339)
    GTLVTVSS (SEQ ID NO: 4170)
    374_D02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISTYVN
    FDSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAVTSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4340)
    GTLVTVSS (SEQ ID NO: 4171)
    365_A10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMHWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLVIYAVTSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4341)
    GTLVTVSS (SEQ ID NO: 4172)
    375_A02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FSSYSMNWVRQAPGKGLEWVAGINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4342)
    GTLVTVSS (SEQ ID NO: 4173)
    371_G03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYVN
    FSSYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4343)
    GTLVTVSS (SEQ ID NO: 4174)
    370_E07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4344)
    GTLVTVSS (SEQ ID NO: 4175)
    375_B04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4345)
    GTLVTVSS (SEQ ID NO: 4176)
    367_G07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4346)
    GTLVTVSS (SEQ ID NO: 4177)
    366_C02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSDYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4347)
    GTLVTVSS (SEQ ID NO: 4178)
    375_C12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4348)
    GTLVTVSS (SEQ ID NO: 4179)
    365_F08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDDYGMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4349)
    GTLVTVSS (SEQ ID NO: 4180)
    368_G09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FDSYGMHWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4350)
    GTLVTVSS (SEQ ID NO: 4181)
    368_E11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FDSYGMHWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4351)
    GTLVTVSS (SEQ ID NO: 4182)
    367_F02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FDSYSMNWVRQAPGKGLEWVANINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4352)
    GTLVTVSS (SEQ ID NO: 4183)
    373_B08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4353)
    GTLVTVSS (SEQ ID NO: 4184)
    374_A11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSDYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4354)
    GTLVTVSS (SEQ ID NO: 4185)
    373_B11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4355)
    GTLVTVSS (SEQ ID NO: 4186)
    373_F03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4356)
    GTLVTVSS (SEQ ID NO: 4187)
    372_D04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVANINYNSG WYQQKPGKAPKLLIYAATSLHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4357)
    GTLVTVSS (SEQ ID NO: 4188)
    366_C01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FSDYGMNWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLLIYAATSPASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4358)
    GTLVTVSS (SEQ ID NO: 4189)
    367_A01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4359)
    GTLVTVSS (SEQ ID NO: 4190)
    366_H05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDSYGMHWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4360)
    GTLVTVSS (SEQ ID NO: 4191)
    369_B09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYGMHWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4361)
    GTLVTVSS (SEQ ID NO: 4192)
    366_D07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSDYGMHWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4362)
    GTLVTVSS (SEQ ID NO: 4193)
    369_D11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYGMHWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4363)
    GTLVTVSS (SEQ ID NO: 4194)
    370_B05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYGMNWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4364)
    GTLVTVSS (SEQ ID NO: 4195)
    366_D02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVASINYNGG WYQQKPGKAPKLLIYATTSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4365)
    GTLVTVSS (SEQ ID NO: 4196)
    368_H12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FDSYSMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4366)
    GTLVTVSS (SEQ ID NO: 4197)
    368_F12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FDDYSMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4367)
    GTLVTVSS (SEQ ID NO: 4198)
    370_A06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FSSYSMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4368)
    GTLVTVSS (SEQ ID NO: 4199)
    369_F12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FSSYSMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLLIYAVTSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4369)
    GTLVTVSS (SEQ ID NO: 4200)
    366_A09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSDYGMHWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4370)
    GTLVTVSS (SEQ ID NO: 4201)
    368_H07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMHWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4371)
    GTLVTVSS (SEQ ID NO: 4202)
    370_C04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYGMNWVRQAPGKGLEWVASINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4372)
    GTLVTVSS (SEQ ID NO: 4203)
    373_E02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVRYLN
    FDSYGMHWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4373)
    GTLVTVSS (SEQ ID NO: 4204)
    374_E09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FSDYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4374)
    GTLVTVSS (SEQ ID NO: 4205)
    371_C09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4375)
    GTLVTVSS (SEQ ID NO: 4206)
    369_B12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYATTSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4376)
    GTLVTVSS (SEQ ID NO: 4207)
    369_B02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4377)
    GTLVTVSS (SEQ ID NO: 4208)
    365_C09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSDYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4378)
    GTLVTVSS (SEQ ID NO: 4209)
    374_B09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVRYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4379)
    GTLVTVSS (SEQ ID NO: 4210)
    374_D12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4380)
    GTLVTVSS (SEQ ID NO: 4211)
    374_C02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4381)
    GTLVTVSS (SEQ ID NO: 4212)
    374_H08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSLHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4382)
    GTLVTVSS (SEQ ID NO: 4213)
    369_D06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4383)
    GTLVTVSS (SEQ ID NO: 4214)
    366_B06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYAAPSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYXTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4384)
    GTLVTVSS (SEQ ID NO: 4215)
    367_A11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYGMHWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLVIYATTSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4385)
    GTLVTVSS (SEQ ID NO: 4216)
    369_F04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FSSYGMNWVRQAPGKGLEWVSGINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4386)
    GTLVTVSS (SEQ ID NO: 4217)
    369_A01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4387)
    GTLVTVSS (SEQ ID NO: 4218)
    373_H12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSDYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4388)
    GTLVTVSS (SEQ ID NO: 4219)
    376_C07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4389)
    GTLVTVSS (SEQ ID NO: 4220)
    366_E02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4390)
    GTLVTVSS (SEQ ID NO: 4221)
    376_G01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FDDYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAVTSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4391)
    GTLVTVSS (SEQ ID NO: 4222)
    373_F02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4392)
    GTLVTVSS (SEQ ID NO: 4223)
    376_E09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4393)
    GTLVTVSS (SEQ ID NO: 4224)
    365_H04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSDYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4394)
    GTLVTVSS (SEQ ID NO: 4225)
    369_E04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSDYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4395)
    GTLVTVSS (SEQ ID NO: 4226)
    374_B11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4396)
    GTLVTVSS (SEQ ID NO: 4227)
    376_G11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYVN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4397)
    GTLVTVSS (SEQ ID NO: 4228)
    374_E04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4398)
    GTLVTVSS (SEQ ID NO: 4229)
    373_B08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDSYGMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAVTSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4399)
    GTLVTVSS (SEQ ID NO: 4230)
    375_B10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4400)
    GTLVTVSS (SEQ ID NO: 4231)
    365_E08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYVN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4401)
    GTLVTVSS (SEQ ID NO: 4232)
    374_G02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4402)
    GTLVTVSS (SEQ ID NO: 4233)
    373_D09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4403)
    GTLVTVSS (SEQ ID NO: 4234)
    365_A04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSDYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4404)
    GTLVTVSS (SEQ ID NO: 4235)
    371_B05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSSYSMNWVRQAPGKGLEWVSGINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDETPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4405)
    GTLVTVSS (SEQ ID NO: 4236)
    376_H08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDSLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4406)
    GTLVTVSS (SEQ ID NO: 4237)
    367_G08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4407)
    GTLVTVSS (SEQ ID NO: 4238)
    372_H03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIITYVN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4408)
    GTLVTVSS (SEQ ID NO: 4239)
    366_E03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4409)
    GTLVTVSS (SEQ ID NO: 4240)
    371_F12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSNNLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4410)
    GTLVTVSS (SEQ ID NO: 4241)
    366_C03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4411)
    GTLVTVSS (SEQ ID NO: 4242)
    376_A01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4412)
    GTLVTVSS (SEQ ID NO: 4243)
    365_E03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSLHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDERPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4413)
    GTLVTVSS (SEQ ID NO: 4244)
    371_B10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4414)
    GTLVTVSS (SEQ ID NO: 4245)
    369_G09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4415)
    GTLVTVSS (SEQ ID NO: 4246)
    369_A06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSDYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4416)
    GTLVTVSS (SEQ ID NO: 4247)
    369_C08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FSDYGMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4417)
    GTLVTVSS (SEQ ID NO: 4248)
    373_A07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDNLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4418)
    GTLVTVSS (SEQ ID NO: 4249)
    367_D02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYVN
    FDDYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYENPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4419)
    GTLVTVSS (SEQ ID NO: 4250)
    374_C07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIISYLN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4420)
    GTLVTVSS (SEQ ID NO: 4251)
    374_A03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4421)
    GTLVTVSS (SEQ ID NO: 4252)
    365_A02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4422)
    GTLVTVSS (SEQ ID NO: 4253)
    365_D06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4423)
    GTLVTVSS (SEQ ID NO: 4254)
    366_C07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVSNINYNGG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4424)
    GTLVTVSS (SEQ ID NO: 4255)
    367_F12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FDDYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4425)
    GTLVTVSS (SEQ ID NO: 4256)
    369_E09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4426)
    GTLVTVSS (SEQ ID NO: 4257)
    365_G02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FSDYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLVIYAVTSLHSGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYELPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4427)
    GTLVTVSS (SEQ ID NO: 4258)
    373_D02 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSSYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4428)
    GTLVTVSS (SEQ ID NO: 4259)
    374_E03 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4429)
    GTLVTVSS (SEQ ID NO: 4260)
    374_D11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYLN
    FDSYGMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4430)
    GTLVTVSS (SEQ ID NO: 4261)
    370_D07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSSYGMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYESPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4431)
    GTLVTVSS (SEQ ID NO: 4262)
    374_A08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FDSYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4432)
    GTLVTVSS (SEQ ID NO: 4263)
    374_G01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDSYSMNWVRQAPGKGLEWVSNINYNSG WYQQKPGKAPKLLIYATTSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4433)
    GTLVTVSS (SEQ ID NO: 4264)
    374_G12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FDDYGMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLVIYAATSLASGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNSPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4434)
    GTLVTVSS (SEQ ID NO: 4265)
    375_G10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FSSYGMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLVIYAATSRHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4435)
    GTLVTVSS (SEQ ID NO: 4266)
    369_H11 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FSDYGMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4436)
    GTLVTVSS (SEQ ID NO: 4267)
    375_G12 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDSYGMHWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4437)
    GTLVTVSS (SEQ ID NO: 4268)
    366_F06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISTYLN
    FSDYGMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4438)
    GTLVTVSS (SEQ ID NO: 4269)
    368_G07 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYSMHWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4439)
    GTLVTVSS (SEQ ID NO: 4270)
    367_H04 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILTYVN
    FSSYSMNWVRQAPGKGLEWVSSINYNGG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSDNNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4440)
    GTLVTVSS (SEQ ID NO: 4271)
    374_E06 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYLN
    FDSYSMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4441)
    GTLVTVSS (SEQ ID NO: 4272)
    370_A10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSILSYVN
    FSDYSMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLLIYAATSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4442)
    GTLVTVSS (SEQ ID NO: 4273)
    368_H10 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FSSYSMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLVIYAVTSLASGVPSRFSGSGSG
    YKGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYETPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4443)
    GTLVTVSS (SEQ ID NO: 4274)
    368_G08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYVN
    FDDYGMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLLIYAATSRHSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYNNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4444)
    GTLVTVSS (SEQ ID NO: 4275)
    365_H09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FSSYGMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YKSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4445)
    GTLVTVSS (SEQ ID NO: 4276)
    370_A08 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVTYLN
    FDSYSMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDLPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4446)
    GTLVTVSS (SEQ ID NO: 4277)
    368_B05 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN
    FDSYSMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4447)
    GTLVTVSS (SEQ ID NO: 4278)
    375_F01 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSIVSYLN
    FSSYSMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLVIYAATSRASGVPSRFSGSGSG
    YTGYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYDNPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4448)
    GTLVTVSS (SEQ ID NO: 4279)
    374_F09 EVQLLESGGGLVQPGGSLRLSCAASGFT DIQMTQSPSSLSASVGDRVTITCRASQSISSYVN
    FSSYGMNWVRQAPGKGLEWVSSINYNSG WYQQKPGKAPKLLIYAATSRASGVPSRFSGSGSG
    YTSYADSVKGRFTISRDNSKNTLYLQMN TDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGT
    SLRAEDTAVYYCARSATWHDTHLDYWGQ KVEIK (SEQ ID NO: 4449)
    GTLVTVSS (SEQ ID NO: 4280)
  • Table 3F provides the amino acid sequences of the CDRs of the antibodies shown in Table 2F.
  • TABLE 3F
    CDR sequences for Group VI antibodies
    Ab HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3
    365_E02 SSYSMN WVANINY AKSATW ISYLNWY LLIYAATSRA QQSYENPL
    (SEQ NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5126) NO:
    4450) NO: NO: 4957) 5295)
    4619) 4788)
    370_G12 SSYSMN WVAGINY ARSATW ITYLNWY LLIYAATSLA QQSDESPL
    (SEQ NGGYKG HDTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5127) NO:
    4451) NO: NO: 4958) 5296)
    4620) 4789)
    368_C01 DSYGMN WVAGINY ARSATWH ITYLNWY LLIYAATSRA QQSYDSPL
    (SEQ NGGYTG DTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5128) NO:
    4452) NO: NO: 4959) 5297)
    4621) 4790)
    376_C06 SSYGMN WVAGINY ARSATWH LSYLNWY LVIYAATSRA QQSYDSPL
    (SEQ NGGYTS DTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5129) NO:
    4453) NO: NO: 4960) 5298)
    4622) 4791)
    368_D10 DSYGMN WVAGINY ARSATWH LSYLNWY LVIYAATSRA QQSYDSPL
    (SEQ NSGYTS DTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5130) NO:
    4454) NO: NO: 4961) 5299)
    4623) 4792)
    365_G12 SSYGMN WVAGINY ARSATWH LSYVNWY LVIYAATSRA QQSYSNPL
    (SEQ NSGYTS DTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5131) NO:
    4455) NO: NO: 4962) 5300)
    4624) 4793)
    367_C03 SSYSMN WVANINY ARSATW LSYVNWY LVIYATTSRA QQSYENPL
    (SEQ NGGYTG HDTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5132) NO:
    4456) NO: NO: 4963) 5301)
    4625) 4794)
    367_H07 SSYSMN WVANINY ARSATWH LSYVNWY LVIYATTSRA QQSYENPL
    (SEQ NGGYTG DTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5133) NO:
    4457) NO: NO: 4964) 5302)
    4626) 4795)
    371_D03 DSYGMN WVANINY ARSATW LTYVNWY LVIYAATSLA QQSYNTPL
    (SEQ NGGYTS HDTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5134) NO:
    4458) NO: NO: 4965) 5303)
    4627) 4796)
    369_C10 SSYSMN WVANINY ARSATW VTYLNWY LLIYAATSLH QQSDSLPL
    (SEQ NGGYTS HDTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5135) NO:
    4459) NO: NO: 4966) 5304)
    4628) 4797)
    367_F05 SSYGMN WVASINY ARSATW LSYVNWY LLIYAATSRA QQSYSSPL
    (SEQ NGGYTG HDTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5136) NO:
    4460) NO: NO: 4967) 5305)
    4629) 4798)
    365_C07 SDYGMN WVASINY ARSATW VSYVNWY LLIYAATSRA QQSYDTPL
    (SEQ NGGYTS HDTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5137) NO:
    4461) NO: NO: 4968) 5306)
    4630) 4799)
    374_C08 DSYGMN WVSGINY ARSATW LSYVNWY LLIYAVTSRA QQSYDSPL
    (SEQ NSGYKS HDTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5138) NO:
    4462) NO: NO: 4969) 5307)
    4631) 4800)
    376_A06 DSYSMN WVSGINY ARSATW LSYLNWY LVIYYVSNRA QQSYDNPL
    (SEQ NSGYTS HDTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5139) NO:
    4463) NO: NO: 4970) 5308)
    4632) 4801)
    376_B07 DSYSMN WVSGINY ARSATW LSYLNWY LVIYYVSNRA QQSYDNPL
    (SEQ NSGYTS HDTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5140) NO:
    4464) NO: NO: 4971) 5309)
    4633) 4802)
    365_F07 SSYSMN WVSNINY ARSATW LSYVNWY LVIYAATSRA QQSYDLPL
    (SEQ NGGYKS HDTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5141) NO:
    4465) NO: NO: 4972) 5310)
    4634) 4803)
    369_E10 SSYSMN WVSNINY ARSATW LSYVNWY LVIYAATSRA QQSYDLPL
    (SEQ NGGYKS HDTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5142) NO:
    4466) NO: NO: 4973) 5311)
    4635) 4804)
    373_E03 DSYGMN WVSNINY ARSATWH LSYVNWY LVIYAATSRA QQSYDLPL
    (SEQ NGGYTG DTALD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5143) NO:
    4467) NO: NO: 4974) 5312)
    4636) 4805)
    366_B04 DSYSMN WVAGINY ARSATWH LTYVNWY LVIYAATSRH QQSYDTPL
    (SEQ NGGYKG DTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5144) NO:
    4468) NO: NO: 4975) 5313)
    4637) 4806)
    376_F12 DDYSMN WVAGINY ARSATW ISYVNWY LLIYAASSLQ QQSYSTPL
    (SEQ NGGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5145) NO:
    4469) NO: NO: 4976) 5314)
    4638) 4807)
    369_F07 DSYSMN WVAGIN ARSATW LSYVNWY LVIYAATSRA QQSYESPL
    (SEQ YNGGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5146) NO:
    4470) NO: NO: 4977) 5315)
    4639) 4808)
    368_C06 DSYSMN WVAGINY ARSATW SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ NGGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5147) NO:
    4471) NO: NO: 4978) 5316)
    4640) 4809)
    376_E12 SSYSMN WVAGINY ARSATW LSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ NGGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5148) NO:
    4472) NO: NO: 4979) 5317)
    4641) 4810)
    371_H01 DSYSMN WVAGINY ARSATW ITYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ NGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5149) NO:
    4473) NO: NO: 4980) 5318)
    4642) 4811)
    367_E02 DSYSMN WVAGINY ARSATW SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ NGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5150) NO:
    4474) NO: NO: 4981) 5319)
    4643) 4812)
    365_F04 SSYGMN WVAGINY ARSATW VTYVNWY LLIYAATSRA QQSYDTPL
    (SEQ NGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5151) NO:
    4475) NO: NO: 4982) 5320)
    4644) 4813)
    370_A09 SSYSMN WVAGINY ARSATW LTYLNWY LVIYAATSRA QQSYDTPL
    (SEQ NGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5152) NO:
    4476) NO: NO: 4983) 5321)
    4645) 4814)
    365_B03 SSYSMN WVAGINY ARSATW VSYLNWY LLIYAATSRA QQSYENPL
    (SEQ NGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5153) NO:
    4477) NO: NO: 4984) 5322)
    4646) 4815)
    369_A05 SSYSMN WVAGINY ARSATW LTYVNWY LVIYAATSRA QQSYESPL
    (SEQ NGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5154) NO:
    4478) NO: NO: 4985) 5323)
    4647) 4816)
    373_H10 SSYSMN WVAGINY ARSATW LSYVNWY LLIYAATSRA QQSYSLPL
    (SEQ NGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5155) NO:
    4479) NO: NO: 4986) 5324)
    4648) 4817)
    367_A09 DSYGMN WVAGINY ARSATW LSYVNWY LVIYAATSRH QQSYDTPL
    (SEQ NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5156) NO:
    4480) NO: NO: 4987) 5325)
    4649) 4818)
    370_F08 DSYSMN WVAGINY ARSATW ISYVNWY LLIYAATSRH QQSYNLPL
    (SEQ NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5157) NO:
    4481) NO: NO: 4988) 5326)
    4650) 4819)
    376_B01 DSYSMN WVAGINY ARSATW LTYVNWY LVIYAATSRA QQSYNLPL
    (SEQ NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5158) NO:
    4482) NO: NO: 4989) 5327)
    4651) 4820)
    365_D05 DSYSMN WVAGINY ARSATW LTYVNWY LLIYAATSRA QQSYNSPL
    (SEQ NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5159) NO:
    4483) NO: NO: 4990) 5328)
    4652) 4821)
    373_E04 DSYSMN WVAGINY ARSATW LTYVNWY LLIYAATSRA QQSYNSPL
    (SEQ NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5160) NO:
    4484) NO: NO: 4991) 5329)
    4653) 4822)
    368_G05 DSYSMN WVAGINY ARSATW LTYVNWY LLIYAATSLH QQSYNTPL
    (SEQ NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5161) NO:
    4485) NO: NO: 4992) 5330)
    4654) 4823)
    365_A01 SDYGMN WVAGINY ARSATW LTYVNWY LVIYATTSLA QQSYSTPL
    (SEQ NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5162) NO:
    4486) NO: NO: 4993) 5331)
    4655) 4824)
    373_H06 SSYGMH WVAGINY ARSATW ISYVNWY LLIYAATSLA QQSYDLPL
    (SEQ NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5163) NO:
    4487) NO: NO: 4994) 5332)
    4656) 4825)
    369_G07 SSYSMN WVAGINY ARSATW LTYVNWY LVIYAATSRA QQSYDNPL
    (SEQ NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    ID NO: (SEQ ID (SEQ ID NO: NO: 5164) NO:
    4488) NO: NO: 4995) 5333)
    4657) 4826)
    373_G05 SSYSMN WVAGINY ARSATW LSYLNWY LLIYAATSLA QQSYELPL
    (SEQ ID NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: 4489) (SEQ ID (SEQ ID NO: 4996) NO: 5165) NO: 
    NO: NO: 4827) 5334)
    4658)
    372_F07 DDYSMN WVAGINY ARSATW LTYLNWY LVIYAATSRA QQSYELPL
    (SEQ ID NSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: 4490) (SEQ ID (SEQ ID NO: 4997) NO: 5166) NO: 5335)
    NO: NO: 4828)
    4659)
    370_H03 DSYSMN WVAGINY ARSATW LTYLNWY LLIYAATSLA QQSYDTPL
    (SEQ ID NSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: 4491) (SEQ ID (SEQ ID NO: 4998) NO: 5167) NO: 5336)
    NO: NO: 4829)
    4660)
    366_A03 DSYSMN WVAGINY ARSATW SSYLNWY LLIYAATSLA QQSYSNPL
    (SEQ ID NSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: 4492) (SEQ ID (SEQ ID NO: 4999) NO: 5168) NO: 5337)
    NO: NO: 4830)
    4661)
    365_A07 SSYGMN WVAGINY ARSATW VSYLNWY LLIYAATSRA QQSYNLPL
    (SEQ ID NSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: 4493) (SEQ ID (SEQ ID NO: 5000) NO: 5169) NO: 5338)
    NO: NO: 4831)
    4662)
    376_B06 SSYSMN WVAGINY ARSATW LTYLNWY LLIYAATSRA QQSYDLPL
    (SEQ ID NSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: 4494) (SEQ ID (SEQ ID NO: 5001) NO: 5170) NO: 5339)
    NO: NO: 4832)
    4663)
    374_C11 SSYSMN WVAGINY ARSATW LTYLNWY LLIYAATSRA QQSYESPL
    (SEQ ID NSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: 4495) (SEQ ID (SEQ ID NO: 5002) NO: 5171) NO: 5340)
    NO: NO: 4833)
    4664)
    375_A06 SSYSMN WVAGINY ARSATW LTYVNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID NSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: 4496) (SEQ ID (SEQ ID NO: 5003) NO: 5172) NO: 5341)
    NO: NO: 4834)
    4665)
    365_B09 DSYSMN WVAGINY ARSATW LRYLNWY LLIYAATSLH QQSYDNPL
    (SEQ ID NSGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: 4497) (SEQ ID (SEQ ID NO: 5004) NO: 5173) NO: 5342)
    NO: NO: 4835)
    4666)
    373_E06 DSYSMN WVAGINY ARSATW LRYLNWY LLIYAATSLH QQSYDNPL
    (SEQ ID NSGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: 4498) (SEQ ID (SEQ ID NO: 5005) NO: 5174) NO: 5343)
    NO: NO: 4836)
    4667)
    374_C05 DSYSMN WVAGINY ARSAT IRYLNWY LVIYAATSRA QQSYDNPL
    (SEQ ID NSGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4499) NO: NO: 5006) 5175) 5344)
    4668) 4837)
    376_C11 DSYSMN WVAGINY ARSAT LTYLNWY LVIYAATSRA QQSYDNPL
    (SEQ ID NSGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4500) NO: NO: 5007) 5176) 5345)
    4669) 4838)
    373_C09 DSYSMN WVAGINY ARSAT LTYLNWY LVIYAATSRA QQSYELPL
    (SEQ ID NSGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4501) NO: NO: 5008) 5177) 5346)
    4670) 4839)
    368_H01 SSYSMN WVAGINY ARSAT LSYLNWY LLIYATTSLA QQSYDNPL
    (SEQ ID NSGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4502) NO: NO: 5009) 5178) 5347)
    4671) 4840)
    373_B03 SSYSMN WVAGINY ARSAT LTYLNWY LVIYAATSLA QQSYDNPL
    (SEQ ID NSGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4503) NO: NO: 5010) 5179) 5348)
    4672) 4841)
    374__C04 SSYSMN WVAGINY ARSAT LTYLNWY LLIYAASSLQ QQSYELPL
    (SEQ ID NSGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4504) NO: NO: 5011) 5180) 5349)
    4673) 4842)
    371_F05 SSYSMN WVAGINY ARSAT LSYLNWY LLIYAATSRH QQSYENPL
    (SEQ ID NSGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4505) NO: NO: 5012) 5181) 5350)
    4674) 4843)
    369__A10 DSYSMN WVAGINY ARSAT LSYLNWY LLIYAATSRA QQSYELPL
    (SEQ ID NSGY WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: TG (SEQ ID NO: NO: NO:
    4506) (SEQ ID NO: 5013) 5182) 5351)
    NO: 4844)
    4675)
    366_A05 SSYSMN WVAGINY ARSAT LTYVNWY LVIYAATSLA QQSYNTPL
    (SEQ ID NSGY WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: TG (SEQ ID NO: NO: NO:
    4507) (SEQ ID NO: 5014) 5183) 5352)
    NO: 4845)
    4676)
    375_G07 DSYSMN WVAGINY ARSAT LSYLNWY LVIYAATSLA QQSYDLPL
    (SEQ ID NSGY WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: TS (SEQ ID NO: NO: NO:
    4508) (SEQ ID NO: 5015) 5184) 5353)
    NO: 4846)
    4677)
    374_D02 DSYSMN WVAGINY ARSAT STYVNWY LLIYAVTSLA QQSYDSPL
    (SEQ ID NSGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO: 5354)
    4509) NO: NO: 5016) 5185)
    4678) 4847)
    365_A10 SSYGMH WVAGINY ARSAT LTYLNWY LVIYAVTSLA QQSYDSPL
    (SEQ ID NSGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: 5017) NO: NO: 5355)
    4510) NO: NO: 5186)
    4679) 4848)
    375_A02 SSYSMN WVAGINY ARSAT SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID NSGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: 5018) NO: NO: 5356)
    4511) NO: NO: 5187)
    4680) 4849)
    371_G03 SSYGMN WVANINY ARSAT VTYVNWY LVIYAATSLA QQSYNLPL
    (SEQ ID NGGYKG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: 5019) NO: NO: 5357)
    4512) NO: NO: 5188)
    4681) 4850)
    370_E07 DSYSMN WVANINY ARSAT LTYLNWY LLIYAATSRA QQSYDNPL
    (SEQ ID NGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: 5020) NO: NO: 5358)
    4513) NO: NO: 5189)
    4682) 4851)
    375_B04 DSYSMN WVANINY ARSAT LTYLNWY LLIYAATSRA QQSYDNPL
    (SEQ ID NGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: 5021) NO: NO:
    4514) NO: NO: 5190) 5359)
    4683) 4852)
    367_G07 DSYSMN WVANINY ARSAT LTYVNWY LLIYAATSRA QQSYDNPL
    (SEQ ID NGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: 5022) NO: NO: 5360)
    4515) NO: NO: 5191)
    4684) 4853)
    366_C02 SDYSMN WVANINY ARSAT VSYLNWY LLIYAATSRA QQSYDNPL
    (SEQ ID NGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: 5023) NO: NO: 5361)
    4516) NO: NO: 5192)
    4685) 4854)
    375_C12 SSYSMN WVANINY ARSAT LTYLNWY LLIYAATSRA QQSYDLPL
    (SEQ ID NGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: 5024) NO: NO: 5362)
    4517) NO: NO: 5193)
    4686) 4855)
    365_F08 DDYGMN WVANINY ARSAT LSYVNWY LLIYAATSRH QQSYSLPL
    (SEQ ID NGGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: 5025) NO: NO: 5363)
    4518) NO: NO: 5194)
    4687) 4856)
    368_G09 DSYGMH WVANIN ARSAT VSYLN LVIYAATSRA QQSYDTPL
    (SEQ ID YNGGYTS WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4519) NO: NO: NO: 5195) 5364)
    4688) 4857) 5026)
    368_E11 DSYGMH WVANIN ARSAT ISYVN LLIYAATSRH QQSYELPL
    (SEQ ID YNGGYTS WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4520) NO: NO: NO: 5196) 5365)
    4689) 4858) 5027)
    367_F02 DSYSMN WVANIN ARSAT ISYVN LLIYAATSRH QQSYESPL
    (SEQ ID YNGGYTS WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4521) NO: NO: NO: 5197) 5366)
    4690) 4859) 5028)
    373_B08 DSYSMN WVANIN ARSAT LTYLN LVIYAATSLA QQSYENPL
    (SEQ ID YNSGYKG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4522) NO: NO: NO: 5198) 5367)
    4691) 4860) 5029)
    374_A11 SDYSMN WVANIN ARSAT LSYVN LVIYAATSRA QQSYSSPL
    (SEQ ID YNSGYKG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4523) NO: NO: NO: 5199) 5368)
    4692) 4861) 5030)
    373_B11 SSYSMN WVANIN ARSAT LSYLN LLIYAATSRA QQSYDNPL
    (SEQ ID YNSGYKG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4524) NO: NO: NO: 5200) 5369)
    4693) 4862) 5031)
    373_F03 DSYSMN WVANIN ARSAT LTYVN LLIYAATSRH QQSYDSPL
    (SEQ ID YNSGYTG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4525) NO: NO: NO: 5201) 5370)
    4694) 4863) 5032)
    372_D04 SSYSMN WVANIN ARSAT LTYLN LLIYAATSLH QQSYDLPL
    (SEQ ID YNSGYTG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4526) NO: NO: NO: 5202) 5371)
    4695) 4864) 5033)
    366_C01 SDYGMN WVASIN ARSAT VTYLN LLIYAATSPA QQSYELPL
    (SEQ ID YNGGYTG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4527) NO: NO: NO: 5203) 5372)
    4696) 4865) 5034)
    367_A01 SSYSMN WVASIN ARSAT LTYLN LLIYAATSRA QQSYDLPL
    (SEQ ID YNGGYTG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4528) NO: NO: NO: 5204) 5373)
    4697) 4866) 5035)
    366_H05 DSYGMH WVASIN ARSAT LSYVNWY LLIYAATSLA QQSYDLPL
    (SEQ ID YNGGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4529) NO: NO: 5036) 5205) 5374)
    4698) 4867)
    369_B09 DSYGMH WVASIN ARSAT LTYLNWY LLIYAATSRA QQSYENPL
    (SEQ ID YNGGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4530) NO: NO: 5037) 5206) 5375)
    4699) 4868)
    366_D07 SDYGMH WVASIN ARSAT LTYLNWY LLIYAATSLA QQSYSSPL
    (SEQ ID YNGGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4531) NO: NO: 5038) 5207) 5376)
    4700) 4869)
    369_D11 SSYGMH WVASIN ARSAT LTYLNWY LVIYAATSLA QQSDELPL
    (SEQ ID YNGGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4532) NO: NO: 5039) 5208) 5377)
    4701) 4870)
    370_B05 SSYGMN WVASIN ARSAT LTYVNWY LVIYAATSRA QQSYENPL
    (SEQ ID YNGGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4533) NO: NO: 5040) 5209) 5378)
    4702) 4871)
    366_D02 SSYSMN WVASIN ARSAT LSYVNWY LLIYATTSLA QQSYDLPL
    (SEQ ID YNGGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4534) NO: NO: 5041) 5210) 5379)
    4703) 4872)
    368_H12 DSYSMN WVASIN ARSAT VTYLNWY LLIYAATSRA QQSYESPL
    (SEQ ID YNSGYKG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4535) NO: NO: 5042) 5211) 5380)
    4704) 4873)
    368_F12 DDYSMN WVASIN ARSAT VTYLNWY LVIYAATSLA QQSYDLPL
    (SEQ ID YNSGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4536) NO: NO: 5043) 5212) 5381)
    4705) 4874)
    370_A06 SSYSMN WVASIN ARSAT VTYLNWY LVIYAATSLA QQSYDLPL
    (SEQ ID YNSGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4537) NO: NO: 5044) 5213) 5382)
    4706) 4875)
    369_F12 SSYSMN WVASIN ARSAT ISYLNWY LLIYAVTSLA QQSYENPL
    (SEQ ID YNSGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4538) NO: NO: 5045) 5214) 5383)
    4707) 4876)
    366_A09 SDYGMH WVAS ARSATW LTYLNW LLIYAATSRH QQSYETPL
    (SEQ ID INYN HDTHLD Y (SEQ ID (SEQ ID
    NO: SGYTS (SEQ ID (SEQ ID NO: NO:
    4539) (SEQ ID NO: NO: 5215) 5384)
    NO: 4877) 5046)
    4708)
    368_H07 SSYCMH WVAS ARSATW LSYLNW LLIYAATSRA QQSYENPL
    (SEQ ID INYN HDTHLD Y (SEQ ID (SEQ ID
    NO: SGYTS (SEQ ID (SEQ ID NO: NO:
    4540) (SEQ ID NO: NO: 5216) 5385)
    NO: 4878) 5047)
    4709)
    370_C04 SSYGMN WVAS ARSATW LSYLNW LLIYAASSLQ QQSYENPL
    (SEQ ID INYN HDTHLD Y (SEQ ID (SEQ ID
    NO: SGYTS (SEQ ID (SEQ ID NO: NO:
    4541) (SEQ ID NO: NO: 5217) 5386)
    NO: 4879) 5048)
    4710)
    373_E02 DSYGMH WVSG ARSATW VRYLNW LLIYAASSLQ QQSYSTPL
    (SEQ ID INYNG HDTHLD Y (SEQ ID (SEQ ID
    NO: GYKG (SEQ ID (SEQ ID NO: NO:
    4542) (SEQ ID NO: NO: 5218) 5387)
    NO: 4880) 5049)
    4711)
    374_E09 SDYSMN WVSG ARSATW VTYLNW LVIYAATSRA QQSYDSPL
    (SEQ ID INYNG HDTHLD Y (SEQ ID (SEQ ID
    NO: GYKG (SEQ ID (SEQ ID NO: NO:
    4543) (SEQ ID NO: NO: 5219) 5388)
    NO: 4881) 5050)
    4712)
    371_C09 DSYSMN WVSG ARSATW LTYVNW LLIYAASSLQ QQSYDNPL
    (SEQ ID INYNG HDTHLD Y (SEQ ID (SEQ ID
    NO: GYKS (SEQ ID (SEQ ID NO: NO:
    4544) (SEQ ID NO: NO: 5220) 5389)
    NO: 4882) 5051)
    4713)
    369_B12 DSYSMN WVS ARSATW LTYVNW LLIYATTSLA QQSYDSPL
    (SEQ ID GINYN HDTHLD Y (SEQ ID (SEQ ID
    NO: GGYKS (SEQ ID (SEQ ID NO: NO:
    4545) (SEQ ID NO: NO: 5221) 5390)
    NO: 4883) 5052)
    4714)
    369_B02 DSYSMN WVSG ARSATW LSYLNW LVIYAATSRA QQSYNLPL
    (SEQ ID INYN HDTHLD Y (SEQ ID (SEQ ID
    NO: GGYKS (SEQ ID (SEQ ID NO: NO:
    4546) (SEQ ID NO: NO: 5222) 5391)
    NO: 4884) 5053)
    4715)
    365_C09 SDYGMN W ARSATW VSYVNW LLIYAATSRA QQSYDTPL
    (SEQ ID VSGIN HDTHLD Y (SEQ ID (SEQ ID
    NO: YNGGYKS (SEQ ID (SEQ ID NO: NO:
    4547) (SEQ ID NO: NO: 5223) 5392)
    NO: 4885) 5054)
    4716)
    374_B09 SSYSMN WVSGIN ARSATW VRYLNW LVIYAATSLA QQSYELPL
    (SEQ ID YNGGYKS HDTHLD Y (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4548) NO: NO: NO: 5224) 5393)
    4717) 4886) 5055)
    374_D12 DSYSMN WVSGINY ARSATW VSYVNWY LVIYAATSRA QQSYDLPL
    (SEQ ID NGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4549) NO: NO: 5056) 5225) 5394)
    4718) 4887)
    374_C02 DSYSMN WVSGINY ARSATW LSYLNWY LLIYAATSRH QQSYDSPL
    (SEQ ID NGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4550) NO: NO: 5057) 5226) 5395)
    4719) 4888)
    374_H08 DSYSMN WVSGINY ARSATW LSYLNWY LLIYAATSLH QQSYENPL
    (SEQ ID NGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4551) NO: NO: 5058) 5227) 5396)
    4720) 4889)
    369_D06 DSYSMN WVSGINY ARSATW LTYLNWY LLIYAATSRA QQSYETPL
    (SEQ ID NGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4552) NO: NO: 5059) 5228) 5397)
    4721) 4890)
    366_B06 DSYSMN WVSGINY ARSATW LTYVNWY LVIYAAPSLA QQSYXTPL
    (SEQ ID NGGYTS (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID HDTHLD NO: NO: NO:
    4553) NO: (SEQ ID 5060) 5229) 5398)
    4722) NO:
    4891)
    367_A11 SSYGMH WVSGINY ARSATW LSYVNWY LVIYATTSLA QQSY
    (SEQ ID NGGYTS HDTHLD (SEQ ID (SEQ ID NSPL
    NO: (SEQ ID (SEQ ID NO: NO: (SEQ ID
    4554) NO: NO: 5061) 5230) NO:
    4723) 4892) 5399)
    369_F04 SSYGMN WVSGINY ARSATW ISYVNWY LLIYAATSRH QQSYDNPL
    (SEQ ID NGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4555) NO: NO: 5062) 5231) 5400)
    4724) 4893)
    369_A01 DSYSMN WVSGINY ARSATW LTYVNWY LVIYAATSLA QQSYELPL
    (SEQ ID NSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4556) NO: NO: 5063) 5232) 5401)
    4725) 4894)
    373_H12 SDYSMN WVSGINY ARSATW LTYLNWY LLIYAATSRA QQSY
    (SEQ ID NSGYKG HDTHLD (SEQ ID (SEQ ID NSPL
    NO: (SEQ ID (SEQ ID NO: NO: (SEQ ID
    4557) NO: NO: 5064) 5233) NO:
    4726) 4895) 5402)
    376_C07 SSYSMN WVSGINY ARSATW LSYVNWY LLIYAATSRH QQSYDLPL
    (SEQ ID NSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4558) NO: NO: 5065) 5234) 5403)
    4727) 4896)
    366_E02 SSYSMN WVSGIN ARSATW SSYLNWY LLIYAASSLQ QQSYNSPL
    (SEQ ID YNSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4559) NO: NO: 5066) 5235) 5404)
    4728) 4897)
    376_G01 DDYSMN WVSGIN ARSATW LSYVNWY LVIYAVTSRA QQSYELPL
    (SEQ ID YNSGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4560) NO: NO: 5067) 5236) 5405)
    4729) 4898)
    373_F02 DSYSMN WVSGIN ARSATW LTYLNWY LLIYAATSRA QQSYDTPL
    (SEQ ID YNSGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4561) NO: NO: 5068) 5237) 5406)
    4730) 4899)
    376_E09 DSYSMN WVSGIN ARSATW LTYLNWY LLIYAATSRH QQSYDTPL
    (SEQ ID YNSGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4562) NO: NO: 5069) 5238) 5407)
    4731) 4900)
    365_H04 SDYGMN WVSGIN ARSATW LTYVNWY LVIYAATSRA QQSYESPL
    (SEQ ID YNSGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4563) NO: NO: 5070) 5239) 5408)
    4732) 4901)
    369_E04 SDYSMN WVSGIN ARSATW LSYVNWY LVIYAATSRA QQSYSLPL
    (SEQ ID YNSGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4564) NO: NO: 5071) 5240) 5409)
    4733) 4902)
    374_B11 SSYSMN WVSGIN ARSATW LTYVNWY LVIYAATSRA QQSYDLPL
    (SEQ ID YNSGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4565) NO: NO: 5072) 5241) 5410)
    4734) 4903)
    376_G11 SSYSMN WVSGIN ARSATW VTYVNWY LVIYAATSLA QQSYNLPL
    (SEQ ID YNSGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4566) NO: NO: 5073) 5242) 5411)
    4735) 4904)
    374_E04 SSYSMN WVSGIN ARSATW LSYLNWY LLIYAVTSRA QQSYNNPL
    (SEQ ID YNSGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4567) NO: NO: 5074) 5243) 5412)
    4736) 4905)
    373_E08 DSYGMN WVSGIN ARSATW VSYVNWY LLIYAVTSRA QQSYESPL
    (SEQ ID YNSGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4568) NO: NO: 5075) 5244) 5413)
    4737) 4906)
    375_B10 DSYSMN WVSGIN ARSAT LSYLNWY LLIYAATSRH QQSYDLPL
    (SEQ ID YNSGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4569) NO: NO: 5076) 5245) 5414)
    4738) 4907)
    365_E08 DSYSMN WVSGIN ARSAT ISYVNWY LVIYAATSLA QQSYDLPL
    (SEQ ID YNSGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4570) NO: NO: 5077) 5246) 5415)
    4739) 4908)
    374_G02 DSYSMN WVSGIN ARSAT LTYLNWY LLIYAASSLQ QQSYDTPL
    (SEQ ID YNSGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4571) NO: NO: 5078) 5247) 5416)
    4740) 4909)
    373_D09 DSYSMN WVSGIN ARSAT LTYLNWY LVIYAATSRH QQSYENPL
    (SEQ ID YNSGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4572) NO: NO: 5079) 5248) 5417)
    4741) 4910)
    365_A04 SDYSMN WVSGIN ARSAT VSYVNWY LVIYAATSLA QQSYSTPL
    (SEQ ID YNSGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4573) NO: NO: 5080) 5249) 5418)
    4742) 4911)
    371_B05 SSYSMN WVSGIN ARSAT LTYLNWY LVIYAATSLA QQSDETPL
    (SEQ ID YNSGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4574) NO: NO: 5081) 5250) 5419)
    4743) 4912)
    376_H08 DSYGMN WVSNIN ARSAT LTYLNWY LLIYAATSRH QQSDSLPL
    (SEQ ID YNGGYKG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4575) NO: NO: 5082) 5251) 5420)
    4744) 4913)
    367_G08 DSYGMN WVSNIN ARSAT LSYLNWY LLIYAATSRA QQSYENPL
    (SEQ ID YNGGYKG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4576) NO: NO: 5083) 5252) 5421)
    4745) 4914)
    372_H03 DSYGMN WVSNIN ARSAT ITYVNWY LLIYAATSLA QQSYNLPL
    (SEQ ID YNGGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4577) NO: NO: 5084) 5253) 5422)
    4746) 4915)
    366_E03 DSYGMN WVSNIN ARSAT LTYLNWY LVIYAATSRH QQSYSNPL
    (SEQ ID YNGGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4578) NO: NO: 5085) 5254) 5423)
    4747) 4916)
    371_F12 DSYSMN WVSNIN ARSAT ISYLNWY LLIYAATSRA QQSNNLPL
    (SEQ ID YNGGYKS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4579) NO: NO: 5086) 5255) 5424)
    4748) 4917)
    366_C03 DSYGMN WVSNIN ARSAT LSYLNWY LVIYAATSRA QQSYSNPL
    (SEQ ID YNGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4580) NO: NO: 5087) 5256) 5425)
    4749) 4918)
    376_A01 DSYGMN WVSNIN ARSAT VSYLNWY LLIYAATSRA QQSYSTPL
    (SEQ ID YNGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4581) NO: NO: 5088) 5257) 5426)
    4750) 4919)
    365_E03 DSYSMN WVSNIN ARSAT LTYVNWY LLIYAATSLH QQSDERPL
    (SEQ ID YNGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4582) NO: NO: 5089) 5258) 5427)
    4751) 4920)
    371_B10 DSYSMN WVSNIN ARSAT VSYVNWY LLIYAATSRA QQSYDLPL
    (SEQ ID YNGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4583) NO: NO: 5090) 5259) 5428)
    4752) 4921)
    369_G09 DSYSMN WVSNIN ARSAT VTYLNWY LLIYAATSRA QQSYDLPL
    (SEQ ID YNGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4584) NO: NO: 5091) 5260) 5429)
    4753) 4922)
    369_A06 SDYGMN WVSNIN ARSAT LSYVNWY LLIYAATSLA QQSYDLPL
    (SEQ ID YNGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4585) NO: NO: 5092) 5261) 5430)
    4754) 4923)
    369_C08 SDYGMN WVSNIN ARSAT LTYLNWY LVIYAATSLA QQSYENPL
    (SEQ ID YNGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4586) NO: NO: 5093) 5262) 5431)
    4755) 4924)
    373_A07 SSYSMN WVSNIN ARSAT LTYVNWY LLIYAATSRA QQSDNLPL
    (SEQ ID YNGGYTG WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4587) NO: NO: 5094) 5263) 5432)
    4756) 4925)
    367_D02 DDYSMN WVSNIN ARSAT VTYVNWY LLIYAATSRA QQSYENPL
    (SEQ ID YNGGYTS WHDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4588) NO: NO: 5095) 5264) 5433)
    4757) 4926)
    374_C07 DSYSMN WVSNIN ARSATW ISYLNWY LLIYAATSRA QQSDELPL
    (SEQ ID YNGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4589) NO: NO: 5096) 5265) 5434)
    4758) 4927)
    374_A03 DSYSMN WVSNIN ARSATW LTYLNWY LLIYAATSRA QQSYDNPL
    (SEQ ID YNGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4590) NO: NO: 5097) 5266) 5435)
    4759) 4928)
    365_A02 DSYSMN WVSNIN ARSATW LTYVNWY LLIYAATSRA QQSYNSPL
    (SEQ ID YNGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4591) NO: NO: 5098) 5267) 5436)
    4760) 4929)
    365_D06 DSYSMN WVSNIN ARSATW LTYVNWY LLIYAATSRA QQSYSLPL
    (SEQ ID YNGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4592) NO: NO: 5099) 5268) 5437)
    4761) 4930)
    366_C07 SSYSMN WVSNIN ARSATW LTYVNWY LLIYAATSRA QQSYNSPL
    (SEQ ID YNGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4593) NO: NO: 5100) 5269) 5438)
    4762) 4931)
    367_F12 DDYSMN WVSNIN ARSATW SSYLNWY LLIYAASSLQ QQSYSTPL
    (SEQ ID YNSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4594) NO: NO: 5101) 5270) 5439)
    4763) 4932)
    369_E09 DSYSMN WVSNIN ARSATW LSYLNWY LVIYAATSRA QQSYDLPL
    (SEQ ID YNSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4595) NO: NO: 5102) 5271) 5440)
    4764) 4933)
    365_G02 SDYSMN WVSNIN ARSATW VTYLNWY LVIYAVTSLH QQSYELPL
    (SEQ ID YNSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4596) NO: NO: 5103) 5272) 5441)
    4765) 4934)
    373_D02 SSYSMN WVSNIN ARSATW LSYLNWY LLIYAATSLA QQSYDLPL
    (SEQ ID YNSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4597) NO: NO: 5104) 5273) 5442)
    4766) 4935)
    374_E03 SSYSMN WVSNIN ARSATW LTYVNWY LVIYAATSLA QQSYDTPL
    (SEQ ID YNSGYKG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4598) NO: NO: 5105) 5274) 5443)
    4767) 4936)
    374_D11 DSYGMN WVSNIN ARSATW LTYLNWY LLIYAATSRA QQSYETPL
    (SEQ ID YNSGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4599) NO: NO: 5106) 5275) 5444)
    4768) 4937)
    370_D07 SSYGMN WVSNIN ARSATW LSYVNWY LVIYAATSLA QQSYESPL
    (SEQ ID YNSGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4600) NO: NO: 5107) 5276) 5445)
    4769) 4938)
    374_A08 DSYSMN WVSNIN ARSATW VTYLNWY LLIYAATSLA QQSYDLPL
    (SEQ ID YNSGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4601) NO: NO: 5108) 5277) 5446)
    4770) 4939)
    374_G01 DSYSMN WVSNIN ARSATW LTYVNWY LLIYATTSRH QQSYNLPL
    (SEQ ID YNSGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4602) NO: NO: 5109) 5278) 5447)
    4771) 4940)
    374_G12 DDYGMN WVSSIN ARSATW LTYVNWY LVIYAATSLA QQSYNSPL
    (SEQ ID YNGGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4603) NO: NO: 5110) 5279) 5448)
    4772) 4941)
    375_G10 SSYGMN WVSSIN ARSATW VTYLNWY LVIYAATSRH QQSYDTPL
    (SEQ ID YNGGYKS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4604) NO: NO: 5111) 5280) 5449)
    4773) 4942)
    369_H11 SDYGMN WVSSIN ARSATW LSYLNWY LLIYAATSRH QQSYDLPL
    (SEQ ID YNGGYTG HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4605) NO: NO: 5112) 5281) 5450)
    4774) 4943)
    375_G12 DSYGMH WVSSIN ARSATW VSYVNWY LLIYAATSRH QQSYDTPL
    (SEQ ID YNGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4606) NO: NO: 5113) 5282) 5451)
    4775) 4944)
    366_F06 SDYGMN WVSSIN ARSATW STYLNWY LLIYAATSLA QQSYSNPL
    (SEQ ID YNGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4607) NO: NO: 5114) 5283) 5452)
    4776) 4945)
    368_G07 SSYSMH WVSSIN ARSATW VSYVNWY LVIYAATSRA QQSYDTPL
    (SEQ ID YNGGYTS HDTHLD (SEQ ID (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID NO: NO: NO:
    4608) NO: NO: 5115) 5284) 5453)
    4777) 4946)
    367_H04 SSYSMN WVSSINY ARSAT LTYVN LLIYAATSRH QQSDNNPL
    (SEQ ID NGGYTS WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4609) NO: NO: NO: 5285) 5454)
    4778) 4947) 5116)
    374_E06 DSYSMN WVSSINY ARSAT LSYLN LLIYAATSRA QQSYDLPL
    (SEQ ID NSGYKG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4610) NO: NO: NO: 5286) 5455)
    4779) 4948) 5117)
    370_A10 SDYSMN WVSSINY ARSAT LSYVN LLIYAATSLA QQSYDTPL
    (SEQ ID NSGYKG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4611) NO: NO: NO: 5287) 5456)
    4780) 4949) 5118)
    368_H10 SSYSMN WVSSINY ARSAT VSYVN LVIYAVTSLA QQSYETPL
    (SEQ ID NSGYKG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4612) NO: NO: NO: 5288) 5457)
    4781) 4950) 5119)
    368_G08 DDYGMN WVSSINY ARSAT VSYVN LLIYAATSRH QQSY
    (SEQ ID NSGYKS WHDTHLD WY (SEQ ID NNPL
    NO: (SEQ ID (SEQ ID (SEQ ID NO: (SEQ ID
    4613) NO: NO: NO: 5289) NO:
    4782) 4951) 5120) 5458)
    365_H09 SSYGMN WVSSINY ARSAT SSYLN LLIYAASSLQ QQSYSTPL
    (SEQ ID NSGYKS WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4614) NO: NO: NO: 5290) 5459)
    4783) 4952) 5121)
    370_A08 DSYSMN WVSSINY ARSAT VTYLN LVIYAATSRA QQSYDLPL
    (SEQ ID NSGYTG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4615) NO: NO: NO: 5291) 5460)
    4784) 4953) 5122)
    368_B05 DSYSMN WVSSINY ARSAT SSYLN LLIYAASSLQ QQSYSTPL
    (SEQ ID NSGYTG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4616) NO: NO: NO: 5292) 5461)
    4785) 4954) 5123)
    375_F01 SSYSMN WVSSINY ARSAT VSYLN LVIYAATSRA QQSYDNPL
    (SEQ ID NSGYTG WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4617) NO: NO: NO: 5293) 5462)
    4786) 4955) 5124)
    374_F09 SSYGMN WVSSINY ARSAT SSYVN LLIYAATSRA QQSYSTPL
    (SEQ ID NSGYTS WHDTHLD WY (SEQ ID (SEQ ID
    NO: (SEQ ID (SEQ ID (SEQ ID NO: NO:
    4618) NO: NO: NO: 5294) 5463)
    4787) 4956) 5125)
  • The consensus sequences for each of these CDRs shown in FIG. 3F are as follows:
  • HCDR1:
    (SEQ ID NO: 6584)
    D/SS/DYS/GMN/H
    HCDR2:
    (SEQ ID NO: 6585)
    WVA/SG/N/SINYNG/SGYT/KS/G
    HCDR3:
    (SEQ ID NO: 6586)
    ARSATWHDTH/ALD
    LCDR1:
    (SEQ ID NO: 6588)
    L/V/I/SS/T/RYL/VNWY
    LCDR2:
    (SEQ ID NO: 6590)
    LL/VIYA/YA/V/TT/SS/NR/LA/H/Q
    LCDR3:
    (SEQ ID NO: 6591)
    QQSY/DD/E/S/NL/N/T/SPL
  • The present antibody may exhibit high affinity binding to ACVR2A. For example, the antibody may binds to ACVR2 with an affinity of at least about 10−7 M, at least about 10−8M, at least about 10−9 M, at least about 10−10 M, at least about 10−11 M, or at least about 10−12 M, or greater than 10−12 M. The present antibody binds to ACVR2A with a substantially lower affinity, e.g., at least 10 fold, 50 fold, 100 fold, 500 fold, 1000 fold, 5000 fold, 10,000 fold, 50,000 fold 100,000, or 500,000 fold lower affinity.
  • The present antibody may reduce binding of ACVR2A to GDF8 and/or other activins. For example, the antibody may reduce binding of ACVR2A to GDF8 and/or other activins by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or more, compared to the degree of binding between ACVR2A and GDF8 and/or other activins in the absence of the antibody.
  • In some embodiments, an antibody comprises one or more (e.g., one or two) heavy chain variable regions (VH) and/or one or more (e.g., one or two) light chain variable regions (VL), or subfragments thereof capable of binding an epitope. The VH and VL regions can be further subdivided into regions of hypervariability, termed “complementarity determining regions (CDR)”, interspersed with regions that are more conserved, termed “framework regions (FR)”. The extent of the FR and CDRs has been precisely defined (see, Kabat, et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242; Chothia et al. (1987) J. Mol. Biol. 196: 901-917). A VH can comprise three CDRs and four FRs arranged from N-terminus to C-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. Similarly, a VL can comprise three CDRs and four FRs arranged from N-terminus to C-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
  • The VH or VL chain of an antibody can further include all or part of a heavy or light chain constant region, to thereby form a heavy or light immunoglobulin chain, respectively. In one embodiment, the antibody is a tetramer of two heavy and two light chains, wherein the heavy and light chains are interconnected by, for example, disulphide bonds. The heavy chain constant region is comprised of three domains, CH1, CH2 and CH3. The light chain constant region is comprised of one domain, CL. The variable regions of the heavy and light chains comprise binding regions that interact with antigen. The constant regions of the antibodies typically mediate the binding of the antibody to host tissues and factors, including various cells of the immune system and the first component of the complement system. The term “antibody” includes intact immunoglobulins of types IgA, IgG, IgE, IgD, IgM and subtypes thereof. In some embodiments, a subject antibody is an IgG isotype.
  • As used herein the term “immunoglobulin” refers to a protein consisting of one or more polypeptides substantially encoded by immunoglobulin genes. The recognized human immunoglobulin genes include the kappa, lambda, alpha (IgA1 and IgA2), gamma (IgG1, IgG2, IgG3, IgG4), delta, epsilon and mu constant region genes; and numerous immunoglobulin variable region genes. Full-length immunoglobulin light chains (about 25 kD or 214 amino acids) are encoded by a variable region gene at the N-terminus (about 110 amino acids) and a kappa or lambda constant region at the C-terminus. Full-length immunoglobulin heavy chains (about 50 kD or 446 amino acids) are encoded by a variable region gene at the N-terminus (about 116 amino acids) and one of the other aforementioned constant region genes at the C-terminus, e.g. gamma (encoding about 330 amino acids). In some embodiments, a subject antibody comprises full-length immunoglobulin heavy chain and a full-length immunoglobulin light chain.
  • In some embodiments, a subject antibody does not comprise a full-length immunoglobulin heavy chain and a full-length immunoglobulin light chain, and instead comprises antigen-binding fragments of a full-length immunoglobulin heavy chain and a full-length immunoglobulin light chain. In some embodiments, the antigen-binding fragments are contained on separate polypeptide chains; in other embodiments, the antigen-binding fragments are contained within a single polypeptide chain. The term “antigen-binding fragment” refers to one or more fragments of a full-length antibody that are capable of specifically binding to ACVR2A as described above. Examples of binding fragments include (i) a Fab fragment (a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab′)2 fragment (a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment (consisting of the VH and CH1 domains); (iv) a Fv fragment (consisting of the VH and VL domains of a single arm of an antibody); (v) a dAb fragment (consisting of the VH domain); (vi) an isolated CDR; (vii) a single chain Fv (scFv) (consisting of the VH and VL domains of a single arm of an antibody joined by a synthetic linker using recombinant means such that the VH and VL domains pair to form a monovalent molecule); (viii) diabodies (consisting of two scFvs in which the VH and VL domains are joined such that they do not pair to form a monovalent molecule; the VH of each one of the scFv pairs with the VL domain of the other scFv to form a bivalent molecule); (ix) bi-specific antibodies (consisting of at least two antigen binding regions, each region binding a different epitope). In some embodiments, a subject antibody fragment is a Fab fragment. In some embodiments, a subject antibody fragment is a single-chain antibody (scFv).
  • In some embodiments, a subject antibody is a recombinant or modified antibody, e.g., a chimeric, humanized, deimmunized or an in vitro generated antibody. The term “recombinant” or “modified” antibody as used herein is intended to include all antibodies that are prepared, expressed, created, or isolated by recombinant means, such as (i) antibodies expressed using a recombinant expression vector transfected into a host cell; (ii) antibodies isolated from a recombinant, combinatorial antibody library; (iii) antibodies isolated from an animal (e.g. a mouse) that is transgenic for human immunoglobulin genes; or (iv) antibodies prepared, expressed, created, or isolated by any other means that involves splicing of human immunoglobulin gene sequences to other DNA sequences. Such recombinant antibodies include humanized, CDR grafted, chimeric, deimmunized, and in vitro generated antibodies; and can optionally include constant regions derived from human germline immunoglobulin sequences.
  • In some embodiments, a subject antibody comprises, in order from N-terminus to C-terminus: a light chain FR1 region; a CDR1; a light chain FR2 region; a CDR2; a light chain FR3 region; a CDR3; optionally a light chain FR4 region; a linker region; optionally a heavy chain FR1 region; a CDR1; a heavy chain FR2 region; a CDR2; a heavy chain FR3 region; a CDR3; and a heavy chain FR4 region. In some of these embodiments, each of the FR regions is a human FR region. The linker region can be from about 5 amino acids to about 50 amino acids in length, e.g., from about 5 aa to about 10 aa, from about 10 aa to about 15 aa, from about 15 aa to about 20 aa, from about 20 aa to about 25 aa, from about 25 aa to about 30 aa, from about 30 aa to about 35 aa, from about 35 aa to about 40 aa, from about 40 aa to about 45 aa, or from about 45 aa to about 50 aa in length.
  • Linkers suitable for use a subject antibody include “flexible linkers”. If present, the linker molecules are generally of sufficient length to permit some flexible movement between linked regions. The linker molecules are generally about 6-50 atoms long. The linker molecules may also be, for example, aryl acetylene, ethylene glycol oligomers containing 2-10 monomer units, diamines, diacids, amino acids, or combinations thereof. Other linker molecules which can bind to polypeptides may be used in light of this disclosure.
  • Suitable linkers can be readily selected and can be of any of a suitable of different lengths, such as from 1 amino acid (e.g., Gly) to 20 amino acids, from 2 amino acids to 15 amino acids, from 3 amino acids to 12 amino acids, including 4 amino acids to 10 amino acids, 5 amino acids to 9 amino acids, 6 amino acids to 8 amino acids, or 7 amino acids to 8 amino acids, and may be 1, 2, 3, 4, 5, 6, or 7 amino acids.
  • Exemplary flexible linkers include glycine polymers (G)n, glycine-serine polymers (including, for example, (GS)n, GSGGSn (SEQ ID NO: 6599) and GGGSn(SEQ ID NO: 6600), where n is an integer of at least one), glycine-alanine polymers, alanine-serine polymers, and other flexible linkers known in the art. Glycine and glycine-serine polymers are of interest since both of these amino acids are relatively unstructured, and therefore may serve as a neutral tether between components. Glycine polymers are of particular interest since glycine accesses significantly more phi-psi space than even alanine, and is much less restricted than residues with longer side chains (see Scheraga, Rev. Computational Chem. 11173-142 (1992)). Exemplary flexible linkers include, but are not limited GGSG (SEQ ID NO:6601), GGSGG (SEQ ID NO:6602), GSGSG (SEQ ID NO: 6603), GSGGG (SEQ ID NO:6604), GGGSG (SEQ ID NO: 6605), GSSSG (SEQ ID NO: 6606), and the like. The ordinarily skilled artisan will recognize that design of a peptide conjugated to any elements described above can include linkers that are all or partially flexible, such that the linker can include a flexible linker as well as one or more portions that confer less flexible structure.
  • In some embodiments, a subject antibody is “humanized” The term “humanized antibody” refers to an antibody comprising at least one chain comprising variable region framework residues substantially from a human antibody chain (referred to as the acceptor immunoglobulin or antibody) and at least one CDR substantially from a mouse antibody, (referred to as the donor immunoglobulin or antibody). See, Queen et al., Proc. Natl. Acad. Sci. USA 86:10029 10033 (1989), U.S. Pat. Nos. 5,530,101, 5,585,089, 5,693,761, WO 90/07861, and U.S. Pat. No. 5,225,539. The constant region(s), if present, can also be substantially or entirely from a human immunoglobulin. In some embodiments, a subject antibody may comprise one or more CDRs and one or more FR regions from a human antibody. Methods of making humanized antibodies are known in the art. See, e.g., U.S. Pat. No. 7,256,273.
  • The substitution of mouse CDRs into a human variable domain framework can result in retention of their correct spatial orientation where, e.g., the human variable domain framework adopts the same or similar conformation to the mouse variable framework from which the CDRs originated. This can be achieved by obtaining the human variable domains from human antibodies whose framework sequences exhibit a high degree of sequence identity with the murine variable framework domains from which the CDRs were derived. The heavy and light chain variable framework regions can be derived from the same or different human antibody sequences. The human antibody sequences can be the sequences of naturally occurring human antibodies or can be consensus sequences of several human antibodies. See Kettleborough et al., Protein Engineering 4:773 (1991); Kolbinger et al., Protein Engineering 6:971 (1993).
  • Having identified the complementarity determining regions of the murine donor immunoglobulin and appropriate human acceptor immunoglobulins, the next step is to determine which, if any, residues from these components should be substituted to optimize the properties of the resulting humanized antibody. In general, substitution of human amino acid residues with murine should be minimized, because introduction of murine residues increases the risk of the antibody eliciting a human-anti-mouse-antibody (HAMA) response in humans. Art-recognized methods of determining immune response can be performed to monitor a HAMA response in a particular patient or during clinical trials. Patients administered humanized antibodies can be given an immunogenicity assessment at the beginning and throughout the administration of the therapy. The HAMA response is measured, for example, by detecting antibodies to the humanized therapeutic reagent, in serum samples from the patient using a method known to one in the art, including surface plasmon resonance technology (BIACORE) and/or solid-phase ELISA analysis. In many embodiments, a subject humanized antibody does not substantially elicit a HAMA response in a human subject.
  • Certain amino acids from the human variable region framework residues are selected for substitution based on their possible influence on CDR conformation and/or binding to antigen. The unnatural juxtaposition of murine CDR regions with human variable framework region can result in unnatural conformational restraints, which, unless corrected by substitution of certain amino acid residues, lead to loss of binding affinity.
  • The selection of amino acid residues for substitution can be determined, in part, by computer modeling. Computer hardware and software for producing three-dimensional images of immunoglobulin molecules are known in the art. In general, molecular models are produced starting from solved structures for immunoglobulin chains or domains thereof. The chains to be modeled are compared for amino acid sequence similarity with chains or domains of solved three-dimensional structures, and the chains or domains showing the greatest sequence similarity is/are selected as starting points for construction of the molecular model. Chains or domains sharing at least 50% sequence identity are selected for modeling, and preferably those sharing at least 60%, 70%, 80%, 90% sequence identity or more are selected for modeling. The solved starting structures are modified to allow for differences between the actual amino acids in the immunoglobulin chains or domains being modeled, and those in the starting structure. The modified structures are then assembled into a composite immunoglobulin. Finally, the model is refined by energy minimization and by verifying that all atoms are within appropriate distances from one another and that bond lengths and angles are within chemically acceptable limits.
  • CDR and framework regions are as defined by Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md., 1987 and 1991). An alternative structural definition has been proposed by Chothia et al., J. Mol. Biol. 196:901 (1987); Nature 342:878 (1989); and J. Mol. Biol. 186:651 (1989) (collectively referred to as “Chothia”). When framework residues, as defined by Kabat, supra, constitute structural loop residues as defined by Chothia, supra, the amino acids present in the mouse antibody may be selected for substitution into the humanized antibody. Residues which are “adjacent to a CDR region” include amino acid residues in positions immediately adjacent to one or more of the CDRs in the primary sequence of the humanized immunoglobulin chain, for example, in positions immediately adjacent to a CDR as defined by Kabat, or a CDR as defined by Chothia (See e.g., Chothia and Lesk JMB 196:901 (1987)). These amino acids are particularly likely to interact with the amino acids in the CDRs and, if chosen from the acceptor, to distort the donor CDRs and reduce affinity. Moreover, the adjacent amino acids may interact directly with the antigen (Amit et al., Science, 233:747 (1986)) and selecting these amino acids from the donor may be desirable to keep all the antigen contacts that provide affinity in the original antibody.
  • In some embodiments, a subject antibody comprises scFv multimers. For example, in some embodiments, a subject antibody is an scFv dimer (e.g., comprises two tandem scFv (scFv2)), an scFv trimer (e.g., comprises three tandem scFv (scFv3)), an scFv tetramer (e.g., comprises four tandem scFv (scFv4)), or is a multimer of more than four scFv (e.g., in tandem). The scFv monomers can be linked in tandem via linkers of from about 2 amino acids to about 10 amino acids in length, e.g., 2 aa, 3 aa, 4 aa, 5 aa, 6 aa, 7 aa, 8 aa, 9 aa, or 10 aa in length. Suitable linkers include, e.g., (Gly)x, where x is an integer from 2 to 10. Other suitable linkers are those discussed above. In some embodiments, each of the scFv monomers in a subject scFV multimer is humanized, as described above.
  • In some embodiments, a subject antibody comprises a constant region of an immunoglobulin (e.g., an Fc region). The Fc region, if present, can be a human Fc region. If constant regions are present, the antibody can contain both light chain and heavy chain constant regions. Suitable heavy chain constant region include CH1, hinge, CH2, CH3, and CH4 regions. The antibodies described herein include antibodies having all types of constant regions, including IgM, IgG, IgD, IgA and IgE, and any isotype, including IgG1, IgG2, IgG3 and IgG4. An example of a suitable heavy chain Fc region is a human isotype IgG1 Fc. Light chain constant regions can be lambda or kappa. A subject antibody (e.g., a subject humanized antibody) can comprise sequences from more than one class or isotype. Antibodies can be expressed as tetramers containing two light and two heavy chains, as separate heavy chains, light chains, as Fab, Fab′ F(ab′)2, and Fv, or as single chain antibodies in which heavy and light chain variable domains are linked through a spacer.
  • In some embodiments, a subject antibody comprises a free thiol (—SH) group at the carboxyl terminus, where the free thiol group can be used to attach the antibody to a second polypeptide (e.g., another antibody, including a subject antibody), a scaffold, a carrier, etc.
  • In some embodiments, a subject antibody comprises one or more non-naturally occurring amino acids. In some embodiments, the non-naturally encoded amino acid comprises a carbonyl group, an acetyl group, an aminooxy group, a hydrazine group, a hydrazide group, a semicarbazide group, an azide group, or an alkyne group. See, e.g., U.S. Pat. No. 7,632,924 for suitable non-naturally occurring amino acids. Inclusion of a non-naturally occurring amino acid can provide for linkage to a polymer, a second polypeptide, a scaffold, etc. For example, a subject antibody linked to a water-soluble polymer can be made by reacting a water-soluble polymer (e.g., PEG) that comprises a carbonyl group to an the subject antibody that comprises a non-naturally encoded amino acid that comprises an aminooxy, hydrazine, hydrazide or semicarbazide group. As another example, a subject antibody linked to a water-soluble polymer can be made by reacting a subject antibody that comprises an alkyne-containing amino acid with a water-soluble polymer (e.g., PEG) that comprises an azide moiety; in some embodiments, the azide or alkyne group is linked to the PEG molecule through an amide linkage. A “non-naturally encoded amino acid” refers to an amino acid that is not one of the 20 common amino acids or pyrolysine or selenocysteine. Other terms that may be used synonymously with the term “non-naturally encoded amino acid” are “non-natural amino acid,” “unnatural amino acid,” “non-naturally-occurring amino acid,” and variously hyphenated and non-hyphenated versions thereof. The term “non-naturally encoded amino acid” also includes, but is not limited to, amino acids that occur by modification (e.g. post-translational modifications) of a naturally encoded amino acid (including but not limited to, the 20 common amino acids or pyrolysine and selenocysteine) but are not themselves naturally incorporated into a growing polypeptide chain by the translation complex. Examples of such non-naturally-occurring amino acids include, but are not limited to, N-acetylglucosaminyl-L-serine, N-acetylglucosaminyl-L-threonine, and O-phosphotyrosine.
  • In some embodiments, a subject antibody is linked (e.g., covalently linked) to a polymer (e.g., a polymer other than a polypeptide). Suitable polymers include, e.g., biocompatible polymers, and water-soluble biocompatible polymers. Suitable polymers include synthetic polymers and naturally-occurring polymers. Suitable polymers include, e.g., substituted or unsubstituted straight or branched chain polyalkylene, polyalkenylene or polyoxyalkylene polymers or branched or unbranched polysaccharides, e.g. a homo- or hetero-polysaccharide. Suitable polymers include, e.g., ethylene vinyl alcohol copolymer (commonly known by the generic name EVOH or by the trade name EVAL); polybutylmethacrylate; poly(hydroxyvalerate); poly(L-lactic acid); polycaprolactone; poly(lactide-co-glycolide); poly(hydroxybutyrate); poly(hydroxybutyrate-co-valerate); polydioxanone; polyorthoester; polyanhydride; poly(glycolic acid); poly(D,L-lactic acid); poly(glycolic acid-co-trimethylene carbonate); polyphosphoester; polyphosphoester urethane; poly(amino acids); cyanoacrylates; poly(trimethylene carbonate); poly(iminocarbonate); copoly(ether-esters) (e.g., poly(ethylene oxide)-poly(lactic acid) (PEO/PLA) co-polymers); polyalkylene oxalates; polyphosphazenes; biomolecules, such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic acid; polyurethanes; silicones; polyesters; polyolefins; polyisobutylene and ethylene-alphaolefin copolymers; acrylic polymers and copolymers; vinyl halide polymers and copolymers, such as polyvinyl chloride; polyvinyl ethers, such as polyvinyl methyl ether; polyvinylidene halides, such as polyvinylidene fluoride and polyvinylidene chloride; polyacrylonitrile; polyvinyl ketones; polyvinyl aromatics, such as polystyrene; polyvinyl esters, such as polyvinyl acetate; copolymers of vinyl monomers with each other and olefins, such as ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl acetate copolymers; polyamides, such as Nylon 66 and polycaprolactam; alkyd resins; polycarbonates; polyoxymethylenes; polyimides; polyethers; epoxy resins; polyurethanes; rayon; rayon-triacetate; cellulose; cellulose acetate; cellulose butyrate; cellulose acetate butyrate; cellophane; cellulose nitrate; cellulose propionate; cellulose ethers; amorphous Teflon; poly(ethylene glycol); and carboxymethyl cellulose.
  • Suitable synthetic polymers include unsubstituted and substituted straight or branched chain poly(ethyleneglycol), poly(propyleneglycol) poly(vinylalcohol), and derivatives thereof, e.g., substituted poly(ethyleneglycol) such as methoxypoly(ethyleneglycol), and derivatives thereof. Suitable naturally-occurring polymers include, e.g., albumin, amylose, dextran, glycogen, and derivatives thereof.
  • Suitable polymers can have an average molecular weight in a range of from 500 Da to 50000 Da, e.g., from 5000 Da to 40000 Da, or from 25000 to 40000 Da. For example, in some embodiments, where a subject antibody comprises a poly(ethylene glycol) (PEG) or methoxypoly(ethyleneglycol) polymer, the PEG or methoxypoly(ethyleneglycol) polymer can have a molecular weight in a range of from about 0.5 kiloDaltons (kDa) to 1 kDa, from about 1 kDa to 5 kDa, from 5 kDa to 10 kDa, from 10 kDa to 25 kDa, from 25 kDa to 40 kDa, or from 40 kDa to 60 kDa.
  • As noted above, in some embodiments, a subject antibody is covalently linked to a PEG polymer. In some embodiments, a subject scFv multimer is covalently linked to a PEG polymer. See, e.g., Albrecht et al. (2006) J. Immunol. Methods 310:100. Methods and reagents suitable for PEGylation of a protein are well known in the art and may be found in, e.g., U.S. Pat. No. 5,849,860. PEG suitable for conjugation to a protein is generally soluble in water at room temperature, and has the general formula R(O—CH2—CH2)nO—R, where R is hydrogen or a protective group such as an alkyl or an alkanol group, and where n is an integer from 1 to 1000. Where R is a protective group, it generally has from 1 to 8 carbons.
  • The PEG conjugated to the subject antibody can be linear. The PEG conjugated to the subject protein may also be branched. Branched PEG derivatives such as those described in U.S. Pat. No. 5,643,575, “star-PEG's” and multi-armed PEG's such as those described in Shearwater Polymers, Inc. catalog “Polyethylene Glycol Derivatives 1997-1998.” Star PEGs are described in the art including, e.g., in U.S. Pat. No. 6,046,305.
  • A subject antibody can be glycosylated, e.g., comprise a covalently linked carbohydrate or polysaccharide moiety. Glycosylation of antibodies 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 tripeptide 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 tripeptide 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 may also be used.
  • Addition of glycosylation sites to an antibody is conveniently accomplished by altering the amino acid sequence such that it contains one or more of the above-described tripeptide sequences (for N-linked glycosylation sites). The alteration may also be made by the addition of, or substitution by, one or more serine or threonine residues to the sequence of the original antibody (for O-linked glycosylation sites). Similarly, removal of glycosylation sites can be accomplished by amino acid alteration within the native glycosylation sites of an antibody.
  • A subject antibody will in some embodiments comprise a “radiopaque” label, e.g. a label that can be easily visualized using for example x-rays. Radiopaque materials are well known to those of skill in the art. The most common radiopaque materials include iodide, bromide or barium salts. Other radiopaque materials are also known and include, but are not limited to organic bismuth derivatives (see, e.g., U.S. Pat. No. 5,939,045), radiopaque multiurethanes (see U.S. Pat. No. 5,346,981), organobismuth composites (see, e.g., U.S. Pat. No. 5,256,334), radiopaque barium multimer complexes (see, e.g., U.S. Pat. No. 4,866,132), and the like.
  • A subject antibody can be covalently linked to a second moiety (e.g., a lipid, a polypeptide other than a subject antibody, a synthetic polymer, a carbohydrate, and the like) using for example, glutaraldehyde, a homobifunctional cross-linker, or a heterobifunctional cross-linker. Glutaraldehyde cross-links polypeptides via their amino moieties. Homobifunctional cross-linkers (e.g., a homobifunctional imidoester, a homobifunctional N-hydroxysuccinimidyl (NHS) ester, or a homobifunctional sulfhydryl reactive cross-linker) contain two or more identical reactive moieties and can be used in a one step reaction procedure in which the cross-linker is added to a solution containing a mixture of the polypeptides to be linked. Homobifunctional NHS ester and imido esters cross-link amine containing polypeptides. In a mild alkaline pH, imido esters react only with primary amines to form imidoamides, and overall charge of the cross-linked polypeptides is not affected. Homobifunctional sulfhydryl reactive cross-linkers includes bismaleimidhexane (BMH), 1,5-difluoro-2,4-dinitrobenzene (DFDNB), and 1,4-di-(3′,2′-pyridyldithio) propinoamido butane (DPDPB).
  • Heterobifunctional cross-linkers have two or more different reactive moieties (e.g., amine reactive moiety and a sulfhydryl-reactive moiety) and are cross-linked with one of the polypeptides via the amine or sulfhydryl reactive moiety, then reacted with the other polypeptide via the non-reacted moiety. Multiple heterobifunctional haloacetyl cross-linkers are available, as are pyridyl disulfide cross-linkers. Carbodiimides are a classic example of heterobifunctional cross-linking reagents for coupling carboxyls to amines, which results in an amide bond.
  • A subject antibody can be immobilized on a solid support. Suitable supports are well known in the art and comprise, inter alia, commercially available column materials, polystyrene beads, latex beads, magnetic beads, colloid metal particles, glass and/or silicon chips and surfaces, nitrocellulose strips, nylon membranes, sheets, duracytes, wells of reaction trays (e.g., multi-well plates), plastic tubes, etc. A solid support can comprise any of a variety of substances, including, e.g., glass, polystyrene, polyvinyl chloride, polypropylene, polyethylene, polycarbonate, dextran, nylon, amylose, natural and modified celluloses, polyacrylamides, agaroses, and magnetite. Suitable methods for immobilizing a subject antibody onto a solid support are well known and include, but are not limited to ionic, hydrophobic, covalent interactions and the like. Solid supports can be soluble or insoluble, e.g., in aqueous solution. In some embodiments, a suitable solid support is generally insoluble in an aqueous solution.
  • A subject antibody will in some embodiments comprise a detectable label. Suitable detectable labels include any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. Suitable include, but are not limited to, magnetic beads (e.g. Dynabeads™), fluorescent dyes (e.g., fluorescein isothiocyanate, texas red, rhodamine, a green fluorescent protein, a red fluorescent protein, a yellow fluorescent protein, and the like), radiolabels (e.g., 3H, 125I 35S, 14C, or 32P), enzymes (e.g., horse radish peroxidase, alkaline phosphatase, luciferase, and others commonly used in an enzyme-linked immunosorbent assay (ELISA)), and colorimetric labels such as colloidal gold or colored glass or plastic (e.g. polystyrene, polypropylene, latex, etc.) beads.
  • In some embodiments, a subject antibody comprises a contrast agent or a radioisotope, where the contrast agent or radioisotope is one that is suitable for use in imaging, e.g., imaging procedures carried out on humans. Non-limiting examples of labels include radioisotope such as 1231I (iodine), 18F (fluorine), 99Tc (technetium), 111In (indium), and 67Ga (gallium), and contrast agent such as gadolinium (Gd), dysprosium, and iron. Radioactive Gd isotopes (153Gd) also are available and suitable for imaging procedures in non-human mammals. A subject antibody can be labeled using standard techniques. For example, a subject antibody can be iodinated using chloramine T or 1,3,4,6-tetrachloro-3α,6α-dephenylglycouril. For fluorination, fluorine is added to a subject antibody during the synthesis by a fluoride ion displacement reaction. See, Muller-Gartner, H., TIB Tech., 16:122-130 (1998) and Saji, H., Crit. Rev. Ther. Drug Carrier Syst., 16(2):209-244 (1999) for a review of synthesis of proteins with such radioisotopes. A subject antibody can also be labeled with a contrast agent through standard techniques. For example, a subject antibody can be labeled with Gd by conjugating low molecular Gd chelates such as Gd diethylene triamine pentaacetic acid (GdDTPA) or Gd tetraazacyclododecanetetraacetic (GdDOTA) to the antibody. See, Caravan et al., Chem. Rev. 99:2293-2352 (1999) and Lauffer et al., J. Magn. Reson. Imaging, 3:11-16 (1985). A subject antibody can be labeled with Gd by, for example, conjugating polylysine-Gd chelates to the antibody. See, for example, Curtet et al., Invest. Radiol., 33(10):752-761 (1998). Alternatively, a subject antibody can be labeled with Gd by incubating paramagnetic polymerized liposomes that include Gd chelator lipid with avidin and biotinylated antibody. See, for example, Sipkins et al., Nature Med., 4:623-626 (1998).
  • Suitable fluorescent proteins that can be linked to a subject antibody include, but are not limited to, a green fluorescent protein from Aequoria victoria or a mutant or derivative thereof e.g., as described in U.S. Pat. Nos. 6,066,476; 6,020,192; 5,985,577; 5,976,796; 5,968,750; 5,968,738; 5,958,713; 5,919,445; 5,874,304; e.g., Enhanced GFP, many such GFP which are available commercially, e.g., from Clontech, Inc.; a red fluorescent protein; a yellow fluorescent protein; any of a variety of fluorescent and colored proteins from Anthozoan species, as described in, e.g., Matz et al. (1999) Nature Biotechnol. 17:969-973; and the like.
  • A subject antibody will in some embodiments be linked to (e.g., covalently or non-covalently linked) a fusion partner, e.g., a ligand; an epitope tag; a peptide; a protein other than an antibody; and the like. Suitable fusion partners include peptides and polypeptides that confer enhanced stability in vivo (e.g., enhanced serum half-life); provide ease of purification, e.g., (His)n, e.g., 6His, and the like; provide for secretion of the fusion protein from a cell; provide an epitope tag, e.g., GST, hemagglutinin (HA; e.g., CYPYDVPDYA; SEQ ID NO:6607), FLAG (e.g., DYKDDDDK; SEQ ID NO:6608), c-myc (e.g., CEQKLISEEDL; SEQ ID NO:6609), and the like; provide a detectable signal, e.g., an enzyme that generates a detectable product (e.g., β-galactosidase, luciferase), or a protein that is itself detectable, e.g., a green fluorescent protein, a red fluorescent protein, a yellow fluorescent protein, etc.; provides for multimerization, e.g., a multimerization domain such as an Fc portion of an immunoglobulin; and the like.
  • The fusion may also include an affinity domain, including peptide sequences that can interact with a binding partner, e.g., such as one immobilized on a solid support, useful for identification or purification. Consecutive single amino acids, such as histidine, when fused to a protein, can be used for one-step purification of the fusion protein by high affinity binding to a resin column, such as nickel sepharose. Exemplary affinity domains include His5 (HHHHH) (SEQ ID NO:6610), HisX6 (HHHHHH) (SEQ ID NO:6611), C-myc (EQKLISEEDL) (SEQ ID NO:6612), Flag (DYKDDDDK) (SEQ ID NO:6608), StrepTag (WSHPQFEK) (SEQ ID NO:6613), hemagglutinin, e.g., HA Tag (YPYDVPDYA; SEQ ID NO:6614), glutathinone-S-transferase (GST), thioredoxin, cellulose binding domain, RYIRS (SEQ ID NO:6615), Phe-His-His-Thr (SEQ ID NO:6616), chitin binding domain, S-peptide, T7 peptide, SH2 domain, C-end RNA tag, WEAAAREACCRECCARA (SEQ ID NO:6617), metal binding domains, e.g., zinc binding domains or calcium binding domains such as those from calcium-binding proteins, e.g., calmodulin, troponin C, calcineurin B, myosin light chain, recoverin, S-modulin, visinin, VILIP, neurocalcin, hippocalcin, frequenin, caltractin, calpain large-subunit, 5100 proteins, parvalbumin, calbindin D9K, calbindin D28K, and calretinin, inteins, biotin, streptavidin, MyoD, leucine zipper sequences, and maltose binding protein.
  • A subject antibody will in some embodiments be fused to a polypeptide that binds to an endogenous blood brain barrier (BBB) receptor Linking a subject antibody to a polypeptide that binds to an endogenous BBB receptor facilitates crossing the BBB, e.g., in a subject treatment method (see below) involving administration of a subject antibody to an individual in need thereof. Suitable polypeptides that bind to an endogenous BBB include antibodies, e.g., monoclonal antibodies, or antigen-binding fragments thereof, that specifically bind to an endogenous BBB receptor. Suitable endogenous BBB receptors include, but are not limited to, an insulin receptor, a transferrin receptor, a leptin receptor, a lipoprotein receptor, and an insulin-like growth factor receptor. See, e.g., U.S. Patent Publication No. 2009/0156498.
  • In some embodiments, a subject antibody comprises a polyamine modification. Polyamine modification of a subject antibody enhances permeability of the modified antibody at the BBB. A subject antibody can be modified with polyamines that are either naturally occurring or synthetic. See, for example, U.S. Pat. No. 5,670,477. Useful naturally occurring polyamines include putrescine, spermidine, spermine, 1,3-deaminopropane, norspermidine, syn-homospermidine, thermine, thermospermine, caldopentamine, homocaldopentamine, and canavalmine. Putrescine, spermidine and spermine are particularly useful. Synthetic polyamines are composed of the empirical formula CxHyNz, can be cyclic or acyclic, branched or unbranched, hydrocarbon chains of 3-12 carbon atoms that further include 1-6 NR or N(R)2 moieties, wherein R is H, (C1-C4) alkyl, phenyl, or benzyl. Polyamines can be linked to an antibody using any standard crosslinking method.
  • In some embodiments, a subject antibody is modified to include a carbohydrate moiety, where the carbohydrate moiety can be covalently linked to the antibody. In some embodiments, a subject antibody is modified to include a lipid moiety, where the lipid moiety can be covalently linked to the antibody. Suitable lipid moieties include, e.g., an N-fatty acyl group such as N-lauroyl, N-oleoyl, etc.; a fatty amine such as dodecyl amine, oleoyl amine, etc.; a C3-C16 long-chain aliphatic lipid; and the like. See, e.g., U.S. Pat. No. 6,638,513). In some embodiments, a subject antibody is incorporated into a liposome.
  • Methods of Producing a Subject Antibody
  • The present antibody can be produced by any known method, e.g., conventional synthetic methods for protein synthesis; recombinant DNA methods; etc.
  • Where a subject antibody is a single chain polypeptide, it can synthesized using standard chemical peptide synthesis techniques. Where a polypeptide is chemically synthesized, the synthesis may proceed via liquid-phase or solid-phase. Solid phase polypeptide synthesis (SPPS), in which the C-terminal amino acid of the sequence is attached to an insoluble support followed by sequential addition of the remaining amino acids in the sequence, is an example of a suitable method for the chemical synthesis of a subject antibody. Various forms of SPPS, such as Fmoc and Boc, are available for synthesizing a subject antibody. Techniques for solid phase synthesis are described by Barany and Merrifield, Solid-Phase Peptide Synthesis; pp. 3-284 in The Peptides: Analysis, Synthesis, Biology. Vol. 2: Special Methods in Peptide Synthesis, Part A., Merrifield, et al. J. Am. Chem. Soc., 85: 2149-2156 (1963); Stewart et al., Solid Phase Peptide Synthesis, 2nd ed. Pierce Chem. Co., Rockford, Ill. (1984); and Ganesan A. 2006 Mini Rev. Med Chem. 6:3-10 and Camarero J A et al. 2005 Protein Pept Lett. 12:723-8. Briefly, small insoluble, porous beads are treated with functional units on which peptide chains are built. After repeated cycling of coupling/deprotection, the free N-terminal amine of a solid-phase attached is coupled to a single N-protected amino acid unit. This unit is then deprotected, revealing a new N-terminal amine to which a further amino acid may be attached. The peptide remains immobilized on the solid-phase and undergoes a filtration process before being cleaved off.
  • Standard recombinant methods can be used for production of a subject antibody. For example, nucleic acids encoding light and heavy chain variable regions, optionally linked to constant regions, are inserted into expression vectors. The light and heavy chains can be cloned in the same or different expression vectors. The DNA segments encoding immunoglobulin chains are operably linked to control sequences in the expression vector(s) that ensure the expression of immunoglobulin polypeptides. Expression control sequences include, but are not limited to, promoters (e.g., naturally-associated or heterologous promoters), signal sequences, enhancer elements, and transcription termination sequences. The expression control sequences can be eukaryotic promoter systems in vectors capable of transforming or transfecting eukaryotic host cells (e.g., COS or CHO cells). Once the vector has been incorporated into the appropriate host, the host is maintained under conditions suitable for high level expression of the nucleotide sequences, and the collection and purification of the antibodies.
  • Because of the degeneracy of the code, a variety of nucleic acid sequences can encode each immunoglobulin amino acid sequence. The desired nucleic acid sequences can be produced by de novo solid-phase DNA synthesis or by polymerase chain reaction (PCR) mutagenesis of an earlier prepared variant of the desired polynucleotide. Oligonucleotide-mediated mutagenesis is an example of a suitable method for preparing substitution, deletion and insertion variants of target polypeptide DNA. See Adelman et al., DNA 2:183 (1983). Briefly, the target polypeptide DNA is altered by hybridizing an oligonucleotide encoding the desired mutation to a single-stranded DNA template. After hybridization, a DNA polymerase is used to synthesize an entire second complementary strand of the template that incorporates the oligonucleotide primer, and encodes the selected alteration in the target polypeptide DNA.
  • Suitable expression vectors are typically replicable in the host organisms either as episomes or as an integral part of the host chromosomal DNA. Commonly, expression vectors contain selection markers (e.g., ampicillin-resistance, hygromycin-resistance, tetracycline resistance, kanamycin resistance or neomycin resistance) to permit detection of those cells transformed with the desired DNA sequences.
  • Escherichia coli is an example of a prokaryotic host cell that can be used for cloning a subject antibody-encoding polynucleotide. Other microbial hosts suitable for use include bacilli, such as Bacillus subtilis, and other enterobacteriaceae, such as Salmonella, Serratia, and various Pseudomonas species. In these prokaryotic hosts, one can also make expression vectors, which will typically contain expression control sequences compatible with the host cell (e.g., an origin of replication). In addition, any number of a variety of well-known promoters will be present, such as the lactose promoter system, a tryptophan (trp) promoter system, a beta-lactamase promoter system, or a promoter system from phage lambda. The promoters will typically control expression, optionally with an operator sequence, and have ribosome binding site sequences and the like, for initiating and completing transcription and translation.
  • Other microbes, such as yeast, are also useful for expression. Saccharomyces (e.g., S. cerevisiae) and Pichia are examples of suitable yeast host cells, with suitable vectors having expression control sequences (e.g., promoters), an origin of replication, termination sequences and the like as desired. Typical promoters include 3-phosphoglycerate kinase and other glycolytic enzymes. Inducible yeast promoters include, among others, promoters from alcohol dehydrogenase, isocytochrome C, and enzymes responsible for maltose and galactose utilization.
  • In addition to microorganisms, mammalian cells (e.g., mammalian cells grown in in vitro cell culture) can also be used to express and produce the polypeptides of the present invention (e.g., polynucleotides encoding immunoglobulins or fragments thereof). See Winnacker, From Genes to Clones, VCH Publishers, N.Y., N.Y. (1987). Suitable mammalian host cells include CHO cell lines, various Cos cell lines, HeLa cells, myeloma cell lines, and transformed B-cells or hybridomas. Expression vectors for these cells can include expression control sequences, such as an origin of replication, a promoter, and an enhancer (Queen et al., Immunol. Rev. 89:49 (1986)), and necessary processing information sites, such as ribosome binding sites, RNA splice sites, polyadenylation sites, and transcriptional terminator sequences. Examples of suitable expression control sequences are promoters derived from immunoglobulin genes, SV40, adenovirus, bovine papilloma virus, cytomegalovirus and the like. See Co et al., J. Immunol. 148:1149 (1992).
  • Once synthesized (either chemically or recombinantly), the whole antibodies, their dimers, individual light and heavy chains, or other forms of a subject antibody (e.g., scFv, etc.) can be purified according to standard procedures of the art, including ammonium sulfate precipitation, affinity columns, column chromatography, high performance liquid chromatography (HPLC) purification, gel electrophoresis, and the like (see generally Scopes, Protein Purification (Springer-Verlag, N.Y., (1982)). A subject antibody can be substantially pure, e.g., at least about 80% to 85% pure, at least about 85% to 90% pure, at least about 90% to 95% pure, or 98% to 99%, or more, pure, e.g., free from contaminants such as cell debris, macromolecules other than a subject antibody, etc.
  • Compositions
  • The present disclosure provides a composition comprising a subject antibody. A subject antibody composition can comprise, in addition to a subject antibody, one or more of: a salt, e.g., NaCl, MgCl2, KCl, MgSO4, etc.; a buffering agent, e.g., a Tris buffer, N-(2-Hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid) (HEPES), 2-(N-Morpholino)ethanesulfonic acid (MES), 2-(N-Morpholino)ethanesulfonic acid sodium salt (MES), 3-(N-Morpholino)propanesulfonic acid (MOPS), N-tris[Hydroxymethyl]methyl-3-aminopropanesulfonic acid (TAPS), etc.; a solubilizing agent; a detergent, e.g., a non-ionic detergent such as Tween-20, etc.; a protease inhibitor; glycerol; and the like.
  • Nucleic Acids
  • The present disclosure provides nucleic acids comprising nucleotide sequences encoding a subject antibody. A nucleotide sequence encoding a subject antibody can be operably linked to one or more regulatory elements, such as a promoter and enhancer, that allow expression of the nucleotide sequence in the intended target cells (e.g., a cell that is genetically modified to synthesize the encoded antibody).
  • Suitable promoter and enhancer elements are known in the art. For expression in a bacterial cell, suitable promoters include, but are not limited to, lad, lacZ, T3, T7, gpt, lambda P and trc. For expression in a eukaryotic cell, suitable promoters include, but are not limited to, light and/or heavy chain immunoglobulin gene promoter and enhancer elements; cytomegalovirus immediate early promoter; herpes simplex virus thymidine kinase promoter; early and late SV40 promoters; promoter present in long terminal repeats from a retrovirus; mouse metallothionein-I promoter; and various art-known tissue specific promoters.
  • In some embodiments, e.g., for expression in a yeast cell, a suitable promoter is a constitutive promoter such as an ADH1 promoter, a PGK1 promoter, an ENO promoter, a PYK1 promoter and the like; or a regulatable promoter such as a GAL1 promoter, a GAL10 promoter, an ADH2 promoter, a PHO5 promoter, a CUP1 promoter, a GAL7 promoter, a MET25 promoter, a MET3 promoter, a CYC1 promoter, a HIS3 promoter, an ADH1 promoter, a PGK promoter, a GAPDH promoter, an ADC1 promoter, a TRP1 promoter, a URA3 promoter, a LEU2 promoter, an ENO promoter, a TP1 promoter, and AOX1 (e.g., for use in Pichia). Selection of the appropriate vector and promoter is well within the level of ordinary skill in the art.
  • Suitable promoters for use in prokaryotic host cells include, but are not limited to, a bacteriophage T7 RNA polymerase promoter; a trp promoter; a lac operon promoter; a hybrid promoter, e.g., a lac/tac hybrid promoter, a tac/trc hybrid promoter, a trp/lac promoter, a T7/lac promoter; a trc promoter; a tac promoter, and the like; an araBAD promoter; in vivo regulated promoters, such as an ssaG promoter or a related promoter (see, e.g., U.S. Patent Publication No. 20040131637), a pagC promoter (Pulkkinen and Miller, J. Bacteriol., 1991: 173(1): 86-93; Alpuche-Aranda et al., PNAS, 1992; 89(21): 10079-83), a nirB promoter (Harborne et al. (1992) Mol. Micro. 6:2805-2813), and the like (see, e.g., Dunstan et al. (1999) Infect. Immun. 67:5133-5141; McKelvie et al. (2004) Vaccine 22:3243-3255; and Chatfield et al. (1992) Biotechnol. 10:888-892); a sigma70 promoter, e.g., a consensus sigma70 promoter (see, e.g., GenBank Accession Nos. AX798980, AX798961, and AX798183); a stationary phase promoter, e.g., a dps promoter, an spy promoter, and the like; a promoter derived from the pathogenicity island SPI-2 (see, e.g., WO96/17951); an actA promoter (see, e.g., Shetron-Rama et al. (2002) Infect. Immun. 70:1087-1096); an rpsM promoter (see, e.g., Valdivia and Falkow (1996). Mol. Microbiol. 22:367); a tet promoter (see, e.g., Hillen,W. and Wissmann,A. (1989) In Saenger,W. and Heinemann,U. (eds), Topics in Molecular and Structural Biology, Protein—Nucleic Acid Interaction. Macmillan, London, UK, Vol. 10, pp. 143-162); an SP6 promoter (see, e.g., Melton et al. (1984) Nucl. Acids Res. 12:7035); and the like. Suitable strong promoters for use in prokaryotes such as Escherichia coli include, but are not limited to Trc, Tac, T5, T7, and PLambda. Non limiting examples of operators for use in bacterial host cells include a lactose promoter operator (Lad repressor protein changes conformation when contacted with lactose, thereby preventing the Lad repressor protein from binding to the operator), a tryptophan promoter operator (when complexed with tryptophan, TrpR repressor protein has a conformation that binds the operator; in the absence of tryptophan, the TrpR repressor protein has a conformation that does not bind to the operator), and a tac promoter operator (see, for example, deBoer et al. (1983) Proc. Natl. Acad. Sci. U.S.A. 80:21-25).
  • A nucleotide sequence encoding a subject antibody can be present in an expression vector and/or a cloning vector. Where a subject antibody comprises two separate polypeptides, nucleotide sequences encoding the two polypeptides can be cloned in the same or separate vectors. An expression vector can include a selectable marker, an origin of replication, and other features that provide for replication and/or maintenance of the vector.
  • Large numbers of suitable vectors and promoters are known to those of skill in the art; many are commercially available for generating a subject recombinant constructs. The following vectors are provided by way of example. Bacterial: pBs, phagescript, PsiX174, pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene, La Jolla, Calif., USA); pTrc99A, pKK223-3, pKK233-3, pDR540, and pRIT5 (Pharmacia, Uppsala, Sweden). Eukaryotic: pWLneo, pSV2cat, pOG44, PXR1, pSG (Stratagene) pSVK3, pBPV, pMSG and pSVL (Pharmacia).
  • Expression vectors generally have convenient restriction sites located near the promoter sequence to provide for the insertion of nucleic acid sequences encoding heterologous proteins. A selectable marker operative in the expression host may be present. Suitable expression vectors include, but are not limited to, viral vectors (e.g. viral vectors based on vaccinia virus; poliovirus; adenovirus (see, e.g., Li et al., Invest Opthalmol Vis Sci 35:2543 2549, 1994; Borras et al., Gene Ther 6:515 524, 1999; Li and Davidson, PNAS 92:7700 7704, 1995; Sakamoto et al., H Gene Ther 5:1088 1097, 1999; WO 94/12649, WO 93/03769; WO 93/19191; WO 94/28938; WO 95/11984 and WO 95/00655); adeno-associated virus (see, e.g., Ali et al., Hum Gene Ther 9:81 86, 1998, Flannery et al., PNAS 94:6916 6921, 1997; Bennett et al., Invest Opthalmol Vis Sci 38:2857 2863, 1997; Jomary et al., Gene Ther 4:683 690, 1997, Rolling et al., Hum Gene Ther 10:641 648, 1999; Ali et al., Hum Mol Genet 5:591 594, 1996; Srivastava in WO 93/09239, Samulski et al., J. Vir. (1989) 63:3822-3828; Mendelson et al., Virol. (1988) 166:154-165; and Flotte et al., PNAS (1993) 90:10613-10617); SV40; herpes simplex virus; human immunodeficiency virus (see, e.g., Miyoshi et al., PNAS 94:10319 23, 1997; Takahashi et al., J Virol 73:7812 7816, 1999); a retroviral vector (e.g., Murine Leukemia Virus, spleen necrosis virus, and vectors derived from retroviruses such as Rous Sarcoma Virus, Harvey Sarcoma Virus, avian leukosis virus, human immunodeficiency virus, myeloproliferative sarcoma virus, and mammary tumor virus); and the like.
  • As noted above, a subject nucleic acid comprises a nucleotide sequence encoding a subject antibody. A subject nucleic acid can comprise a nucleotide sequence encoding heavy- and light-chain CDRs. In some embodiments, a subject nucleic acid comprises a nucleotide sequence encoding heavy- and light-chain CDRs, where the CDR-encoding sequences are interspersed with FR-encoding nucleotide sequences. In some embodiments, the FR-encoding nucleotide sequences are human FR-encoding nucleotide sequences.
  • In some embodiments, a subject nucleic acid comprises a nucleotide sequence having at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100%, nucleotide sequence identity to the nucleotide sequence set forth in herein. In some embodiments, a subject nucleic acid comprises a nucleotide sequence having at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100%, nucleotide sequence identity to the nucleotide sequence set forth in herein.
  • Cells
  • The present disclosure provides isolated genetically modified host cells (e.g., in vitro cells) that are genetically modified with a subject nucleic acid. In some embodiments, a subject isolated genetically modified host cell can produce a subject antibody.
  • Suitable host cells include eukaryotic host cells, such as a mammalian cell, an insect host cell, a yeast cell; and prokaryotic cells, such as a bacterial cell. Introduction of a subject nucleic acid into the host cell can be effected, for example by calcium phosphate precipitation, DEAE dextran mediated transfection, liposome-mediated transfection, electroporation, or other known method.
  • Suitable mammalian cells include primary cells and immortalized cell lines. Suitable mammalian cell lines include human cell lines, non-human primate cell lines, rodent (e.g., mouse, rat) cell lines, and the like. Suitable mammalian cell lines include, but are not limited to, HeLa cells (e.g., American Type Culture Collection (ATCC) No. CCL-2), CHO cells (e.g., ATCC Nos. CRL9618, CCL61, CRL9096), 293 cells (e.g., ATCC No. CRL-1573), Vero cells, NIH 3T3 cells (e.g., ATCC No. CRL-1658), Huh-7 cells, BHK cells (e.g., ATCC No. CCL10), PC12 cells (ATCC No. CRL1721), COS cells, COS-7 cells (ATCC No. CRL1651), RAT1 cells, mouse L cells (ATCC No. CCLI.3), human embryonic kidney (HEK) cells (ATCC No. CRL1573), HLHepG2 cells, and the like.
  • Suitable yeast cells include, but are not limited to, Pichia pastoris, Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia sp., Saccharomyces cerevisiae, Saccharomyces sp., Hansenula polymorpha, Kluyveromyces sp., Kluyveromyces lactis, Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium sp., Fusarium gramineum, Fusarium venenatum, Neurospora crassa, Chlamydomonas reinhardtii, and the like.
  • Suitable prokaryotic cells include, but are not limited to, any of a variety of laboratory strains of Escherichia coli, Lactobacillus sp., Salmonella sp., Shigella sp., and the like. See, e.g., Carrier et al. (1992) J. Immunol. 148:1176-1181; U.S. Pat. No. 6,447,784; and Sizemore et al. (1995) Science 270:299-302. Examples of Salmonella strains which can be employed in the present invention include, but are not limited to, Salmonella typhi and S. typhimurium. Suitable Shigella strains include, but are not limited to, Shigella flexneri, Shigella sonnei, and Shigella disenteriae. Typically, the laboratory strain is one that is non-pathogenic. Non-limiting examples of other suitable bacteria include, but are not limited to, Bacillus subtilis, Pseudomonas pudita, Pseudomonas aeruginosa, Pseudomonas mevalonii, Rhodobacter sphaeroides, Rhodobacter capsulatus, Rhodospirillum rubrum, Rhodococcus sp., and the like. In some embodiments, the host cell is Escherichia coli.
  • Compositions
  • The present disclosure provides compositions, including pharmaceutical compositions, comprising a subject antibody. In general, a formulation comprises an effective amount of a subject antibody. An “effective amount” means a dosage sufficient to produce a desired result, e.g., an increase of muscle mass or amelioration of a symptom of a disease. Generally, the desired result is at least a reduction in a symptom of an ACVR2A-associated conditino, as compared to a control. A subject antibody can be delivered in such a manner as to avoid the blood-brain barrier, as described in more detail below. A subject antibody can be formulated and/or modified to enable the antibody to cross the blood-brain barrier.
  • Formulations
  • In the subject methods, a subject antibody can be administered to the host using any convenient means capable of resulting in the desired therapeutic effect or diagnostic effect. Thus, the agent can be incorporated into a variety of formulations for therapeutic administration. More particularly, a subject antibody can be formulated into pharmaceutical compositions by combination with appropriate, pharmaceutically acceptable carriers or diluents, and may be formulated into preparations in solid, semi-solid, liquid or gaseous forms, such as tablets, capsules, powders, granules, ointments, solutions, suppositories, injections, inhalants and aerosols.
  • In pharmaceutical dosage forms, a subject antibody can be administered in the form of their pharmaceutically acceptable salts, or they may also be used alone or in appropriate association, as well as in combination, with other pharmaceutically active compounds. The following methods and excipients are merely exemplary and are in no way limiting.
  • For oral preparations, a subject antibody can be used alone or in combination with appropriate additives to make tablets, powders, granules or capsules, for example, with conventional additives, such as lactose, mannitol, corn starch or potato starch; with binders, such as crystalline cellulose, cellulose derivatives, acacia, corn starch or gelatins; with disintegrators, such as corn starch, potato starch or sodium carboxymethylcellulose; with lubricants, such as talc or magnesium stearate; and if desired, with diluents, buffering agents, moistening agents, preservatives and flavoring agents.
  • A subject antibody can be formulated into preparations for injection by dissolving, suspending or emulsifying them in an aqueous or nonaqueous solvent, such as vegetable or other similar oils, synthetic aliphatic acid glycerides, esters of higher aliphatic acids or propylene glycol; and if desired, with conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifying agents, stabilizers and preservatives.
  • Pharmaceutical compositions comprising a subject antibody are prepared by mixing the antibody having the desired degree of purity with optional physiologically acceptable carriers, excipients, stabilizers, surfactants, buffers and/or tonicity agents. Acceptable carriers, excipients and/or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid, glutathione, cysteine, methionine and citric acid; preservatives (such as ethanol, benzyl alcohol, phenol, m-cresol, p-chlor-m-cresol, methyl or propyl parabens, benzalkonium chloride, or combinations thereof); amino acids such as arginine, glycine, ornithine, lysine, histidine, glutamic acid, aspartic acid, isoleucine, leucine, alanine, phenylalanine, tyrosine, tryptophan, methionine, serine, proline and combinations thereof; monosaccharides, disaccharides and other carbohydrates; low molecular weight (less than about 10 residues) polypeptides; proteins, such as gelatin or serum albumin; chelating agents such as EDTA; sugars such as trehalose, sucrose, lactose, glucose, mannose, maltose, galactose, fructose, sorbose, raffinose, glucosamine, N-methylglucosamine, galactosamine, and neuraminic acid; and/or non-ionic surfactants such as Tween, Brij Pluronics, Triton-X, or polyethylene glycol (PEG).
  • The pharmaceutical composition may be in a liquid form, a lyophilized form or a liquid form reconstituted from a lyophilized form, wherein the lyophilized preparation is to be reconstituted with a sterile solution prior to administration. The standard procedure for reconstituting a lyophilized composition is to add back a volume of pure water (typically equivalent to the volume removed during lyophilization); however solutions comprising antibacterial agents may be used for the production of pharmaceutical compositions for parenteral administration; see also Chen (1992) Drug Dev Ind Pharm 18, 1311-54.
  • Exemplary antibody concentrations in a subject pharmaceutical composition may range from about 1 mg/mL to about 200 mg/ml or from about 50 mg/mL to about 200 mg/mL, or from about 150 mg/mL to about 200 mg/mL.
  • An aqueous formulation of the antibody may be prepared in a pH-buffered solution, e.g., at pH ranging from about 4.0 to about 7.0, or from about 5.0 to about 6.0, or alternatively about 5.5. Examples of buffers that are suitable for a pH within this range include phosphate-, histidine-, citrate-, succinate-, acetate-buffers and other organic acid buffers. The buffer concentration can be from about 1 mM to about 100 mM, or from about 5 mM to about 50 mM, depending, e.g., on the buffer and the desired tonicity of the formulation.
  • A tonicity agent may be included in the antibody formulation to modulate the tonicity of the formulation. Exemplary tonicity agents include sodium chloride, potassium chloride, glycerin and any component from the group of amino acids, sugars as well as combinations thereof. In some embodiments, the aqueous formulation is isotonic, although hypertonic or hypotonic solutions may be suitable. The term “isotonic” denotes a solution having the same tonicity as some other solution with which it is compared, such as physiological salt solution or serum. Tonicity agents may be used in an amount of about 5 mM to about 350 mM, e.g., in an amount of 100 mM to 350 nM.
  • A surfactant may also be added to the antibody formulation to reduce aggregation of the formulated antibody and/or minimize the formation of particulates in the formulation and/or reduce adsorption. Exemplary surfactants include polyoxyethylensorbitan fatty acid esters (Tween), polyoxyethylene alkyl ethers (Brij), alkylphenylpolyoxyethylene ethers (Triton-X), polyoxyethylene-polyoxypropylene copolymer (Poloxamer, Pluronic), and sodium dodecyl sulfate (SDS). Examples of suitable polyoxyethylenesorbitan-fatty acid esters are polysorbate 20, (sold under the trademark Tween 20™) and polysorbate 80 (sold under the trademark Tween 80™). Examples of suitable polyethylene-polypropylene copolymers are those sold under the names Pluronic® F68 or Poloxamer 188™. Examples of suitable Polyoxyethylene alkyl ethers are those sold under the trademark Brij™. Exemplary concentrations of surfactant may range from about 0.001% to about 1% w/v.
  • A lyoprotectant may also be added in order to protect the labile active ingredient (e.g. a protein) against destabilizing conditions during the lyophilization process. For example, known lyoprotectants include sugars (including glucose and sucrose); polyols (including mannitol, sorbitol and glycerol); and amino acids (including alanine, glycine and glutamic acid). Lyoprotectants can be included in an amount of about 10 mM to 500 nM.
  • In some embodiments, a subject formulation includes a subject antibody, and one or more of the above-identified agents (e.g., a surfactant, a buffer, a stabilizer, a tonicity agent) and is essentially free of one or more preservatives, such as ethanol, benzyl alcohol, phenol, m-cresol, p-chlor-m-cresol, methyl or propyl parabens, benzalkonium chloride, and combinations thereof. In other embodiments, a preservative is included in the formulation, e.g., at concentrations ranging from about 0.001 to about 2% (w/v).
  • For example, a subject formulation can be a liquid or lyophilized formulation suitable for parenteral administration, and can comprise: about 1 mg/mL to about 200 mg/mL of a subject antibody; about 0.001% to about 1% of at least one surfactant; about 1 mM to about 100 mM of a buffer; optionally about 10 mM to about 500 mM of a stabilizer; and about 5 mM to about 305 mM of a tonicity agent; and has a pH of about 4.0 to about 7.0.
  • As another example, a subject parenteral formulation is a liquid or lyophilized formulation comprising: about 1 mg/mL to about 200 mg/mL of a subject antibody; 0.04% Tween 20 w/v; 20 mM L-histidine; and 250 mM Sucrose; and has a pH of 5.5.
  • As another example, a subject parenteral formulation comprises a lyophilized formulation comprising: 1) 15 mg/mL of a subject antibody; 0.04% Tween 20 w/v; 20 mM L-histidine; and 250 mM sucrose; and has a pH of 5.5; or 2) 75 mg/mL of a subject antibody; 0.04% Tween 20 w/v; 20 mM L-histidine; and 250 mM sucrose; and has a pH of 5.5; or 3) 75 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 20 mM L-histidine; and 250 mM Sucrose; and has a pH of 5.5; or 4) 75 mg/mL of a subject antibody; 0.04% Tween 20 w/v; 20 mM L-histidine; and 250 mM trehalose; and has a pH of 5.5; or 6) 75 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 20 mM L-histidine; and 250 mM trehalose; and has a pH of 5.5.
  • As another example, a subject parenteral formulation is a liquid formulation comprising: 1) 7.5 mg/mL of a subject antibody; 0.022% Tween 20 w/v; 120 mM L-histidine; and 250 125 mM sucrose; and has a pH of 5.5; or 2) 37.5 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 10 mM L-histidine; and 125 mM sucrose; and has a pH of 5.5; or 3) 37.5 mg/mL of a subject antibody; 0.01% Tween 20 w/v; 10 mM L-histidine; and 125 mM sucrose; and has a pH of 5.5; or 4) 37.5 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 10 mM L-histidine; 125 mM trehalose; and has a pH of 5.5; or 5) 37.5 mg/mL of a subject antibody; 0.01% Tween 20 w/v; 10 mM L-histidine; and 125 mM trehalose; and has a pH of 5.5; or 6) 5 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 20 mM L-histidine; and 250 mM trehalose; and has a pH of 5.5; or 7) 75 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 20 mM L-histidine; and 250 mM mannitol; and has a pH of 5.5; or 8) 75 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 20 mM L histidine; and 140 mM sodium chloride; and has a pH of 5.5; or 9) 150 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 20 mM L-histidine; and 250 mM trehalose; and has a pH of 5.5; or 10) 150 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 20 mM L-histidine; and 250 mM mannitol; and has a pH of 5.5; or 11) 150 mg/mL of a subject antibody; 0.02% Tween 20 w/v; 20 mM L-histidine; and 140 mM sodium chloride; and has a pH of 5.5; or 12) 10 mg/mL of a subject antibody; 0.01% Tween 20 w/v; 20 mM L-histidine; and 40 mM sodium chloride; and has a pH of 5.5.
  • A subject antibody can be utilized in aerosol formulation to be administered via inhalation. A subject antibody can be formulated into pressurized acceptable propellants such as dichlorodifluoromethane, propane, nitrogen and the like.
  • Furthermore, a subject antibody can be made into suppositories by mixing with a variety of bases such as emulsifying bases or water-soluble bases. A subject antibody can be administered rectally via a suppository. The suppository can include vehicles such as cocoa butter, carbowaxes and polyethylene glycols, which melt at body temperature, yet are solidified at room temperature.
  • Unit dosage forms for oral or rectal administration such as syrups, elixirs, and suspensions may be provided wherein each dosage unit, for example, teaspoonful, tablespoonful, tablet or suppository, contains a predetermined amount of the composition containing one or more inhibitors. Similarly, unit dosage forms for injection or intravenous administration may comprise a subject antibody in a composition as a solution in sterile water, normal saline or another pharmaceutically acceptable carrier.
  • The term “unit dosage form,” as used herein, refers to physically discrete units suitable as unitary dosages for human and animal subjects, each unit containing a predetermined quantity of compounds of the present invention calculated in an amount sufficient to produce the desired effect in association with a pharmaceutically acceptable diluent, carrier or vehicle. The specifications for a subject antibody may depend on the particular antibody employed and the effect to be achieved, and the pharmacodynamics associated with each antibody in the host.
  • Other modes of administration will also find use with the subject invention. For instance, a subject antibody can be formulated in suppositories and, in some cases, aerosol and intranasal compositions. For suppositories, the vehicle composition will include traditional binders and carriers such as, polyalkylene glycols, or triglycerides. Such suppositories may be formed from mixtures containing the active ingredient in the range of about 0.5% to about 10% (w/w), e.g., about 1% to about 2%.
  • Intranasal formulations will usually include vehicles that neither cause irritation to the nasal mucosa nor significantly disturb ciliary function. Diluents such as water, aqueous saline or other known substances can be employed with the subject invention. The nasal formulations may also contain preservatives such as, but not limited to, chlorobutanol and benzalkonium chloride. A surfactant may be present to enhance absorption of the subject proteins by the nasal mucosa.
  • A subject antibody can be administered as an injectable formulation. Typically, injectable compositions are prepared as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection may also be prepared. The preparation may also be emulsified or the antibody encapsulated in liposome vehicles.
  • Suitable excipient vehicles are, for example, water, saline, dextrose, glycerol, ethanol, or the like, and combinations thereof. In addition, if desired, the vehicle may contain minor amounts of auxiliary substances such as wetting or emulsifying agents or pH buffering agents. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in the art. See, e.g., Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa., 17th edition, 1985. The composition or formulation to be administered will, in any event, contain a quantity of a subject antibody adequate to achieve the desired state in the subject being treated.
  • The pharmaceutically acceptable excipients, such as vehicles, adjuvants, carriers or diluents, are readily available to the public. Moreover, pharmaceutically acceptable auxiliary substances, such as pH adjusting and buffering agents, tonicity adjusting agents, stabilizers, wetting agents and the like, are readily available to the public.
  • In some embodiments, a subject antibody is formulated in a controlled release formulation. Sustained-release preparations may be prepared using methods well known in the art. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody in which the matrices are in the form of shaped articles, e.g. films or microcapsules. Examples of sustained-release matrices include polyesters, copolymers of L-glutamic acid and ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, hydrogels, polylactides, degradable lactic acid-glycolic acid copolymers and poly-D-(−)-3-hydroxybutyric acid. Possible loss of biological activity and possible changes in immunogenicity of antibodies comprised in sustained-release preparations may be prevented by using appropriate additives, by controlling moisture content and by developing specific polymer matrix compositions.
  • Controlled release within the scope of this invention can be taken to mean any one of a number of extended release dosage forms. The following terms may be considered to be substantially equivalent to controlled release, for the purposes of the present invention: continuous release, controlled release, delayed release, depot, gradual release, long-term release, programmed release, prolonged release, proportionate release, protracted release, repository, retard, slow release, spaced release, sustained release, time coat, timed release, delayed action, extended action, layered-time action, long acting, prolonged action, repeated action, slowing acting, sustained action, sustained-action medications, and extended release. Further discussions of these terms may be found in Lesczek Krowczynski, Extended-Release Dosage Forms, 1987 (CRC Press, Inc.).
  • The various controlled release technologies cover a very broad spectrum of drug dosage forms. Controlled release technologies include, but are not limited to physical systems and chemical systems.
  • Physical systems include, but are not limited to, reservoir systems with rate-controlling membranes, such as microencapsulation, macroencapsulation, and membrane systems; reservoir systems without rate-controlling membranes, such as hollow fibers, ultra microporous cellulose triacetate, and porous polymeric substrates and foams; monolithic systems, including those systems physically dissolved in non-porous, polymeric, or elastomeric matrices (e.g., nonerodible, erodible, environmental agent ingression, and degradable), and materials physically dispersed in non-porous, polymeric, or elastomeric matrices (e.g., nonerodible, erodible, environmental agent ingression, and degradable); laminated structures, including reservoir layers chemically similar or dissimilar to outer control layers; and other physical methods, such as osmotic pumps, or adsorption onto ion-exchange resins.
  • Chemical systems include, but are not limited to, chemical erosion of polymer matrices (e.g., heterogeneous, or homogeneous erosion), or biological erosion of a polymer matrix (e.g., heterogeneous, or homogeneous). Additional discussion of categories of systems for controlled release may be found in Agis F. Kydonieus, Controlled Release Technologies: Methods, Theory and Applications, 1980 (CRC Press, Inc.).
  • There are a number of controlled release drug formulations that are developed for oral administration. These include, but are not limited to, osmotic pressure-controlled gastrointestinal delivery systems; hydrodynamic pressure-controlled gastrointestinal delivery systems; membrane permeation-controlled gastrointestinal delivery systems, which include microporous membrane permeation-controlled gastrointestinal delivery devices; gastric fluid-resistant intestine targeted controlled-release gastrointestinal delivery devices; gel diffusion-controlled gastrointestinal delivery systems; and ion-exchange-controlled gastrointestinal delivery systems, which include cationic and anionic drugs. Additional information regarding controlled release drug delivery systems may be found in Yie W. Chien, Novel Drug Delivery Systems, 1992 (Marcel Dekker, Inc.).
  • Dosages
  • A suitable dosage can be determined by an attending physician or other qualified medical personnel, based on various clinical factors. As is well known in the medical arts, dosages for any one patient depend upon many factors, including the patient's size, body surface area, age, the particular compound to be administered, sex of the patient, time, and route of administration, general health, and other drugs being administered concurrently. A subject antibody may be administered in amounts between 1 ng/kg body weight and 20 mg/kg body weight per dose, e.g. between 0.1 mg/kg body weight to 10 mg/kg body weight, e.g. between 0.5 mg/kg body weight to 5 mg/kg body weight; however, doses below or above this exemplary range are envisioned, especially considering the aforementioned factors. If the regimen is a continuous infusion, it can also be in the range of 1 μg to 10 mg per kilogram of body weight per minute.
  • Those of skill will readily appreciate that dose levels can vary as a function of the specific antibody, the severity of the symptoms and the susceptibility of the subject to side effects. Preferred dosages for a given compound are readily determinable by those of skill in the art by a variety of means.
  • Routes of Administration
  • A subject antibody is administered to an individual using any available method and route suitable for drug delivery, including in vivo and ex vivo methods, as well as systemic and localized routes of administration.
  • Conventional and pharmaceutically acceptable routes of administration include intranasal, intramuscular, intratracheal, subcutaneous, intradermal, topical application, intravenous, intraarterial, rectal, nasal, oral, and other enteral and parenteral routes of administration. Routes of administration may be combined, if desired, or adjusted depending upon the antibody and/or the desired effect. A subject antibody composition can be administered in a single dose or in multiple doses. In some embodiments, a subject antibody composition is administered orally. In some embodiments, a subject antibody composition is administered via an inhalational route. In some embodiments, a subject antibody composition is administered intranasally. In some embodiments, a subject antibody composition is administered locally. In some embodiments, a subject antibody composition is administered intracranially. In some embodiments, a subject antibody composition is administered intravenously.
  • The agent can be administered to a host using any available conventional methods and routes suitable for delivery of conventional drugs, including systemic or localized routes. In general, routes of administration contemplated by the invention include, but are not necessarily limited to, enteral, parenteral, or inhalational routes.
  • Parenteral routes of administration other than inhalation administration include, but are not necessarily limited to, topical, transdermal, subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, and intravenous routes, i.e., any route of administration other than through the alimentary canal. Parenteral administration can be carried to effect systemic or local delivery of a subject antibody. Where systemic delivery is desired, administration typically involves invasive or systemically absorbed topical or mucosal administration of pharmaceutical preparations.
  • A subject antibody can also be delivered to the subject by enteral administration. Enteral routes of administration include, but are not necessarily limited to, oral and rectal (e.g., using a suppository) delivery.
  • By treatment is meant at least an amelioration of the symptoms associated with the pathological condition afflicting the host, where amelioration is used in a broad sense to refer to at least a reduction in the magnitude of a parameter, e.g. symptom, associated with the pathological condition being treated, such as muscle atrophy. As such, treatment also includes situations where the pathological condition, or at least symptoms associated therewith, are completely inhibited, e.g. prevented from happening, or stopped, e.g. terminated, such that the host no longer suffers from the pathological condition, or at least the symptoms that characterize the pathological condition.
  • In some embodiments, a subject antibody is administered by injection and/or delivery, e.g., to a site in a brain artery or directly into brain tissue. A subject antibody can also be administered directly to a target site e.g., by biolistic delivery to the target site.
  • A variety of hosts (wherein the term “host” is used interchangeably herein with the terms “subject,” “individual,” and “patient”) are treatable according to the subject methods. Generally such hosts are “mammals” or “mammalian,” where these terms are used broadly to describe organisms which are within the class mammalia, including the orders carnivore (e.g., dogs and cats), rodentia (e.g., mice, guinea pigs, and rats), and primates (e.g., humans, chimpanzees, and monkeys). In some embodiments, the hosts will be humans.
  • Kits with unit doses of a subject antibody, e.g. in oral or injectable doses, are provided. In such kits, in addition to the containers containing the unit doses will be an informational package insert describing the use and attendant benefits of the antibody in treating pathological condition of interest. Preferred compounds and unit doses are those described herein above.
  • Treatment Methods
  • The present disclosure provides methods of treating an ACVR2A-associated condition, the methods generally involving administering to an individual in need thereof (e.g., an individual having a ACVR2A-associated condition) an effective amount of a subject antibody, alone (e.g., in monotherapy) or in combination (e.g., in combination therapy) with one or more additional therapeutic agents. In certain embodiments, an ACVR2A-specific antibody can be used for treating or preventing a disease or condition that can be treated by decreasing ACVR2A signaling. In certain embodiments, the present invention provides methods of treating or preventing a disease, disorder, or condition in an individual in need thereof through administering to the individual a therapeutically effective amount of an ACVR2A-specific antibody as described above. These methods are particularly aimed at therapeutic and prophylactic treatments of animals, and more particularly, humans.
  • Mice genetically deficient in the inhibin-α subunit are deficient in inhibin A and inhibin B, have gonadal tumors that overexpress activins A and B (Matzuk et al., 1992, Nature 360:313-319; Matzuk et al., 1994, Proc Natl Acad Sci USA 91:8817-8821). All such mice develop these tumors and eventually die of a cancer cachexia-like syndrome mediated by high levels of tumor-derived activin acting through ACVR2A (Coerver et al., 1996, Mol Endocrinol 10:534-543). While not wishing to limit the present invention, an antibody that specifically blocks binding of a ligand to ACVR2A may be useful for treating a variety of conditions that are related to muscle atrophy. For example, an ACVR2A-specific antibody may be used to reduce the effects of activin-producing tumors, alleviating activin-mediated cachexia, and prolonging patient survival. In some embodiments, the subject may have a muscle-wasting disorder such as insufficient lean body mass, a decrease in muscle mass or muscle function, cachexia or sarcopenia.
  • ACVR2A and ACVR2A-ligand complexes play essential roles in tissue growth as well as early developmental processes such as the correct formation of various structures or in one or more post-developmental capacities including sexual development, pituitary hormone production, and creation of bone and cartilage. Thus, ACVR2A-associated conditions include abnormal tissue growth and developmental defects. In addition, ACVR2A-associated conditions include, but are not limited to, disorders of cell growth and differentiation such as inflammation, allergy, autoimmune diseases, infectious diseases, and tumors.
  • Exemplary ACVR2A-associated conditions include neuromuscular disorders (e.g., muscular dystrophy and muscle atrophy), congestive obstructive pulmonary disease or pulmonary emphysema (and associated muscle wasting), muscle wasting syndrome, sarcopenia, cachexia, adipose tissue disorders (e.g., obesity), type 2 diabetes, and bone degenerative disease (e.g., osteoporosis). Other exemplary ACVR2A-associated conditions include musculodegenerative and neuromuscular disorders, tissue repair (e.g., wound healing), neurodegenerative diseases (e.g., amyotrophic lateral sclerosis), immunologic disorders (e.g., disorders related to abnormal proliferation or function of lymphocytes), and obesity or disorders related to abnormal proliferation of adipocytes.
  • In certain embodiments, an ACVR2A-specific antibody may be used as part of a treatment for a muscular dystrophy. The term “muscular dystrophy” refers to a group of degenerative muscle diseases characterized by gradual weakening and deterioration of skeletal muscles and sometimes the heart and respiratory muscles. Muscular dystrophies are genetic disorders characterized by progressive muscle wasting and weakness that begin with microscopic changes in the muscle. As muscles degenerate over time, the person's muscle strength declines. Exemplary muscular dystrophies that can be treated with a regimen including the subject ACVR2A-specific antibodies include: Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), fascioscapulohumeral muscular dystrophy (FSH or FSHD) (also known as Landouzy-Dejerine), myotonic muscular dystrophy (MMD) (also known as Steinert's Disease), oculopharyngeal muscular dystrophy (OPMD), distal muscular dystrophy (DD), congenital muscular dystrophy (CMD), and scapulohumeral muscular dystrophy (SMD).
  • Duchenne muscular dystrophy (DMD) was first described by the French neurologist Guillaume Benjamin Amand Duchenne in the 1860s. Becker muscular dystrophy (BMD) is named after the German doctor Peter Emil Becker, who first described this variant of DMD in the 1950s. DMD is one of the most frequent inherited diseases in males, affecting one in 3,500 boys. DMD occurs when the dystrophin gene, located on the short arm of the X chromosome, is broken. Since males only carry one copy of the X chromosome, they only have one copy of the dystrophin gene. Without the dystrophin protein, muscle is easily damaged during cycles of contraction and relaxation. While early in the disease muscle compensates by regeneration, later on muscle progenitor cells cannot keep up with the ongoing damage and healthy muscle is replaced by non-functional fibro-fatty tissue.
  • In other embodiments, ACVR2A-specific antibodies may also be used to treat or prevent muscular atrophy due to myopathies, examples of which include inflammatory myopathy, metabolic myopathy, and myotonia. Subject ACVR2A-specific antibodies have application in treating congenital myopathies such as myotubular myopathy, nemalene myopathy, and mitochondrial myopathy. The subject ACVR2A-specific antibodies may be used to treat inclusion body myositis, myoglobinurias, rhabdomyolysis, myositis ossificans, polymyositis, or dermatomyositis. In addition, ACVR2A-specific antibodies may treat or prevent muscle atrophy arising from glucocorticoid treatment, sarcopenia, prolonged bed rest, skeletal immobilization, sepsis, or congestive heart failure.
  • An ACVR2A-specific antibody may provide an effective means to increase muscle mass in other neuromuscular diseases or conditions that are in need of muscle growth. For example, amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease or motor neuron disease) is a chronic, incurable, and unstoppable CNS disorder that attacks the motor neurons, components of the CNS that connect the brain to the skeletal muscles. In ALS, the motor neurons deteriorate and eventually die, and though a person's brain normally remains fully functioning and alert, the command to move cannot reach the muscles, Most people who develop ALS are between 40 and 70 years old. The first motor neurons that weaken are those leading to the arms or legs. Those with ALS may have trouble walking, they may drop things, fall, slur their speech, and laugh or cry uncontrollably. Eventually the muscles in the limbs begin to atrophy from disuse. This muscle weakness will become debilitating and a person will need a wheel chair or become unable to function out of bed. Most ALS patients die from respiratory failure or from complications of ventilator assistance like pneumonia, 3-5 years from disease onset. Other neuromuscular diseases in which ACVR2A-specific antibodies may be useful include paralysis due to spinal cord injury or stroke; denervation due to trauma or degenerative, metabolic, or inflammatory neuropathy; adult motor neuron disease; autoimmune motor neuropathy with multifocal conductor block; and infantile or juvenile spinal muscular atrophy.
  • Increased muscle mass induced by ACVR2A-specific antibodies might also benefit those suffering from muscle wasting diseases. Gonzalez-Cadavid et al. (1998, Proc. Natl. Acad. Sci. USA 95:14938-43) reported that that GDF8 expression correlates inversely with fat-free mass in humans and that increased expression of the GDF8 gene is associated with weight loss in men with AIDS wasting syndrome. By inhibiting the function of GDF8 in AIDS patients, at least certain symptoms of AIDS may be alleviated, if not completely eliminated, thus significantly improving quality of life in AIDS patients.
  • The cancer anorexia-cachexia syndrome is among the most debilitating and life-threatening aspects of cancer. Progressive weight loss in cancer anorexia-cachexia syndrome is a common feature of many types of cancer and is responsible not only for a poor quality of life and poor response to chemotherapy, but also a shorter survival time than is found in patients with comparable tumors without weight loss. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. It is one of the most common causes of death among cancer patients and is present in 80% at death. It is a complex example of metabolic chaos effecting protein, carbohydrate, and fat metabolism. Tumors produce both direct and indirect abnormalities, resulting in anorexia and weight loss. Currently, there is no treatment to control or reverse the process. Cancer anorexia-cachexia syndrome affects cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Although anorexia is common, a decreased food intake alone is unable to account for the changes in body composition seen in cancer patients, and increasing nutrient intake is unable to reverse the wasting syndrome. Cachexia is generally suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a six-month period.
  • Since systemic overexpression of GDF8 in adult mice was found to induce profound muscle and fat loss analogous to that seen in human cachexia syndromes (Zimmers et al., 2002, Science 296:1486-1488), the subject ACVR2A-specific antibodies can be, beneficially used to prevent, treat, or alleviate the symptoms of the cachexia syndrome, where muscle growth is desired. This would include cachexia associated with cancer as well as cachexia associated with rheumatoid arthritis.
  • Combination Therapy
  • In some embodiments, a subject treatment method involves administering a subject antibody and one or more additional therapeutic agents. Suitable additional therapeutic agents include, but are not limited to, anabolic steroids, deacetylase inhibitors and selective adrenergic receptor modulators (SARMs).
  • Subjects Suitable for Treatment
  • A variety of subjects are suitable for treatment with a subject method. Suitable subjects include any individual, e.g., a human, who has an ACVR2A-associated condition, who has been diagnosed with an ACVR2A-associated condition, who is at risk for developing an ACVR2A-associated condition, who has had an ACVR2A-associated condition and is at risk for recurrence of the an ACVR2A-associated condition, or who is recovering from an ACVR2A-associated condition.
    • EXAMPLES
  • The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the present invention, and are not intended to limit the scope of what the inventors regard as their invention nor are they intended to represent that the experiments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g. amounts, temperature, etc.) but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Celsius, and pressure is at or near atmospheric. Standard abbreviations may be used, e.g., bp, base pair(s); kb, kilobase(s); pl, picoliter(s); s or sec, second(s); min, minute(s); h or hr, hour(s); aa, amino acid(s); kb, kilobase(s); bp, base pair(s); nt, nucleotide(s); i.m., intramuscular(ly); i.p., intraperitoneal(ly); s.c., subcutaneous(ly); and the like.
    • Example 1 Phage Display Screening
  • Phagemid expression of diversified monovalent Fab libraries was accomplished by standard methods. TG-1 cells transformed with expression plasmids were grown to mid log (O.D. 600.about.0.3) in 2-YT media supplemented with 100 mcg/ml ampicillin and 2% glucose repression and then infected with m13K07 helper phage and grown overnight in 2-YT media supplemented with 100 mcg ampicillin, 70 mcg/ml kanamycin, and 200 micromolar IPTG. Phage containing supernatants were precipitated using polyethylene glycol and PBS resuspended phage were used to pan on immobilized ACVR2.
  • Panning of the libraries was performed by using recombinant soluble extracellular domains of ACVR2 (Peprotech or R&D Systems) immobilized on the wells of a microtiter dish or biotinylated ACVR2 immobilized on streptavidin derivatized magnetic beads (Dynal-Life Technologies).
  • To identify phage clones that encoded ACVR2-binding monovalent Fabs, a portion of the eluted phage were used to infect E. coli HB2151 allowing expression of periplasmic phage-encoded monovalent Fabs. Individual clones were picked into deep-well plates and grown overnight in 2YT containing ampicillin and 0.2 mM IPTG. Bacteria were lysed in BPERII and the lysates were applied to ACVR2 coated plates. Following washing, binding of antibodies was detected using an HRP-conjugated anti-human kappa and lambda light chain antibody (Bethyl). Daughter plates were also inoculated and grown in 2YT-Amp-glucose for Sanger-based sequencing to determine the antibody heavy and light chain sequences.
    • Example 2 Initial ELISA Assays
  • The binding of ACVR2A-specific monoclonal antibodies to human ACVR2A, mouse ACVR2A, biotinylated goat anti-human kappa light chain (positive control) and human Fc (negative control) were determined by ELISA.
  • The results of this assay are shown in Table 4 below. The values shown are optical densities. The data in this table shows that the antibodies listed I specifically bind to ACVR2A. The sequences of the heavy and light chains of the antibodies listed in Table 4 are shown above in FIGS. 2A-2F.
  • TABLE 4
    Goat
    anti-
    Human Mouse Human Human
    Ab ACVR2A ACVR2A Kappa Fc
    365_B04 1.993 2.179 3.121 0.271
    365_B10 2.819 2.782 3.212 0.322
    365_C03 2.257 2.648 3.499 0.332
    365_C06 1.785 2.229 3.447 0.318
    365_D04 2.269 2.389 3.517 0.316
    365_E04 2.342 2.401 3.54 0.46
    365_F11 2.01 2.141 3.502 0.302
    365_G07 2.424 2.596 3.467 0.331
    365_H08 2.674 2.607 3.589 0.488
    366_A02 2.448 2.687 3.583 0.336
    366_A04 1.823 1.988 3.397 0.319
    366_D01 2.361 2.46 3.484 0.374
    366_D03 2.233 2.375 3.475 0.318
    366_F10 2.048 2.211 3.518 0.28
    366_G06 2.676 2.818 3.407 0.341
    367_B09 2.422 2.429 3.365 0.476
    367_B11 2.34 2.463 3.598 0.37
    367_C09 2.413 2.771 3.445 0.263
    367_D11 2.395 2.54 3.39 0.304
    367_F06 2.008 2.045 3.345 0.265
    367_H01 2.817 2.695 3.654 0.388
    368_A02 2.573 2.741 3.691 0.376
    368_A06 2.249 2.515 3.282 0.483
    368_A12 3.009 2.781 3.693 0.425
    368_B03 2.045 2.045 3.377 0.297
    368_B08 1.979 2.182 3.208 0.314
    368_B10 2.349 2.417 3.024 0.412
    368_B11 2.14 2.35 3.607 0.286
    368_C09 2.478 2.611 3.461 0.341
    368_D09 2.194 2.11 3.461 0.212
    368_F02 2.184 2.272 3.653 0.317
    368_F10 2.254 2.602 3.522 0.328
    369_B03 3.321 3.314 3.521 0.62
    369_G10 3.37 3.295 3.491 0.423
    369_H03 2.829 3.085 3.469 0.498
    370_B01 3.375 3.473 3.752 0.47
    370_D06 2.257 2.658 3.483 0.334
    370_G04 1.825 2.125 3.513 0.423
    370_H08 2.937 3.24 3.647 0.538
    371_A04 1.008 1.173 3.532 0.315
    371_A09 1.855 1.998 3.617 0.302
    371_D07 2.661 2.902 3.59 0.299
    371_D12 1.89 1.999 3.435 0.337
    371_H02 1.881 2.026 3.623 0.388
    372_A09 2.433 2.56 3.498 0.31
    372_B11 2.309 2.575 3.73 0.438
    372_E02 2.841 2.743 3.581 0.431
    373_E11 3.301 3.361 3.172 0.243
    373_H02 3.245 3.257 3.239 0.287
    374_B02 3.421 3.537 3.024 0.179
    374_F03 3.532 3.617 3.233 0.185
    375_A04 3.72 3.734 3.101 0.177
    375_A11 3.729 3.696 3.047 0.176
    375_C10 3.459 3.596 3.333 0.294
    375_F12 2.951 3.143 3.17 0.175
    375_H01 2.787 3.059 3.104 0.216
    376_G02 3.694 3.696 3.546 0.285
    365_A05 2.34 2.229 3.454 0.331
    365_B08 1.137 1.257 3.037 0.229
    365_B12 2.334 2.289 3.427 0.307
    365_D03 2.351 2.484 3.526 0.346
    365_D08 2.264 2.355 3.614 0.35
    365_E06 1.988 2.063 3.295 0.301
    365_F10 2.752 2.789 3.655 0.386
    365_G06 2.198 2.021 3.343 0.32
    365_G08 2.527 2.581 3.498 0.346
    366_B09 2.304 2.532 3.386 0.283
    366_C05 2.007 2.362 3.405 0.269
    366_E07 1.677 1.856 3.144 0.262
    366_G02 2.163 2.316 3.565 0.357
    366_H01 2.794 2.775 3.715 0.384
    367_C06 2.119 2.513 3.496 0.29
    367_C12 2.065 2.103 3.576 0.31
    367_E08 2.042 2.372 3.426 0.299
    367_E10 2.765 2.975 3.481 0.271
    367_F08 2.079 2.193 3.539 0.299
    367_F10 2.215 2.357 3.425 0.253
    367_G03 2.591 2.632 3.595 0.341
    367_G11 2.559 2.672 3.557 0.305
    367_H08 2.266 2.473 3.544 0.312
    368_B04 2.266 2.729 3.292 0.304
    368_B12 2.514 2.471 3.486 0.567
    368_C04 2.485 2.474 3.67 0.302
    368_C07 2.577 2.367 3.309 0.282
    368_C12 2.488 2.446 3.617 0.346
    368_D03 2.394 2.552 3.494 0.374
    368_D06 2.027 2.109 3.407 0.265
    368_D07 2.2 2.463 3.262 0.309
    368_E05 1.868 2.067 3.369 0.266
    368_E08 2.267 2.669 3.5 0.255
    368_G11 2.105 2.368 3.502 0.306
    368_H03 2.44 2.727 3.558 0.343
    369_A04 2.761 2.858 3.505 0.353
    369_A12 3.175 3.243 3.721 0.461
    369_B07 2.631 2.898 3.386 0.319
    369_B08 2.751 2.879 3.29 0.309
    369_C06 2.755 3.065 3.175 0.414
    369_C09 2.883 3.054 3.412 0.32
    369_C11 2.799 2.912 3.484 0.378
    369_E03 3.147 3.356 3.373 0.63
    370_B06 2.876 3.092 3.371 0.441
    370_B07 1.914 2.196 3.482 0.336
    370_E12 3.388 3.435 3.658 0.656
    370_H05 2.939 3.138 3.612 0.364
    371_A05 3.047 3.24 3.605 0.369
    371_B02 2 2.279 3.59 0.449
    371_B11 3.182 3.261 3.594 0.549
    371_C02 2.918 2.877 3.656 0.372
    371_D05 2.718 3.112 3.438 0.339
    371_F07 2.784 2.893 3.342 0.425
    371_G07 2.8 2.988 3.413 0.548
    372_D07 2.684 2.993 3.704 0.472
    373_B01 3.258 3.584 3.114 0.197
    373_D11 3.572 3.546 3.202 0.364
    373_G06 3.397 3.525 3.231 0.196
    374_A10 3.557 3.587 2.999 0.23
    374_A12 3.312 3.256 3.063 0.308
    374_B01 3.143 3.369 2.918 0.173
    374_B07 3.713 3.705 3.295 0.25
    374_H02 3.263 3.257 3.183 0.197
    375_C03 3.001 3.243 3.162 0.217
    375_C05 3.457 3.584 3.316 0.193
    375_D02 3.629 3.558 3.202 0.191
    375_G08 3.332 3.432 3.267 0.259
    375_H04 3.106 3.159 3.148 0.181
    376_D08 3.815 3.711 3.471 0.232
    376_F09 3.501 3.588 3.353 0.25
    376_H12 3.234 3.082 3.487 0.344
    365_C05 2.564 2.808 3.527 0.271
    365_E10 1.823 2.053 3.337 0.273
    365_E12 3.321 3.276 3.522 0.338
    365_F02 2.781 3.049 3.396 0.326
    365_F03 2.631 2.99 3.574 0.347
    365_G03 2.242 2.543 3.543 0.321
    365_G04 2.096 2.48 3.295 0.295
    365_G05 2.442 2.539 3.352 0.319
    365_G09 2.617 2.933 3.671 0.288
    365_H07 2.514 2.745 3.431 0.33
    366_A06 1.97 2.254 3.24 0.334
    366_A08 1.653 1.734 3.23 0.243
    366_B05 2.385 2.461 2.955 0.24
    366_B07 1.796 1.915 3.222 0.215
    366_E01 2.693 2.717 3.66 0.397
    366_E08 1.973 2.002 3.349 0.272
    366_F02 2.149 2.108 3.597 0.371
    366_G12 2.713 2.828 3.586 0.372
    366_H04 2.69 2.829 3.524 0.359
    367_A03 2.576 2.451 3.438 0.347
    367_A06 2.339 2.566 3.358 0.378
    367_A08 2.057 2.091 3.337 0.252
    367_A10 1.892 2.163 3.392 0.315
    367_A12 2.439 2.416 3.647 0.39
    367_B01 2.839 2.907 3.674 0.408
    367_B04 2.664 3.099 3.342 0.265
    367_B12 3.015 3.028 3.745 0.414
    367_C07 2.468 2.516 3.414 0.387
    367_C10 2.529 2.61 3.386 0.233
    367_D03 2.594 2.451 3.455 0.29
    367_D06 2.045 2.353 3.25 0.283
    367_D08 2.183 2.373 3.501 0.237
    367_D12 2.435 2.689 3.569 0.309
    367_E05 2.353 2.639 3.466 0.333
    367_F01 2.425 2.757 3.724 0.33
    367_G01 1.8 1.944 3.578 0.356
    367_G04 2.978 3.042 3.356 0.287
    367_H02 1.077 1.199 3.616 0.378
    367_H03 2.041 2.2 3.341 0.377
    368_A03 2.834 2.833 3.411 0.348
    368_A04 2.349 2.352 3.565 0.283
    368_B09 2.543 2.808 3.434 0.258
    368_C02 1.377 1.488 3.513 0.321
    368_C08 2.259 2.432 3.383 0.289
    368_E12 1.286 1.554 3.652 0.347
    368_F09 2.389 2.449 3.578 0.242
    368_H02 2.406 2.544 3.578 0.348
    368_H05 1.954 2.197 3.342 0.277
    369_A07 3.548 3.564 3.421 0.288
    369_B05 2.777 3.057 3.44 0.314
    369_C05 2.545 2.718 3.022 0.32
    369_D03 3.277 3.554 3.606 0.391
    369_D07 3.069 2.914 3.259 0.363
    369_D09 3.303 3.051 3.446 0.287
    369_E06 3.134 3.109 3.515 0.306
    369_F08 0.503 0.589 3.099 0.302
    369_G08 3.297 3.492 3.582 0.312
    370_A02 2.901 2.907 3.624 0.425
    370_B03 3.714 3.567 3.607 0.3
    370_B11 2.076 2.449 3.685 0.326
    370_B12 2.925 3.077 3.563 0.478
    370_D01 3.137 3.17 3.664 0.382
    370_D05 2.976 3.125 3.49 0.333
    370_F03 1.136 1.25 3.301 0.373
    370_H02 3.301 3.39 3.667 0.386
    370_H07 3 3.245 3.511 0.403
    371_A10 2.812 2.779 3.477 0.338
    371_B03 1.634 1.935 3.482 0.367
    371_B04 2.465 3.129 2.269 0.295
    371_B09 0.825 0.827 2.702 0.292
    371_B12 2.555 2.4 3.483 0.378
    371_C01 2.001 2.273 3.594 0.402
    371_C04 2.049 2.246 3.453 0.314
    371_C05 1.24 1.355 3.079 0.269
    371_C12 3.099 3.196 3.683 0.544
    371_D02 2.939 2.991 3.578 0.385
    371_D04 1.023 1.295 3.3 0.276
    371_E06 3.003 3.029 3.443 0.33
    371_E07 3.091 3.348 3.437 0.337
    371_E10 3.062 3.052 3.486 0.341
    371_F10 2.339 2.31 3.529 0.299
    371_F11 3.039 3.253 3.676 0.331
    371_G02 3.118 3.06 3.673 0.514
    371_G04 3.625 3.577 3.544 0.325
    371_G09 2.745 3.066 3.577 0.315
    371_G11 2.84 2.752 3.666 0.399
    371_H04 3.258 3.507 3.576 0.35
    371_H05 1.202 1.245 3.271 0.321
    371_H06 3.027 3.111 3.698 0.346
    371_H08 1.662 2.039 3.472 0.309
    371_H10 2.189 2.553 3.548 0.358
    372_B02 3.172 3.509 3.665 0.371
    372_C06 3.206 3.536 3.491 0.489
    372_D03 3.042 3.289 3.603 0.319
    372_E01 3.341 3.34 3.598 0.409
    372_G12 2.409 2.725 3.495 0.439
    373_A01 3.177 3.477 2.952 0.177
    373_A03 3.647 3.634 3.079 0.189
    373_A05 3.45 3.423 3.033 0.172
    373_A09 3.66 3.615 3.107 0.248
    373_A11 3.763 3.679 3.086 0.184
    373_A12 3.59 3.315 3.093 0.179
    373_B05 3.586 3.526 3.233 0.184
    373_B07 3.661 3.61 3.304 0.208
    373_C03 3.69 3.654 3.304 0.171
    373_C07 3.569 3.578 3.298 0.206
    373_C10 3.653 3.645 3.235 0.318
    373_D03 3.745 3.694 3.18 0.18
    373_D12 3.398 3.207 3.212 0.224
    373_E10 3.722 3.636 3.2 0.188
    373_F08 3.76 3.701 3.215 0.202
    373_F11 3.354 3.46 3.319 0.204
    373_F12 3.245 3.217 3.063 0.158
    373_G08 3.651 3.673 3.284 0.172
    373_H03 3.268 3.289 3.221 0.172
    373_H07 3.253 3.27 3.233 0.199
    373_H09 0.93 1.354 3.084 0.166
    374_A06 3.775 3.747 2.999 0.173
    374_A09 3.583 3.644 2.971 0.231
    374_B03 3.687 3.697 3.066 0.166
    374_B05 3.681 3.652 3.164 0.168
    374_B08 3.6 3.629 3.124 0.188
    374_B10 3.711 3.686 3.004 0.17
    374_C01 2.685 2.929 3.078 0.167
    374_C09 3.431 3.509 3.14 0.154
    374_C12 3.667 3.326 3.145 0.308
    374_D03 3.3 3.48 3.025 0.216
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    373_H10 3.243 3.251 3.189 0.2
    367_A09 2.178 2.41 3.454 0.259
    370_F08 2.339 2.994 3.587 0.495
    376_B01 3.278 3.67 3.242 0.308
    365_D05 2.578 2.72 3.514 0.357
    373_E04 3.556 3.546 3.301 0.251
    368_G05 2.175 2.421 3.354 0.245
    365_A01 2.765 2.9 3.508 0.528
    373_H06 3.004 3.151 3.3 0.2
    369_G07 3.322 3.369 2.976 0.32
    373_G05 3.612 3.615 3.224 0.273
    372_F07 3.248 3.241 3.401 0.296
    370_H03 3.426 3.565 3.558 0.381
    366_A03 1.152 1.119 3.314 0.303
    365_A07 2.244 2.255 3.407 0.284
    376_B06 3.697 3.773 3.457 0.222
    374_C11 3.641 3.593 3.215 0.471
    375_A06 3.653 3.707 3.114 0.298
    365_B09 3.264 3.319 3.282 0.272
    373_E06 3.706 3.639 3.221 0.187
    374_C05 3.698 3.693 3.176 0.175
    376_C11 3.704 3.626 3.46 0.23
    373_C09 3.64 3.597 3.22 0.17
    368_H01 3.027 3.142 3.693 0.374
    373_B03 3.638 3.621 3.161 0.18
    374_C04 3.741 3.741 3.166 0.201
    371_F05 2.89 3.149 3.33 0.297
    369_A10 3.375 3.139 3.414 0.348
    366_A05 2.624 2.596 3.477 0.284
    375_G07 3.633 3.672 3.197 0.178
    374_D02 3.06 3.2 2.994 0.204
    365_A10 2.185 2.492 3.451 0.293
    375_A02 2.977 3.178 3.066 0.186
    371_G03 3.121 3.267 3.593 0.359
    370_E07 3.442 3.496 3.453 0.379
    375_B04 3.693 3.73 3.259 0.19
    367_G07 3.019 3.197 3.287 0.295
    366_C02 3.033 3.04 3.43 0.341
    375_C12 3.662 3.328 3.266 0.197
    365_F08 2.246 2.611 3.626 0.437
    368_G09 2.438 2.815 3.62 0.281
    368_E11 2.573 2.923 3.73 0.341
    367_F02 2.375 2.268 3.522 0.315
    373_B08 3.698 3.663 3.218 0.17
    374_A11 3.645 3.722 2.806 0.15
    373_B11 3.719 3.652 3.217 0.178
    373_F03 3.652 3.603 3.213 0.179
    372_D04 3.401 3.408 3.384 0.419
    366_C01 2.307 2.406 3.601 0.382
    367_A01 3.182 3.284 3.51 0.391
    366_H05 2.445 2.737 3.47 0.418
    369_B09 1.624 1.577 2.216 0.253
    366_D07 2.413 2.623 3.383 0.418
    369_D11 2.988 2.99 3.454 0.35
    370_B05 2.839 3.111 3.492 0.593
    366_D02 2.274 2.549 3.567 0.349
    368_H12 2.636 2.693 3.572 0.381
    368_F12 1.689 1.702 3.515 0.349
    370_A06 2.594 2.769 3.471 0.331
    369_F12 2.732 2.819 3.596 0.434
    366_A09 1.787 1.926 3.277 0.266
    368_H07 2.707 2.864 3.553 0.421
    370_C04 2.319 2.632 3.6 0.334
    373_E02 3.612 3.643 2.921 0.158
    374_E09 3.671 3.578 3.157 0.162
    371_C09 3.369 3.289 3.393 0.308
    369_B12 2.666 2.759 3.562 0.4
    369_B02 3.4 3.546 3.522 0.456
    365_C09 2.052 2.178 3.272 0.266
    374_B09 3.621 3.652 3.194 0.172
    374_D12 3.55 3.28 3.087 0.235
    374_C02 3.676 3.64 3.059 0.167
    374_H08 3.307 3.271 3.089 0.199
    369_D06 3.438 3.346 3.11 0.324
    366_B06 2.474 2.453 3.104 0.415
    367_A11 2.344 2.521 3.611 0.3
    369_F04 1.949 2.171 3.459 0.369
    369_A01 3.6 3.66 3.546 0.456
    373_H12 3.061 2.985 3.004 0.162
    376_C07 3.697 3.714 3.419 0.265
    366_E02 2.257 2.581 3.456 0.37
    376_G01 3.341 3.663 3.18 0.227
    373_F02 3.623 3.6 3.149 0.175
    376_E09 3.741 3.76 3.483 0.246
    365_H04 2.471 2.588 3.495 0.371
    369_E04 2.883 3.304 3.516 0.387
    374_B11 3.692 3.657 3.175 0.17
    376_G11 3.646 3.604 3.538 0.285
    374_E04 3.74 3.716 3.187 0.169
    373_E08 2.966 3.235 3.199 0.165
    375_B10 3.651 3.74 3.138 0.17
    365_E08 2.591 2.585 3.331 0.298
    374_G02 3.515 3.538 3.174 0.175
    373_D09 3.463 3.505 3.043 0.16
    365_A04 1.487 1.405 3.28 0.25
    371_B05 1.051 1.243 1.653 0.246
    376_H08 3.305 3.279 3.527 0.274
    367_G08 2.686 2.779 3.319 0.33
    372_H03 2.322 2.697 3.642 0.437
    366_E03 2.551 2.724 3.536 0.384
    371_F12 2.474 2.304 3.616 0.413
    366_C03 2.414 2.736 3.549 0.274
    376_A01 3.243 3.661 2.985 0.239
    365_E03 2.559 2.692 3.332 0.314
    371_B10 3.313 3.36 3.441 0.387
    369_G09 3.36 3.269 3.605 0.395
    369_A06 2.891 3.012 3.32 0.394
    369_C08 2.32 2.325 2.797 0.241
    373_A07 3.525 3.594 3.114 0.177
    367_D02 2.464 2.464 3.462 0.321
    374_C07 3.651 3.698 3.22 0.225
    374_A03 3.58 3.71 3.05 0.178
    365_A02 3.028 2.962 3.492 0.374
    365_D06 2.953 3.075 3.421 0.319
    366_C07 3.016 3.06 3.368 0.301
    367_F12 2.38 2.285 3.599 0.355
    369_E09 3.627 3.767 3.483 0.278
    365_G02 1.984 2.155 3.447 0.325
    373_D02 3.729 3.645 3.187 0.18
    374_E03 3.716 3.789 3.127 0.176
    374_D11 3.639 3.579 2.905 0.162
    370_D07 2.806 3.141 3.384 0.309
    374_A08 3.589 3.673 2.944 0.16
    374_G01 3.344 3.595 2.922 0.161
    374_G12 3.195 3.215 3.149 0.214
    375_G10 3.481 3.639 3.302 0.175
    369_H11 1.445 1.639 2.21 0.382
    375_G12 3.356 3.29 3.304 0.199
    366_F06 1.874 2.155 3.445 0.394
    368_G07 1.788 2.048 3.164 0.29
    367_H04 1.623 1.849 3.395 0.289
    374_E06 3.844 3.755 3.245 0.191
    370_A10 2.581 2.878 3.467 0.434
    368_H10 2.281 2.156 3.359 0.281
    368_G08 1.603 1.752 3.291 0.329
    365_H09 2.384 2.563 3.53 0.365
    370_A08 2.406 2.335 3.522 0.319
    368_B05 1.732 1.755 3.257 0.281
    375_F01 3.16 3.455 2.956 0.166
    374_F09 3.533 3.617 3.142 0.157
    • Example 3 Ligand Competition Assays
  • The ability of several of the antibodies identified in Example 2 to block Activin A and GDF8 binding to ACVR2A or ACVR2B was assessed by ELISA. Activin A (R&D systems) and GDF8 (R&D systems) were coated on 384-well Immunolon plates in 1× coating buffer (SurModics) at 0.5 μg/mL. Antibodies were serially diluted in a 10-point curve starting at 1 μM in 3-fold steps. ACVR2A and ACVR2B proteins were purchased from R&D Systems and biotinylated using the EZ-Link NHS-PEG4-biotin kit (Thermo Fisher). The antibodies were pre-incubated with biotinylated human ACVR2A-Fc, mouse ACVR2A-Fc, human ACVR2B-Fc, or mouse ACVR2B-Fc at a concentration of 500 ng/mL in 1% BSA in PBST for 1 hour. The mixtures of antibodies and biotinylated receptors were added to the Activin A/GDF8-coated plates for 1 hour. The inhibition of ligand-receptor interaction was detected with streptavidin-HRP (Jackson ImmunoResearch) at a concentration of 10 ng/mL and TMB.
  • The results of this assay are shown in columns A-D of Table 5 below. The values shown are IC50 values. The data in this table shows that the antibodies can specifically block Activin A and GDF8 binding to ACVR2A.
    • Example 4 ALK5/ACVR2B DIMERIZATION ASSAY
  • The ability of several of the antibodies identified in Example 2 to specifically block GDF8-induced dimerization between ACVR2A and ALK5 in U2OS cells was assessed using the DiscoverX receptor dimerization assay. In these assays, two receptors are tagged with ProLink™ (PK) or Enzyme Acceptor (EA). Upon ligand-induced activation, the receptors dimerize forcing the two β-gal components to complement and create an active enzyme. Active β-gal generates a chemiluminescent signal in the presence of substrate. In these assays, approximately 5000 U2OS cells were transferred into each well in total volume of 20 ul, antibody was dispensed into each well in total volume of 5 ul, the treated cells were incubated for 3 hr at 37° C., 5 ul of GDF8 was dispensed into wells in total volume of 5 ul (final conc 100 ng/ml), the cells were incubated for 16 hr at 37° C. and 30 ul of 1× Flash detection reagent was added to each well. The reactions were incubated for 1 hr at room temperature and then read on a plate reader.
  • The results of this assay are shown in columns E and F of Table 5 below. The values shown are IC50 values. The data in this table shows that the antibodies block GDF8-induced dimerization of ALK5/ACVR2A but not ALK5/ACVR2B.
    • Example 5 Quantitative ELISA Assays
  • The binding of several of the antibodies identified in Example 2 to human ACVR2A, mouse ACVR2A, human ACVR2B, and mouse ACVR2B were quantified by ELISA. His-tagged recombinant proteins (Sino Biological, Inc.) were His-tagged Human ACVR2A, Mouse ACVR2A, Human ACVR2B, or Mouse ACVR2B were coated on Immunolon 384-well plates at a concentration of 0.5 μg/mL in 1× coating buffer (SurModics). Antibodies were diluted to 1 μM in PBS buffer containing 1% BSA and diluted 3-fold in a 10-point curve. Detection of the antibody binding to the antigen was performed using biotinylated goat anti-human kappa light chain (Bethyl Laboratories). Detection of the secondary antibody was determined using streptavidin-HRP and TMB reagent. All assays were performed at room temperature. Curve-fitting software was used to determine the EC50 for each antibody (MatLab).
  • The results of this assay are shown in columns G-L of Table 5 below. The values shown are EC50 values. The data in this table shows that the antibodies specifically bind to ACVR2A, not ACVR2B.
    • Example 6 Activity on Skeletal Muscle Cells
  • The ability of several of the antibodies identified in Example 2 to alter SMAD3 activity in muscle cells was tested. Primary human myoblasts (Lonza) cultured in Ham's F-10 supplemented with SkGM-2 Single-Quots (Lonza). Myoblasts were differentiated in DMEM/F-12K (50:50) supplemented with 2% horse serum (Corning) and 1% Penicillin/Streptomycin. After 4 days of differentiation, myotubes were pre-treated with antibodies for 1 hour at a starting concentration of 1 μM and diluted serially 3-fold in a 10-point curve. GDF8 (R&D) was added for 1 hour at 100 ng/mL. Cells were lysed in 30 μL of PBS+0.1% Triton-X+lx Halt Protease/Phosphastase inhibitors (Thermo Fisher). Phospho-SMAD3 (Ser423/425) activity was assessed in primary human myotubes by AlphaLisa (Perkin-Elmer) according to manufacturer's instructions.
  • The results of this assay are shown in column M of Table 5 below. The data in this table shows that the antibodies reduce GDF8-induced SMAD3 phosphorylation in muscle cells.
    • Example 7 Smad Reporter 293 Assay
  • The ability of several of the antibodies identified in Example 2 to specifically inhibit GDF8-induced SMAD activation in HEK293 was tested cells using a smad2/3 luciferase reporter construct. In these experiments, a smad2/3 luciferase reporter (SBI #TR203VA-P) was introduced into HEK293 cells. Endogenous ACVR2A and ACVR2B function was knocked out using custom made CRISPR/CAS9 targeting sequences. Finally, individual reporter lines were generated by reintroduction of ACVR2A or ACVR2B expression vectors. This method involved dispensing 30,000 cells into each well in total volume of 80 ul, dispensing antibody into each well in total volume of 10 ul, incubating the treated cells for 1 hr at 37° C., dispensing GDF8 into wells in total volume of 10 ul (final conc. 100 ng/ml), incubating the stimulated cells for 24 hr at 37° C., adding 100 ul of 1X ONE-Glo detection reagent to each well, incubate the plate for 5 min at room temperature and then reading luminescence using a plate reader.
  • The results of this assay are shown in column N of Table 5 below. The values shown are IC50 values. The data in this table shows that the antibodies inhibit GDF8-induced SMAD3 phosphorylation in HEK293 cells.
    • Example 8 Smad Reporter 4E1 Assay
  • The ability of several of the antibodies identified in Example 2 to specifically inhibit GDF8-induced SMAD activation was tested cells using the following protocol. In this assay, HEK293 cells were infected with a lentiviral SMAD2/3/4 reporter (pGF-SMAD2/3/4-mCMV-EF1-Puro System Biosciences). The lentiviral based reporter expresses both GFP and luciferase under the control of a Smad3-responsive element (CAGA)12. Cells were sorted for their responsiveness to GDF8 based on their GFP expression. Single cell clones were expanded and transcriptional activation was tested by GDF8-induced luciferase activity. Clone 4E1 was unresponsive to GDF8 or Activin A. This clone was further transfected with Human or Mouse ACVR2A or ACVR2B plasmids. The ability of the antibodies to inhibit luciferase induction by GDF8 or Activin A in these cell lines was tested.
  • The results of this assay are shown in column 0 of Table 5 below. These values are IC50 values. The data in this table shows that the antibodies inhibit GDF8 and Activin A-mediated induction of SMAD2/3/4 in HEK293 cells.
  • TABLE 5
    A B C D E F G H I J K L M
    Comp ELISA Comp ELISA Comp ELISA Comp ELISA Dimer Dimer ELISA ELISA- ELISA- ELISA ELISA ELISA Phospho- N O
    Human Human Mouse Mouse ALK5/ ALK5/ Human Human Human Mouse Mouse Mouse SMAD3 SMAD 2/3/4 Clone 4E1 +
    ACVR2A ACVR2A ACVR2A ACVR2A ACVR2A ACVR2B ACVR2A ACVR2A ACVR2B ACVR2A ACVR2A ACVR2B Human Skeletal Reporter Human ACVR2A,
    Ab Activin A GDF8 Activin A GDF8 GDF8 GDF8 (10 pt) (8 pt) (10 pt) (10 pt) (8 pt) (10 pt) Muscle GDF8 HEK293 Activin A, 10pt
    365_B10 0.0819 0.0009 0.0066 0.0002 0.6247 9999 0.0013 0.001 9999 0.001 0.0009 9999 0.031 0.3643 0.0364
    365_E04 0.004 0.0048
    365_H08 0.4151 0.0116 0.1949 0.0044 9999 9999 0.1963 0.0089 9999 0.0959 0.0055 9999 9999 9999
    366_D01 0.338 0.0292 0.2896 0.0133 6.372 9999 0.0017 9999 0.0011 9999 0.1323 0.4973 0.1006
    366_G06 0.0059 0.0041
    367_H01 0.0363 0.0035 0.0125 0.0014 6.578 9999 0.0064 0.0009 9999 0.0054 0.0025 9999 0.0248 3.679 0.3607
    368_A02 0.008 0.008
    368_A12 0.081 0.002 0.0348 0.0007 2.303 9999 0.0016 0.0028 9999 0.0015 0.0024 9999 0.046 0.9454 0.1142
    368_B10 0.0077 0.0025 0.0084 0.0032 0.4969 9999 0.0053 0.0043 9999 0.0053 0.0045 9999 0.0469 1.387 0.0632
    368_F10 0.1033 0.0069 0.1028 0.004 3.946 9999 0.0039 9999 0.0022 9999 0.2567 0.8681 0.2092
    369_B03 0.0164 0.0044 0.0115 0.0033 1.761 9999 0.0051 0.0031 9999 0.006 0.0024 9999 0.0157 0.3055 0.1569
    369_H03 0.1782 0.0017 0.0246 0.0001 8.179 9999 0.0073 0.003 9999 0.0052 0.01 9999 0.3262 9999 0.0957
    370_B01 0.0036 0.0006 0.0027 0.0004 0.1589 9999 0.0004 0.0011 9999 0.0004 0.001 9999 0.0121 0.0535 0.0154
    371_D07 0.0271 0.0032 0.0344 0.0035 1.182 9999 0.0093 0.013 9999 0.0057 0.01 9999 0.1265 4.187 0.2217
    372_B11 0.0623 0.0059 0.0718 7.11E−05 2.191 9999 0.0042 9999 0.0032 9999 0.3973 4.276 0.2726
    373_E11 0.0208 0.0012 0.021 8.31E−05 0.9392 9999 0.0013 9999 0.0012 9999 0.0229 0.4333 0.1403
    373_H02 0.01 0.0036 0.006 0.0032 0.7633 9999 0.0032 0.001 9999 0.003 0.0011 9999 0.0145 0.3413 0.0251
    374_B02 0.1374 0.0206 0.0771 0.0112 5.938 9999 0.0653 0.01 9999 0.0378 0.0032 9999 0.1183 9999 0.1766
    375_A04 0.0025 0.0015 0.0018 0.0011 0.0481 9999 0.0007 0.0006 9999 0.0007 0.0004 9999 0.0076 0.0551 0.0071
    375_A11 0.0167 0.0082 0.0105 0.0047 0.939 9999 0.0047 0.0009 9999 0.003 0.0007 9999 0.0127 0.5299 0.0359
    375_H01 0.015 0.015
    376_G02 0.0144 0.0051 0.0111 0.0041 0.8281 9999 0.0029 0.0018 9999 0.002 0.002 9999 0.1901 0.3337 0.0836
    365_G06 0.0151 0.0034 0.0226 0.0028 0.4743 9999 0.0035 0.0026 9999 0.0031 0.0073 9999 0.0875 0.2124 0.0309
    367_F10 0.0186 0.0035 0.0168 0.0026 2.249 9999 0.0019 0.0136 9999 0.0017 0.0119 9999 0.1176 0.4684 0.369
    368_B12 0.0074 0.0035 0.0128 0.0033 0.4249 9999 0.0047 0.0053 9999 0.0051 0.006 9999 0.0918 1.746 0.1613
    369_A12 0.0205 0.0005 0.0119 0.0002 0.3311 9999 0.001 0.0017 9999 0.0008 0.0014 9999 0.0119 0.0948 0.0311
    369_E03 0.0777 0.0006 0.0346 0.0049 0.8456 9999 0.001 0.0059 9999 0.0009 0.0043 5.543 0.0235 1.043 0.1305
    370_B06 0.018 0.0007 0.0107 0.0002 0.9481 9999 0.0032 0.0018 9999 0.0023 0.0015 9999 0.0061 0.3843 0.0467
    371_B11 0.0268 0.0038 0.0147 0.157 0.3699 9999 0.0011 0.0012 9999 0.001 0.0011 9999 0.015 0.2384 0.0316
    371_C02 0.0519 0.0043 0.0577 0.0087 3.394 9999 0.0025 0.0045 9999 0.0021 0.0045 9999 0.0488 1.01 0.0956
    373_D11 0.0037 0.0005 0.004 0.0001 0.1968 9999 0.0003 9999 0.0003 9999 0.0081 0.3066 0.0225
    373_G06 0.0478 0.0053 0.0325 0.0044 9999 9999 0.0052 0.0009 9999 0.0047 0.0021 9999 0.0231 1.969 0.0383
    376_D08 0.0027 0.0007 0.0019 0.0007 0.075 9999 0.0006 9999 0.0005 9999 0.0065 0.0343 0.41
    376_F09 0.0094 0.0015 0.0101 0.0016 0.3541 9999 0.0046 0.0046 9999 0.0041 0.0028 9999 0.0855 0.4007 0.0407
    365_E12 0.0019 0.0017
    365_F02 0.0077 0.0022 0.0078 0.0014 0.2793 9999 0.0006 0.0005 9999 0.0006 0.0005 9999 0.026 0.8487 0.0639
    365_G05 0.0073 0.0072
    367_A03 0.0136 0.0132
    367_C07 0.0298 0.0042 0.03 0.0041 1.082 9999 0.0008 9999 0.0007 9999 0.0716 9999 0.1569
    369_A07 0.0056 0.0039 0.0029 0.0013 0.5726 9999 0.001 0.0005 9999 0.0008 0.0006 9999 0.0149 0.1323 0.0155
    369_B05 0.0027 0.0018
    370_A02 0.0022 0.005
    370_H02 0.0254 0.0005 0.0123 1.00E−14 0.9495 9999 0.0009 0.0016 9999 0.0008 0.0012 9999 0.0226 0.6343 0.0355
    371_A10 0.0058 0.0056
    371_C12 0.043 0.0004 0.024 0.0043 0.3096 9999 0.0006 0.0011 9999 0.0005 0.0007 9999 0.0206 0.5658 0.0187
    371_D02 0.0028 0.0017
    371_G09 0.0019 0.0019
    371_G11 0.0062 0.0004 0.0066 0.0045 7.363 9999 0.0042 0.0039 9999 0.0034 0.0031 9999 0.1361 9999 0.3384
    372_B02 0.0099 0.0001 0.0045 0.0004 2.192 9999 0.0019 0.0026 9999 0.0014 0.0017 9999 0.1605 1.675 0.1778
    372_D03 0.003 0.0004 0.0013 0.0006 0.7064 9999 0.0011 0.0012 9999 0.0009 0.0009 9999 0.058 0.1379 0.0466
    373_A03 0.0053 0.0023 0.0031 0.0021 0.2914 9999 0.001 0.001 9999 0.0008 0.0007 9999 0.0148 0.559 0.009
    373_A05 0.0032 0.0022
    373_A09 0.0012 0.0009
    373_A11 0.0009 0.0006
    373_B05 0.0022 0.0021
    373_C07 0.0126 0.004 0.0087 0.0011 1.215 9999 0.0028 0.0015 9999 0.0025 0.0014 9999 0.0048 1.208 0.0686
    373_F08 0.0022 0.0015 0.0017 0.0004 0.0919 9999 0.0006 0.0007 2.32 0.0004 0.0005 2 0.005 0.3677 0.0315
    373_F12 0.0016 0.0009
    373_G08 0.0041 0.0012 0.0033 0.001 0.2649 9999 0.0009 0.001 9999 0.0007 0.0009 9999 0.0057 0.3073 0.0711
    373_H03 0.0199 0.0074 0.0117 0.0066 2.093 9999 0.003 9999 0.0024 9999 0.0129 0.808 0.1144
    374_B03 0.0031 0.0015 0.002 0.0006 0.2057 9999 0.0008 0.0009 9999 0.0008 0.0006 9999 0.027 0.2394 0.0399
    374_C01 0.3127 0.0191 0.2885 0.0033 9999 9999 0.022 9999 0.0263 9999 1.115 0.8145 4.942
    374_C09 0.0467 0.0088 0.0496 0.0047 1.402 9999 0.011 0 9999 0.007 0.004 9999 0.1888 0.7011 0.2959
    374_C12 0.0045 0.0023 0.0038 0.0026 0.2619 9999 0.0016 0.0005 0.4162 0.0012 0.0005 0.397 0.027 0.1579 0.083
    374_D05 0.0392 0.0065 0.0258 0.0068 1.646 9999 0.0074 0.0022 9999 0.0066 0.0018 9999 0.0177 1.697 0.0851
    374_D10 0.0781 0.0038 0.0653 0.0027 3.186 9999 0.0032 1.021 0.0022 1.053 0.1264 9999 4.658
    374_G08 0.0056 0.0025 0.0056 0.0017 0.608 9999 0.0018 0.0009 9999 0.0014 0.0009 9999 0.034 0.542 0.0781
    375_A01 0.0012 0.001
    375_A07 0.0097 0.0025 0.0221 0.0025 0.4117 9999 0.001 9999 0.001 9999 0.014 0.0154 0.0922
    375_A12 0.0047 0.0011 0.0033 0.0003 0.3345 9999 0.0007 9999 0.0005 9999 0.0469 1.051 0.0415
    375_D10 0.0023 0.0019
    375_E05 0.0009 0.0007
    375_E10 0.0036 0.002 0.0023 0.0009 0.2255 9999 0.0007 0.0006 9999 0.0007 0.0006 9999 0.0091 0.2237 0.0215
    375_F02 0.0288 0.0034 0.0184 0.006 0.8957 9999 0.0037 9999 0.0028 9999 0.0076 0.6181 0.0247
    375_G05 0.0008 0.0005 0.001 0.0004 0.1347 9999 0.0005 0.0007 2.852 0.0004 0.0005 2 0.0052 0.0108 0.0668
    375_H05 0.0067 0.0019 0.0043 9.34E−05 0.4237 9999 0.0008 0.0006 9999 0.0007 0.0005 9999 0.0346 0.2948 0.0342
    376_A03 0.0022 0.0014
    376_B10 0.0021 0.0017
    376_C08 0.0243 0.0046 0.0272 0.0046 0.9254 9999 0.0044 9999 0.0048 9999 0.0605 1.353 0.1794
    376_F01 0.1328 0.0177 0.1264 0.0177 2.893 9999 0.0076 0.0082 0.0922 0.008 0.003 0.0924 0.5947 9999 0.6449
    376_F06 0.0352 0.0032 0.021 0.002 0.5714 9999 0.0034 0.0024 9999 0.0032 0.0017 9999 0.0544 9999 0.1295
    375_G05 0.0081 0.0036 0.008 0.0032 0.9329 9999 0.0017 0.0006 9999 0.0014 0.0005 9999 0.0658 0.3712 0.0755
    376_G10 0.0031 0.0032
    376_H01 0.005 0.0025 0.0044 0.0013 0.5641 9999 0.001 0.0012 0.1094 0.0009 0.001 0.0981 0.0562 0.6002 0.0329
    376_H11 0.0008 0.0007 0.0013 0.0007 0.0368 9999 0.0004 0.0005 9999 0.0004 0.0004 9999 0.0042 0.0775 0.0084
    367_A02 0.0685 0.0168 0.0757 0.0117 1.404 9999 0.0099 9999 0.0053 9999 0.1591 2.765 0.065
    368_G03 0.1025 0.0013 0.0477 0.0003 5.011 9999 0.0033 0.0068 9999 0.0026 0.008 9999 0.299 1.678 0.4619
    368_H06 0.0138 0.0023
    369_C12 0.0022 0.0007 0.0016 0.0006 0.137 9999 0.0007 0.0008 9999 0.0007 0.0005 9999 0.0094 0.0821 0.0435
    369_E08 0.0028 0.0023
    369_F09 0.0204 0.0007 0.0196 0.0004 0.793 9999 0.0012 2 0.001 2 0.0325 1.095 0.1356
    369_H08 0.0721 0.0014 0.0431 0.0002 1.385 9999 0.0013 0.0034 9999 0.001 0.0025 9999 0.0308 0.7511 0.074
    369_H12 0.0154 0.001 0.0112 0.0001 1.812 9999 0.0006 0.0011 9999 0.0005 0.001 9999 0.0303 0.3774 0.0815
    370_C06 0.0148 0.0005 0.0083 6.83E−05 0.7631 9999 0.0005 0.0009 9999 0.0005 0.0008 9999 0.0111 4999 0.05
    370_C07 0.0219 0.0011 0.0064 0.0006 0.3774 9999 0.0006 0.0006 9999 0.0006 0.0005 9999 0.0044 0.1452 0.0213
    370_D03 0.0163 0.0025 0.0103 0.0042 0.8872 9999 0.0023 0.0017 9999 0.0017 0.0015 9999 0.0165 0.4708 0.0649
    370_E04 0.0067 0.0023 0.0065 0.0005 0.8152 9999 0.0008 0.0007 9999 0.0008 0.0005 9999 0.0136 0.5966 0.0416
    370_F12 0.005 0.0002 0.0025 2.65E−05 0.3859 9999 0.0009 0.0006 9999 0.0007 0.0005 9999 0.0066 0.1268 0.0096
    371_B01 0.003 0.0006 0.0024 0.0002 0.1059 9999 0.0005 0.0017 9999 0.0005 0.0018 9999 0.0076 0.0454 0.0091
    371_E12 0.0023 0.0043 0.0022 0.0024 0.5962 9999 0.0012 9999 0.0011 9999 0.0374 0.3155 0.1173
    371_F09 0.0054 0.0006 0.0047 0.0003 0.2882 9999 0.0006 9999 0.0005 9999 0.0311 0.31 0.0405
    371_G01 0.0013 0.0012
    371_H11 0.0011 0.0008
    372_B09 0.0022 0.0002 0.0007 0.0003 0.6034 9999 0.0006 0.0009 9999 0.0006 0.0008 9999 0.0182 0.4639 0.055
    372_D06 0.0085 0.001 0.0083 0.0003 0.3887 9999 0.0004 9999 0.0003 9999 0.0303 0.4069 0.0807
    373_F07 0.0091 0.002 0.0056 0.0039 3.811 9999 0.0015 9999 0.0014 9999 0.0069 0.397 0.0413
    374_A05 0.0023 0.0002 0.0021 0.0005 0.0998 9999 0.0003 0.0008 9999 0.0003 0.0006 9999 0.0081 0.2057 0.0166
    374_C10 0.0137 0.003 0.0064 0.0023 0.4673 9999 0.001 0.0013 9999 0.0007 0.001 9999 0.0582 0.0544 0.3012
    374_G05 0.0074 0.002 0.0042 0.0027 0.5471 9999 0.0021 0.0006 9999 0.0017 0.0006 9999 0.0132 0.4163 0.0192
    365_A12 0.3112 0.0015 0.1194 5.64E−05 9999 9999 0.0103 0.0084 0.7569 0.0059 0.0071 0.3945 0.9032 5.406 1.133
    365_B11 0.003 0.0032
    365_E05 0.0435 0.0098 0.0528 0.0071 0.8445 9999 0.0045 9999 0.0042 9999 0.2437 0.367 0.0548
    365_E07 0.3702 0.0105 0.1501 0.0122 9999 9999 0.011 0.008 9999 0.0048 0.0101 9999 0.5183 9999 0.9486
    366_B12 0.0304 0.0115 0.0185 0.0114 0.8558 9999 0.0012 0.0013 9999 0.0009 0.001 9999 0.0392 0.3748 0.053
    367_F03 0.01 0.007
    367_H06 0.0744 0.0035 0.0653 0.0034 0.8666 9999 0.0018 9999 0.0012 9999 0.108 0.9681 0.3781
    367_H11 0.0389 0.0044 0.0258 0.0035 0.4515 9999 0.0057 0.004 9999 0.003 0.0008 9999 0.0703 1.207 0.118
    368_F03 0.4171 0.0005 0.0323 0.0001 9999 9999 0.022 0.1 9999 0.0189 0.1503 9999 0.8118 3.259 3.216
    369_D02 0.0031 0.0006 0.0039 2.58E−05 0.2671 9999 0.0004 9999 0.0004 9999 0.0135 0.1746 0.0252
    369_F01 0.0147 0.0013 0.0147 0.0002 0.4998 9999 0.0008 9999 0.0007 9999 0.0317 0.5266 0.1112
    369_F06 0.0038 0.0032
    369_G01 0.0112 0.0008 0.0061 0.0001 0.7538 9999 0.0004 9999 0.0004 9999 0.0116 0.1187 0.0275
    369_H06 0.0106 0.0028 0.0082 3.81E−05 9999 9999 0.0005 0.0004 9999 0.0005 0.0002 9999 0.0068 9999 0.0225
    370_A01 0.0045 0.0039
    370_A12 0.0061 0.0023 0.0136 0.0024 0.1245 9999 0.0009 0.0016 9999 0.0008 0.0015 9999 0.0632 0.031 0.0036
    370_C01 0.0017 0.0015
    370_C03 0.0007 0.0004 0.0006 0.0004 0.0388 9999 0.0004 0.0003 9999 0.0004 0.0004 9999 0.0029 0.0133 0.0035
    370_C05 0.0053 0.0032 0.0036 0.0024 0.927 9999 0.0012 0.0033 9999 0.0011 0.0024 9999 0.0082 0.2655 0.0343
    370_C08 0.021 0.0016
    370_D04 0.0055 0.0012 0.0038 0.0013 0.1029 9999 0.0005 0.0007 9999 0.0004 0.0006 9999 0.0074 0.0452 0.0153
    370_E09 0.0043 0.0009 0.0021 0.0006 0.2656 9999 0.0006 0.0007 9999 0.0005 0.0006 9999 0.0093 0.1226 0.009
    370_H01 0.0084 0.0006 0.0056 2.61E−05 2.84 9999 0.0005 0.0004 9999 0.0005 0.0003 9999 0.0093 4999 0.039
    371_A06 0.0014 0.0014
    371_B07 0.0161 0.0023 0.0155 0.0003 1.236 9999 0.0012 0.0014 1.77 0.0011 0.0012 9999 0.0402 0.4951 0.0734
    371_F01 0.005 0.0046
    371_F04 0.0023 0.0022
    372_A04 0.0031 0.0028 0.0051 0.0022 0.3792 9999 0.0008 9999 0.0007 9999 0.0193 0.0367 0.0423
    372_D02 0.0029 0.0027
    372_F03 0.0047 0.0005 0.0041 0.0002 0.1903 9999 0.0003 0.0008 9999 0.0004 0.0008 9999 0.0646 0.1972 0.0233
    372_F08 0.0031 0.0113 0.0026 0.0113 0.371 9999 0.0009 9999 0.0008 9999 0.023 0.3148 0.0248
    372_F09 0.0053 0.0002 0.0113 0.0029 1.012 9999 0.001 0.0009 9999 0.0009 0.0008 9999 0.018 1.8 0.087
    373_A10 0.0028 0.002 0.0055 0.0018 0.3578 2.53 0.0006 9999 0.0006 9999 0.0111 0.0965 0.0534
    373_B04 0.0186 0.0023 0.0103 0.0031 1.268 9999 0.0026 0.0018 9999 0.0027 0.0013 9999 0.0093 1.028 0.1154
    373_C02 0.0302 0.0052 0.0179 0.0022 3.29 9999 0.0053 9999 0.0052 9999 0.0083 1.389 0.1045
    373_C06 0.001 0.001
    373_D04 0.0019 0.0013 0.0023 0.0012 0.1467 9999 0.0006 9999 0.0005 9999 0.0078 0.137 0.0189
    373_D10 0.0069 0.0018 0.0033 0.0004 0.2803 9999 0.0015 0.0008 9999 0.0012 0.0005 9999 0.006 0.0821 0.0176
    374_B04 0.0043 0.0018 0.0029 0.0016 0.2473 9999 0.0014 0.0003 9999 0.0015 0.0003 9999 0.0093 0.1014 0.0156
    374_B06 0.0614 0.0041 0.0513 0.0001 0.5987 9999 0.0011 0.004 9999 0.0009 0.004 9999 0.0407 0.3649 0.0717
    374_C03 0.0016 0.001 0.0026 0.0007 0.1284 9999 0.0005 9999 0.0004 9999 0.0094 0.0468 0.0144
    374_C06 0.0105 0.0039 0.0059 0.0032 0.5205 9999 0.0019 0.0008 9999 0.0015 0.0007 9999 0.0138 0.296 0.015
    374_D08 0.9536 0.0698 0.6104 0.0621 9999 9999 0.3558 0.01 9999 0.2008 0.01 9999 0.2299 9999 1.286
    374_E01 0.0013 0.001
    374_E05 0.0074 0.0023 0.0079 0.0019 0.3051 9999 0.0013 0.0016 0.1534 0.0014 0.0011 0.1414 0.0497 0.6496 2.729
    365_E02 0.4962 0.0046 0.1616 0.0012 12.07 9999 0.0095 0.008 9999 0.0047 0.0013 9999 0.3412 9999 0.4773
    376_C06 0.0349 0.0049 0.0238 0.0053 0.711 9999 0.0042 0.0016 9999 0.0022 0.001 9999 0.0107 0.1983 0.0817
    368_D10 0.0119 0.0045 0.0195 0.0033 0.4824 9999 0.0019 9999 0.0014 9999 0.0601 0.2942 0.0389
    374_C08 0.182 0.0325 0.194 0.0223 9999 9999 0.0462 9999 0.0285 9999 0.5848 9999 9999
    376_A06 0.0011 0.0006 0.0009 0.0004 0.0189 9999 0.0004 0.0004 9999 0.0004 0.0003 9999 0.0043 0.0203 0.0037
    365_F07 0.0044 0.0017 0.0037 0.0006 0.136 9999 0.0012 0.0006 9999 0.0013 0.0007 9999 0.011 0.0925 0.0354
    376_B01 0.0035 0.0006 0.0039 8.50E−05 0.2036 9999 0.0004 9999 0.0004 9999 0.0086 0.369 0.0283
    365_D05 0.0146 0.0025 0.0149 0.0009 0.9169 9999 0.0008 9999 0.0008 9999 0.0209 0.6678 0.1817
    369_G07 0.0068 0.001 0.0075 0.0001 9999 9999 0.0007 9999 0.0006 9999 0.012 0.0327 0.1333
    373_G05 0.0023 0.0002 0.0021 0.0002 0.1636 9999 0.0003 9999 0.0002 9999 0.0059 0.1546 0.0202
    376_B06 0.0016 0.001 0.0014 0.0007 0.0381 9999 0.0005 0.0006 9999 0.0005 0.0004 9999 0.0042 0.0005 0.0164
    374_C11 0.0192 0.0015 0.0105 0.0034 0.9402 9999 0.0018 0.3945 0.0015 0.3304 0.0266 0.6324 0.0328
    375_A06 0.0032 0.0016 0.0025 0.0013 0.1302 9999 0.0012 0.0005 9999 0.0011 0.0004 9999 0.0318 0.1546 0.014
    373_E06 0.0002 0.0002 0.0002 0.0001 0.0082 9999 0.0002 0.0002 9999 0.0002 0.0002 9999 0.0005 0.0089 0.0022
    374_C05 0.0009 0.0005 0.0011 0.0004 0.1344 9999 0.0007 0.0005 9999 0.0007 0.0004 9999 0.0124 0.0142 9999
    368_H01 0.0017 0.0014
    373_B03 0.0006 0.0005
    369_A10 0.017 0.0005 0.0077 8.47E−05 5000 9999 0.001 0.0015 9999 0.001 0.0005 9999 0.0076 5000 0.071
    366_A05 0.7418 9999 0.0004 0.0006 9999 0.0005 0.0005 9999 0.0244 0.6492 0.0524
    375_G07 0.0085 0.0032 0.0053 0.0031 0.7814 9999 0.0022 0.0012 9999 0.0016 0.001 9999 0.0112 0.2215 0.0786
    371_G03 0.001 0.001
    370_E07 0.0009 0.0005 0.0013 0.0005 0.1001 9999 0.0007 0.0003 9999 0.0008 0.0003 9999 0.0046 0.0764 0.013
    367_G07 0.0007 0.0009 0.0011 0.0007 0.1113 9999 0.0011 0.0005 9999 0.0009 0.0004 9999 0.0068 0.0843 0.0124
    375_C12 0.0006 0.0003 0.0007 0.0004 0.0414 9999 0.0004 0.0003 0.4421 0.0004 0.0003 0.4194 0.0063 0.0237 0.2784
    373_B08 0.003 0.0012 0.002 0.0012 0.3478 9999 0.0015 0.0005 9999 0.0017 0.0004 9999 0.0102 0.1201 0.017
    374_A11 0.0038 0.0015 0.0027 0.0015 0.6038 9999 0.0013 0.0004 9999 0.0011 0.0003 9999 0.0086 0.079 0.0188
    373_B11 0.0003 0.0002 0.0005 0.0003 0.0185 9999 0.0002 9999 0.0003 9999 0.0008 0.024 0.0036
    372_D04 0.0022 0.0008 0.0026 0.0317 0.1255 9999 0.0009 0.0005 9999 0.0009 0.0005 9999 0.0114 0.0938 0.0179
    367_A01 0.0021 0.0009 0.0041 0.0011 0.1471 9999 0.0012 0.0009 9999 0.0011 0.0007 9999 0.0065 0.1617 0.0355
    373_E02 0.0034 0.0013 0.0021 0.0013 4999 9999 0.0012 0.0006 9999 0.0012 0.0005 9999 0.0049 4999 4999
  • While the present invention has been described with reference to the specific embodiments thereof, it should be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the true spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation, material, composition of matter, process, process step or steps, to the objective, spirit and scope of the present invention. All such modifications are intended to be within the scope of the claims appended hereto.

Claims (24)

1. An antibody that specifically binds to ACVR2A, wherein the antibody comprises:
(a) a variable domain comprising:
i. heavy chain CDR1, CDR2 and CDR3 regions that are identical the heavy chain CDR1, CDR2 and CDR3 regions of an antibody selected from any of Tables 2A-2F; and
ii. light chain CDR1, CDR2 and CDR3 regions that are identical the light chain CDR1, CDR2 and CDR3 regions of the antibody selected from any of Tables 2A-2F; or
(b) a variant of said variable domain of (a) that is otherwise identical to said antibody variable domain except for up to 15 amino acid substitutions in said CDR regions.
2. An antibody that specifically binds to ACVR2A, wherein the antibody comprises:
a heavy chain variable domain comprising: a heavy chain framework, a CDR1 region, a CDR2 region, and a CDR3 region of sequence AxxAxWHDTxLD (SEQ ID NO: 6618); and
a light chain variable domain comprising: a light chain framework, a CDR1 region, a CDR2 region, and a CDR3 region.
3. The antibody of claim 1, wherein the heavy chain variable domain comprises a CDR3 region of sequence ARSATWHDTxLD (SEQ ID NO: 6549), ARAATWHDTxLD (SEQ ID NO: 6540), ARGANWHDTxLD (SEQ ID NO: 6542), ARGATWHDTxLD (SEQ ID NO: 6544), ARSANWHDTxLD (SEQ ID NO: 6546) or ARSATWHDTxLD (SEQ ID NO: 6548).
4. The antibody of claim 1, wherein the antibody comprises:
a heavy chain variable domain comprising:
i. a CDR1 region that has a sequence of D/SS/DYG/SMH/N (SEQ ID NO: 6550),
ii. a CDR2 region that has a sequence of WVA/SS/G/NINYNG/SGYT/KS/G (SEQ ID NO: 6619), and
iii. a CDR3 region that has a sequence of ARAANWHDTA/HLD (SEQ ID NO: 6620); and
a light chain variable domain comprising:
i. a CDR1 region that has a sequence of L/V/I/SS/T/RYL/VNWY (SEQ ID NO: 6554),
ii. a CDR2 region that has a sequence of LV/LIYA/YNA/V/TT/S/NS/NR/LA/H/Q/P (SEQ ID NO: 6621), and
iii. a CDR3 region that has a sequence of QQ/HSY/DD/E/S/NL/N/S/TPL (SEQ ID NO: 6593).
5. The antibody of claim 1, wherein the antibody comprises:
a heavy chain variable domain comprising:
i. a CDR1 region that has a sequence of D/SS/DYG/SMH/N (SEQ ID NO: 6550),
ii. a CDR2 region that has a sequence of WVA/SS/G/NINYNG/SGYT/KS/G (SEQ ID NO: 6551), and
iii. a CDR3 region that has a sequence of ARAATWHDTH/ALD (SEQ ID NO: 6559); and
a light chain variable domain comprising:
i. a CDR1 region that has a sequence of L/V/I/SS/TYL/VNWY (SEQ ID NO: 6561),
ii. a CDR2 region that has a sequence of LL/VIYA/YA/T/VT/S/NS/NR/LA/P/Q (SEQ ID NO: 6563), and
iii. a CDR3 region that has a sequence of QQSY/D/ND/E/S/NL/S/T/NPL (SEQ ID NO: 6565).
6. The antibody of claim 1, wherein the antibody comprises:
a heavy chain variable domain comprising:
i. a CDR1 region that has a sequence of S/DS/DYS/GMN/H (SEQ ID NO: 6566),
ii. a CDR2 region that has a sequence of WVS/AG/S/NINYNG/SGYT/KS/G (SEQ ID NO: 6567), and
iii. a CDR3 region that has a sequence of ARGANWHDTA/HLD (SEQ ID NO: 6543); and
a light chain variable domain comprising:
i. a CDR1 region that has a sequence of L/V/S/IS/TYL/VNWY (SEQ ID NO: 6569),
ii. a CDR2 region that has a sequence of LL/VIYAA/V/TT/SSR/LA/H/Q (SEQ ID NO: 6571), and
iii. a CDR3 region that has a sequence of QQSY/DD/E/S/NS/T/N/LPL (SEQ ID NO: 6573).
7. The antibody of claim 1, wherein the antibody comprises:
a heavy chain variable domain comprising:
i. a CDR1 region that has a sequence of S/DS/DYS/GMN/H (SEQ ID NO: 6574),
ii. a CDR2 region that has a sequence of WVA/SG/N/SINYNG/SGYT/KS/G (SEQ ID NO: 6575), and
iii. a CDR3 region that has a sequence of ARGATWHDTH/ALD (SEQ ID NO: 6595); and
a light chain variable domain comprising:
i. a CDR1 region that has a sequence of L/I/V/SS/TYL/VNWY (SEQ ID NO: 6596),
ii. a CDR2 region that has a sequence of LL/VIYAA/V/TT/SSR/LA/H/Q (SEQ ID NO: 6571), and
iii. a CDR3 region that has a sequence of QQSY/DD/E/S/NT/S/N/LPL (SEQ ID NO: 6577).
8. The antibody of claim 1, wherein the antibody comprises:
a heavy chain variable domain comprising:
i. a CDR1 region that has a sequence of S/DS/DYG/SMN/H (SEQ ID NO: 6578),
ii. a CDR2 region that has a sequence of WVS/AG/N/SINYNG/SGYT/KS/G (SEQ ID NO: 6579), and
iii. a CDR3 region that has a sequence of AR/KSANWHDTA/HLD (SEQ ID NO: 6580); and
a light chain variable domain comprising:
i. a CDR1 region that has a sequence of L/V/I/SS/TYL/VNWY (SEQ ID NO: 6561),
ii. a CDR2 region that has a sequence of LL/VIYA/YAN/TT/SS/NR/LA/H/Q (SEQ ID NO: 6582), and
iii. a CDR3 region that has a sequence of QQSY/DD/E/N/SS/T/L/NPL (SEQ ID NO: 6598).
9. The antibody of claim 1, wherein the antibody comprises:
a heavy chain variable domain comprising:
i. a CDR1 region that has a sequence of D/SS/DYS/GMN/H (SEQ ID NO: 6584),
ii. a CDR2 region that has a sequence of WVA/SG/N/SINYNG/SGYT/KS/G (SEQ ID NO: 6585), and
iii. a CDR3 region that has a sequence of ARSATWHDTH/ALD (SEQ ID NO: 6586); and
a light chain variable domain comprising:
i. a CDR1 region that has a sequence of L/V/I/SS/T/RYL/VNWY (SEQ ID NO: 6588),
ii. a CDR2 region that has a sequence of LL/VIYA/YAN/TT/SS/NR/LA/H/Q (SEQ ID NO: 6590), and
iii. a CDR3 region that has a sequence of QQSY/DD/E/S/NL/N/T/SPL (SEQ ID NO: 6591).
10. The antibody of claim 1, wherein the antibody comprises:
a heavy chain variable domain comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of the heavy chain variable domain of an antibody selected from any of Tables 2A-2F; and
a light chain variable domain comprising an amino acid sequence that is at least 80% identical to the light chain variable domain of the antibody selected from any of Tables 2A-2F.
11. The antibody of claim 1, wherein the heavy chain variable domain and the light chain variable domain are present in separate polypeptides.
12. The antibody of claim 1, wherein the heavy chain variable domain and the light chain variable domain are present in a single polypeptide.
13. The antibody of claim 1, wherein the antibody binds ACVR2A with an affinity in the range of 107 M−1 to 1012 M−1.
14. The antibody of claim 1, wherein the antibody comprises a covalently linked non-peptide synthetic polymer.
15. The antibody of claim 14, wherein the synthetic polymer is poly(ethylene glycol) polymer.
16. The antibody of claim 1, wherein the antibody comprises a covalently linked lipid or fatty acid moiety.
17. The antibody of claim 1, wherein the antibody comprises a covalently linked polysaccharide or carbohydrate moiety.
18. The antibody of claim 1, wherein the antibody is a single chain Fv (scFv) antibody.
19. The antibody of claim 18, wherein the scFv is multimerized.
20-22. (canceled)
23. A method of treating a condition in a patient comprising administering to a patient in need thereof an effective amount of the antibody of claim 1.
24. The method according to claim 23, wherein the condition is associated with muscle atrophy.
25. The method according to claim 23, wherein the condition is characterized by a decrease in muscle mass or muscle function, or insufficient lean body mass.
26. The method according to claim 23, wherein the condition is cachexia or sarcopenia.
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