RU2795348C2 - Anti-cd39 antibodies, compositions containing anti-cd39 antibodies and methods of application of anti-cd39 antibodies - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: invention relates to an isolated antibody molecule capable of binding to human CD39 (hCD39), as well as to a method for its production. Also an isolated nucleic acid encoding the above antibody is disclosed, as well as a vector and a cell containing it are disclosed. The invention also relates to a method for inducing or enhancing an immune response in a subject, using the above antibody molecule.

EFFECT: invention is effective for treatment of cancer, chronic infection, as well as inflammatory disease.

19 cl, 22 dwg, 2 tbl, 21 ex

Description

RELATED APPLICATION

[0001] This application claims priority to U.S. Provisional Application No. 62/539,527, filed July 31, 2017, which is hereby incorporated by reference in its entirety.

REGION

[0002] Provided herein are antibodies with CD39 binding specificity and compositions containing these antibodies, including pharmaceutical compositions, diagnostic compositions, and kits. Also provided herein are methods of using anti-CD39 antibodies for therapeutic and diagnostic purposes.

PRIOR ART

[0003] CD39 is an integral membrane protein that phosphohydrolyses ATP to produce ADP and AMP. Human CD39 is a 510 amino acid protein with seven potential N-linked glycosylation sites, 11 cysteine residues, and two transmembrane regions. Structurally, it is characterized by two transmembrane domains, a small cytoplasmic domain containing NH ₂ - and COOH terminal segments, and a large extracellular hydrophobic domain consisting of five highly conserved domains known as apyrase-conserved regions (ACR) 1-5, which play central role in the catabolic activity of the enzyme. CD39 becomes catalytically active when it is localized to the cell surface, and its glycosylation is important for protein folding, membrane targeting, and enzymatic activity.

[0004] CD39 is expressed constitutively in the spleen, thymus, lung, and placenta, and in these tissues it is associated primarily with endothelial cells and immune cell populations such as B cells, natural killer cells, dendritic cells, Langerhans, monocytes, macrophages, mesangial cells, neutrophils and regulatory T-lymphocytes (Treg). Given that CD39, along with other enzymes, causes the degradation of ATP, ADP, and AMP to adenosine, CD39 can be considered an immunological switch that shifts the ATP-driven activity of pro-inflammatory immune cells into an adenosine-mediated anti-inflammatory state.

[0005] Under neoplastic conditions, cancer and immune cells can interact closely to create an immunosuppressive environment through the release of immunomodulatory factors that promote neoplasm growth. CD39 expression is elevated in many solid tumors (eg, colorectal cancer, head and neck cancer, pancreatic cancer (Kunzli et al., Am J Physiol, 2006, 292: 223-230), bladder cancer, brain cancer, cancer breast, gastric cancer, hepatocellular carcinoma, lung cancer, non-small cell lung cancer (Li et al., Oncoimmunology, 2017, 6:6), chronic lymphocytic leukemia (Pulte et al., Clin Lymphoma Myeloma Leuk, 2011, 11(4):367 -372) and lymphomas, melanomas (Dzhandzhugazyan et al., FEBS Letters, 1998, 430: 227-230), ovarian cancer, and prostate cancer, among others), indicating that this enzyme is involved in the development and progression of malignant neoplasms. CD39 modulators may find use in the treatment of these types of cancer.

[0006] The interaction between tumor cells and their microenvironment is important for tumorigenesis. CD39 may be involved in tumor escape from immune surveillance by inhibiting the activation, clonal expansion, and homing of tumor-specific T cells, impairing tumor cell killing by effector T lymphocytes. In addition to such immunoregulatory functions, CD39 may be directly involved in the modulation of growth, differentiation, invasion, cancer cell migration, metastasis, and angiogenesis. CD39 is important for both the initiation of angiogenesis and the progression of neovascularization. CD39 in the vasculature mediates the process of angiogenesis in mouse models of melanoma, lung and liver malignancies.

[0007] Modulators of CD39 activity may also find use in the treatment of conditions associated with CD39, which include, but are not limited to, autoimmune diseases and infections. In particular, modulators of CD39 activity may find use in the treatment of diseases such as, but not limited to, celiac disease (Cook et al., American Academy of Allergy, Asthma & Immunology, 2017, Article in Press), colitis (Longhi et al. , JCI Insight. 2017, 2(9)), thrombotic diseases (Marcus et al., Journal of Pharmacology and Experimental Therapeutics, 2003, 305, 1: 9-16), HIV infection (zur Wiesch et al., Journal of Virology, 2011, Feb: 1287-1297), HBV infection, chronic infection with IFN-alpha-resistant hepatitis C virus and inflammatory bowel disease (Friedman et al. PNAS, 2009, 106, 39: 16788-16793) and Crohn's disease ( Bai et al., J Immunol, 2014, 3366-3377).

SUMMARY OF THE INVENTION

[0008] Provided herein are antibodies that selectively bind to CD39. In some embodiments, such antibodies bind to human CD39. In some embodiments, such antibodies also bind to homologues of human CD39.

[0009] In some embodiments, the antibodies contain at least one CDR sequence defined by the consensus sequence provided in the present description of the invention. In some embodiments, the antibodies comprise an exemplary CDR, V _H or V _L sequence as provided herein, a heavy chain or light chain as provided herein, or a variant thereof. In some aspects, such a variant is one with one or more conservative amino acid substitutions.

[0010] Compositions and kits containing these antibodies are also provided. In some embodiments, such compositions are pharmaceutical compositions. Any suitable pharmaceutical composition may be used. In some embodiments, the implementation of such a pharmaceutical composition is a composition for parenteral administration.

[0011] The present disclosure also provides methods for using the anti-CD39 antibodies described herein. In some embodiments, such method is a treatment method. In some embodiments, this method is a diagnostic method. In some embodiments, this method is an analysis method. In some embodiments, the implementation of this method is a method of purification and/or quantitative determination of CD39.

[0012] In some embodiments, such antibodies are used to treat a disease or disorder. In some aspects, such disease or disorder is selected from cancer, autoimmune disease, and infection.

BRIEF DESCRIPTIONS OF THE DRAWINGS

[0013] FIG. 1 is a table showing the monovalent affinity of anti-huCD39 antibodies for the extracellular domain of recombinant human CD39. The table shows the binding kinetics of anti-CD39 antibodies interacting with the extracellular domain (ECD) of soluble recombinant human CD39 (ENTDP1) by biolayer interferometry (ForteBio Octet). Anti-CD39 antibodies were captured on an anti-human Fc antibody sensor and exposed to recombinant human CD39 ECD at a concentration in the range of 10-300 nM. These kinetic data were globally matched with a simple 1:1 Langmuir binding model, resulting in association rate (kon) and dissociation rate (koff) values. Equilibrium dissociation constants (K _D ) were calculated from the values of kon and koff.

[0014] FIG. 2A-E show inhibition of enzymatic catabolism of ATP and ADP in Pi by the extracellular domain (ECD) of human CD39. Recombinant human CD39 at a final concentration of 10 nM (AD) or 5 nM (E) was incubated with anti-CD39 IgGs at a final concentration of 1 μM (AD) or 0.25 μM (E) in 25 mM Tris, 5 mM CaCl ₂ , pH 7.5 , at room temperature for 2 hours. ATP (500 μM) was added to the reaction mixture and incubated at 37°C for 60 minutes. Residual ATP levels in the reaction mixture were measured using the CellTiter-Glo assay method. The data values are the values of two parallel analyses.

[0015] FIG. 2F shows antibodies that bind to Chinese hamster ovary (CHO) cells expressing human or cynomolgus CD39.

[0016] FIG. 3 shows an analysis of antibody binding to MEL-28 (A) and 721 (B) cells. Anti-CD39 antibodies (numbers of all antibody clones are shown in the figure) were titrated in the range from 15 to 0.001 µg/mL. EC ₅₀ was calculated using GraphPad Prism software. The figure shows three independent experiments.

[0017] FIG. 4 shows an assessment of antibody-driven inhibition of CD39 ATP hydrolysis on MEL-28 cells in a short-term ATP assay. FIG. 4A shows the results of a comparison of anti-CD39 antibodies with non-specific small molecular weight inhibitors of POM-1 and ARL. Inhibition is determined by a decrease in phosphate release (Pi). Data are representative of a minimum of 10 independent experiments. Anti-CD39 antibodies (numbers of all antibody clones are shown in the figure) were titrated in the range from 15 to 0.001 µg/mL. IC50 values were calculated using the GraphPad Prism software as can be seen in FIG. 4B. Three independent experiments were carried out.

[0018] FIG. 5 is an illustration of the quantitation when MEL-28 cells are exposed to enzymatic inhibitors of CD39. FIG. 5A shows the evaluation of ATP levels after incubation of MEL-28 cells with dose titration of anti-CD39 antibodies that inhibit enzyme activity. FIG. 5B shows IC50 values calculated using the GrapPad Prism. At least three independent experiments were carried out.

[0019] FIG. 6 shows that antibodies were tested for inhibition of CD39 enzyme activity overnight on MEL-28 cells. FIG. 6A shows that anti-CD39 antibodies (each number represents a unique clone shown in the figure) were titrated from 100 nM to 0.000610 nM. FIG. 6B shows IC50 values calculated using the GraphPad Prism software. Three independent experiments are presented.

[0020] FIG. 7 shows the results of tests for CD39 binding antibodies on primary human and cynomolgus monkey B cells. FIG. 7A shows that anti-CD39 antibodies were titered on purified B cells from a healthy donor and detected with a secondary anti-human IgG-PE antibody. The EC50 value was calculated using the GrapPad Prism software. FIG. 7B shows that anti-CD39 antibodies were titrated on cynomolgus monkey peripheral blood mononuclear cells and detected with a secondary anti-human IgG-PE antibody. B cells were gated using FlowJo software, EC ₅₀ values were calculated using GraphPad Prism.

[0021] FIG. 8 shows antibodies that have been assayed for inhibition of CD39 activity on primary human B cells. Anti-CD39 antibodies (each unique antibody clone number is shown in the figure) were titrated from 100 to 0.00013 nM.

[0022] FIG. 9 shows an assessment of the inhibition of CD39 activity on primary human (a) and cynomolgus monkey (b) monocytes. Anti-CD39 antibodies (each number represents a unique antibody clone number, as shown in the figure) were titrated from 100 to 0.00013 nM and incubated with monocytes in the presence of ATP. Phosphate release upon exposure to CD39 on ATP was quantified by analysis using malachite green.

[0023] FIG. 10 shows the binding of anti-CD39 antibodies to purified human CD4 ⁺ CD25 ⁺ CD127 ^dull regulatory T cells by a fluorescence-activated cell sorting assay. Anti-CD39 antibodies were titrated on purified regulatory T cells from a healthy donor and detected with a secondary anti-human IgG antibody. EC ₅₀ was calculated using GraphPad Prism software.

[0024] FIG. 11 shows the results of an analysis of the ability of antibodies to inhibit CD39 activity of primary regulatory T cells. CD24 ⁺ CD25 ⁺ CD127 ^dull regulatory T cells were incubated with serially diluted anti-CD39 antibodies and analyzed for ATPase activity after the addition of exogenous ATP. Free phosphate (Pi) was used to determine CD39 activity.

[0025] FIG. 12 shows that the use of anti-CD39 antibodies increases the percentage of IFN-gamma producing CD8 ⁺ T cells that respond to CMV peptides in the secondary antigen response assay.

[0026] FIG. 13 shows the evaluation for antibodies to inhibition of CD39 activity on MEL-28 (FIG. 13A.) and human monocytes (FIG. 13B.) compared to anti-CD39 antibodies generated from Innate/Orega (BY-40v9) and Igenica ( 9-8B), and their variants. Anti-CD39 antibodies were titrated as directed and incubated in the presence of ATP. Phosphate release upon exposure to CD39 on ATP was quantified by analysis using malachite green.

[0027] FIG. 14A-G show examples of antibodies. FIG. 14A shows examples of antibodies that bind to the ECD of soluble recombinant CD39 and cellular CD39, but do not inhibit ATPase activity and do not compete with cellular inhibitors for binding to ECD inhibitors. FIG. 14B shows examples of antibodies that have a limited ability to inhibit the ATPase activity of soluble recombinant and cellular CD39 and bind separately from other inhibitors of cellular CD39. FIG. 14C shows examples of antibodies that inhibit soluble recombinant CD39 ECD ATPase activity but do not inhibit cellular CD39 and bind separately from other CD39 ECD inhibitors. FIG. 14D shows examples of antibodies that inhibit ECD and cellular CD39 ATPase activity and bind separately from other CD39 ECD inhibitors and/or cellular inhibitors. FIG. 14E shows examples of inhibitory antibodies that apparently bind to CD39. FIG. 14E shows two tables. Table 1 and Table 2. Table 1 provides examples of inhibitory antibodies that apparently bind to CD39. Table 2 lists examples of inhibitory antibodies that bind to critical, apparently binding residues to CD39. FIG. 14F and FIG. 14G are plots of a fluorescence-activated cell sorting assay indicating the importance of certain human CD39 residues.

[0028] FIG. 15 shows that anti-CD39 antibodies inhibit CD39 by 75-90%. Anti-CD39 antibodies (100 nM), isotype control antibody (100 nM) or ARL (200 μM) were incubated with MEL-28 cells endogenously expressing CD39 for 2 hours. ATP was then added and the rate of ATP hydrolysis to Pi by CD39 was monitored using the EnzChek kinetic Pi detection assay. The initial enzyme rate, v0, was determined from the linear region of the Pi versus time curve during the first 15 minutes after ATP addition. Each value represents the value of 3 parallel analyses.

[0029] FIG. 16A-B show that the CD39 inhibitor 29872 is not a competitive inhibitor due to suppression of V _max suppression.

[0030] FIG. 17 shows that anti-CD39 antibodies can induce CD39 internalization on cynomolgus monkey monocytes.

(Eds.), Antibody Engineering vol. 2 (pp. 33-51). Springer-Verlag, Berlin Heidelberg.[0031] FIG. 18 compares the Kabat and Chothia numbering systems for the CDR-H1. Source: Martin ACR (2010). Protein Sequence and Structure Analysis of Antibody Variable Domains. In R. Kontermann & S.

(Eds.), Antibody Engineering vol. 2 (pp. 33-51). Springer Verlag, Berlin Heidelberg.

[0032] FIG. 19 shows that the anti-CD39 antibody increases the proliferation of stimulated CD4 ⁺ and CD8 ⁺ T cells.

[0033] FIG. 20 shows that the anti-CD39 antibody increases stimulated peripheral blood mononuclear cell secretion of INF-γ, TNF-α, and IL-2.

[0034] FIG. 21 shows that the anti-CD39 antibody increases stimulated peripheral blood mononuclear cell secretion of INF-γ, TNF-α, IL-2 and IL-1β.

[0035] FIG. 22 shows that inhibition of CD39 leads to ATP accumulation and blocks the creation of adenosine.

DETAILED DESCRIPTION

1. Definitions

[0036] Unless otherwise defined, all technical terms, symbols and other scientific terminology used in this document have the meanings that are usually understood by experts in the field of technology to which this invention pertains. In some instances, terms with commonly understood meanings are used herein for purposes of clarity and/or convenience, and the inclusion of such definitions herein should not necessarily be construed as indicating a departure from what is commonly understood in the art. The techniques and procedures described or referred to herein are generally well known and widely used using conventional techniques by those skilled in the art, such as the widely used molecular cloning techniques described in Sambrook et al., Molecular Cloning: A Laboratory Manual 2nd ed. (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. Where applicable, procedures involving the use of commercially available kits and reagents are generally performed according to the protocols and/or parameters described by the manufacturer, unless otherwise specified.

[0037] In the context of this document, the singular means the use of the plural, unless the context clearly requires otherwise.

[0038] The term "about" means and includes the specified value and the range of values above and below this value. In some embodiments, the term "about" means the specified value of ±10%, ±5%, or ±1%. In some embodiments, the term "about" means a specified value ± one standard deviation from a given value.

[0039] The term "combination thereof" includes any possible combination of the elements to which the term refers.

[0040] The terms "CD39" and "CD39 antigen" and "differentiation cluster 39" are used interchangeably herein. CD39 is also known as ectonucleoside triphosphate diphosphohydrolase-1 (gene: ENTPD1; protein: NTPDase1, See www.ncbi.nlm.nih.gov/gene/953). CD39 is also referred to as ATP diphosphohydrolase and SPG64. All of these terms may be used interchangeably. Unless otherwise indicated, these terms include any variants, isoforms, and species homologues of human CD39 that are naturally expressed by cells or that are expressed by cells transfected with the CD39 gene. In some embodiments, the CD39 proteins include murine CD39. In some embodiments, the CD39 proteins include cynomolgus monkey CD39.

[0041] The term "immunoglobulin" means a class of structurally related proteins, usually containing two pairs of polypeptide chains: one pair of light (L) chains and one pair of heavy (H) chains. In "intact immunoglobulin" all four of these chains are interconnected by disulfide bonds. To date, the structure of immunoglobulins has been well characterized. See, for example, Paul, Fundamental Immunology 7th ed., Ch. 5 (2013) Lippincott Williams & Wilkins, Philadelphia, PA. In short, each heavy chain typically contains a heavy chain variable region (V _H ) and a heavy chain constant region ( _CH ). The heavy chain constant region typically contains three domains. C _H1 , C _H2 and C _H3 . Each light chain typically contains a light chain variable region (V _L ) and a light chain constant region. The light chain constant region typically contains a single domain, which is abbreviated as C _L .

[0042] The term "antibody" describes a type of immunoglobulin molecule and is used herein in its broadest sense. In particular, the term "antibody" includes intact antibodies (eg, intact immunoglobulins) and antibody fragments. Antibodies include at least one antigen-binding domain. One example of an antigen-binding domain is an antigen-binding domain formed by a V _H -V _L dimer. "CD39 antibody,""anti-CD39antibody,""CD39Ab,""CD39-specificantibody" or "anti-CD39 Ab" means an antibody described herein that specifically binds to the CD39 antigen. In some embodiments, the antibody binds to the extracellular domain of CD39.

[0043] The V _H and V _L regions can be further divided into regions of hypervariability ("hypervariable regions (HVR)"; also referred to as "complementarity determining regions" (CDR)) interspersed with regions that are more conserved. These more conserved regions are called framework regions (FRs). Each V _H and V _L region typically contains three CDRs and four FRs, organized in the following sequence (from N-terminus to C-terminus): FR1 - CDR1 -FR2 - CDR2 - FR3 - CDR3 - FR4. CDRs are involved in antigen binding and provide antigen specificity and antibody binding affinity. See Kabat et al., Sequences of Proteins of Immunological Interest 5th ed. (1991) Public Health Service, National Institutes of Health, Bethesda, MD, which is hereby incorporated by reference in its entirety.

[0044] A light chain from any vertebrate species can be assigned to one of two types, called kappa and lambda, depending on the sequence of the constant domain.

[0045] A heavy chain from any vertebrate species can be assigned to one of five different classes (or isotypes): IgA, IgD, IgE, IgG, and IgM. These classes are also denoted α, δ, ε, γ, and μ, respectively. The IgG and IgA classes are further divided into subclasses based on differences in sequence and function. For humans, the following subclasses are distinguished: IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2.

, J. Mol. Biol., 2001, 309:657-70 (номенклатура АНо), каждая из которых включается в настоящий документ полностью посредством ссылки.[0046] One skilled in the art can define the amino acid sequence boundaries of the CDRs using one of several known nomenclatures, including those described by Kabat et al., supra (Kabat's nomenclature); Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948 (Chothia nomenclature); MaeCallum et al., 1996, J. Mol. Biol. 262:732-745 (Contact nomenclature); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (IMGT nomenclature); and Honegge and

, J. Mol. Biol., 2001, 309:657-70 (AHO nomenclature), each of which is incorporated herein in its entirety by reference.

[0047] Table 1 lists the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3 according to Kabat and Chothia nomenclature. For CDR-H1, the numbering of residues is indicated for both Kabat and Chothia nomenclatures. FIG. 1 compares the Kabat and Chothia nomenclatures for CDR-H1. See Martin (2010), supra.

[0048] Unless otherwise indicated, Kabat/Chothia nomenclature is used herein as a nomenclature for identifying a specific CDR region. In case there are discrepancies for the residues that are covered by these two nomenclatures, it is indicated which nomenclature is used - Kabata or Chothia.

[0049] "EC Nomenclature" is commonly used to refer to a residue in the heavy chain constant region of an antibody (eg, see Kabat et al., supra). Unless otherwise indicated, EU nomenclature is used to refer to residues in the antibody heavy chain constant regions described herein.

[0050] "Antibody fragment" means a portion of an intact antibody, such as the antigen-binding or variable region of an intact antibody. Antibody fragments include, for example, Fv fragments. Fab fragments, F(ab') ₂ fragments. Fab' fragments, scFv (sFv) fragments and scFv-Fc fragments.

[0051] "Fv" fragments include a non-covalently linked dimer of one heavy chain variable domain and one light chain variable domain.

[0052] "Fab" fragments include, in addition to the heavy and light chain variable domains, a light chain constant domain and a heavy chain first constant domain (C _H1 ). Fab fragments can be generated, for example, by papain digestion of a full length antibody.

[0053] "F(ab') ₂ " fragments contain two Fab' fragment connected by disulfide bonds near the hinge region. F(ab') ₂ fragments can be generated, for example, by pepsin digestion of an intact antibody. F(ab') fragments can be dissociated, for example, under the influence of β-mercaptoethanol.

A. (1994). Antibodies from Escherichia coli. In Rosenberg M. & Moore G.P. (Eds.), The Pharmacology of Monoclonal Antibodies vol. 113 (pp. 269-315). Springer-Verlag, New York, включенные в настоящий документ полностью посредством ссылки. "scFv-Fc" фрагменты содержат scFv, присоединенный к Fc домену. Например, Fc домен может присоединяться к С-концу scFv. Fc может следовать за V_H или V_L, в зависимости от ориентации вариабельных доменов в scFv (i.e., V_H-V_L или V_L-V_H). Может использоваться любой подходящий Fc домен, известный в данной области техники или описанный в настоящей работе.[0054] "Single chain Fv" or "sFv" or "scFv" antibody fragments contain a V _H domain and a V _L domain in the same polypeptide chain. V _H and V _L are usually connected by a peptide linker. See works

A. (1994). Antibodies from Escherichia coli. In Rosenberg M. & Moore G. P. (Eds.), The Pharmacology of Monoclonal Antibodies vol. 113 (pp. 269-315). Springer-Verlag, New York, incorporated herein by reference in their entirety. "scFv-Fc" fragments contain scFv attached to an Fc domain. For example, the Fc domain can be attached to the C-terminus of the scFv. Fc may follow V _H or V _L depending on the orientation of the variable domains in the scFv (ie, V _H -V _L or V _L -V _H ). Any suitable Fc domain known in the art or described herein can be used.

[0055] The term "monoclonal antibody" means an antibody from a population of primarily homogeneous antibodies. The population of mostly homogeneous antibodies includes antibodies that are mostly similar and that bind to the same epitope(s), with the exception of variations that may normally occur during the formation of a monoclonal antibody. Such variants are usually only present in minor amounts. A monoclonal antibody is usually obtained in a process that involves selecting one antibody from a plurality of antibodies. For example, such a selection process may be to select a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones. The selected antibody can be further modified, for example, to improve affinity for the target ("affinity maturation"), to humanize the antibody, to improve its production in cell culture, and/or to reduce its immunogenicity in the subject.

[0056] The term "chimeric antibody" means an antibody in which part of the heavy and/or light chain is derived from a specific source or species, and the remainder of the heavy and/or light chain is derived from another source or species.

[0057] "Humanized" forms of non-human antibodies are chimeric antibodies that contain a minimal sequence derived from the non-human antibody. A humanized antibody is typically a human immunoglobulin (recipient antibody) in which residues from one or more CDRs are replaced with residues from one or more CDRs of a non-human antibody (donor antibody). The donor antibody may be any suitable non-human antibody, such as a mouse, rat, chicken, or non-human primate antibody, with the desired specificity, affinity, or biological activity. In some cases, selected framework region residues from the recipient antibody are replaced by corresponding framework region residues from the donor antibody. Humanized antibodies may also contain residues that are not found in the recipient antibody or the donor antibody. Such modifications can be made to further improve antibody function. For more information, see Jones et al., Nature, 1986, 321:522-525; Riechmann et al., Nature, 1988, 332:323-329; and Presta, Curr. Op. Struct. Biol., 1992, 2:593-596, each of which is incorporated herein in its entirety by reference.

[0058] "Human antibody" means an antibody that has an amino acid sequence corresponding to that of an antibody generated by a human or a human cell, or derived from a non-human source that uses a spectrum of human antibodies or sequences encoding a human antibody (e.g., derived from sources of human origin). or created de novo). It should be specifically noted that human antibodies do not include humanized antibodies.

[0059] An "isolated antibody" is an antibody that has been isolated and/or reconstituted from a component of its natural environment. Components of the natural environment may include enzymes, hormones, and other proteinaceous or non-proteinaceous materials. In some embodiments, the isolated antibody is purified to a degree sufficient to obtain at least 15 residues of the N-terminus or internal amino acid sequence, for example, using a rotary beaker sequencer. In some embodiments, the isolated antibody is purified to homogeneity by electrophoresis (eg, SDS-PAGE) under reducing or non-reducing conditions, with detection using Coomassie blue or silver. An isolated antibody includes an antibody in situ in recombinant cells if at least one component of the antibody's natural environment is missing. In some aspects, the isolated antibody is prepared by at least one purification step.

[0060] In some embodiments, the isolated antibody is purified to at least 80%, 85%, 90%, 95%, or 99% by weight. In some embodiments, the isolated antibody is provided as a solution containing at least 85%, 90%, 95%, 98%, 99%-100% by weight of the antibody, with the remainder of the weight being the weight of other materials dissolved in the solvent.

[0061] "Affinity" refers to the strength of the set of non-covalent interactions between one binding site of a molecule (eg, an antibody) and its binding partner (eg, an antigen). Unless otherwise indicated, as used herein, "binding affinity" means true binding affinity, which reflects a 1:1 interaction between members of a binding pair (eg, antibody and antigen). The affinity of a molecule X for its partner Y can generally be represented by a dissociation constant (K _D ). Affinity can be measured by common methods known in the art, including the methods described herein. Affinity can be determined, for example, using Surface Plasma Resonance (SPR) technology, such as the ^Biacore® instrument.

[0062] With regard to the binding of an antibody to a target molecule, the terms "specific binding", "specifically binds to", "specific to", "selectively binds" and "selective to" in relation to a particular antigen (e.g., target polypeptide) or epitope on a specific antigen means a binding that is significantly different from a non-specific or non-selective interaction. Specific binding can be measured, for example, by determining the binding of a molecule compared to the binding of a control molecule. Specific binding can also be determined by competition with a control molecule that is similar to the target, eg the predominant unlabeled target. In this case, specific binding is determined if binding of the labeled target to the probe is competitively inhibited by the predominant unlabeled target.

[0063] The term "k _d " (sec ^-1 ) in the context of this document means the rate constant of dissociation of a certain interaction of antibodies and antigen. This value is also referred to as the k _off value.

[0064] The term " _ka " (M ^-1 xsec ^-1 ) as used herein means the association rate constant of a particular interaction between an antibody and an antigen. This value is also referred to as the k _on value.

[0065] The term "K _D " (M) in the context of this document means the equilibrium constant for the dissociation of a certain interaction of an antibody and antigen. K _D \u003d k _d /k _a .

[0066] The term "K _A " (M ^-1 ) in the context of this document means the equilibrium constant in the association of a certain interaction of an antibody and an antigen. K _A \u003d k _a / k _d .

[0067] An "affinity matured" antibody is an antibody with one or more changes in one or more CDR or FR regions that result in an improvement in the affinity of the antibody for its antigen, compared to the parent antibody that does not have such change(s). In one embodiment, the affinity matured antibody has nanomolar or picomolar affinity for the target antigen. Affinity matured antibodies can be generated using a variety of techniques known in the art. For example, Marks et al. (Bio/Technology, 1992, 10:779-783, incorporated herein by reference in its entirety) describe affinity maturation by shuffling the V _H and V _L domains. Random mutagenesis of CDR and/or scaffold residues is described, for example, by Barbas et al. (Proc. Nat. Acad. Sci. USA, 1994, 91:3809-3813); Schier et al., Gene, 1995, 169:147-155; Yelton et al., J. Immunol., 1995, 155:1994-2004; Jackson et al., J. Immunol., 1995, 154:3310-33199; and Hawkins et al., J. Mol. Biol., 1992, 226:889-896, each of which is incorporated herein in its entirety by reference.

[0068] When used herein in the context of two or more antibodies, the term "competes with" or "cross-competes with" means that two or more antibodies compete for binding to an antigen (eg, CD39). In one exemplary assay, CD39 is loaded onto a plate and allowed to bind to a first antibody, after which a second, labeled antibody is added. If the presence of the first antibody reduces the binding of the second antibody, then these antibodies compete. The term "competes with" also includes combinations of antibodies in which one antibody reduces the binding of another antibody, but in which competition is not observed when the antibodies are added in reverse order. However, in some embodiments, the first and second antibodies inhibit each other's binding regardless of the order in which they are added. In some embodiments, one antibody reduces the binding of another antibody to its antigen by at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%.

[0069] The term "epitope" means the portion of an antigen capable of specific binding to an antibody. Epitopes often consist of surface-accessible amino acid residues and/or sugar side chains and may have specific three-dimensional structural characteristics as well as specific charging characteristics. Conformational and non-conformational epitopes differ in that binding to the former, but not to the latter, is lost in the presence of denaturing solvents. An epitope may contain amino acid residues that are directly involved in binding and other amino acid residues that are not directly involved in binding. The epitope to which an antibody binds can be determined using known epitope detection methods, such as, for example, antibody binding tests for CD39 variants with various point mutations.

[0070] "Percent identity" between a polypeptide sequence and a reference sequence is defined as the percentage of amino acid residues in the polypeptide sequence that are identical to amino acid residues in the reference sequence, after aligning the sequences and gaps, if necessary, to achieve the maximum percent sequence identity. Alignment to determine percent amino acid sequence identity can be achieved by various methods known in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, or CLUSTAL OMEGA. Those skilled in the art can determine appropriate parameters for sequence alignment, including any algorithms necessary to achieve maximum alignment over the entire length of the compared sequences.

[0071] "Conservative substitution" or "conservative amino acid substitution" means the replacement of one or more amino acids with one or more chemically or functionally similar amino acids. Conservative substitution tables representing similar amino acids are well known in the art. Polypeptide sequences with such substitutions are known as "conservatively modified variants". Such conservatively modified variants complement, but do not exclude, polymorphic variants, interspecies homologues, and alleles. For example, the following groups of amino acids are considered conservative substitutions for each other.

Additional conservative substitutions can be found, for example, in Creighton, Proteins: Structures and Molecular Properties 2nd ed. (1993) W.H. Freeman & Co., New York, NY. An antibody created by using one or more conservative amino acid residue substitutions in the parent antibody is referred to as a "conservatively modified variant".

[0072] The term "amino acid" refers to the twenty common naturally occurring amino acids. Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C); glutamic acid (Glu; E), glutamine (Gln; Q), glycine (Gly; G); histidine (H-; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), series (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y) and valine (Val; V).

[0073] "Treatment" of any disease or disorder means, in some embodiments, amelioration of the disease or disorder present in a subject. In another embodiment, "treating" includes reducing the intensity of at least one physical parameter that the subject may not perceive. In another embodiment, "treating" includes modulating the disease or disorder physically (eg, by stabilizing an unperceived symptom), or physiologically (eg, by stabilizing a physical parameter), or both physically and physiologically at the same time. In another embodiment, "treating" includes delaying or preventing the onset of a disease or disorder.

[0074] As used herein, a "therapeutically effective amount" or "effective amount" means an amount of an antibody or composition that, when administered to a subject, is effective in treating a disease or disorder.

[0075] As used herein, "subject" means a mammalian subject. Examples of subjects include, but are not limited to, humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, birds, goats, and sheep. In some embodiments, such a subject is a human. In some embodiments, the subject has a cancer, autoimmune disease or condition and/or infection that can be treated with the antibodies described herein. In some embodiments, such a subject is a human suspected of having cancer, an autoimmune disease or condition, and/or an infection.

2. Antibodies

[0076] Here are antibodies that selectively bind to human CD39, as well as nucleic acids that encode antibodies. In some aspects, the antibody selectively binds to the extracellular domain of human CD39.

[0077] In some aspects, the antibody binds to homologues of human CD39. In some aspects, the antibody binds to a human CD39 homologue from a species selected from monkeys, mice, dogs, cats, rats, cows, horses, goats, and sheep. In some aspects, such a homologue is a cynomolgus monkey. In some aspects, such a homologue is a mouse homologue.

[0078] In some embodiments, the implementation of the antibody has one or more CDR with certain lengths, in terms of the number of amino acid residues. In some embodiments, the CDR-H1 of the Chothia antibody is 6, 7, 8, or 9 residues in length. In some embodiments, the CDR-H1 of the Kabat antibody is 4, 5, 6, or 7 residues in length. In some embodiments, the CDR-H2 of the Chothia antibody is 5, 6, or 7 residues in length. In some embodiments, the CDR-H2 of the Kabat antibody is 15, 16, 17, or 18 residues in length. In some embodiments, the CDR-H3 of the Kabat/Chothia antibody is 5, 6, 7, 8, 9, 10, 11, or 12 residues in length.

[0079] In some aspects, the CDR-L1 of the Kabat/Chothia antibody is 9, 10, 11, 12, 13, 14, 15, or 16 residues in length. In some aspects, the CDR-L2 of the Kabat/Chothia antibody is 6, 7, or 8 residues in length. In some aspects, the CDR-L3 of the Kabat/Chothia antibody is 8, 9, 10, 11, or 12 residues in length.

[0080] In some embodiments, the antibody comprises a light chain. In some aspects, such a light chain is a kappa light chain. In some embodiments, such a light chain is a lambda light chain.

[0081] In some embodiments, the antibody comprises a heavy chain. In some aspects, the heavy chain is IgA. In some aspects, the heavy chain is IgD. In some aspects, the heavy chain is IgE. In some aspects, the heavy chain is IgG. In some aspects, the heavy chain is IgM. In some aspects, this heavy chain is IgG1. In some aspects, this heavy chain is IgG2. In some aspects, the heavy chain is IgG3. In some aspects, this heavy chain is IgG4. In some aspects, this heavy chain is IgA1. In some aspects, this heavy chain is IgA2.

[0082] In some embodiments, such an antibody is an antibody fragment. In some aspects, such an antibody fragment is an Fv fragment. In some aspects, such an antibody fragment is a Fab fragment. In some aspects, such an antibody fragment is a F(ab') ₂ fragment. In some aspects, such an antibody fragment is a Fab' fragment. In some aspects, such an antibody fragment is an scFv (sFv) fragment. In some aspects, such an antibody fragment is a scFv-Fc fragment.

[0083] In some embodiments, such an antibody is a monoclonal antibody. In some embodiments, such an antibody is a polyclonal antibody.

[0084] In some embodiments, such an antibody is a chimeric antibody. In some embodiments, such an antibody is a humanized antibody. In some embodiments, such an antibody is a human antibody.

[0085] In some embodiments, such an antibody is an affinity matured antibody. In some aspects, such an antibody is an affinity matured antibody derived from the exemplary sequence provided herein.

[0086] In some aspects, the antibody inhibits the CD39 enzyme's conversion of ATP to ADP and/or ADP to AMP. In some aspects, the antibody reduces the levels of phosphate, ADP, AMP and/or adenosine and/or increases the levels of ATP.

[0087] In some embodiments, the implementation of the antibody increases the proliferation of stimulated CD4 ⁺ and CD8 ⁺ T cells. In some embodiments, the antibody increases stimulated peripheral blood mononuclear cell secretion of INF-γ, TNF-α, IL-2, and/or IL-1β.

[0088] In some embodiments, the implementation of the antibody increases the function of effector T cells. In some embodiments, the antibody reduces the number of regulatory T cells in tissues or in circulating blood. In some embodiments, the implementation of the antibody suppresses the activity of regulatory or T cells. In some embodiments, the antibody enhances B cell function. In some embodiments, the antibody enhances the function of antigen-presenting cells. In some embodiments, the antibody reduces or prevents the activation of phosphoantigen-specific T cells selected from mucosal-associated invariant cells and gamma delta T cells.

[0089] In some aspects, such a decrease is a decrease of about or less than 10%, a decrease of about or less than 20%, a decrease of about or less than 30%, a decrease of about or less than 40%, a decrease of about or less than 50%, a decrease of about or less than 60 %, decrease of about or less than 70%, decrease of about or less than 80%, decrease of about or less than 90%, or almost complete decrease. In some aspects, the increase is about or more than 10%, about or more than 20%, about or more than 30%, about or more than 40%, about or more than 50%, about or more than 60%, about or more than 70%, an increase of about or more than 80%, an increase of about or more than 90%, or a complete increase.

[0090] Given that ATP and ADP are degraded to adenosine by CD39, CD39 can be considered an immunological switch that shifts the ATP-driven activity of pro-inflammatory immune cells into an adenosine-mediated anti-inflammatory state. CD39 is involved in regulating the function of several types of immune cells, including lymphocytes, neutrophils, monocytes/macrophages, dendritic cells, and endothelial cells, and flipping this switch can have a significant impact on disease. For example, the creation of adenosine by CD39 has been recognized as a major mechanism for the immunosuppressive function of regulatory T cells (Treg).

[0091] The antibodies provided herein may be useful in the treatment of various diseases and conditions, including cancer, autoimmune diseases, and infections. In some embodiments, the antibody inhibits CD39 function on tumor cells. In some embodiments, the antibody inhibits angiogenesis.

[0092] CD39 ⁺ Treg frequency and cell surface expression are elevated in several human cancers, and the importance of CD39 ⁺ Treg in promoting tumor growth and metastasis has been demonstrated in several in vivo models. Immunohistochemical staining of normal and tumor tissues showed that CD39 expression is significantly higher in several types of human cancer than in normal tissues. In cancer samples, CD39 is expressed by infiltrating lymphocytes, tumor stroma, and/or tumor cells. CD39 in cancer cells exhibits ATPase activity and creates adenosine. CD39 ⁺ cancer cells inhibited the proliferation of CD4 and CD8 T cells and the creation of cytotoxic and effector CD8 T cells (CTLs) in a CD39- and adenosine-dependent manner.

2.1. CDR-H3 sequences

[0093] In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 82-109. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 82. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 83. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 84. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of consisting of the sequence of SEQ ID: 85. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 86. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or , primarily consisting of the sequence of SEQ ID: 87. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 88. In some aspects, the antibody contains a CDR-H3 sequence containing , consisting of or primarily consisting of the sequence of SEQ ID: 89. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 90. In some aspects, the antibody contains CDR-H3 An H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 91. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 92. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 93. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 94 In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 95. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence SEQ ID: 96. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 97. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily , consisting of the sequence of SEQ ID: 98. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 99. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of or primarily consisting of the sequence of SEQ ID: 100. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 101. In some aspects, the antibody contains a CDR-H3 sequence, comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 102. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 103. In some aspects, the antibody comprises a CDR -H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 104. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 105. In some In certain aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 106. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 106. 107. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 108. In some aspects, the antibody contains a CDR-H3 sequence containing, consisting of, or primarily consisting of sequences SEQ ID: 109.

[0094] In some aspects, the CDR-H3 sequence comprises, consists of, or primarily consists of a variant of the exemplary CDR-H3 sequence provided herein: In some aspects, the CDR-H3 sequence comprises, consists of, or primarily consists of consists of a sequence having a minimum of 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-H3 sequences provided herein. In some aspects, a CDR-H3 sequence comprises, consists of, or primarily consists of any of the illustrative CDR-H3 sequences provided herein, with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

2.2. V _H sequences containing exemplary CDRs

[0095] In some embodiments, the antibody comprises a V _H sequence comprising one or more CDR-H sequences comprising, consisting of, or primarily consisting of one or more of the illustrative CDR-H sequences provided herein, and its options.

2.2.1. V _H sequences containing exemplary Kabat CDRs

[0096] In some embodiments, the antibody comprises a V _H sequence comprising one or more Kabat CDR-H sequences comprising, consisting of, or primarily consisting of one or more of the exemplary Kabat CDR-H sequences provided herein. invention and its variants.

2.2.1.1. CDR-H3 by Kabat

[0097] In some embodiments, the antibody comprises a V _H sequence comprising a CDR-H3 Kabat sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 82-109. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 82. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 83. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 84. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H3 Kabat sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 85. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H3 sequence according to Kabat, containing, consisting of, or mainly consisting of the sequence of SEQ ID: 86. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 Kabat sequence, containing, consisting of, or mainly consisting of the sequence of SEQ ID: 87. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H3 Kabat sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 88. In some aspects, the antibody comprises a V _H sequence comprising a CDR- A Kabat H3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 89. In some aspects, an antibody comprises a V _H sequence comprising a CDR-H3 Kabat sequence comprising, consisting of, or primarily consisting of sequence of SEQ ID: 90. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 91. In some aspects, the antibody contains a V _H sequence containing A Kabat CDR-H3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 92. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 93. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 94. In some aspects, the antibody contains a V _H sequence , containing a Kabat CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 95. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H3 sequence containing, consisting of, or mainly consisting of the sequence of SEQ ID: 96. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 97. In some aspects, the antibody contains V _{An H} sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 98. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or , primarily consisting of the sequence of SEQ ID: 99. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 100. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 101. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of of or primarily consisting of the sequence of SEQ ID: 102. In some aspects, the antibody comprises a V _H sequence containing a CDR-H3 Kabat sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 103. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 104. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H3 sequence comprising consisting of or primarily consisting of the sequence of SEQ ID: 105. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 106. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 107. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 108. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 109.

2.2.1.2. CDR-H2 by Kabat

[0098] In some embodiments, the antibody comprises a V _H sequence comprising a CDR-H2 Kabat sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 63-81. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 63. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 64. In some aspects, the antibody contains a V _H sequence containing a CDR-H2 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 65. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H2 Kabat sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 66. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H2 sequence according to Kabat, containing, consisting of, or mainly consisting of the sequence of SEQ ID: 67. In some aspects, the antibody contains a V _H sequence containing a CDR-H2 sequence according to Kabat, containing, consisting of, or mainly consisting of the sequence of SEQ ID: 68. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H2 Kabat sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 69. In some aspects, the antibody comprises a V _H sequence comprising a CDR- A Kabat H2 sequence comprising, consisting of, or primarily consisting of SEQ ID: 70. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H2 Kabat sequence comprising, consisting of, or primarily consisting of sequence of SEQ ID: 71. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 72. In some aspects, the antibody contains a V _H sequence containing A Kabat CDR-H2 sequence comprising, consisting of, or primarily consisting of SEQ ID: 73. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 74. In some aspects, the antibody contains a V _H sequence containing a CDR-H2 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 75. In some aspects, the antibody contains a V _H sequence , containing a Kabat CDR-H2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 76. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H2 sequence containing, consisting of, or mainly consisting of the sequence of SEQ ID: 77. In some aspects, the antibody contains a V _H sequence containing a CDR-H2 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 78. In some aspects, the antibody contains V _{An H} sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or primarily consisting of SEQ ID: 79. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or , primarily consisting of the sequence of SEQ ID: 80, In some aspects, the antibody contains a V _H sequence containing a CDR-H2 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 81.

2.2.1.3. CDR-H1 by Kabat

[0099] In some embodiments, the antibody comprises a V _H sequence comprising a CDR-H1 Kabat sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 25-45. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 25. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 26. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 27. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H1 Kabat sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 28. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H1 sequence according to Kabat, containing, consisting of, or mainly consisting of the sequence of SEQ ID: 29. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 Kabat sequence, containing, consisting of, or mainly consisting of the sequence of SEQ ID: 30. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H1 Kabat sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 31. In some aspects, the antibody comprises a V _H sequence comprising a CDR- A Kabat H1 sequence comprising, consisting of, or primarily consisting of SEQ ID: 32. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H1 Kabat sequence comprising, consisting of, or primarily consisting of sequence of SEQ ID: 33. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 34. In some aspects, the antibody contains a V _H sequence containing A Kabat CDR-H1 sequence comprising, consisting of, or primarily consisting of SEQ ID: 35. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 36. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 37. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 38. In some aspects, the antibody comprises a V _H sequence containing a Kabat CDR-H1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 39. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 40. In some aspects, the antibody contains V _{An H} sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or primarily consisting of SEQ ID: 41. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or , primarily consisting of the sequence of SEQ ID: 42. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 Kabat sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 43. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 44. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of of or primarily consisting of the sequence of SEQ ID: 45.

2.2.1.4. CDR-H3 by Kabat + CDR-H2 by Kabat

[00100] In some embodiments, the antibody comprises a V _H sequence comprising a CDR-H3 Kabat sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 82-109, and a CDR-H2 sequence of Kabatu containing, consisting of or mainly consisting of a sequence selected from the sequences of SEQ ID: 63-81. In some aspects, the CDR-H3 Kabat sequence and the CDR-H2 Kabat sequence are both derived from the same exemplary V _H sequence provided herein. For example, in some aspects, Kabat CDR-H3 and Kabat CDR-H2 are both derived from the same exemplary V _H sequence selected from SEQ ID: 179-218.

2.2.1.5. CDR-H3 by Kabat + CDR-H1 by Kabat

[00101] In some embodiments, the antibody comprises a V _H sequence comprising a CDR-H3 Kabat sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 82-109, and a CDR-H1 sequence of Kabatu containing, consisting of, or mainly consisting of a sequence selected from the sequences of SEQ ID: 25-45. In some aspects, the CDR-H3 Kabat sequence and the CDR-H1 Kabat sequence are both derived from the same exemplary V _H sequence provided herein. For example, in some aspects, Kabat CDR-H3 and Kabat CDR-H1 are both derived from the same exemplary V _H sequence selected from SEQ ID: 179-218.

2.2.1.6. CDR-H1 by Kabat + CDR-H2 by Kabat

[00102] In some embodiments, the antibody comprises a V _H sequence comprising a CDR-H1 Kabat sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 25-45, and a CDR-H2 sequence of Kabatu containing, consisting of, or mainly consisting of a sequence selected from the sequences of SEQ ID: 63-81. In some aspects, the CDR-H1 Kabat sequence and the CDR-H2 Kabat sequence are both derived from the same illustrative V _H sequence provided herein. For example, in some aspects, Kabat CDR-H1 and Kabat CDR-H2 are both derived from the same exemplary V _H sequence selected from SEQ ID: 179-218.

2.2.1.7. CDR-H1 by Kabat + CDR-H2 by Kabat + CDR-H3 by Kabat

[00103] In some embodiments, the antibody comprises a V _H sequence comprising a CDR-H1 Kabat sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 25-45, and a CDR-H2 sequence of Kabatu containing, consisting of or mainly consisting of a sequence selected from the sequences of SEQ ID: 63-81, and a CDR-H3 sequence according to Kabat containing, consisting of or mainly consisting of a sequence selected from the sequences of SEQ ID: 82-109. In some aspects, the CDR-H1 Kabat sequence, the CDR-H2 Kabat sequence, and the CDR-H3 Kabat sequence are all derived from a single exemplary V _H sequence provided herein. For example, in some aspects, Kabat CDR-H1, Kabat CDR-H2, and Kabat CDR-H3 are all derived from a single exemplary V _H sequence selected from SEQ ID: 179-218.

[00104] In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 25, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 63, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 26, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 64, and a CDR-H3 sequence of Kabat containing the sequence of SEQ ID: 83. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 27, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 65, and a CDR- A Kabat H3 sequence comprising SEQ ID: 84. In some aspects, an antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID: 26, a Kabat CDR-H2 sequence comprising SEQ ID: 64, and a Kabat CDR-H3 sequence comprising SEQ ID: 85. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID: 26, a Kabat CDR-H2 sequence comprising SEQ ID: 26. : 64, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 86. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 25, a Kabat CDR-H2 sequence containing sequence of SEQ ID: 66, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 26, a CDR-H2 sequence of Kabat containing the sequence of SEQ ID: 65, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 27, CDR- A Kabat H2 sequence containing the sequence of SEQ ID: 65, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 28 , a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 67, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 29, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 68, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing the Kabat CDR-H1 sequence, containing the sequence of SEQ ID: 26, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 64, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing the CDR-H1 sequence Kabat sequence containing the sequence SEQ ID: 30, a Kabat CDR-H2 sequence containing the sequence SEQ ID: 69, and a Kabat CDR-H3 sequence containing the sequence SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing the CDR -H1 Kabat sequence containing the sequence of SEQ ID: 31, CDR-H2 Kabat sequence containing the sequence of SEQ ID: 70, and CDR-H3 Kabat sequence containing the sequence of SEQ ID: 88. In some aspects, the antibody contains a V _H sequence , containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 32, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 71, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 89. In some aspects, the antibody contains A V _H sequence containing a Kabat CDR-H1 sequence containing SEQ ID: 33, a Kabat CDR-H2 sequence containing SEQ ID: 70, and a Kabat CDR-H3 sequence containing SEQ ID: 90. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 34, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 72, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 91 In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 30, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 71, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 92. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 35, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 70, and a Kabat CDR-H3 sequence, containing the sequence of SEQ ID: 93. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 33, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 70, and a CDR-H3 sequence according to Kabat, containing the sequence of SEQ ID: 92. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Kabat, containing the sequence of SEQ ID: 36, a CDR-H2 sequence according to Kabat, containing the sequence of SEQ ID: 72, and a CDR -H3 Kabat sequence comprising SEQ ID: 87. In some aspects, the antibody comprises a V _H sequence comprising Kabat CDR-H1 sequence comprising SEQ ID: 30, Kabat CDR-H2 sequence comprising SEQ ID: 73 , and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 37, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 74, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 38, a Kabat CDR-H2 sequence, containing the sequence of SEQ ID: 75, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 94. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 39, a CDR-H2 sequence according to Kabat, containing the sequence of SEQ ID: 76, and a CDR-H3 sequence according to Kabat, containing the sequence of SEQ ID: 95. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Kabat, containing the sequence of SEQ ID: 40, CDR -H2 sequence according to Kabat, containing the sequence of SEQ ID: 76, and a CDR-H3 sequence according to Kabat, containing the sequence of SEQ ID: 96. In some aspects, the antibody contains a V _H sequence, containing a CDR-H1 sequence according to Kabat, containing the sequence of SEQ ID: 39, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 76, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 94. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence SEQ ID: 38, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 69, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 97. In some aspects, the antibody contains a V _H sequence containing the CDR-H1 sequence of Kabat , containing the sequence of SEQ ID: 41, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 69, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 98. In some aspects, the antibody contains a V _H sequence containing CDR-H1 a Kabat sequence containing the sequence of SEQ ID: 41, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 69, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 99. In some aspects, the antibody contains a V _H sequence containing A Kabat CDR-H1 sequence containing the sequence of SEQ ID: 41, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 69, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 100. In some aspects, the antibody contains V _H a sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 38, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 75, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 101. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing SEQ ID: 42, a Kabat CDR-H2 sequence containing SEQ ID: 78, and a Kabat CDR-H3 sequence containing SEQ ID: 102. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 38, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 75, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 103. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 43, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 79, and a Kabat CDR-H3 sequence containing the sequence SEQ ID: 104. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 38, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 69, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 103. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 38, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 69, and a CDR-H3 a Kabat sequence comprising SEQ ID: 106. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID: 38, a Kabat CDR-H2 sequence comprising SEQ ID: 69, and A Kabat CDR-H3 sequence comprising SEQ ID: 107. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID: 44, a Kabat CDR-H2 sequence comprising SEQ ID: 80, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 108. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 45, a Kabat CDR-H2 sequence containing the sequence SEQ ID: 81, and a Kabat CDR-H3 sequence containing SEQ ID: 109.

[00105] In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 26, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 65, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 83. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 26, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 65, and a CDR-H3 sequence of Kabat containing the sequence of SEQ ID: 84. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 26, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 65, and a CDR- A Kabat H3 sequence comprising SEQ ID: 85. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID: 26, a Kabat CDR-H2 sequence comprising SEQ ID: 65, and a Kabat CDR-H3 sequence comprising SEQ ID: 86. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID: 26, a Kabat CDR-H2 sequence comprising SEQ ID: 26. : 64, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 84. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 26, a Kabat CDR-H2 sequence containing sequence of SEQ ID: 64, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 86. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 27, a CDR-H2 sequence of Kabat containing the sequence of SEQ ID: 65, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 83. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 27, CDR- A Kabat H2 sequence comprising SEQ ID: 65 and a Kabat CDR-H3 sequence comprising SEQ ID: 86. In some aspects, the antibody comprises a V _H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID: 30 , a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 71, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 93. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 30, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 73, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence, containing the sequence of SEQ ID: 30, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 72, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing the CDR-H1 sequence Kabat sequence containing the sequence SEQ ID: 30, a Kabat CDR-H2 sequence containing the sequence SEQ ID: 70, and a Kabat CDR-H3 sequence containing the sequence SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing the CDR -H1 Kabat sequence containing the sequence of SEQ ID: 31, CDR-H2 Kabat sequence containing the sequence of SEQ ID: 70, and CDR-H3 Kabat sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence , containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 31, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 71, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains A V _H sequence containing a Kabat CDR-H1 sequence containing SEQ ID: 32, a Kabat CDR-H2 sequence containing SEQ ID: 71, and a Kabat CDR-H3 sequence containing SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 33, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 71, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 87 In some aspects, the antibody comprises a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 33, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 72, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 33, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 70, and a Kabat CDR-H3 sequence, containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 33, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 71, and a CDR-H3 sequence according to Kabat containing the sequence of SEQ ID: 93. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Kabat containing the sequence of SEQ ID: 33, a CDR-H2 sequence according to Kabat containing the sequence SEQ ID: 70, and a CDR -H3 Kabat sequence comprising SEQ ID: 93. In some aspects, the antibody comprises a V _H sequence comprising Kabat CDR-H1 sequence comprising SEQ ID: 34, Kabat CDR-H2 sequence comprising SEQ ID: 72 , and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 30, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 71, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 35, a Kabat CDR-H2 sequence, containing the sequence of SEQ ID: 70, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 35, a CDR-H2 sequence according to Kabat, containing the sequence of SEQ ID: 70, and a CDR-H3 sequence according to Kabat, containing the sequence of SEQ ID: 90. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Kabat, containing the sequence of SEQ ID: 30, CDR -H2 sequence according to Kabat containing the _sequence of SEQ ID: 70; 39, a Kabat CDR-H2 sequence containing SEQ ID: 76 and a Kabat CDR-H3 sequence containing SEQ ID: 94.

2.2.1.8. Variant V _H sequences containing exemplary Kabat CDRs

[00106] In some embodiments, the V _H sequences described herein comprise a variant of the exemplary Kabat CDR-H3, CDR-H2, and/or CDR-H1 sequence described herein.

[00107] In some aspects, the Kabat CDR-H3 sequence comprises, consists of, or primarily consists of a variant of the exemplary Kabat CDR-H3 sequence described herein. In some aspects, the Kabat CDR-H3 sequence contains, consists of, or primarily consists of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-H3 sequences. according to Kabat, given in the present description of the invention. In some aspects, the Kabat CDR-H3 sequence comprises, consists of, or essentially consists of any of the exemplary Kabat CDR-H3 sequences described herein with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

[00108] In some aspects, the Kabat CDR-H2 sequence comprises, consists of, or primarily consists of a variant of the exemplary Kabat CDR-H2 sequence described herein. In some aspects, the Kabat CDR-H3 sequence contains, consists of, or primarily consists of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-H3 sequences. according to Kabat given in the present description of the invention. In some aspects, the Kabat CDR-H2 sequence comprises, consists of, or essentially consists of any of the exemplary Kabat CDR-H2 sequences described herein with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

[00109] In some aspects, the Kabat CDR-H1 sequence comprises, consists of, or primarily consists of a variant of the exemplary Kabat CDR-H1 sequence described herein. In some aspects, the CDR-H1 sequence according to Kabat contains, consists of, or mainly consists of a sequence having a minimum of 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-H1 sequences according to Kabat given in the present description of the invention. In some aspects, the Kabat CDR-H1 sequence comprises, consists of, or essentially consists of any of the illustrative Kabat CDR-H1 sequences described herein with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

2.2.2. V _H sequences containing exemplary Chothia CDRs

[00110] In some embodiments, the antibody comprises a V _H sequence comprising one or more Chothia CDR-H sequences comprising, consisting of, or primarily consisting of one or more exemplary Chothia CDR-H sequences described herein , and their variants.

2.2.2.1. CDR-H3 by Chothia

[00111] In some embodiments, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 82-109. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 82. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 83. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 84. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 85. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H3 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 86. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 87. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 88. In some aspects, the antibody comprises a V _H sequence comprising a CDR- A Chothia H3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 89. In some aspects, an antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of sequence of SEQ ID: 90. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 91. In some aspects, the antibody contains a V _H sequence containing A Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 92. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 93. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 94. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 95. In some aspects, the antibody comprises a V _H sequence containing a Chothia CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 96. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 97. In some aspects, the antibody contains V _{An H} sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 98. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or , primarily consisting of the sequence of SEQ ID: 99. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 100. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 101. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of of or primarily consisting of the sequence of SEQ ID: 102. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 103. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 104. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising , consisting of or primarily consisting of the sequence of SEQ ID: 105. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 106. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 107. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 108. In some aspects, the antibody contains a V _H sequence containing a CDR-H3 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 109.

2.2.2.2. CDR-H2 by Chothia

[00112] In some embodiments, the antibody comprises a V _H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 46-62. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 46. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 47. In some aspects, the antibody contains a V _H sequence containing a CDR-H2 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 48. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 49. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H2 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 50. In some aspects, the antibody contains a V _H sequence containing a CDR-H2 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 51. In some aspects, the antibody contains a V _H sequence containing a CDR-H2 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 52. In some aspects, the antibody contains a V _H sequence containing CDR- A Chothia H2 sequence comprising, consisting of, or primarily consisting of SEQ ID: 53. In some aspects, an antibody comprises a V _H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or primarily consisting of sequence of SEQ ID: 54. In some aspects, the antibody contains a V _H sequence containing a CDR-H2 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 55. In some aspects, the antibody contains a V _H sequence containing A Chothia CDR-H2 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 56. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 57. In some aspects, the antibody contains a V _H sequence containing a CDR-H2 sequence according to Chothia containing, consisting of, or primarily consisting of the sequence of SEQ ID: 58. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H2 sequence comprising, consisting of, or primarily consisting of the _sequence of SEQ ID: 59. consisting of the sequence of SEQ ID: 60. In some aspects, the antibody contains a V _H sequence containing a CDR-H2 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 61. In some aspects, the antibody contains V _{An H} sequence containing the Chothia CDR-H2 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 62.

2.2.2.3. CDR-H1 by Chothia

[00113] In some embodiments, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 1-24. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of SEQ ID: 1. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 2. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 3. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 4. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H1 sequence Chothia sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 5. In some aspects, the antibody comprises a V _H sequence comprising a CDR-H1 Chothia sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 6. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 7. In some aspects, the antibody contains a V _H sequence containing CDR- A Chothia H1 sequence comprising, consisting of, or primarily consisting of SEQ ID: 8. In some aspects, an antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of sequence of SEQ ID: 9. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 10. In some aspects, the antibody contains a V _H sequence containing A Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 11. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 12. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 13. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of SEQ ID: 14. In some aspects, the antibody comprises a V _H sequence containing a Chothia CDR-H1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 15. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 16. In some aspects, the antibody contains V _{An H} sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 17. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or , primarily consisting of the sequence of SEQ ID: 18. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 19. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 20. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of of or primarily consisting of the sequence of SEQ ID: 21. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 22. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 23. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising consisting of or primarily consisting of the sequence SEQ ID: 24.

2.2.2.4. CDR-H3 by Chothia + CDR-H2 by Chothia

[00114] In some embodiments, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 82-109 and a Chothia CDR-H2 sequence containing, consisting of, or mainly consisting of a sequence selected from the sequences of SEQ ID: 46-62. In some aspects, the Chothia CDR-H3 sequence and the Chothia CDR-H2 sequence are both derived from the same exemplary V _H sequence provided herein. For example, in some aspects, Chothia's CDR-H3 and Chothia's CDR-H2 are both derived from the same exemplary V _H sequence selected from SEQ ID: 179-218.

2.2.2.5. CDR-H3 by Chothia + CDR-H1 by Chothia

[00115] In some embodiments, the antibody comprises a V _H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 82-109, and a CDR-H1 sequence of Chothia containing, consisting of or mainly consisting of a sequence selected from the sequences of SEQ ID: 1-24. In some aspects, the Chothia CDR-H3 sequence and the Chothia CDR-H1 sequence are both derived from the same exemplary V _H sequence provided herein. For example, in some aspects, Chothia's CDR-H3 and Chothia's CDR-H1 are both derived from the same exemplary V _H sequence selected from SEQ ID: 179-218.

2.2.2.6. CDR-H1 by Chothia + CDR-H2 by Chothia

[00116] In some embodiments, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 1-24, and a CDR-H2 sequence of Chothia containing, consisting of or mainly consisting of a sequence selected from the sequences of SEQ ID: 46-62. In some aspects, the Chothia CDR-H1 sequence and the Chothia CDR-H2 sequence are both derived from the same exemplary V _H sequence provided herein. For example, in some aspects, Chothia's CDR-H1 and Chothia's CDR-H2 are both derived from the same exemplary V _H sequence selected from SEQ ID: 179-218.

2.2.2.7. CDR-H1 by Chothia + CDR-H2 by Chothia + CDR-H3 by Chothia

[00117] In some embodiments, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 1-24, and a CDR-H2 sequence of Chothia containing, consisting of or primarily consisting of a sequence selected from the sequences of SEQ ID: 46-62, and a CDR-H3 sequence according to Chothia containing, consisting of or primarily consisting of a sequence selected from the sequences of SEQ ID: 82-109. In some aspects, the Chothia CDR-H1 sequence, Chothia CDR-H2 sequence, and Chothia CDR-H3 sequence are all derived from a single exemplary V _H sequence provided herein. For example, in some aspects, Chothia's CDR-H1, Chothia's CDR-H2, and Chothia's CDR-H3 are all derived from a single exemplary V _H sequence selected from SEQ ID: 179-218.

[00118] In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 1, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 46, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 2, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 47, and a CDR-H3 sequence of Chothia containing the sequence SEQ ID: 83. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence SEQ ID: 1, a CDR-H2 sequence according to Chothia containing the sequence SEQ ID: 46, and CDR- H3 sequence according to Chothia, containing the sequence of SEQ ID: 84. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 2, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 47, and a Chothia CDR-H3 sequence comprising SEQ ID: 83. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID: 3, a Chothia CDR-H2 sequence comprising SEQ ID: NO: 47, and a CDR-H3 sequence according to Chothia, containing the sequence of SEQ ID: 86. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence SEQ ID: 4, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 46, and a CDR-H3 sequence according to Chothia, containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 2, a CDR-H2 sequence by Chothia containing the sequence of SEQ ID: 46, and a CDR-H3 sequence by Chothia containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence by Chothia containing the sequence of SEQ ID: 5, CDR -H2 sequence according to Chothia, _containing the sequence of SEQ ID: 49; 6, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 50, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence SEQ ID: 2, a CDR-H2 sequence according to Chothia containing the sequence of SEQ ID: 47, and a CDR-H3 sequence according to Chothia containing the sequence of SEQ ID: 82. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence of SEQ ID: 7, a CDR-H2 sequence according to Chothia containing the sequence of SEQ ID: 51, and a CDR-H3 sequence according to Chothia containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing CDR-H1 a Chothia sequence comprising SEQ ID: 8, a Chothia CDR-H2 sequence comprising SEQ ID: 52, and a Chothia CDR-H3 sequence comprising SEQ ID: 88. In some aspects, the antibody comprises a V _H sequence comprising A Chothia CDR-H1 sequence containing the sequence of SEQ ID: 9, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 53, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 89. In some aspects, the antibody contains V _H a sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID: 10, a Chothia CDR-H2 sequence comprising SEQ ID: 52, and a Chothia CDR-H3 sequence comprising SEQ ID: 90. In some aspects, an antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence SEQ ID: 11, a CDR-H2 sequence according to Chothia containing the sequence SEQ ID: 54, and a CDR-H3 sequence according to Chothia containing the sequence SEQ ID: 91. B In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 12, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 53, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 92. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 13, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 52, and a Chothia CDR-H3 sequence containing the sequence SEQ ID: 93. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 10, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 52, and a CDR-H3 sequence according to Chothia , containing the sequence of SEQ ID: 92. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 14, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 54, and CDR-H3 a Chothia sequence comprising the sequence of SEQ ID: 87. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising the sequence of SEQ ID: 15, a Chothia CDR-H2 sequence comprising the sequence of SEQ ID: 55, and A Chothia CDR-H3 sequence comprising SEQ ID: 87. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID: 16, a Chothia CDR-H2 sequence comprising SEQ ID: 56, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 17, a Chothia CDR-H2 sequence containing the sequence SEQ ID: 51, and a CDR-H3 sequence according to Chothia, containing the sequence of SEQ ID: 94. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 18, a CDR-H2 sequence according to Chothia , containing the sequence of SEQ ID: 57, and a CDR-H3 sequence according to Chothia, containing the sequence of SEQ ID: 95. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 19, CDR-H2 a Chothia sequence containing the sequence of SEQ ID: 57; and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 96. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 21, A Chothia CDR-H2 sequence comprising SEQ ID: 57 and a Chothia CDR-H3 sequence comprising SEQ ID: 94. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID: : 17, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 51, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 97. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing _sequence of SEQ ID: 22, a CDR-H2 sequence according to Chothia containing the sequence of SEQ ID: 51, and a CDR-H3 sequence according to Chothia containing the sequence of SEQ ID: 98. Chothia containing the sequence of SEQ ID: 22, a CDR-H2 sequence of Chothia containing the sequence of SEQ ID: 51, and a CDR-H3 sequence of Chothia containing the sequence of SEQ ID: 99. In some aspects, the antibody contains a V _H sequence containing the CDR- A Chothia H1 sequence comprising SEQ ID: 22, a Chothia CDR-H2 sequence comprising SEQ ID: 51, and a Chothia CDR-H3 sequence comprising SEQ ID: 100. In some aspects, the antibody comprises a V _H sequence, containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 17, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 51, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 101. In some aspects, the antibody contains V _{An H} sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID: 17, a Chothia CDR-H2 sequence comprising SEQ ID: 59, and a Chothia CDR-H3 sequence comprising SEQ ID: 102. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 17, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 51, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 103. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 23, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 60, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: : 104. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 17, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 51, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 105. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 17, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 51, and a CDR-H3 sequence of Chothia containing the sequence of SEQ ID: 106. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence SEQ ID: 17, a CDR-H2 sequence according to Chothia containing the sequence SEQ ID: 51, and CDR- H3 sequence according to Chothia, containing the sequence of SEQ ID: 107. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 17, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 61, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 108. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 17, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: : 62, and a Chothia CDR-H3 sequence containing SEQ ID: 109.

[00119] In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 2, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 46, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 83. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 2, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 46, and a CDR-H3 sequence of Chothia containing the sequence SEQ ID: 84. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence SEQ ID: 2, a CDR-H2 sequence according to Chothia containing the sequence SEQ ID: 46, and CDR- H3 sequence according to Chothia, containing the sequence of SEQ ID: 85. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 2, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 46, and a Chothia CDR-H3 sequence comprising SEQ ID: 86. In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID: 2, a Chothia CDR-H2 sequence comprising SEQ ID: : 47, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 84. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 2, a Chothia CDR-H2 sequence containing sequence of SEQ ID: 47, and a CDR-H3 sequence according to Chothia, containing the sequence of SEQ ID: 86. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 1, a CDR-H2 sequence of Chothia containing the sequence of SEQ ID: 46, and a CDR-H3 sequence of Chothia containing the sequence of SEQ ID: 83. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence of Chothia containing the sequence of SEQ ID: 1, CDR- A Chothia H2 sequence comprising SEQ ID: 46 and a Chothia CDR-H3 sequence comprising SEQ ID: 86. In some aspects, an antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID: 10 , a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 53, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 93. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 10, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 55, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence of Chothia, containing the sequence of SEQ ID: 10, a CDR-H2 sequence according to Chothia containing the sequence of SEQ ID: 54, and a CDR-H3 sequence according to Chothia containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing the CDR-H1 sequence by Chothia containing the sequence of SEQ ID: 10, a CDR-H2 sequence by Chothia containing the sequence of SEQ ID: 52, and a CDR-H3 sequence by Chothia containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing the CDR -H1 sequence according to Chothia, containing the sequence of SEQ ID: 8, CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 52, and CDR-H3 sequence according to Chothia, containing the sequence SEQ ID: 87. In some aspects, the antibody contains a V _H sequence , containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 8, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 53, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 87. In some aspects, the antibody contains V _H sequence containing Chothia CDR-H1 sequence containing SEQ ID: 9, Chothia CDR-H2 sequence containing SEQ ID: 53, and Chothia CDR-H3 sequence containing SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 10, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 53, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 87 In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising the sequence of SEQ ID: 10, a Chothia CDR-H2 sequence comprising the sequence of SEQ ID: 54, and a Chothia CDR-H3 sequence comprising the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 10, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 52, and a CDR-H3 sequence according to Chothia, containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 10, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 53, and a CDR-H3 sequence by Chothia containing the sequence of SEQ ID: 93. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence by Chothia containing the sequence of SEQ ID: 10, a CDR-H2 sequence by Chothia containing the sequence of SEQ ID: 52, and a CDR -H3 sequence according to Chothia, containing the sequence of SEQ ID: 93. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 11, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 54 , and a CDR-H3 sequence according to Chothia containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence of SEQ ID: 12, a CDR-H2 sequence according to Chothia containing the sequence SEQ ID: 53, and a CDR-H3 sequence according to Chothia, containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 13, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 52, and a CDR-H3 sequence according to Chothia, containing the sequence of SEQ ID: 87. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 13, a CDR-H2 sequence by Chothia containing the sequence of SEQ ID: 52, and a CDR-H3 sequence by Chothia containing the sequence of SEQ ID: 90. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence by Chothia containing the sequence of SEQ ID: 15, CDR -H2 sequence according to Chothia, _containing the sequence of SEQ ID: 52; 18, Chothia CDR-H2 sequence containing SEQ ID: 57 and Chothia CDR-H3 sequence containing SEQ ID: 94.

2.2.2.8. Variant V _H sequences containing exemplary Chothia CDRs

[00120] In some embodiments, the V _H sequences described herein comprise a variant of the exemplary Chothia CDR-H3, CDR-H2, and/or CDR-H1 sequence described herein.

[00121] In some aspects, the Chothia CDR-H3 sequence comprises, consists of, or primarily consists of a variant of the exemplary Chothia CDR-H3 sequence described herein. In some aspects, the Chothia CDR-H3 sequence contains, consists of, or primarily consists of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-H3 sequences. according to Chothia, given in the present description of the invention. In some aspects, the Chothia CDR-H3 sequence comprises, consists of, or essentially consists of any of the exemplary Chothia CDR-H3 sequences provided herein with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

[00122] In some aspects, the Chothia CDR-H2 sequence comprises, consists of, or primarily consists of a variant of the exemplary Chothia CDR-H2 sequence described herein. In some aspects, the Chothia CDR-H2 sequence contains, consists of, or primarily consists of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-H2 sequences. according to Chothia, given in the present description of the invention. In some aspects, the Chothia CDR-H2 sequence comprises, consists of, or essentially consists of any of the exemplary Chothia CDR-H2 sequences provided herein with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

[00123] In some aspects, the Chothia CDR-H1 sequence comprises, consists of, or primarily consists of a variant of the exemplary Chothia CDR-H1 sequence described herein. In some aspects, the Chothia CDR-H1 sequence contains, consists of, or primarily consists of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-H1 sequences. according to Chothia, given in the present description of the invention. In some aspects, the Chothia CDR-H1 sequence comprises, consists of, or essentially consists of any of the exemplary Chothia CDR-H1 sequences provided herein with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

2.3. V _H sequences

[00124] In some embodiments, the antibody comprises a V _H sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 179-218. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 179. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 179. 180. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 181. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 182. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 183. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of sequence of SEQ ID: 184. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 185. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 186. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 187. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily thus consisting of the sequence of SEQ ID: 188. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 189 In some aspects, the antibody contains a V _H sequence containing, consisting of, or, primarily consisting of the sequence of SEQ ID: 190. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 191. In some aspects, the antibody contains a V _H sequence containing, consisting of or primarily consisting of the sequence of SEQ ID: 192. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 193. In some aspects, the antibody contains a V _H sequence containing, consisting of or primarily consisting of the sequence of SEQ ID: 194. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 195. In some aspects, the antibody contains a V _H sequence, comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 196. In some aspects, the antibody comprises a V _H sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 197. In some aspects, the antibody comprises a V _H a sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 198. In some aspects, the antibody comprises a V _H sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 199. In some aspects, the antibody comprises A V _H sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 200. In some aspects, an antibody comprises a V _H sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 201. In some aspects, the antibody comprises a V _H sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 202. In some aspects, the antibody comprises a V _H sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 203. B in some aspects, the antibody comprises a V _H sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 204. In some aspects, the antibody comprises a V _H sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 205 In some aspects, the antibody comprises a V _H sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 206. In some aspects, the antibody comprises a V _H sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: : 207. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 208. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence SEQ ID: 209. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 210. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of from the sequence of SEQ ID: 211. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 212. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily , consisting of the sequence of SEQ ID: 213. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 214. In some aspects, the antibody contains a V _H sequence containing, consisting of, or, primarily consisting of the sequence of SEQ ID: 215. In some aspects, the antibody contains a V _H sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 216. In some aspects, the antibody contains a V _H sequence containing, consisting of or primarily consisting of SEQ ID: 217. In some aspects, the antibody comprises a V _H sequence comprising, consisting of, or primarily consisting of SEQ ID: 218.

2.3.1. Variants of V _H sequences

[00125] In some embodiments, the V _H sequences provided herein comprise, consist of, or primarily consist of a variant of the exemplary V _H sequence provided herein.

[00126] In some aspects, the V _H sequence comprises, consists of, or primarily consists of a variant of the exemplary V _H sequence described herein. In some aspects, the V _H sequence contains, consists of, or primarily consists of a sequence with at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, and 99.5% identity with any of the illustrative V _H sequences given in the present description of the invention.

[00127] In some embodiments, the V _H sequence comprises, consists of, or primarily consists of any of the V _H sequences described herein, 20 or less, 19 or less, 18 or less, 17 or less, 16 15 or less, 14 or less, 13 or less, 12 or less, 11 or less, 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less , 3 or less, 2 or less, or 1 or less amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

2.4. CDR-L3 sequences

[00128] In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 141-166. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 141. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 142. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 143. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of consisting of the sequence of SEQ ID: 144. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 145. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or , primarily consisting of the sequence of SEQ ID: 146. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 147. In some aspects, the antibody contains a CDR-L3 sequence containing , consisting of or primarily consisting of the sequence of SEQ ID: 148. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 149. In some aspects, the antibody contains CDR-L3 An L3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 150. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 151. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 152. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 153 In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 154. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence SEQ ID: 155. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 156. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily , consisting of the sequence of SEQ ID: 157. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 158. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of or primarily consisting of the sequence of SEQ ID: 159. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 160. In some aspects, the antibody contains a CDR-L3 sequence, containing, consisting of, or primarily consisting of the sequence of SEQ ID: 161. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 162. In some aspects, the antibody contains a CDR -L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 163. In some aspects, the antibody contains a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 164. In some In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 165. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 165. 166.

[00129] In some aspects, the CDR-L3 sequence comprises, consists of, or primarily consists of a variant of the exemplary sequence described herein: In some aspects, the CDR-L3 sequence contains, consists of, or primarily consists of the sequence having a minimum of 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-L3 sequences provided herein. In some aspects, the CDR-L3 sequence comprises, consists of, or primarily consists of any of the exemplary CDR-L3 sequences provided herein with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

2.5. V _L sequences containing exemplary CDRs

[00130] In some embodiments, the antibody comprises a V _L sequence comprising one or more CDR-L sequences comprising, consisting of, or primarily consisting of one or more of the illustrative CDR-L sequences described herein, and their options.

2.5.1. CDR-L3

[00131] In some embodiments, the antibody comprises a V _L sequence comprising a CDR-L3 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 141-166. In some aspects, the antibody comprises a V _L sequence comprising a CDR-L3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 141. In some aspects, the antibody comprises a V _L sequence comprising a CDR-L3 sequence comprising, consisting of of or primarily consisting of the sequence of SEQ ID: 142. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 143. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 144. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 145. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 146. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 147. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of sequence of SEQ ID: 148. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 149. In some aspects, the antibody contains a V _L sequence containing CDR-L3 An L3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 150. In some aspects, an antibody comprises a V _L sequence comprising a CDR-L3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 151. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 152. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing , consisting of or primarily consisting of the sequence of SEQ ID: 153. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 154. In some aspects, the antibody comprises a V _L sequence comprising a CDR-L3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 155. In some aspects, the antibody comprises a V _L sequence comprising a CDR-L3 sequence comprising, consisting of, or , primarily consisting of the sequence of SEQ ID: 156. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 157. In some aspects, the antibody contains V _{An L} sequence comprising a CDR-L3 sequence comprising, consisting of, or primarily consisting of SEQ ID: 158. In some aspects, an antibody comprises a V _L sequence comprising a CDR-L3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 159. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 160. In some aspects, the antibody contains a V _L sequence containing A CDR-L3 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 161. In some aspects, the antibody comprises a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 162. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 163. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 164. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 165. In some aspects, the antibody contains a V _L sequence containing a CDR-L3 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 166.

2.5.2. CDR-L2

[00132] In some embodiments, the antibody comprises a V _L sequence comprising a CDR-L2 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 125-140. In some aspects, the antibody comprises a V _L sequence comprising a CDR-L2 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 125. In some aspects, the antibody comprises a V _L sequence comprising a CDR-L2 sequence comprising, consisting of of or primarily consisting of the sequence of SEQ ID: 126. In some aspects, the antibody contains a V _L sequence containing a CDR-L2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 127. In some aspects, the antibody contains a V _L sequence containing a CDR-L2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 128. In some aspects, the antibody contains a V _L sequence containing a CDR-L2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 129. In some aspects, the antibody contains a V _L sequence containing a CDR-L2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 130. In some aspects, the antibody contains a V _L sequence containing a CDR-L2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 131. In some aspects, the antibody contains a V _L sequence containing a CDR-L2 sequence containing, consisting of, or primarily consisting of sequence of SEQ ID: 132. In some aspects, the antibody contains a V _L sequence containing a CDR-L2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 133. In some aspects, the antibody contains a V _L sequence containing CDR-L2 An L2 sequence comprising, consisting of, or primarily consisting of SEQ ID: 134. In some aspects, an antibody comprises a V _L sequence comprising a CDR-L2 sequence comprising, consisting of, or primarily consisting of SEQ ID: 135. In some aspects, the antibody contains a V _L sequence containing a CDR-L2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 136. In some aspects, the antibody contains a V _L sequence containing a CDR-L2 sequence containing , consisting of or primarily consisting of the sequence of SEQ ID: 137. In some aspects, the antibody contains a V _L sequence containing a CDR-L2 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 138. In some aspects, the antibody comprises a V _L sequence comprising a CDR-L2 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 139. In some aspects, the antibody comprises a V _L sequence comprising a CDR-L2 sequence comprising, consisting of, or , mainly consisting of the sequence SEQ ID: 140.

2.5.3. CDR-L1

[00133] In some embodiments, the antibody comprises a V _L sequence comprising a CDR-L1 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 110-124. In some aspects, the antibody comprises a V _L sequence comprising a CDR-L1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 110. In some aspects, the antibody comprises a V _L sequence comprising a CDR-L1 sequence comprising, consisting of of or primarily consisting of the sequence of SEQ ID: 111. In some aspects, the antibody contains a V _L sequence containing a CDR-L1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 112. In some aspects, the antibody contains a V _L sequence containing a CDR-L1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 113. In some aspects, the antibody contains a V _L sequence containing a CDR-L1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 114. In some aspects, the antibody contains a V _L sequence containing a CDR-L1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 115. In some aspects, the antibody contains a V _L sequence containing a CDR-L1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 116. In some aspects, the antibody contains a V _L sequence containing a CDR-L1 sequence containing, consisting of, or primarily consisting of sequence of SEQ ID: 117. In some aspects, the antibody contains a V _L sequence containing a CDR-L1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 118. In some aspects, the antibody contains a V _L sequence containing CDR-L1 An L1 sequence comprising, consisting of, or primarily consisting of SEQ ID: 119. In some aspects, an antibody comprises a V _L sequence comprising a CDR-L1 sequence comprising, consisting of, or primarily consisting of SEQ ID: 120. In some aspects, the antibody contains a V _L sequence containing a CDR-L1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 121. In some aspects, the antibody contains a V _L sequence containing a CDR-L1 sequence containing , consisting of or primarily consisting of the sequence of SEQ ID: 122. In some aspects, the antibody contains a V _L sequence containing a CDR-L1 sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 123. In some In aspects, the antibody comprises a V _L sequence comprising a CDR-L1 sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 124.

2.5.4. CDR-L3 + CDR-L2

[00134] In some embodiments, the antibody comprises a V _L sequence comprising a CDR-L3 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 141-166, and a CDR-L2 sequence comprising, consisting of or mainly consisting of a sequence selected from the sequences of SEQ ID: 125-140. In some aspects, the CDR-L3 sequence and the CDR-L2 sequence are both derived from the same exemplary V _L sequence provided herein. For example, in some aspects, CDR-L3 and CDR-L2 are both derived from the same exemplary V _L sequence selected from SEQ ID NOs: 219-248.

2.5.5. CDR-L3 + CDR-L1

[00135] In some embodiments, the antibody comprises a V _L sequence comprising a CDR-L3 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 141-166, and a CDR-L1 sequence comprising, consisting of or mainly consisting of a sequence selected from the sequences of SEQ ID: 110-124. In some aspects, the CDR-L3 sequence and the CDR-L1 sequence are both derived from the same exemplary V _L sequence provided herein. For example, in some aspects, CDR-L3 and CDR-L1 are both derived from the same exemplary V _L sequence selected from SEQ ID: 219-248.

2.5.6. CDR-L1 + CDR-L2

[00136] In some embodiments, the antibody comprises a V _L sequence comprising a CDR-L1 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 110-124, and a CDR-L2 sequence comprising, consisting of or mainly consisting of a sequence selected from the sequences of SEQ ID: 125-140. In some aspects, the CDR-L1 sequence and the CDR-L2 sequence are both derived from the same exemplary V _L sequence provided herein. For example, in some aspects, CDR-L1 and CDR-L2 are both derived from the same exemplary V _L sequence selected from SEQ ID: 219-248.

2.5.7. CDR-L1 + CDR-L2 + CDR-L3

[00137] In some embodiments, the antibody comprises a V _L sequence comprising a CDR-L1 sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 110-124, and a CDR-L2 sequence comprising, consisting of or primarily consisting of a sequence selected from sequences of SEQ ID: 125-140, and a CDR-L3 sequence containing, consisting of, or primarily consisting of a sequence selected from sequences of SEQ ID: 141-166. In some aspects, the CDR-L1 sequence, CDR-L2 sequence, and CDR-L3 sequence are all derived from a single illustrative V _L sequence provided herein. For example, in some aspects, CDR-L1, CDR-L2, and CDR-L3 are all derived from one exemplary V _L sequence selected from SEQ ID NOs: 219-248.

[00138] In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 141. B in some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 111, a CDR-L2 sequence containing the sequence of SEQ ID: 126, and a CDR-L3 sequence containing the sequence of SEQ ID: 142. In some aspects, the antibody contains A VL sequence comprising a CDR-L1 sequence comprising SEQ ID: 110, a CDR-L2 sequence comprising SEQ ID: 127, and a CDR-L3 sequence comprising a sequence selected from SEQ ID: 142. In some aspects, the antibody comprises A VL sequence comprising a CDR-L1 sequence comprising SEQ ID: 110, a CDR-L2 sequence comprising SEQ ID: 125, and a CDR-L3 sequence comprising SEQ ID: 143. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising the sequence of SEQ ID: 112, a CDR-L2 sequence comprising the sequence of SEQ ID: 128, and a CDR-L3 sequence comprising the sequence of SEQ ID: 144. In some aspects, the antibody comprises a VL sequence comprising the CDR-L1 sequence , containing the sequence of SEQ ID: 111, a CDR-L2 sequence containing the sequence of SEQ ID: 126, and a CDR-L3 sequence containing the sequence of SEQ ID: 145. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 113, a CDR-L2 sequence containing the sequence of SEQ ID: 129, and a CDR-L3 sequence containing the sequence of SEQ ID: 146. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 114, a CDR-L2 sequence containing the sequence of SEQ ID: 130, and a CDR-L3 sequence containing the sequence of SEQ ID: 147. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence , containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 116, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 149. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 a sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 132, and a CDR-L3 sequence containing the sequence SEQ ID NO: 149. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 117, a CDR-L2 sequence containing the sequence of SEQ ID: 133, and a CDR-L3 sequence containing the sequence of SEQ ID: 150. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 134, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 118, a CDR-L2 sequence containing the sequence of SEQ ID: 135, and a CDR-L3 sequence containing the sequence of SEQ ID: 151. In some aspects, the antibody contains a VL a sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 118, a CDR-L2 sequence containing the sequence of SEQ ID: 135, and a CDR-L3 sequence containing the sequence of SEQ ID: 152. In some aspects, the antibody contains a VL sequence containing the CDR -L1 sequence containing the sequence of SEQ ID: 118, CDR-L2 sequence containing the sequence of SEQ ID: 136, and CDR-L3 sequence containing the sequence of SEQ ID: 152. In some aspects, the antibody contains a VL sequence containing the CDR-L1 sequence, containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 153. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: : 119, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 154. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 120, CDR -L2 sequence containing the sequence of SEQ ID: 137, and a CDR-L3 sequence containing the sequence of SEQ ID: 155. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence, containing the sequence of SEQ ID: 138, and a CDR-L3 sequence containing the sequence of SEQ ID: 156. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence containing the sequence of SEQ ID: 156. : 138, and a CDR-L3 sequence containing the sequence of SEQ ID: 157. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 122, a CDR-L2 sequence containing the sequence of SEQ ID: 138, and A CDR-L3 sequence comprising the sequence of SEQ ID: 158. In some aspects, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising the sequence of SEQ ID: 121, a CDR-L2 sequence comprising the sequence of SEQ ID: 138, and a CDR-L3 sequence containing the sequence of SEQ ID: 159. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 118, a CDR-L2 sequence containing the sequence of SEQ ID: 135, and a CDR-L3 sequence containing the sequence of SEQ ID: 160. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence containing the sequence of SEQ ID: 139, and a CDR-L3 sequence containing the sequence of SEQ ID: 161. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 123, a CDR-L2 sequence containing the sequence of SEQ ID: 140, and a CDR-L3 sequence containing the sequence of SEQ ID: 162. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence containing the sequence of SEQ ID: 138, and a CDR-L3 sequence containing the sequence of SEQ ID: 163. In some aspects, the antibody contains a VL sequence, containing a CDR-L1 sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence containing the sequence of SEQ ID: 139, and a CDR-L3 sequence containing the sequence of SEQ ID: 164. In some aspects, the antibody contains a VL sequence containing CDR-L1 a sequence containing the sequence of SEQ ID: 120, a CDR-L2 sequence containing the sequence of SEQ ID: 137, and a CDR-L3 sequence containing the sequence of SEQ ID: 165. In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence SEQ ID: 124, a CDR-L2 sequence containing SEQ ID: 125, and a CDR-L3 sequence containing SEQ ID: 166.

[00139] In some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 128, and a CDR-L3 sequence containing the sequence of SEQ ID: 144. B in some aspects, the antibody contains a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 144. In some aspects, the antibody contains A VL sequence comprising a CDR-L1 sequence comprising SEQ ID: 110, a CDR-L2 sequence comprising SEQ ID: 126, and a CDR-L3 sequence comprising a sequence selected from SEQ ID: 144. In some aspects, the antibody comprises A VL sequence comprising a CDR-L1 sequence comprising SEQ ID: 116, a CDR-L2 sequence comprising SEQ ID: 131, and a CDR-L3 sequence comprising SEQ ID: 150. In some aspects, the antibody comprises a VL sequence comprising CDR-L1 sequence containing SEQ ID: 117, CDR-L2 sequence containing SEQ ID: 134, and CDR-L3 sequence containing SEQ ID: 150.

2.5.8. Variants V _L sequences containing illustrative CDR-L

[00140] In some embodiments, the V _L sequences described herein comprise a variant of the exemplary CDR-L3, CDR-L2, and/or CDR-L1 sequence described herein.

[00141] In some aspects, the CDR-L3 sequence comprises, consists of, or primarily consists of a variant of the exemplary sequence described herein: In some aspects, the CDR-L3 sequence contains, consists of, or primarily consists of the sequence having a minimum of 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-L3 sequences provided herein. In some aspects, the CDR-L3 sequence comprises, consists of, or primarily consists of any of the exemplary CDR-L3 sequences provided herein with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

[00142] In some aspects, the CDR-L2 sequence comprises, consists of, or primarily consists of a variant of the exemplary CDR-L2 sequence described herein. In some aspects, a CDR-L2 sequence contains, consists of, or primarily consists of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-L2 sequences provided in the present description of the invention. In some aspects, the CDR-L2 sequence comprises, consists of, or primarily consists of any of the exemplary CDR-L2 sequences provided herein with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

[00143] In some aspects, the CDR-L1 sequence comprises, consists of, or primarily consists of a variant of the exemplary CDR-L1 sequence described herein. In some aspects, a CDR-L1 sequence contains, consists of, or primarily consists of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-L1 sequences provided in the present description of the invention. In some aspects, the CDR-L1 sequence comprises, consists of, or primarily consists of any of the exemplary CDR-L1 sequences provided herein with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

2.6. V _L sequences

[00144] In some embodiments, the antibody comprises a V _L sequence comprising, consisting of, or primarily consisting of a sequence selected from SEQ ID: 219-248. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 219. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 219. 220. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 221. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 222. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 223. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of sequence of SEQ ID: 224. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 225. In some aspects, the antibody contains a V _L sequence containing, consisting of, or mainly consisting of consisting of the sequence of SEQ ID: 226. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 227. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 228. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 229. In some aspects, the antibody contains a V _L sequence containing, consisting of, or , primarily consisting of the sequence of SEQ ID: 230. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 231. In some aspects, the antibody contains a V _L sequence containing, consisting of or primarily consisting of the sequence of SEQ ID: 232. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 233. In some aspects, the antibody contains a V _L sequence containing , consisting of or primarily consisting of the sequence of SEQ ID: 234. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 235. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 236. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 237. In some aspects, the antibody contains V _{An L} sequence comprising, consisting of, or primarily consisting of SEQ ID: 238. In some aspects, an antibody comprises a V _L sequence comprising, consisting of, or primarily consisting of SEQ ID: 239. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 240. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 241. In some In aspects, the antibody comprises a V _L sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 242. In some aspects, the antibody comprises a V _L sequence comprising, consisting of, or primarily consisting of the sequence of SEQ ID: 243. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 244. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 245. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 246. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 247. In some aspects, the antibody contains a V _L sequence containing, consisting of, or primarily consisting of the sequence of SEQ ID: 248.

2.6.1. Variants of V _L sequences

[00145] In some embodiments, the V _L sequences provided herein comprise, consist of, or primarily consist of a variant of the exemplary V _L sequence described herein.

[00146] In some aspects, the V _L sequence comprises, consists of, or primarily consists of a variant of the exemplary V _L sequence described herein. In some aspects, the V _L sequence contains, consists of, or primarily consists of a sequence with at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, and 99.5% identity with any of the illustrative V _L sequences given in the present description of the invention.

[00147] In some embodiments, the V _L sequence comprises, consists of, or primarily consists of any of the V _L sequences described herein, 20 or less, 19 or less, 18 or less, 17 or less, 16 or less, 15 or less, 14 or less, 13 or less, 12 or less, 11 or less, 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less , 3 or less, 2 or less, or 1 or less amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

2.7. Couples

2.7.1. Pairs CDR-H3 - CDR-L3

[00148] In some embodiments, the antibody comprises a CDR-H3 sequence and a CDR-L3 sequence. In some aspects, the CDR-H3 sequence is part of V _H and the CDR-L3 sequence is part of VL.

[00149] In some aspects, the CDR-H3 sequence is a CDR-H3 sequence containing, consisting of, or primarily consisting of the sequences of SEQ ID: 82-109, and the CDR-L3 sequence is a CDR-L3 sequence containing, consisting of or primarily consisting of the sequences of SEQ ID: 141-166.

[00150] In some aspects, the CDR-H3 sequence is SEQ ID: 82, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00151] In some aspects, the CDR-H3 sequence is SEQ ID: 82, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00152] In some aspects, the CDR-H3 sequence is SEQ ID: 84, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00153] In some aspects, the CDR-H3 sequence is SEQ ID: 85, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00154] In some aspects, the CDR-H3 sequence is SEQ ID: 86, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00155] In some aspects, the CDR-H3 sequence is SEQ ID: 87, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00156] In some aspects, the CDR-H3 sequence is SEQ ID: 88, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00157] In some aspects, the CDR-H3 sequence is SEQ ID: 89, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ED: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00158] In some aspects, the CDR-H3 sequence is SEQ ID: 90, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ LD: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00159] In some aspects, the CDR-H3 sequence is SEQ ID: 91, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ LD: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects, In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 16S. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00160] In some aspects, the CDR-H3 sequence is SEQ ID: 92, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00161] In some aspects, the CDR-H3 sequence is SEQ ID: 93, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00162] In some aspects, the CDR-H3 sequence is SEQ ID: 94, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00163] In some aspects, the CDR-H3 sequence is SEQ ID: 95, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00164] In some aspects, the CDR-H3 sequence is SEQ ID: 96, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00165] In some aspects, the CDR-H3 sequence is SEQ ID: 97, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00166] In some aspects, the CDR-H3 sequence is SEQ ID: 98, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00167] In some aspects, the CDR-H3 sequence is SEQ ID: 99, and the CDR-L3 sequence is selected from sequence IDs: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00168] In some aspects, the CDR-H3 sequence is SEQ ID: 100, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00169] In some aspects, the CDR-H3 sequence is SEQ ID: 101, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00170] In some aspects, the CDR-H3 sequence is SEQ ID: 102, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00171] In some aspects, the CDR-H3 sequence is SEQ ID: 103, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00172] In some aspects, the CDR-H3 sequence is SEQ ID: 104, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ GO. 161. In some aspects, the CDR-L3 sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, CDR-L3 the sequence is SEQ ID: 165. In some aspects of the CDR-L3, the sequence is SEQ ID: 166.

[00173] In some aspects, the CDR-H3 sequence is SEQ ID: 105, and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00174] In some aspects, the CDR-H3 sequence is SEQ ID: 106, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00175] In some aspects, the CDR-H3 sequence is SEQ ID: 107, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00176] In some aspects, the CDR-H3 sequence is SEQ ID: 108, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

[00177] In some aspects, the CDR-H3 sequence is SEQ ID: 109, and the CDR-L3 sequence is selected from SEQ ID: 141-166. In some aspects, the CDR-L3 sequence is SEQ ID: 141. In some aspects, the CDR-L3 sequence is SEQ ID: 142. In some aspects, the CDR-L3 sequence is SEQ ID: 143. In some aspects, the CDR-L3 sequence is sequence of SEQ ID: 144. In some aspects, the CDR-L3 sequence is SEQ ID: 145. In some aspects, the CDR-L3 sequence is SEQ ID: 146. In some aspects, the CDR-L3 sequence is SEQ ID: 147. In some aspects In some aspects, the CDR-L3 sequence is SEQ ID: 148. In some aspects, the CDR-L3 sequence is SEQ ID: 149. In some aspects, the CDR-L3 sequence is SEQ ID: 150. In some aspects, the CDR-L3 sequence is SEQ ID: 151. In some aspects, the CDR-L3 sequence is SEQ ID: 152. In some aspects, the CDR-L3 sequence is SEQ ID: 153. In some aspects, the CDR-L3 sequence is SEQ ID: 154. In some aspects, the CDR The -L3 sequence is SEQ ID: 155. In some aspects, the CDR-L3 sequence is SEQ ID: 156. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 157. In some aspects, the CDR-L3 sequence is SEQ ID: 156. 158. In some aspects, the CDR-L3 sequence is SEQ ID: 159. In some aspects, the CDR-L3 sequence is SEQ ID: 160. In some aspects, the CDR-L3 sequence is SEQ ID: 161. In some aspects, CDR-L3 the sequence is SEQ ID: 162. In some aspects, the CDR-L3 sequence is SEQ ID: 163. In some aspects, the CDR-L3 sequence is SEQ ID: 164. In some aspects, the CDR-L3 sequence is SEQ ID: 165. In some aspects, the CDR-L3 sequence is SEQ ID: 166.

2.7.1.1. Pair options CDR-H3 - CDR-L3

[00178] In some embodiments, the CDR-H3-CDR-L3 pairs described herein comprise a variant of the exemplary CDR-H3 and/or CDR-L1 sequence described herein.

[00179] In some aspects, the CDR-H3 sequence comprises, consists of, or primarily consists of a variant of the exemplary CDR-H3 sequence provided herein: In some aspects, the CDR-H3 sequence comprises, consists of, or primarily consists of consists of a sequence having a minimum of 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-H3 sequences provided herein. In some aspects, a CDR-H3 sequence comprises, consists of, or primarily consists of any of the illustrative CDR-H3 sequences provided herein, with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

[00180] In some aspects, the CDR-L3 sequence comprises, consists of, or primarily consists of a variant of the exemplary sequence described herein: In some aspects, the CDR-L3 sequence contains, consists of, or primarily consists of the sequence having a minimum of 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-L3 sequences provided herein. In some aspects, the CDR-L3 sequence comprises, consists of, or primarily consists of any of the exemplary CDR-L3 sequences provided herein with 1, 2, or 3 amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

2.7.2. Pairs V _H -V _L

[00181] In some embodiments, the antibody comprises a V _H sequence and a V _L sequence.

[00182] In some aspects, the V _H sequence is a V _H sequence comprising, consisting of, or primarily consisting of the sequences of SEQ ID: 179-218, and the V _L sequence is a V _L sequence containing, consisting of, or primarily , consisting of sequences SEQ ID: 219-248.

[00183] In some aspects, the V _H sequence is SEQ ID: 179, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00184] In some aspects, the V _H sequence is SEQ ID: 180, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00185] In some aspects, the V _H sequence is SEQ ID: 181, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00186] In some aspects, the V _H sequence is SEQ ID: 182, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00187] In some aspects, the V _H sequence is SEQ ID: 183, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00188] In some aspects, the V _H sequence is SEQ ID: 184, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 23S. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, the V L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 237. 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245. In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00189] In some aspects, the V _H sequence is SEQ ID: 185, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00190] In some aspects, the V _H sequence is SEQ ID: 186, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V L sequence is SEQ ID: 222 In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 224. : 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is SEQ ID: 230. In some aspects, the V _L sequence is SEQ ID: 231. In some aspects, the V _{L sequence is SEQ ID: 232. In some aspects, the V L} sequence is SEQ ID: 233. In some aspects, the V _L sequence is SEQ ID: 233. In some aspects, the V _L sequence is is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, V _{The L} sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In some aspects, In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245. In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00191] In some aspects, the V _H sequence is SEQ ID: 187, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00192] In some aspects, the V _H sequence is SEQ ID: 188, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00193] In some aspects, the V _H sequence is SEQ ID: 189, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00194] In some aspects, the V _H sequence is SEQ ID: 190, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00195] In some aspects, the V _H sequence is SEQ ID: 191, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00196] In some aspects, the V _H sequence is SEQ ID: 192, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00197] In some aspects, the V _H sequence is SEQ ID: 193, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00198] In some aspects, the V _H sequence is SEQ ID: 194, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00199] In some aspects, the V _H sequence is SEQ ID: 195, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00200] In some aspects, the V _H sequence is SEQ ID: 196, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00201] In some aspects, the V _H sequence is SEQ ID: 197, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00202] In some aspects, the V _H sequence is SEQ ID: 198, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00203] In some aspects, the V _H sequence is SEQ ID: 199, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 22S. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 227. 229. In some aspects, the V _L sequence is SEQ ID: 230. In some aspects, the V _L sequence is SEQ ID: 231. In some aspects, the V _L sequence is SEQ ID: 232. In some aspects, the V _L sequence is SEQ ID: 233. In some aspects, the V _L sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is the sequence of SEQ ID: 237. In some aspects, the V _L sequence is the sequence of SEQ ID: 238. In some aspects, the V _L sequence is the sequence of SEQ ID: 239. In some aspects, the V _L sequence is the sequence of SEQ ID: 240. In some aspects, the V _L sequence the sequence is SEQ ID: 241. In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, The V _L sequence is SEQ ID: 245. In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00204] In some aspects, the V _H sequence is SEQ ID: 200, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00205] In some aspects, the V _H sequence is SEQ ID: 201, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00206] In some aspects, the V _H sequence is SEQ ID: 202, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 22S. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 227. 229. In some aspects, the V _L sequence is SEQ ID: 230. In some aspects, the V _L sequence is SEQ ID: 231. In some aspects, the V _L sequence is SEQ ID: 232. In some aspects, the V _L sequence is SEQ ID: 233. In some aspects, the V _L sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is the sequence of SEQ ID: 237. In some aspects, the V _L sequence is the sequence of SEQ ID: 238. In some aspects, the V _L sequence is the sequence of SEQ ID: 239. In some aspects, the V _L sequence is the sequence of SEQ ID: 240. In some aspects, the V _L sequence the sequence is SEQ ID: 241. In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, The V _L sequence is SEQ ID: 245. In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00207] In some aspects, the V _H sequence is SEQ ID: 203, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00208] In some aspects, the V _H sequence is SEQ ID: 204, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00209] In some aspects, the V _H sequence is SEQ ID: 205, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00210] In some aspects, the V _H sequence is SEQ ID: 206, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00211] In some aspects, the V _H sequence is SEQ ID: 207, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00212] In some aspects, the V _H sequence is SEQ ID: 208, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00213] In some aspects, the V _H sequence is SEQ ID: 209, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00214] In some aspects, the V _H sequence is SEQ ID: 210, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00215] In some aspects, the V _H sequence is SEQ ID: 211, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00216] In some aspects, the V _H sequence is SEQ ID: 212, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00217] In some aspects, the V _H sequence is SEQ ID: 213, and the V _L sequence is selected from SEQ ID NOs: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00218] In some aspects, the V _H sequence is SEQ ID: 214, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227.

In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V L sequence is SEQ ID: 230. In some aspects, the V _L sequence is SEQ ID: 230. In some aspects, the V _L sequence is SEQ ID: 229. 231. In some aspects, the V _L sequence is SEQ ID: 232. In some aspects, the V _L sequence is SEQ ID: 233. In some aspects, the V _L sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, the V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is the sequence of SEQ ID: 239. In some aspects, the V _L sequence is the sequence of SEQ ID: 240. In some aspects, the V _L sequence is the sequence of SEQ ID: 241. In some aspects, the V _L sequence is the sequence of SEQ ID: 242. In some aspects, the V _L sequence the sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245. In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, The V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00219] In some aspects, the V _H sequence is SEQ ID: 215, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00220] In some aspects, the V _H sequence is SEQ ID: 216, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00221] In some aspects, the V _H sequence is SEQ ID: 217, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

[00222] In some aspects, the V _H sequence is SEQ ID: 218, and the V _L sequence is selected from SEQ ID: 219-248. In some aspects, the V _L sequence is SEQ ID: 219. In some aspects, the V _L sequence is SEQ ID: 220. In some aspects, the V L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 221. In some aspects, the V _L sequence is SEQ ID: 220. 222. In some aspects, the V _L sequence is SEQ ID: 223. In some aspects, the V _L sequence is SEQ ID: 224. In some aspects, the V _L sequence is SEQ ID: 225. In some aspects, the V _L sequence is SEQ ID: 226. In some aspects, the V _L sequence is SEQ ID: 227. In some aspects, the V _L sequence is SEQ ID: 228. In some aspects, the V _L sequence is SEQ ID: 229. In some aspects, the V _L sequence is the sequence of SEQ ID: 230. In some aspects, the V _L sequence is the sequence of SEQ ID: 231. In some aspects, the V _L sequence is the sequence of SEQ ID: 232. In some aspects, the V _L sequence is the sequence of SEQ ID: 233. In some aspects, the V _L the sequence is SEQ ID: 234. In some aspects, the V _L sequence is SEQ ID: 235. In some aspects, the V _L sequence is SEQ ID: 236. In some aspects, the V _L sequence is SEQ ID: 237. In some aspects, The V _L sequence is SEQ ID: 238. In some aspects, the V _L sequence is SEQ ID: 239. In some aspects, the V _L sequence is SEQ ID: 240. In some aspects, the V _L sequence is SEQ ID: 241. In In some aspects, the V _L sequence is SEQ ID: 242. In some aspects, the V _L sequence is SEQ ID: 243. In some aspects, the V _L sequence is SEQ ID: 244. In some aspects, the V _L sequence is SEQ ID: 245 In some aspects, the V _L sequence is SEQ ID: 246. In some aspects, the V _L sequence is SEQ ID: 247. In some aspects, the V _L sequence is SEQ ID: 248.

2.7.3. CDR-H1+CDR-H2+CDR-H3+CDR-L1+CDR-L2+CDR-L3

[00223] In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 25, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 63, and a Kabat CDR-H3 sequence containing sequence of SEQ ID: 82, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 141. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 26, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 64, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 83 , and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 111, a CDR-L2 sequence containing the sequence of SEQ ID: 126, and a CDR-L3 sequence containing the sequence of SEQ ID: 142. In some aspects, the antibody contains V _H a sequence containing a Kabat CDR-H1 sequence containing SEQ ID: 27, a Kabat CDR-H2 sequence containing SEQ ID: 65, and a Kabat CDR-H3 sequence containing SEQ ID: 84, and a VL sequence, containing a CDR-L1 sequence containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 141. In some aspects, the antibody contains a V _H sequence containing the CDR- H1 Kabat sequence containing SEQ ID: 26, CDR-H2 Kabat sequence containing SEQ ID: 64, and CDR-H3 Kabat sequence containing SEQ ID: 85, and VL sequence containing CDR-L1 sequence , containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 141. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Kabat, containing the sequence of SEQ ID: 26, a CDR-H2 sequence by Kabat containing the sequence of SEQ ID: 64, and a CDR-H3 sequence by Kabat containing the sequence of SEQ ID: 86, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID : 110, a CDR-L2 sequence containing the sequence of SEQ ID: 127, and a CDR-L3 sequence containing the sequence of SEQ ID: 142. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 25, a Kabat CDR-H2 sequence containing SEQ ID: 66, and a Kabat CDR-H3 sequence containing SEQ ID: 82, and a VL sequence containing a CDR-L1 sequence containing SEQ ID: 110, CDR- L2 sequence containing the sequence of SEQ ID: 125, and CDR-L3 sequence containing the sequence of SEQ ID: 141. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 Kabat sequence containing the sequence of SEQ ID: 26, CDR-H2 a Kabat sequence containing SEQ ID: 65 and a Kabat CDR-H3 sequence containing SEQ ID: 82 and a VL sequence containing a CDR-L1 sequence containing SEQ ID: 110, a CDR-L2 sequence containing the sequence SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 143. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 26, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 65, and the CDR-H3 sequence of Kabat containing the sequence of SEQ ID: 82, and the VL sequence containing the CDR-L1 sequence containing the sequence of SEQ ID: 112, the CDR-L2 sequence containing the sequence of SEQ ID: 128, and a CDR-L3 sequence containing the sequence of SEQ ID: 144. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 27, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 65 , and a Kabat CDR-H3 sequence containing SEQ ID: 82, and a VL sequence containing a CDR-L1 sequence containing SEQ ID: 111, a CDR-L2 sequence containing SEQ ID: 126, and a CDR-L3 sequence containing the sequence of SEQ ID: 145. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 28, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 67, and a CDR-H3 a Kabat sequence containing SEQ ID: 82 and a VL sequence containing a CDR-L1 sequence containing SEQ ID: 113, a CDR-L2 sequence containing SEQ ID: 129, and a CDR-L3 sequence containing SEQ ID: 129 : 146. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 29, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 68, and a Kabat CDR-H3 sequence containing sequence of SEQ ID: 82, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 114, a CDR-L2 sequence containing the sequence of SEQ ID: 130, and a CDR-L3 sequence containing the sequence of SEQ ID: 147. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 26, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 64, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 82 , and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 141. In some aspects, the antibody contains V _H a sequence containing a Kabat CDR-H1 sequence containing SEQ ID: 30, a Kabat CDR-H2 sequence containing SEQ ID: 69, and a Kabat CDR-H3 sequence containing SEQ ID: 87, and a VL sequence, containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing CDR- H1 Kabat sequence containing SEQ ID: 31, CDR-H2 Kabat sequence containing SEQ ID: 70, and CDR-H3 Kabat sequence containing SEQ ID: 88, and VL sequence containing CDR-L1 sequence , containing the sequence of SEQ ID NO: 116, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 149. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Kabat containing the sequence of SEQ ID: 32, a CDR-H2 sequence according to Kabat containing the sequence of SEQ ID: 71, and a CDR-H3 sequence according to Kabat containing the sequence of SEQ ID: 89, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: : 33, CDR-H2 Kabat sequence containing SEQ ID: 70 and CDR-H3 Kabat sequence containing SEQ ID: 90 and VL sequence containing CDR-L1 sequence containing SEQ ID: 115, CDR -L2 sequence containing the sequence of SEQ ID: 132, and CDR-L3 sequence containing the sequence of SEQ ID: 149. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 34, CDR- H2 Kabat sequence containing SEQ ID: 72 and CDR-H3 Kabat sequence containing SEQ ID: 91 and VL sequence containing CDR-L1 sequence containing SEQ ID: 115, CDR-L2 sequence containing sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Kabat, containing the sequence SEQ ID: 30, a CDR-H2 sequence according to Kabat, containing the sequence of SEQ ID: 71, and a CDR-H3 sequence by Kabat containing the sequence of SEQ ID: 92, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131 , and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 35, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 70 and a Kabat CDR-H3 sequence containing SEQ ID: 93 and a VL sequence containing a CDR-L1 sequence containing SEQ ID: 117, a CDR-L2 sequence containing SEQ ID: 133, and a CDR-L3 a sequence containing the sequence of SEQ ID: 150. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 33, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 70, and a CDR- H3 Kabat sequence containing SEQ ID: 92 and VL sequence containing CDR-L1 sequence containing SEQ ID: 115, CDR-L2 sequence containing SEQ ID: 134 and CDR-L3 sequence containing SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 36, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 72, and a Kabat CDR-H3 sequence, containing the sequence of SEQ ID: 87, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 30, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 73, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 87, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains V _H sequence containing Kabat CDR-H1 sequence containing SEQ ID: 37, Kabat CDR-H2 sequence containing SEQ ID: 74, and Kabat CDR-H3 sequence containing SEQ ID: 87, and VL sequence , containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing the CDR -H1 Kabat sequence containing SEQ ID: 38, CDR-H2 Kabat sequence containing SEQ ID: 75, and CDR-H3 Kabat sequence containing SEQ ID: 94, and VL sequence containing CDR-L1 a sequence containing the sequence of SEQ ID: 118, a CDR-L2 sequence containing the sequence of SEQ ID: 135, and a CDR-L3 sequence containing the sequence of SEQ ID: 151. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Kabat , containing the sequence of SEQ ID: 39, a CDR-H2 sequence according to Kabat containing the sequence of SEQ ID: 76, and a CDR-H3 sequence according to Kabat containing the sequence of SEQ ID: 95, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 118, a CDR-L2 sequence containing the sequence of SEQ ID: 135, and a CDR-L3 sequence containing the sequence of SEQ ID: 152. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: : 40, CDR-H2 Kabat sequence containing SEQ ID: 76 and CDR-H3 Kabat sequence containing SEQ ID: 96 and VL sequence containing CDR-L1 sequence containing SEQ ID: 118, CDR -L2 sequence containing the sequence of SEQ ID: 136, and CDR-L3 sequence containing the sequence of SEQ ID: 152. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 39, CDR- H2 Kabat sequence containing SEQ ID: 76 and CDR-H3 Kabat sequence containing SEQ ID: 94 and VL sequence containing CDR-L1 sequence containing SEQ ID: 118, CDR-L2 sequence containing sequence of SEQ ID: 135, and a CDR-L3 sequence containing the sequence of SEQ ID: 152. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Kabat, containing the sequence SEQ ID: 38, a CDR-H2 sequence according to Kabat, containing the sequence of SEQ ID: 69, and a CDR-H3 sequence by Kabat containing the sequence of SEQ ID: 97, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131 , and a CDR-L3 sequence containing the sequence of SEQ ID: 153. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 41, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 69 and a Kabat CDR-H3 sequence containing SEQ ID: 98 and a VL sequence containing a CDR-L1 sequence containing SEQ ID: 119, a CDR-L2 sequence containing SEQ ID: 131, and a CDR-L3 a sequence containing the sequence of SEQ ID: 154. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 41, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 69, and a CDR- H3 Kabat sequence containing SEQ ID: 99 and VL sequence containing CDR-L1 sequence containing SEQ ID: 120, CDR-L2 sequence containing SEQ ID: 137 and CDR-L3 sequence containing SEQ ID: 155. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 41, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 69, and a Kabat CDR-H3 sequence, containing the sequence of SEQ ID: 100, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence containing the sequence of SEQ ID: 138, and a CDR-L3 sequence containing the sequence of SEQ ID: 156. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 38, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 75, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 101, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence containing the sequence of SEQ ID: 138, and a CDR-L3 sequence containing the sequence of SEQ ID: 157. In some aspects, the antibody contains V _H sequence containing Kabat CDR-H1 sequence containing SEQ ID: 42, Kabat CDR-H2 sequence containing SEQ ID: 78, and Kabat CDR-H3 sequence containing SEQ ID: 102, and VL sequence , containing a CDR-L1 sequence containing the sequence of SEQ ID: 122, a CDR-L2 sequence containing the sequence of SEQ ID: 138, and a CDR-L3 sequence containing the sequence of SEQ ID: 158. In some aspects, the antibody contains a V _H sequence containing the CDR -H1 Kabat sequence containing SEQ ID: 38, CDR-H2 Kabat sequence containing SEQ ID: 75 and CDR-H3 Kabat sequence containing SEQ ID: 103 and VL sequence containing CDR-L1 a sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence containing the sequence of SEQ ID: 138, and a CDR-L3 sequence containing the sequence of SEQ ID: 159. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Kabat containing the sequence of SEQ ID: 43, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 79, and a Kabat CDR-H3 sequence containing the sequence of SEQ ID: 104, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 118, a CDR-L2 sequence containing the sequence of SEQ ID: 135, and a CDR-L3 sequence containing the sequence of SEQ ID: 160. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: : 38, CDR-H2 Kabat sequence containing SEQ ID: 75 and CDR-H3 Kabat sequence containing SEQ ID: 103 and VL sequence containing CDR-L1 sequence containing SEQ ID: 121, CDR -L2 sequence containing the sequence of SEQ ID: 139, and CDR-L3 sequence containing the sequence of SEQ ID: 161. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 38, CDR- H2 Kabat sequence containing SEQ ID: 69 and CDR-H3 Kabat sequence containing SEQ ID: 105 and VL sequence containing CDR-L1 sequence containing SEQ ID: 123, CDR-L2 sequence containing sequence of SEQ ID: 140, and a CDR-L3 sequence containing the sequence of SEQ ID: 162. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Kabat, containing the sequence SEQ ID: 38, a CDR-H2 sequence according to Kabat, containing the sequence of SEQ ID: 69, and a CDR-H3 sequence of Kabat containing the sequence of SEQ ID: 106, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence containing the sequence of SEQ ID: 138 , and a CDR-L3 sequence containing the sequence of SEQ ID: 163. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 38, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 69 and a Kabat CDR-H3 sequence containing SEQ ID: 107 and a VL sequence containing a CDR-L1 sequence containing SEQ ID: 121, a CDR-L2 sequence containing SEQ ID: 139, and a CDR-L3 a sequence containing the sequence of SEQ ID: 164. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 44, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 80, and a CDR- H3 Kabat sequence containing SEQ ID: 108 and VL sequence containing CDR-L1 sequence containing SEQ ID: 120, CDR-L2 sequence containing SEQ ID: 137 and CDR-L3 sequence containing SEQ ID: 165. In some aspects, the antibody contains a V _H sequence containing a Kabat CDR-H1 sequence containing the sequence of SEQ ID: 45, a Kabat CDR-H2 sequence containing the sequence of SEQ ID: 81, and a Kabat CDR-H3 sequence, containing the sequence of SEQ ID: 109, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 124, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 166.

[00224] In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 1, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 46, and a Chothia CDR-H3 sequence containing sequence of SEQ ID: 82, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 141. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 2, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 47, and a CDR-H3 sequence according to Chothia, containing the sequence of SEQ ID: 83 , and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 111, a CDR-L2 sequence containing the sequence of SEQ ID: 126, and a CDR-L3 sequence containing the sequence of SEQ ID: 142. In some aspects, the antibody contains V _H a sequence containing a CDR-H1 sequence according to Chothia containing the sequence SEQ ID: 1, a CDR-H2 sequence according to Chothia containing the sequence SEQ ID: 46, and a CDR-H3 sequence according to Chothia containing the sequence SEQ ID: 84, and a VL sequence, containing a CDR-L1 sequence containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 141. In some aspects, the antibody contains a V _H sequence containing the CDR- Chothia H1 sequence containing SEQ ID: 2, Chothia CDR-H2 sequence containing SEQ ID: 47, and Chothia CDR-H3 sequence containing SEQ ID: 85, and VL sequence containing CDR-L1 sequence , containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 141. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 3, a CDR-H2 sequence according to Chothia containing the sequence of SEQ ID NO: 47, and a CDR-H3 sequence according to Chothia containing the sequence of SEQ ID: 86, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 127, and a CDR-L3 sequence containing the sequence of SEQ ID: 142. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: : 4, Chothia CDR-H2 sequence containing SEQ ID: 46 and Chothia CDR-H3 sequence containing SEQ ID: 82 and VL sequence containing CDR-L1 sequence containing SEQ ID: 110, CDR -L2 sequence containing the sequence of SEQ ID: 125, and CDR-L3 sequence containing the sequence of SEQ ID: 141. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 2, CDR- Chothia H2 sequence containing SEQ ID: 46 and Chothia CDR-H3 sequence containing SEQ ID: 82 and VL sequence containing CDR-L1 sequence containing SEQ ID: 110, CDR-L2 sequence containing sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 143. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 2, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 46, and a CDR-H3 sequence of Chothia containing the sequence of SEQ ID: 82, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 112, a CDR-L2 sequence containing the sequence of SEQ ID: 128 , and a CDR-L3 sequence containing the sequence of SEQ ID: 144. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence of SEQ ID: 1, a CDR-H2 sequence according to Chothia containing the sequence SEQ ID: 46 and a Chothia CDR-H3 sequence containing SEQ ID: 82 and a VL sequence containing a CDR-L1 sequence containing SEQ ID: 111, a CDR-L2 sequence containing SEQ ID: 126, and a CDR-L3 a sequence containing the sequence of SEQ ID: 145. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 5, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 49, and a CDR- H3 Chothia sequence containing SEQ ID: 82 and VL sequence containing CDR-L1 sequence containing SEQ ID: 113, CDR-L2 sequence containing SEQ ID: 129 and CDR-L3 sequence containing SEQ ID: 146. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 6, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 50, and a CDR-H3 sequence according to Chothia, containing the sequence of SEQ ID: 82, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 114, a CDR-L2 sequence containing the sequence of SEQ ID: 130, and a CDR-L3 sequence containing the sequence of SEQ ID: 147. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 2, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 47, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 82, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 110, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 141. In some aspects, the antibody contains V _H sequence containing Chothia CDR-H1 sequence containing SEQ ID: 7, Chothia CDR-H2 sequence containing SEQ ID: 51, and Chothia CDR-H3 sequence containing SEQ ID: 87, and VL sequence , containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing the CDR -H1 Chothia sequence containing SEQ ID: 8, CDR-H2 Chothia sequence containing SEQ ID: 52, and Chothia CDR-H3 sequence containing SEQ ID: 88, and VL sequence containing CDR-L1 a sequence containing the sequence of SEQ ID NO: 116, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 149. In some aspects, the antibody contains a V _H sequence containing the CDR-H1 sequence of Chothia containing the sequence of SEQ ID: 9, CDR-H2 sequence of Chothia containing the sequence of SEQ ID: 53, and CDR-H3 sequence of Chothia containing the sequence of SEQ ID: 89, and VL sequence containing the CDR-L1 sequence containing the sequence SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence of SEQ ID: 10, Chothia CDR-H2 sequence containing SEQ ID: 52, and Chothia CDR-H3 sequence containing SEQ ID: 90, and VL sequence containing CDR-L1 sequence containing SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 132, and a CDR-L3 sequence containing the sequence of SEQ ID: 149. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 11, CDR -H2 sequence according to Chothia containing the sequence SEQ ID: 54, and CDR-H3 sequence according to Chothia containing the sequence SEQ ID: 91, and VL sequence containing the CDR-L1 sequence containing the sequence SEQ ID: 115, CDR-L2 sequence, containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence of SEQ ID: 12, a CDR-H2 sequence according to Chothia , containing the sequence of SEQ ID: 53, and a CDR-H3 sequence according to Chothia, containing the sequence of SEQ ID: 92, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence of Chothia containing the sequence of SEQ ID: 13, a CDR-H2 sequence of Chothia containing the sequence of SEQ ID : 52, and a Chothia CDR-H3 sequence containing SEQ ID: 93, and a VL sequence containing a CDR-L1 sequence containing SEQ ID: 117, a CDR-L2 sequence containing SEQ ID: 133, and a CDR- L3 sequence containing the sequence of SEQ ID: 150. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 10, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 52, and a CDR -H3 Chothia sequence containing SEQ ID: 92 and VL sequence containing CDR-L1 sequence containing SEQ ID: 115, CDR-L2 sequence containing SEQ ID: 134 and CDR-L3 sequence containing SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 14, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 54, and a CDR-H3 sequence according to Chothia containing the sequence of SEQ ID: 87, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 15, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 55, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: : 87, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains V _H sequence containing Chothia CDR-H1 sequence containing SEQ ID: 16, Chothia CDR-H2 sequence containing SEQ ID: 56, and Chothia CDR-H3 sequence containing SEQ ID: 87, and VL a sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 115, a CDR-L2 sequence containing the sequence of SEQ ID: 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 148. In some aspects, the antibody contains a V _H sequence containing Chothia CDR-H1 sequence containing SEQ ID: 17, Chothia CDR-H2 sequence containing SEQ ID: 51, and Chothia CDR-H3 sequence containing SEQ ID: 94, and VL sequence containing CDR- An L1 sequence containing the sequence of SEQ ID: 118, a CDR-L2 sequence containing the sequence of SEQ ID: 135, and a CDR-L3 sequence containing the sequence of SEQ ID: 151. In some aspects, the antibody contains a V _H sequence containing the CDR-H1 sequence of Chothia containing the sequence SEQ ID: 18, CDR-H2 sequence according to Chothia containing the sequence SEQ ID: 57, and CDR-H3 sequence according to Chothia containing the sequence SEQ ID: 95, and VL sequence containing the CDR-L1 sequence containing the sequence SEQ ID: 118, a CDR-L2 sequence containing the sequence of SEQ ID: 135, and a CDR-L3 sequence containing the sequence with identification number: 152. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence SEQ ID: 19, Chothia CDR-H2 sequence containing SEQ ID: 57 and Chothia CDR-H3 sequence containing SEQ ID: 96 and VL sequence containing CDR-L1 sequence containing SEQ ID: 118 , a CDR-L2 sequence containing the sequence of SEQ ID: 136, and a CDR-L3 sequence containing the sequence of SEQ ID: 152. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 21, Chothia CDR-H2 sequence containing SEQ ID: 57 and Chothia CDR-H3 sequence containing SEQ ID: 94 and VL sequence containing CDR-L1 sequence containing SEQ ID: 118, CDR-L2 sequence , containing the sequence of SEQ ID: 135, and a CDR-L3 sequence containing the sequence of SEQ ID: 152. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 17, a CDR-H2 sequence of Chothia containing SEQ ID: 51 and Chothia CDR-H3 sequence containing SEQ ID: 97 and VL sequence containing CDR-L1 sequence containing SEQ ID: 115, CDR-L2 sequence containing SEQ ID: 115 : 131, and a CDR-L3 sequence containing the sequence of SEQ ID: 153. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence of SEQ ID: 22, a CDR-H2 sequence according to Chothia containing the sequence SEQ ID: 52, and a Chothia CDR-H3 sequence containing SEQ ID: 98, and a VL sequence containing a CDR-L1 sequence containing SEQ ID: 119, a CDR-L2 sequence containing SEQ ID: 131, and a CDR -L3 sequence containing the sequence of SEQ ID: 154. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence of SEQ ID: 22, a CDR-H2 sequence according to Chothia containing the sequence of SEQ ID: 51, and Chothia CDR-H3 sequence containing SEQ ID: 99 and VL sequence containing CDR-L1 sequence containing SEQ ID: 120, CDR-L2 sequence containing SEQ ID: 137 and CDR-L3 sequence containing the sequence of SEQ ID: 155. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 22, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 51, and a CDR-H3 sequence of Chothia containing SEQ ID: 100 and VL sequence containing CDR-L1 sequence containing SEQ ID: 121, CDR-L2 sequence containing SEQ ID: 138, and CDR-L3 sequence containing SEQ ID: 156 In some aspects, the antibody comprises a V _H sequence comprising a Chothia CDR-H1 sequence comprising the sequence of SEQ ID: 17, a Chothia CDR-H2 sequence comprising the sequence of SEQ ID: 51, and a Chothia CDR-H3 sequence comprising the sequence of SEQ ID: 101, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence containing the sequence of SEQ ID: 138, and a CDR-L3 sequence containing the sequence of SEQ ID: 157. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 17, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 59, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 102, and a VL sequence comprising a CDR-L1 sequence comprising the sequence of SEQ ID: 122, a CDR-L2 sequence comprising the sequence of SEQ ID: 138, and a CDR-L3 sequence comprising the sequence of SEQ ID: 158. In some aspects, the antibody comprises a V _H sequence, containing a CDR-H1 sequence according to Chothia containing the sequence SEQ ID: 17, a CDR-H2 sequence according to Chothia containing the sequence SEQ ID: 51, and a CDR-H3 sequence according to Chothia containing the sequence SEQ ID: 103, and a VL sequence containing the CDR -L1 sequence containing the sequence of SEQ ID: 121, CDR-L2 sequence containing the sequence of SEQ ID: 138, and CDR-L3 sequence containing the sequence of SEQ ID: 159. In some aspects, the antibody contains a V _H sequence containing the CDR-H1 sequence Chothia sequence containing SEQ ID: 23, Chothia CDR-H2 sequence containing SEQ ID: 60, and Chothia CDR-H3 sequence containing SEQ ID: 104, and VL sequence containing CDR-L1 sequence containing sequence of SEQ ID: 118, a CDR-L2 sequence containing the sequence of SEQ ID: 135, and a CDR-L3 sequence containing the sequence of SEQ ID: 160. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence of Chothia containing the sequence SEQ ID: 17, Chothia CDR-H2 sequence containing SEQ ID: 51 and Chothia CDR-H3 sequence containing SEQ ID: 103, and VL sequence containing CDR-L1 sequence containing SEQ ID: 121 , a CDR-L2 sequence containing the sequence of SEQ ID: 139, and a CDR-L3 sequence containing the sequence of SEQ ID: 161. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 17, Chothia CDR-H2 sequence containing SEQ ID: 51 and Chothia CDR-H3 sequence containing SEQ ID: 105 and VL sequence containing CDR-L1 sequence containing SEQ ID: 123, CDR-L2 sequence , containing the sequence of SEQ ID: 140, and a CDR-L3 sequence containing the sequence of SEQ ID: 162. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 17, a CDR-H2 sequence of Chothia containing SEQ ID: 51 and Chothia CDR-H3 sequence containing SEQ ID: 106 and VL sequence containing CDR-L1 sequence containing SEQ ID: 121, CDR-L2 sequence containing SEQ ID: 121 : 138, and a CDR-L3 sequence containing the sequence of SEQ ID: 163. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia containing the sequence of SEQ ID: 17, a CDR-H2 sequence according to Chothia containing the sequence SEQ ID: 51, and a Chothia CDR-H3 sequence containing the sequence of SEQ ID: 107, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 121, a CDR-L2 sequence containing the sequence of SEQ ID: 139, and a CDR -L3 sequence containing the sequence of SEQ ID: 164. In some aspects, the antibody contains a V _H sequence containing a CDR-H1 sequence according to Chothia, containing the sequence of SEQ ID: 17, a CDR-H2 sequence according to Chothia, containing the sequence of SEQ ID: 61, and Chothia CDR-H3 sequence containing SEQ ID: 108 and VL sequence containing CDR-L1 sequence containing SEQ ID: 120, CDR-L2 sequence containing SEQ ID: 137 and CDR-L3 sequence containing the sequence of SEQ ID: 165. In some aspects, the antibody contains a V _H sequence containing a Chothia CDR-H1 sequence containing the sequence of SEQ ID: 17, a Chothia CDR-H2 sequence containing the sequence of SEQ ID: 62, and a CDR-H3 sequence of Chothia containing the sequence of SEQ ID: 109, and a VL sequence containing a CDR-L1 sequence containing the sequence of SEQ ID: 124, a CDR-L2 sequence containing the sequence of SEQ ID: 125, and a CDR-L3 sequence containing the sequence of SEQ ID: 166 .

2.7.3.1. Pair options V _H - V _L

[00225] In some embodiments, the V _H - V _L pairs described herein comprise a variant of the exemplary V _H and/or V _L sequence described herein.

[00226] In some aspects, the V _H sequence comprises, consists of, or primarily consists of a variant of the exemplary V _H sequence described herein. In some aspects, the V _H sequence contains, consists of, or primarily consists of a sequence with at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, and 99.5% identity with any of the illustrative V _H sequences given in the present description of the invention.

[00227] In some embodiments, the V _H sequence comprises, consists of, or primarily consists of any of the V _H sequences described herein, 20 or less, 19 or less, 18 or less, 17 or less, 16 15 or less, 14 or less, 13 or less, 12 or less, 11 or less, 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less , 3 or less, 2 or less, or 1 or less amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

[00228] In some aspects, the V _L sequence comprises, consists of, or primarily consists of a variant of the exemplary V _L sequence described herein. In some aspects, the V _L sequence contains, consists of, or primarily consists of a sequence with at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, and 99.5% identity with any of the illustrative V _L sequences given in the present description of the invention.

[00229] In some embodiments, the V _L sequence comprises, consists of, or primarily consists of any of the V _L sequences described herein, 20 or less, 19 or less, 18 or less, 17 or less, 16 15 or less, 14 or less, 13 or less, 12 or less, 11 or less, 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less , 3 or less, 2 or less, or 1 or less amino acid substitutions. In some aspects, such amino acid substitutions are conservative amino acid substitutions.

2.7.4 HC+LC

[00230] In some embodiments, the antibody comprises or consists of one or more heavy chains consisting of the HC sequence and one or more light chains consisting of the LC sequence. In some embodiments, the antibody contains or consists of two identical heavy chains consisting of the HC sequence and two identical light chains consisting of the LC sequence.

[00231] In some embodiments, such an HC sequence is an HC sequence comprising, consisting of, or primarily consisting of SEQ ID: 255, SEQ ID: 257, SEQ ID: 259, SEQ ID: 261, SEQ ID: 263, SEQ ID: 265, SEQ ID: 267, SEQ ID: 269, SEQ ID: 271, SEQ ID: 273, SEQ ID: 275, SEQ ID: 277, SEQ ID: : 279, SEQ ID: 281, SEQ ID: 283, SEQ ID: 285, SEQ ID: 287, SEQ ID: 289, SEQ ID: 291, SEQ ID: 293, SEQ ID: 295 , the sequences of SEQ ID: 297, and the LC sequence is an LC sequence containing, consisting of, or primarily consisting of the sequence SEQ ID: 256, the sequence SEQ ID: 258, the sequence SEQ ID: 260, the sequence SEQ ID: 256, the sequence SEQ ID: 256, SEQ ID: 256, SEQ ID: 256, SEQ ID: 270, SEQ ID: 272, SEQ ID: 274, SEQ ID: 256, SEQ ID: 256, SEQ ID: : 280, SEQ ID: 282, SEQ ID: 284, SEQ ID: 286, SEQ ID: 288, SEQ ID: 290, SEQ ID: 292, SEQ ID: 294, SEQ ID: 296 , SEQ ID: 298. In some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 255, SEQ ID: 257, SEQ ID: 259, SEQ ID: 261, SEQ ID: 263, SEQ ID: 265, SEQ ID: 267, SEQ ID: 269, SEQ ID: 271, SEQ ID: 273, SEQ ID: 275, SEQ ID: 277, SEQ ID: 279, SEQ ID: 281, SEQ ID: 283, SEQ ID: 285, SEQ ID: 287, SEQ ID: 289, SEQ ID: 291, SEQ ID: 293, SEQ ID: 295, SEQ ID: 297, and the LC sequence is an LC sequence consisting of SEQ ID: 256, SEQ ID: 258, SEQ ID: 260, SEQ ID: 256, SEQ ID: 256, SEQ ID: 256, SEQ ID: : 256, SEQ ID: 270, SEQ ID: 272, SEQ ID: 274, SEQ ID: 256, SEQ ID: 256, SEQ ID: 280, SEQ ID: 282, SEQ ID: 284 , SEQ ID: 286, SEQ ID: 288, SEQ ID: 290, SEQ ID: 292, SEQ ID: 294, SEQ ID: 296, SEQ ID: 298.

[00232] In some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 255, and the LC sequence is an LC sequence consisting of SEQ ID: 256. In some embodiments, such an HC sequence is an HC sequence consisting of sequence of SEQ ID: 257, and the LC sequence is an LC sequence consisting of the sequence SEQ ID: 258. In some embodiments, such an HC sequence is an HC sequence consisting of the sequence SEQ ID: 259, and the LC sequence is an LC sequence consisting of the sequence SEQ ID: 260. In some embodiments, such an HC sequence is an HC sequence consisting of the sequence of SEQ ID: 261, and the LC sequence is an LC sequence consisting of the sequence of SEQ ID: 262. In some embodiments, such an HC sequence is an HC sequence, consisting of SEQ ID: 263, and the LC sequence is an LC sequence consisting of SEQ ID: 264. In some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 265, and the LC sequence is an LC sequence consisting of from SEQ ID: 266. In some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 267, and an LC sequence is an LC sequence consisting of SEQ ID: 268. In some embodiments, such an HC sequence is HC a sequence consisting of SEQ ID: 269 and the LC sequence is an LC sequence consisting of SEQ ID: 270. In some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 271 and the LC sequence is an LC sequence consisting of the sequence SEQ ID: 272. In some embodiments, such an HC sequence is the HC sequence consisting of the sequence SEQ ID: 273, and the LC sequence is the LC sequence consisting of the sequence SEQ ID: 274. In some embodiments, such an HC sequence is is an HC sequence consisting of SEQ ID: 275 and the LC sequence is an LC sequence consisting of SEQ ID: 276. In some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 277 and the LC sequence is An LC sequence consisting of SEQ ID: 278. In some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 279, and an LC sequence is an LC sequence consisting of SEQ ID: 280. In some embodiments, such The HC sequence is the HC sequence consisting of the sequence SEQ ID: 281 and the LC sequence is the LC sequence consisting of the sequence SEQ ID: 282. In some embodiments, such an HC sequence is the HC sequence consisting of the sequence SEQ ID: 283 and the LC the sequence is an LC sequence consisting of SEQ ID: 284. In some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 285, and the LC sequence is an LC sequence consisting of SEQ ID: 286. In some embodiments, such an HC sequence is the HC sequence consisting of the sequence SEQ ID: 287, and the LC sequence is the LC sequence consisting of the sequence SEQ ID: 288. In some embodiments, such an HC sequence is the HC sequence consisting of the sequence SEQ ID: 289, and the LC sequence is an LC sequence consisting of SEQ ID: 290. In some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 291, and the LC sequence is an LC sequence consisting of SEQ ID: 292. B in some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 293, and the LC sequence is an LC sequence consisting of SEQ ID: 294. In some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 295, and the LC sequence is an LC sequence consisting of SEQ ID: 296. In some embodiments, such an HC sequence is an HC sequence consisting of SEQ ID: 297, and the LC sequence is an LC sequence consisting of SEQ ID: 298 .

2.8. Consensus Sequences

[00233] In some embodiments, provided herein are anti-CD39 antibodies comprising one or more sequences defined by consensus sequences. Each consensus sequence is based at least in part on one or more alignments of two or more useful anti-CD39 CDR sequences provided herein. Based on such alignments, one of skill in the art will appreciate that various amino acid residues may be useful at certain CDR positions. Accordingly, each consensus sequence spans two or more useful anti-CD39 CDR sequences.

2.8.1. CDR-H3 consensus sequences

[00234] In some embodiments, the antibody comprises a CDR-H3 sequence defined by the GKREGGTEYLR-Y ₁₂ consensus sequence (SEQ ID: 82-86), where Y ₁₂ is H, K, S, N, or V.

[00235] In some aspects, Y ₁₂ is H. In some aspects, Y ₁₂ is K. In some aspects, Y ₁₂ is S. In some aspects, Y ₁₂ is N. In some aspects, Y ₁₂ is V.

[00236] In some embodiments, the antibody comprises a CDR-H3 sequence defined by the consensus sequence ESG-F ₄ -YRDHRL-F ₁₁ -V (sequence SEQ ID: 94-96), where F ₄ is G or T and F ₁₁ is a D or G.

[00237] In some aspects, P ₄ is G when P ₁₁ is D or G. In some aspects, P ₁₁ is D when P ₄ is G or T.

[00238] In some aspects, P ₄ is G and P ₁₁ is D. In some aspects, P ₄ is T and P ₁₁ is D. In some aspects, P ₄ is G and P ₁₁ is G.

[00239] In some embodiments, the antibody comprises a CDR-H3 sequence defined by the consensus sequence GGAKYA-E ₇ -E ₈ -E ₉ -GMDV (SEQ ID: 87-93), where E ₇ is S, V, G, or R; E ₈ - T, Q, K, G or R; and E ₉ is Y, H, L, or W.

[00240] In some aspects, E ₇ is S when E ₈ is T, Q, or K, and E ₉ is Y, H, L, or W. In some aspects, E ₈ is T when E ₇ is S or R, and E ₉ is Y or H. In some aspects, E ₉ is Y when E ₇ is S, V, G, or R, and E ₈ is T, G, or R.

[00241] In some aspects, E ₇ is S when E ₈ is T and E ₉ is Y. In some aspects, E ₇ is S when E ₈ is T and E ₉ is H. In some aspects, E ₇ is S when E ₈ is Q and E ₉ is L. In some aspects, E ₇ is S when E ₈ is K and E ₉ is W. In some aspects, E ₇ is V, when E ₈ is G and E ₉ is Y. In some aspects, E ₇ is G: when E ₈ is R and E ₉ is Y. In some aspects, E ₇ is R when E ₈ is T and E ₉ is Y.

2.8.2. CDR-H2 consensus sequences by Chothia

[00242] In some embodiments, the antibody comprises a Chothia CDR-H2 sequence defined by the NP-ε ₅ -ε ₆ -GST consensus sequence (sequences SEQ ID: 46-48), where ε ₅ is L, R or S and ε ₆ is G or V.

[00243] In some aspects, when ε ₅ is S, ε ₆ is G or V. In some aspects, when ε ₆ is G, ε ₅ is S, L, or R.

[00244] In some aspects, when ε ₅ is L, ε ₆ is G. In some aspects, when ε ₅ is S, ε ₆ is G. In some aspects, when ε ₅ is S, ε ₆ is V. In some aspects, when ε ₅ is R, ε ₆ is G.

[00245] In some embodiments, the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence α ₃ -α ₄ -α ₅ -α ₆ -GTA (SEQ ID: 51-54), where α ₃ is I or L or missing; α ₄ is P or absent; and α ₅ represents I, G or R; and α ₆ is A, F or G.

[00246] In some aspects, when α ₃ is I, α ₄ is P; α ₅ represents I or R; and α ₆ is F or G. In some aspects, when α ₃ is L, α ₄ is P; α ₅ represents I; and α ₆ is A or G. In some aspects, when α ₄ is P, α ₃ is I or L; α ₅ represents I or R; and α ₆ is A, F, or G. In some aspects, when α ₅ is I, α ₃ is I or L; α ₄ is P; and α ₆ is A, F, or G. In some aspects, when α ₆ is F, α ₃ is I or absent; α ₄ is P or absent; and α ₅ is I or G. In some aspects, when α ₆ is G, α ₃ is I or L; α ₄ is P; and α ₅ is I or R.

[00247] In some aspects, when α ₃ is L, α ₄ is P; α ₅ represents I; and α ₆ is A. In some aspects, when α ₃ is I, α ₄ is P; α ₅ represents I; and α ₆ is F. In some aspects, when α ₃ is absent, α ₄ is absent; α ₅ is G; and α ₆ is F. In some aspects, when α ₃ is L, α ₄ is P; α ₅ represents I; and α ₆ is G. In some aspects, when α ₃ is I, α ₄ is P; α ₅ represents R; and α ₆ is G.

[00248] In some embodiments, the antibody comprises a Chothia CDR-H2 sequence defined by the IP-β ₅ -β ₆ -G-β ₈ -A consensus sequence (SEQ ID: 56-60), where β ₅ is I, E, S or T; β ₆ is F, I or S; and β ₈ is I or T.

[00249] In some aspects, when β ₅ is I, β ₆ is F or S, and β ₈ is T. In some aspects, when β ₆ is F, β ₅ is E, I, or T, and β ₈ is I or T. In some aspects, when β ₈ is T, β ₅ is I, S, or T, and β ₆ is F, I, or S.

[00250] In some aspects, when β ₅ is I, β ₆ is F, and β ₈ is T. In some aspects, when β ₅ is E, β ₆ is F and β ₈ is I. B in some aspects, when β ₅ is S, β ₆ is I, and β ₈ is T. In some aspects, when β ₅ is I, β ₆ is S, and β ₈ is T. In some aspects, when β ₅ is T, β ₆ is S, and β ₈ is T.

2.8.3. CDR-H1 consensus sequences by Chothia

[00251] In some embodiments, the antibody comprises a Chothia CDR-H1 sequence defined by the GYTF-Ω ₅ -SY consensus sequence (SEQ IDs: 1-2 and 4-6), where Ω ₅ is T, K, Q, F or V.

[00252] In some aspects, Ω ₅ is T. In some aspects, Ω ₅ is K. In some aspects, Ω ₅ is Q. In some aspects, Ω ₅ is F. In some aspects, Ω ₅ is V.

[00253] In some embodiments, the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence GGTF-v ₅ -v ₆ -Y (sequences SEQ ID: 17-22 and 24), where v ₅ is S, G, or E and ν ₆ is S, K, R, or S.

[00254] In some aspects, v ₅ is S when v ₆ is S or K. In some aspects, v ₆ is S when v ₅ is S or E.

[00255] In some aspects, ν ₅ is S when ν ₆ is S. In some embodiments, ν ₅ is S when ν ₆ is K. In some embodiments, ν ₅ is G when ν ₆ is is R. IB in some aspects ν ₅ is E when ν ₆ is S.

[00256] In some embodiments, the antibody comprises a Chothia CDR-H1 sequence defined by the GGTF-κ ₅ -κ ₆ -κ ₇ consensus sequence (SEQ ID: 7-16), where κ ₅ is S, Q, P, or A; κ ₆ is S, K, H, L, A or W; and κ ₇ is Y, L, T, N, or M.

[00257] In some aspects, when κ ₅ is S, κ ₆ is S, K, H, L, A, or W, and κ ₇ is Y, L, T, or M. In some aspects, when κ ₆ is is S, κ ₅ is S, Q, P, or A; and κ ₇ is Y, L, or N. In some aspects, when κ ₇ is L, κ ₅ is S, Q, or A, and κ ₆ is S, K, L or W.

[00258] In some aspects, when κ ₅ is S, κ ₆ is S, and κ ₇ is Y. In some aspects, when κ ₅ is S, κ ₆ is S, and κ ₇ is L. B in some aspects when κ ₅ is S, κ ₆ is K, and κ ₇ is L. In some aspects, when κ ₅ is S, κ ₆ is H, and κ ₇ is T. In some aspects, when κ ₅ is S, κ ₆ is L, and κ ₇ is L. In some aspects, when κ ₅ is Q, κ ₆ is S, and κ ₇ is L. In some aspects, when κ ₅ is P, κ ₆ is S and κ ₇ is N. In some aspects, when κ ₅ is S, κ ₆ is A and κ ₇ is M. In some aspects, when κ ₅ is A, κ ₆ is S and κ ₇ is L. In some aspects, when κ ₅ is S, κ ₆ is W and κ ₇ is L.

2.8.4. CDR-H2 consensus sequences according to Kabat

[00259] In some embodiments, the antibody comprises a Kabat CDR-H2 sequence defined by the consensus sequence ε ₁ -INP-ε ₅ -ε ₆ -GST-ε ₁₀ -YAQKFQG (sequences SEQ ID: 63-66 and 68), where ε ₁ is K, S, R or V; ε ₅ is L, R or S; ε ₆ is G or V; and ε ₁₀ is S or W.

[00260] In some aspects, when ε ₁ is V; ε ₅ is L or S; ε ₆ is G; and ε ₁₀ is S. In some aspects, when ε ₁ is R; ε ₅ is S; ε ₆ is V or G; and ε ₁₀ is W. In some aspects, when ε ₅ is S; ε ₁ is R or V; ε ₆ is G or V; and ε ₁₀ is S or W. In some aspects, when ε ₆ is G; ε ₁ R or V; ε ₅ is S; and ε ₁₀ is S or W. In some aspects, when ε ₁₀ is S; ε ₁ is V or S; ε ₅ is L, R or S; and ε ₆ is G. In some aspects, when ε ₁₀ is W; ε ₁ is K or R; ε ₅ is S; and ε ₆ is G or V.

[00261] In some aspects, when ε ₁ is V; ε ₅ is L; ε ₆ is G; and ε ₁₀ is S. In some aspects, when ε ₁ is V; ε ₅ is S; ε ₆ is G; and ε ₁₀ is S. In some aspects, when ε ₁ is R; ε ₅ is S; ε ₆ is V; and ε ₁₀ is W. In some aspects, when ε ₁ is R; ε ₅ is S; ε ₆ is G; and ε ₁₀ is W. In some aspects, when ε ₁ is K; ε ₅ is S; ε ₆ is G; and ε ₁₀ is W. In some aspects, when ε ₁ is S; ε ₅ is R; ε ₆ is G; and ε ₁₀ is S.

[00262] In some embodiments, the antibody comprises a CDR-H2 Kabat sequence defined by the consensus sequence GI-α ₃ -α ₄ -α ₅ -α ₆ -GTANYAQKFQG (SEQ ID: 69-72), where α ₃ is I or L or missing; α ₄ is P or absent; and α ₅ represents I, G or R; and α ₆ is A, F or G.

[00263] In some aspects, when α ₃ is I, α ₄ is P; α ₅ represents I or R; and α ₆ is F or G. In some aspects, when α ₃ is L, α ₄ is P; α ₅ represents I; and α ₆ is A or G. In some aspects, when α ₄ is P, α ₃ is I or L; α ₅ represents I or R; and α ₆ is A, F, or G. In some aspects, when α ₅ is I, α ₃ is I or L; α ₄ is P; and α ₆ is A, F, or G. In some aspects, when α ₆ is F, α ₃ is I or absent; α ₄ is P or absent; and α ₅ is I or G. In some aspects, when α ₆ is G, α ₃ is I or L; α ₄ is P; and α ₅ is I or R.

[00264] In some aspects, when α ₃ is L, α ₄ is P; α ₅ represents I; and α ₆ is A. In some aspects, when α ₃ is I, α ₄ is P; α ₅ represents I; and α ₆ is F. In some aspects, when α ₃ is absent, α ₄ is absent; α ₅ is G; and α ₆ is F. In some aspects, when α ₃ is L, α ₄ is P; α ₅ represents I; and α ₆ is G. In some aspects, when α ₃ is I, α ₄ is P; α ₅ represents R; and α ₆ is G.

[00265] In some embodiments, the antibody comprises a Kabat CDR-H2 sequence defined by the consensus sequence β ₁ -IIP-β ₅ -β ₆ -G-β ₈ -ANYAQKFGQ (sequences SEQ ID: 74 and 76-79), where β ₁ is S or G; β ₅ represents I, E, S, or T; β ₆ is F, I or S; and β ₈ is I or T.

[00266] In some aspects, when β ₁ is S, β ₅ is E, I, or S; β ₆ is I or F; and β ₈ is I or T. In some aspects, when β ₁ is G, β ₅ is I or T; β ₆ is F or S; and β ₈ is T. In some aspects, when β ₅ is I, β ₁ is G or S; β ₆ is F or S; and β ₈ is T. In some aspects, when β ₆ is F, β ₁ is G or S; β ₅ represents E, I or T; and β ₈ is I or T. In some aspects, when β ₈ is T, β ₁ is G or S; β ₅ represents I, S or T; and β ₆ is F, I or S.

[00267] In some aspects, when β ₁ is S, β ₅ is I; β ₅ is F; and β ₈ is T. In some aspects, when β ₁ is S, β ₅ is E; β ₅ is F; and β ₈ is I. In some aspects, when β ₁ is S, β ₅ is S; β ₅ represents I; and β ₈ is T. In some aspects, when β ₁ is G, β ₅ is I; β ₅ is F; and β ₈ is T. In some aspects, when β ₁ is G, β ₅ is I; β ₅ is S; and β ₈ is T. In some aspects, when β ₁ is G, β ₅ is T; β ₅ is F; and β ₈ is T.

2.8.5. CDR-H1 consensus sequences according to Kabat

[00268] In some embodiments, the antibody comprises a Kabat CDR-H1 sequence defined by the SY-Δ ₃ -M-Δ ₅ consensus sequence (sequences SEQ ID: 25-29 and 44-45), where Δ ₃ is E, F , Q or Y and Δ ₅ represents H or Y.

[00269] In some aspects, when Δ ₃ is Y, Δ ₅ is H or Y. In some aspects, when Δ ₅ is H, Δ ₃ is E, F, Q, or Y.

[00270] In some aspects, Δ ₃ is Y when Δ ₅ is H. In some aspects, Δ ₃ is Y when Δ ₅ is Y. In some aspects, Δ ₃ is E when Δ ₅ is H. B in some aspects, Δ ₃ is Q when Δ ₅ is H. In some aspects, Δ ₃ is F when Δ ₅ is H.

[00271] In some embodiments, the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence θ ₁ -θ ₂ -θ ₃ -IS (SEQ ID: 30-37), where θ ₁ is A, H, K, L, S or W; θ ₂ is L, M, N or T; and θ ₃ is A or P.

[00272] In some aspects, when θ ₁ is S, θ ₂ is L or N, and θ ₃ is A or P. In some aspects, when θ ₂ is L, θ ₁ is K, L, S or W and θ ₃ is A or P. In some aspects, when θ ₃ is A, θ ₁ is A, H, K, L, S, or W, and θ ₂ is L, M, N, or T.

[00273] In some aspects, θ ₁ is S when θ ₂ is L and θ ₃ is A. In some aspects, θ ₁ is K when θ ₂ is L and θ ₃ is A. In some aspects θ ₁ is H when θ ₂ is T and θ ₃ is A. In some aspects, θ ₁ is S when θ ₂ is L and θ ₃ is P. In some aspects, θ ₁ is L, when θ ₂ is L and θ ₃ is A. In some aspects, θ ₁ is S when θ ₂ is N and θ ₃ is A. In some aspects, θ ₁ is A when θ ₂ is M and θ ₃ is A. In some aspects, θ ₁ is W when θ ₂ is L and θ ₃ is A.

[00274] In some embodiments, the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence η ₁ -Y-η ₃ -IS (SEQ ID: 38-41), where η ₁ is S, K, N, or R and η ₃ is A or G.

[00275] In some aspects, η ₁ is S, where η ₃ is A or G. In some aspects, η ₃ is A, where η ₁ is N or S. In some aspects, η ₃ is G, where η ₁ is K, R or S.

[00276] In some aspects, when η ₁ is S, η ₃ is A. In some aspects, when η ₁ is S, η ₃ is G. In some aspects, when η ₁ is K, η ₃ is G. In some aspects, when η ₁ is R, η ₃ is G. In some aspects, when η ₁ is N, η ₃ is A.

2.8.6. CDR-L3 consensus sequences

[00277] In some embodiments, the antibody comprises a CDR-L3 sequence defined by the consensus sequence QQY-π ₄ -π ₅ -π ₆ -π ₇ -T (SEQ ID: 141-147), where π ₄ is G, H or Y; π ₅ represents S, N, F, G or R; π ₆ is S, Y, A, G or R; and π ₇ is P, I, or L.

[00278] In some aspects, you are H when π ₅ is S, N, G, or R; π ₆ represents Y, A, G or R; and π ₇ is I or L. In some aspects, π ₅ is S when π ₄ is G or H; π ₆ is S, Y or A; and π ₇ is P, I, or L. In some aspects, π ₆ is Y when π ₄ is H or Y; π ₅ is S or F; and π ₇ is I. In some aspects, π ₆ is A when π ₄ is H; π ₅ represents N or S; and π ₇ is I or L. In some aspects, π ₇ is I when π ₄ is H or Y; π ₅ represents S, N, F, G or R; and π ₆ is Y, A, G, or R.

[00279] In some aspects, π ₄ is G when π ₅ is S; π ₆ is S; and π ₇ is P. In some aspects, π ₄ is H when π ₅ is S; π ₆ represents Y; and π ₇ is I. In some aspects, π ₄ is H when π ₅ is N; π ₆ represents I; and π ₇ is A. In some aspects, π ₄ is Y when π ₅ is F; π ₆ represents Y; and π ₇ is I. In some aspects, π ₄ is H when π ₅ is S; π ₆ is A; and π ₇ is L. In some aspects, π ₄ is H when π ₅ is G; π ₆ is G; and π ₇ is I. In some aspects, π ₄ is H when π ₅ is R; π ₆ is R; and π ₇ is I.

[00280] In some embodiments, the antibody comprises a CDR-L3 sequence defined by the consensus sequence QQ-λ ₃ -λ ₄ -λ ₅ -λ ₆ -P-T (sequence SEQ ID: 148-150), where λ ₃ is R, F, H, S, L, D, Y or V; λ ₄ is S, V, T, G, L, Y, or N; λ ₅ is N, L, F, K or V; and λ ₆ is W, F, Y, or L.

[00281] In some aspects, λ ₃ is R when λ ₄ is S or N; λ ₅ is N or F; and λ ₆ is W or Y. In some aspects, λ ₃ is H when λ ₄ is V or T; λ ₅ is N or V; and λ ₆ is F or W. In some aspects, λ ₃ is S when λ ₄ is V or Y; λ ₅ is F; and λ ₆ is W or L. In some aspects, λ ₄ is V when λ ₃ is F, H, S, or D; λ ₅ is L, N or F; and λ ₆ is W or F. In some aspects, λ ₄ is T when λ ₃ is L or H; λ ₅ is K or V; and λ ₆ is W. In some aspects, λ ₅ is N when λ ₃ is R, H, or V; λ ₄ is S, V or L; and λ ₆ is W, F, or Y. In some aspects, λ ₅ is L when λ ₃ is F, D, or Y; λ ₄ is V or G; and λ ₆ is W or F. In some aspects, λ ₅ is F when λ ₃ is S or R; λ ₄ is V, Y or N; and λ ₆ is W, L, or Y. In some aspects, λ ₆ is W when λ ₃ is R, F, S, L, D, or H; λ ₄ is S, V or T; and λ ₅ is N, L, F, K, or V. In some aspects, λ ₆ is F when λ ₃ is H or Y; λ ₄ is V or G; and λ ₅ is N or L. In some aspects, λ ₆ is Y when λ ₃ is V or R; λ ₄ is L or N; and λ ₅ is N or F.

[00282] In some aspects, λ ₃ is R when λ ₄ is S; λ ₅ is N; and λ ₆ is W. In some aspects, λ ₃ is F when λ ₄ is V; λ ₅ is L; and λ ₆ is W. In some aspects, λ ₃ is H when λ ₄ is V; λ ₅ is N; and λ ₆ is F. In some aspects, λ ₃ is S when λ ₄ is V; λ ₅ is F; and λ ₆ is W. In some aspects, λ ₃ is L when λ ₄ is T; λ ₅ is K; and λ ₆ is W. In some aspects, λ ₃ is D when λ ₄ is V; λ ₅ is L; and λ ₆ is W. In some aspects, λ ₃ is Y when λ ₄ is G; λ ₅ is L; and λ ₆ is F. In some aspects, λ ₃ is H when λ ₄ is T; λ ₅ is V; and λ ₆ is W. In some aspects, λ ₃ is V when λ ₄ is L; λ ₅ is N; and λ ₆ is Y. In some aspects, λ ₃ is S when λ ₄ is Y; λ ₅ is F; and λ ₆ is L. In some aspects, λ ₃ is R when λ ₄ is N; λ ₅ is F; and λ ₆ is Y.

[00283] In some embodiments, the antibody comprises a CDR-L3 sequence defined by the QQY-ρ ₃ -ρ ₄ -WPLT consensus sequence (SEQ ID: 151 and 152), where ρ ₃ is N or L and ρ ₄ is N or L.

[00284] In some aspects, ρ ₃ is N when ρ ₄ is L. In some aspects, ρ ₃ is L when ρ ₄ is L.

[00285] In some embodiments, the antibody comprises a CDR-L3 sequence defined by the consensus sequence QQ-ω ₃ -ω ₄ -ω ₅ -ω ₆ -P-ω ₈ -T (sequences SEQ ID: 153-156), where ω ₃ is Y or F; ω ₄ represents Y or W; ω ₅ is S, L, T or F; ω ₆ is T, Y or F; and ω ₈ is L or P.

[00286] In some aspects, ω ₃ is Y when ω ₄ is Y or W; ω ₅ represents S, L or T; ω ₆ is T or Y; and ω ₈ is L. In some aspects, ω ₄ is Y when ω ₃ is Y or F; ω ₅ is S, L or F; ω ₆ is T or Y; and ω ₈ is L or P. In some aspects, ω ₆ is Y when ω ₃ is Y; ω ₄ represents Y or W; ω ₅ is L or T; and ω ₈ is L. In some aspects, ω ₈ is L when ω ₃ is Y; ω ₄ represents Y or W; ω ₅ represents S, L or T; and ω ₆ is T or Y.

[00287] In some aspects, ω ₃ is Y when ω ₄ is Y; ω ₅ is S; ω ₆ is T; and ω ₈ is L. In some aspects, ω ₃ is Y when ω ₄ is Y; ω ₅ is L; ω ₆ is Y; and ω ₈ is L. In some aspects, ω ₃ is Y when ω ₄ is W; ω ₅ is T; ω ₆ is Y; and ω ₈ is L. In some aspects, ω ₃ is F when ω ₄ is Y; ω ₅ is F; ω ₆ is F; and ω ₈ is R.

2.8.7. CDR-L2 consensus sequences

[00288] In some embodiments, the antibody comprises a CDR-L2 sequence defined by the consensus sequence ψ ₁ -AS-ψ ₄ -R-ψ ₆ -ψ ₇ (SEQ ID: 125-136), where ψ ₁ is G or Y , ψ ₄ represents S or N; ψ ₆ is A or H; and ψ ₇ is T, Y or N.

[00289] In some aspects, is G when ψ ₄ is S or N; ψ ₆ is A or H; and ψ ₇ is T or N. In some aspects, ψ ₁ is Y when it is S or N; ψ ₆ is A; and ψ ₇ is Y or T. In some aspects, ψ ₄ is S when ψ ₁ is G or Y; ψ ₆ is A; and ψ ₇ is T, Y, or N. In some aspects, ψ ₄ is N when it is G or Y; ψ ₆ is H or A; and ψ ₇ is T. In some aspects, ψ ₆ is A when it is G or Y; ψ ₄ is S or N; and ψ ₇ is T, Y, or N. In some aspects, ψ ₇ is T when ψ ₁ is G or Y; ψ ₄ is S or N; and ψ ₆ is A or H.

[00290] In some aspects, ψ ₁ is G when ψ ₄ is S; ψ ₆ is A; and ψ ₇ is T. In some aspects, ψ ₁ is G when ψ ₄ is N; ψ ₆ is H; and ψ ₇ is T. In some aspects, ψ ₁ is Y when ψ ₄ is S; ψ ₆ is A; and ψ ₇ is Y. In some aspects, ψ ₁ is G when ψ ₄ is S; ψ ₆ is A; and ψ ₇ is N. In some aspects, ψ ₁ is Y when ψ ₄ is N; ψ ₆ is A; and ψ ₇ is T.

представляет собой N или K.[00291] In some embodiments, the antibody comprises a CDR-L2 sequence defined by the DAS-χ ₄ -RAT consensus sequence (sequences SEQ ID: 138 and 139), where

is N or K.

[00292] In some aspects, χ ₄ is N. In some aspects, χ ₄ is K.

[00293] In some embodiments, the antibody comprises a CDR-L2 sequence defined by the WASTR-σ ₆ -S consensus sequence (SEQ ID: 131 and 133-134), where σ ₆ is A, E, or Q.

[00294] In some aspects, σ ₆ is A. In some aspects, σ ₆ is E. In some aspects, σ ₆ is Q.

2.8.8. CDR-L1 consensus sequences

[00295] In some embodiments, the antibody comprises a CDR-L1 sequence defined by the consensus sequence φ ₁ -AS-φ ₄ -φ ₅ -V-φ ₇ -φ ₈ -φ ₉ -YL-A (sequence SEQ ID: 1101-114 ), where φ ₁ represents E, K or R; φ ₄ is Q or E; φ ₅ is S or Y; φ ₇ is S or A; φ ₈ is S or Y; and φ ₉ is D or S.

[00296] In some aspects, φ ₁ is R when φ ₄ is Q or E; φ ₅ is S or Y; φ ₇ is S or A; φ ₈ is S or Y; and φ ₉ is S or D. In some aspects, φ ₄ is E when φ ₁ is K or R; φ ₅ is S; φ ₇ is S; φ ₈ is S; and φ ₉ is S. In some aspects, φ ₄ is Q when φ ₁ is E or R; φ ₅ is S or Y; φ ₇ is S or A; φ ₈ is S or Y; and φ ₉ is S or D. In some aspects, φ ₅ is S when φ ₁ is E, K, or R; φ ₄ is E or Q; φ ₇ is S or A; φ ₈ is S or Y; and φ ₉ is S or D. In some aspects, φ ₇ is S when φ ₁ is E, K, or R; φ ₄ is E or Q; φ ₅ is S or Y; φ ₈ is S or Y; and φ ₉ is S or D. In some aspects, φ ₈ is S when φ ₁ is K or R; φ ₄ is E or Q; φ ₅ is S or 5; φ ₇ is A or S; and φ ₉ is S or D. In some aspects, φ ₈ is R when φ ₁ is E or R; φ ₄ is Q; φ ₅ is S; φ ₇ is S; and φ ₉ - S. In some aspects, φ ₉ is S when φ ₁ is E, K, or R; φ ₄ is E or Q; φ ₅ is S or Y; φ ₇ is A or S; and φ ₈ is S or Y.

[00297] In some aspects, φ ₁ is K when φ ₄ is E; φ ₅ is S; φ ₇ is S; φ ₈ is S; and φ ₉ is S. In some aspects, φ ₁ is E when φ ₄ is Q; φ ₅ is S; φ ₇ is S; φ ₈ is Y; and φ ₉ is S. In some aspects, φ ₁ is R when φ ₄ is Q; φ ₅ is S; φ ₇ is S; φ ₈ is S; and φ ₉ is D. In some aspects, φ ₁ is R when φ ₄ is Q; φ ₅ is S; φ ₇ is S; φ ₈ - S; and φ ₉ is S. In some aspects, φ ₁ is R when φ ₄ is Q; φ ₅ is S; φ ₇ is A; φ ₈ is S; and φ ₉ is S. In some aspects, φ ₁ is R when φ ₄ is Q; φ ₅ is S; φ ₇ is S; φ ₈ is Y; and φ ₉ is S. In some aspects, φ ₁ is R when φ ₄ is E; φ ₅ is S; φ ₇ is S; φ ₈ is S; and φ ₉ is S. In some aspects, φ ₁ is R when φ ₄ is Q; φ ₅ is Y; φ ₇ is S; φ ₈ is S; and φ ₉ is S.

[00298] In some embodiments, the antibody comprises a CDR-L1 sequence defined by the consensus sequence σ ₁ -ASQ-σ ₅ -σ ₆ -σ ₇ -σ ₈ -σ ₉ -L-σ ₁₁ (sequence SEQ ID: 118 and 120- 123), where σ ₁ is Q or R1; σ ₅ is D or S; σ ₆ is I or V; σ ₇ is G or S; σ ₈ is N, R or S; σ ₉ is N, Y or W; and σ ₁₁ is A or N.

[00299] In some aspects, when σ ₁ is R, σ ₅ is S; σ ₆ is I or V; σ ₇ is G or S; σ ₈ - R or S; σ ₉ is N, Y or W; and σ ₁₁ is A. In some aspects, when σ ₅ is S, σ ₁ is R; σ ₆ is I or V; σ ₇ is G or S; σ ₈ is R or S; σ ₉ is N, Y, or W; and σ ₁₁ is A. In some aspects, when σ ₆ is I, σ ₁ is Q or R; σ ₅ is D or S; σ ₇ is S; σ ₈ is N or S; σ ₉ is Y or W; and σ ₁₁ is A or N. In some aspects, when σ ₆ is V, σ ₁ is R; σ ₅ is S; σ ₇ is G or S; σ ₈ is R or S; σ ₉ is N or W; and σ ₁₁ is A. In some aspects, when σ ₇ is S, σ ₁ is Q or R; σ ₅ is D or S; σ ₆ is I or V; σ ₈ is N, S or R; σ ₉ is Y or W; and σ ₁₁ is A or N. In some aspects, when σ ₈ is S, σ ₁ is R; σ ₅ is S; σ ₆ is I or V; σ ₇ is S; σ ₉ is N, Y or W; and σ ₁₁ is A. In some aspects, when σ ₉ is Y, σ ₁ is Q or R; σ ₅ is D or S; σ ₆ is I or V; σ ₇ is S; σ ₈ is N, S or R; and σ ₁₁ is A or N. In some aspects, when σ ₁₁ is A, σ ₁ is R; σ ₅ is S; σ ₆ is I or V; σ ₇ is S or G; σ ₈ is S or R; and σ ₉ is N, W or Y.

[00300] In some aspects, when σ ₁ is R, σ ₅ is S; σ ₆ is V; σ ₇ is S; σ ₈ is S; σ ₉ is Y; and σ ₁₁ is A. In some aspects, when σ ₁ is Q, σ ₅ is D; σ ₆ is I; σ ₇ is S; σ ₈ is N; σ ₉ is Y; and σ ₁₁ is N. In some aspects, when σ ₁ is R, σ ₅ is S; σ ₆ is V; σ ₇ is S; σ ₈ is R; σ ₉ is Y; and σ ₁₁ is A. In some aspects, when σ ₁ is R, σ ₅ is S; σ ₆ is V; σ ₇ is G; σ ₈ is S; σ ₉ is N; and σ ₁₁ is A. In some aspects, when σ ₁ is R, σ ₅ is S; σ ₆ is I; σ ₇ is S; σ ₈ is S; σ ₉ is W; and σ ₁₁ is A.

[00301] In some embodiments, the antibody comprises a CDR-L1 sequence defined by the consensus sequence KSS-G ₄ -SVL-G ₈ -S-G ₁₀ -NNKNYLA (sequence SEQ ID: 115-117), where G ₄ is Q, R or K; D ₈ is F or Y; and G ₁₀ is S or N.

[00302] In some aspects, G ₄ is Q when G ₈ is F or Y and G ₁₀ is S. In some aspects, G ₈ is F when G ₄ is Q or R and G ₁₀ is S In some aspects, G ₈ is Y when G ₄ is K or Q and G ₁₀ is S or N. In some aspects, G ₁₀ is S when G ₄ is R or Q and G ₈ is F or Y.

[00303] In some aspects, G ₄ is Q when G ₈ is Y and G ₁₀ is S. In some aspects, G ₄ is K when G ₈ is Y and G ₁₀ is N. In some aspects, G ₄ is Q when G ₈ is F and G ₁₀ is S. In some aspects, G ₄ is R when G ₈ is F and G ₁₀ is S.

3. Germline

[00304] In some embodiments, an antibody that specifically binds to CD39 is an antibody containing a variable region that is encoded by a specific germline gene, or a variant thereof. Exemplary antibodies provided herein comprise variable regions that are encoded by the VH1-46, VH1-69, 1-69 and VH1-46 heavy chain variable region germline genes, or variants thereof; and the light chain variable region germline genes VK3-20, VK3-11, VK4-01, VK3 and VK3-15, or variants thereof. One skilled in the art will appreciate that the CDR sequences provided herein may also be useful when combined with variable regions encoded by other variable region germline genes, or variants thereof. In particular, the CDR sequences provided herein may be useful when combined with variable regions encoded by variable region germline genes, or variants thereof, that are structurally similar to the above variable region germline genes. For example, in some embodiments, the CDR-H sequence provided herein can be combined with a variable region encoded by a variable region germline gene selected from the VH1 or VH3 family, or a variant thereof. In some embodiments, the CDR-L sequence provided herein can be combined with a variable region encoded by a variable region germline gene selected from the Vλ3, Vκ1, Vκ3, and Vκ4 families, or a variant thereof.

4. Affinity

[00305] In some embodiments, the affinity of the antibody for CD39, which shows a K _D less than about 10 ^-5 M, less than about 10 ^-6 M, less than about 10 ^-7 M, less than about 10 ^{- 8} M, less than about 10 ^-9 M, less than about 10 ^-10 M, less than about 10 ^-11 M, or less than about 10 ^-12 M. In some embodiments, the affinity of the antibody is in the range of about 10 ^-7 M to 10 ^-11 M. In some embodiments, the affinity of the antibody is in the range of about 10 ^-7 M to 10 ^-10 M. In some embodiments, the affinity of the antibody is in the range of about 10 ^-7 M to 10 ^{- 9} M. In some embodiments, the affinity of the antibody is in the range of about 10 ^-7 M to 10 ^-8 M. In some embodiments, the affinity of the antibody is in the range of about 10 ^-8 M to 10 ^-11 M. In some embodiments, the affinity is antibody is in the range of 10 ^-8 M to 10 ^-10 M. In some embodiments, the affinity of the antibody is in the range of 10 ^-9 M to 10 ^-11 M. In some embodiments, the affinity of the antibody is in the range of 10 ^-10 M to 10 ^-11 M.

[00306] In some embodiments, the affinity of the antibody for human CD39 is in the range of about 4.09×10 ^-7 M to 7.31×10 ^-11 M. In some embodiments, the affinity of the antibody for human CD39 is about 1.14×10 ^-7 M, about 1.31×10 ^-7 M, approx. 1.67×10 ^-7 M, approx. 1.43×10 ^-7 M, approx. 1.30×10 ^-7 M, approx. 1.27× ^{10 -8 M} , approx. 10 ^-8 M, approx. 1.34×10 ^-9 M, approx. 1.16×10 ^-9 M, approx. 7.31×10 ^-11 M, approx. 7.60× ^{10 -10 M} , approx ^{. 10} M, about 6.72×10 ^-10 M, about 9.24×10 ^-10 M, about 5.58×10 ^-10 M, about 5.48×10 ^-8 M, about 3.37×10 ^-8 M, about 3.11×10 ^-8 M , about 1.88×10 ^-8 M, about 1.63×10 ^-8 M about 1.64×10 ^-8 M, about 1.01×10 ^-8 M, about 2.44×10 ^-7 M, about 4.09×10 ^-7 M, about 3.35 ×10 ^-8 M, about 1.91×10 ^-8 M, about 1.73×10 ^-8 M or about 2.39×10 ^-8 M.

[00307] In some embodiments, the antibody has a k _on when associated with human CD39 from about 1.93×10 ⁴ M ^-1 s ^-1 to about 1.72 x 10 ⁶ M ^-1 s ^-1 . In some embodiments, the antibody has a _ka when associated with human CD39 of about 6.59x10 ⁴ M ^-1 s ^-1 , about 1.93x10 ⁴ M ^-1 s ^-1 , about 4.44x10 ⁵ M ^-1 s ^{-1 1 , approx . _ _ _ _ _ _ _ _} sec ^-1 , about 2.11×10 ⁵ M ^-1 × sec ^-1 , about 1.17×10 ⁵ M ^-1 × sec ^-1 , about 2.02×10 ⁵ M ^-1 × sec ^-1 , about 1.76×10 ⁵ M ^{- 1} × sec ^-1 , about 1.72 × 10 ⁵ M ^-1 × sec ^-1 , about 2.73 × 10 ⁵ M ^-1 × sec ^-1 , about 1.43 × 10 ⁵ M ^-1 × sec ^-1 , about 9.01 × 10 ⁵ M ^-1 × s ^-1 , about 3.13 × 10 ⁵ M ^-1 × s ^-1 , about 5.03 × 10 ⁵ M ^-1 × s ^-1 , about 3.02 × 10 ⁵ M ^-1 × s ^-1 , about 2.73 × 10 ⁵ M ^-1 × s ^-1 , about 1.78 × 10 ⁵ M ^-1 × s ^-1 , about 2.98 × 10 ⁵ M ^-1 × s ^-1 , about 4.31 × 10 ⁵ M ^-1 × s ^-1 2.27×10 ⁵ M ^-1 × s ^-1 , about 3.14 × 10 ⁵ M ^-1 × s ^-1 , about 2.81 × 10 ⁵ M ^-1 × s ^-1 , about 4.73 × 10 ⁵ M ^-1 × s ^-1 , about 3.26×10 ⁵ M ^-1 ×sec ^-1 , about 1.73×10 ⁵ M ^-1 ×sec ^-1 , about 2.68×10 5 M ^-1 ×sec ^-1 , about 2.63× ^{10 5} M ^-1 ×sec ^{-1 , approx . _ _ _ _ _ _ _ _ ×} sec ^{-1 ,} approx ^. 4.63 ^× 10 ⁵ M ^-1 ×sec ^{-1 , approx . -1} ×sec ^-1 or about 3.53×10 ⁵ M ^-1 ×sec ^-1 .

[00308] In some embodiments, the antibody has a k _{off of} about 7.51x10 ^-3 sec ^-1 , about 6.33x10 ^-2 sec ^-1 , about 4.70x10 ^-2 sec ^-1 , about 7.82x10 ^-4 sec ^-1 , about 4.70×10 ^-2 sec ^-1 , about 1.05×10 ^-2 sec ^-1 , about 3.65×10 ^-1 sec ^-1 , about 1.60×10 ^-1 sec ^-1 , about 7.11×10 ^-3 sec ^-1 , about 6.44×10 ^-3 sec ^-1 , about 3.85×10 ^-2 sec ^-1 , about 2.30×10 ^-2 sec ^-1 , about 5.33×10 ^-2 sec ^-1 , about 9.14×10 ^-2 sec ^-1 , about 1.80×10 ^-3 sec ^-1 , about 8.15×10 ^-3 sec ^-1 , about 3.85×10 ^-4 sec ^-1 , about 1.34×10 ^-4 sec ^-1 , about 2.29×10 ^-4 sec ^-1 , about 4.37×10 ^-3 sec ^-1 , about 3.71×10 ^-3 sec ^-1 , about 4.06×10 ^-3 sec ^-1 , about 6.66×10 ^-2 sec ^-1 , about 2.02×10 ^-3 sec ^-1 , about 2.00×10 ^-4 sec ^-1 , about 5.26×10 ^-3 sec ^-1 , about 1.13×10 ^-2 sec ^-1 , about 3.28×10 ^-3 sec ^-1 , about 2.76×10 ^-3 sec ^-1 , about 2.86×10 ^-4 sec ^-1 , about 2.43×10 ^-4 sec ^-1 , about 2.13×10 ^-4 sec ^-1 , about 6.09×10 ^-4 sec ^-1 , about 8.39×10 ^-4 sec ^-1 , about 8.15×10 ^-3 sec ^-1 , about 1.32×10 ^-4 sec ^-1 , about 1.11×10 ^-4 sec ^-1 , about 2.43×10 ^-4 sec ^-1 , about 2.13×10 ^-4 sec ^-1 , about 6.09×10 ^-4 sec ^-1 , about 8.15×10 ^-3 sec ^-1 , about 1.32×10 ^-4 sec ^-1 or about 1.11×10 ^-4 sec ^-1 .

[00309] In some aspects, K _D , k _a and k _d are determined at 25°C. In some embodiments, K _D , k _{a ,} and k _d are determined by surface plasma resonance. In some embodiments, K _D , k _a , and k _d are determined using the methods described in the examples.

5. Inhibition of CD39

[00310] In some aspects, the antibody reduces the affinity of CD39 for its substrate. In some aspects, the antibody inhibits the function of CD39 on tumor cells. In some aspects, the antibody inhibits or blocks the release of ADP or AMP from CD39. In some aspects, the antibody inhibits or blocks CD39 processivity.

[00311] In some aspects, the antibody binds to CD39 but does not inhibit ATPase. In some aspects, the antibody binds to CD39 and inhibits extracellular CD39 activity but not cellular ATPase activity. In some aspects, the antibody binds to both the extracellular domain of CD39 and cellular CD39 and can inhibit both the extracellular domain of CD39 and cellular CD39. In some aspects, these antibodies do not compete with A1 and/or other antibodies for binding to the extracellular domain.

6. CD39 analysis

[00312] In some embodiments, the antibody binds to a CD39 epitope. In some aspects, CD39 has a sequence identical to the amino acid sequence shown in SEQ ID: 249. In some aspects, the epitope has a sequence that is identical to the amino acid sequence shown in SEQ ID: 249. In some aspects, the epitope is in the extracellular domain of CD39. In some aspects, the extracellular domain corresponds to all or at least a portion of amino acids 38-478 of SEQ ID: 249. In some aspects, an epitope has an amino acid sequence that is 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to the sequence presented in the sequence of SEQ ID: 249, or the extracellular domain in whole or in part. In some aspects, the epitope has a sequence that is identical to or corresponds to residues 143-158 and/or residues 274-277 of SEQ ID: 249. In some aspects, the epitope is located in the E143-N158 region on a human CD39 polypeptide with the sequence shown in SEQ ID: 249. : 249. In some aspects, the epitope has a sequence that is 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% identical to residues 143-158 or 274-277 of the sequence presented in the SEQ sequence ID: 249. In some aspects, the epitope has 1, 2, 3, 4, 5, 6, 7, 8, or 9 substitutions from residues 143-158 of the sequence shown in SEQ ID: 249. In some aspects, the epitope has 1, 2 or 3 substitutions from residues 274-277 of SEQ ID: 249. In some aspects, the antibody is contacted with any of the residues indicated in FIG. 14E, Table 1. In some aspects, the antibody is contacted with any of the residues indicated in FIG. 14E, Table 2. In some aspects, the antibody binds to D150, E153 and/or R154 or N99 and none, one, two or three of D150, E153 and R154 or any of the above, individually or in combinations.

[00313] In some aspects, the antibody competes with 1, 2, 3, 4, or 5 antibodies 27536, 27571, 28347, 27579, or 27597 as shown in FIG. 14A. In some aspects, the antibody competes with 1, 2, 3, 4, or 5 antibodies 27536, 27571, 28347, 27579, or 27597 as shown in FIG. 14A. In some aspects, the antibody competes with 1, 2, or 3 antibodies 25571, 27536, or 27549 as shown in FIG. 14C. In some aspects, the antibody competes with 1, 2, or 3 antibodies 25571, 27536, or 27549 as shown in FIG. 14C.

[00314] In some aspects, the antibody inhibits the CD39 enzyme's conversion of ATP to ADP and/or ADP to AMP. In some aspects, the antibody inhibits platelet aggregation. In some aspects, the antibody reduces or prevents the activation of phospho antigen-specific T cells selected from mucosal-associated invariant cells and γδ T cells. In some aspects, the antibody inhibits angiogenesis. In some aspects, the antibody reduces phosphate, ADP, AMP and/or adenosine levels and/or increases ATP levels. In some aspects, the antibody increases the function of effector T cells. In some aspects, the antibody reduces the number of regulatory T cells in tissues or in circulating blood. In some aspects, the antibody reduces the number of regulatory T cells or the activity of regulatory T cells. In some aspects, the antibody enhances B cell function. In some aspects, the antibody enhances the function of antigen-presenting cells. In some aspects, the antibody inhibits the processing of at least one phospho antigen from a phosphorylated isoprenoid, a phosphorylated vitamin B metabolite, and/or a phosphorylated riboflavin.

[00315] In some aspects, the antibody has a limited ability to limit the ATPase of the soluble or extracellular domain. In some aspects, the antibody has a limited ability to inhibit the ATPase of the cellular and/or extracellular domain of CD39.

7. Variants of glycosylation

[00316] In certain embodiments, an antibody can be modified to increase, decrease, or eliminate the degree to which it is glycosylated. Glycosylation of polypeptides is usually either "N-linked" or "O-linked".

[00317] "N-linked" glycosylation refers to the attachment of a carbohydrate moiety to the side chain of an aspartic residue. The tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are recognizable sequences for enzymatic attachment of a carbohydrate moiety to an aspartic side chain. Thus, the presence of any of these tripeptide sequences in a polypeptide creates a potential glycosylation site.

[00318] "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.

[00319] The addition or removal of N-linked glycosylation sites to an antibody can be accomplished by changing the amino acid sequence when one or more of the tripeptide sequences described above are created or deleted. Adding or removing O-linked glycosylation sites to an antibody can be accomplished by adding, deleting, or substituting one or more serine or threonine residues to or within the sequence of the antibody, as the case may be.

[00320] In certain embodiments, such an antibody is glycosylated. In certain embodiments, such an antibody is deglycosylated. Carbohydrates can be removed by standard methods. In certain embodiments, such an antibody is aglycosylated, for example, by expression in a system that is not glycosylated.

8. Variants of the Fc region

[00321] In certain embodiments, amino acid modifications can be introduced into the Fc region of an antibody provided herein to create a variant Fc region. In certain embodiments, the Fc region variant has some, but not all, effector functions. Such antibodies may be useful, for example, in applications where the in vivo half-life of the antibody is important, but where certain effector functions are unnecessary or detrimental. Examples of effector functions include complement-dependent cytotoxicity (CDC) and antibody-directed complement-mediated cytotoxicity (ADCC). Numerous substitutions or divisions with altered effector function are known in the art.

[00322] A change in CDC and/or ADCC activity can be checked using an in vitro and/or in vivo assay. For example, to measure FcγR binding, an Fc receptor (FcR) binding assay can be performed. Primary cells for mediating ADCC, natural killer cells, express only FcγRIII, while monocytes express FcγRI, FcγRII and FcγRIII. FcR expression in hematopoietic cells is described by Ravetch and Kinet, Ann. Rev. Immunol., 1991, 9:457-492.

[00323] Non-limiting examples of an in vitro assay to assess ADCC activity of a molecule of interest are presented in US Patent Nos. 5,500,362 and 5,821,337; Hellstrom et al., Proc. Natl. Acad. sci. U.S.A., 1986, 83:7059-7063; Hellstrom et al., Proc. Natl. Acad. sci. U.S.A., 1985, 82:1499-1502; and Bruggemann et al., J. Exp. Med., 1987, 166:1351-1361. Useful effector cells for this assay include peripheral blood mononuclear cells (PBMC) and natural killer (NK) cells. Alternatively, or additionally, the ADCC activity of a molecule of interest can be assayed in vivo using an animal model, such as that described by Clynes et al. Proc. Natl. Acad. sci. U.S.A., 1998, 95:652-656.

[00324] A C1q binding assay can also be performed to verify that the antibody is unable to bind to C1q and therefore has no CDC activity. Examples of C1q binding assays include those described in WO 2006/029879 and WO 2005/100402.

[00325] Complement fixation reactions include those described, for example, in Gazzano-Santoro et al., J. Immunol. Methods, 1996, 202:163-171; Cragg et al., Blood, 2003, 101:1045-1052; and Cragg and Glennie, Blood, 2004, 103:2738-2743.

[00326] FcRn binding and in vivo clearance (half-life determination) can also be measured, for example, using the methods described in Petkova et al., Intl. Immunol., 2006, 18:1759-1769.

9. Antibody preparation

9.1. Antigen preparation

[00327] The CD39 antigen that is used to produce antibodies may be intact CD39 or a fragment of CD39. Intact CD39 or a CD39 fragment may be in the form of an isolated protein or may be expressed by the cell. Those of skill in the art will also recognize other forms of CD39 useful in generating antibodies.

9.2. Monoclonal antibodies

[00328] Monoclonal antibodies can be obtained, for example, using the hybridoma method, first described in the work of Kohler and others. Nature, 1975, 256:495-497, and / or using methods with recombinant DNA (see, for example, Patent USA No. 4,816,567). Monoclonal antibodies can also be obtained, for example, using phage or yeast libraries. See, for example. US Patents 8,258,082 and 8,691,730.

[00329] According to the hybridoma method, a mouse model or other suitable animal host model is immunized to induce lymphocytes that produce or are capable of producing antibodies that specifically bind to the protein used for immunization. Alternatively, lymphocytes can be immunized in vitro. The lymphocytes are then fused with myeloma cells using a suitable fusion factor such as polyethylene glycol, resulting in a hybridoma cell. See Goding JW, Monoclonal Antibodies: Principles and Practice ^3rd ed. (1986) Academic Press, San Diego, CA.

[00330] Hybridoma cells are seeded and grown in a suitable culture medium that contains one or more substances that inhibit the growth or survival of non-fused, parental myeloma cells. For example, if the parent myeloma cells are deficient in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT), hybridoma culture media will typically contain hypoxanthine, aminopterine, and thymidine (HAT medium), substances that inhibit the growth of HGPRT-deficient cells.

[00331] Beneficial myeloma cells are cells that fuse efficiently, maintain stable high levels of antibody production by selected antibody-producing cells, and are sensitive to environmental conditions such as the presence or absence of HAT medium. Among such cells, preferred myeloma cell lines are mouse myeloma lines derived from MOP-21 and MC-11 mouse tumors (available from the Salk Institute Cell Distribution Center, San Diego, CA) and SP-2 or X63-Ag8- 653 (available from American Type Culture Collection, Rockville, MD). There are also descriptions of the production of human monoclonal antibodies by human myeloma and mouse-human heteromyeloma cell lines. See, for example, Kozbor, J. Immunol., 1984, 133:3001.

[00332] Once hybridoma cells have been identified that produce antibodies with the desired specificity, affinity, and/or biological activity, selected clones can be subcloned in limiting dilution procedures and grown by standard methods. See Goding, above. Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium. In addition, hybridoma cells can be grown in vivo as ascitic tumors in an animal.

[00333] DNA encoding monoclonal antibodies can be immediately isolated and sequenced using standard procedures (eg, using oligonucleotide probes capable of specifically binding to genes encoding heavy and light chains of monoclonal antibodies). Thus, hybridoma cells can serve as a useful source of DNA encoding antibodies with desired properties. Once isolated, the DNA can be placed into expression vectors which are then transfected into host cells such as bacteria (eg E. coli), yeast (eg Saccharomyces or Pichia sp.), COS cells, Chinese hamster ovary cells, or myeloma cells, which do not otherwise produce antibody to produce monoclonal antibodies.

9.3. Humanized antibodies

[00334] Humanized antibodies can be created by replacing most or all of the structural parts of a monoclonal antibody with the corresponding human antibody sequences. Accordingly, a hybrid molecule is created in which only the antigen-specific variable, or CDR, consists of a sequence of non-human origin. Methods for making humanized antibodies include methods described, for example, in Winter and Milstein, Nature, 1991, 349:293-299; Rader et al., Proc. Nat. Acad. sci. U.S.A., 1998, 95:8910-8915; Steinberger et al., J. Biol. Chem., 2000, 275:36073-36078; Queen et al., Proc. Natl. Acad. sci. U.S.A., 1989, 86:10029-10033; and US Patent Nos. 5,585,089, 5,693,761, 5,693,762 and 6,180,370.

9.4. human antibodies

[00335] Human antibodies can be generated by a variety of methods known in the art, such as using transgenic animals (eg, humanized mice). See, for example, Jakobovits et al., Proc. Natl. Acad. sci. U.S.A., 1993, 90:2551; Jakobovits et al., Nature, 1993, 362:255-258; Bruggermann et al., Year in Immuno., 1993, 7:33; and U.S. Patent Nos. 5,591,669, 5,589,369 and 5,545,807. Human antibodies can also be obtained from phage display libraries (see, for example, Hoogenboom et al., J. Mot. Biol., 1991, 227:381-388; Marks et al., J. Mol. Biol., 1991, 222:581-597; and U.S. Patent Nos. 5,565,332 and 5,573,905). Human antibodies can also be generated using in vitro activated B cells (see, for example, US Pat. Nos. 5,567,610 and 5,229,275). Human antibodies can also be obtained from yeast libraries (see, for example, US Pat. No. 8,691,730).

10. Vectors, host cells and recombinant methods

[00336] The present invention also provides isolated nucleic acids encoding anti-CD39 antibodies, vectors and host cells containing nucleic acids, and recombinant methods for producing antibodies.

[00337] For recombinant production of an antibody, the nucleic acid encoding it can be isolated and introduced into a replicable vector for further cloning (eg, DNA amplification) or expression. In some aspects, the nucleic acid can be obtained through homologous recombination, such as that described in US Patent No. 5,204,244.

[00338] Many different vectors are known in the art. Vector components typically include, but are not limited to, one or more of the following: a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence, such as those described in US Pat. No. 5,534,615.

[00339] The following are illustrative examples of suitable host cells.

Examples of suitable host cells are not limited to those given.

[00340] Suitable host cells include any prokaryotic (eg, bacterial), lower eukaryotic (eg, yeast) or higher eukaryotic (eg, mammalian) cell. Suitable prokaryotes include eubacteria such as gram-negative or gram-positive organisms, e.g. enterobacteria such as Escherichia (E. coli), Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella (S. typhimurium), Serratia (S. marcescans), Shigella, Bacilli (B. subtilis and B. licheniformis), Pseudomonas (P. aeruginosa) and Streptomyces. One useful host for cloning E. coli is E. coli 294, although other strains such as E. coli B, E. coli X1776 and E. coli W3110 are also suitable.

[00341] In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeasts are also suitable cloning or expression hosts for anti-CD39 antibody-encoding vectors. Saccharomyces cerevisiae, or common baker's yeast, is a commonly used lower eukaryotic host microorganism. However, a number of other genera, species and strains are available and useful, such as Schizosaccharomyces pombe, Kluyveromyces (K. lactis, K. fragilis, K. bulgaricus K. wickeramii, K. waltii, K. drosophilarum, K. thermotolerans, and K. marxianus), Yarrowia, Pichia pastoris, Candida (C. albicans), Trichoderma reesia, Neurospora crassa, Schwanniomyces (S. occidentalis), and filamentous fungi such as Penicillium, Tolypocladium and Aspergillus (A. nidulans and A. niger ).

[00342] Useful mammalian host cells include COS-7 cells, HEK293 cells; newborn hamster kidney (BHK) cells; Chinese hamster ovary (CHO) cells; mouse sertoli cells; African green monkey kidney cells (VERO-76) and the like.

[00343] The host cells used to produce the anti-CD39 antibody described herein can be cultured in a variety of media. Commercially available media such as Ham's F10, Minimal Culture Medium (MEM), RPMI-1640, and Dulbecco's Modified Eagle's Medium (DMEM) are suitable for culturing host cells. In addition, any of the media described in Ham et al., Meth. Enz., 1979, 58:44; Bames et al., Anal. Biochem., 1980, 102:255; and US Pat.

[00344] Any of these media can optionally be supplemented with hormones and/or other growth factors (such as insulin, transferrin, or epidermal growth factor), salts (such as sodium chloride, calcium, magnesium, and phosphate), buffers (such as HEPES) , nucleotides (such as adenosine and thymidine), antibiotics, micronutrients (defined as inorganic compounds typically present in micromolar final concentrations), and glucose or an equivalent energy source. Any other necessary additives may also be included at appropriate concentrations known to those skilled in the art.

[00345] Environmental conditions such as temperature, pH and the like are conditions that have previously been used for host cells selected for expression and are obvious to those skilled in the art.

[00346] When using recombinant methods, the antibody can be produced intracellularly, in the periplasmic space, or directly released into the environment. If the antibody is produced intracellularly, as a first step, debris, either host cells or lysed fragments, is removed, for example, by centrifugation or ultrafiltration. For example, Carter et al. (Bio/Technology, 1992, 10:163-167) describe a procedure for isolating antibodies that are secreted into the periplasmic space of E. coli. Briefly, the cell suspension is thawed in the presence of sodium acetate (pH 3.5), EDTA and phenylmethylsulfonyl fluoride (PMSF) for about 30 minutes. Cellular debris can be removed by centrifugation.

[00347] In some embodiments, the antibody is produced in a cell-free system. In some aspects, such a cell-free system is the in vitro transcription and translation system described in Yin et al., mAbs, 2012, 4:217-225, which is incorporated herein in its entirety by reference. In some aspects, the cell-free system uses a cell-free extract from a eukaryotic cell or from a prokaryotic cell. In some aspects, such a prokaryotic cell is E. coli. Cell-free expression of an antibody may be useful, for example, in cases where the antibody accumulates in the cell as an insoluble aggregate or when the yield from periplasmic expression is low.

[00348] When an antibody is released into the medium, supernatants from such expression systems are typically first concentrated using a commercially available protein concentration filter, such as an Amicon® or Millipore® Pellcon® ultrafiltration unit. In any of the preceding steps, a protease inhibitor such as PMSF may be used to inhibit proteolysis, and antibiotics may be used to prevent the growth of adventitious contaminants.

[00349] An antibody formulation prepared from cells can be purified, for example, by hydroxyapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, with affinity chromatography being a particularly useful purification method. The suitability of Protein A as an affinity ligand depends on the species and isotype of any immunoglobulin Fc domain present in the antibody. Protein A can be used to purify antibodies based on human γ1, γ2 or γ4 heavy chains (Lindmark et al., J. Immunol. Meth., 1983, 62:1-13). Protein G is useful for all mouse isotopes and for human γ3 (Guss et al., EMBO J., 1986, 5:1567-1575).

[00350] The matrix to which the affinity ligand is attached is most often agarose, but other matrices are also available. Mechanically stable matrices such as pore size glass or poly(styrenedivinyl)benzene provide higher flow rates and faster processing times than agarose. If the antibody contains a C _H3 domain, BakerBond ABX® resin is used for purification.

[00351] Other methods of protein purification also exist and can be used by those skilled in the art, such as ion exchange column fractionation, ethanol precipitation, reverse phase HPLC, silicon chromatography, heparin Sepharose® chromatography, chromatofocusing, electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate (SDS-PAGE) and fractionation with ammonium sulfate.

[00352] After any preliminary purification step(s) the mixture containing the antibody of interest and contaminants can be subjected to low pH hydrophobic interaction chromatography using an elution buffer at a pH in the range of about 2.5 to about 4.5, which is typically performed at low salt concentrations (eg, from about 0 to about 0.25 M salt).

11. Pharmaceutical compositions and routes of administration

[00353] Any of the compounds described herein may be included in any appropriate pharmaceutical composition and may be administered by any suitable route of administration. Suitable routes of administration include, but are not limited to, inhalation, intra-arterial, intradermal, intramuscular, intraperitoneal, intravenous, nasal, parenteral, pulmonary, and subcutaneous routes.

[00354] Such a pharmaceutical composition may contain one or more pharmaceutical excipients. Any suitable pharmaceutical excipient can be used, and suitable pharmaceutical excipients can be selected by one skilled in the art. Accordingly, the following pharmaceutical excipients are illustrative and these examples are not limiting. Additional pharmaceutical excipients include, for example, those described in the Handbook of Pharmaceutical Excipients, Rowe et al. (Eds.) 6th Ed. (2009)), which is incorporated herein in its entirety by reference.

[00355] In some embodiments, such a pharmaceutical composition contains an antifoam. Any suitable defoamer may be used. In some aspects, the defoamer is selected from alcohol, ether, oil, wax, silicone, surfactant, and combinations thereof. In some aspects, the defoamer is selected from mineral oil, vegetable oil, ethylene bis stearamide, paraffin wax, ether wax, fatty alcohol wax, long chain fatty alcohol, fatty acid soap, fatty acid ester, silicone glycol, fluorosilicone, polyethylene glycol-polypropylene glycol copolymer, polydimethylsiloxane - silicon dioxide, ether, octane alcohol, caprylic alcohol, sorbitan trioleate, ethyl alcohol, 2-ethyl-hexanol, dimethicone, oleyl alcohol, simethicone and combinations thereof.

[00356] In some embodiments, such a pharmaceutical composition contains a co-solvent. Illustrative examples of co-solvents include ethanol, poly(ethylene) glycol, butylene glycol dimethylacetamide, glycerin and propylene glycol.

[00357] In some embodiments, such a pharmaceutical composition contains a buffer. Illustrative examples of buffers include acetate, borate, carbonate, lactate, malate, phosphate, citrate, hydroxide, diethanolamine, monoethanolamine, glycine, methionine, guar gum, and monosodium glutamate.

[00358] In some embodiments, such a pharmaceutical composition contains a carrier or excipient. Illustrative examples of carriers or excipients include lactose, maltodextrin, mannitol, sorbitol, chitosan, stearic acid, xanthan gum, and guar gum.

[00359] In some embodiments, such a pharmaceutical composition contains a surfactant. Illustrative examples of surfactants include d-alpha tocopherol, benzalkonium chloride, benzethonium chloride, cetrimide, cetylpyridinium chloride, sodium docusate, glyceryl behenate, glyceryl monooleate, lauric acid, macrogol 15 hydroxystearate, myristyl alcohol, phospholipids, polyoxyethylene alkyl esters, polyoxyethylene sorbitol esters and fatty acids, polyoxyethylene stearates, polyoxylglycerides, sodium lauryl sulfate, sorbitan esters, and vitamin E polyethylene glycol succinate.

[00360] In some embodiments, such a pharmaceutical composition contains an anti-caking agent. Illustrative examples of anti-caking agents include calcium phosphate (tertiary), hydroxymethylcellulose, hydroxypropylcellulose, and magnesium oxide.

[00361] Other excipients that can be used in pharmaceutical compositions include, for example, albumin, antioxidants, antibacterial agents, antifungal agents, biodegradable polymers, chelating agents, controlled release agents, diluents, dispersing agents, dissolution enhancers, emulsifying agents, gelling agents, ointment bases, penetration enhancers, preservatives, solubilizing agents, solvents, stabilizing agents and sugars. Specific examples of each of these agents are described, for example, in the Handbook of Pharmaceutical Excipients, Rowe et al. (Eds.) 6th Ed. (2009), The Pharmaceutical Press, which is hereby incorporated by reference in its entirety.

[00362] In some embodiments, such a pharmaceutical composition contains a solvent. In some aspects, such a solvent is saline, such as sterile isotonic saline or dextrose solution. In some aspects, such a solvent is water for injection.

[00363] In some embodiments, the implementation of pharmaceutical compositions exist in the form of particles, such as microparticles or nanoparticles. Microparticles and nanoparticles can be formed from any suitable material such as a polymer or lipid. In some aspects, such microparticles or nanoparticles are micelles, liposomes, or polymersomes. In certain embodiments, the composition provided herein is a pharmaceutical composition or unit dosage form. The pharmaceutical compositions and unit dosage forms provided herein contain a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic antibodies.

[00364] Anhydrous pharmaceutical compositions and dosage forms containing an antibody are presented hereinafter, since water can accelerate the degradation of some antibodies.

[00365] The anhydrous pharmaceutical compositions and dosage forms described herein can be prepared using anhydrous or low moisture ingredients and low moisture or low air humidity conditions. Pharmaceutical compositions and dosage forms that contain lactose and at least one active ingredient that contains a primary or secondary amine may be anhydrous if significant exposure to moisture and/or air humidity is expected during manufacture, packaging and/or storage.

[00366] Anhydrous pharmaceutical composition should be prepared and stored in such a way that its anhydrous nature is preserved. Accordingly, anhydrous compositions can be packaged using materials known to prevent exposure to water so that they can be included in suitable formulary sets. Examples of suitable packaging include, but are not limited to, hermetically sealed foil pouches, plastic packaging, single dose packages (eg, ampoules), blister packs, and strip packs.

11.1. Dosage forms for parenteral use

[00367] In certain embodiments, parenteral dosage forms are provided. Dosage forms for parenteral use can be administered to subjects in various ways, including, but not limited to, subcutaneous, intravenous (including intravenous bolus), intramuscular and intraarterial administration. Because their administration generally bypasses the subject's natural defenses against contaminants, parenteral dosage forms are typically sterile or sterilizable prior to administration to a subject. Examples of parenteral dosage forms include, but are not limited to, solutions ready for injection, dry products ready for solution or suspension in a pharmaceutically acceptable vehicle for injection, suspensions ready for injection, and emulsions.

[00368] Suitable bases that can be used to prepare parenteral dosage forms are well known to those skilled in the art. Examples include, but are not limited to: US F. Water for Injection; aqueous bases such as, but not limited to, saline for injection, Ringer's solution for injection, dextrose for injection, saline dextrose for injection, and lactate Ringer's solution for injection; water soluble bases such as but not limited to ethyl alcohol, polyethylene glycol and polypropylene glycol; and non-aqueous bases such as but not limited to corn oil, cottonseed oil, peanut oil, sesame oil, ethyl oleate, isopropyl myristate, and benzyl benzoate.

[00369] Adjuvants that increase the solubility of one or more of the antibodies provided herein may also be included in parenteral dosage forms.

11.2. Dosed and single dosage forms

[00370] In the treatment of a human, the physician determines the dosage that he considers most appropriate in accordance with the prophylactic or therapeutic treatment and in accordance with the age, weight, condition and other factors related to the subject receiving treatment.

[00371] The amount of an antibody or composition that will be therapeutically or prophylactically effective in treating a disease or one or more of its symptoms will depend on the nature and severity of the disease or condition, as well as the route of administration of the antibody. The frequency and dosage will also vary according to factors specific to each subject depending on the specific treatment (eg, therapeutic or prophylactic agents), the severity of the disorder, the disease or condition, the route of administration, as well as age, body type, weight, response, and subject's history. Effective doses can be extrapolated from dose-response curves obtained from in vitro test systems or based on an animal model.

[00372] In some embodiments, exemplary dosages of the composition include amounts of antibody in milligrams or micrograms per kilogram of subject or sample weight (e.g., from about 10 micrograms per kilogram to about 50 milligrams per kilogram, from about 100 micrograms per kilogram to about 25 milligrams per kilogram, or from about 100 micrograms per kilogram to about 10 milligrams per kilogram). In certain embodiments, the dosage of the antibody herein, based on the weight of the antibody that is administered to a subject to prevent, treat, control, or alleviate a disease or one or more of its symptoms, is 0.1 mg/kg, 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 10 mg/kg, or 15 mg/kg or more of the subject's body weight. In another embodiment, the dose of a given composition, or a composition provided herein, administered to a subject to prevent, treat, control, or alleviate a disease or one or more of its symptoms is 0.1 mg to 200 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, from 0.1 mg to 25 mg, from 0.1 mg to 20 mg, from 0.1 mg to 15 mg, from 0.1 mg to 10 mg, from 0.1 mg to 7.5 mg, from 0.1 mg to 5 mg, from 0.1 mg to 2.5 mg, 0.25 mg to 20 mg, 0.25 mg to 15 mg, up to 0.25 mg to 12 mg, 0.25 to 10 mg, 0.25 mg to 7.5 mg, 0.25 mg to 5 mg, 0.5 mg to 2.5 mg , 1 mg to 20 mg, 1 mg to 15 mg, 1 mg to 12 mg, 1 mg to 10 mg, 1 mg to 7.5 mg, 1 mg to 5 mg, or 1 mg to 2.5 mg.

[00373] This dose may be administered on a suitable schedule, such as once, twice, three times, or four times a week. In some cases, it may be necessary to use doses of antibodies outside the ranges specified here, if it will be obvious to experts in this field. Moreover, it is noted that the clinician or treating physician will know how and when to interrupt, modify or discontinue treatment according to the response of the subject.

[00374] Various therapeutically effective amounts may be used for different diseases and conditions, which will be known to those skilled in the art. Similarly, amounts sufficient to prevent, control, treat, or alleviate such diseases, but not sufficient to cause adverse effects, or sufficient to reduce such effects associated with the antibodies specified herein, are also included in the doses and dosage schedules described here. doses. Further, when multiple doses of a composition as described herein are administered to a subject, not all doses need to be the same. For example, the dose administered to a subject may be increased to improve the prophylactic or therapeutic effect of the composition, or may be reduced to reduce one or more side effects experienced by a particular subject.

[00375] In certain embodiments, treatment or prophylaxis may begin with one or more loading doses of an antibody or composition as defined herein, followed by one or more maintenance doses.

[00376] In certain embodiments, a dose of an antibody or composition as defined herein may be used to achieve a steady state concentration of the antibody in the blood or serum of a subject. Stationary concentration can be determined by measurements in accordance with methods known to those skilled in the art, or it can be based on the physical characteristics of the subject, such as height, weight and age.

[00377] In certain embodiments, administration of the same composition may be repeated, and such administrations may be separated by at least 1 day, 2 days, 3 days, 5 days, 10 days, 15 days, 30 days, 45 days, 2 months, 75 days , 3 months or 6 months. In other embodiments, administration of the same prophylactic or therapeutic agent may be repeated and such administrations may be separated by at least 1 day, 2 days, 3 days, 5 days, 10 days, 15 days, 30 days, 45 days, 2 months, 75 days , 3 months or 6 months.

12. Therapeutic use

[00378] For therapeutic use, the antibodies provided herein are administered to a mammal, typically a human, in a pharmaceutically acceptable dosage form, such as those known in the art and those described above. For example, the antibodies provided herein may be administered to a human by intravenous bolus or continuous infusion over a period of time, intramuscular, intraperitoneal, intracerebrospinal, subcutaneous, intraarterial, intraarticular, intrathecal, or intratumoral routes. The presented antibodies can also be administered near the tumor, inside the focus or near the focus to provide local and systemic therapeutic effects. The intraperitoneal route of administration may be particularly useful, for example, in the treatment of an ovarian tumor.

[00379] The antibodies provided herein may be useful in the treatment of any disease or condition associated with CD39, such as cancer, autoimmune disease, and infections.

[00380] The antibodies provided herein can be used in the treatment of any appropriate type of cancer. Illustrative relevant cancers include, for example, acute lymphoblastic leukemia, acute myeloid leukemia, adrenocortical carcinoma, anal cancer, appendix cancer, astrocytoma, basal cell carcinoma, brain tumor, bile duct cancer, bladder cancer, bone cancer, breast cancer, bronchial tumor, Burkitt's lymphoma, primary undiagnosed carcinoma, cardiac tumor, cervical cancer, chordoma, chronic lymphocytic leukemia, chronic granulocytic leukemia, chronic myeloproliferative neoplasm, colon cancer, colorectal cancer, craniopharyngioma, cutaneous T-cell lymphoma, ductal carcinoma, embryonic tumor, endometrial cancer, ependymoma, esophageal cancer, esthesioneuroblastoma, fibrous histiocytoxanthoma, Ewing's sarcoma, eye cancer, germ cell tumor, gallbladder cancer, gastrointestinal tract cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, gestapionic trophoblastic disease, glioma, head and neck cancer, hairy cell leukemia, hepatic cell carcinoma, histiocytosis, Hodgkin's lymphoma, hypopharyngeal cancer, intraocular melanoma, pancreatic islet tumor, Kaloshi's sarcoma, kidney cancer, Langerhans cell histiocytosis, laryngeal cancer, leukemia, cancer of the lips and oral cavity, liver cancer, lobular carcinoma in situ, lung cancer, lymphoma, macroglobulinemia, malignant fibrous histiocytoma, melanoma, Merkel skin cancer, mesothelioma, metastatic squamous cell occult neck cancer, NUT median carcinoma, oral cancer, multiple endocrine neoplasia syndrome, multiple myeloma, mycosis fungoides, myelodysplastic syndrome, myelodysplastic/myeloproliferative neoplasm, nasal and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-Hodgkin's lymphoma, non-small cell lung cancer, oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, papillomatosis, paraganglioma, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromoblastoma, pituitary tumor, pleuropulmonary blastoma, primary brain lymphoma, prostate cancer, rectal cancer, renal cell carcinoma, renal pelvis and ureter cancer, retinoblastoma, rhabdoid tumor, salivary gland cancer , Cesari syndrome, skin cancer, small cell lung cancer, small intestine cancer, soft tissue sarcoma, spinal cord cancer, gastric cancer, T-cell lymphoma, teratoid tumor, testicular cancer, throat cancer, thymoma and thymus cancer, thyroid cancer, urethral cancer, uterine cancer, vaginal cancer, vulvar cancer, and Wilms tumor.

[00381] The antibodies provided herein can be used in the treatment of any appropriate autoimmune disease. Illustrative examples of autoimmune diseases, or diseases with an autoimmune component, include, for example, acute disseminated encephalomyelitis, acute necrotizing hemorrhagic leukoencephalitis, Addison's disease, agammaglobulinemia, alopecia areata, amipoidosis, ankylosing spondylitis, anti-MPM/anti-MBM nephritis, antiphospholipid syndrome, and autoimmune angioedema, autoimmune aplastic anemia, autoimmune vegetative-vascular dystonia, autoimmune hepatitis, autoimmune hyperlipidemia, autoimmune immunodeficiency, autoimmune inner ear disease, autoimmune myocarditis, autoimmune oophoritis, autoimmune pan creatitis, autoimmune retinopathy, idiopathic thrombocytopenic purpura, autoimmune ophthalmopathy, autoimmune urticaria, axonal and neuronal neuropathies, Balo's disease, Behcet's disease, bullous pemphigoid, cardiomyopathy, Castleman's disease, celiac disease, Chagas disease, chronic fatigue syndrome, chronic inflammatory demyelinating polyneuropathy, chronic recurrent osteomyelitis multiplex, Churg-Strauss syndrome, scarring pemphigoid/benign mucosal pemphigoid, Crohn's disease , Cogan's syndrome, cold agglutination syndrome, colitis, congenital heart block, Coxsackie myocarditis, CREST disease, mixed primary cryoglobulinemia, demyelinating neuropathy, dermatitis herpetiformis, dermatomyositis, Devic's disease (optocomyelitis), discoid lupus, Dressler's syndrome, endometriosis, eosinophilic esophagitis eosinophilic fasciitis erythema nodosum Guillain's syndrome - Barre, Hashimoto's encephalitis, Hashimoto's thyroiditis, hemolytic anemia, Henoch-Schonlein purpura, gestational herpes, hypogammaglobulinemia, idiopathic thrombocytopenic purpura, IgA nephropathy, IgG4-associated sclerosing disease, immunoregulatory lipoproteins, inclusion myositis, inflammatory bowel disease, interstitial cial cystitis, juvenile arthritis, juvenile diabetes (Type I diabetes), juvenile myositis, Kawasaki syndrome, Lambert-Eaton syndrome, leukocystoclastic vasculitis, Wilson's lichen, lichen sclerosus, ligneous conjunctivitis, IgA dependent linear dermatosis, lupus (SLE), Lyme disease (chronic), Meniere's disease, microscopic polyangiitis, mixed connective tissue disease, Moray's ulcer, Mucha-Habermann's disease, multiple sclerosis, myasthenia gravis, myositis, narcolepsy, optomyelitis (Devika), neutropenia, ocular scarring pemphigoid, optic neuritis, palindromic rheumatism, PANDAS syndrome ( childhood autoimmune neuropsychiatric disorders associated with streptococcal infections), paraneoplastic cerebellar degeneration, paroxysmal nocturnal hemoglobinuria, Parry-Romberg syndrome, Parsonage-Turner syndrome, parsplanitis (peripheral uveitis), pemphigus, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia, POE MS- syndrome, polyarteritis nodosa, autoimmune polyglandular syndromes type I, II and III, polymyalgia rheumatica, polymyositis, dressler's postinfarction autoimmune syndrome, postcardiotomy syndrome, progesterone dermatitis, primary biliary cirrhosis, primary sclerosing cholangitis, psoriasis, psoriatic arthritis, idiopathic pulmonary fibrosis, prioderma gangrenosum , true erythrocyte aplasia, vibrodisease, reactive arthritis, sympathetic reflex dystrophy, Reiter's syndrome, relapsing polychondritis, restless legs syndrome, retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis, sarcoidosis, Schmidt's syndrome, scleritis, scleroderma, Sjögren's syndrome, sperm and testicular autoimmunity, stiff man syndrome, subacute septic endocarditis, Susak syndrome, sympathetic ophthalmia, Takayasu syndrome, temporal arteritis/giant cell arteritis, thrombotic disease, thrombocytopenic purpura, Tholos-Hunt syndrome, transverse myelitis, Type 1 diabetes, ulcerative colitis, undifferentiated connective tissue disease, uveitis , vasculitis, vesiculobullous dermatosis, vitiligo and Wegener's granulomatosis (modern name - eosinophilic granulomatosis).

[00382] The antibodies provided herein can be used in the treatment of any appropriate infection. Illustrative examples of suitable infections include, for example, hepatitis A virus, hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and other viral infections.

13. Diagnostic use

[00383] In some embodiments, the antibodies provided herein are used for diagnostic purposes. For example, an anti-CD39 antibody can be used in a CD39 protein assay. In some aspects, the antibody can be used to determine the expression of CD39 in various cells and tissues. Such an analysis may be useful, for example, in the evaluation of cancer and autoimmune disease.

[00384] For some diagnostic purposes, an antibody can be labeled with a detectable fragment. Suitable detectable moieties include, but are not limited to, radioisotopes, fluorescent labels, and enzyme-substrate labels. In another embodiment, the anti-CD39 antibody does not need to be labeled, but its presence can be determined using a labeled antibody that specifically binds to the anti-CD39 antibody.

14. Reagents for affinity purification

[00385] The antibodies of the present invention can be used as affinity purification agents. In this process, antibodies can be immobilized on a solid phase, such as resin or filter paper, using methods known in the art. The immobilized antibody is combined with a sample containing the CD39 protein (or fragment) to be purified, and then the substrate is washed with a suitable solvent that substantially removes all material in the sample except for CD39, which is associated with the immobilized antibody. Finally, the support is washed with another suitable solvent, such as glycine buffer, pH 5.0, which releases the CD39 protein from the antibody.

15. Sets

[00386] In some embodiments, an anti-CD39 antibody provided herein is provided in the form of a kit, namely a packaged combination of reagents in predetermined quantities with instructions for performing the procedure. In some embodiments, such a procedure is a diagnostic analysis. In other embodiments, the implementation of such a procedure is a therapeutic procedure.

[00387] In some embodiments, such a kit also contains a diluent for reconstitution of the anti-CD39 antibody. In some embodiments, the anti-CD39 antibody is provided in the form of a pharmaceutical composition.

EXAMPLES

Example 1 Selection of CD39 Antigen Binding Proteins

[00388] CD39 antigen-binding proteins are selected from a synthetic library of human antibodies present on the surface of yeast cells in IgG format as described in general, for example, in documents WO2009036379; WO2010105256; WO2012009568; and in Xu et al. Protein Eng. Des. Sel., 2013, 26:663-670 (each of which is incorporated herein in its entirety by reference), and in more detail below. The sequences and characteristics of the antigen-binding proteins isolated from the recombinant library are shown in Table S.

[00389] Eight naive human synthetic yeast libraries, each with ^~ 10E+09 diversity, were propagated as described in WO2009036379; WO2010105256; WO2012009568; and in Xu et al. Protein Eng. Des. Sel., 2013, 26:663-670; each of which is incorporated herein in its entirety by reference. For the first two rounds of selection, a magnetic microcarrier sorting method was used using the Miltenyi MACS® system as described by Siegel et al., J. Immunol. Meth., 2004, 286:141-153. The next rounds of selection were carried out using sorting based on flow cytometry. For all rounds of selection, the antigen was the extracellular domain (previously referred to as ECD) of biotinylated human CD39, and decreasing concentrations of antigen were used at each subsequent round of selection. In addition to antigen selection, several rounds of selection were performed to reduce the number of non-specific binding components using soluble membrane proteins from Chinese hamster ovary cells (see references WO2014179363 and Xu et al., Protein Eng. Des. Sel., 2013, 26:663 -670, each of which is incorporated herein in its entirety by reference). After the last round of sorting, the yeast was plated and individual colonies were selected for characterization and for selection of clones for affinity maturation.

[00390] Antibody variable domains of interest have been synthesized, with codon optimization to maximize transient expression in host cells. The variable regions were cloned into expression vectors containing human immunoglobulin constant domains and their sequence checked. The antibody heavy and light chain vector pairs were transfected into Expi293 cells using the Expifectamine system (Invitrogen). Transient cultures were harvested on Day 4 and the IgG titer of the clarified cell culture supernatant was analyzed by biolayer interferometry using the Octet platform (ForteBio). The antibodies were then purified on a Protein A column and eluted using low pH glycine. The purified antibody samples were then buffer exchanged or dialyzed into buffers compatible with further processes.

[00391] The purity of the antibodies was assessed by testing samples by polyacrylamide gel electrophoresis in the presence of sodium dodepil sulfate and on an analytical size exclusion chromatography column.

[00392] Light chain shuffling: Light chain plasmids were extracted from naive products (described herein) and transformed into a complete naive light chain library with 10E+06 diversity. Selections were performed as described above with one round of magnetic sorting and three rounds of fluorescent sorting using decreasing amounts of biotinylated ECD antigen for the respective rounds. Selected individual heavy chains in the primary discovery process were also independently transformed into individual off-the-shelf light chain libraries with 10E+06 diversity, and selections were made as described above with one round of magnetic sorting and three rounds of fluorescence sorting using a reducing amount of biotinylated ECD antigen. for the respective rounds.

Example 2: Affinity Maturation

[00393] Optimization of naive clones was performed using three maturation strategies; diversification of CDR-H1 and CDR-H2; diversification of CDR-H3; diversification of CDR-L1, L2 and L3; permutations of diversified heavy and light chains.

[00394] Selection of CDR-H1 and CDR-H2: CDR-H3 from clones selected from each of the light chain batch diversification, light chain diversification, and naïve component detection assay were independently recombined into finished libraries with CDR-H1 and CDR-H2 variants with >10E+8 diversity, and selections were made using the ECD antigen. Affinity pressures were applied using decreasing concentrations of antigen.

[00395] CDR-H3 Selection: Clones obtained from the CDR-H1 and CDR-H2 selection procedure were subjected to additional rounds of affinity maturation via heavy chain dimeric mutagenesis. Selections were made using ECD as the antigen, generally as described above, but with the addition that fluorescent sorting was used for all rounds of selection.

[00396] CDR-L1, L2, L3 Selection: Clones obtained from the CDR-H1 and CDR-H2 selection procedure were subjected to additional rounds of affinity maturation via light chain mutagenesis. The source of CDR-L1 and CDR-L2 diversity was the off-the-shelf library and the source of CDR-L3 diversity was dimeric mutagenesis. Selections were made using ECD as the antigen, generally as described above, but with the addition that fluorescent sorting was used for all rounds of selection, with one round of magnetic sorting followed by three rounds of fluorescent sorting in the CDR process described here. -L1, L2, L3.

[00397] Diversified Heavy Chain and Light Chain Swapping: Products from heavy chain diversification and light chain diversification described above were recombined and selections were made using ECD as antigen, generally as described above, but with the addition that fluorescent sorting was used for all selection rounds.

Example 3: Monovalent affinity of anti-hCD39 antibodies for the extracellular domain of recombinant CD39

[00398] Binding kinetics were measured using the Octet Red96 system (ForteBio) at 25° C. in running buffer (1x Pall ForteBio Kinetic Buffer diluted in PBS or Tris pH 7.4). Briefly, 1.25 mg/ml of unlabeled anti-hCD39 antibodies were immobilized onto sensors based on antibodies to the human Fc fragment. After a short reference step in running buffer, the sensors were exposed to various concentrations (10-300 nM) of rhCD39-ECD-His (R&D Systems) for the association step. The dissociation of the complex was monitored by once again exposing the sensors to the action of the running buffer. Data were processed using the ForteBio Octet software with initial subtraction, global fitting, and a 1:1 binding model to obtain association and dissociation rates. K _D was calculated based on the ratio of k _d to k _a .

[00399] For the data shown in FIG. ^1R2 >0.980. PF=poor fit. Association and dissociation kinetic analysis data were globally matched to a simple 1:1 Langmuir binding model, resulting in association rate (kon) and dissociation rate (koff) values. Equilibrium dissociation constants (K _D ) were calculated from the values of kon and koff. The kon values ranged from 1.93E+04 to 1.72E+06 M ^-1 s ^-1 , and the koff values ranged from 3.65E-01 to 1.HE-04 s ^-1 . K _D values ranged from 4.09E-07 to 7.31E-011 M, indicating that all antibodies bind to human CD39 ECD with moderate to high affinity.

[00400] The paralog specificity of anti-CD39 antibodies was assessed by biolayer interferometry using soluble recombinant human ENTDP2 and soluble recombinant human ENTDP3 (both R&D Systems). ENTDP2 and ENTDP3 are enzymes with functions similar to those of CD39. None of the antibodies showed detectable binding to ENTDP2 or ENTDP3 (data not shown). Thus, all antibodies show specific binding to human CD39.

Example 4 Inhibition of the extracellular domain of recombinant human CD39

[00401] Inhibition of the extracellular domain (ECD) of recombinant human CD39 by anti-CD39 antibodies was measured as follows. Recombinant human CD39/ENTPD1 (4397-EN from R&D systems), (final concentration 5 or 10 nM) combined with anti-CD39 IgGs (final concentration 0.25 or 1 μM) in 25 mM Tris, 5 mM CaCl ₂ , pH 7.5 at 96 well plate and incubated at room temperature for 2 hours. Then ATP (Sigma A1852-1VL) was added to a final concentration of 500 μm and kept at 37°C for 60 minutes. The plate was then placed in room temperature media and CellTiter-Glo luminescent cell viability assay solution was added to each well of the assay plate, mixed and read on a microplate reader using the "CellTiter-Glo luminescent" presets. Control reactions consisting of IgG negative control, IgG only (no ATP), ATP only (no CD39) were performed using the same method. The data values are the values of two parallel analyses.

[00402] Inhibition of human CD39 ECD enzyme activity by anti-CD39 antibodies was determined by measuring ATP levels using the CellTiter-Glo assay (FIGS. 2A-E). ATP enzymatic catabolism by CD39 ECD was controlled in the presence of isotype control antibody or without IgG with mean luminescence signal intensities ranging from 38 to 857 relative light units. luminescence signals were significantly higher than for the isotope control antibody (average luminescence signal intensities range from 4890 to 20329). In contrast, the reference antibody BY40va did not show significant inhibition of CD39 ECD in this assay because its luminescence signal intensity values were comparable to those of the isotope control antibody (average luminescence signal intensities range from 11 to 415).

Example 5 Antibodies Bind to Chinese Hamster Ovary Cells Expressing Human and Cynomolgus CD39

[00403] Binding of anti-CD39 IgGs to Chinese Hamster Ovary K1 CD39 cells. 100 nM IgGs (each antibody shown as a unique clone number in FIG.) were incubated at 25° C. for 30 minutes on ice in PBS with parental Chinese Hamster Ovary cells or genetically engineered Chinese Hamster Ovary cells for CD39 expression. human or cynomolgus macaque (Macaca fascicularis) (CD39 Chinese hamster ovary cells). Cells were then washed with ice-cold phosphate buffered saline and incubated with fluorescently labeled goat anti-human IgG for 20 minutes on ice. Cells were washed and resuspended in ice-cold phosphate-buffered saline before analysis by flow cytometry. The binding levels shown are the ratio of mean fluorescence intensity (MFI) values for anti-CD39 antibodies binding to CD39 Chinese hamster ovary cells to the MFI values for anti-CD39 antibodies binding to parental Chinese hamster ovary cells.

[00404] Anti-CD39 antibodies bound to Chinese hamster ovary cells expressing cellular human CD39 (CD39 Chinese hamster ovary cells) and showed no significant binding to parental Chinese hamster ovary cells (FIGS. 2F-J). The binding of these antibodies to Chinese Hamster Ovary CD39 cells ranged from 10-fold to 2033-fold relative to baseline data. Antibodies 28337 and 27575 did not show significant binding to Chinese Hamster Ovary CD39 cells (only fold 2 to 4 fold relative to baseline) (FIGS. 2F-J), indicating that these antibodies do not have low affinity for the human cellular form. CD39.

[00405] The orthologous specificity of anti-CD39 antibodies was assessed by flow cytometry using Chinese hamster ovary cells engineered to express cynomolgus or mouse CD39. Anti-CD39 antibodies bound to cynomolgus monkey CD39 to the same extent as human CD39 (FIG. 2 F-J). None of the anti-CD39 antibodies showed detectable binding to mouse CD39. Thus, anti-CD39 antibodies are cross-reactive with cynomolgus monkey CD39 but not with mouse CD39.

Example 6 Short Term ATPase Assay of Cell Surface CD39 Antibodies Binding in MEL-28 or 721 Cells and CD39 Inhibiting Antibodies on MEL-28 Cells

[00406] Cells were incubated with serially diluted anti-CD39 antibodies for 30 minutes at 4°C. Cells were washed 3 times in fluorescence activated cell sorting (FACS) assay buffer (PS, 2% PBS and 2 mM EDTA) and then incubated with a secondary antibody (goat anti-human IgG, Southern Biotech) at a ratio of 1:100 for 30 minutes at 4°C. Cells were washed, resuspended in FACS buffer and analyzed for binding by flow cytometry on a BD Celesta.

[00407] 3.5×10 ⁴ MEL-28 cells per well were washed with Tris buffer and incubated with serially diluted (100-0.00013 nM) antibody for 30 minutes at 37°C. 50 μM ATP was added to each well and incubated with cells in within 15 minutes. Supernatants were collected and analyzed in a malachite green assay (R&D) according to the manufacturer's protocol. Phosphate released as a result of ATP processing by the CD39 enzyme was used as an indicator of enzyme activity. Palivizumab was used as an isotopic control, and ARL (Tocris) and POM-1 (Alpha Aesar), non-specific small molecule inhibitors of CD39, were used as positive controls at 100 μm.

[00408] All antibodies bound endogenously expressed CD39 on both cell lines with similar affinity with EC50 ranges of 0.05-0.28 µg/mL on MEL-28 (see Figure 3A) and ranges of 0.2-7.5 µg/mL on the cell line 721.22 (see Fig. 3B). The maximum signal (mean fluorescence intensity) differed between analyzed antibodies, even when the EC50 values were similar (FIGS. 3A-B).

[00409] After confirmation of cellular binding, anti-CD39 antibodies were analyzed for inhibition of ATPase activity on MEL-28 cells in a short-term 30-minute phosphate assay using malachite green. Isotype control was used to determine the maximum possible signal from ATP processing in MEL-28 cells - the addition of 50 μM ATP to cells typically gave a phosphate signal of 55-60 μM for this assay (see Fig. 4A and B). Anti-CD39 antibodies inhibited ATPase activity in MEL-28 cells by 60-80% at the highest concentration of antibodies analyzed (100 nM) - this level of inhibition was similar to non-specific ATPase inhibitors ARL and POM1 (see Fig. 4A). All IC50 values for anti-CD39 antibodies in MEL-28 analysis using malachite green were in the subnanomolar range (see Fig. 4B).

Example 7 ATP Conservation Quantified by Exposing MEL-28 Cells to CD39 Enzymatic Inhibitors

[00410] 3.5x10 ⁴ MEL-28 cells were plated overnight at 37°C. Cells were washed with Tris buffer to remove phosphate. 100 nM monoclonal antibodies titrated to 0.005 pM were incubated with cells for 30 minutes at 37°C. 50 μM ATP was added and incubated for 15 minutes. The supernatants were collected and frozen. Supernatants were thawed and analyzed for ATP using EnzyLight (EnzyLight ATP Assay Kit, BioAssay Systems). Palivizumab was used as an isotype control, and ARL (Tocris) and POM-1 (Alpha Aesar) used at 100 μM, which are non-specific small molecule inhibitors, were used as CD39 positive controls.

[00411] Virtually no ATP was detected 30 minutes after ATP was added to cells in untreated and/or isotype-treated samples (see Figure 5A), and all anti-CD39 antibodies analyzed prevented ATP processing in a dose-dependent manner (see Fig. 5A, B). Most of the analyzed anti-CD39 antibodies prevented ATP processing by the CD39 enzyme to the same extent as ARL (see Fig. 5A). The IC50 values of the anti-CD39 antibody in the ATP conservation assay ranged from 0.02-0.1 nM. The total antibody activity in this assay was comparable to the results of a phosphate assay using malachite green.

Example 8: Analysis of Antibody Inhibition of CD39 Activity in MEL-28 Overnight

[00412] 3.5x10 ⁴ MEL-28 cells per well were plated and incubated with antibodies overnight at 37°C. Cells were washed to remove PBS. Cells were then exposed to antibodies in X-VIVO 15 FBS-free medium overnight at 37°C. ATP was then added at a concentration of 50 μM over 15 minutes. Supernatants were collected and analyzed using the AMP-Glo kit according to the manufacturer's instructions (Promega). Palivizumab was used as an isotype control and POM-1 (Alpha Aesar), a non-specific small molecule inhibitor of CD39, was used as a positive control at 100 μM.

[00413] Anti-CD39 antibodies assayed by AMPGlo analysis on MEL-28 cells showed persistent inhibition of ATPase activity as indicated by reduced levels of AMP present in supernatants (see FIG. 6A). Inhibition of CD39 activity by antibodies was equivalent to or greater than POM-1 exposure. These data were comparable to those obtained from short-term analysis of CD39 using malachite green on MEL-28 (see FIG. 4). Antibodies tested in overnight assays showed IC50 values in the CD39 AMPGlo inhibition assay ranged from 0.01 to 0.3 nM. (see Fig. 6B).

Example 9: Anti-CD 39 antibodies bind to primary cynomolgus monkey and human B cells

[00414] B cells were isolated from a human donor leukopaque using the EasySep B cell isolation kit (STEMCELL Technologies). Cynomolgus monkey monocytes were isolated from fresh cynomolgus monkey blood using a non-human primate CD 14 positive selection kit (Miltenyi), and the filtrate was collected and stained with CD4, CD8, CD20, CD16 and CD3 antibodies (BD). Human or cynomolgus B cells were incubated with serially diluted anti-CD39 antibodies (15 μg/ml, 7.5-fold serial dilution, 8-point) for 30 minutes at 4°C. Cells were washed 3 times in FACS buffer ( PS, 2% FBS, and 2 mM EDTA) and incubated with a secondary antibody (mouse anti-human IgG, southern biotech) at a ratio of 1:100 for 30 minutes at 4°C. Cells were washed 2 times in FACS buffer and resuspended in FACS buffer and analyzed on BD Celesta.

[00415] The detection of antibody binding is as described in FIG. 7, where B cells were incubated with serially diluted antibodies and detected using a fluorescently labeled antibody and analyzed by flow cytometry. The results are shown in FIG. 7 and appear to indicate that the antibodies specifically bind to both cynomolgus monkey B cells and human cells with EC506 values ranging from 0.02 µg/mL to 3.18 µg/mL (human) and from 0.03 µg/ml to 0.17 µg/ml (Javanese macaques). Similar binding was observed in human tumor cell lines (FIG. 3) where one antibody subset had a low maximum mean fluorescence intensity and one subpopulation had a high mean fluorescence intensity for both cynomolgus and human B cells.

Example 10 Antibodies Inhibit CD39 Activity on Human B Cells

[00416] B cells were isolated from human leukopaque using the EasySep B cell isolation kit (STEMCELL Technologies). 5×10 ⁴ B cells per well were washed with Tris buffer and incubated with serially diluted (100-0.00013 nM) antibodies for 30 minutes at 37°C. 50 μM ATP was added to each well and incubated with cells for 2 hours. Supernatants were collected and analyzed in a malachite green assay (R&D) according to the manufacturer's protocol. Phosphate released as a result of ATP processing by the CD39 enzyme was used as an indicator of enzyme activity. Palivizumab was used as an isotype control and ARL (Tocris) and POM-1 (Alpha Aesar), non-specific small molecule inhibitors of CD39, were used as positive controls at 100 μm.

[00417] The antibodies were found to bind to primary human and cynomolgus B cells (see FIG. 7) and the next step was to evaluate inhibition of ATP hydrolysis by detecting free phosphate (Pi) in a malachite green assay. The results are shown in FIG. 8 and they indicate that anti-CD39 antibodies inhibit enzymatic inhibition/dephosphorylation of ATP by primary human B cells. The ability of antibodies to inhibit enzyme activity was comparable regardless of the ratio of high and low max. the average intensity of fluorescence detected when binding to human B cells (FIG. 7).

Example 11 Anti-CD39 Antibodies Inhibit ATPase Activity on Human and Cynomolgus Monocytes

[00418] Human monocytes were isolated from the leukopaque using the EasySep Human Monocyte Isolation Kit (STEMCELL). Cynomolgus monkey monocytes were isolated from cynomolgus monkey whole blood using a non-human primate CD 14 positive selection kit (Miltenyi). Monocytes at a concentration of 5×10 ⁴ cells per well were washed with Tris buffer and incubated with serially diluted (100-0.00013 nM) anti-CD39 antibodies for 30 minutes at 37C. 50 μM ATP was added to the cells and incubated for 15 minutes at 37°C, then the supernatants were collected and analyzed using malachite green (R&D) for phosphate levels. Palivizumab was used as an isotype control and ARL (Tocris) and POM-1 (Alpha Aesar), non-specific small molecule inhibitors of CD39, were used as positive controls at 100 μM.

[00419] CD39 expression was determined on human leukocytes with the highest expression found on monocytes (Thromb Res. 2007; 121(3):309-17). In view of this information, it was important to evaluate the ability of anti-CD39 antibodies to inhibit ATPase activity on the cell surface. As shown in FIG. 7, anti-CD39 antibodies bind to both human and cynomolgus monkey B cells. The inhibition of enzyme activity on human and cynomolgus monkey monocytes should be assessed. The results show that all antibodies are able to inhibit CD39 ATPase activity on human and cynomolgus monkey monocytes with similar activity.

Example 12 Anti-CD39 Antibodies Bind to Primary Human TRegs and Inhibit CD39 Enzyme Activity

[00420] Treg cells were isolated from human donor leukopaque using CD4 ⁺ CD25 ⁺ CD127 ^dim regulatory T cell isolation kit II (Miltenyi). Human Treg cells were incubated with serially diluted anti-CD39 antibodies (100 nM - 0.00064 nM) for 30 minutes at 4°C. Cells were washed 3 times in FACS buffer (PS, 2% PBS and 2 mM EDTA) and incubated with secondary antibody (mouse antibodies to human IgG, southern biotech) at a ratio of 1:100 for 30 minutes at 4°C. Cells were washed 2 times in FACS buffer, resuspended in FACS buffer and analyzed on BD Fortessa.

[00421] CD4 ⁺ CD25 ⁺ CD127 ^dim human Treg cells were washed 3 times with Tris buffer. Cells were incubated with anti-CD39 antibodies (100 nM - 0.00064 nM) for 30 minutes at 37C. 50 μM ATP was added to the cells and supernatants were collected after incubation for 15 minutes at 37°C. Supernatants were analyzed for phosphate levels using a malachite green reagent kit (R&D). Palivizumab was used as an isotype control and ARL (Tocris) and POM-1 (Alpha Aesar), non-specific small molecule inhibitors of CD39, were used as positive controls at 100 μm.

[00422] CD39 has been found to be expressed on human regulatory T cells (Treg) and is important for their suppressive function via ATP hydrolysis to the immunosuppressive adenosine. (Blood. 2007 Aug 15;110(4):1225-32, Cellular & Molecular Immunology (2017) 14,521-528; doi:10.1038/cmi.2016.30). To determine whether anti-CD39 antibodies were able to inhibit CD39 enzymatic activity, it was important to evaluate binding to human Tregs. Treg cells were isolated from human peripheral blood mononuclear cells and Treg was purified and antibodies were analyzed for binding by flow cytometry. The result shows that anti-CD39 antibodies bind to human Tregs (FIG. 10). Of note, both high peak and low mean fluorescence intensity profiles were observed, similar to human B cell staining (see FIG. 8). Also analyzed the ability of antibodies to inhibit ATPase ability on human Treg cells. All antibodies inhibit CD39 Treg enzyme activity (see FIG. 11) as well, regardless of the observed staining with the maximum average fluorescence intensity.

Example 13 Anti-CD39 Antibodies Enhance CD8 ⁺ T Cell Response in CMV Secondary Response Assay

[00423] Frozen peripheral blood mononuclear cells (PBMCs) were thawed and resuspended at 3×10 ⁶ /ml and cultured in the presence of CMV peptides (Miltenyi, PeptTivator CMV pp65) for 3 days in complete (10% PBS) medium at 37°C The T cells were then purified (STEMCELL, EasyStep) and left for 24 hours at 37°C ^. per well and left overnight at 37°C. The next day, 5×10 ⁴ T cells were added to APC. Antibodies were added at 25 μg/ml plus 100 μM ATP + 1 μM EGNA and Golgi Plug/Stop with CMV peptides and incubated at 37°C for 5 hours. T cells were stained and analyzed for intracellular IFN-gamma on a Fortessa flow cytometer (Becton Diclandson).

[00424] Adenosine has been found to inhibit T cell activation. (bit J Oncol. 2008 Mar; 32(3):527-35). As a rate-limiting enzyme in the ATP/ADP-AMP-adenosine pathway, inhibitory CD39 reduced the levels of immunosuppressive adenosine and increased the level of immunoactivating ATP, which increased T cell activity. In order to evaluate the role of anti-CD39 antibodies in inhibiting ATP/ADP-AMP hydrolysis, preventing the formation of adenosine, which could lead to an increased T cell response, an analysis of the secondary CMV response was performed. PBMCs were cultured in the presence of CMV peptide pool for 3 days and then T cells were purified and cultured with autologous PBMCs + CMV peptides and ATP + EGNA. After 5 hours, T cells were analyzed for the production of IFN-gamma. The results show that some of the anti-CD39 antibodies were able to increase the activity of CD8 ⁺ T cells in the secondary CMV response assay. This demonstrates that inhibition of CD39 enzyme activity prevents adenosine formation and preserves ATP levels, resulting in a robust T cell response to the peptide:MHC complex. In addition, not all antibodies that bind to CD39 and inhibit cell surface enzymatic activity are capable of enhancing T cell response, and the specific interaction between the antibody and CD39 is important.

Example 14 Evaluation of Antibodies for Inhibition of CD39 Activity on Mel-28 and Human Monocytes

[00425] 3.5×10 ⁴ MEL-28 cells per well were incubated with 100 nM to 0.32 pM monoclonal antibodies for 30 minutes. 50 μM ATP was added and incubated for 15 minutes. The supernatant was analyzed for free phosphate (Pi) using a Malachite Green Phosphate Detection Kit (R&D Systems cat. no. DY996). Palivizumab was used as an isotype control and ARL (Tocris) and POM-1 (Alpha Aesar) used at 100 μM, which are non-specific small molecule inhibitors, were used as positive controls. Cynomolgus monkey monocytes were isolated from cynomolgus monkey whole blood using a non-human primate CD 14 positive selection kit (Miltenyi). Monocytes at a concentration of 5×10 ⁴ cells per well were washed with Tris buffer and incubated as described above.

[00426] Differences were found when comparing anti-CD39 antibodies for enzyme inhibition in short term analyses. Some were able to block the release of free phosphate (Pi) as measured by the malachite green assay, while others showed very little activity. For example, BY40v9 and 9-8 B exhibited very little or no enzyme inhibition at 100 nM concentrations using MEL-28 cells or primary human monocytes compared to other anti-CD39 antibodies (eg, 29579 and 28347), which able to inhibit ATPase activity at low nanomolar concentrations.

[00427] 9-8B was produced as described in US 2017/0335007 A1 using SEQ ID 22 and 23 as hIgG4. BY40v9 is an engineered variant of the BY40 antibody described in WO 2009/095478 A1, SEQ ID 1 and 5. We have attempted to express BY40 as described for human IgG4, but repeated attempts have been unsuccessful. The VH described in the SEQ 1 sequence appears to be missing a few N-terminal residues compared to the germline VH, so we engineered the missing residues with the closest germline sequence from IMGT (http://imgt. org/), which gave BY40-v9, which was expressed and specifically associated with rhCD39-ECD and cellular ECD.

Example 15 Construction of a Chimera and Region of Expressed Binding

(a) Exemplary antibodies that bind to the ECD of soluble recombinant CD39 and cellular CD39 but do not inhibit ATPase activity and do not compete with cellular inhibitors for binding to ECD inhibitors

[00428] 0.04-3.3 nM rhCD39-ECD (R&D Systems) was incubated with buffer, 50 µg/ml antibody or 100 µM POM-1 (Alpha Aesar) for 1 hour at 37°C in assay buffer (25 mM Tris pH 7.5 , 5 mm CaCl ₂ ), then added ATP (Sigma) to a final concentration of 10 μm, and the reaction mixture was further incubated for 30 min at 37°C. Free phosphate production (Pi) was further measured using a Malachite Green Phosphate Detection Kit (R&D Systems).

[00429] These cells were incubated in assay buffer with 10-25 μg/ml antibody, 100 μM POM-1, or 100 μM ARL for 30 min at 37°C 5% CO ₂ . ATP was added to a final concentration of 50 μM and incubation was continued for 15 minutes. The supernatant was analyzed for free phosphate (Pi) using a malachite green phosphate detection kit. Palivizumab is used as an isotopic control, while POM-1 and ARL are non-specific small molecule inhibitors of CD39.

[00430] The A1 antibody was immobilized onto an anti-mouse IgG-Fc (AMC) biosensor (ForteBio). hCD39-ECD association was then monitored for 180 seconds by biolayer interferometry using the Octet system (ForteBio), after which the biosensor was immersed in a competitive antibody and continued to be monitored for another 180 seconds. The association of the second antibody was recorded as an upward shift in the interference notation and indicates that the antibodies bind to different epitopes on CD39. No change in the interference recording indicated that A1 was preventing the second antibody from binding to CD39.

[00431] Although A1 binds hCD39 cECD (FIG. 1), it does not inhibit its ATPase activity. Although A1 binds to cellular CD39 (FIG. 2), it does not directly inhibit the ATPase activity of CD39 expressed on OAW42 to a significant extent. Capture of the hCD39 ECD by A1 prevents subsequent binding to A1 (FIG. 14A, sensogram lower right), but does not prevent binding of inhibitory antibodies such as 27536, 27571, 27579, 27597, or 38347.

[00432] Commercially available antibody A1 is a group of anti-human CD39 monoclonal antibodies that do not directly inhibit CD39 ATPase activity and do not bind to any other anti-CD39 antibodies described herein. More than 30 antibodies have been found that do not inhibit ECD ATPase activity, do not inhibit cellular CD39 ATPase activity, but do not compete with A1 for ECD binding. These antibodies can be considered to bind to the anti-hCD39 A1 antibody.

(b) Example of antibodies that have a limited ability to inhibit the ATPase activity of soluble recombinant and cellular CD39 and bind separately from other inhibitors of cellular CD39

[00433] The same methods as described above were used, except that instead of A1, a representative antibody was immobilized using an anti-human IgG-Fc (ANC) biosensor.

[00434] The anti-hCD39 antibodies represented by 27536 and 28337 are a group of antibodies that bind to soluble ECD and cellular CD39 and have the ability to inhibit their ATPase activity, but do not compete with other inhibitors for binding to CD39. Both 27536 and 28337 are able to inhibit ATP hydrolysis by hCD39 ECD compared to isotype or buffer controls as indicated by μM Pi as described here (upper left panel). 27536 and 28337 inhibit hydrolysis of CD39 expressed on MEL-28 and OAW42 cells as shown compared to isotype control. Antibodies 27536 and 28337 represent a strong binding group of inhibitory anti-hCD39 antibodies because they are prevented from binding to CD39 ECD by another binding group that does not interfere with other inhibitory antibodies 27571, 27579, 27597 and 38347 (see inset (c) at the bottom of Fig. 14B ).

(c) Example of antibodies that inhibit the ATPase activity of the ECD of soluble recombinant CD39. but do not inhibit cellular CD39 and bind separately from other CD39 ECD inhibitors.

[00435] Methods are used as described above, with the addition of an experimental design in which inhibition of 0.37 nM CD39 by 50 microns/ml antibody was prevented by an ATP concentration of 3-100 microns. Also for antibodies applied incubation for 18 hours with antibody or isotype control. Finally, an additional 30 second control dip in buffer was applied between antigen capture and a 300 second dip in the second competitive antibody.

[00436] The anti-hCD39 antibodies represented by 27549 are a group of antibodies that can bind to ECD and cellular CD39, but can only inhibit the ATPase activity of ECD but not the ATPase activity of cellular CD39. FIG. 14C (top left) shows that antibody 27549 is able to inhibit ATP hydrolysis by hCD39 ECD compared to isotype and buffer controls. Also in FIG. 14C (upper right) it can be seen that 27549 is unable to inhibit the hydrolysis of CD39 expressed on MEL-28 cells compared to the isotype control. Antibodies 27536 and 28337 represent a strong binding group of anti-hCD39 inhibitory antibodies because they are prevented from binding to CD39 ECD by a different binding group that does not interfere with other inhibitory antibodies such as 27571, 27579, 27597 and 38347 (see FIG. 14C, bottom) .

[00437] Antibody 27549 is a group of anti-human CD39 monoclonal antibodies that directly inhibit the ATPase activity of soluble CD39 ECD while inhibiting cellular CD39 despite being able to bind to CD39 expressed on cells (FIG. 2). It does not compete with A1 or any of the other anti-CD39 inhibitory antibodies described here for binding to ECD, so 27549 represents another binding group of anti-hCD39 antibodies (see FIG. 14C).

(d) An example of antibodies that inhibit the ATPase activity of ECD and cellular CD39 and bind separately from other CD39 ECD inhibitors and/or cellular inhibitors

[00438] The methods described above are used.

[00439] Antibodies 27571, 27579, and 28347 represent a group of anti-human CD39 antibodies that directly inhibit the ATPase activity of soluble CD39 ECD and inhibit cellular CD39 without competing with A1, cellular inhibitors 27536 or 28337, or ECD inhibitor 27549 (FIG. 14A- C) for binding to the ECD. 27571, 27579 and 28347 were able to inhibit ATP hydrolysis by hCD39 ECD compared to isotype and buffer controls (see FIG. 14D, left). 27571, 27579 and 28347 also inhibit the hydrolysis of CD39 expressed on MEL-28 cells compared to the isotype control (see FIG. 14D, right). These cellular inhibitors represent another binding group of anti-hCD39 antibodies (see FIG. 14D).

(e) Examples of inhibitory antibodies that strongly contact CD39

[00440] Chimeras were created by replacing the human CD39 sequence with the mouse CD39 sequence in mammalian expression vectors. The chimeras were expressed in Chinese hamster ovary cells and the ability of anti-human CD39 antibodies to bind to the chimeras was tested by a fluorescence-activated cell sorting (FACS) assay. Briefly, the cells were washed and blocked in FACS buffer (PBS/2% PBS) for 30 minutes on ice. They were then incubated in 15 μg/ml of anti-human CD39 antibody diluted in FACS buffer × 1 h on ice. After 2 washes, cells were incubated with fluorescently labeled anti-human Fc, anti-mouse Fc or anti-mCD39 (R&D Systems 495826) diluted in FACS buffer according to manufacturer's instructions x 30 min. on ice. After 2 washes, cells were resuspended in FACS buffer and analyzed for BD Fortessa. The data was processed using FlowJo. Positive binding was labeled "yes" and no binding was labeled "no". Examples of FACS plots used to create this table are shown in FIG. 14.F and 14.G.

[00441] Chimeras formed between human and murine CD39 differ in regions critical for antibody contact that are unique to inhibitory antibodies such as 31414, 31895, 31873, 31901, 31905, reference antibodies such as BY40v9 and 9-8 B, and commercial antibodies such as A1 and 498403. Columns 1 and 3 describe the human CD39 sequences flanking the mouse CD39 sequence described in column 2. Column 4 gives the exact mouse amino sequence in the chimera.

[00442] The antibodies described so far have no or minimal cross-reactivity to mouse CD39, which is 78% identical to human CD39 in the extracellular domain. In this regard, chimeras were created between human and mouse CD39 to determine the region(s) that are critical for antibody recognition and binding. To this end, 8 chimeras were generated with sequence substitutions selected based on sequence diversity between human and mouse CD39 and surface exposure potential based on the crystal structures of rat ENTPD1 and rat ENTPD2. Thus, these 8 chimeras do not fully interrogate all potential contact residues. All antibodies tested were able to bind to Chimeras Nos. 1, 3, 5, 6, 7 and 8, indicating that these chimeras retained a common global structural integrity. A1 and 498403 lost their ability to bind to Chimera #4, indicating that residues critical to their contact with human CD39 had been lost. A1, 498403, BY40v9, and 9-8B were able to communicate with Chimera #2, indicating that this Chimera maintained overall global structural integrity. In contrast, inhibitory antibodies 31414, 31895, 31901, 31905, and 31873 were able to bind to all chimeras except Chimera #2. Thus. Chimera #2 has lost residues critical to binding to these antibodies, and therefore E143-N158 form part or all of the human CD39 epitope for these antibodies. Notably, these antibodies belong to the binding group represented by 27571, 27579 and 28347 in FIG. 14D, i.e. they do not bind to the binding groups of anti-CD39 antibodies represented by antibodies A1, 27536 or 27549.

[00443] Chimeras were generated by mutagenesis of Chimera #2 or WT hCD39 expression vectors. Residues for mutagenesis were chosen based on the divergence between human and mouse CD39. Chimeras were expressed in Chinese Hamster Ovary cells, and the ability of anti-human CD39 antibodies to bind to chimeras was tested by a fluorescence-activated cell sorting (FACS) assay, as described in FIG. 14E. Table 2 Positive binding was labeled "yes" and no binding was labeled "no". Examples of FACS plots used to create this table are shown in FIG. 14.F and 14.G.

[00444] Specific residues critical for antibody binding can distinguish inhibitory antibodies 31414, 31418, and 31895 from 31901, 31905, and 31873. Individual amino acids in the murine human-mouse Chimera #2 sequence, when converted back to the corresponding human residue (in resulting in Chimeras #9,10), restore the ability of antibodies 31895, 31414, 31418 to bind to CD39, but not the ability of 31901,31905 or 31873 to bind to CD39. Mutation of individual residues in the context of fully human CD39 (Chimera No. 11, 12) did not affect the binding ability of any of the analyzed antibodies. The co-mutation of two human residues into cognate mouse residues (Chimeras Nos. 13, 14) did not affect the binding of antibodies 31414, 31418, or 31895. On the contrary, antibodies 31901, 31905, and 31873 completely lost their ability to bind to Chimeras Nos. 13 and 14. The ability of these antibodies to bind to said chimera was determined by a fluorescence-activated cell sorting (FACS) assay. In particular, FIG. 14F and FIG. 14G show representative FACS plots used to populate this table, and FIG. 14G shows the importance of human CD39 N99, R154, and/or S153 residues in recognition by antibodies represented by 31901, 31905 and 31873.

[00445] As shown in FIG. 14E, Table 1, inhibitory antibodies 31414, 31418, 31895, 31901, 31905, and 31873 can be distinguished from other anti-CD39 monoclonal antibodies based on their ability to recognize Chimera #2. In Table 2, these antibodies also differ in the increase or loss of the ability to bind to hCD39 specific point mutants or Chimera #2. Thus, these antibodies, by binding to the same general region of human CD39, form distinct associations with various critical residues in hCD39. Because these antibodies share the requirement for residues E143-N158, they may share some common bond residues yet differ based on the demonstrated bond points.

(f) FACS plots indicating the importance of human CD39 residue D150 and/or E153 in recognition of the antibodies represented by 31414, 31418 and 31895. and FACS plots indicating the importance of human CD39 residues N99. R154 and/or E153, for recognition by antibodies represented by 31901. 31905 and 31873

[00446] The same methods are used as described above for examples of inhibitory antibodies that form strong associations with CD39.

[00447] The ability of said antibodies to bind to said chimera was determined by FACS.

[00448] While all antibodies 31414, 31418, 31895, 31873, 31901, and 31905 share a common requirement for human CD39 residues E143-N158, these antibodies enter into various critical associations with residues within or outside of this region. Thus, antibodies belonging to the binding group represented by antibodies 27571, 27579 and 28347 (FIG. 14.D) can also be divided into at least two more groups based on sensitivity to expressed residues. There are at least 5 binding groups: (1) A1-like antibodies that compete with each other for ECD binding do not inhibit ECD activity, but do not compete with antibodies in binding groups 2, 3, 4 or 5 for ECD binding and form critical bindings to N275-1277, as indicated by loss of binding to Chimera #4; (2) 27536/28337-like antibodies that compete with each other for binding to ECD and can inhibit the ATPase activity of both ECD and cellular CD39, but do not compete with antibodies in binding groups 1, 3, 4, or 5 for binding to ECD ; (3) 27549-like antibodies that compete with each other for ECD binding and can inhibit CD39 ECD but not cellular CD39 and do not compete with antibodies in binding groups 1, 2, 4, or 5 for ECD binding; (4) 31414/31418/31895-like antibodies that form critical bonds with E143-N158 in cellular CD39, including (but not limited to) D150 and E153, inhibit the ATPase activity of both ECD and cellular CD39, compete with each other for binding to ECD, but do not compete with antibodies in binding groups 1, 2, or 3 for binding to ECD; and (5) 31873/31901/31905-like antibodies that form critical associations with E143-N158 in cellular CD39, including (but not limited to) E153 and R154, as well as sensitivity to the N99 residue, inhibit the ATPase activity of both ECD and cellular CD39 , compete with each other for ECD binding, but do not compete with each other in binding groups 1, 2, or 3 for ECD binding. Thus, there are anti-human CD39 antibodies that can differ based on their affinity for ECD, affinity for cells, ability to inhibit ECD ATPase activity, ability to inhibit cellular ATPase activity, and CD39 binding points. For example, 27549 binds well to both ECD (FIG. 1) and cells (FIG. 2), but can only inhibit ECD ATPase activity. 27579 binds weakly to ECD but is a potent inhibitor of cellular CD39.

Example 16 Anti-CD39 Antibodies Are Reversible Allosteric Non-Competing Inhibitors Due to _Vmax Suppression of _Vmax

[00449] An anti-CD39 or isotype control antibody (100 nM final concentration) was incubated with MEL-28 cells (35,000 MEL-28 cells per well) endogenously expressing human CD39 at 37°C for 20 minutes in the presence of EnzChek reagents ( PNP & MESG). Immediately after addition of ATP (final concentrations range from 0-450 μM), the rate of hydrolysis of ATP to free phosphate (Pi) by CD39 was monitored over time at Abs360nm using a SpectraMax i3x plate reader. The initial enzyme rate, ν0, was determined from the linear region of the Pi versus time curve for each ATP concentration. A plot of ν0 and [ATP] was plotted using non-linear regression of the Michaelis-Menten kinetic model.

[00450] The rate of ATP hydrolysis by CD39 expressed on MEL-28 cells can be significantly reduced by anti-CD39 antibodies (see FIG. 15). The rate of ATP hydrolysis in the presence of anti-CD39 antibodies varies from 1.2 to 2.7 μM Pi per minute, which is much less than the rate of ATP hydrolysis observed in the presence of an isotype control antibody (7.7 μM Pi per minute), and is similar in value to a pan-ATPase inhibitor ARL (1.2 μM Pi per minute).

[00451] A plot of initial rate and ATP concentration for multiple concentrations of anti-CD39 antibody 29872 shows that the mechanism of inhibition of this IgG antibody is non-competitive (see FIG. 16A.). The decrease in initial rate is constant for ATP concentrations above 100 µM (100, 200, 300 and 500 µM) in the presence of 5 nM 29872. ). The monovalent Fab form of the anti-CD39 antibody 29872 showed a very similar inhibition profile (see FIG. 16B), indicating that the CD39 inhibitory activity of 29872 is independent of the bivalent IgG structure and the potential properties that may result from IgG bivalence. eg CD39 cross-linking.

[00452] Many of the other anti-CD39 antibodies tested in this assay showed a similar profile for enzymatic inhibition of CD39 (data not shown), indicating that they may also be non-competitive inhibitors, non-competitive inhibitors, or mixed inhibitors of CD39. The mechanism of enzymatic inhibition of these antibodies indicates that they retain their complete inhibition of enzymatic inhibition of CD39 at high concentrations of ATP. Apparently, anti-CD39 antibodies are reversible inhibitors.

Example 17 Anti-CD39 Antibodies Can Induce CD39 Internalization on Cynomolgus Monocytes

[00453] Anti-CD39 antibodies were injected into cynomolgus monkeys to test their ability to down-regulate CD39 on the cell surface of cynomolgus monkey monocytes. CD39 internalization was analyzed by fluorescence-activated cell sorting of pre-dose whole blood samples on Day 1, Day 7 and Day 14 after antibody treatment. A non-competing anti-CD39-PE antibody (clone A1) was used to measure CD39 levels on CD14+ gated monocytes. Data are shown as mean A1-PE fluorescence intensity on gated cynomolgus monkey monocytes in FIG. 17.

[00454] Cynomolgus monkeys were injected with an anti-CD39 antibody at a concentration of 10 mg/kg. Blood samples were taken before injection and on Day 1, Day 7 and Day 14 after treatment. For each time point, 50 µl of cynomolgus whole blood was incubated with 30 µl of staining buffer (PBS, 2% PBS, 2 mM EDTA, 3% mouse serum, 5% goat serum) containing CD14 and CD20 antibodies (eBioscience) and Fc blocking reagent (BD) for 30 minutes at 40C. The CD39 antibody (clone eBioA1, eBioscience) was added to the sample and incubated for an additional 40 minutes at 4°C. After incubation, the samples were exposed to ASA lysis buffer. (ThermoFisher) for 10 minutes at room temperature to lyse red blood cells. Samples were washed several times with staining buffer and mixed with 1% PFA (Sigma) prior to analysis on a BD Fortessa X-20 flow cytometer. The total expression of the CD39 receptor on CD14 positive monocytes was determined by the average fluorescence intensity.

[00455] CD39 was highly expressed on cynomolgus monkey monocytes before antibody treatment in all blood samples analyzed (pre-dose). Anti-CD39 antibodies assayed in vivo had pronounced internalization profiles where antibody 1 treatment resulted in down-regulation of CD39 on the monocyte cell surface and antibody 2 had no effect on total CD39 levels. The apparent decrease in CD39 levels after treatment with antibody 1 was not due to competition of antibody A1 with antibody 1 for binding to CD39, since the epigones for A1 and antibody 1 are different from each other.

Example 18: Anti-CD39 antibody increases proliferation of stimulated human CD4 ⁺ and CD8 ⁺ T cells in the presence of exogenous ATP

[00456] Anti-CD3 + anti-CD28 stimulated peripheral blood mononuclear cells were exposed to anti-CD39 antibody 31895 or isotype control in the presence of 50 μM ATP for 96 hours. The proliferation of CD4 ⁺ and CD8 ⁺ T cells was measured by flow cytometry using the Cell Trace Violet kit.

[00457] FIG. 19 shows that an anti-CD39 antibody increases the proliferation of stimulated human CD4 ⁺ and CD8 ⁺ T cells in the presence of exogenous ATP. The left side shows CD8 ⁺ T cells, where the x-axis shows the antibody (nM) and the y-axis shows the % proliferation of CD8 ⁺ T cells. The right side shows CD4 ⁺ T cells where the x-axis shows antibody (nM) and the y-axis shows % CD4 ⁺ T cell proliferation. The inset on the right shows the symbols for the respective antibodies and controls.

Example 19 Anti-CD39 antibody increases stimulated peripheral blood mononuclear cell secretion of INF-γ, TNF-α and IL-2.

[00458] Human peripheral blood mononuclear cells were exposed to anti-CD3 ⁺ anti-CD28 and incubated with anti-CD39 antibody 31895 or isotype control in the presence (B) or absence (A) of exogenous ATP (50 μM). Supernatants were harvested 96 hours later and cytokine levels were measured using the Meso Scale Discovery Human Cytokine Level Kit.

[00459] FIG. 20 shows that anti-CD39 antibody 31895 increases cytokine secretion by activated anti-CD3 ⁺ anti-CD28 peripheral blood mononuclear cells in the absence (A) or presence (B) of exogenous ATP in a dose-dependent manner. The top row shows the results with the addition of exogenous ATP, and the bottom row shows the results without the addition of exogenous ATP. The x-axis shows the antibody (nM) and the y-axis shows the secretion of INF-γ, TNF-α and IL-2, respectively.

Example 20 Anti-CD39 antibody increases stimulated peripheral blood mononuclear cell secretion of INF-γ, TNF-α, IL-2 and IL-1β.

[00460] Human peripheral blood mononuclear cells were stimulated with anti-CD ⁺ anti-CD28 and incubated with anti-CD39 antibodies 31895, HAO-391 (see SEQ ID 10/SEQ ID 11 of WO 2017/089334), HAO mAb4 (see SEQ ID 12/ SEQ ID 13 of WO 2017157948) or isotopically controlled at a fixed concentration of 50 μg/ml in the presence of ATP. Supernatants were collected after 96 hours and analyzed using the Meso Scale Discovery Human Cytokine Level Kit.

[00461] FIG. 21 shows that anti-CD39 antibody 31895 increased cytokine release by activated peripheral blood mononuclear cells to a higher level than anti-CD39 antibody HAO-391 (VL SEQ ID 10; VH SEQ ID 11 from WO 2017/089334) and HAO mAb4 (VL SEQ ID 12; VH SEQ ID 13 of WO2017157948). The x-axis shows the antibody and/or conditions, and the y-axis shows INF-γ, TNF-α, IL-2 and IL-1β, respectively.

Example 21: Anti-39 antibody 31895 increases extracellular ATP accumulation and reduces adenosine production by CD39 ⁺ CD73 ⁺ SK-MEL-28 cells

[00462] SK-MEL-28 cells were exposed to 31895 isotype controls or small molecule inhibitors (EGNA, ARL or POM-1) for 1 hour and 50 μM ATP was added for 15 minutes, after which the supernatants were collected. Supernatants were analyzed for ATP levels using the AmpGlo Kit (A) and for adenosine levels by liquid chromatography with mass spectrometry (B). % Adenosine levels were normalized for isotype control (100%) and SK-MEL-28 CD39 KO cells (0%).

[00463] The results are shown in FIG. 22. The left graph shows the accumulation of ATP, and the right graph shows the formation of adenosine (liquid chromatography with mass spectrometry). The x-axis for each graph shows the conditions. The y-axis for the left graph shows ATP (µM) and the y-axis for the right graph shows % adenosine levels.

Example S: Sequences

[00464] Table S lists the sequences mentioned here.

Equivalents

[00465] The invention described above may cover many individual inventions with independent utility. While each of these inventions has been disclosed in its preferred form(s), the specific embodiments thereof disclosed and illustrated herein are not to be construed in a limiting sense as many variations are possible. The subject matter of the inventions includes all novel and non-obvious combinations and sub-combinations of various elements, characteristics, functions and/or features disclosed herein. In the following paragraphs, in particular, certain combinations and subcombinations are singled out, which are considered new and non-obvious. Inventions embodied in other combinations and subcombinations of characteristics, functions, elements and/or properties may be described in this application, in applications claiming priority with respect to this application, or in related applications. Such claims, whether directed to another invention or to the same invention, and whether they are broader, narrower, similar or different in scope than the original claims, are also considered to be included in the subject matter of the inventions. of the present invention.

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SEQUENCE LIST

<110> TIZONA THERAPEUTICS

SOROS, Vanessa

KOVALENKO, Maria

CORBIN, John

BEERS, Courtney

WIDBOOM, Paul Fredrick

WARFIELD, Joseph Robert

<120> ANTI-CD39 ANTIBODIES, COMPOSITIONS CONTAINING ANTI-CD39 ANTIBODIES,

AND METHODS OF APPLICATION OF ANTI-CD39 ANTIBODIES

<130> 117851.00014

<150> US 62/539,527

<151> 2017-07-31

<160> 298

<170>PatentIn version 3.5

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Gly Tyr Thr Phe Gln Ser Tyr

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<210> 5

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 5

Gly Tyr Thr Phe Phe Ser Tyr

15

<210> 6

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 6

Gly Tyr Thr Phe Val Ser Tyr

15

<210> 7

<211> 10

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 7

Gly Gly Thr Phe Ser Ser Leu Ala Ile Ser

1 5 10

<210> 8

<211> 10

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 8

Gly Gly Thr Phe Ser Lys Leu Ala Ile Ser

1 5 10

<210> 9

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 9

Gly Gly Thr Phe Ser His Thr

15

<210> 10

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 10

Gly Gly Thr Phe Ser Ser Leu

15

<210> 11

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 11

Gly Gly Thr Phe Ser Leu Leu

15

<210> 12

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 12

Gly Gly Thr Phe Gln Ser Leu

15

<210> 13

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 13

Gly Gly Thr Phe Pro Ser Asn

15

<210> 14

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 14

Gly Gly Thr Phe Ser Ala Met

15

<210> 15

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 15

Gly Gly Thr Phe Ala Ser Leu

15

<210> 16

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 16

Gly Gly Thr Phe Ser Trp Leu

15

<210> 17

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 17

Gly Gly Thr Phe Ser Ser Tyr

15

<210> 18

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 18

Gly Gly Thr Phe Gly Ser Tyr

15

<210> 19

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 19

Gly Gly Thr Phe Ser Lys Tyr

15

<210> 20

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 20

Gly Gly Thr Phe Gly Arg Tyr

15

<210> 21

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 21

Gly Gly Thr Phe Glu Ser Tyr

15

<210> 22

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 22

Gly Gly Thr Phe Ser Asn Tyr

15

<210> 23

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 23

Gly Gly Ala Phe Ser Ser Tyr

15

<210> 24

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Chothia

<400> 24

Gly Phe Thr Phe Ser Ser Tyr

15

<210> 25

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 25

Ser Tyr Tyr Met His

15

<210> 26

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 26

Ser Tyr Glu Met His

15

<210> 27

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 27

Ser Tyr Gln Met His

15

<210> 28

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 28

Ser Tyr Tyr Met Tyr

15

<210> 29

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 29

Ser Tyr Phe Met His

15

<210> 30

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 30

Ser Leu Ala Ile Ser

15

<210> 31

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 31

Lys Leu Ala Ile Ser

15

<210> 32

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 32

His Thr Ala Ile Ser

15

<210> 33

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 33

Ser Leu Pro Ile Ser

15

<210> 34

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 34

Leu Leu Ala Ile Ser

15

<210> 35

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 35

Ser Asn Ala Ile Ser

15

<210> 36

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 36

Ala Met Ala Ile Ser

15

<210> 37

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 37

Trp Leu Ala Ile Ser

15

<210> 38

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 38

Ser Tyr Ala Ile Ser

15

<210> 39

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 39

Ser Tyr Gly Ile Ser

15

<210> 40

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 40

Lys Tyr Gly Ile Ser

15

<210> 41

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 41

Asn Tyr Ala Ile Ser

15

<210> 42

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 42

Ser Tyr Ala Thr Ser

15

<210> 43

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 43

Ser Tyr Ala Ile Gly

15

<210> 44

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 44

Ser Tyr Ser Met Asn

15

<210> 45

<211> 5

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H1, Kabat

<400> 45

Ser Tyr Gly Met Asn

15

<210> 46

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 46

Asn Pro Ser Gly Gly Ser Thr

15

<210> 47

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 47

Asn Pro Ser Val Gly Ser

15

<210> 48

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 48

Asn Pro Ser Gly Gly Ser

15

<210> 49

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 49

Asn Pro Leu Gly Gly Gly

15

<210> 50

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 50

Asn Pro Arg Gly Gly Ser

15

<210> 51

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 51

Ile Pro Ile Phe Gly Thr

15

<210> 52

<211> 4

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 52

Gly Phe Gly Thr

1

<210> 53

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 53

Leu Pro Ile Gly Gly Thr

15

<210> 54

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 54

Leu Pro Ile Ala Gly Thr

15

<210> 55

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 55

Leu Pro Ile Phe Gly Glu

15

<210> 56

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 56

Ile Pro Arg Gly Gly Thr

15

<210> 57

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 57

Ile Pro Glu Phe Gly Ile

15

<210> 58

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 58

Ile Pro Ser Ile Gly Thr

15

<210> 59

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 59

Ile Pro Ile Ser Gly Thr

15

<210> 60

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 60

Ile Pro Thr Phe Gly Thr

15

<210> 61

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 61

Ser Ser Ser Ser Ser Tyr

15

<210> 62

<211> 6

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Chothia

<400> 62

Trp Tyr Asp Gly Ser Asn

15

<210> 63

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 63

Val Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 64

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 64

Arg Ile Asn Pro Ser Val Gly Ser Thr Trp Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 65

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 65

Arg Ile Asn Pro Ser Gly Gly Ser Thr Trp Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 66

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 66

Lys Ile Asn Pro Ser Gly Gly Ser Thr Trp Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 67

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 67

Val Ile Asn Pro Leu Gly Gly Gly Thr Ser Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 68

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 68

Ser Ile Asn Pro Arg Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 69

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 69

Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 70

<211> 15

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 70

Gly Ile Gly Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly

1 5 10 15

<210> 71

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 71

Gly Ile Leu Pro Ile Gly Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 72

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 72

Gly Ile Leu Pro Ile Ala Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 73

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 73

Gly Ile Leu Pro Ile Phe Gly Glu Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 74

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 74

Gly Ile Ile Pro Arg Gly Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 75

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 75

Ser Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Arg

1 5 10 15

gly

<210> 76

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 76

Ser Ile Ile Pro Glu Phe Gly Ile Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 77

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 77

Ser Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 78

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 78

Gly Ile Ile Pro Ile Ser Gly Thr Ala Asn Tyr Ala Gln Glu Phe Gln

1 5 10 15

gly

<210> 79

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 79

Gly Ile Ile Pro Thr Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 80

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 80

Ser Ile Ser Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 81

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H2, Kabat

<400> 81

Val Ile Trp Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 82

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 82

Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg His

1 5 10

<210> 83

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 83

Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Lys

1 5 10

<210> 84

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 84

Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Ser

1 5 10

<210> 85

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 85

Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Asn

1 5 10

<210> 86

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 86

Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Val

1 5 10

<210> 87

<211> 13

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 87

Gly Gly Ala Lys Tyr Ala Ser Thr Tyr Gly Met Asp Val

1 5 10

<210> 88

<211> 13

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 88

Gly Gly Ala Lys Tyr Ala Ser Thr His Gly Met Asp Val

1 5 10

<210> 89

<211> 13

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 89

Gly Gly Ala Lys Tyr Ala Ser Gln Leu Gly Met Asp Val

1 5 10

<210> 90

<211> 13

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 90

Gly Gly Ala Lys Tyr Ala Ser Lys Trp Gly Met Asp Val

1 5 10

<210> 91

<211> 13

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 91

Gly Gly Ala Lys Tyr Ala Val Gly Tyr Gly Met Asp Val

1 5 10

<210> 92

<211> 13

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 92

Gly Gly Ala Lys Tyr Ala Gly Arg Tyr Gly Met Asp Val

1 5 10

<210> 93

<211> 13

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 93

Gly Gly Ala Lys Tyr Ala Arg Thr Tyr Gly Met Asp Val

1 5 10

<210> 94

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 94

Glu Ser Gly Gly Tyr Arg Asp His Arg Leu Asp Val

1 5 10

<210> 95

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 95

Glu Ser Gly Thr Tyr Arg Asp His Arg Leu Asp Val

1 5 10

<210> 96

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 96

Glu Ser Gly Gly Tyr Arg Asp His Arg Leu Gly Val

1 5 10

<210> 97

<211> 15

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 97

Asp Phe Thr Asp Tyr Ser Ser Gly Tyr Ser Ser Gly Trp Thr Tyr

1 5 10 15

<210> 98

<211> 14

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 98

Asp Thr Leu Tyr Ser Ser Gly Ala Tyr Tyr Gly Tyr Asn Val

1 5 10

<210> 99

<211> 15

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 99

Ala Lys Arg Gly Tyr Asp Ser Tyr Gly Gly Val Tyr Phe Asp Tyr

1 5 10 15

<210> 100

<211> 18

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 100

Gly Pro Thr Val Thr Ala Thr Thr Ser Ile Gly Thr His Asn Trp Phe

1 5 10 15

Asp Pro

<210> 101

<211> 28

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 101

Glu Gly Arg Gly Tyr Asp Ser Ser Arg Tyr Tyr Lys Phe Trp Phe Asp

1 5 10 15

Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

20 25

<210> 102

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 102

Asp Gly Gly Gly Tyr Arg His His Tyr Phe Asp Leu

1 5 10

<210> 103

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 103

Glu Ser Gly Gly Tyr Arg Asp His Lys Leu Asp Val

1 5 10

<210> 104

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 104

Asp Gly Gly Gly Tyr Gln His His Tyr Phe Asp Leu

1 5 10

<210> 105

<211> 11

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 105

Asp Ser Gly Tyr His Arg His Tyr Ser Asp Tyr

1 5 10

<210> 106

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 106

Asp Pro Leu Gly Ile Arg Lys His Trp Phe Asp Pro

1 5 10

<210> 107

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 107

Asp Thr Pro Arg Trp Arg Tyr His Tyr Phe Asp Tyr

1 5 10

<210> 108

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 108

Glu Arg Arg Gly Ser Leu Ala Leu Gly Met Asp Val

1 5 10

<210> 109

<211> 19

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-H3

<400> 109

Asp Leu Gly Gly Tyr Ser Tyr Gly Glu Pro Tyr Tyr Tyr Tyr Tyr Gly

1 5 10 15

Met Asp Val

<210> 110

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 110

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 111

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 111

Arg Ala Ser Gln Ser Val Ala Ser Ser Tyr Leu Ala

1 5 10

<210> 112

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 112

Glu Ala Ser Gln Ser Val Ser Tyr Ser Tyr Leu Ala

1 5 10

<210> 113

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 113

Lys Ala Ser Glu Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 114

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 114

Arg Ala Ser Gln Tyr Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 115

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 115

Lys Ser Ser Gln Ser Val Leu Phe Ser Ser Asn Asn Lys Asn Tyr Leu

1 5 10 15

Ala

<210> 116

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 116

Lys Ser Ser Arg Ser Val Leu Phe Ser Ser Asn Asn Lys Asn Tyr Leu

1 5 10 15

Ala

<210> 117

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 117

Lys Ser Ser Lys Ser Val Leu Tyr Ser Asn Asn Asn Lys Asn Tyr Leu

1 5 10 15

Ala

<210> 118

<211> 11

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 118

Arg Ala Ser Gln Ser Val Gly Ser Asn Leu Ala

1 5 10

<210> 119

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 119

Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu

1 5 10 15

Ala

<210> 120

<211> 11

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 120

Gln Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn

1 5 10

<210> 121

<211> 11

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 121

Arg Ala Ser Gln Ser Val Ser Ser Tyr Leu Ala

1 5 10

<210> 122

<211> 11

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 122

Arg Ala Ser Gln Ser Val Ser Arg Tyr Leu Ala

1 5 10

<210> 123

<211> 11

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 123

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 124

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L1

<400> 124

Arg Ala Ser Gln Ser Val Ser Ser Asp Tyr Leu Ala

1 5 10

<210> 125

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 125

Gly Ala Ser Ser Arg Ala Thr

15

<210> 126

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 126

Gly Ala Ser Asn Arg His Thr

15

<210> 127

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 127

Tyr Ala Ser Ser Arg Ala Tyr

15

<210> 128

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 128

Gly Ala Ser Ser Arg Ala Asn

15

<210> 129

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 129

Tyr Ala Ser Ser Arg Ala Thr

15

<210> 130

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 130

Tyr Ala Ser Asn Arg Ala Thr

15

<210> 131

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 131

Trp Ala Ser Thr Arg Glu Ser

15

<210> 132

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 132

Trp Ala Ser Ser Arg Glu Ser

15

<210> 133

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 133

Trp Ala Ser Thr Arg Gln Ser

15

<210> 134

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 134

Trp Ala Ser Thr Arg Ala Ser

15

<210> 135

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 135

Gly Ala Ser Thr Arg Ala Thr

15

<210> 136

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 136

Gly Ala Ser Thr Arg Ala Ser

15

<210> 137

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 137

Asp Ala Ser Asn Leu Glu Thr

15

<210> 138

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 138

Asp Ala Ser Asn Arg Ala Thr

15

<210> 139

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 139

Asp Ala Ser Lys Arg Ala Thr

15

<210> 140

<211> 7

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L2

<400> 140

Lys Ala Ser Ser Leu Glu Ser

15

<210> 141

<211> 8

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 141

Gln Gln Tyr His Ser Tyr Ile Thr

15

<210> 142

<211> 8

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 142

Gln Gln Tyr His Asn Ala Ile Thr

15

<210> 143

<211> 8

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 143

Gln Gln Tyr Tyr Phe Tyr Ile Thr

15

<210> 144

<211> 8

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 144

Gln Gln Tyr His Ser Ala Leu Thr

15

<210> 145

<211> 8

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 145

Gln Gln Tyr His Gly Gly Ile Thr

15

<210> 146

<211> 8

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 146

Gln Gln Tyr His Arg Arg Ile Thr

15

<210> 147

<211> 8

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 147

Gln Gln Tyr His Ser Gly Ile Thr

15

<210> 148

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 148

Gln Gln Tyr Tyr Leu Tyr Pro Leu Thr

15

<210> 149

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 149

Gln Gln Tyr Trp Thr Tyr Pro Leu Thr

15

<210> 150

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 150

Gln Gln Tyr Leu Leu Tyr Pro Leu Thr

15

<210> 151

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 151

Gln Gln Tyr Leu Ile Trp Pro Leu Thr

15

<210> 152

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 152

Gln Gln Tyr Leu Leu Trp Pro Leu Thr

15

<210> 153

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 153

Gln Gln Phe Tyr Phe Phe Pro Pro Thr

15

<210> 154

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 154

Gln Gln Ala Tyr Thr Phe Pro Pro Thr

15

<210> 155

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 155

Gln Gln Tyr Tyr Ile Phe Pro Pro Thr

15

<210> 156

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 156

Gln Gln Arg Asn Phe Tyr Pro Pro Thr

15

<210> 157

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 157

Gln Gln Phe Val Leu Trp Pro Arg Thr

15

<210> 158

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 158

Gln Gln His Val Asn Phe Pro Leu Thr

15

<210> 159

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 159

Gln Gln Ser Val Phe Trp Pro Ile Thr

15

<210> 160

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 160

Gln Gln Leu Thr Lys Trp Pro Leu Thr

15

<210> 161

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 161

Gln Gln Asp Val Leu Trp Pro Leu Thr

15

<210> 162

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 162

Gln Gln Tyr Gly Leu Phe Pro Ile Thr

15

<210> 163

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 163

Gln Gln His Thr Val Trp Pro Ile Thr

15

<210> 164

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 164

Gln Gln Val Leu Asn Tyr Pro Leu Thr

15

<210> 165

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 165

Gln Gln Ser Tyr Phe Leu Pro Pro Thr

15

<210> 166

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: CDR-L3

<400> 166

Gln Gln Ala His Ser Ser Pro Tyr Thr

15

<210> 167

<211> 22

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: Leader for scFV, scFv-Fc, Leader

<400> 167

Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala

1 5 10 15

Ala Gln Pro Ala Met Ala

20

<210> 168

<211> 15

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: Linker for scFV, scFV-FC, Linker

<400> 168

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

1 5 10 15

<210> 169

<211> 11

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: C-Term Tag for scFV, scFV-FC, C-Term Tag

<400> 169

Gly Pro Gly Gly Gln His His His His His His

1 5 10

<210> 170

<211> 231

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: C-Term Tag for scFv, scFV-FC, C-Term Tag

<400> 170

Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro

1 5 10 15

Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

20 25 30

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

35 40 45

Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp

50 55 60

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr

65 70 75 80

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

85 90 95

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

100 105 110

Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

115 120 125

Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr Lys

130 135 140

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

145 150 155 160

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

165 170 175

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

180 185 190

Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser

195 200 205

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

210 215 220

Leu Ser Leu Ser Pro Gly Lys

225 230

<210> 171

<211> 276

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: scFv, 29872

<400> 171

Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala

1 5 10 15

Ala Gln Pro Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu

20 25 30

Val Lys Glu Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Pro Gly

35 40 45

Tyr Thr Phe Thr Ser Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly

50 55 60

Gln Gly Leu Glu Trp Met Gly Val Ile Asn Pro Ser Gly Gly Ser Thr

65 70 75 80

Ser Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr

85 90 95

Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp

100 105 110

Thr Ala Val Tyr Tyr Cys Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu

115 120 125

Tyr Leu Arg His Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile

145 150 155 160

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

165 170 175

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu

180 185 190

Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

195 200 205

Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu

225 230 235 240

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Tyr Ile Thr Phe

245 250 255

Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Pro Gly Gly Gln His His

260 265 270

His His His His

275

<210> 172

<211> 276

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: scFv, 31895

<400> 172

Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala

1 5 10 15

Ala Gln Pro Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu

20 25 30

Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly

35 40 45

Tyr Thr Phe Lys Ser Tyr Glu Met His Trp Val Arg Gln Ala Pro Gly

50 55 60

Gln Gly Leu Glu Trp Met Gly Arg Ile Asn Pro Ser Val Gly Ser Thr

65 70 75 80

Trp Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr

85 90 95

Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp

100 105 110

Thr Ala Val Tyr Tyr Cys Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu

115 120 125

Tyr Leu Arg Lys Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile

145 150 155 160

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

165 170 175

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ala Ser Ser Tyr Leu

180 185 190

Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

195 200 205

Gly Ala Ser Asn Arg His Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu

225 230 235 240

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Asn Ala Ile Thr Phe

245 250 255

Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Pro Gly Gly Gln His His

260 265 270

His His His His

275

<210> 173

<211> 276

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: scFv, 31414

<400> 173

Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala

1 5 10 15

Ala Gln Pro Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu

20 25 30

Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly

35 40 45

Tyr Thr Phe Lys Ser Tyr Glu Met His Trp Val Arg Gln Ala Pro Gly

50 55 60

Gln Gly Leu Glu Trp Met Gly Arg Ile Asn Pro Ser Val Gly Ser Thr

65 70 75 80

Trp Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr

85 90 95

Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp

100 105 110

Thr Ala Val Tyr Tyr Cys Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu

115 120 125

Tyr Leu Arg Asn Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile

145 150 155 160

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

165 170 175

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu

180 185 190

Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

195 200 205

Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu

225 230 235 240

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Tyr Ile Thr Phe

245 250 255

Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Pro Gly Gly Gln His His

260 265 270

His His His His

275

<210> 174

<211> 281

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: scFv, 31905

<400> 174

Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala

1 5 10 15

Ala Gln Pro Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu

20 25 30

Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly

35 40 45

Gly Thr Phe Pro Ser Asn Ala Ile Ser Trp Val Arg Gln Ala Pro Gly

50 55 60

Gln Gly Leu Glu Trp Met Gly Gly Ile Gly Phe Gly Thr Ala Asn Tyr

65 70 75 80

Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr

85 90 95

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Arg Gly Gly Ala Lys Tyr Ala Arg Thr Tyr Gly

115 120 125

Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val

145 150 155 160

Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala

165 170 175

Thr Ile Asn Cys Lys Ser Ser Lys Ser Val Leu Tyr Ser Asn Asn Asn

180 185 190

Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys

195 200 205

Leu Leu Ile Tyr Trp Ala Ser Thr Arg Gln Ser Gly Val Pro Asp Arg

210 215 220

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

225 230 235 240

Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Leu Leu

245 250 255

Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Pro

260 265 270

Gly Gly Gln His His His His His His His

275 280

<210> 175

<211> 496

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: scFv-Fc, 29872

<400> 175

Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala

1 5 10 15

Ala Gln Pro Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu

20 25 30

Val Lys Glu Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Pro Gly

35 40 45

Tyr Thr Phe Thr Ser Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly

50 55 60

Gln Gly Leu Glu Trp Met Gly Val Ile Asn Pro Ser Gly Gly Ser Thr

65 70 75 80

Ser Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr

85 90 95

Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp

100 105 110

Thr Ala Val Tyr Tyr Cys Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu

115 120 125

Tyr Leu Arg His Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile

145 150 155 160

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

165 170 175

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu

180 185 190

Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

195 200 205

Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu

225 230 235 240

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Tyr Ile Thr Phe

245 250 255

Gly Gly Gly Thr Lys Val Glu Ile Lys Pro Lys Ser Cys Asp Lys Thr

260 265 270

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

275 280 285

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

290 295 300

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

305 310 315 320

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

325 330 335

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

340 345 350

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

355 360 365

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

370 375 380

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

385 390 395 400

Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

405 410 415

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

420 425 430

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

435 440 445

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

450 455 460

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

465 470 475 480

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

485 490 495

<210> 176

<211> 496

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: scFv-Fc, 31895

<400> 176

Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala

1 5 10 15

Ala Gln Pro Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu

20 25 30

Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly

35 40 45

Tyr Thr Phe Lys Ser Tyr Glu Met His Trp Val Arg Gln Ala Pro Gly

50 55 60

Gln Gly Leu Glu Trp Met Gly Arg Ile Asn Pro Ser Val Gly Ser Thr

65 70 75 80

Trp Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr

85 90 95

Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp

100 105 110

Thr Ala Val Tyr Tyr Cys Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu

115 120 125

Tyr Leu Arg Lys Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile

145 150 155 160

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

165 170 175

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ala Ser Ser Tyr Leu

180 185 190

Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

195 200 205

Gly Ala Ser Asn Arg His Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu

225 230 235 240

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Asn Ala Ile Thr Phe

245 250 255

Gly Gly Gly Thr Lys Val Glu Ile Lys Pro Lys Ser Cys Asp Lys Thr

260 265 270

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

275 280 285

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

290 295 300

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

305 310 315 320

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

325 330 335

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

340 345 350

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

355 360 365

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

370 375 380

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

385 390 395 400

Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

405 410 415

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

420 425 430

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

435 440 445

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

450 455 460

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

465 470 475 480

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

485 490 495

<210> 177

<211> 496

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: scFv-Fc, 31414

<400> 177

Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala

1 5 10 15

Ala Gln Pro Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu

20 25 30

Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly

35 40 45

Tyr Thr Phe Lys Ser Tyr Glu Met His Trp Val Arg Gln Ala Pro Gly

50 55 60

Gln Gly Leu Glu Trp Met Gly Arg Ile Asn Pro Ser Val Gly Ser Thr

65 70 75 80

Trp Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr

85 90 95

Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp

100 105 110

Thr Ala Val Tyr Tyr Cys Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu

115 120 125

Tyr Leu Arg Asn Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile

145 150 155 160

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

165 170 175

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu

180 185 190

Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

195 200 205

Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu

225 230 235 240

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Tyr Ile Thr Phe

245 250 255

Gly Gly Gly Thr Lys Val Glu Ile Lys Pro Lys Ser Cys Asp Lys Thr

260 265 270

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

275 280 285

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

290 295 300

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

305 310 315 320

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

325 330 335

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

340 345 350

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

355 360 365

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

370 375 380

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

385 390 395 400

Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

405 410 415

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

420 425 430

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

435 440 445

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

450 455 460

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

465 470 475 480

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

485 490 495

<210> 178

<211> 501

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: scFv-Fc, 31905

<400> 178

Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala

1 5 10 15

Ala Gln Pro Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu

20 25 30

Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly

35 40 45

Gly Thr Phe Pro Ser Asn Ala Ile Ser Trp Val Arg Gln Ala Pro Gly

50 55 60

Gln Gly Leu Glu Trp Met Gly Gly Ile Gly Phe Gly Thr Ala Asn Tyr

65 70 75 80

Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr

85 90 95

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Arg Gly Gly Ala Lys Tyr Ala Arg Thr Tyr Gly

115 120 125

Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val

145 150 155 160

Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala

165 170 175

Thr Ile Asn Cys Lys Ser Ser Lys Ser Val Leu Tyr Ser Asn Asn Asn

180 185 190

Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys

195 200 205

Leu Leu Ile Tyr Trp Ala Ser Thr Arg Gln Ser Gly Val Pro Asp Arg

210 215 220

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

225 230 235 240

Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Leu Leu

245 250 255

Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Pro Lys

260 265 270

Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu

275 280 285

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

290 295 300

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

305 310 315 320

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

325 330 335

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

340 345 350

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

355 360 365

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

370 375 380

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

385 390 395 400

Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr Lys Asn Gln

405 410 415

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

420 425 430

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

435 440 445

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

450 455 460

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

465 470 475 480

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

485 490 495

Leu Ser Pro Gly Lys

500

<210> 179

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27579

<400> 179

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Glu Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Pro Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Val Ile Asn Pro Ser Gly Ser Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg His Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 180

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31895

<400> 180

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Lys Ser Tyr

20 25 30

Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Val Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Lys Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 181

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31415

<400> 181

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Gln Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Ser Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 182

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31414

<400> 182

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Lys Ser Tyr

20 25 30

Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Val Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Asn Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 183

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31891

<400> 183

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Lys Ser Tyr

20 25 30

Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Val Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Val Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 184

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 29871

<400> 184

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Gln Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Lys Ile Asn Pro Ser Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg His Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 185

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31418

<400> 185

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Lys Ser Tyr

20 25 30

Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg His Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 186

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31431

<400> 186

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Gln Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg His Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 187

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31421

<400> 187

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Phe Ser Tyr

20 25 30

Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Val Ile Asn Pro Leu Gly Gly Gly Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg His Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 188

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31429

<400> 188

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Val Ser Tyr

20 25 30

Phe Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Asn Pro Arg Gly Ser Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg His Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 189

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 29872

<400> 189

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Lys Ser Tyr

20 25 30

Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Val Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg His Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 190

<211> 122

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 28347

<400> 190

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Leu

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Asn Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gly Ala Lys Tyr Ala Ser Thr Tyr Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 191

<211> 120

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31896

<400> 191

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Lys Leu

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Gly Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly

50 55 60

Arg Val Thr Ile Thr Ala Asp Glu Ser Ala Ser Thr Ala Tyr Met Glu

65 70 75 80

Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

85 90 95

Gly Gly Ala Lys Tyr Ala Ser Thr His Gly Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 192

<211> 122

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31432

<400> 192

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser His Thr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Leu Pro Ile Gly Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gly Ala Lys Tyr Ala Ser Gln Leu Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 193

<211> 120

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31915

<400> 193

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Leu

20 25 30

Pro Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Gly Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly

50 55 60

Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu

65 70 75 80

Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

85 90 95

Gly Gly Ala Lys Tyr Ala Ser Lys Trp Gly Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 194

<211> 122

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31436

<400> 194

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Leu Leu

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Leu Pro Ile Ala Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gly Ala Lys Tyr Ala Val Gly Tyr Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 195

<211> 122

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31437

<400> 195

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Gln Ser Leu

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Leu Pro Ile Gly Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gly Ala Lys Tyr Ala Gly Arg Tyr Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 196

<211> 120

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31905

<400> 196

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Pro Ser Asn

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Gly Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly

50 55 60

Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu

65 70 75 80

Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

85 90 95

Gly Gly Ala Lys Tyr Ala Arg Thr Tyr Gly Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 197

<211> 120

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31901

<400> 197

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Leu

20 25 30

Pro Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Gly Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly

50 55 60

Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu

65 70 75 80

Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

85 90 95

Gly Gly Ala Lys Tyr Ala Gly Arg Tyr Gly Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 198

<211> 122

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 29852

<400> 198

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ala Met

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Leu Pro Ile Ala Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gly Ala Lys Tyr Ala Ser Thr Tyr Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 199

<211> 122

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 29851

<400> 199

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ala Ser Leu

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Leu Pro Ile Phe Gly Glu Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gly Ala Lys Tyr Ala Ser Thr Tyr Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 200

<211> 122

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 29857

<400> 200

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Trp Leu

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Arg Gly Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gly Ala Lys Tyr Ala Ser Thr Tyr Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 201

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27571

<400> 201

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Ala Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Arg Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Thr Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ser Gly Gly Tyr Arg Asp His Arg Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 202

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31861

<400> 202

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Gly Ser Tyr

20 25 30

Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Glu Phe Gly Ile Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ser Gly Thr Tyr Arg Asp His Arg Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 203

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31873

<400> 203

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Lys Tyr

20 25 30

Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Glu Phe Gly Ile Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ser Gly Gly Tyr Arg Asp His Arg Leu Gly Val Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 204

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 31393

<400> 204

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Glu Ser Tyr

20 25 30

Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Glu Phe Gly Ile Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Thr Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ser Gly Gly Tyr Arg Asp His Arg Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 205

<211> 124

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27534

<400> 205

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Phe Thr Asp Tyr Ser Ser Gly Tyr Ser Ser Gly Trp Thr

100 105 110

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 206

<211> 123

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27536

<400> 206

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Asn Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Thr Leu Tyr Ser Ser Gly Ala Tyr Tyr Gly Tyr Asn Val

100 105 110

Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 207

<211> 124

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27588

<400> 207

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Asn Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Lys Arg Gly Tyr Asp Ser Tyr Gly Gly Val Tyr Phe Asp

100 105 110

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 208

<211> 127

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27590

<400> 208

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Asn Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Pro Thr Val Thr Ala Thr Thr Ser Ile Gly Thr His Asn

100 105 110

Trp Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 209

<211> 126

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27597

<400> 209

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Arg Gly Tyr Asp Ser Ser Arg Tyr Tyr Lys Phe Trp

100 105 110

Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 210

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27575

<400> 210

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Glu Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Thr Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Thr Ala Asn Tyr Ala Gln Glu Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Gly Gly Gly Tyr Arg His His Tyr Phe Asp Leu Trp Gly

100 105 110

Arg Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 211

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27568

<400> 211

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Pro Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Glu Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Gly Glu Ser Gly Gly Tyr Arg Asp His Lys Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Val Val Thr Val Ser Ser

115 120

<210> 212

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27577

<400> 212

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Ala Phe Ser Ser Tyr

20 25 30

Ala Ile Gly Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Thr Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Gly Gly Gly Tyr Gln His His Tyr Phe Asp Leu Trp Gly

100 105 110

Arg Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 213

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27587

<400> 213

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ser Gly Gly Tyr Arg Asp His Lys Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 214

<211> 120

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27589

<400> 214

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Ser Gly Tyr His Arg His Tyr Ser Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 215

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27596

<400> 215

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Pro Leu Gly Ile Arg Lys His Trp Phe Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 216

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27535

<400> 216

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Thr Pro Arg Trp Arg Tyr His Tyr Phe Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 217

<211> 121

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27550

<400> 217

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Ser Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Arg Arg Gly Ser Leu Ala Leu Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 218

<211> 128

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VH, 27549

<400> 218

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Gly Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ala Val Ile Trp Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Leu Gly Gly Tyr Ser Tyr Gly Glu Pro Tyr Tyr Tyr Tyr

100 105 110

Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120 125

<210> 219

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27579

<400> 219

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Tyr Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 220

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31895

<400> 220

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ala Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Asn Arg His Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Asn Ala Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 221

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31891

<400> 221

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Tyr Ala Ser Ser Arg Ala Tyr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Asn Ala Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 222

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31418

<400> 222

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Phe Tyr Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 223

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31430

<400> 223

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Glu Ala Ser Gln Ser Val Ser Tyr Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Asn Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Ala Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 224

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31431

<400> 224

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ala Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Asn Arg His Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Gly Gly Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 225

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31421

<400> 225

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Lys Ala Ser Glu Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Tyr Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Arg Arg Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 226

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31429

<400> 226

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Tyr Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Tyr Ala Ser Asn Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Gly Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 227

<211> 113

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 28347

<400> 227

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Phe Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Leu Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 228

<211> 113

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31896

<400> 228

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Arg Ser Val Leu Phe Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Trp Thr Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 229

<211> 113

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31915

<400> 229

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Phe Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Ser Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Trp Thr Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 230

<211> 113

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31905

<400> 230

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Lys Ser Val Leu Tyr Ser

20 25 30

Asn Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Gln Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Leu Leu Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 231

<211> 113

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31901

<400> 231

Gly Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Phe Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Ala Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Leu Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 232

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27571

<400> 232

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Leu Ile Trp Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 233

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31861

<400> 233

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Leu Leu Trp Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 234

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 31873

<400> 234

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Leu Leu Trp Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 235

<211> 113

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 28337

<400> 235

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Phe Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Phe Tyr Phe Tyr Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 236

<211> 113

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27536

<400> 236

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Ala Tyr Thr Phe Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 237

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27588

<400> 237

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Tyr Ile Phe Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 238

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27590

<400> 238

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Asn Phe Tyr Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 239

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27597

<400> 239

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Phe Val Leu Trp Pro Arg

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 240

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27575

<400> 240

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln His Val Asn Phe Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 241

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27568

<400> 241

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Val Phe Trp Pro Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 242

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27577

<400> 242

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Leu Thr Lys Trp Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 243

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27587

<400> 243

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Lys Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Asp Val Leu Trp Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 244

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27589

<400> 244

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Gly Leu Phe Pro Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 245

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27596

<400> 245

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln His Thr Val Trp Pro Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 246

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27535

<400> 246

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Lys Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Val Leu Asn Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 247

<211> 107

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27550

<400> 247

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Phe Leu Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 248

<211> 108

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: VL, 27549

<400> 248

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asp

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ala His Ser Ser Pro

85 90 95

Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 249

<211> 510

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: hCD39

<400> 249

Met Glu Asp Thr Lys Glu Ser Asn Val Lys Thr Phe Cys Ser Lys Asn

1 5 10 15

Ile Leu Ala Ile Leu Gly Phe Ser Ser Ile Ile Ala Val Ile Ala Leu

20 25 30

Leu Ala Val Gly Leu Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys

35 40 45

Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile

50 55 60

Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln

65 70 75 80

Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln

85 90 95

Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala

100 105 110

Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu

115 120 125

Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu

130 135 140

Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro

145 150 155 160

Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala

165 170 175

Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys

180 185 190

Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr

195 200 205

Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val

210 215 220

Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg

225 230 235 240

Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr

245 250 255

Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val

260 265 270

Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys

275 280 285

Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg

290 295 300

Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly

305 310 315 320

Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser

325 330 335

Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro

340 345 350

Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys

355 360 365

Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu

370 375 380

Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser

385 390 395 400

Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly

405 410 415

Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp

420 425 430

Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala

435 440 445

Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala

450 455 460

Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr Tyr Val Phe Leu

465 470 475 480

Met Val Leu Phe Ser Leu Val Leu Phe Thr Val Ala Ile Ile Gly Leu

485 490 495

Leu Ile Phe His Lys Pro Ser Tyr Phe Trp Lys Asp Met Val

500 505 510

<210> 250

<211> 510

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: mCD39

<400> 250

Met Glu Asp Ile Lys Asp Ser Lys Val Lys Arg Phe Cys Ser Lys Asn

1 5 10 15

Ile Leu Ile Ile Leu Gly Phe Thr Ser Ile Leu Ala Val Ile Ala Leu

20 25 30

Ile Ala Val Gly Leu Thr Gln Asn Lys Pro Leu Pro Glu Asn Val Lys

35 40 45

Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Asn Leu Tyr Ile

50 55 60

Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val Gln Gln

65 70 75 80

Leu Glu Glu Cys Gln Val Lys Gly Pro Gly Ile Ser Lys Tyr Ala Gln

85 90 95

Lys Thr Asp Glu Ile Gly Ala Tyr Leu Ala Glu Cys Met Glu Leu Ser

100 105 110

Thr Glu Leu Ile Pro Thr Ser Lys His His Gln Thr Pro Val Tyr Leu

115 120 125

Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Gln Ser

130 135 140

Ala Asp Glu Val Leu Ala Ala Val Ser Thr Ser Leu Lys Ser Tyr Pro

145 150 155 160

Phe Asp Phe Gln Gly Ala Lys Ile Ile Thr Gly Gln Glu Glu Gly Ala

165 170 175

Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Arg Phe Thr Gln Glu

180 185 190

Gln Ser Trp Leu Ser Leu Ile Ser Asp Ser Gln Lys Gln Glu Thr Phe

195 200 205

Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Ile Thr Phe Val Pro

210 215 220

Gln Asn Ser Thr Ile Glu Ser Pro Glu Asn Ser Leu Gln Phe Arg Leu

225 230 235 240

Tyr Gly Glu Asp Tyr Thr Val Tyr Thr His Ser Phe Leu Cys Tyr Gly

245 250 255

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ser

260 265 270

Ser Gly Gly Val Leu Lys Asp Pro Cys Phe Asn Pro Gly Tyr Glu Lys

275 280 285

Val Val Asn Val Ser Glu Leu Tyr Gly Thr Pro Cys Thr Lys Arg Phe

290 295 300

Glu Lys Lys Leu Pro Phe Asp Gln Phe Arg Ile Gln Gly Thr Gly Asp

305 310 315 320

Tyr Glu Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Asn Ser His

325 330 335

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Val Phe Leu Pro Pro Leu

340 345 350

His Gly Ser Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Asp Phe

355 360 365

Phe Lys Lys Val Ala Lys Asn Ser Val Ile Ser Gln Glu Lys Met Thr

370 375 380

Glu Ile Thr Lys Asn Phe Cys Ser Lys Ser Trp Glu Glu Thr Lys Thr

385 390 395 400

Ser Tyr Pro Ser Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser

405 410 415

Gly Ala Tyr Ile Leu Ser Leu Leu Gln Gly Tyr Asn Phe Thr Asp Ser

420 425 430

Ser Trp Glu Gln Ile His Phe Met Gly Lys Ile Lys Asp Ser Asn Ala

435 440 445

Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala

450 455 460

Glu Gln Pro Leu Ser Pro Pro Leu Pro His Ser Thr Tyr Ile Gly Leu

465 470 475 480

Met Val Leu Phe Ser Leu Leu Leu Val Ala Val Ala Ile Thr Gly Leu

485 490 495

Phe Ile Tyr Ser Lys Pro Ser Tyr Phe Trp Lys Glu Ala Val

500 505 510

<210> 251

<211> 532

<212> PRT

<213> Macaca fascicularis

<220>

<221> misc_feature

<222> (1)..(532)

<223> Macaca fascicularis cCD39

<400> 251

Met Leu Phe Asp Ser Ile Leu Ser Thr Val Gly Leu Ser Lys Leu Val

1 5 10 15

Ser Val Val Ser Ser Pro Ala Ala Ala Leu Ser Lys Ser Asn Val Lys

20 25 30

Thr Phe Cys Ser Lys Asn Ile Leu Ala Ile Leu Gly Phe Ser Ser Ile

35 40 45

Ile Ala Val Ile Ala Leu Leu Ala Val Gly Leu Thr Gln Asn Lys Ala

50 55 60

Leu Pro Glu Asn Ile Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser

65 70 75 80

His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp

85 90 95

Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly

100 105 110

Ile Ser Lys Tyr Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr

115 120 125

Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln

130 135 140

Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg

145 150 155 160

Met Glu Ser Glu Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg

165 170 175

Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr

180 185 190

Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu

195 200 205

Gly Lys Phe Ser Gln Lys Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu

210 215 220

Thr Asn Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser

225 230 235 240

Thr Gln Ile Thr Phe Val Pro Gln Asn Gln Thr Thr Glu Ser Pro Asp

245 250 255

Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr

260 265 270

His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu

275 280 285

Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys

290 295 300

Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys

305 310 315 320

Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe

325 330 335

Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Val Leu

340 345 350

Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn

355 360 365

Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala

370 375 380

Phe Tyr Phe Val Met Asn Phe Leu Asn Leu Thr Ser Glu Lys Val Ser

385 390 395 400

Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ser Gln Pro Trp

405 410 415

Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser

420 425 430

Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly

435 440 445

Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys

450 455 460

Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu

465 470 475 480

Thr Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His

485 490 495

Ser Thr Tyr Val Phe Leu Met Val Leu Phe Ser Leu Val Leu Val Ile

500 505 510

Val Ala Ile Ile Gly Leu Leu Ile Phe His Lys Pro Ser Tyr Phe Trp

515 520 525

Lys Asp Met Val

530

<210> 252

<211> 473

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: hCD39 ECD

<400> 252

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala

20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg

35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile

50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro

65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly

85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Thr Arg Trp Phe Ser

145 150 155 160

Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr Phe Gly Ala Leu Asp

165 170 175

Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr

180 185 190

Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp

195 200 205

Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala

210 215 220

Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile

225 230 235 240

Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val

245 250 255

Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu

260 265 270

Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys

275 280 285

His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser

290 295 300

Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe

305 310 315 320

Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr

325 330 335

Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe

340 345 350

Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys

355 360 365

Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser

370 375 380

Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile

385 390 395 400

His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly

405 410 415

Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln Pro Leu Ser

420 425 430

Thr Pro Leu Ser His Ser Thr Tyr Val Phe Leu Met Val Leu Phe Ser

435 440 445

Leu Val Leu Phe Thr Val Ala Ile Ile Gly Leu Leu Ile Phe His Lys

450 455 460

Pro Ser Tyr Phe Trp Lys Asp Met Val

465 470

<210> 253

<211> 473

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: mCD39 ECD

<400> 253

Thr Gln Asn Lys Pro Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

1 5 10 15

Asp Ala Gly Ser Ser His Thr Asn Leu Tyr Ile Tyr Lys Trp Pro Ala

20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val Gln Gln Leu Glu Glu Cys Gln

35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Tyr Ala Gln Lys Thr Asp Glu Ile

50 55 60

Gly Ala Tyr Leu Ala Glu Cys Met Glu Leu Ser Thr Glu Leu Ile Pro

65 70 75 80

Thr Ser Lys His His Gln Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly

85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Gln Ser Ala Asp Glu Val Leu

100 105 110

Ala Ala Val Ser Thr Ser Leu Lys Ser Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Lys Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Arg Phe Thr Gln Glu Gln Ser Trp Leu Ser

145 150 155 160

Leu Ile Ser Asp Ser Gln Lys Gln Glu Thr Phe Gly Ala Leu Asp Leu

165 170 175

Gly Gly Ala Ser Thr Gln Ile Thr Phe Val Pro Gln Asn Ser Thr Ile

180 185 190

Glu Ser Pro Glu Asn Ser Leu Gln Phe Arg Leu Tyr Gly Glu Asp Tyr

195 200 205

Thr Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu

210 215 220

Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ser Ser Gly Gly Val Leu

225 230 235 240

Lys Asp Pro Cys Phe Asn Pro Gly Tyr Glu Lys Val Val Asn Val Ser

245 250 255

Glu Leu Tyr Gly Thr Pro Cys Thr Lys Arg Phe Glu Lys Lys Leu Pro

260 265 270

Phe Asp Gln Phe Arg Ile Gln Gly Thr Gly Asp Tyr Glu Gln Cys His

275 280 285

Gln Ser Ile Leu Glu Leu Phe Asn Ser His Cys Pro Tyr Ser Gln

290 295 300

Cys Ala Phe Asn Gly Val Phe Leu Pro Pro Leu His Gly Ser Phe Gly

305 310 315 320

Ala Phe Ser Ala Phe Tyr Phe Val Met Asp Phe Phe Lys Lys Val Ala

325 330 335

Lys Asn Ser Val Ile Ser Gln Glu Lys Met Thr Glu Ile Thr Lys Asn

340 345 350

Phe Cys Ser Lys Ser Trp Glu Glu Thr Lys Thr Ser Tyr Pro Ser Val

355 360 365

Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Ala Tyr Ile Leu

370 375 380

Ser Leu Leu Gln Gly Tyr Asn Phe Thr Asp Ser Ser Ser Trp Glu Gln Ile

385 390 395 400

His Phe Met Gly Lys Ile Lys Asp Ser Asn Ala Gly Trp Thr Leu Gly

405 410 415

Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln Pro Leu Ser

420 425 430

Pro Pro Leu Pro His Ser Thr Tyr Ile Gly Leu Met Val Leu Phe Ser

435 440 445

Leu Leu Leu Val Ala Val Ala Ile Thr Gly Leu Phe Ile Tyr Ser Lys

450 455 460

Pro Ser Tyr Phe Trp Lys Glu Ala Val

465 470

<210> 254

<211> 473

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: cCD39 ECD

<400> 254

Thr Gln Asn Lys Ala Leu Pro Glu Asn Ile Lys Tyr Gly Ile Val Leu

1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala

20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg

35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Tyr Val Gln Lys Val Asn Glu Ile

50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro

65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly

85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Thr Arg Trp Phe Ser

145 150 155 160

Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr Phe Gly Ala Leu Asp

165 170 175

Leu Gly Gly Ala Ser Thr Gln Ile Thr Phe Val Pro Gln Asn Gln Thr

180 185 190

Thr Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp

195 200 205

Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala

210 215 220

Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile

225 230 235 240

Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val

245 250 255

Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu

260 265 270

Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys

275 280 285

His Gln Ser Val Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser

290 295 300

Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe

305 310 315 320

Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Asn Phe Leu Asn Leu Thr

325 330 335

Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe

340 345 350

Cys Ser Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys

355 360 365

Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser

370 375 380

Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile

385 390 395 400

His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly

405 410 415

Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln Pro Leu Ser

420 425 430

Thr Pro Leu Ser His Ser Thr Tyr Val Phe Leu Met Val Leu Phe Ser

435 440 445

Leu Val Leu Val Ile Val Ala Ile Ile Gly Leu Leu Ile Phe His Lys

450 455 460

Pro Ser Tyr Phe Trp Lys Asp Met Val

465 470

<210> 255

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31895

<400> 255

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Lys Ser Tyr

20 25 30

Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Val Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Lys Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 256

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31895

<400> 256

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ala Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Asn Arg His Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Asn Ala Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 257

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31415

<400> 257

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Gln Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Ser Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 258

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31415

<400> 258

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Tyr Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 259

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31891

<400> 259

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Lys Ser Tyr

20 25 30

Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Val Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Val Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 260

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31891

<400> 260

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Tyr Ala Ser Ser Arg Ala Tyr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Asn Ala Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 261

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31418

<400> 261

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Lys Ser Tyr

20 25 30

Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg His Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 262

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31418

<400> 262

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Phe Tyr Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 263

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31430

<400> 263

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Lys Ser Tyr

20 25 30

Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg His Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 264

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31430

<400> 264

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Glu Ala Ser Gln Ser Val Ser Tyr Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Asn Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Ala Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 265

<211> 447

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31915

<400> 265

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Leu

20 25 30

Pro Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Gly Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly

50 55 60

Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu

65 70 75 80

Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

85 90 95

Gly Gly Ala Lys Tyr Ala Ser Lys Trp Gly Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 266

<211> 220

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31915

<400> 266

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Phe Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Ser Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Trp Thr Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp

115 120 125

Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn

130 135 140

Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu

145 150 155 160

Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp

165 170 175

Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185 190

Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser

195 200 205

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215 220

<210> 267

<211> 447

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31905

<400> 267

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Pro Ser Asn

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Gly Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly

50 55 60

Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu

65 70 75 80

Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

85 90 95

Gly Gly Ala Lys Tyr Ala Arg Thr Tyr Gly Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 268

<211> 220

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31905

<400> 268

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Lys Ser Val Leu Tyr Ser

20 25 30

Asn Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Gln Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Leu Leu Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp

115 120 125

Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn

130 135 140

Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu

145 150 155 160

Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp

165 170 175

Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185 190

Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser

195 200 205

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215 220

<210> 269

<211> 447

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31901

<400> 269

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Leu

20 25 30

Pro Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Gly Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly

50 55 60

Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu

65 70 75 80

Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

85 90 95

Gly Gly Ala Lys Tyr Ala Gly Arg Tyr Gly Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 270

<211> 220

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31901

<400> 270

Gly Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Phe Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Ala Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Leu Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp

115 120 125

Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn

130 135 140

Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu

145 150 155 160

Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp

165 170 175

Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185 190

Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser

195 200 205

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215 220

<210> 271

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31861

<400> 271

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Gly Ser Tyr

20 25 30

Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Glu Phe Gly Ile Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ser Gly Thr Tyr Arg Asp His Arg Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 272

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31861

<400> 272

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Leu Leu Trp Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 273

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31873

<400> 273

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Lys Tyr

20 25 30

Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Glu Phe Gly Ile Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ser Gly Gly Tyr Arg Asp His Arg Leu Gly Val Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 274

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31873

<400> 274

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Leu Leu Trp Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 275

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31393

<400> 275

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Glu Ser Tyr

20 25 30

Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Glu Phe Gly Ile Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Thr Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ser Gly Gly Tyr Arg Asp His Arg Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 276

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31393

<400> 276

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Leu Leu Trp Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 277

<211> 453

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 27597

<400> 277

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Arg Gly Tyr Asp Ser Ser Arg Tyr Tyr Lys Phe Trp

100 105 110

Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr

130 135 140

Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

195 200 205

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

225 230 235 240

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

245 250 255

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

260 265 270

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

275 280 285

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser

290 295 300

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

305 310 315 320

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser

325 330 335

Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

340 345 350

Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln

355 360 365

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

370 375 380

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

385 390 395 400

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu

405 410 415

Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser

420 425 430

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

435 440 445

Leu Ser Leu Gly Lys

450

<210> 278

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 27597

<400> 278

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Phe Val Leu Trp Pro Arg

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 279

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 27575

<400> 279

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Glu Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Thr Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Thr Ala Asn Tyr Ala Gln Glu Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Gly Gly Gly Tyr Arg His His Tyr Phe Asp Leu Trp Gly

100 105 110

Arg Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 280

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 27575

<400> 280

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln His Val Asn Phe Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 281

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 27568

<400> 281

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Pro Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Glu Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Gly Glu Ser Gly Gly Tyr Arg Asp His Lys Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Val Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 282

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 27568

<400> 282

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Val Phe Trp Pro Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 283

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 27577

<400> 283

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Ala Phe Ser Ser Tyr

20 25 30

Ala Ile Gly Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Thr Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Gly Gly Gly Tyr Gln His His Tyr Phe Asp Leu Trp Gly

100 105 110

Arg Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 284

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 27577

<400> 284

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Leu Thr Lys Trp Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 285

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 27587

<400> 285

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ser Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ser Gly Gly Tyr Arg Asp His Lys Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 286

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 27587

<400> 286

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Lys Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Asp Val Leu Trp Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 287

<211> 447

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 27589

<400> 287

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Ser Gly Tyr His Arg His Tyr Ser Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 288

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 27589

<400> 288

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Gly Leu Phe Pro Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 289

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 27596

<400> 289

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Pro Leu Gly Ile Arg Lys His Trp Phe Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 290

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 27596

<400> 290

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln His Thr Val Trp Pro Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 291

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 27535

<400> 291

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Thr Pro Arg Trp Arg Tyr His Tyr Phe Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 292

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 27535

<400> 292

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Lys Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Val Leu Asn Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 293

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 27550

<400> 293

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Ser Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Arg Arg Gly Ser Leu Ala Leu Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 294

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 27550

<400> 294

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Phe Leu Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 295

<211> 455

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 27549

<400> 295

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Gly Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ala Val Ile Trp Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Leu Gly Gly Tyr Ser Tyr Gly Glu Pro Tyr Tyr Tyr Tyr

100 105 110

Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120 125

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg

130 135 140

Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr

145 150 155 160

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser

165 170 175

Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser

180 185 190

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr

195 200 205

Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys

210 215 220

Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro

225 230 235 240

Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

245 250 255

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

260 265 270

Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp

275 280 285

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe

290 295 300

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

305 310 315 320

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu

325 330 335

Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

340 345 350

Glu Pro Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys

355 360 365

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

370 375 380

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

385 390 395 400

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

405 410 415

Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser

420 425 430

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

435 440 445

Leu Ser Leu Ser Leu Gly Lys

450 455

<210> 296

<211> 215

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 27549

<400> 296

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asp

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ala His Ser Ser Pro

85 90 95

Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala

100 105 110

Ala Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser

115 120 125

Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu

130 135 140

Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser

145 150 155 160

Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu

165 170 175

Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val

180 185 190

Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys

195 200 205

Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 297

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: HC, 31414

<400> 297

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Lys Ser Tyr

20 25 30

Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Ser Val Gly Ser Thr Trp Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Lys Arg Glu Gly Gly Thr Glu Tyr Leu Arg Asn Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 298

<211> 214

<212> PRT

<213> Artificial Sequence

<220>

<223> Synthetic: LC, 31414

<400> 298

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Tyr Ile

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<---

Claims (49)

1. An isolated antibody molecule capable of binding to human CD39 (hCD39) containing a heavy chain variable region (VH) and a light chain variable region (VL), while VH contains: a) VHCDR1 with the sequence set forth in SEQ ID NO: 2 or SEQ ID NO: 26, b) VHCDR2 with the sequence set forth in SEQ ID NO: 47 or SEQ ID NO: 64, and c) VHCDR3 with the sequence set forth in SEQ ID NO: 83; And VL contains: a) VLCDR1 with the sequence set forth in SEQ ID NO: 111, b) VLCDR2 with the sequence set forth in SEQ ID NO: 126, and c) VLCDR3 with the sequence set forth in SEQ ID NO: 142. 2. An isolated antibody molecule capable of binding to human CD39 (hCD39) according to claim 1, comprising a VH sequence that is at least 85%, 90%, or 95% identical to the amino acid sequence set forth in SEQ ID NO: 180, and a VL sequence that is at least 85%, 90%, or 95% identical to the amino acid sequence set forth in SEQ ID NO: 220. 3. An isolated nucleic acid encoding an isolated antibody molecule according to claim 1 or 2. 4. An expression vector containing a nucleic acid according to claim 3. 5. A prokaryotic or eukaryotic host cell producing an isolated antibody molecule containing the vector of claim 4. 6. A method for obtaining an isolated antibody molecule, comprising the steps of expressing a nucleic acid according to claim 3 in a prokaryotic or eukaryotic host cell and obtaining an antibody molecule from a cell or cell culture supernatant. 7. An isolated antibody molecule capable of binding to human CD39 (hCD39) comprising a heavy chain and a light chain, wherein the heavy chain contains a molecule with the sequence consisting of the sequence of SEQ ID NO: 255 and the light chain contains a molecule with the sequence consisting of the sequences of SEQ ID NO: 256. 8. An isolated antibody molecule capable of binding to human CD39 (hCD39) comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH contains a VH having the sequence set forth in SEQ ID NO: 180 and VL contains a VL having the sequence set forth in SEQ ID NO: 220. 9. A method of treating cancer in a subject, comprising administering to the subject an antibody molecule according to any one of paragraphs. 1, 2, 7 or 8. 10. A method of treating a chronic infection in a subject, comprising administering to the subject an antibody molecule according to any one of paragraphs. 1, 2, 7 or 8. 11. A method of treating an inflammatory disease in a subject, comprising administering to the subject an antibody molecule according to any one of paragraphs. 1, 2, 7 or 8. 12. The method of claim 9 wherein the cancer is a solid cancer. 13. The method of claim 9 wherein the cancer is hematological cancer. 14. A method for modulating immune system function in a subject in need of such modulation, comprising the step of contacting the subject's immune cell population with an antibody molecule according to any one of paragraphs. 1, 2, 7 or 8, under conditions in which the immune system is modulated. 15. A method of inducing or enhancing an immune response in a subject in need thereof, comprising the step of administering to the subject an antibody molecule according to any one of paragraphs. 1, 2, 7 or 8, where the immune response is generated against the tumor antigen. 16. The method of claim 14 or 15, wherein the subject is a human. 17. The method of claim 15 or 16, wherein the antibody molecule is administered in an amount sufficient to achieve in the subject 1, 2, 3, 4, 5, 6, or 7 of the following: a) reducing the ATPase activity of CD39 in the target cell population; b) reducing regulatory T cell suppression of effector T cell activity; c) decreased levels of regulatory T cells; d) activation of effector T cells; e) inducing or enhancing the proliferation of effector T cells; f) tumor growth inhibition and/or g) inducing tumor regression, optionally, where the target cell population contains T cells, B cells, monocytes, macrophages, dendritic cells, myeloid suppressor cells and/or tumor cells. 18. The method according to any one of paragraphs. 15-17, where the method includes one or more of the following: a) administration of chemotherapy; b) the use of radiation therapy and/or c) administering one or more additional therapeutic agents, optionally where: i) one or more additional therapeutic agents contains one or more immunostimulatory agents; ii) one or more immunostimulatory agents contain an antagonist to an inhibitory immune cell receptor; not necessary, where the inhibitory receptor is at least one of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, Tim3, neuritin, BTLA, CECAM-1, CECAM-5, VISTA, LAIR1, CD160, 2B4, TGF -R and/or killer cell immunoglobulin-like receptor (KIR); iii) one or more immunostimulatory agents comprise an immune cell co-stimulatory receptor agonist, optionally where such a costimulatory receptor is OX40, CD2, CD27, CDS, ICAM-1, LFA-1, ICOS (CD278), 4-1BB (CD137), GITR, CD28, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C , SLAMF7, NKp80, CD160, B7-H3, or CD83 ligand, optionally wherein such LFA-1 costimulatory receptor or ligand further comprises CD18 of LFA-1 β chain and/or CD11a of LFA-1 α chain; iv) one or more immunostimulatory agents contain a cytokine, optionally, where such cytokine is at least one of IL-2, IL-5, IL-7, IL-12, IL-15 and/or IL-21; v) one or more immunostimulatory agents contain an oncolytic virus, optionally where such oncolytic virus is herpes simplex virus, vesicular stomatitis virus, adenovirus, Newcastle disease virus, vaccinia virus or marab virus; vi) one or more immunostimulatory agents comprise an engineered T cell with a chimeric antigen receptor; vii) one or more immunostimulatory agents contain a bi- or multispecific antibody directed to T cells; or viii) one or more additional therapeutic agents comprise at least one immunosuppressive agent decoy, optionally wherein at least one immunosuppressive agent decoy comprises at least one of anti-TGF-beta antibody, TGFb receptor, anti-IL-10 antibody and/or anti -IL-10 receptor and/or anti-IL-35 antibody decoy and/or anti-IL-35 receptor decoy. 19. The method according to any one of paragraphs. 9-18, wherein administration of the antibody molecule results in induction or enhancement of T effector cell proliferation, or modulation of I-kappaB and/or NF-κB in T cells, or modulation of CD39 activity in T cells, or receptor-induced T cell signaling in the T-effector cell or a combination thereof.

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