Methods and compositions for modulating v-beta-17 chain mediated immunity

Abstract

The present disclosure relates to bispecific molecules targeting Vβ17 and CD19, nucleic acids and expression vectors encoding said molecules, recombinant cells containing the vectors, and compositions comprising the molecules. Methods of making the antibodies, and methods of using the antibodies to treat autoimmune diseases, are also provided.

Description

094669.0103PATENT METHODS AND COMPOSITIONS FOR MODULATING V-BETA-17 CHAIN MEDIATED IMMUNITYCROSS-REFERENCES TO RELATED APPLICATIONS This application claims the benefit of priority to U. S. Provisional Patent Application No. 63 / 736,561, filed December 19, 2024, the content of which is incorporated herein by reference in its entirety, and to which priority is claimed.FIELD OF THE INVENTION A Sequence Listing conforming to the rules of WIPO Standard ST.26 is hereby incorporated by reference. Said Sequence Listing has been filed as an electronic document via PatentCenter encoded as XML in UTF-8 text. The electronic document, created on December 11, 2025, is entitled “094669.0103_ST26.xml”, and is 88,921 bytes in size.FIELD OF THE INVENTIONThe present disclosure relates to bispecific molecules targeting Vβ17 and CD19, nucleic acids and expression vectors encoding said molecules, recombinant cells containing the vectors, and compositions comprising the molecules. Methods of making the antibodies, and methods of using the antibodies to kill cancer cells, are also provided.BACKGROUND OF THE INVENTIONCytotoxic T cells (e.g., CD8+ T cells) can be utilized to directly deplete B cells. Finding a way to direct cytotoxic T cells to a B cell could lead to the killing of such cells and an inhibition of cancer cell propagation. It has been demonstrated that cytotoxic T cells can be activated against B cells, by bringing said cytotoxic T cells into close proximity to said B cells for an extended period of time using a bi specific antibody that binds both the cytotoxic T cell and the B cell. A variety of potential complications to this approach of killing B cells exist, such as selecting T cell and B cell antigens that mediate T cell activation, selecting parental antibodies that have adequate affinity to mediate binding in the context of a bispecific antibody, and choosing a B cell antigen that activates T cells to act specifically against B cells, rather than elicit nonspecific T cell activation. These complications are only compounded in the context of attempting to activate T cells to deplete B cells in an animal subject.094669.0103PATENTSUMMARY OF THE INVENTIONIn certain non-limiting embodiments, the present disclosure provides a bispecific antibody targeting Vβ17 and CD19. In certain embodiments, the bispecific antibody comprises: (a) a first binding domain that binds Vβ17 comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 26, and a second binding domain that binds CD19 comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 30; (b) a first binding domain that binds Vβ17 comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 26, and a second binding domain that binds CD19 comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 33; or (c) a first binding domain that binds Vβ17 comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 26, and a second binding domain that binds CD19 comprising a heavy chain complementarity determining region 1 (HCDR1), a094669.0103PATENTheavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 36. In certain embodiments, each CDR is designated by a method selected from Kabat, Clothia, AbM, or IMGT.In certain embodiments, the first binding domain comprises a single chain Fab. In certain embodiments, the first binding domain comprises the amino acid sequence set forth in SEQ ID NO: 26.In certain embodiments, the second binding domain comprises a single chain Fab. In certain embodiments, the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 30. In certain embodiments, the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 33. In certain embodiments, the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 36.In certain embodiments, the first binding domain comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28. In certain embodiments, the first binding domain comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the first binding domain comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29.In certain embodiments, the second binding domain comprises an spFv. In certain embodiments, the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 31. In certain embodiments, the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 34. In certain embodiments, the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 37.In certain embodiments, the second binding domain comprises an scFv. In certain embodiments, the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 32. In certain embodiments, the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 38.In certain non-limiting embodiments, the present disclosure provides a bispecific antibody comprising: (a) a single chain Fab binding Vβ17 comprising the amino acid sequence094669.0103PATENTset forth in SEQ ID NO: 26, and (b) a single chain Fab binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 30.In certain non-limiting embodiments, the present disclosure provides a bispecific antibody comprising: (a) a single chain Fab binding Vβ17 comprising the amino acid sequence set forth in SEQ ID NO: 26, and (b) a single chain Fab binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 33.In certain non-limiting embodiments, the present disclosure provides a bispecific antibody comprising: (a) a single chain Fab binding Vβ17 comprising the amino acid sequence set forth in SEQ ID NO: 26, and (b) a single chain Fab binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 36.In certain non-limiting embodiments, the present disclosure provides a bispecific antibody comprising: (a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29; and (b) an spFv binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 31.In certain non-limiting embodiments, the present disclosure provides a bispecific antibody comprising: (a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29; and (b) an spFv binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 34.In certain non-limiting embodiments, the present disclosure provides a bispecific antibody comprising: (a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29; and (b) an spFv binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 37.In certain non-limiting embodiments, the present disclosure provides a bispecific antibody comprising: (a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29; and (b) an scFv binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 32.In certain non-limiting embodiments, the present disclosure provides a bispecific antibody comprising: (a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29;094669.0103PATENTand (b) an scFv binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 35.In certain non-limiting embodiments, the present disclosure provides a bispecific antibody comprising: (a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29; and (b) an scFv binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 38.In certain non-limiting embodiments, the present disclosure provides a nucleic acid encoding the bispecific antibody disclosed herein. In certain embodiments, the nucleic acid comprises a first polynucleotide encoding the first binding domain that binds Vβ17. In certain embodiments, the nucleic acid comprises a second polynucleotide encoding the second binding domain that binds CD 19.In certain non-limiting embodiments, the present disclosure provides a vector comprising the nucleic acid disclosed herein. In certain non-limiting embodiments, the present disclosure provides a host cell comprising the nucleic acid or the vector disclosed herein. In certain non-limiting embodiments, the present disclosure provides a composition comprising the bispecific antibody, the nucleic acid, the vector, or the host cell disclosed herein. In certain embodiments, the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.In certain non-limiting embodiments, the present disclosure provides a method for treating an autoimmune disease in a subject in need thereof, the method comprising administering an effective amount of the bispecific antibody or the composition disclosed herein. In certain embodiments, the autoimmune disease is selected from lupus, lupus erythematosus, systemic lupus erythematosus, refractory systemic lupus erythematosus, or external lupus (cutaneous lupus erythematosus). In certain embodiments, the autoimmune disease is selected from nephritis, lupus nephritis, goodpasture’s syndrome, membranous nephropathy, ANCA-associated renal vasculitis, Henoch–Schönlein purpura, polyarteritis nodosa (PAN), sarcoidosis, scleroderma nephritis, or immune nephritis. In certain embodiments, the autoimmune disease is selected from systemic sclerosis, limited cutaneous systemic sclerosis (IcSSc), diffuse cutaneous systemic sclerosis (dcSSc), systemic sclerosis sine scleroderma, scleroderma, localized scleroderma, systemic scleroderma, limited cutaneous scleroderma, or diffuse cutaneous scleroderma. In certain embodiments, the autoimmune disease is selected from arthritis, rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis (JIA), lupus arthritis, reactive arthritis, Lyme arthritis,094669.0103PATENTor gout. In certain embodiments, the autoimmune disease is selected from multiple sclerosis, clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS). In certain embodiments, the autoimmune disease is selected from atopic dermatitis, psoriasis, pemphigus, bullous pemphigoid, dermatitis herpetiformis, Behçet's disease, or vasculitis. In certain embodiments, the autoimmune disease is selected from asthma, interstitial lung disease (ILD), pulmonary hypertension, bronchiectasis, lung nodules, or Sjogren’s syndrome. In certain embodiments, the autoimmune disease is selected from antiphospholipid syndrome. In certain embodiments, the autoimmune disease is selected from myositis, idiopathic inflammatory myopathies (IIMs), polymyositis, dermatomyositis, sporadic inclusion body myositis, inclusion body myositis, or dermatomyositis. In certain embodiments, the autoimmune disease is selected from generalized myasthenia gravis. In certain embodiments, the autoimmune disease is selected from neuromyelitis optica, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), or acute disseminated encephalomyelitis (ADEM).In certain non-limiting embodiments, the present disclosure provides a method for depleting B cells in a subject in need thereof, the method comprising administering an effective amount of the bi specific antibody or the composition disclosed herein. In certain non-limiting embodiments, the present disclosure provides a method of promoting T cell mediated killing of B cells expressing CD 19 in a subject in need thereof, the method comprising administering an effective amount of the bispecific antibody or the composition disclosed herein.In certain non-limiting embodiments, the present disclosure provides a method of directing a Vβ17-expressing T cell to a B cell in a subject in need thereof, the method comprising administering an effective amount of the bispecific antibody or the composition disclosed herein. In certain embodiments, the T cell is a CD8 T cell or a CD4 T cell.BRIEF DESCRIPTION OF THE DRAWINGSThe foregoing summary, as well as the following detailed description of preferred embodiments of the present application, will be better understood when read in conjunction with the appended drawings. It should be understood, however, that the application is not limited to the precise embodiments shown in the drawings.Figs. 1A-1D depict binding of bispecific antibodies to high CD19 expressing Daudi cell line. Different formats of Vβ17xCD19 bispecific antibodies were tested for binding on Daudi cells which have high expression of CD19 on the surface.094669.0103PATENTFigs. 2A-2D depict binding of bispecific antibodies to low CD19 expressing HBL-1 cell line. Different formats of Vβ17xCD19 bispecific antibodies were tested for binding on HBL-1 cells which have low expression of CD19 on the surface.Figs. 3A-3D depict binding of bispecific antibodies to low CD 19 expressing WIL2-S cell line. Different formats of Vβ17xCD19 bispecific antibodies were tested for binding on WIL2-S cells which have low expression of CD19 on the surface.Figs. 4A-4D depict binding of bispecific antibodies to medium CD 19 expressing NALM-6 cell line. Different formats of Vβ17xCD19 bispecific antibodies were tested for binding on NALM-6 cells which have medium expression of CD19 on the surface.Figs. 5A-5D depict bispecific antibodies to isolated and expanded Vb17 cells from Donor 1.Figs. 6A-6D depict bispecific antibodies to isolated and expanded Vb17 cells from Donor 2.Figs. 7A-7H depict IncuCyte-based Cytotoxicity assays using isolated and expanded Vβ17 cells.Figs. 8A-8F depict IncuCyte-based Cytotoxicity assays using isolated pan-T cells. Figs. 9A-9J depict plasmid quality analysis by agarose gel electrophoresis.DETAILED DESCRIPTION OF THE INVENTIONThe present disclosure provides isolated anti-Vβ17 / anti-CD19 bispecific molecules (e.g., bispecific antibodies) targeting Vβ17 and CD19 or antigen-binding fragments thereof, nucleic acids and expression vectors encoding the molecules, recombinant cells containing the vectors, and compositions comprising the bispecific molecules (e.g., bispecific antibodies). Methods of making the molecules (e.g., bispecific antibodies), and methods of using the same to treat diseases, including autoimmune diseases, are also provided herein. The bispecific molecules (e.g., bispecific antibodies) disclosed herein possess one or more desirable functional properties including, but not limited to, high-affinity binding to Vβ17 and / or CD19, high specificity to Vβ17 and / or CD19, improved stability and lower aggregation risks, and the ability to treat or prevent cancer when administered alone or in combination with other therapies for autoimmune diseases.Definitions094669.0103PATENTUnless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure pertains. Otherwise, certain terms used herein have the meanings as set forth in the specification.Unless otherwise stated, any numerical values, such as a concentration or a concentration range described herein, are to be understood as being modified in all instances by the term “about.” Thus, a numerical value typically includes ± 10% of the recited value. For example, a concentration of 1 mg / mL includes 0.9 mg / mL to 1.1 mg / mL. Likewise, a concentration range of 1% to 10% (w / v) includes 0.9% (w / v) to 11% (w / v). As used herein, the use of a numerical range expressly includes all possible subranges, all individual numerical values within that range, including integers within such ranges and fractions of the values unless the context clearly indicates otherwise.Unless otherwise indicated, the term “at least” preceding a series of elements is to be understood to refer to every element in the series. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the present disclosure. Such equivalents are intended to be encompassed by the present disclosure.It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise.As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains” or “containing,” or any other variation thereof, will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers and are intended to be non-exclusive or open-ended. For example, a composition, a mixture, a process, a method, an article, or an apparatus that comprises a list of elements is not necessarily limited to only those elements but can include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus. Further, unless expressly stated to the contrary, “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).As used herein, the conjunctive term “and / or” between multiple recited elements is understood as encompassing both individual and combined options. For instance, where two elements are conjoined by “and / or,” a first option refers to the applicability of the first element without the second. A second option refers to the applicability of the second element without094669.0103PATENTthe first. A third option refers to the applicability of the first and second elements together. Any one of these options is understood to fall within the meaning, and therefore satisfy the requirement of the term “and / or” as used herein. Concurrent applicability of more than one of the options is also understood to fall within the meaning, and therefore satisfy the requirement of the term “and / or.”It should also be understood that the terms “about,” “approximately,” “generally,” “substantially,” and like terms, used herein when referring to a dimension or characteristic of a component of the present disclosure, indicate that the described dimension / characteristic is not a strict boundary or parameter and does not exclude minor variations therefrom that are functionally the same or similar, as would be understood by one having ordinary skill in the art. At a minimum, such references that include a numerical parameter would include variations that, using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.), would not vary the least significant digit.The terms “identical” or percent “identity,” in the context of two or more nucleic acids or polypeptide sequences (e.g., anti-Vβ17 / anti-CD19 bispecific antibodies and polynucleotides that encode them, Vβ17 polypeptides and Vβ17 polynucleotides that encode them, CD19 polypeptides and CD19 polynucleotides that encode them), refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same, when compared and aligned for maximum correspondence, as measured using one of the following sequence comparison algorithms or by visual inspection.For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters.Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat’l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr.,094669.0103PATENTMadison, WI), or by visual inspection (see generally, Current Protocols in Molecular Biology, F. M. Ausubel et al., eds., Current Protocols, a joint venture between Greene Publishing Associates, Inc. and John Wiley & Sons, Inc., (1995 Supplement) (Ausubel)).Examples of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1990) J. Mol. Biol. 215: 403-410 and Altschul et al. (1997) Nucleic Acids Res.25: 3389-3402, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased.As used herein, the term "antibody" is used in a broad sense and includes immunoglobulin or antibody molecules including human, humanized, composite and chimeric antibodies and antibody fragments that are monoclonal or polyclonal. Antibodies are proteins or peptide chains that exhibit binding specificity to a specific antigen. Antibody structures are well known. Immunoglobulins can be assigned to five major classes (i.e., IgA, IgD, IgE, IgG and IgM), depending on the heavy chain constant domain amino acid sequence. IgA and IgG are further subclassified as the isotypes IgAl, IgA2, IgGl, IgG2, IgG3 and IgG4. Accordingly, the antibodies provided herein can be of any of the five major classes or corresponding subclasses. In certain embodiments, the antibodies provided herein are IgGl, IgG2, IgG3, or IgG4. Antibody light chains of vertebrate species can be assigned to one of two clearly distinct types, namely kappa and lambda, based on the amino acid sequences of their constant domains. Accordingly, the antibodies provided herein can include a kappa or lambda light chain constant domain. In certain embodiments, the antibodies disclosed herein include heavy and / or light chain constant regions from rat or human antibodies.In addition to the heavy and light constant domains, antibodies contain an antigen-binding region that is made up of a light chain variable region (VL) and a heavy chain variable region (VH), each of which contains three domains (i.e., complementarity determining regions 1 (CDR1), CDR2 and CDR3). A " CDR" refers to one of three hypervariable regions (HCDR1, HCDR2 or HCDR3) within the non-framework region094669.0103PATENTof the immunoglobulin (Ig or antibody) VH (P-sheet framework, or one of three hypervariable regions (LCDR1, LCDR2 or LCDR3) within the non-framework region of the antibody VL (P-sheet framework. Accordingly, CDRs are variable region sequences interspersed within the framework region sequences. CDR regions are well known to those skilled in the art and have been defined by multiple designation methods (e.g., Kabat, Chothia, AbM, IMGT, etc.).The light chain variable region CDR1 domain is interchangeably referred to herein as LCDR1 or VL CDR1. The light chain variable region CDR2 domain is interchangeably referred to herein as LCDR2 or VL CDR2. The light chain variable region CDR3 domain is interchangeably referred to herein as LCDR3 or VL CDR3. The heavy chain variable region CDR1 domain is interchangeably referred to herein as HCDR1 or VH CDR1. The heavy chain variable region CDR2 domain is interchangeably referred to herein as HCDR2 or VH CDR2. The heavy chain variable region CDR1 domain is interchangeably referred to herein as HCDR3 orVH CDR3.The term "hypervariable region," such as a VH or VL, when used herein refers to the regions of an antibody variable region that are hypervariable in sequence and / or form structurally defined loops. Generally, antibodies comprise six hypervariable regions; three in the VH (HCDR1, HCDR2, HCDR3), and three in the VL (LCDR1, LCDR2, LCDR3).The term "constant region" or "constant domain" refers to a carboxy terminal portion of the light and heavy chain which is not directly involved in binding of the antibody to antigen but exhibits various effector function, such as interaction with the Fc receptor. The terms refer to the portion of an immunoglobulin molecule having a more conserved amino acid sequence relative to the other portion of the immunoglobulin, the variable region, which contains the antigen binding site. The constant region may contain the CHI, CH2 and CH3 regions of the heavy chain and the CL region of the light chain.The term "framework" or " FR" residues are those variable region residues flanking the CDRs. FR residues are present, for example, in chimeric, humanized, human, domain antibodies, diabodies, linear antibodies, and bispecific antibodies. FR residues are those variable domain residues other than the hypervariable region residues or CDR residues.As used herein, the term an "isolated antibody" refers to an antibody which is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds to Vβ17 is substantially free of antibodies that do not bind to Vβ17; an isolated antibody that specifically binds to CD19 is substantially free of antibodies that does not bind to CD 19. In addition, an isolated antibody is substantially free of other cellular material and / or chemicals.094669.0103PATENTAs used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that can be present in minor amounts. The monoclonal antibodies disclosed herein can be made by the hybridoma method, phage display technology, single lymphocyte gene cloning technology, or by recombinant DNA methods. For example, the monoclonal antibodies can be produced by a hybridoma which includes a B cell obtained from a transgenic nonhuman animal, such as a transgenic mouse or rat, having a genome comprising a human heavy chain transgene and a light chain transgene.As used herein, the term "antigen-binding fragment" refers to an antibody fragment such as, for example, a diabody, a Fab, a Fab', a F(ab')2, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a bispecific dsFv (dsFv-dsFv1), a disulfide stabilized diabody (ds diabody), a single-chain antibody molecule (scFv), a single domain antibody (sdAb) an scFv dimer (bivalent diabody), a multispecific antibody formed from a portion of an antibody comprising one or more CDRs, a camelized single domain antibody, a nanobody, a domain antibody, a bivalent domain antibody, an spFv or any other antibody fragment that binds to an antigen but does not comprise a complete antibody structure. An antigen-binding fragment is capable of binding to the same antigen to which the parent antibody or a parent antibody fragment binds. In certain embodiments, the antigen-binding fragment comprises a light chain variable region, a light chain constant region, and an Fd segment of the heavy chain. In certain embodiments, the antigen-binding fragment comprises Fab and F(ab').As used herein, a “binding domain” refers to that part of a molecule that specifically binds to a target epitope, antigen, ligand, or receptor. Binding domains include, for example, antibodies, antibody fragments thereof (such as Fab fragments, Fab' 2, scFv antibodies, spFv antibodies, SMIP, domain antibodies, diabodies, minibodies, scFv-Fc, affibodies, nanobodies) and VH and / or VL domains of antibodies.As used herein, the term "single-chain antibody" refers to a conventional single-chain antibody in the field, which comprises a heavy chain variable region and a light chain variable region connected by a short peptide of about 15 to about 20 amino acids. As used herein, the term "single domain antibody" refers to a conventional single domain antibody in the field, which comprises a heavy chain variable region and a heavy chain constant region or which comprises only a heavy chain variable region.094669.0103PATENTAs used herein, the term "human antibody" refers to an antibody produced by a human or an antibody having an amino acid sequence corresponding to an antibody produced by a human made using any technique known in the art. This definition of a human antibody includes intact or full-length antibodies, fragments thereof, and / or antibodies comprising at least one human heavy and / or light chain polypeptide.As used herein, the term "humanized antibody" refers to a non-human antibody that is modified to increase the sequence homology to that of a human antibody, such that the antigenbinding properties of the antibody are retained, but its antigenicity in the human body is reduced.As used herein, the term "chimeric antibody" refers to an antibody wherein the amino acid sequence of the immunoglobulin molecule is derived from two or more species. The variable region of both the light and heavy chains often correspond to the variable region of an antibody derived from one species of mammal (e.g., mouse, rat, rabbit, etc.) having the desired specificity, affinity, and capability, while the constant regions correspond to the sequences of an antibody derived from another species of mammal (e.g., human) to avoid eliciting an immune response in that species.The term "specificity" refers to selective recognition of an antigen binding protein (such as an antibody) for a particular epitope of an antigen. Natural antibodies, for example, are monospecific. The term "multispecific" as used herein denotes that an antigen binding protein (such as an antibody) has two or more antigen-binding sites of which at least two bind different antigens. " Bispecific" as used herein denotes that an antigen binding protein has two different antigen-binding specificities.As used herein, the term "multispecific antibody" refers to an antibody that comprises a plurality of immunoglobulin variable domain sequences, wherein a first immunoglobulin variable domain sequence of the plurality has binding specificity for a first epitope and a second immunoglobulin variable domain sequence of the plurality has binding specificity for a second epitope. In certain embodiments, the first and second epitopes do not overlap or do not substantially overlap. In certain embodiments, the first and second epitopes are on different antigens, e.g., the different proteins (or different subunits of a multimeric protein). In an embodiment, a multispecific antibody comprises a third, fourth, or fifth immunoglobulin variable domain. In certain embodiments, a multispecific antibody is a bispecific antibody molecule, a trispecific antibody molecule, or a tetraspecific antibody molecule.094669.0103PATENTAs used herein, the terms “spFv” or “stapled Fv” refer to a stabilized scFv including a linker that contains one or two cysteine residues capable of forming a disulfide bond with an anchor point cysteine. spFv antibodies are further described in International Patent Publication No. WO 2021 / 030657, which is incorporated by reference herein in its entirety.As used herein, the term “bispecific antibody” refers to a multispecific antibody that binds no more than two epitopes or two antigens. A bispecific antibody comprises a first binding domain and a second binding domain. In certain embodiments, the first binding domain comprises a first immunoglobulin heavy and light chain pair which has binding specificity for a first epitope (e.g., an epitope on a Vβ17 antigen). In certain embodiments, the second binding domain comprises a second immunoglobulin heavy and light chain pair that has binding specificity for a second epitope (e.g., an epitope on a CD19 antigen). In certain embodiments, the first binding domain comprises a first immunoglobulin heavy and light chain pair which has binding specificity for Vβ17. In certain embodiments, the second binding domain comprises a second immunoglobulin heavy and light chain pair that has binding specificity for CD 19. In certain embodiments, the first and second epitopes are on different antigens, e.g., the different proteins (or different subunits of a multimeric protein). In certain embodiments, a bispecific antibody comprises a heavy chain variable domain sequence and a light chain variable domain sequence which have binding specificity for a first epitope and a heavy chain variable domain sequence and a light chain variable domain sequence which have binding specificity for a second epitope. In certain embodiments, a bispecific antibody comprises a half antibody, or fragment thereof, having binding specificity for a first epitope and a half antibody, or fragment thereof, having binding specificity for a second epitope. In certain embodiments, a bispecific antibody comprises a scFv, or fragment thereof, having binding specificity for a first epitope, and a scFv, or fragment thereof, having binding specificity for a second epitope. In certain embodiments, a bispecific antibody comprises a half antibody, or fragment thereof, having binding specificity for a first epitope and a scFv, or fragment thereof, having binding specificity for a second epitope. In certain embodiments, a bispecific antibody comprises a half antibody, or fragment thereof, having binding specificity for a first epitope and a spFv, or fragment thereof, having binding specificity for a second epitope. In certain embodiments, a bispecific antibody comprises a scFv, or fragment thereof, having binding specificity for a first epitope and a half antibody, or fragment thereof, having binding specificity for a second epitope. In certain embodiments, a bispecific antibody094669.0103PATENTcomprises a spFv, or fragment thereof, having binding specificity for a first epitope and a half antibody, or fragment thereof, having binding specificity for a second epitope.The term "half antibody" as used herein refers to one immunoglobulin heavy chain associated with one immunoglobulin light chain. One skilled in the art will readily appreciate that a half-antibody can encompass a fragment thereof and can also have an antigen binding domain consisting of a single variable domain, e.g., originating from a camelidae.The term “KD” refers to the dissociation constant, which is obtained from the ratio of Kd to Ka (i.e., Kd / Ka) and is expressed as a molar concentration (M). KD values for antibodies can be determined using methods in the art in view of the present disclosure. For example, the KD of an antibody can be determined by using surface plasmon resonance, such as by using a biosensor system, e.g., a Biacore® system, or by using bio-layer interferometry technology, such as an Octet RED96 system.The smaller the value of the KD of an antibody, the higher affinity that the antibody binds to a target antigen.Bispecific Molecules and Bispecific AntibodiesThe present disclosure provides isolated anti-Vβ17 / anti-CD19 bispecific molecules (e.g., bispecific antibodies) targeting Vβ17 and CD19 or antigen-binding fragments thereof, nucleic acids and expression vectors encoding the molecules, recombinant cells containing the vectors, and compositions comprising the bispecific molecules (e.g., bispecific antibodies). Methods of making the molecules (e.g., bispecific antibodies), and methods of using the same to treat diseases, including autoimmune diseases, are also provided herein. The bispecific molecules (e.g., bispecific antibodies) disclosed herein possess one or more desirable functional properties including, but not limited to, high-affinity binding to Vβ17 and / or CD19, high specificity to Vβ17 and / or CD19, and the ability to treat autoimmune diseases when administered alone or in combination with other therapies.As used herein, the term “Vβ17” refers to a T cell receptor, which is expressed in response to an immune response on a cytotoxic T cell. Vβ17-expressing CD8+ T cells are commonly produced in response to influenza A virus exposure in a subject. Vβ17-expressing CD8+ T cells provide great recall in response to influenza exposure in the subject. The term “Vβ17” includes any Vβ17 variant, isoform, and species homolog, which is naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNA094669.0103PATENTencoding the polypeptide. Unless noted, preferably the Vβ17 is a human Vβ17. A human Vβ17 amino acid sequence is provided by GenBank Accession Number AAB49730.1.As used herein, an antibody that “specifically binds to Vβ17” refers to an antibody that binds to a Vβ17, preferably a human Vβ17, with a KD of 1 x 107M or less, preferably 1 *108M or less, more preferably 5 x 109M or less, I / 109M or less, 5 x 1010M or less, or 1 x 1010M or less. The term “KD” refers to the dissociation constant, which is obtained from the ratio of Kd to Ka (i.e., Kd / Ka) and is expressed as a molar concentration (M). KD values for antibodies can be determined using methods in the art in view of the present disclosure. For example, the KD of an antibody can be determined by using surface plasmon resonance, such as by using a biosensor system, e.g., a Biacore® system, or by using bio-layer interferometry technology, such as an Octet RED96 system.In certain embodiments, the present disclosure relates to a bispecific molecule comprising a first binding domain that binds Vβ17 and a second binding domain that binds CD 19. In certain embodiments, the bispecific molecule is a bispecific antibody or antigenbinding fragment thereof. In certain embodiments, the bispecific antibody comprises (a) a first heavy chain (HC1), (b) a second heavy chain (HC2), (c) a first light chain (LC1), and (d) a second light chain (LC2). In certain embodiments, the HC1 can be associated with the LC1 and the HC2 can be associated with LC2.In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain and a light chain.In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 1, a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 2, a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 3, a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 4, a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 5, a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 6.In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 1, a heavy chain complementarity determining region 2 (HCDR2)094669.0103PATENTcomprising the amino acid sequence set forth in SEQ ID NO: 2, a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 3, a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 25, a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 5, a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 6In certain embodiments, the first binding domain that binds Vβ17 comprises one or more modification to improve antibody developability. In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 8. In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 9 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 10.In certain embodiments, the first binding domain that binds Vβ17 comprises one or more modification to improve stability and lower aggregation risks. In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 11 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 12. In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 13 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 14.In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 15 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 16. In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 17 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 18.In certain embodiments, the first binding domain that binds Vβ17 comprises a singlechain antibody molecule (scFv) comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 7 and a light chain variable region comprising094669.0103PATENTthe amino acid sequence set forth in SEQ ID NO: 8. In certain embodiments, the scFv comprises the amino acid sequence set forth in SEQ ID NO: 19.In certain embodiments, the first binding domain that binds Vβ17 comprises a singlechain antibody molecule (scFv) comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 9 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 10. In certain embodiments, the scFv comprises the amino acid sequence set forth in SEQ ID NO: 20.In certain embodiments, the first binding domain that binds Vβ17 comprises an spFv comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 11 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 12. In certain embodiments, the scFv comprises the amino acid sequence set forth in SEQ ID NO: 21.In certain embodiments, the first binding domain that binds Vβ17 comprises an spFv comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 13 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 14.In certain embodiments, the first binding domain that binds Vβ17 comprises an spFv comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 15 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 16. In certain embodiments, the scFv comprises the amino acid sequence set forth in SEQ ID NO: 22.In certain embodiments, the first binding domain that binds Vβ17 comprises an spFv comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 17 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 18.In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 23. In certain embodiments, the first binding domain that binds Vβ17 comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO: 24. In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 23 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 24.094669.0103PATENTIn certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 26. In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain and a light chain of the amino acid sequence set forth in SEQ ID NO: 26. In certain embodiments, the first binding domain that binds Vβ17 comprises the amino acid sequence set forth in SEQ ID NO: 26.In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 27. In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain and a light chain of the amino acid sequence set forth in SEQ ID NO: 27. In certain embodiments, the first binding domain that binds Vβ17 comprises the amino acid sequence set forth in SEQ ID NO: 27.In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), and a heavy chain complementarity determining region 3 (HCDR3) of the amino acid sequence set forth in SEQ ID NO: 28. In certain embodiments, the first binding domain that binds Vβ17 comprises a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), and a heavy chain complementarity determining region 3 (HCDR3) of the amino acid sequence set forth in SEQ ID NO: 28; and a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3094669.0103PATENT(LCDR3) of the amino acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28. In certain embodiments, the first binding domain that binds Vβ17 comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the first binding domain that binds Vβ17 comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29.SEQ ID Nos: 1-29 are provided in Table 1 below.Table 1SEQ ID SequenceNO1 SGYFWN2 YISYDGSNNYNPSLKS3 PSPGTGYAVDY4 RSSQSLVHSSGNTYLH5 KVSNRFS6 SQSTHVPFT7 QVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQPPGKGLEWIGYISYDGSNNYN PSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGQGTLVTVSS8 DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSSGNTYLHWYQQKPGKAPKFLIYKVSNRFS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIK9 QVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQFPGKGLEWMGYISYDGSNNYN PSLKSRITISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGQGTTVTVSS10 DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSNRNTYLHWYQQKPGKAPKLLIYKVSNRFS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIK11 QVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQPPGKGLEWIGYISYDGSNNYN PSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGCGTLVTVSS12 DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSSGNTYLHWYQQKPGCAPKFLIYKVSNRFS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIK13 QVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQPPGCGLEWIGYISYDGSNNYN PSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGQGTLVTVSS14 DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSSGNTYLHWYQQKPGKAPKFLIYKVSNRFS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGCGTKLEIK15 QVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQFPGKGLEWMGYISYDGSNNYN PSLKSRITISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGCGTTVTVSS16 DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSNRNTYLHWYQQKPGCAPKLLIYKVSNRFS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIK17 QVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQFPGCGLEWMGYISYDGSNNYN PSLKSRITISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGQGTTVTVSS18 DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSNRNTYLHWYQQKPGKAPKLLIYKVSNRFS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGCGTKLEIK19 DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSSGNTYLHWYQQKPGKAPKFLYKVSNRFSG VPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIKGGSEGKSSGSG SESKSTGGSQVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQPPGKGLEWIGYI SYDGSNNYNPSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGQGTLVTVSS094669.0103PATENT DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSNRNTYLHWYQQKPGKAPKLLIYKVSNRFS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIKGGSEGKSSGS GSESKSTGGSQVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQFPGKGLEWMGY ISYDGSNNYNPSLKSRITISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGQ GTTVTVSS DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSSGNTYLHWYQQKPGCAPKFLIYKVSNRFS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIKGGGSGGSGGC PPCGGSGGQVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQPPGKGLEWIGYIS YDGSNNYNPSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGCGT LVTVSS DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSNRNTYLHWYQQKPGCAPKLLIYKVSNRFS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIKGGGSGGSGGC PPCGGSGGQVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQFPGKGLEWMGYIS YDGSNNYNPSLKSRITISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGCGT TVTVSS QVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQPPGKGLEWIGYISYDGSNNYN PSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGQGTLVTVSSAS TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF LFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQV SLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFS CSVMHEALHNRFTQKSLSLSPGK DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSSGNTYLHWYQQKPGKAPKFLIYKVSNRFS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIKRTVAAPSVFI FPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC RSSQSLVHSNRNTYLH MVLQTQVFISLLLWISGAYGDIQMTQSPSSLSASVGDRVTITCRSSQSLVHSNGNTYLHWY QQKPGKAPKFLIYKVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSEG KSSGSGSESKSTEGKSSGSGSESKSTGGSQVQLQESGPGLVKPSETLSLTCTVSGYSITSG YFWNWIRQPPGKGLEWIGYISYDGSNNYNPSLKSRVTISRDTSKNQFSLKLSSVTAADTAV YYCASPSPGTGYAVDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD KKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGK MVLQTQVFISLLLWISGAYGDIQMTQSPSSLSASVGDRVTITCRSSQSLVHSNGNTYLHWY QQKPGCAPKFLIYKVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFT FGQGTKLEIKGGGSGGSGGCPPCGGSGGQVQLQESGPGLVKPSETLSLTCTVSGYSITSGY FWNWIRQPPGKGLEWIGYISYDGSNNYNPSLKSRVTISRDTSKNQFSLKLSSVTAADTAVY YCASPSPGTGYAVDYWGCGTLVTVSSEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDT LMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALH NHYTQKSLSLSPGK MAWVWTLLFLMAAAQSIQAQVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQPP GKGLEWIGYISYDGSNNYNPSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGT GYAVDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSG ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK THTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR094669.0103PATENT EPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGK29 MAWVWTLLFLMAAAQSIQADIQMTQSPSSLSASVGDRVTITCRSSQSLVHSSGNTYLHWYQ QKPGKAPKFLIYKVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTF GQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECIn certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain and a light chain.The term “CD 19” as used herein refers to a cell-surface 95 kDa glycoprotein present on normal B cells from early in their development until differentiation into plasma cells. CD 19 is expressed on the surface of B cells, and its presence is associated with autoimmune diseases. Targeting CD19 with therapies has been shown to effectively deplete autoreactive B cells, which are considered key players in the development of many autoimmune conditions including, but without any limitation, systemic lupus erythematosus (SLE) and rheumatoid arthritis. CD 19 is a member of the immunoglobulin superfamily and a component of a cell surface signal transduction complex that includes Leul3, CD81, and CD21, which positively regulates signal transduction through the B cell receptor. The term “CD 19” includes any CD 19 variant, isoform, and species homolog, which is naturally expressed by cells (including tumor cells) or can be expressed on cells transfected with genes or cDNA encoding the polypeptide. In certain embodiments, the CD 19 is a human CD 19. The extracellular domain of human CD 19 comprises, according to UniProt Accession Number P15391, amino acids 20-291. The term “antibody targeting CD 19,” “antibody binding CD 19,” or “anti-CD19 antibody” as used herein relates to an antibody specifically binding to CD 19.As used herein, an antibody that “specifically binds to CD 19” refers to an antibody that binds to a CD 19, e.g., a human CD 19, with a KD of 1×10-7M or less, preferably 1×10-8M or less, more preferably 5×10-9M or less, 1×10-9M or less, 5×10-10M or less, or 1×10-10M or less.In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 30. In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain and a light chain of the amino acid sequence set forth in SEQ ID NO: 30. In certain094669.0103PATENTembodiments, the second binding domain that binds CD 19 comprises the amino acid sequence set forth in SEQ ID NO: 30.In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 31. In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain and a light chain of the amino acid sequence set forth in SEQ ID NO: 31. In certain embodiments, the second binding domain that binds CD 19 comprises the amino acid sequence set forth in SEQ ID NO: 31.In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 32. In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain and a light chain of the amino acid sequence set forth in SEQ ID NO: 32. In certain embodiments, the second binding domain that binds CD 19 comprises the amino acid sequence set forth in SEQ ID NO: 32. SEQ ID NOs: 30-32 are provided in Table 2.Table 2SEQ ID SequenceNO30 MVLQTQVFISLLLWISGAYGDIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQ QIPGQPPKLLIYDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTF GGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSEGK SSGSGSESKSTEGKSSGSGSESKSTGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYW MNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESSSTAYMQLSSLASEDSAVY FCARRETTTVGRYYYAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK094669.0103PATENT31 MVLQTQVFISLLLWISGAYGDIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQ QIPGCPPKLLIYDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTF GGGTKLEIKGGGSGGSGGCPPCGGSGGQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWM NWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESSSTAYMQLSSLASEDSAVYF CARRETTTVGRYYYAMDYWGCGTTVTVSSEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKP KDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGK32 MVLQTQVFISLLLWISGAYGDIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQ QIPGQPPKLLIYDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTF GGGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWV KQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESSSTAYMQLSSLASEDSAVYFCAR RETTTVGRYYYAMDYWGQGTTVTVSSEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDT LMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIn certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 33. In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain and a light chain of the amino acid sequence set forth in SEQ ID NO: 33. In certain embodiments, the second binding domain that binds CD 19 comprises the amino acid sequence set forth in SEQ ID NO: 33.In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 34. In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain and a light chain of the amino acid sequence set forth in SEQ ID NO: 34. In certain embodiments, the second binding domain that binds CD 19 comprises the amino acid sequence set forth in SEQ ID NO: 34.In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity094669.0103PATENTdetermining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain and a light chain of the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, the second binding domain that binds CD 19 comprises the amino acid sequence set forth in SEQ ID NO: 35. SEQ ID NOs: 33-35 are provided in Table 3.Table 3SEQ ID SequenceNO33 MVLQTQVFISLLLWISGAYGEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKP GQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRFTFGPG TKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQES VTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSEGKSSG SGSESKSTEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGSSVKVSCKDSGGTFSSYAISW VRQAPGQGLEWMGGIIPIFGTTNYAQQFQGRVTITADESTSTAYMELSSLRSEDTAVYYCA REAVAADWLDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP KSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK34 MVLQTQVFISLLLWISGAYGEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKP GCAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRFTFGPG TKVDIKGGGSGGSGGCPPCGGSGGQVQLVQSGAEVKKPGSSVKVSCKDSGGTFSSYAISWV RQAPGQGLEWMGGIIPIFGTTNYAQQFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR EAVAADWLDPWGCGTLVTVSSEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISR TPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK35 MVLQTQVFISLLLWISGAYGEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKP GQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRFTFGPG TKVDIKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGSSVKVSCKDSGGTFSSYAISWVRQA PGQGLEWMGGIIPIFGTTNYAQQFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAV AADWLDPWGQGTLVTVSSEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPE VTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIn certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3094669.0103PATENT(HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 36. In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain and a light chain of the amino acid sequence set forth in SEQ ID NO: 36. In certain embodiments, the second binding domain that binds CD 19 comprises the amino acid sequence set forth in SEQ ID NO: 36.In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 37. In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain and a light chain of the amino acid sequence set forth in SEQ ID NO: 37. In certain embodiments, the second binding domain that binds CD 19 comprises the amino acid sequence set forth in SEQ ID NO: 37.In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 38. In certain embodiments, the second binding domain that binds CD 19 comprises a heavy chain and a light chain of the amino acid sequence set forth in SEQ ID NO: 38. In certain embodiments, the second binding domain that binds CD 19 comprises the amino acid sequence set forth in SEQ ID NO: 38. SEQ ID NOs: 36-38 are provided in Table 4.Table 4SEQ ID SequenceNO36 MVLQTQVFISLLLWISGAYGAIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPG KAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPYTFGQGT KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESV TEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGSEVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWIGWV094669.0103PATENT RQMPGKGLEWMGIIYPDDSDTRYSPSFQGQVTISADKSIRTAYLQWSSLKASDTAMYYCAR HVTMIWGVI IDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVE PKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK37 MVLQTQVFISLLLWISGAYGAIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPG CAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPYTFGQGT KLEIKGGGSGGSGGCPPCGGSGGEVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWIGWVR QMPGKGLEWMGIIYPDDSDTRYSPSFQGQVTISADKSIRTAYLQWSSLKASDTAMYYCARH VTMIWGVIIDFWGCGTLVTVSSEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMIS RTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGK38 MVLQTQVFISLLLWISGAYGAIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPG KAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPYTFGQGT KLEIKGGGGSGGGGSGGGGSEVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWIGWVRQMP GKGLEWMGIIYPDDSDTRYSPSFQGQVTISADKSIRTAYLQWSSLKASDTAMYYCARHVTM IWGVIIDFWGQGTLVTVSSEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTP EVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIn certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19. In certain embodiments, the first binding domain comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 26. In certain embodiments, the second binding domain comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 30.In certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19. In certain embodiments, the first binding domain comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity094669.0103PATENTdetermining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 26. In certain embodiments, the second binding domain comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 33.In certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19. In certain embodiments, the first binding domain comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 26. In certain embodiments, the second binding domain comprises a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 36.In certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19. In certain embodiments, the first binding domain comprises a single chain Fab (scFab) comprising the amino acid sequence set forth in SEQ ID NO: 26. In certain embodiments, the second binding domain comprises a single chain Fab (scFab) comprising the amino acid sequence set forth in SEQ ID NO: 30.In certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19. In certain embodiments, the first binding domain comprises a single chain Fab (scFab) comprising the amino acid sequence set forth in SEQ ID NO: 26. In certain embodiments, the second binding domain comprises a single chain Fab (scFab) comprising the amino acid sequence set forth in SEQ ID NO: 33.094669.0103PATENTIn certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19. In certain embodiments, the first binding domain comprises a single chain Fab (scFab) comprising the amino acid sequence set forth in SEQ ID NO: 26. In certain embodiments, the second binding domain comprises a single chain Fab (scFab) comprising the amino acid sequence set forth in SEQ ID NO: 36.In certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19, wherein the second binding domain comprises a spFv. In certain embodiments, the first binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the second binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 31.In certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19, wherein the second binding domain comprises a spFv. In certain embodiments, the first binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the second binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 34.In certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19, wherein the second binding domain comprises a spFv. In certain embodiments, the first binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the second binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 37.In certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19, wherein the second binding domain comprises a scFv. In certain embodiments, the first binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the second binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 32.094669.0103PATENTIn certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19, wherein the second binding domain comprises a scFv. In certain embodiments, the first binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the second binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 35.In certain embodiments, the bispecific molecule comprises a first binding domain that binds Vβ17 and a second binding domain that binds CD 19, wherein the second binding domain comprises a scFv. In certain embodiments, the first binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the second binding domain comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 38.In certain embodiments, the Vβ17 is on the surface of a CD8+or CD4+T cell. In certain embodiments, the CD19 is on the surface of a disease cell (e.g., a B cell).In certain embodiments, the disease is an autoimmune disease or an inflammatory disease. Non-limiting examples of autoimmune diseases and inflammatory diseases include arthritis, e.g., rheumatoid arthritis (RA), Type I diabetes, systemic lupus erythematosus (SLE), inflammatory bowel disease, ulcerative colitis, psoriasis, psoriatic arthritis, scleroderma, autoimmune thyroid disease, Grave's disease, Crohn's disease, multiple sclerosis, systemic sclerosis, asthma, organ transplant rejection, a disease or condition associated with transplant, Takayasu arteritis, giant-cell arteritis, Kawasaki disease, polyarteritis nodosa, Behcet's syndrome, Wegener's granulomatosis, ANCA-vasculitides, Churg-Strauss syndrome, microscopic polyangiitis, vasculitis of connective tissue diseases, Hennoch-Schonlein purpura, cryoglobulinemic vasculitis, cutaneous leukocytoclastic angiitis, Sarcoidosis, Cogan's syndrome, Wiskott-Aldrich Syndrome, primary angiitis of the CNS, thromboangiitis obliterans, paraneoplastic arteritis, myelodysplastic syndrome, erythema elevatum diutinum, amyloidosis, autoimmune myositis, Guillain-Barre Syndrome, histiocytosis, atopic dermatitis, pulmonary fibrosis, glomerulonephritis, Whipple's disease, Still's disease, Sjogren's syndrome, osteomyelofibrosis, chronic inflammatory demyelinating polyneuropathy, Kimura's disease, systemic sclerosis, chronic periaortitis, chronic prostatitis, idiopathic pulmonary fibrosis, chronic granulomatous disease, idiopathic, bleomycin-induced lung inflammation, cytarabine-094669.0103PATENTinduced lung inflammation, autoimmune thrombocytopenia, autoimmune neutropenia, autoimmune hemolytic anemia, autoimmune lymphocytopenia, chronic autoimmune thyroiditis, autoimmune hepatitis, Hashimoto's thyroiditis, atopic thyroiditis, Graves disease, autoimmune polyglandular syndrome, autoimmune Addison syndrome, and / or myasthenia gravis.In certain embodiments, the autoimmune disease is selected from lupus, lupus erythematosus, systemic lupus erythematosus, refractory systemic lupus erythematosus, or external lupus (cutaneous lupus erythematosus).In certain embodiments, the autoimmune disease is selected from nephritis, lupus nephritis, goodpasture’s syndrome, membranous nephropathy, ANCA-associated renal vasculitis, Henoch–Schönlein purpura, polyarteritis nodosa (PAN), sarcoidosis, scleroderma nephritis, or immune nephritis.In certain embodiments, the autoimmune disease is selected from systemic sclerosis, limited cutaneous systemic sclerosis (IcSSc), diffuse cutaneous systemic sclerosis (dcSSc), systemic sclerosis sine scleroderma, scleroderma, localized scleroderma, systemic scleroderma, limited cutaneous scleroderma, or diffuse cutaneous scleroderma.In certain embodiments, the autoimmune disease is selected from arthritis, rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis (JIA), lupus arthritis, reactive arthritis, lyme arthritis, or gout.In certain embodiments, the autoimmune disease is selected from multiple sclerosis, clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS).In certain embodiments, the autoimmune disease is selected from atopic dermatitis, psoriasis, pemphigus, bullous pemphigoid, dermatitis herpetiformis, Behçet's disease, or vasculitis.In certain embodiments, the autoimmune disease is selected from asthma, interstitial lung disease (ILD), pulmonary hypertension, bronchiectasis, lung nodules, or Sjogren’s syndrome.In certain embodiments, the autoimmune disease is antiphospholipid syndrome.In certain embodiments, the autoimmune disease is selected from myositis, idiopathic inflammatory myopathies (IIMs), polymyositis, dermatomyositis, sporadic inclusion body myositis, inclusion body myositis, or dermatomyositis.In certain embodiments, the autoimmune disease is generalized myasthenia gravis (e.g., class I myasthenia gravis, class II myasthenia gravis, etc.).094669.0103PATENTIn certain embodiments, the autoimmune disease is selected from neuromyelitis optica, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), or acute disseminated encephalomyelitis (ADEM).In certain embodiments, the disease is a B cell malignancy (e.g., B cell leukemia, B cell lymphoma, B cell chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), pro-lymphocytic leukemias, hairy cell leukemias, common acute lymphocytic leukemias, Null-acute lymphoblastic leukemias, non-Hodgkin lymphomas, diffuse large B cell lymphomas (DLBCLs), multiple myelomas, follicular lymphoma, splenic, marginal zone lymphoma, mantle cell lymphoma, indolent B cell lymphoma, Hodgkin lymphoma).In certain embodiments, the bispecific antibodies disclosed herein can take the form of a diabody, a cross-body, or a bispecific antibody obtained via a controlled Fab arm exchange as described herein.In certain embodiments, the bispecific antibodies include IgG-like molecules with complementary CH3 domains that promote heterodimerization; recombinant IgG-like dual targeting molecules, wherein the two sides of the molecule each contain the Fab fragment or part of the Fab fragment of at least two different antibodies; IgG fusion molecules, wherein full length IgG antibodies are fused to an extra Fab fragment or parts of Fab fragment; Fc fusion molecules, wherein single chain Fv molecules or stabilized diabodies are fused to heavy-chain constant-domains, Fc-regions or parts thereof; Fab fusion molecules, wherein different Fab-fragments are fused together; ScFv- and diabody -based and heavy chain antibodies (e.g., domain antibodies, nanobodies) wherein different single chain Fv molecules or different diabodies or different heavy-chain antibodies (e.g. domain antibodies, nanobodies) are fused to each other or to another protein or carrier molecule.In certain embodiments, IgG-like molecules with complementary CH3 domains molecules include the Triomab / Quadroma (Trion Pharma / Fresenius Biotech), the Knobs-into-Holes (Genentech), CrossMAbs (Roche) and the electrostatically-matched (Amgen), the LUZ-Y (Genentech), the Strand Exchange Engineered Domain body (SEEDbody) (EMD Serono), the Biclonic (Merus) and the DuoBody (Genmab A / S).In certain embodiments, recombinant IgG-like dual targeting molecules include Dual Targeting (DT)-Ig (GSK / Domantis), Two-in-one Antibody (Genentech), Cross-linked Mabs (Karmanos Cancer Center), mAb2 (F-Star) and CovX-body (CovX / Pfizer).In certain embodiments, IgG fusion molecules include Dual Variable Domain (DVD)-Ig (Abbott), IgG-like Bispecific (InnClone / Eli Lilly), Ts2Ab (Medlmmune / AZ) and BsAb (Zymogenetics), HERCULES (Biogen Idee) and TvAb (Roche).094669.0103PATENTIn certain embodiments, Fc fusion molecules can include ScFv / Fc Fusions (Academic Institution), SCORPION (Emergent BioSolutions / Trubion, Zymogenetics / BMS), Dual Affinity Retargeting Technology (Fc-DART) (MacroGenics) and Dual(ScFv)2-Fab (National Research Center for Antibody Medicine— China).In certain embodiments, Fab fusion bispecific antibodies include F(ab)2(Medarex / AMGEN), Dual-Action or Bis-Fab (Genentech), Dock-and-Lock (DNL) (ImmunoMedics), Bivalent Bispecific (Biotecnol) and Fab-Fv (UCB-Celltech). ScFv-, diabody -based, and domain antibodies, include but are not limited to, Bispecific T Cell Engager (BiTE) (Micromet), Tandem Diabody (Tandab) (Affimed), Dual Affinity Retargeting Technology (DART) (MacroGenics), Single-chain Diabody (Academic), TCR-like Antibodies (AIT, ReceptorLogics), Human Serum Albumin ScFv Fusion (Merrimack) and COMBODY (Epigen Biotech), dual targeting nanobodies (Ablynx), dual targeting heavy chain only domain antibodies.Full length bispecific antibodies disclosed herein can be generated for example using Fab arm exchange (or half molecule exchange) between two mono specific bivalent antibodies by introducing substitutions at the heavy chain CH3 interface in each half molecule to favor heterodimer formation of two antibody half molecules having distinct binding specificity either in vitro in cell-free environment or using co-expression. The Fab arm exchange reaction is the result of a disulfide-bond isomerization reaction and dissociation-association of CH3 domains. The heavy-chain disulfide bonds in the hinge regions of the parent mono specific antibodies are reduced. The resulting free cysteines of one of the parent monospecific antibodies form an inter heavy-chain disulfide bond with cysteine residues of a second parent mono specific antibody molecule and simultaneously CH3 domains of the parent antibodies release and reform by dissociation-association. The CH3 domains of the Fab arms can be engineered to favor heterodimerization over homodimerization. The resulting product is a bispecific antibody having two Fab arms or half molecules, each binding a distinct epitope, i.e., an epitope on Vβ17 and an epitope on a tumor antigen.“Homodimerization,” as used herein, refers to an interaction of two heavy chains having identical CH3 amino acid sequences. “Homodimer,” as used herein, refers to an antibody having two heavy chains with identical CH3 amino acid sequences.The “knob-in-hole” strategy (see, e.g., International Patent Publication No. WO 2006 / 028936) can be used to generate full length bispecific antibodies. Briefly, selected amino acids forming the interface of the CH3 domains in human IgG can be mutated at positions affecting CH3 domain interactions to promote heterodimer formation. An amino acid with a094669.0103PATENTsmall side chain (hole) is introduced into a heavy chain of an antibody specifically binding a first antigen and an amino acid with a large side chain (knob) is introduced into a heavy chain of an antibody specifically binding a second antigen. After co-expression of the two antibodies, a heterodimer is formed as a result of the preferential interaction of the heavy chain with a “hole” with the heavy chain with a “knob”. Exemplary CH3 substitution pairs forming a knob and a hole are (expressed as modified position in the first CH3 domain of the first heavy chain / modified position in the second CH3 domain of the second heavy chain): T366Y / F405A, T366W / F405W, F405W / Y407A, T394W / Y407T, T394S / Y407A, T366W / T394S, F405W / T394S and T366W / T366S_L368A_Y407V.Other strategies such as promoting heavy chain heterodimerization using electrostatic interactions by substituting positively charged residues at one CH3 surface and negatively charged residues at a second CH3 surface can be used, as described in US Pat. Publ. No. US2010 / 0015133; US Pat. Publ. No. US2009 / 0182127; US Pat. Publ. No. US2010 / 028637; or US Pat. Publ. No. US2011 / 0123532. In other strategies, heterodimerization can be promoted by the following substitutions (expressed as modified position in the first CH3 domain of the first heavy chain / modified position in the second CH3 domain of the second heavy chain): L351 Y_F405 AY407V / T394W, T366I_K392M_T394W / F405 A_Y407V, T366L_K392M_T394W / F405A_Y407V, L351 Y_Y407A / T366A_K409F, L351Y_Y407A / T366V K409F Y407A / T366A_K409F, or T350V_L351Y_F405A Y407V / T350V_T366L_K392L_T394W as described in U. S. Pat. Publ. No. US2012 / 0149876 or U. S. Pat. Publ. No. US2013 / 0195849.In addition to methods described above, bispecific antibodies disclosed herein can be generated in vitro in a cell-free environment by introducing asymmetrical mutations in the CH3 regions of two mono specific homodimeric antibodies and forming the bispecific heterodimeric antibody from two parent monospecific homodimeric antibodies in reducing conditions to allow disulfide bond isomerization according to methods described in International Patent Publication No. WO 2011 / 131746. In the methods, the first monospecific bivalent antibody (and the second monospecific bivalent antibody are engineered to have certain substitutions at the CH3 domain that promotes heterodimer stability; the antibodies are incubated together under reducing conditions sufficient to allow the cysteines in the hinge region to undergo disulfide bond isomerization; thereby generating the bispecific antibody by Fab arm exchange. The incubation conditions can optionally be restored to non-reducing conditions. Exemplary reducing agents that may be used are 2-mercaptoethylamine (2-MEA), dithiothreitol (DTT), di thioerythritol (DTE), glutathione, tris (2-carboxyethyl) phosphine (TCEP), L-cysteine and094669.0103PATENTbeta-mercaptoethanol, preferably a reducing agent selected from the group consisting of: 2-mercaptoethylamine, dithiothreitol and tris (2-carboxyethyl) phosphine. For example, incubation for at least 90 min at a temperature of at least 20° C in the presence of at least 25 mM 2-MEA or in the presence of at least 0.5 mM dithiothreitol at a pH from 5-8, for example at pH of 7.0 or at pH of 7.4 may be used.In certain embodiments, the present disclosure relates to an anti-Vβ17 / anti-CD19 bispecific antibody that induces antibody-dependent cell-mediated cytotoxicity (ADCC). The anti-Vβ17 / anti-CD19 bispecific antibody can, for example, induce ADCC in vitro.In certain embodiments, immune effector properties of the bispecific antibodies provided herein can be enhanced or silenced through Fc modifications by techniques known to those skilled in the art. For example, Fc effector functions such as Clq binding, complement dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), down regulation of cell surface receptors (e.g., B cell receptor; BCR), etc. can be provided and / or controlled by modifying residues in the Fc responsible for these activities.“Antibody-dependent cell-mediated cytotoxicity” or “ADCC” refers to a cell-mediated reaction in which non-specific cytotoxic cells that express Fc receptors (FcRs) (e.g., Natural Killer (NK) cells, neutrophils, and macrophages) recognize bound antibody on a target cell and subsequently cause lysis of the target cell.The ability of antibodies to induce ADCC can be enhanced by engineering their oligosaccharide component. Human IgGl or IgG3 are N-glycosylated at Asn297 with the majority of the glycans in the well-known biantennary GO, G0F, Gl, GIF, G2 or G2F forms. Antibodies produced by non-engineered CHO cells typically have a glycan fucose content of about at least 85%. The removal of the core fucose from the biantennary complex-type oligosaccharides attached to the Fc regions enhances the ADCC of antibodies via improved FcyRIIIa binding without altering antigen-binding or CDC activity. Such Abs can be achieved using different methods reported to lead to the successful expression of relatively high defucosylated antibodies bearing the biantennary complex-type of Fc oligosaccharides such as control of culture osmolality (Konno et al., Cytotechnology 64:249-65, 2012), application of a variant CHO line Lecl3 as the host cell line (Shields et al., J Biol Chem 277:26733-26740, 2002), application of a variant CHO line EB66 as the host cell line (Olivier et al., MAbs; 2(4), 2010; Epub ahead of print; PMID:20562582), application of a rat hybridoma cell line YB2 / 0 as the host cell line (Shinkawa et al., J Biol Chem 278:3466-3473, 2003), introduction of small094669.0103PATENTinterfering RNA specifically against the α-1,6-fucosyltrasferase (FUT8) gene (Mori et al., Biotechnol Bioeng 88:901-908, 2004), or coexpression of β-1,4-N-acetylglucosaminyltransferase III and golgi α-mannosidase II or a potent alpha-mannosidase I inhibitor, kifunensine (Ferrara et al., J Biol Chem 281:5032-5036, 2006, Ferrara et al., Biotechnol Bioeng 93:851-861, 2006; Xhou et al., Biotechnol Bioeng 99:652-65, 2008).In certain embodiments, ADCC elicited by the bispecific antibodies provided herein can also be enhanced by certain substitutions in the antibody Fc. Exemplary substitutions include, for example, substitutions at amino acid positions 256, 290, 298, 312, 356, 330, 333, 334, 360, 378 or 430 (residue numbering according to the EU index) as described in U. S. Pat. No. 6,737,056.In certain embodiments, the presently disclosed bispecific antibody is chimeric. In certain embodiments, the presently disclosed bispecific antibody is human. In certain embodiments, the presently disclosed bispecific antibody is humanized.Furthermore, in certain non-limiting embodiments, the present disclosure relates to nucleic acids encoding the antibodies and molecules disclosed herein. In certain embodiments, the disclosure relates to isolated nucleic acids encoding the bispecific antibodies or antigenbinding fragments thereof disclosed herein. It will be appreciated by those skilled in the art that the coding sequence of a protein can be changed (e.g., replaced, deleted, inserted, etc.) without changing the amino acid sequence of the protein. Accordingly, it will be understood by those skilled in the art that nucleic acid sequences encoding monoclonal antibodies and / or bispecific antibodies disclosed herein can be altered without changing the amino acid sequences of the proteins.In certain embodiments, the nucleic acids encoding the antibodies and molecules disclosed herein comprise one or more nucleotide sequence set forth in SEQ ID Nos: 39-49, which are provided in Table 5 below.Table 5SEQ ID NO Sequence39 ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTATACAGGCC CAGGTCCAGCTGCAAGAGTCTGGCCCTGGACTGGTCAAGCCTTCCGAGACACTGTCT CTGACCTGCACCGTGTCCGGCTACTCCATCACCAGCGGCTACTTTTGGAACTGGATC CGGCAGCCTCCTGGCAAAGGACTGGAATGGATCGGCTACATCTCCTACGACGGCTCC AACAACTACAACCCCAGCCTGAAGTCCAGAGTGACCATCTCTCGGGACACCTCCAAG AACCAGTTCTCCCTGAAGCTGTCCTCTGTGACCGCTGCCGATACCGCCGTGTACTAC TGTGCTTCTCCTTCTCCTGGCACCGGCTACGCTGTGGATTATTGGGGACAGGGCACA CTCGTGACCGTGTCCTCTGCTTCTACAAAGGGGCCCTCTGTGTTCCCTCTGGCTCCTTCCTCTAAATCCACCTCTGGCGGAACCGCTGCTCTGGGCTGTCTGGTCAAGGATTAC094669.0103PATENT TTCCCTGAGCCTGTGACAGTGTCCTGGAACTCTGGTGCTCTGACATCCGGCGTGCAC ACCTTTCCAGCTGTGCTGCAGTCCTCTGGCCTGTACTCTCTGTCTAGCGTCGTGACA GTGCCTTCCAGCTCTCTGGGCACCCAGACCTACATCTGCAACGTGAACCACAAGCCT AGCAACACCAAGGTGGACAAGAAGGTGGAACCCAAGTCCTGCGACAAGACCCACACC TGTCCTCCATGTCCTGCTCCAGAAGCTGCTGGCGGACCCTCCGTTTTCCTGTTTCCA CCTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACCTGCGTGGTG GTGTCTGTGTCTCACGAGGATCCCGAAGTGAAGTTCAATTGGTACGTGGACGGCGTG GAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAACAGTACAACTCCACCTACAGA GTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAACGGCAAAGAGTACAAG TGCAAGGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCTCCAAGGCT AAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATG ACCAAGAATCAGGTGTCCCTGTCCTGCGCCGTGAAGGGCTTCTACCCTTCTGATATC GCCGTGGAATGGGAGTCCAACGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCT GTGCTGGACTCCGACGGCTCATTCTTCCTGGTGTCCAAGCTGACAGTGGACAAGTCC AGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATGCACGAGGCCCTGCACAAC CGGTTCACCCAGAAATCCCTGTCTCTGTCCCCTGGCAAGtgatag ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTATACAGGCC GACATCCAGATGACCCAGTCTCCATCCTCTCTGTCTGCCTCTGTGGGCGACAGAGTG ACCATCACCTGTCGGAGTTCTCAGTCCCTGGTGCACTCCTCTGGCAACACCTACCTG CACTGGTATCAGCAGAAGCCCGGCAAGGCCCCTAAGTTCCTGATCTACAAGGTGTCC AACCGGTTCTCCGGCGTGCCCTCTAGATTTTCTGGCTCTGGATCTGGCACCGACTTC ACCCTGACCATCAGTTCTCTGCAGCCTGAGGACTTCGCCACCTACTACTGCTCCCAG TCTACCCACGTGCCATTCACCTTTGGCCAGGGCACCAAGCTGGAAATCAAGAGAACC GTGGCCGCTCCTTCCGTGTTCATCTTCCCACCTTCCGACGAGCAGCTGAAGTCTGGC ACAGCTTCTGTCGTGTGCCTGCTGAACAACTTCTACCCTCGGGAAGCCAAGGTGCAG TGGAAGGTGGACAATGCCCTGCAGTCCGGCAACTCCCAAGAGTCTGTGACCGAGCAG GACTCCAAGGACTCTACCTACAGCCTGTCCTCCACACTGACCCTGTCTAAGGCCGAC TACGAGAAGCACAAGGTGTACGCCTGTGAAGTGACCCACCAGGGCCTGTCTAGCCCT GTGACCAAGTCTTTCAACCGGGGCGAGTGTtgatag ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTAC GGCGACATCCAGCTGACCCAGTCTCCAGCTTCTCTGGCTGTGTCTCTGGGACAGAGA GCCACCATCTCTTGCAAGGCCTCTCAGTCTGTGGACTACGACGGCGACTCCTACCTG AACTGGTATCAGCAGATCCCCGGCCAGCCTCCTAAGCTGCTGATCTACGATGCCTCC AACCTGGTGTCTGGCATCCCTCCTAGATTCTCCGGCTCTGGCTCTGGCACCGACTTC ACCCTGAACATCCATCCTGTGGAAAAGGTGGACGCCGCCACCTACCACTGTCAGCAG TCTACCGAAGATCCCTGGACCTTTGGCGGAGGCACCAAGCTGGAAATCAAGAGAACC GTGGCCGCTCCTTCCGTGTTCATCTTCCCACCATCTGACGAGCAGCTGAAGTCCGGC ACAGCTTCTGTCGTGTGCCTGCTGAACAACTTCTACCCTCGGGAAGCCAAGGTGCAG TGGAAGGTGGACAATGCCCTGCAGTCCGGCAACTCCCAAGAGTCTGTGACCGAGCAG GACTCCAAGGACTCTACCTACAGCCTGTCCTCCACACTGACCCTGTCTAAGGCCGAC TACGAGAAGCACAAGGTGTACGCCTGTGAAGTGACCCACCAGGGACTGTCTAGCCCC GTGACCAAGTCTTTCAACAGAGGCGAGTGTGGCGGCTCCGAGGGCAAATCTAGTGGC TCCGGATCTGAGTCTAAGTCCACCGAGGGAAAGTCCTCTGGCAGCGGCTCTGAATCT AAGAGCACAGGCGGATCTCAGGTCCAGTTGCAGCAATCTGGCGCCGAACTCGTCAGA CCTGGCTCCTCTGTGAAGATCAGCTGCAAGGCTTCCGGCTACGCCTTCTCCTCCTAC TGGATGAACTGGGTCAAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGACAAATT TGGCCTGGCGACGGCGATACCAACTACAACGGCAAGTTCAAGGGCAAAGCTACCCTG ACCGCCGACGAGTCCTCTTCTACCGCCTATATGCAGCTGTCCTCTCTGGCCTCTGAG GACTCTGCCGTGTACTTCTGCGCTCGGAGAGAGACAACCACCGTCGGCAGATATTAC TACGCCATGGATTACTGGGGCCAGGGCACCACAGTGACCGTGTCCTCTGCTTCTACC AAGGGACCCTCTGTGTTCCCTCTGGCTCCTTCCAGCAAGTCTACCTCTGGTGGAACC GCTGCTCTGGGCTGCCTGGTCAAGGATTACTTTCCTGAGCCTGTGACAGTGTCCTGGAACTCTGGTGCTCTGACCAGCGGCGTGCACACTTTTCCAGCTGTTCTGCAGTCCTCC094669.0103PATENT GGCCTGTACTCTCTGTCCTCTGTCGTGACAGTGCCTTCCAGCTCTCTGGGCACCCAG ACCTACATCTGCAACGTGAACCACAAGCCTAGCAACACCAAAGTGGACAAGAAGGTG GAACCCAAGTCCTGCGACAAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCT GCAGGCGGTCCCTCCGTTTTCCTGTTTCCACCTAAGCCTAAGGACACCCTGATGATC TCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCCACGAGGACCCAGAA GTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCT AGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCAC CAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCT GCTCCTATCGAAAAGACCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTT TACACCCTGCCTCCATCTCGGGAAGAGATGACCAAGAATCAGGTGTCCCTGTGGTGC CTGGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAATGGGAGTCCAATGGCCAG CCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTC CTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCC TGCTCTGTGATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTG TCCCCTGGCAAGTGATGA ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTAC GGCGATATCCAGCTGACCCAAAGTCCGGCTTCCCTAGCTGTGAGCTTGGGCCAGCGT GCCACTATTTCCTGTAAAGCATCCCAGTCCGTAGACTATGACGGTGACTCCTATCTG AATTGGTATCAGCAGATCCCTGGATGCCCCCCCAAGCTGCTCATCTATGACGCATCT AATCTGGTCTCAGGCATCCCTCCCCGCTTCAGTGGTTCAGGGTCCGGGACAGACTTC ACCCTTAATATACACCCTGTCGAAAAAGTTGATGCTGCTACATACCACTGTCAACAG TCCACTGAAGATCCCTGGACTTTCGGAGGGGGCACCAAACTGGAGATTAAAGGGGGA GGATCTGGAGGGTCAGGGGGATGTCCCCCATGTGGTGGTTCCGGCGGTCAGGTTCAA CTCCAGCAGAGCGGCGCTGAGTTGGTGAGGCCAGGCAGTTCTGTGAAGATCAGTTGT AAGGCTAGTGGATATGCATTCTCAAGCTACTGGATGAATTGGGTTAAACAGCGACCA GGACAGGGACTGGAATGGATCGGTCAGATTTGGCCAGGAGACGGCGATACTAATTAT AACGGTAAATTTAAAGGCAAGGCTACCCTCACCGCTGATGAGAGTAGCAGTACTGCC TACATGCAGCTGTCCTCCCTGGCAAGCGAGGATTCCGCCGTCTATTTCTGTGCCAGA CGGGAAACTACTACTGTCGGAAGGTATTATTACGCCATGGACTATTGGGGTTGCGGC ACTACCGTCACTGTGAGCTCCGAACCCAAGTCCTCCGACAAGACCCACACCTGTCCA CCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGTTTCCACCTAAG CCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCT GTGTCCCACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTG CACAACGCCAAGACCAAGCCTAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTG TCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAA GTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCAGCAAGGCTAAGGGC CAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGACCAAG AATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATATCGCCGTG GAATGGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTG GACTCCGACGGCTCATTCTTCCTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGG CAGCAGGGCAACGTGTTCTCCTGCTCTGTGATGCACGAGGCCCTGCACAACCACTAC ACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGATGA ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTAC GGCGATATCCAGCTGACGCAATCCCCCGCTAGTCTAGCCGTTTCACTCGGTCAGAGG GCCACCATAAGCTGCAAGGCTAGCCAGTCAGTGGACTACGATGGCGATAGCTATCTA AATTGGTACCAACAGATCCCTGGGCAGCCCCCTAAGCTGCTGATCTACGATGCTAGC AATCTGGTCTCTGGAATTCCCCCTCGGTTTTCCGGTTCAGGTAGCGGAACCGATTTC ACCCTGAATATCCACCCAGTTGAAAAGGTCGACGCCGCCACCTACCACTGTCAACAA TCTACCGAAGATCCCTGGACCTTTGGCGGGGGCACTAAACTCGAAATCAAAGGCGGA GGCGGGTCTGGGGGCGGAGGCTCCGGAGGCGGCGGATCCCAGGTTCAGCTCCAACAG AGTGGCGCCGAACTGGTGAGACCTGGCAGTTCCGTTAAAATTTCTTGTAAGGCATCA GGTTACGCATTCTCCTCCTATTGGATGAACTGGGTGAAGCAGCGCCCAGGACAGGGC CTGGAATGGATTGGTCAGATCTGGCCCGGGGATGGCGATACAAATTACAATGGAAAG TTTAAGGGAAAGGCCACCCTGACAGCTGATGAGAGTTCTAGCACAGCCTACATGCAGCTCAGCAGTCTGGCTAGTGAAGATTCTGCCGTGTATTTCTGCGCACGGCGGGAAACT094669.0103PATENT ACCACCGTAGGTAGGTACTACTACGCTATGGATTACTGGGGGCAGGGGACTACTGTC ACCGTCAGTTCCGAACCCAAGTCCTCCGACAAGACCCACACCTGTCCACCATGTCCT GCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGTTTCCACCTAAGCCTAAGGAC ACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCCAC GAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCC AAGACCAAGCCTAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTG ACCGTGCTGCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAAC AAGGCCCTGCCTGCTCCTATCGAAAAGACCATCAGCAAGGCTAAGGGCCAGCCTCGG GAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGACCAAGAATCAGGTG TCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAATGGGAG TCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGAC GGCTCATTCTTCCTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGC AACGTGTTCTCCTGCTCTGTGATGCACGAGGCCCTGCACAACCACTACACACAGAAG TCCCTGTCTCTGTCCCCTGGCAAGTGATGA ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTAC GGCGAAATAGTACTTACACAGTCCCCCGGGACACTTTCTCTTAGCCCAGGTGAACGT GCTACACTCAGCTGCCGTGCATCCCAATCAGTCAGTAGCTCTTATCTCGCATGGTAC CAGCAGAAACCCGGGCAAGCTCCTCGGCTGTTGATCTACGGCGCATCCAGTCGTGCC ACCGGAATACCGGACAGGTTCTCCGGCTCTGGTAGCGGTACCGACTTTACTTTGACT ATTTCAAGGCTTGAGCCAGAGGACTTCGCTGTGTACTATTGCCAACAGTATGGCTCA AGTAGGTTCACCTTTGGGCCGGGTACTAAAGTTGATATCAAACGAACTGTCGCCGCT CCTTCTGTATTCATTTTCCCACCTAGTGACGAGCAACTGAAATCCGGAACTGCTAGT GTCGTTTGCCTGCTCAACAACTTTTATCCTCGGGAAGCCAAAGTCCAGTGGAAAGTT GACAATGCCCTGCAAAGTGGGAACTCTCAAGAGTCCGTAACCGAGCAGGATAGCAAG GATAGCACCTACAGTCTGTCTTCAACCCTGACACTTTCAAAAGCTGATTACGAGAAA CACAAAGTTTATGCATGTGAAGTCACCCATCAAGGTCTTTCTTCCCCGGTCACCAAG AGCTTCAACAGAGGAGAATGCGGCGGAAGTGAAGGCAAATCTAGTGGCAGCGGGAGC GAGAGCAAAAGTACGGAAGGGAAAAGTTCAGGTTCCGGAAGTGAGTCTAAGTCCACT GGCGGGAGTCAAGTTCAACTCGTGCAATCTGGAGCTGAAGTGAAGAAACCTGGGAGC TCAGTGAAGGTGAGCTGTAAGGATTCAGGCGGTACATTCTCTTCATACGCTATTAGC TGGGTCCGACAAGCCCCAGGGCAAGGCCTGGAATGGATGGGCGGGATTATTCCCATC TTCGGCACGACTAACTATGCCCAGCAATTCCAAGGCAGAGTTACTATAACCGCCGAC GAATCAACTTCCACTGCATACATGGAACTAAGCTCTCTGCGCAGCGAAGACACCGCA GTGTATTACTGTGCCCGGGAAGCTGTGGCAGCAGATTGGCTGGACCCCTGGGGACAA GGAACTCTCGTCACTGTCTCCTCTGCTTCTACCAAGGGACCCTCTGTGTTCCCTCTG GCTCCTTCCAGCAAGTCTACCTCTGGTGGAACCGCTGCTCTGGGCTGCCTGGTCAAG GATTACTTTCCTGAGCCTGTGACAGTGTCCTGGAACTCTGGTGCTCTGACCAGCGGC GTGCACACTTTTCCAGCTGTTCTGCAGTCCTCCGGCCTGTACTCTCTGTCCTCTGTC GTGACAGTGCCTTCCAGCTCTCTGGGCACCCAGACCTACATCTGCAACGTGAACCAC AAGCCTAGCAACACCAAAGTGGACAAGAAGGTGGAACCCAAGTCCTGCGACAAGACC CACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTG TTTCCACCTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGC GTGGTGGTGTCTGTGTCCCACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGAC GGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAACAGTACAACTCCACC TACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAACGGCAAAGAG TACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCAGC AAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAA GAGATGACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCC GATATCGCCGTGGAATGGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACC CCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTGTACTCCAAGCTGACTGTGGAC AAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATGCACGAGGCCCTG CACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGATGA ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTAC GGCGAAATCGTGTTGACCCAATCTCCAGGCACCTTGTCTCTCTCTCCTGGAGAGAGGGCAACACTGTCATGCCGTGCAAGTCAGTCTGTCTCTAGCTCCTATCTTGCTTGGTAT094669.0103PATENT CAACAAAAGCCCGGGTGCGCTCCTAGACTGCTAATTTATGGCGCCTCATCCCGTGCT ACCGGCATTCCCGATCGGTTTTCCGGTTCAGGCTCTGGTACCGATTTTACGCTTACG ATTAGTAGGCTAGAGCCCGAGGACTTCGCAGTGTACTATTGCCAACAATATGGTTCT TCCCGCTTCACATTTGGACCGGGGACCAAGGTGGACATAAAAGGCGGCGGCTCAGGT GGCTCAGGCGGCTGCCCGCCTTGTGGCGGATCAGGCGGACAAGTACAACTTGTGCAA TCTGGAGCTGAGGTGAAGAAACCAGGCTCTTCTGTGAAGGTCAGCTGCAAAGATTCT GGCGGCACATTCTCTTCATATGCAATTTCCTGGGTAAGACAGGCTCCCGGACAAGGA TTGGAATGGATGGGTGGCATTATACCGATATTCGGTACGACGAATTACGCACAACAG TTTCAGGGTCGGGTGACTATTACCGCAGACGAATCCACCAGCACTGCCTATATGGAA CTCAGCTCACTGAGAAGTGAGGATACGGCTGTCTATTATTGTGCCAGAGAAGCCGTG GCAGCTGACTGGTTGGACCCATGGGGCTGTGGGACCCTCGTTACTGTCAGTAGCGAA CCCAAGTCCTCCGACAAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCA GGCGGTCCCTCCGTTTTCCTGTTTCCACCTAAGCCTAAGGACACCCTGATGATCTCT CGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCCACGAGGACCCAGAAGTG AAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGA GAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAG GATTGGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCT CCTATCGAAAAGACCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTAC ACCCTGCCTCCATCTCGGGAAGAGATGACCAAGAATCAGGTGTCCCTGTGGTGCCTG GTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAATGGGAGTCCAATGGCCAGCCT GAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTG TACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGC TCTGTGATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCC CCTGGCAAGTGATGA ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTAC GGCGAAATAGTACTTACACAGTCCCCCGGGACACTTTCTCTTAGCCCAGGTGAACGT GCTACACTCAGCTGCCGTGCATCCCAATCAGTCAGTAGCTCTTATCTCGCATGGTAC CAGCAGAAACCCGGGCAAGCTCCTCGGCTGTTGATCTACGGCGCATCCAGTCGTGCC ACCGGAATACCGGACAGGTTCTCCGGCTCTGGTAGCGGTACCGACTTTACTTTGACT ATTTCAAGGCTTGAGCCAGAGGACTTCGCTGTGTACTATTGCCAACAGTATGGCTCA AGTAGGTTCACCTTTGGGCCGGGTACTAAAGTTGATATCAAAGGCGGAGGCGGGTCT GGGGGCGGAGGCTCCGGAGGCGGCGGATCCCAAGTTCAACTCGTGCAATCTGGAGCT GAAGTGAAGAAACCTGGGAGCTCAGTGAAGGTGAGCTGTAAGGATTCAGGCGGTACA TTCTCTTCATACGCTATTAGCTGGGTCCGACAAGCCCCAGGGCAAGGCCTGGAATGG ATGGGCGGGATTATTCCCATCTTCGGCACGACTAACTATGCCCAGCAATTCCAAGGC AGAGTTACTATAACCGCCGACGAATCAACTTCCACTGCATACATGGAACTAAGCTCT CTGCGCAGCGAAGACACCGCAGTGTATTACTGTGCCCGGGAAGCTGTGGCAGCAGAT TGGCTGGACCCCTGGGGACAAGGAACTCTCGTCACTGTCTCCTCTGAACCCAAGTCC TCCGACAAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCC TCCGTTTTCCTGTTTCCACCTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCT GAAGTGACATGCGTGGTGGTGTCTGTGTCCCACGAGGACCCAGAAGTGAAGTTCAAT TGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAACAG TACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTG AACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAA AAGACCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCT CCATCTCGGGAAGAGATGACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGC TTTTACCCTTCCGATATCGCCGTGGAATGGGAGTCCAATGGCCAGCCTGAGAACAAT TACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTGTACTCCAAG CTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATG CACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAG T GAT GA ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTAC GGCGCTATCCAGCTGACCCAGTCTCCATCCTCTCTGTCTGCCTCTGTGGGCGACAGA GTGACCATCACCTGTAGAGCCAGCCAGGGCATCTCTTCTGCTCTGGCCTGGTATCAGCAGAAGCCTGGCAAGGCTCCCAAGCTGCTGATCTACGACGCCTCCTCTCTGGAATCT094669.0103PATENT GGCGTGCCATCCAGATTCTCCGGCTCTGGCTCTGGCACCGACTTTACCCTGACAATC AGCTCCCTGCAGCCTGAGGACTTCGCCACCTACTACTGCCAGCAGTTCAACAGCTAC CCCTACACCTTTGGCCAGGGCACCAAGCTGGAAATCAAGAGAACCGTGGCCGCTCCT TCCGTGTTCATCTTTCCACCTTCCGACGAGCAGCTGAAGTCCGGCACAGCTTCTGTC GTGTGCCTGCTGAACAACTTCTACCCTCGGGAAGCCAAGGTGCAGTGGAAAGTGGAT AATGCCCTGCAGTCCGGCAACTCCCAAGAGTCTGTGACCGAGCAGGACTCCAAGGAC TCTACCTACAGCCTGTCCTCCACACTGACCCTGTCTAAGGCCGACTACGAGAAGCAC AAGGTGTACGCCTGTGAAGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGTCT TTCAACAGAGGCGAGTGTGGCGGCTCCGAGGGCAAATCTAGTGGCTCCGGATCTGAG TCCAAGTCCACCGAGGGAAAGTCCTCTGGAAGCGGCAGCGAGTCTAAGTCTACCGGC GGATCTGAAGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTGGCGAGTCC CTGAAGATCTCCTGCAAAGGCTCCGGCTACTCCTTCTCCTCTTCTTGGATCGGCTGG GTCCGACAGATGCCAGGCAAAGGACTGGAATGGATGGGCATCATCTACCCCGACGAC AGCGACACCAGATACAGCCCTAGCTTTCAGGGCCAAGTGACAATCTCCGCCGACAAG TCCATCAGAACCGCCTACCTGCAGTGGTCCTCTCTGAAGGCCTCTGACACCGCCATG TACTACTGTGCCAGACACGTGACCATGATCTGGGGCGTGATCATCGATTTCTGGGGC CAGGGAACACTGGTCACCGTGTCATCTGCTTCTACCAAGGGACCCTCTGTGTTCCCT CTGGCTCCTTCCAGCAAGTCTACCTCTGGTGGAACCGCTGCTCTGGGCTGCCTGGTC AAGGATTACTTTCCTGAGCCTGTGACAGTGTCCTGGAACTCTGGTGCTCTGACCAGC GGCGTGCACACTTTTCCAGCTGTTCTGCAGTCCTCCGGCCTGTACTCTCTGTCCTCT GTCGTGACAGTGCCTTCCAGCTCTCTGGGCACCCAGACCTACATCTGCAACGTGAAC CACAAGCCTAGCAACACCAAAGTGGACAAGAAGGTGGAACCCAAGTCCTGCGACAAG ACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTC CTGTTTCCACCTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACA TGCGTGGTGGTGTCTGTGTCCCACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTG GACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAACAGTACAACTCC ACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAACGGCAAA GAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATC AGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGG GAAGAGATGACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCT TCCGATATCGCCGTGGAATGGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACA ACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTGTACTCCAAGCTGACTGTG GACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATGCACGAGGCC CTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGATGA ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTAC GGCGCTATCCAGCTGACCCAGTCTCCATCCTCTCTGTCTGCCTCTGTGGGCGACAGA GTGACCATCACCTGTAGAGCCAGCCAGGGCATCTCTTCTGCTCTGGCCTGGTATCAG CAGAAGCCTGGCTGCGCTCCTAAGCTGCTGATCTACGACGCCTCCTCTCTGGAATCT GGCGTGCCATCCAGATTCTCCGGCTCTGGCTCTGGCACCGACTTTACCCTGACAATC AGCTCCCTGCAGCCTGAGGACTTCGCCACCTACTACTGCCAGCAGTTCAACAGCTAC CCCTACACCTTTGGCCAGGGCACCAAGCTGGAAATCAAAGGCGGAGGTAGCGGCGGA TCTGGCGGATGTCCTCCTTGCGGAGGTTCTGGCGGAGAAGTGCAGTTGGTTCAGTCT GGCGCCGAAGTGAAGAAGCCCGGCGAGTCTCTGAAGATCTCCTGCAAAGGCTCCGGC TACTCCTTCTCCTCTTCTTGGATCGGCTGGGTCCGACAGATGCCTGGCAAAGGACTG GAATGGATGGGCATCATCTACCCCGACGACAGCGACACCAGATACAGCCCATCTTTC CAGGGCCAAGTGACAATCTCCGCCGACAAGTCCATCAGAACCGCCTACCTGCAGTGG TCCTCTCTGAAGGCCTCTGACACCGCCATGTACTACTGTGCCAGACACGTGACCATG ATCTGGGGCGTGATCATCGATTTCTGGGGCTGTGGCACACTGGTCACCGTGTCATCT GAACCCAAGTCCTCCGACAAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCT GCAGGCGGTCCCTCCGTTTTCCTGTTTCCACCTAAGCCTAAGGACACCCTGATGATC TCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCCACGAGGACCCAGAA GTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCT AGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCAC CAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTT094669.0103PATENT TACACCCTGCCTCCATCTCGGGAAGAGATGACCAAGAATCAGGTGTCCCTGTGGTGC CTGGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAATGGGAGTCCAATGGCCAG CCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTC CTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCC TGCTCTGTGATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTG TCCCCTGGCAAGTGATGA49 ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTAC GGCGCTATCCAGCTGACCCAGTCTCCATCCTCTCTGTCTGCCTCTGTGGGCGACAGA GTGACCATCACCTGTAGAGCCAGCCAGGGCATCTCTTCTGCTCTGGCCTGGTATCAG CAGAAGCCTGGCAAGGCTCCCAAGCTGCTGATCTACGACGCCTCCTCTCTGGAATCT GGCGTGCCATCCAGATTCTCCGGCTCTGGCTCTGGCACCGACTTTACCCTGACAATC AGCTCCCTGCAGCCTGAGGACTTCGCCACCTACTACTGCCAGCAGTTCAACAGCTAC CCCTACACCTTTGGCCAGGGCACCAAGCTGGAAATCAAGGGCGGAGGCGGGTCTGGG GGCGGAGGCTCCGGAGGCGGCGGATCCGAAGTGCAGCTGGTGCAGTCTGGCGCCGAA GTGAAGAAACCTGGCGAGTCCCTGAAGATCTCCTGCAAAGGCTCCGGCTACTCCTTC TCCTCTTCTTGGATCGGCTGGGTCCGACAGATGCCAGGCAAAGGACTGGAATGGATG GGCATCATCTACCCCGACGACAGCGACACCAGATACAGCCCTAGCTTTCAGGGCCAA GTGACAATCTCCGCCGACAAGTCCATCAGAACCGCCTACCTGCAGTGGTCCTCTCTG AAGGCCTCTGACACCGCCATGTACTACTGTGCCAGACACGTGACCATGATCTGGGGC GTGATCATCGATTTCTGGGGCCAGGGAACACTGGTCACCGTGTCATCTGAACCCAAG TCCTCCGACAAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGT CCCTCCGTTTTCCTGTTTCCACCTAAGCCTAAGGACACCCTGATGATCTCTCGGACC CCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCCACGAGGACCCAGAAGTGAAGTTC AATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAA CAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGG CTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATC GAAAAGACCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTG CCTCCATCTCGGGAAGAGATGACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAG GGCTTTTACCCTTCCGATATCGCCGTGGAATGGGAGTCCAATGGCCAGCCTGAGAAC AATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTGTACTCC AAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTG ATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGATGAIn certain embodiments, the present disclosure relates to vectors comprising the isolated nucleic acids disclosed herein. Any vector known to those skilled in the art in view of the present disclosure can be used, such as a plasmid, a cosmid, a phage vector or a viral vector. In certain embodiments, the vector is a recombinant expression vector such as a plasmid. The vector can include any element to establish a conventional function of an expression vector, for example, a promoter, ribosome binding element, terminator, enhancer, selection marker, and origin of replication. The promoter can be a constitutive, inducible or repressible promoter. A number of expression vectors capable of delivering nucleic acids to a cell are known in the art and can be used herein for production of an antibody or antigen-binding fragment thereof in the cell. Conventional cloning techniques or artificial gene synthesis can be used to generate a recombinant expression vector according to embodiments disclosed herein. Such techniques are well known to those skilled in the art in view of the present disclosure.094669.0103PATENTIn certain embodiments, the present disclosure relates to host cells comprising the isolated nucleic acids encoding the monoclonal antibodies and / or bispecific antibodies or antigen-binding fragments thereof disclosed herein. Any host cell known to those skilled in the art in view of the present disclosure can be used for recombinant expression of antibodies or antigen-binding fragments thereof disclosed herein. In some embodiments, the host cells are E. coli TGI or BL21 cells (for expression of, e.g., an scFv or Fab antibody), CHO-DG44 or CHO-K1 cells or HEK293 cells (for expression of, e.g., a full-length IgG antibody). According to particular embodiments, the recombinant expression vector is transformed into host cells by conventional methods such as chemical transfection, heat shock, or electroporation, where it is stably integrated into the host cell genome such that the recombinant nucleic acid is effectively expressed.In certain embodiments, the present disclosure relates to a method of producing a bispecific antibody disclosed herein. The methods comprise culturing a cell comprising a nucleic acid encoding the bispecific antibody under conditions to produce a bispecific antibody disclosed herein, and recovering the antibody or antigen-binding fragment thereof from the cell or cell culture (e.g., from the supernatant). Expressed antibodies or antigen-binding fragments thereof can be harvested from the cells and purified according to conventional techniques known in the art and as described herein.Pharmaceutical CompositionsIn certain embodiments, the present disclosure relates to a pharmaceutical composition comprising an isolated bispecific antibody provided herein and a pharmaceutically acceptable carrier. Also provided is a method of producing the pharmaceutical composition, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition. In certain embodiments, provided herein is a pharmaceutical composition comprising a comprising: (a) a first binding domain that binds to Vβ17, and (b) a second binding domain that binds to CD 19, and a pharmaceutically acceptable carrier. The term “pharmaceutical composition,” as used herein, means a product comprising an antibody provided herein together with a pharmaceutically acceptable carrier. Antibodies provided herein and compositions comprising them are also useful in the manufacture of a medicament for therapeutic applications mentioned herein.Also provided herein are methods of producing compositions comprising the bispecific antibodies or antigen-binding fragments disclosed herein, such as buffered compositions or purified compositions and the like. For example, the methods may comprise combining the094669.0103PATENTbispecific antibody with a buffer acceptable that is acceptable for storage and use of the bispecific antibody.As used herein, the term “carrier” refers to any excipient, diluent, filler, salt, buffer, stabilizer, solubilizer, oil, lipid, lipid containing vesicle, microsphere, liposomal encapsulation, or other material well known in the art for use in pharmaceutical formulations. It will be understood that the characteristics of the carrier, excipient or diluent will depend on the route of administration for a particular application. As used herein, the term “pharmaceutically acceptable carrier” refers to a non-toxic material that does not interfere with the effectiveness of a composition according to the invention or the biological activity of a composition provided herein. In certain embodiments, in view of the present disclosure, any pharmaceutically acceptable carrier suitable for use in an antibody pharmaceutical composition can be used herein.The formulation of pharmaceutically active ingredients with pharmaceutically acceptable carriers is known in the art, e.g., Remington: The Science and Practice of Pharmacy (e.g., 21st edition (2005), and any later editions). Non-limiting examples of additional ingredients include: buffers, diluents, solvents, tonicity regulating agents, preservatives, stabilizers, and chelating agents. One or more pharmaceutically acceptable carriers can be used in formulating the pharmaceutical compositions provided herein.In certain embodiments, the pharmaceutical composition is a liquid formulation. A preferred example of a liquid formulation is an aqueous formulation, i.e., a formulation comprising water. The liquid formulation can comprise a solution, a suspension, an emulsion, a microemulsion, a gel, and the like. An aqueous formulation typically comprises at least 50% w / w water, or at least 60%, 70%, 75%, 80%, 85%, 90%, or at least 95% w / w of water.In certain embodiments, the pharmaceutical composition can be formulated as an injectable which can be injected, for example, via an injection device (e.g., a syringe or an infusion pump). The injection can be delivered subcutaneously, intramuscularly, intraperitoneally, intravitreally, or intravenously, for example.In certain embodiments, the pharmaceutical composition is a solid formulation, e.g., a freeze-dried or spray-dried composition, which can be used as is, or whereto the physician or the patient adds solvents, and / or diluents prior to use. Solid dosage forms can include tablets, such as compressed tablets, and / or coated tablets, and capsules (e.g., hard or soft gelatin capsules). The pharmaceutical composition can also be in the form of sachets, dragees, powders, granules, lozenges, or powders for reconstitution, for example.094669.0103PATENTThe dosage forms can be immediate release, in which case they can comprise a water-soluble or dispersible carrier, or they can be delayed release, sustained release, or modified release, in which case they can comprise water insoluble polymers that regulate the rate of dissolution of the dosage form in the gastrointestinal tract or under the skin.In certain embodiments, the pharmaceutical composition can be delivered intranasally, intrabuccally, or sublingually.The pH in an aqueous formulation can be between pH 3 and pH 10. In one embodiment provided herein, the pH of the formulation is from about 7.0 to about 9.5. In another embodiment provided herein, the pH of the formulation is from about 3.0 to about 7.0.In certain embodiments, the pharmaceutical composition comprises a buffer. Nonlimiting examples of buffers include arginine, aspartic acid, bicine, citrate, disodium hydrogen phosphate, fumaric acid, glycine, glycylglycine, histidine, lysine, maleic acid, malic acid, sodium acetate, sodium carbonate, sodium dihydrogen phosphate, sodium phosphate, succinate, tartaric acid, tricine, and tris(hydroxymethyl)-aminomethane, and mixtures thereof. The buffer can be present individually or in the aggregate, in a concentration from about 0.01 mg / ml to about 50 mg / ml, for example from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific buffers constitute alternative embodiments provided herein.In certain embodiments, the pharmaceutical composition comprises a preservative. Non-limiting examples of preservatives include: benzethonium chloride, benzoic acid, benzyl alcohol, bronopol, butyl 4- hydroxybenzoate, chlorobutanol, chlorocresol, chlorohexidine, chlorphenesin, o- cresol, m-cresol, p-cresol, ethyl 4-hydroxybenzoate, imidurea, methyl 4-hydroxybenzoate, phenol, 2-phenoxyethanol, 2-phenylethanol, propyl 4- hydroxybenzoate, sodium dehydroacetate, thiomerosal, and mixtures thereof. The preservative can be present individually or in the aggregate, in a concentration from about 0.01 mg / ml to about 50 mg / ml, for example from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific preservatives constitute alternative embodiments provided herein.In certain embodiments, the pharmaceutical composition comprises an isotonic agent. Non-limiting examples of isotonic agents include a salt (such as sodium chloride), an amino acid (such as glycine, histidine, arginine, lysine, isoleucine, aspartic acid, tryptophan, and threonine), an alditol (such as glycerol, 1,2- propanediol propyleneglycol), 1,3 -propanediol, and 1,3 -butanediol), polyethyleneglycol (e.g., PEG400), and mixtures thereof. Another example of an isotonic agent includes a sugar. Non-limiting examples of sugars can include094669.0103PATENTmono-, di-, or polysaccharides, or water-soluble glucans, including for example fructose, glucose, mannose, sorbose, xylose, maltose, lactose, sucrose, trehalose, dextran, pullulan, dextrin, cyclodextrin, alpha and beta- HPCD, soluble starch, hydroxy ethyl starch, and sodium carboxymethyl-cellulose. Another example of an isotonic agent is a sugar alcohol, wherein the term “sugar alcohol” is defined as a C(4-8) hydrocarbon having at least one -OH group. Nonlimiting examples of sugar alcohols include mannitol, sorbitol, inositol, galactitol, dulcitol, xylitol, and arabitol. The isotonic agent can be present individually or in the aggregate, in a concentration from about 0.01 mg / ml to about 50 mg / ml, for example from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific isotonic agents constitute alternative provided herein.In certain embodiments, the pharmaceutical composition comprises a chelating agent. Non-limiting examples of chelating agents include citric acid, aspartic acid, salts of ethylenediaminetetraacetic acid (EDTA), and mixtures thereof. The chelating agent can be present individually or in the aggregate, in a concentration from about 0.01 mg / ml to about 50 mg / ml, for example from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific chelating agents constitute alternative embodiments of the invention.In certain embodiments, the pharmaceutical composition comprises a stabilizer. Nonlimiting examples of stabilizers include one or more aggregation inhibitors, one or more oxidation inhibitors, one or more surfactants, and / or one or more protease inhibitors.In certain embodiments, the pharmaceutical composition comprises a stabilizer, wherein said stabilizer is carboxy - / hydroxy cellulose and derivates thereof (such as HPC, HPC-SL, HPC-L and HPMC), cyclodextrins, 2- methylthioethanol, polyethylene glycol (such as PEG 3350), polyvinyl alcohol (PVA), polyvinyl pyrrolidone, salts (such as sodium chloride), sulphur-containing substances such as monothioglycerol), or thioglycolic acid. The stabilizer can be present individually or in the aggregate, in a concentration from about 0.01 mg / ml to about 50 mg / ml, for example from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific stabilizers constitute alternative embodiments provided herein.In certain embodiments, the pharmaceutical composition comprises one or more surfactants, preferably a surfactant, at least one surfactant, or two different surfactants. The term “surfactant” refers to any molecules or ions that are comprised of a water-soluble (hydrophilic) part, and a fat-soluble (lipophilic) part. The surfactant can, for example, be selected from the group consisting of anionic surfactants, cationic surfactants, nonionic094669.0103PATENTsurfactants, and / or zwitterionic surfactants. The surfactant can be present individually or in the aggregate, in a concentration from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific surfactants constitute alternative embodiments provided herein.In certain embodiments, the pharmaceutical composition comprises one or more protease inhibitors, such as, e.g., EDTA, and / or benzamidine hydrochloric acid (HCl). The protease inhibitor can be present individually or in the aggregate, in a concentration from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific protease inhibitors constitute alternative embodiments provided herein.In certain embodiments, the present disclosure also relates to a method of producing a pharmaceutical composition comprising a bispecific antibody disclosed herein, comprising combining a bispecific antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.Methods of useThe present disclosure provides a method of directing a T cell expressing Vβ17 to a target cell expressing CD 19. In certain embodiments, the method comprises contacting the T cell with a bispecific antibody provided herein. In certain embodiments, the contacting directs the T cell to the target cell.Also provided is a method of targeting CD 19 expressed on the surface of a target cell, the method comprising exposing the target cell to the bispecific molecules disclosed herein or a pharmaceutical composition thereof.The functional activity of bispecific antibodies and antigen-binding fragments thereof disclosed herein can be characterized by methods known in the art and as described herein. Methods for characterizing antibodies and antigen-binding fragments thereof that bind Vβ17 and CD 19 include, but are not limited to, affinity and specificity assays including Biacore, ELISA, and OctetRed analysis; binding assays to detect the binding of antibodies to target cells by FACS; binding assays to detect the binding of antibodies to Vβ17 on T cells.Also provided is a method of directing Vβ17-expressing T cells to a cell expressing CD 19. The methods can comprise contacting the Vβ17-expressing T cell with a bispecific antibody disclosed herein,Also provided is a method for inhibiting growth or proliferation of target cells expressing CD 19. The methods can comprise contacting the Vβ17-expressing T cells with the presently disclosed bispecific antibody or antigen binding fragment thereof, wherein contacting094669.0103PATENTthe target cells expressing CD 19 with the presently disclosed bispecific antibody or composition thereof inhibits the growth or proliferation of the target cells. Also provided is a method of inhibiting growth or proliferation of target cells expressing a second target antigen on the cell surface, the method comprising contacting the target cells with a bispecific antibody provided herein, wherein contacting the target cells with the pharmaceutical composition inhibits growth or proliferation of the target cells.Moreover, provided herein is a method for eliminating target cells expressing CD 19 in a subject, comprising administering an effective amount of a bispecific antibody, as provided herein, to the subject. In certain non-limiting embodiments, the present disclosure relates to a method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a bispecific antibody or antigen binding fragment thereof that specifically binds Vβ17 and CD 19 presented on the surface of a target cell, or a pharmaceutical composition disclosed herein. In certain embodiments, provided herein is a method for eliminating target cells expressing CD19 or treating a disease caused all or in part by target cells expressing CD19 in a subject, comprising administering an effective amount of a bispecific antibody provided herein to the subject. In certain embodiments, the subject is a subject in need thereof. In certain embodiments, the subject is a human.Furthermore, the present disclosure provides methods of directing a Vβ17-expressing CD8+ or CD4+ T cell to an autoreactive B cell expressing CD 19 (e.g., a B cell producing autoantibodies against the body's own tissues). The methods comprise contacting a Vβ17-expressing CD8+ or CD4+ T cell with an anti-Vβ17 / anti-CD19 bispecific antibodies or composition thereof disclosed herein. Contacting the Vβ17-expressing CD8+ or CD4+ T cell with the anti-Vβ17 / anti-CD19 bispecific antibodies or compositions thereof can direct the Vβ17-expressing CD8+ or CD4+ T cell to an autoreactive B cell expressing CD19 (e.g., a B cell producing autoantibodies against the body's own tissues). Also provided are methods for inhibiting growth or proliferation of autoreactive B cells (e.g., B cells producing autoantibodies against the body's own tissues). The methods comprise contacting the autoreactive B cell (e.g., a B cell producing autoantibodies against the body's own tissues) with the bispecific antibodies disclosed herein. Contacting the autoreactive B cells with the described antibodies can, for example, inhibit the growth or proliferation of the autoreactive B cells, or promote T cell mediated killing of the autoreactive B cells.In certain embodiments, the autoreactive B cells are B cells of an autoimmune disease or an inflammatory disease. Non-limiting examples of autoimmune diseases and inflammatory diseases include arthritis, e.g., rheumatoid arthritis (RA), Type I diabetes, systemic lupus094669.0103PATENTerythematosus (SLE), inflammatory bowel disease, ulcerative colitis, psoriasis, psoriatic arthritis, scleroderma, autoimmune thyroid disease, Grave's disease, Crohn's disease, multiple sclerosis, systemic sclerosis, asthma, organ transplant rejection, a disease or condition associated with transplant, Takayasu arteritis, giant-cell arteritis, Kawasaki disease, polyarteritis nodosa, Behcet's syndrome, Wegener's granulomatosis, ANCA-vasculitides, Churg-Strauss syndrome, microscopic polyangiitis, vasculitis of connective tissue diseases, Hennoch-Schonlein purpura, cryoglobulinemic vasculitis, cutaneous leukocytoclastic angiitis, Sarcoidosis, Cogan's syndrome, Wiskott-Aldrich Syndrome, primary angiitis of the CNS, thromboangiitis obliterans, paraneoplastic arteritis, myelodysplastic syndrome, erythema elevatum diutinum, amyloidosis, autoimmune myositis, Guillain-Barre Syndrome, histiocytosis, atopic dermatitis, pulmonary fibrosis, glomerulonephritis, Whipple's disease, Still's disease, Sjogren's syndrome, osteomyelofibrosis, chronic inflammatory demyelinating polyneuropathy, Kimura's disease, systemic sclerosis, chronic periaortitis, chronic prostatitis, idiopathic pulmonary fibrosis, chronic granulomatous disease, idiopathic, bleomycin-induced lung inflammation, cytarabine-induced lung inflammation, autoimmune thrombocytopenia, autoimmune neutropenia, autoimmune hemolytic anemia, autoimmune lymphocytopenia, chronic autoimmune thyroiditis, autoimmune hepatitis, Hashimoto's thyroiditis, atopic thyroiditis, Graves disease, autoimmune polyglandular syndrome, autoimmune Addison syndrome, and / or myasthenia gravis.In certain embodiments, the autoimmune disease is selected from lupus, lupus erythematosus, systemic lupus erythematosus, refractory systemic lupus erythematosus, or external lupus (cutaneous lupus erythematosus).In certain embodiments, the autoimmune disease is selected from nephritis, lupus nephritis, goodpasture’s syndrome, membranous nephropathy, ANCA-associated renal vasculitis, Henoch–Schönlein purpura, polyarteritis nodosa (PAN), sarcoidosis, scleroderma nephritis, or immune nephritis.In certain embodiments, the autoimmune disease is selected from systemic sclerosis, limited cutaneous systemic sclerosis (IcSSc), diffuse cutaneous systemic sclerosis (dcSSc), systemic sclerosis sine scleroderma, scleroderma, localized scleroderma, systemic scleroderma, limited cutaneous scleroderma, or diffuse cutaneous scleroderma.In certain embodiments, the autoimmune disease is selected from arthritis, rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis (JIA), lupus arthritis, reactive arthritis, lyme arthritis, or gout.094669.0103PATENTIn certain embodiments, the autoimmune disease is selected from multiple sclerosis, clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS).In certain embodiments, the autoimmune disease is selected from atopic dermatitis, psoriasis, pemphigus, bullous pemphigoid, dermatitis herpetiformis, Behçet's disease, or vasculitis.In certain embodiments, the autoimmune disease is selected from asthma, interstitial lung disease (ILD), pulmonary hypertension, bronchiectasis, lung nodules, or Sjogren’s syndrome.In certain embodiments, the autoimmune disease is antiphospholipid syndrome.In certain embodiments, the autoimmune disease is selected from myositis, idiopathic inflammatory myopathies (IIMs), polymyositis, dermatomyositis, sporadic inclusion body myositis, inclusion body myositis, or dermatomyositis.In certain embodiments, the autoimmune disease is generalized myasthenia gravis (e.g., class I myasthenia gravis, class II myasthenia gravis, etc.).In certain embodiments, the autoimmune disease is selected from neuromyelitis optica, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), or acute disseminated encephalomyelitis (ADEM).Also provided are methods of directing a Vβ17-expressing CD8+ or CD4+ T cell to a cancer cell expressing CD19. The methods comprise contacting a Vβ17-expressing CD8+ or CD4+ T cell with an anti-Vβ17 / anti-CD19 bispecific antibodies or composition thereof disclosed herein. Contacting the Vβ17-expressing CD8+ or CD4+ T cell with the anti-Vβ17 / anti-CD19 bispecific antibodies or compositions thereof can direct the Vβ17-expressing CD8+ or CD4+ T cell to a cancer cell expressing CD 19. Also provided are methods for inhibiting growth or proliferation of cancer cells. The methods comprise contacting the cancer cells with the bispecific antibodies disclosed herein. Contacting the cancer cells with the described antibodies can, for example, inhibit the growth or proliferation of the cancer cells, or promote T cell mediated killing of the cancer cells. In certain embodiments, the cancer cell is a cell of Hodgkin lymphoma, leukemia, multiple myeloma, or non-Hodgkin lymphoma. In certain embodiments, the described anti-Vβ17 / anti-CD19 bispecific antibody can be provided in a buffered composition for storage or use. Suitable buffers for the storage of the described anti-Vβ17 / anti-CD19 bispecific antibody would serve to maintain the stability of the antibody or antibody fragment by minimizing deterioration while stored, not promoting aggregation of the antibody or antibody fragment, or minimizing adhesion to the storage vessel.094669.0103PATENTAs used herein, the term “effective amount” refers to an amount of an active ingredient or component that elicits the desired biological or medicinal response in a subject.In certain embodiments, an effective amount refers to the amount of therapy which is sufficient to achieve one, two, three, four, or more of the following effects: (i) reduce or ameliorate the severity of the disease, disorder or condition to be treated or a symptom associated therewith; (ii) reduce the duration of the disease, disorder or condition to be treated, or a symptom associated therewith; (iii) prevent the progression of the disease, disorder or condition to be treated, or a symptom associated therewith; (iv) cause regression of the disease, disorder or condition to be treated, or a symptom associated therewith; (v) prevent the development or onset of the disease, disorder or condition to be treated, or a symptom associated therewith; (vi) prevent the recurrence of the disease, disorder or condition to be treated, or a symptom associated therewith; (vii) reduce hospitalization of a subject having the disease, disorder or condition to be treated, or a symptom associated therewith; (viii) reduce hospitalization length of a subject having the disease, disorder or condition to be treated, or a symptom associated therewith; (ix) increase the survival of a subject with the disease, disorder or condition to be treated, or a symptom associated therewith; (xi) inhibit or reduce the disease, disorder or condition to be treated, or a symptom associated therewith in a subject; and / or (xii) enhance or improve the prophylactic or therapeutic effect(s) of another therapy.The effective amount or dosage can vary according to various factors, such as the disease, disorder or condition to be treated, the means of administration, the target site, the physiological state of the subject (including, e.g., age, body weight, health), whether the subject is a human or an animal, other medications administered, and whether the treatment is prophylactic or therapeutic. Treatment dosages are optimally titrated to optimize safety and efficacy.In certain embodiments, the compositions described herein are formulated to be suitable for the intended route of administration to a subject. For example, the compositions described herein can be formulated to be suitable for intravenous, subcutaneous, or intramuscular administration. Additionally or alternatively, in certain exemplary embodiments, the compositions described herein can be formulated to be delivered subcutaneously, intramuscularly, intraperitoneally, intravitreally, intravenously, intranasally, intrabuccally, or sublingually.As used herein, the terms “treat,” “treating,” and “treatment” are all intended to refer to an amelioration or reversal of at least one measurable physical parameter related to a cancer, which is not necessarily discernible in the subject, but can be discernible in the subject. The094669.0103PATENTterms “treat,” “treating,” and “treatment,” can also refer to causing regression, preventing the progression, or at least slowing down the progression of the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to an alleviation, prevention of the development or onset, or reduction in the duration of one or more symptoms associated with the disease, disorder, or condition, such as a tumor or more preferably a cancer. In a particular embodiment, “treat,” “treating,” and “treatment” refer to prevention of the recurrence of the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to an increase in the survival of a subject having the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to elimination of the disease, disorder, or condition in the subject.In certain embodiments, the presently disclosed antibodies or compositions thereof can be used in combination with a supplemental therapy.As used herein, the term “in combination,” in the context of the administration of two or more therapies to a subject, refers to the use of more than one therapy. The use of the term “in combination” does not restrict the order in which therapies are administered to a subject. For example, a first therapy (e.g., a composition described herein) can be administered prior to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), concomitantly with, or subsequent to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the administration of a second therapy to a subject.In certain embodiments, the above-described methods can comprise administering the presently disclosed bispecific antibody in combination with a checkpoint immune blockade agent.EXAMPLESThe following examples are based on the premise that T cells demonstrate potent antitumor functions. These cells express TCR-haplotype-Vβ17 and majority of these cells exhibit efficient cytotoxicity of tumor target cells. This ability is then harnessed using bispecific antibodies constructed such that one arm binds to the Vβ17 structure and the other arm binds to an antigen expressed by the cancer cells. Thus, the bispecific antibody bridges the effector and target cells together resulting in cancer cell killing.094669.0103PATENTExample 1This example covers the cloning of Vβ17 and CD 19 antibody light chain (LC) and heavy chain (HC) genes into the mammalian expression vector pTT5, transfection, purification, and Quality Control (QC).LC and HC insert variants of Vb17 and CD19 were synthesized in a suitable way for expression by CHO cells. The pTT5 vector backbones containing LC and HC constant regions were PCR amplified and subsequently gel purified. Next, strings of HC and LC fragments were cloned into the pTT 5 vector backbone using the Infusion HD Cloning method (Clontech®) according to the manufacturer’s instructions. A 4.0 pL infusion mix was transformed into 30 pL of DH5a chemically competent cells using the standard heat shock method at 42°C. After regeneration, the cells were pelleted and plated on LB agar media containing carbenicillin (100 pg / mL), then incubated at 37°C overnight. Colonies were observed the next day; 10 colonies were patched, and five were submitted for colony sequencing. One sequence-confirmed clone from each construct was inoculated into 50 mL of Circle Grow media supplemented with carbenicillin (100 pg / mL) and incubated overnight at 37°C with shaking at 250 rpm. All the plasmid constructs were isolated using the Mdi Endotoxin-Free Maxi Kit according to the manufacturer’s instructions. The concentration and quality of the isolated plasmids were assessed using a NanoDrop and gel electrophoresis. The coding DNA sequences of each scaled-up plasmid were reconfirmed by Sanger sequencing.For plasmid scaleup, approximately 100 ng of each plasmid constructs, encoding either the heavy or light chain plasmids of AB397 were transformed into 30 pL of DH5a chemically competent cells using the standard heat shock method at 42°C. After regeneration, 100 pL of culture was plated on LB agar media containing carbenicillin (100 pg / mL), then incubated at 37°C overnight. Colonies were observed the next day; 5 colonies were patched, and one colony was inoculated into 10 mL of LB media supplemented with carbenicillin (100 pg / mL) as a primary culture and incubated for 5-6 h at 37 °C with shaking at 250 rpm. The grown 10 mL culture was further inoculated into 50ml (maxi) / 800mL (Giga) of Circle Grow media supplemented with carbenicillin (100 pg / mL) and incubated overnight at 37 °C with shaking at 250 rpm. The plasmid construct was isolated using the Mdi Endotoxin-Free Maxi / Giga Kit according to the manufacturer’s instructions. The concentration and quality of the isolated plasmids were assessed using a NanoDrop and gel electrophoresis. The coding DNA sequences of each scaled-up plasmid were reconfirmed by Sanger sequencing before being handed over to the expression group.094669.0103PATENTFor upstream process, ExpiCHO-S seed maintenance was performed. Briefly, cells were maintained at a cell density of ~ 4 x 106- 6 x106viable cells / mL, > 95% viability for routine maintenance, and incubated at 37°C with 8% CO2 and 95-100 RPM. Alternatively, ExpiCHO-S seeding for transfection was performed. In a protocol used for scFab formats, 24h before transfection ExpiCHO-S™ Cells, with a viability of >99% cells, were seeded at ~2.5 x 106 - 2.8 x 106 viable cells / mL into required volume of ExpiCHO expression medium. In the protocol for spFv / scFv formats, 24h before transfection ExpiCHO-S™ Cells, with a viability of >99% cells, were centrifuged at 800 rpm for 5 min and the pellet was re-suspended at ~2.5xl06cells / mL into required volume of ExpiCHO expression medium.Two protocols were follows for transactions. For scFab formats: on the day of transfection, the cell density was ~6 x106viable cells / mL; for required transfection volume, 1.0 mg / L DNA (1 Knob: 2 Hole) was diluted to cold OptiPRO SFM Medium and filter sterilized; required amount of ExpiFectamine CHO Reagent was diluted to cold OptiPRO SFM Medium; diluted DNA and ExpiFectamine CHO Reagent were mixed and incubated for 2 min; after the incubation, the complex was added immediately to the flasks containing the cells and gently swirled; flasks were incubated at 37°C, 8% CO2 and 95-100 RPM. Additionally, spFv / scFv formats: on the day of transfection, the cell density was ~6.8 - 8 x106viable cells / mL; for required transfection volume, 1.0 mg / L DNA (1 Knob: 2 Hole) was diluted to cold OptiPRO SFM Medium and filter sterilized; required amount of ExpiFectamine CHO Reagent was diluted to cold OptiPRO SFM Medium; diluted DNA and ExpiFectamine CHO Reagent were mixed and incubated for 2 min; after the incubation, the complex was added immediately to the flasks containing the cells and gently swirled; flasks were incubated at 37°C, 8% CO2 and 95-100 RPM.Feeding Strategy: Day 1: 16% ExpiCHO Feed, 0.6% Enhancer were added. Temperature shifted to 32°C and incubated at 5% CO2 and 100 RPM. Day 5: 16% ExpiCHO Feed was added.Batches were harvested, when viability dropped to 60-70%. The harvest culture was centrifuged at 4000 rpm for 60 minutes. The supernatant was filter sterilized using 0.2p filter and handed over to DSP for purification.The concentration and quality of the isolated plasmids were assessed using a NanoDrop and gel electrophoresis, which is captured in Figures 9A-9J. Details on the gel loading details of Figures 9A-9J are provided in the table below.Table 6:094669.0103PATENTFigureLane details Sample detailsNumberIkb DNA ladder (Thermo) (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, Lane -Ml4.0, 5.0, 6.0, 8.0, 10.0kb) ↑Lane-1 Agn-001 #1 (PLB095175) Fig. 9A Lane -2 Agn-001 #2 (PLB095176)Lane -3 Agn-002 (PLB095177)Lane -4 Agn-003 #1 (PLB095178) Lane -5 Agn-003 #2 (PLB095179)Ikb DNA ladder (Thermo) (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, Lane -Ml4.0, 5.0, 6.0, 8.0, 10.0kb) ↑Fig. 9B Lane-1 Agn-002(PLB096340)Lane -2 Agn-007(PLB096368)Lane -3 Agn-019(PLB097031)Ikb DNA ladder (Thermo) (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, Lane -Ml4.0, 5.0, 6.0, 8.0, 10.0kb) ↑Fig. 9C Lane-1 Agn-014(PLB095871)Lane -2 Agn-017(PLB095873)Ikb DNA ladder (Thermo) (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, Lane -Ml4.0, 5.0, 6.0, 8.0, 10.0kb) ↑Lane-1 Agn 030 (PLB097185 )Fig. 9D Lane -2 Agn 032 (PLB097187 )Lane -3 Agn 033 (PLB097188 )Lane -4 Agn 035 (PLB097189 )Ikb DNA ladder (Thermo) (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, Lane -Ml4.0, 5.0, 6.0, 8.0, 10.0kb) ↑Fig. 9E Lane-1 Agn 37 (PLB097885 )Lane -2 Agn 38 (PLB097886 )Lane -3 Agn 39 (PLB098275 )Ikb DNA ladder (Thermo) (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, Lane -MlFig. 9F 4.0, 5.0, 6.0, 8.0, 10.0kb) ↑Lane-1 Agn 031(PLB098757)Ikb DNA ladder (Thermo) (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, Lane -Ml4.0, 5.0, 6.0, 8.0, 10.0kb) ↑Fig. 9G Lane-1 pIOS000169(PLB097127)Lane -2 pIOS000171(PLB097128)Ikb DNA ladder (Thermo) (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, Lane -Ml4.0, 5.0, 6.0, 8.0, 10.0kb) ↑Lane-1 PIOS 131 #2 (PLB098552) Fig. 9H Lane -2 PIOS 131 #3(PLB098553)Lane -3 PBD000105996 #1 (PLB098554) Lane -4 PBD000105996 #2 (PLB098555)Ikb DNA ladder (Thermo) (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, Lane -Ml4.0, 5.0, 6.0, 8.0, 10.0kb) ↑Fig. 91 Lane-1 pIOS000131(PLB099064)Lane -2 pIOS000169(PLB099062)Lane -3 pIOS000171(PLB099063)094669.0103PATENTFigureLane details Sample detailsNumberLane -4 PBD000105996(PLB099065)Ikb DNA ladder (Thermo) (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, Lane -MlFig. 9 J 4.0, 5.0, 6.0, 8.0, 10.0kb) ↑Lane-1 Agn 036(PLB097635)

[0001] Both nucleotide and amino acid sequences are provided below.AgnOl:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGACATCCA GCTGACCCAGTCTCCAGCTTCTCTGGCTGTGTCTCTGGGACAGAGAGCCACCATCTCTTGCAAGGCCT CTCAGTCTGTGGACTACGACGGCGACTCCTACCTGAACTGGTATCAGCAGATCCCCGGCCAGCCTCCT AAGCTGCTGATCTACGATGCCTCCAACCTGGTGTCTGGCATCCCTCCTAGATTCTCCGGCTCTGGCTC TGGCACCGACTTCACCCTGAACATCCATCCTGTGGAAAAGGTGGACGCCGCCACCTACCACTGTCAGC AGTCTACCGAAGATCCCTGGACCTTTGGCGGAGGCACCAAGCTGGAAATCAAGAGAACCGTGGCCGCT CCTTCCGTGTTCATCTTCCCACCATCTGACGAGCAGCTGAAGTCCGGCACAGCTTCTGTCGTGTGCCT GCTGAACAACTTCTACCCTCGGGAAGCCAAGGTGCAGTGGAAGGTGGACAATGCCCTGCAGTCCGGCA ACTCCCAAGAGTCTGTGACCGAGCAGGACTCCAAGGACTCTACCTACAGCCTGTCCTCCACACTGACC CTGTCTAAGGCCGACTACGAGAAGCACAAGGTGTACGCCTGTGAAGTGACCCACCAGGGACTGTCTAG CCCCGTGACCAAGTCTTTCAACAGAGGCGAGTGTGGCGGCTCCGAGGGCAAATCTAGTGGCTCCGGAT CTGAGTCTAAGTCCACCGAGGGAAAGTCCTCTGGCAGCGGCTCTGAATCTAAGAGCACAGGCGGATCT CAGGTCCAGTTGCAGCAATCTGGCGCCGAACTCGTCAGACCTGGCTCCTCTGTGAAGATCAGCTGCAA GGCTTCCGGCTACGCCTTCTCCTCCTACTGGATGAACTGGGTCAAGCAGAGGCCTGGACAGGGACTCG AGTGGATCGGACAAATTTGGCCTGGCGACGGCGATACCAACTACAACGGCAAGTTCAAGGGCAAAGCT ACCCTGACCGCCGACGAGTCCTCTTCTACCGCCTATATGCAGCTGTCCTCTCTGGCCTCTGAGGACTC TGCCGTGTACTTCTGCGCTCGGAGAGAGACAACCACCGTCGGCAGATATTACTACGCCATGGATTACT GGGGCCAGGGCACCACAGTGACCGTGTCCTCTGCTTCTACCAAGGGACCCTCTGTGTTCCCTCTGGCT CCTTCCAGCAAGTCTACCTCTGGTGGAACCGCTGCTCTGGGCTGCCTGGTCAAGGATTACTTTCCTGA GCCTGTGACAGTGTCCTGGAACTCTGGTGCTCTGACCAGCGGCGTGCACACTTTTCCAGCTGTTCTGC AGTCCTCCGGCCTGTACTCTCTGTCCTCTGTCGTGACAGTGCCTTCCAGCTCTCTGGGCACCCAGACC TACATCTGCAACGTGAACCACAAGCCTAGCAACACCAAAGTGGACAAGAAGGTGGAACCCAAGTCCTG CGACAAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGT TTCCACCTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCT GTGTCCCACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAA GACCAAGCCTAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACC AGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAA AAGACCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGA AGAGATGACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATATCGCCG TGGAATGGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGAC GGCTCATTCTTCCTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTC CTGCTCTGTGATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCA AGTGATGAAgn02:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGACATCCA GATGACCCAGTCTCCATCCTCTCTGTCTGCCTCTGTGGGCGACAGAGTGACCATCACCTGTCGGAGTT CTCAGTCCCTGGTGCACTCCAACGGCAACACCTACCTGCACTGGTATCAGCAGAAGCCCGGCAAGGCC CCTAAGTTCCTGATCTACAAGGTGTCCAACCGGTTCTCCGGCGTGCCCTCTAGATTTTCTGGCTCTGG ATCTGGCACCGACTTCACCCTGACCATCAGTTCTCTGCAGCCTGAGGACTTCGCCACCTACTACTGCT CCCAGTCTACCCACGTGCCATTCACCTTTGGCCAGGGCACCAAGCTGGAAATCAAGAGAACCGTGGCC GCTCCTTCCGTGTTCATCTTCCCACCATCTGACGAGCAGCTGAAGTCCGGCACAGCTTCTGTCGTGTG CCTGCTGAACAACTTCTACCCTCGGGAAGCCAAGGTGCAGTGGAAGGTGGACAATGCCCTGCAGTCCG GCAACTCCCAAGAGTCTGTGACCGAGCAGGACTCCAAGGACTCTACCTACAGCCTGTCCTCCACACTG ACCCTGTCTAAGGCCGACTACGAGAAGCACAAGGTGTACGCCTGTGAAGTGACCCACCAGGGCCTGTC094669.0103PATENT TAGCCCTGTGACCAAGTCTTTCAACAGAGGCGAGTGTGGCGGCTCCGAGGGAAAATCTTCTGGCTCCG GCTCTGAGTCCAAGTCCACAGAGGGAAAGTCTAGCGGCTCCGGCAGCGAGTCTAAGTCTACTGGTGGA AGCCAGGTCCAGCTGCAAGAATCTGGCCCTGGACTGGTCAAGCCTTCCGAGACACTGTCTCTGACCTG CACCGTGTCCGGCTACTCCATCACCAGCGGCTACTTTTGGAACTGGATCAGACAGCCTCCTGGCAAGG GACTCGAGTGGATCGGCTACATCTCCTACGACGGCTCCAACAACTACAACCCCAGCCTGAAGTCCCGC GTGACCATCTCCAGAGACACCTCCAAGAACCAGTTCTCCCTGAAGCTGTCTAGCGTGACCGCCGCTGA TACCGCCGTGTACTATTGTGCCTCTCCTTCTCCTGGAACCGGCTACGCTGTGGATTATTGGGGACAGG GCACACTCGTGACCGTGTCCTCTGCTTCTACCAAGGGACCCTCTGTGTTCCCTCTGGCTCCTTCCAGC AAGTCTACCTCTGGTGGAACCGCTGCTCTGGGCTGCCTGGTCAAGGATTACTTTCCTGAGCCTGTGAC AGTGTCCTGGAACTCTGGTGCTCTGACCAGCGGCGTGCACACTTTTCCAGCTGTTCTGCAGTCCTCCG GCCTGTACTCTCTGTCCTCTGTCGTGACAGTGCCTTCCAGCTCTCTGGGCACCCAGACCTACATCTGC AACGTGAACCACAAGCCTAGCAACACCAAAGTGGACAAGAAGGTGGAACCCAAGTCCTGCGACAAGAC CCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGTTTCCACCTA AGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCCAC GAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCC TAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGC TGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATC AGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGAC CAAGAATCAGGTGTCCCTGTCCTGCGCCGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAATGGG AGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTC TTCCTGGTGTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGT GATGCACGAGGCCCTGCACAACAGATTCACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGATGAAgn03:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGACATCCA GCTGACCCAGTCTCCAGCTTCTCTGGCTGTGTCTCTGGGACAGAGAGCCACCATCTCTTGCAAGGCCT CTCAGTCTGTGGACTACGACGGCGACTCCTACCTGAACTGGTATCAGCAGATCCCCGGCCAGCCTCCT AAGCTGCTGATCTACGATGCCTCCAACCTGGTGTCTGGCATCCCTCCTAGATTCTCCGGCTCTGGCTC TGGCACCGACTTCACCCTGAACATCCATCCTGTGGAAAAGGTGGACGCCGCCACCTACCACTGTCAGC AGTCTACCGAAGATCCCTGGACCTTTGGCGGAGGCACCAAGCTGGAAATCAAAGGTGGCGGAGGAAGC GGAGGCGGAGGATCTGGCGGTGGTGGATCTCAGGTTCAGTTGCAGCAATCTGGCGCTGAACTCGTGCG GCCTGGAAGCTCTGTGAAGATCAGCTGCAAGGCTTCCGGCTACGCCTTCTCCTCCTACTGGATGAACT GGGTCAAGCAGAGGCCTGGACAGGGACTCGAGTGGATCGGACAAATTTGGCCTGGCGACGGCGATACC AACTACAACGGCAAGTTCAAGGGCAAAGCTACCCTGACCGCCGACGAGTCCTCTTCTACCGCCTATAT GCAGCTGTCCTCTCTGGCCTCTGAGGACTCTGCCGTGTACTTCTGCGCTCGGAGAGAGACAACCACCG TCGGCAGATATTACTACGCCATGGATTACTGGGGCCAGGGCACCACAGTGACAGTTAGTTCTGGCGGC GGAGGCTCCGATATCAAACTGCAGCAAAGCGGCGCTGAGCTGGCTAGACCTGGCGCCTCTGTGAAAAT GTCCTGCAAGACCAGCGGCTACACCTTCACCAGATACACCATGCACTGGGTTAAGCAAAGACCCGGCC AAGGCCTGGAATGGATCGGCTACATCAACCCTTCTCGGGGCTACACCAATTACAACCAGAAGTTTAAG GACAAGGCCACACTGACCACCGACAAGTCTAGCTCCACAGCTTACATGCAGCTGAGCAGCCTGACCTC CGAGGACAGCGCCGTGTATTACTGTGCCCGGTACTACGACGACCACTACTGCCTGGACTATTGGGGAC AGGGAACCACTCTGACCGTGTCCTCTGTTGAAGGTGGAAGTGGTGGTTCAGGCGGTAGTGGCGGATCA GGTGGTGTCGACGATATTCAGCTGACACAGAGCCCCGCCATCATGTCTGCTAGTCCTGGCGAGAAAGT GACAATGACCTGCAGAGCCTCCTCCTCCGTGTCTTACATGAATTGGTATCAACAAAAGTCCGGCACAA GCCCCAAGCGGTGGATCTACGACACATCTAAGGTGGCCTCTGGCGTGCCCTACAGATTTTCTGGCTCC GGCAGCGGCACCAGCTACTCCCTGACAATCTCTAGCATGGAAGCCGAGGATGCCGCTACCTACTATTG CCAGCAGTGGTCTAGCAACCCTCTGACCTTTGGAGCCGGAACAAAGCTGGAACTGAAGCACCACCACC AT GAG GAG T GAT GAAgn07:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCCAGACAGT GGTGACTCAGGAGCCCTCTCTCACAGTTTCCCCCGGCGGCACCGTCACTCTGACTTGCCGCAGTAGTA CAGGCGCAGTCACTACTAGCAATTACGCAAATTGGGTGCAGCAGAAGCCCGGTCAAGCACCCCGGGGC CTGATCGGCGGGACTAACAAGAGGGCTCCTGGGACCCCCGCACGGTTTAGCGGCAGTCTGCTGGGCGG AAAGGCAGCACTGACACTTTCCGGTGTTCAACCCGAAGATGAGGCCGAATATTACTGCGCCCTTTGGT ATTCAAACCTCTGGGTATTTGGAGGCGGGACAAAACTGACCGTCCTCGGCCAGCCCAAGGCCGCCCCA094669.0103PATENT TCTGTGACACTGTTCCCCCCTAGTTCAGAGGAACTGCAAGCAAATAAGGCTACTCTCGTTTGTCTGAT CTCCGATTTCTACCCTGGTGCCGTTACTGTCGCATGGAAAGCTGATAGCAGCCCAGTTAAGGCAGGGG TTGAGACTACCACTCCTTCAAAGCAGAGCAATAATAAGTACGCTGCTAGTTCATACCTCTCACTGACA CCCGAGCAGTGGAAGTCACATCGGTCATACAGTTGCCAGGTGACCCACGAAGGCTCTACCGTCGAGAA GACCGTAGCTCCTACGGAGTGCAGTGGCGGCTCCGAGGGTAAGAGCAGTGGCAGTGGCTCCGAGAGCA AGTCCACTGAAGGAAAGTCCTCAGGCAGCGGGTCCGAAAGCAAAAGCACAGGCGGCTCTGAAGTCCAG TTGGTGGAAAGCGGTGGAGGCTTGGTGCAGCCTGGGGGCAGTCTTAGGCTGTCTTGCGCTGCTAGCGG CTTCACCTTCAATACCTATGCCATGAATTGGGTGAGGCAGGCCCCTGGCAAAGGTCTGGAGTGGGTAG CTAGAATCCGCAGTAAGTATAACAATTATGCTACTTACTACGCTGCATCTGTTAAAGGGCGTTTCACC ATCTCTCGGGACGACTCCAAAAATTCACTGTACCTGCAGATGAATTCTCTAAAGACTGAGGACACAGC CGTGTATTACTGTGCTAGGCACGGAAATTTCGGTAACAGCTACGTTTCTTGGTTCGCATACTGGGGCC AAGGCACACTCGTGACCGTCTCATCTGCTTCTACCAAGGGACCCTCTGTGTTCCCTCTGGCTCCTTCC AGCAAGTCTACCTCTGGTGGAACCGCTGCTCTGGGCTGCCTGGTCAAGGATTACTTTCCTGAGCCTGT GACAGTGTCCTGGAACTCTGGTGCTCTGACCAGCGGCGTGCACACTTTTCCAGCTGTTCTGCAGTCCT CCGGCCTGTACTCTCTGTCCTCTGTCGTGACAGTGCCTTCCAGCTCTCTGGGCACCCAGACCTACATC TGCAACGTGAACCACAAGCCTAGCAACACCAAAGTGGACAAGAAGGTGGAACCCAAGTCCTGCGACAA GACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGTTTCCAC CTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCC CACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAA GCCTAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATT GGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACC ATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGAT GACCAAGAATCAGGTGTCCCTGTCCTGCGCCGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAAT GGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCA TTCTTCCTGGTGTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTC TGTGATGCACGAGGCCCTGCACAACAGATTCACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGAT GAAgnl4:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGACATAGT CATGACGCAGTCTCCAGATTCTCTTGCTGTCAGTCTAGGCGAAAGGGCCACAATTAATTGCAGAGCCA GTCAATCTGTTGATAACGGTATTTCCTATATGCACTGGTATCAGCAGAAACCTGGACAACCCCCTAAA CTACTGATTTACGCTGCCAGTAATCCCGAGAGTGGAGTTCCCGACCGATTCAGTGGATCAGGGAGCGG TACCGATTTTACTCTCACAATTAGTTCCCTGCAGGCTGAGGATGTGGCTGTGTACTACTGTCAGCAGA TAATTGAAGACCCATGGACCTTCGGGCAGGGGACTAAAGTTGAAATTAAGCGAACAGTCGCCGCCCCA TCCGTGTTTATTTTCCCACCAAGCGACGAGCAGTTGAAGTCTGGAACTGCTAGTGTGGTCTGCCTGCT CAACAACTTCTACCCTCGCGAAGCAAAGGTTCAGTGGAAGGTGGATAACGCCTTGCAGAGTGGAAATT CCCAGGAATCTGTCACCGAGCAGGACTCAAAAGATTCCACTTACTCATTGTCTAGTACCCTGACTCTT TCTAAGGCAGATTACGAGAAGCACAAGGTCTACGCATGCGAAGTGACTCACCAAGGTTTGTCATCTCC AGTTACTAAGAGTTTCAACAGGGGGGAGTGCGGAGGGTCCGAAGGAAAATCTTCTGGGAGCGGATCTG AGAGTAAGAGTACAGAAGGCAAAAGTTCCGGCTCAGGGAGCGAAAGCAAGAGTACAGGCGGATCTCAG ATCACCCTAAAGGAATCAGGTCCCACGCTGGTCAAGCCAACCCAGACACTTACTCTGACATGTACATT CTCTGGATTCAGCCTGTCCACATCAGGAATGGGTGTTTCCTGGATTAGACAGCCTCCTGGCAAGGCCT TGGAGTGGCTCGCCCACATCTATTGGGACGACGACAAGAGGTATAATCCCAGCCTCAAGAGCAGGCTG ACTATCACCAAAGACACAAGCAAAAACCAGGTGGTTCTGACCATGACTAACATGGACCCCGTGGACAC AGCTACTTACTACTGCGCCCGACTCTATGGTTTCACCTACGGCTTTGCATATTGGGGACAGGGCACTT TGGTAACAGTCTCCTCTGCTTCTACCAAGGGACCCTCTGTGTTCCCTCTGGCTCCTTCCAGCAAGTCT ACCTCTGGTGGAACCGCTGCTCTGGGCTGCCTGGTCAAGGATTACTTTCCTGAGCCTGTGACAGTGTC CTGGAACTCTGGTGCTCTGACCAGCGGCGTGCACACTTTTCCAGCTGTTCTGCAGTCCTCCGGCCTGT ACTCTCTGTCCTCTGTCGTGACAGTGCCTTCCAGCTCTCTGGGCACCCAGACCTACATCTGCAACGTG AACCACAAGCCTAGCAACACCAAAGTGGACAAGAAGGTGGAACCCAAGTCCTGCGACAAGACCCACAC CTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGTTTCCACCTAAGCCTA AGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCCACGAGGAC CCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGA GGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAACG GCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCAGCAAG094669.0103PATENT GCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGACCAAGAA TCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAATGGGAGTCCA ATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTG TACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATGCA CGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGATGAAgnl7:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGAAATAGT ACTTACACAGTCCCCCGGGACACTTTCTCTTAGCCCAGGTGAACGTGCTACACTCAGCTGCCGTGCAT CCCAATCAGTCAGTAGCTCTTATCTCGCATGGTACCAGCAGAAACCCGGGCAAGCTCCTCGGCTGTTG ATCTACGGCGCATCCAGTCGTGCCACCGGAATACCGGACAGGTTCTCCGGCTCTGGTAGCGGTACCGA CTTTACTTTGACTATTTCAAGGCTTGAGCCAGAGGACTTCGCTGTGTACTATTGCCAACAGTATGGCT CAAGTAGGTTCACCTTTGGGCCGGGTACTAAAGTTGATATCAAACGAACTGTCGCCGCTCCTTCTGTA TTCATTTTCCCACCTAGTGACGAGCAACTGAAATCCGGAACTGCTAGTGTCGTTTGCCTGCTCAACAA CTTTTATCCTCGGGAAGCCAAAGTCCAGTGGAAAGTTGACAATGCCCTGCAAAGTGGGAACTCTCAAG AGTCCGTAACCGAGCAGGATAGCAAGGATAGCACCTACAGTCTGTCTTCAACCCTGACACTTTCAAAA GCTGATTACGAGAAACACAAAGTTTATGCATGTGAAGTCACCCATCAAGGTCTTTCTTCCCCGGTCAC CAAGAGCTTCAACAGAGGAGAATGCGGCGGAAGTGAAGGCAAATCTAGTGGCAGCGGGAGCGAGAGCA AAAGTACGGAAGGGAAAAGTTCAGGTTCCGGAAGTGAGTCTAAGTCCACTGGCGGGAGTCAAGTTCAA CTCGTGCAATCTGGAGCTGAAGTGAAGAAACCTGGGAGCTCAGTGAAGGTGAGCTGTAAGGATTCAGG CGGTACATTCTCTTCATACGCTATTAGCTGGGTCCGACAAGCCCCAGGGCAAGGCCTGGAATGGATGG GCGGGATTATTCCCATCTTCGGCACGACTAACTATGCCCAGCAATTCCAAGGCAGAGTTACTATAACC GCCGACGAATCAACTTCCACTGCATACATGGAACTAAGCTCTCTGCGCAGCGAAGACACCGCAGTGTA TTACTGTGCCCGGGAAGCTGTGGCAGCAGATTGGCTGGACCCCTGGGGACAAGGAACTCTCGTCACTG TCTCCTCTGCTTCTACCAAGGGACCCTCTGTGTTCCCTCTGGCTCCTTCCAGCAAGTCTACCTCTGGT GGAACCGCTGCTCTGGGCTGCCTGGTCAAGGATTACTTTCCTGAGCCTGTGACAGTGTCCTGGAACTC TGGTGCTCTGACCAGCGGCGTGCACACTTTTCCAGCTGTTCTGCAGTCCTCCGGCCTGTACTCTCTGT CCTCTGTCGTGACAGTGCCTTCCAGCTCTCTGGGCACCCAGACCTACATCTGCAACGTGAACCACAAG CCTAGCAACACCAAAGTGGACAAGAAGGTGGAACCCAAGTCCTGCGACAAGACCCACACCTGTCCACC ATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGTTTCCACCTAAGCCTAAGGACACCC TGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCCACGAGGACCCAGAAGTG AAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAACAGTA CAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAACGGCAAAGAGT ACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCAGCAAGGCTAAGGGC CAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGACCAAGAATCAGGTGTC CCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAATGGGAGTCCAATGGCCAGC CTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTGTACTCCAAG CTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATGCACGAGGCCCT GCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGATGAAgn19:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGCTATCCA GCTGACCCAGTCTCCATCCTCTCTGTCTGCCTCTGTGGGCGACAGAGTGACCATCACCTGTAGAGCCA GCCAGGGCATCTCTTCTGCTCTGGCCTGGTATCAGCAGAAGCCTGGCAAGGCTCCCAAGCTGCTGATC TACGACGCCTCCTCTCTGGAATCTGGCGTGCCATCCAGATTCTCCGGCTCTGGCTCTGGCACCGACTT TACCCTGACAATCAGCTCCCTGCAGCCTGAGGACTTCGCCACCTACTACTGCCAGCAGTTCAACAGCT ACCCCTACACCTTTGGCCAGGGCACCAAGCTGGAAATCAAGAGAACCGTGGCCGCTCCTTCCGTGTTC ATCTTTCCACCTTCCGACGAGCAGCTGAAGTCCGGCACAGCTTCTGTCGTGTGCCTGCTGAACAACTT CTACCCTCGGGAAGCCAAGGTGCAGTGGAAAGTGGATAATGCCCTGCAGTCCGGCAACTCCCAAGAGT CTGTGACCGAGCAGGACTCCAAGGACTCTACCTACAGCCTGTCCTCCACACTGACCCTGTCTAAGGCC GACTACGAGAAGCACAAGGTGTACGCCTGTGAAGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAA GTCTTTCAACAGAGGCGAGTGTGGCGGCTCCGAGGGCAAATCTAGTGGCTCCGGATCTGAGTCCAAGT CCACCGAGGGAAAGTCCTCTGGAAGCGGCAGCGAGTCTAAGTCTACCGGCGGATCTGAAGTGCAGCTG GTGCAGTCTGGCGCCGAAGTGAAGAAACCTGGCGAGTCCCTGAAGATCTCCTGCAAAGGCTCCGGCTA CTCCTTCTCCTCTTCTTGGATCGGCTGGGTCCGACAGATGCCAGGCAAAGGACTGGAATGGATGGGCA TCATCTACCCCGACGACAGCGACACCAGATACAGCCCTAGCTTTCAGGGCCAAGTGACAATCTCCGCC094669.0103PATENT GACAAGTCCATCAGAACCGCCTACCTGCAGTGGTCCTCTCTGAAGGCCTCTGACACCGCCATGTACTA CTGTGCCAGACACGTGACCATGATCTGGGGCGTGATCATCGATTTCTGGGGCCAGGGAACACTGGTCA CCGTGTCATCTGCTTCTACCAAGGGACCCTCTGTGTTCCCTCTGGCTCCTTCCAGCAAGTCTACCTCT GGTGGAACCGCTGCTCTGGGCTGCCTGGTCAAGGATTACTTTCCTGAGCCTGTGACAGTGTCCTGGAA CTCTGGTGCTCTGACCAGCGGCGTGCACACTTTTCCAGCTGTTCTGCAGTCCTCCGGCCTGTACTCTC TGTCCTCTGTCGTGACAGTGCCTTCCAGCTCTCTGGGCACCCAGACCTACATCTGCAACGTGAACCAC AAGCCTAGCAACACCAAAGTGGACAAGAAGGTGGAACCCAAGTCCTGCGACAAGACCCACACCTGTCC ACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGTTTCCACCTAAGCCTAAGGACA CCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCCACGAGGACCCAGAA GTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAACA GTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAACGGCAAAG AGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCAGCAAGGCTAAG GGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGACCAAGAATCAGGT GTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAATGGGAGTCCAATGGCC AGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTGTACTCC AAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATGCACGAGGC CCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGATGAAgn30:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGATATCCA GCTGACCCAAAGTCCGGCTTCCCTAGCTGTGAGCTTGGGCCAGCGTGCCACTATTTCCTGTAAAGCAT CCCAGTCCGTAGACTATGACGGTGACTCCTATCTGAATTGGTATCAGCAGATCCCTGGATGCCCCCCC AAGCTGCTCATCTATGACGCATCTAATCTGGTCTCAGGCATCCCTCCCCGCTTCAGTGGTTCAGGGTC CGGGACAGACTTCACCCTTAATATACACCCTGTCGAAAAAGTTGATGCTGCTACATACCACTGTCAAC AGTCCACTGAAGATCCCTGGACTTTCGGAGGGGGCACCAAACTGGAGATTAAAGGGGGAGGATCTGGA GGGTCAGGGGGATGTCCCCCATGTGGTGGTTCCGGCGGTCAGGTTCAACTCCAGCAGAGCGGCGCTGA GTTGGTGAGGCCAGGCAGTTCTGTGAAGATCAGTTGTAAGGCTAGTGGATATGCATTCTCAAGCTACT GGATGAATTGGGTTAAACAGCGACCAGGACAGGGACTGGAATGGATCGGTCAGATTTGGCCAGGAGAC GGCGATACTAATTATAACGGTAAATTTAAAGGCAAGGCTACCCTCACCGCTGATGAGAGTAGCAGTAC TGCCTACATGCAGCTGTCCTCCCTGGCAAGCGAGGATTCCGCCGTCTATTTCTGTGCCAGACGGGAAA CTACTACTGTCGGAAGGTATTATTACGCCATGGACTATTGGGGTTGCGGCACTACCGTCACTGTGAGC TCCGAACCCAAGTCCTCCGACAAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGG TCCCTCCGTTTTCCTGTTTCCACCTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGA CATGCGTGGTGGTGTCTGTGTCCCACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTG GAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGT GCTGACCGTGCTGCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCC TGCCTGCTCCTATCGAAAAGACCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACC CTGCCTCCATCTCGGGAAGAGATGACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTA CCCTTCCGATATCGCCGTGGAATGGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTC CTGTGCTGGACTCCGACGGCTCATTCTTCCTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAG CAGGGCAACGTGTTCTCCTGCTCTGTGATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCT GTCTCTGTCCCCTGGCAAGTGATGAAgn31:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGACATTGT TATGACCCAGTCCCCAGATAGTCTGGCCGTCAGTTTGGGGGAGCGCGCCACTATAAATTGTCGCGCTA GCCAGTCCGTGGACTACAACGGAATAAGTTATATGCATTGGTATCAGCAAAAGCCTGGCTGTCCTCCT AAACTCCTGATTTATGCCGCCTCAAACCCTGAGTCCGGGGTGCCGGACCGGTTCTCAGGGAGCGGGAG CGGCACGGACTTTACTTTGACAATTTCTTCTCTGCAGGCCGAGGACGTGGCCGTTTACTACTGTCAAC AGATCATCGAGGATCCCTGGACTTTTGGGCAAGGGACCAAAGTTGAGATCAAAGGGGGAGGATCCGGC GGATCTGGGGGATGCCCACCATGTGGGGGCAGTGGCGGACAAATCACACTCAAGGAGTCCGGGCCGAC CCTGGTAAAGCCAACTCAGACTCTCACTCTCACTTGCACCTTCTCCGGCTTCAGCTTGTCTACCTCTG GTATGGGAGTGAGCTGGATCAGACAGCCCCCTGGCAAGGCTCTGGAGTGGCTGGCTCACATCTATTGG GATGACGACAAGAGATACAATCCAAGTCTCAAGTCCCGTCTGACTATCACCAAGGATACATCTAAAAA CCAGGTGGTACTGACAATGACGAATATGGACCCAGTGGATACCGCTACTTATTATTGCGCCCGGCTTT ACGGCTTCACCTATGGCTTTGCCTACTGGGGATGTGGAACCCTTGTGACAGTCTCCTCAGAACCCAAG094669.0103PATENT TCCTCCGACAAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTT CCTGTTTCCACCTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGG TGTCTGTGTCCCACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAAC GCCAAGACCAAGCCTAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCT GCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTA TCGAAAAGACCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCT CGGGAAGAGATGACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATAT CGCCGTGGAATGGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACT CCGACGGCTCATTCTTCCTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTG TTCTCCTGCTCTGTGATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCC TGGCAAGTGATGAAgn32:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGATATCCA GCTGACGCAATCCCCCGCTAGTCTAGCCGTTTCACTCGGTCAGAGGGCCACCATAAGCTGCAAGGCTA GCCAGTCAGTGGACTACGATGGCGATAGCTATCTAAATTGGTACCAACAGATCCCTGGGCAGCCCCCT AAGCTGCTGATCTACGATGCTAGCAATCTGGTCTCTGGAATTCCCCCTCGGTTTTCCGGTTCAGGTAG CGGAACCGATTTCACCCTGAATATCCACCCAGTTGAAAAGGTCGACGCCGCCACCTACCACTGTCAAC AATCTACCGAAGATCCCTGGACCTTTGGCGGGGGCACTAAACTCGAAATCAAAGGCGGAGGCGGGTCT GGGGGCGGAGGCTCCGGAGGCGGCGGATCCCAGGTTCAGCTCCAACAGAGTGGCGCCGAACTGGTGAG ACCTGGCAGTTCCGTTAAAATTTCTTGTAAGGCATCAGGTTACGCATTCTCCTCCTATTGGATGAACT GGGTGAAGCAGCGCCCAGGACAGGGCCTGGAATGGATTGGTCAGATCTGGCCCGGGGATGGCGATACA AATTACAATGGAAAGTTTAAGGGAAAGGCCACCCTGACAGCTGATGAGAGTTCTAGCACAGCCTACAT GCAGCTCAGCAGTCTGGCTAGTGAAGATTCTGCCGTGTATTTCTGCGCACGGCGGGAAACTACCACCG TAGGTAGGTACTACTACGCTATGGATTACTGGGGGCAGGGGACTACTGTCACCGTCAGTTCCGAACCC AAGTCCTCCGACAAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGT TTTCCTGTTTCCACCTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGG TGGTGTCTGTGTCCCACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCAC AACGCCAAGACCAAGCCTAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGT GCTGCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTC CTATCGAAAAGACCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCA TCTCGGGAAGAGATGACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGA TATCGCCGTGGAATGGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGG ACTCCGACGGCTCATTCTTCCTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAAC GTGTTCTCCTGCTCTGTGATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTC CCCTGGCAAGTGATGAAgn33:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGATATCCA AATGACTCAGTCACCTAGTAGTCTGTCTGCCAGCGTGGGCGATCGGGTGACCATCACATGTCGATCCA GCCAGTCACTCGTCCATAGCAACGGTAATACTTACCTGCATTGGTACCAGCAGAAACCGGGATGTGCT CCTAAATTCCTGATCTACAAAGTTAGTAACAGATTTAGCGGAGTTCCAAGCCGATTCAGTGGCTCTGG TAGCGGTACAGACTTCACCTTGACTATCTCTTCACTCCAGCCCGAGGATTTTGCTACATATTATTGCT CCCAGTCCACACACGTGCCGTTCACTTTCGGACAAGGAACAAAGCTGGAGATTAAGGGCGGGGGGAGT GGCGGTAGTGGAGGATGCCCACCTTGTGGAGGAAGCGGCGGCCAGGTTCAGCTACAGGAGTCTGGACC CGGGCTCGTGAAGCCATCAGAGACCCTGAGCTTGACCTGCACTGTCAGCGGCTACTCAATTACCTCTG GGTATTTCTGGAATTGGATCAGGCAGCCCCCCGGCAAGGGTCTGGAGTGGATCGGCTACATTTCTTAC GACGGTAGCAACAACTATAACCCCAGCCTTAAATCCCGGGTGACGATCTCCCGGGACACATCTAAGAA CCAGTTTTCCTTGAAACTATCTAGTGTTACCGCCGCCGACACAGCTGTATACTACTGCGCATCTCCCA GCCCCGGAACCGGCTACGCCGTCGACTATTGGGGTTGTGGGACACTCGTAACAGTGTCTTCCGAACCC AAGTCCTCCGACAAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGT TTTCCTGTTTCCACCTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGG TGGTGTCTGTGTCCCACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCAC AACGCCAAGACCAAGCCTAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGT GCTGCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTC CTATCGAAAAGACCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCA094669.0103PATENT TCTCGGGAAGAGATGACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGA TATCGCCGTGGAATGGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGG ACTCCGACGGCTCATTCTTCCTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAAC GTGTTCTCCTGCTCTGTGATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTC CCCTGGCAAGTGATGAAgn35:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGAAATCGT GTTGACCCAATCTCCAGGCACCTTGTCTCTCTCTCCTGGAGAGAGGGCAACACTGTCATGCCGTGCAA GTCAGTCTGTCTCTAGCTCCTATCTTGCTTGGTATCAACAAAAGCCCGGGTGCGCTCCTAGACTGCTA ATTTATGGCGCCTCATCCCGTGCTACCGGCATTCCCGATCGGTTTTCCGGTTCAGGCTCTGGTACCGA TTTTACGCTTACGATTAGTAGGCTAGAGCCCGAGGACTTCGCAGTGTACTATTGCCAACAATATGGTT CTTCCCGCTTCACATTTGGACCGGGGACCAAGGTGGACATAAAAGGCGGCGGCTCAGGTGGCTCAGGC GGCTGCCCGCCTTGTGGCGGATCAGGCGGACAAGTACAACTTGTGCAATCTGGAGCTGAGGTGAAGAA ACCAGGCTCTTCTGTGAAGGTCAGCTGCAAAGATTCTGGCGGCACATTCTCTTCATATGCAATTTCCT GGGTAAGACAGGCTCCCGGACAAGGATTGGAATGGATGGGTGGCATTATACCGATATTCGGTACGACG AATTACGCACAACAGTTTCAGGGTCGGGTGACTATTACCGCAGACGAATCCACCAGCACTGCCTATAT GGAACTCAGCTCACTGAGAAGTGAGGATACGGCTGTCTATTATTGTGCCAGAGAAGCCGTGGCAGCTG ACTGGTTGGACCCATGGGGCTGTGGGACCCTCGTTACTGTCAGTAGCGAACCCAAGTCCTCCGACAAG ACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGTTTCCACC TAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCC ACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAG CCTAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTG GCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCA TCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATG ACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAATG GGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCAT TCTTCCTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCT GTGATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGATG AAgn36:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGCTATCCA GCTGACCCAGTCTCCATCCTCTCTGTCTGCCTCTGTGGGCGACAGAGTGACCATCACCTGTAGAGCCA GCCAGGGCATCTCTTCTGCTCTGGCCTGGTATCAGCAGAAGCCTGGCTGCGCTCCTAAGCTGCTGATC TACGACGCCTCCTCTCTGGAATCTGGCGTGCCATCCAGATTCTCCGGCTCTGGCTCTGGCACCGACTT TACCCTGACAATCAGCTCCCTGCAGCCTGAGGACTTCGCCACCTACTACTGCCAGCAGTTCAACAGCT ACCCCTACACCTTTGGCCAGGGCACCAAGCTGGAAATCAAAGGCGGAGGTAGCGGCGGATCTGGCGGA TGTCCTCCTTGCGGAGGTTCTGGCGGAGAAGTGCAGTTGGTTCAGTCTGGCGCCGAAGTGAAGAAGCC CGGCGAGTCTCTGAAGATCTCCTGCAAAGGCTCCGGCTACTCCTTCTCCTCTTCTTGGATCGGCTGGG TCCGACAGATGCCTGGCAAAGGACTGGAATGGATGGGCATCATCTACCCCGACGACAGCGACACCAGA TACAGCCCATCTTTCCAGGGCCAAGTGACAATCTCCGCCGACAAGTCCATCAGAACCGCCTACCTGCA GTGGTCCTCTCTGAAGGCCTCTGACACCGCCATGTACTACTGTGCCAGACACGTGACCATGATCTGGG GCGTGATCATCGATTTCTGGGGCTGTGGCACACTGGTCACCGTGTCATCTGAACCCAAGTCCTCCGAC AAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGTTTCC ACCTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGT CCCACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACC AAGCCTAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGA TTGGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGA CCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAG ATGACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGA ATGGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCT CATTCTTCCTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGC TCTGTGATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTG AT GA094669.0103PATENTAgn37:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGAAATAGT ACTTACACAGTCCCCCGGGACACTTTCTCTTAGCCCAGGTGAACGTGCTACACTCAGCTGCCGTGCAT CCCAATCAGTCAGTAGCTCTTATCTCGCATGGTACCAGCAGAAACCCGGGCAAGCTCCTCGGCTGTTG ATCTACGGCGCATCCAGTCGTGCCACCGGAATACCGGACAGGTTCTCCGGCTCTGGTAGCGGTACCGA CTTTACTTTGACTATTTCAAGGCTTGAGCCAGAGGACTTCGCTGTGTACTATTGCCAACAGTATGGCT CAAGTAGGTTCACCTTTGGGCCGGGTACTAAAGTTGATATCAAAGGCGGAGGCGGGTCTGGGGGCGGA GGCTCCGGAGGCGGCGGATCCCAAGTTCAACTCGTGCAATCTGGAGCTGAAGTGAAGAAACCTGGGAG CTCAGTGAAGGTGAGCTGTAAGGATTCAGGCGGTACATTCTCTTCATACGCTATTAGCTGGGTCCGAC AAGCCCCAGGGCAAGGCCTGGAATGGATGGGCGGGATTATTCCCATCTTCGGCACGACTAACTATGCC CAGCAATTCCAAGGCAGAGTTACTATAACCGCCGACGAATCAACTTCCACTGCATACATGGAACTAAG CTCTCTGCGCAGCGAAGACACCGCAGTGTATTACTGTGCCCGGGAAGCTGTGGCAGCAGATTGGCTGG ACCCCTGGGGACAAGGAACTCTCGTCACTGTCTCCTCTGAACCCAAGTCCTCCGACAAGACCCACACC TGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGTTTCCACCTAAGCCTAA GGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCCACGAGGACC CAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAG GAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAACGG CAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCAGCAAGG CTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGACCAAGAAT CAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAATGGGAGTCCAA TGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTGT ACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATGCAC GAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGATGAAgn38:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCGCTATCCA GCTGACCCAGTCTCCATCCTCTCTGTCTGCCTCTGTGGGCGACAGAGTGACCATCACCTGTAGAGCCA GCCAGGGCATCTCTTCTGCTCTGGCCTGGTATCAGCAGAAGCCTGGCAAGGCTCCCAAGCTGCTGATC TACGACGCCTCCTCTCTGGAATCTGGCGTGCCATCCAGATTCTCCGGCTCTGGCTCTGGCACCGACTT TACCCTGACAATCAGCTCCCTGCAGCCTGAGGACTTCGCCACCTACTACTGCCAGCAGTTCAACAGCT ACCCCTACACCTTTGGCCAGGGCACCAAGCTGGAAATCAAGGGCGGAGGCGGGTCTGGGGGCGGAGGC TCCGGAGGCGGCGGATCCGAAGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTGGCGAGTC CCTGAAGATCTCCTGCAAAGGCTCCGGCTACTCCTTCTCCTCTTCTTGGATCGGCTGGGTCCGACAGA TGCCAGGCAAAGGACTGGAATGGATGGGCATCATCTACCCCGACGACAGCGACACCAGATACAGCCCT AGCTTTCAGGGCCAAGTGACAATCTCCGCCGACAAGTCCATCAGAACCGCCTACCTGCAGTGGTCCTC TCTGAAGGCCTCTGACACCGCCATGTACTACTGTGCCAGACACGTGACCATGATCTGGGGCGTGATCA TCGATTTCTGGGGCCAGGGAACACTGGTCACCGTGTCATCTGAACCCAAGTCCTCCGACAAGACCCAC ACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTTCCTGTTTCCACCTAAGCC TAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGGTGTCTGTGTCCCACGAGG ACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGA GAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAA CGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCAGCA AGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGACCAAG AATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATATCGCCGTGGAATGGGAGTC CAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCC TGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATG CACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCCTGGCAAGTGATGAAgn39:ATGGTGCTGCAGACCCAGGTGTTCATTTCCCTGCTGCTGTGGATCTCTGGCGCTTACGGCCAGACAGT GGTCACCCAAGAACCTAGCCTGACAGTGTCTCCTGGCGGCACCGTGACACTGACCTGTAGATCTTCTA CCGGCGCTGTGACCACCTCCAACTACGCTAATTGGGTGCAGCAGAAGCCCGGCCAGGCTCCTAGAGGA CTGATCGGCGGAACAAACAAGAGAGCCCCTGGCACACCAGCCAGATTCTCAGGATCTCTGCTCGGCGG AAAGGCCGCTCTGACATTGTCTGGCGTGCAGCCTGAGGATGAGGCCGAGTACTACTGTGCCCTGTGGT ACTCCAACCTGTGGGTGTTCGGCGGAGGCACAAAACTGACAGTTCTCGGAGGCGGAGGAAGTGGTGGC GGAGGATCTGGCGGTGGTGGATCTGAAGTGCAGCTGGTTGAATCTGGCGGCGGATTGGTTCAGCCTGG094669.0103PATENT CGGATCTTTGAGACTGTCTTGTGCCGCCTCCGGCTTCACCTTCAACACCTACGCCATGAACTGGGTCC GACAGGCTCCTGGCAAAGGACTGGAATGGGTCGCCCGGATCAGATCCAAGTACAACAATTACGCCACC TACTACGCCGCCAGCGTGAAGGGCAGATTCACCATCTCTCGGGACGACTCCAAGAACTCCCTGTACCT GCAGATGAACAGCCTGAAAACCGAGGACACCGCTGTGTACTACTGCGCCAGACACGGCAACTTCGGCA ACTCCTATGTGTCTTGGTTTGCCTACTGGGGCCAGGGCACACTGGTCACAGTTAGCTCTGAACCCAAG TCCTCCGACAAGACCCACACCTGTCCACCATGTCCTGCTCCAGAAGCTGCAGGCGGTCCCTCCGTTTT CCTGTTTCCACCTAAGCCTAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACATGCGTGGTGG TGTCTGTGTCCCACGAGGACCCAGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAAC GCCAAGACCAAGCCTAGAGAGGAACAGTACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCT GCACCAGGATTGGCTGAACGGCAAAGAGTACAAGTGCAAAGTGTCCAACAAGGCCCTGCCTGCTCCTA TCGAAAAGACCATCAGCAAGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCT CGGGAAGAGATGACCAAGAATCAGGTGTCCCTGTGGTGCCTGGTGAAGGGCTTTTACCCTTCCGATAT CGCCGTGGAATGGGAGTCCAATGGCCAGCCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACT CCGACGGCTCATTCTTCCTGTACTCCAAGCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTG TTCTCCTGCTCTGTGATGCACGAGGCCCTGCACAACCACTACACACAGAAGTCCCTGTCTCTGTCCCC TGGCAAGTGATGApIGS000169:ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTATACAGGCCCAGGTCCAGCT GCAAGAGTCTGGCCCTGGACTGGTCAAGCCTTCCGAGACACTGTCTCTGACCTGCACCGTGTCCGGCT ACTCCATCACCAGCGGCTACTTTTGGAACTGGATCCGGCAGCCTCCTGGCAAAGGACTGGAATGGATC GGCTACATCTCCTACGACGGCTCCAACAACTACAACCCCAGCCTGAAGTCCAGAGTGACCATCTCTCG GGACACCTCCAAGAACCAGTTCTCCCTGAAGCTGTCCTCTGTGACCGCTGCCGATACCGCCGTGTACT ACTGTGCTTCTCCTTCTCCTGGCACCGGCTACGCTGTGGATTATTGGGGACAGGGCACACTCGTGACC GTGTCCTCTGCTTCTACAAAGGGGCCCTCTGTGTTCCCTCTGGCTCCTTCCTCTAAATCCACCTCTGG CGGAACCGCTGCTCTGGGCTGTCTGGTCAAGGATTACTTCCCTGAGCCTGTGACAGTGTCCTGGAACT CTGGTGCTCTGACATCCGGCGTGCACACCTTTCCAGCTGTGCTGCAGTCCTCTGGCCTGTACTCTCTG TCTAGCGTCGTGACAGTGCCTTCCAGCTCTCTGGGCACCCAGACCTACATCTGCAACGTGAACCACAA GCCTAGCAACACCAAGGTGGACAAGAAGGTGGAACCCAAGTCCTGCGACAAGACCCACACCTGTCCTC CATGTCCTGCTCCAGAAGCTGCTGGCGGACCCTCCGTTTTCCTGTTTCCACCTAAGCCTAAGGACACC CTGATGATCTCTCGGACCCCTGAAGTGACCTGCGTGGTGGTGTCTGTGTCTCACGAGGATCCCGAAGT GAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAACAGT ACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAACGGCAAAGAG TACAAGTGCAAGGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCTCCAAGGCTAAGGG CCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGACCAAGAATCAGGTGT CCCTGTCCTGCGCCGTGAAGGGCTTCTACCCTTCTGATATCGCCGTGGAATGGGAGTCCAACGGCCAG CCTGAGAACAATTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTGGTGTCCAA GCTGACAGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATGCACGAGGCCC TGCACAACCGGTTCACCCAGAAATCCCTGTCTCTGTCCCCTGGCAAGtgatagpIGS000171:ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTATACAGGCCGACATCCAGAT GACCCAGTCTCCATCCTCTCTGTCTGCCTCTGTGGGCGACAGAGTGACCATCACCTGTCGGAGTTCTC AGTCCCTGGTGCACTCCTCTGGCAACACCTACCTGCACTGGTATCAGCAGAAGCCCGGCAAGGCCCCT AAGTTCCTGATCTACAAGGTGTCCAACCGGTTCTCCGGCGTGCCCTCTAGATTTTCTGGCTCTGGATC TGGCACCGACTTCACCCTGACCATCAGTTCTCTGCAGCCTGAGGACTTCGCCACCTACTACTGCTCCC AGTCTACCCACGTGCCATTCACCTTTGGCCAGGGCACCAAGCTGGAAATCAAGAGAACCGTGGCCGCT CCTTCCGTGTTCATCTTCCCACCTTCCGACGAGCAGCTGAAGTCTGGCACAGCTTCTGTCGTGTGCCT GCTGAACAACTTCTACCCTCGGGAAGCCAAGGTGCAGTGGAAGGTGGACAATGCCCTGCAGTCCGGCA ACTCCCAAGAGTCTGTGACCGAGCAGGACTCCAAGGACTCTACCTACAGCCTGTCCTCCACACTGACC CTGTCTAAGGCCGACTACGAGAAGCACAAGGTGTACGCCTGTGAAGTGACCCACCAGGGCCTGTCTAG CCCTGTGACCAAGTCTTTCAACCGGGGCGAGTGTtgatagpIGS000131:ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTATACAGGCCCAGATCACCCT GAAAGAGAGCGGCCCTACACTGGTCAAGCCCACACAGACCCTGACACTGACCTGCACCTTCTCCGGCT094669.0103PATENT TCTCCCTGTCTACCTCTGGCATGGGAGTGTCTTGGATCAGACAGCCTCCTGGCAAGGCTCTGGAATGG CTGGCTCACATCTACTGGGACGACGACAAGCGGTACAACCCTAGCCTGAAGTCTCGGCTGACCATCAC CAAGGACACCTCCAAGAATCAGGTGGTGCTGACCATGACAAACATGGACCCTGTGGACACCGCCACCT ACTACTGTGCCAGACTGTACGGCTTCACCTACGGCTTTGCTTATTGGGGCCAGGGCACCCTGGTTACC GTGTCCTCTGCTTCTACAAAGGGGCCCTCTGTGTTCCCTCTGGCTCCTAGCTCTAAGTCCACCTCTGG TGGAACCGCTGCTCTGGGCTGTCTGGTCAAGGATTACTTCCCTGAGCCTGTGACAGTGTCCTGGAACT CTGGTGCTCTGACCTCCGGCGTGCACACATTTCCAGCTGTGCTGCAGTCCTCCGGCCTGTACTCTCTG TCCTCTGTCGTGACCGTGCCTTCTAGCTCTCTGGGCACCCAGACCTACATCTGCAACGTGAACCACAA GCCTTCCAACACCAAAGTGGACAAGAAGGTGGAACCCAAGTCCTGCGACAAGACCCACACCTGTCCTC CATGTCCTGCTCCAGAAGCTGCTGGCGGACCCTCCGTTTTCCTGTTTCCACCTAAGCCTAAGGACACC CTGATGATCTCTCGGACCCCTGAAGTGACCTGCGTGGTGGTGTCTGTGTCTCACGAGGATCCCGAAGT GAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAACAGT ACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAACGGCAAAGAG TACAAGTGCAAGGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCTCTAAGGCCAAGGG CCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGACAAAGAACCAGGTGT CCCTGTCCTGCGCCGTGAAGGGCTTCTACCCTTCTGATATCGCCGTGGAATGGGAGAGCAACGGCCAG CCTGAGAACAACTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTGGTGTCCAA GCTGACTGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATGCACGAGGCCC TGCACAACCGGTTCACCCAGAAATCCCTGTCTCTGTCCCCTGGCAAGtgatag PBD000105996_vDR363:ATGGCCTGGGTTTGGACCCTGCTGTTCCTGATGGCTGCCGCTCAGTCTATTCAGGCCGATATTGTGAT GACCCAGTCCCCCGATTCTCTCGCTGTCTCTCTGGGCGAACGGGCTACAATCAACTGTAGGGCTTCAC AGTCTGTCGACTACAACGGCATCTCTTACATGCATTGGTACCAGCAGAAACCTGGACAGCCACCAAAA CTCCTCATCTACGCCGCTTCCAATCCTGAATCTGGCGTGCCCGACCGATTTTCCGGATCCGGCTCTGG CACCGACTTTACACTCACTATTAGTAGCCTCCAGGCCGAGGATGTGGCCGTGTACTACTGTCAGCAGA TCATCGAGGATCCTTGGACATTTGGACAGGGAACCAAAGTGGAGATCAAACGTACGGTGGCTGCACCA TCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCT GAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACT CCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTG AGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCC CGTCACAAAGAGCTTCAACAGGGGAGAGTGTtgatagpIGS000237:ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTATACAGGCCCAAGTGACCCT GAGAGAGTCTGGCCCTGCTCTGGTCAAGCCTACACAGACCCTGACACTGACCTGCACCTTCTCCGGCT TTTCTCTGTCTACCGCTGGCATGTCCGTCGGCTGGATTAGACAGCCTCCTGGCAAAGCTCTGGAATGG CTGGCCGACATTTGGTGGGACGACAAGAAGCACTACAACCCCAGCCTGAAGGACCGGCTGACCATCTC CAAGGACACCTCCAAGAACCAGGTGGTGCTGAAAGTGACCAACATGGACCCTGCCGACACCGCCACCT ACTACTGCGCCAGAGACATGATCTTCAACTTCTACTTCGACGTGTGGGGCCAGGGCACCACAGTGACA GTTTCTTCCGCTTCTACCAAGGGGCCCAGCGTTTTCCCTCTGGCTCCATCCTCTAAGTCCACCTCTGG TGGAACCGCTGCTCTGGGCTGTCTCGTGAAGGATTACTTCCCTGAGCCTGTGACCGTGTCCTGGAACT CTGGTGCTCTGACATCCGGCGTGCACACCTTTCCAGCTGTGCTGCAGTCCTCTGGCCTGTACTCTCTG TCCTCTGTCGTGACCGTGCCTTCTAGCTCTCTGGGCACCCAGACCTACATCTGCAACGTGAACCACAA GCCTTCCAACACAAAGGTGGACAAGAAGGTGGAACCCAAGTCCTGCGACAAGACCCACACCTGTCCTC CATGTCCTGCTCCAGAAGCTGCTGGCGGACCCTCTGTGTTCCTGTTTCCTCCAAAGCCTAAGGACACC CTGATGATCTCTCGGACCCCTGAAGTGACCTGCGTGGTGGTGTCTGTGTCTCACGAGGATCCCGAAGT GAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGAGAGGAACAGT ACAACTCCACCTACAGAGTGGTGTCCGTGCTGACCGTGCTGCACCAGGATTGGCTGAACGGCAAAGAG TACAAGTGCAAGGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCAGCAAGGCTAAGGG CCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGACAAAGAATCAGGTGT CCCTGTCCTGCGCCGTGAAGGGCTTCTACCCTTCTGATATCGCCGTGGAATGGGAGTCCAACGGCCAG CCTGAGAACAACTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCCTGGTGTCCAA GCTGACAGTGGACAAGTCCAGATGGCAGCAGGGCAACGTGTTCTCCTGCTCTGTGATGCACGAGGCCC TGCACAACCGGTTCACCCAGAAATCCCTGTCTCTGTCCCCTGGCAAGTGATAGA094669.0103PATENTpIGS000223:ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTATACAGGCCGACATCCAGAT GACCCAGTCTCCATCCACACTGTCTGCCTCTGTGGGCGACAGAGTGACCATCACCTGTTCCGCATCCT CCAGAGTGGGCTACATGCACTGGTATCAGCAGAAGCCTGGCTGCGCCCCTAAGCTGCTGATCTACGAT ACCTCTAAGCTGGCCTCCGGCGTGCCCTCTAGATTTTCTGGCTCTGGATCTGGCACCGAGTTCACCCT GACCATCTCTAGCCTGCAGCCTGACGACTTCGCCACCTACTACTGTTTCCAAGGCAGCGGCTACCCCT TCACCTTTGGCGGAGGAACAAAGGTGGAAATCAAAGGCGGAGGCAGCGGAGGATCTGGCGGATGTCCT CCTTGTGGTGGTTCTGGCGGACAAGTGACCCTGAGAGAATCTGGCCCTGCTCTGGTCAAGCCCACACA GACCCTGACACTGACCTGCACCTTCTCCGGCTTTTCTCTGTCTACCGCTGGCATGTCCGTCGGCTGGA TTAGACAGCCTCCTGGCAAAGCTCTGGAATGGCTGGCCGACATTTGGTGGGACGACAAGAAGCACTAC AACCCCAGCCTGAAGGACCGGCTGACCATCAGCAAGGACACCTCCAAGAACCAGGTGGTGCTGAAAGT GACCAACATGGACCCTGCCGACACCGCTACCTACTATTGCGCCAGAGACATGATCTTCAACTTCTACT TCGACGTGTGGGGCTGCGGCACCACAGTGACAGTGTCCTCTGAGCCTAAGTCCTCCGACAAGACCCAC ACCTGTCCTCCATGTCCTGCTCCAGAAGCTGCTGGCGGACCCTCTGTGTTCCTGTTTCCTCCAAAGCC TAAGGACACCCTGATGATCTCTCGGACCCCTGAAGTGACCTGCGTGGTGGTGTCTGTGTCTCACGAGG ATCCCGAAGTGAAGTTCAATTGGTACGTGGACGGCGTGGAAGTGCACAACGCCAAGACCAAGCCTAGA GAGGAACAGTACAACTCCACCTACAGAGTGGTGTCAGTGCTGACCGTGCTGCACCAGGATTGGCTGAA CGGCAAAGAGTACAAGTGCAAGGTGTCCAACAAGGCCCTGCCTGCTCCTATCGAAAAGACCATCTCCA AGGCTAAGGGCCAGCCTCGGGAACCTCAGGTTTACACCCTGCCTCCATCTCGGGAAGAGATGACAAAG AATCAGGTGTCCCTGTGGTGTCTCGTGAAGGGCTTCTACCCTTCCGATATCGCCGTGGAATGGGAGTC CAATGGCCAGCCTGAGAACAACTACAAGACAACCCCTCCTGTGCTGGACTCCGACGGCTCATTCTTCC TGTACTCCAAGCTGACAGTGGACAAGTCTCGGTGGCAGCAGGGCAACGTGTTCTCCTGTTCTGTGATG CACGAGGCCCTGCACAACCACTACACCCAGAAGTCCCTGTCTCTGTCCCCTGGCAAATGATAGpIGS000238:ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTATACAGGCCGACATCCAGAT GACCCAGTCTCCATCCACACTGTCTGCCTCTGTGGGCGACAGAGTGACCATCACCTGTTCCGCATCCT CCAGAGTGGGCTACATGCACTGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGCTGCTGATCTACGAT ACCTCCAAGCTGGCCTCTGGCGTGCCCTCTAGATTTTCTGGCTCTGGCTCCGGCACCGAGTTCACCCT GACAATTTCTAGCCTGCAGCCTGACGACTTCGCCACCTACTACTGTTTCCAAGGCAGCGGCTACCCCT TCACCTTTGGCGGAGGAACAAAGGTGGAAATCAAGCGGACCGTGGCCGCTCCTTCCGTGTTTATCTTC CCACCTTCCGACGAGCAGCTGAAGTCTGGCACAGCTTCTGTCGTGTGCCTGCTGAACAACTTCTACCC TCGGGAAGCCAAGGTGCAGTGGAAGGTGGACAATGCCCTGCAGTCCGGCAACTCCCAAGAGTCTGTGA CCGAGCAGGACTCCAAGGACTCTACCTACAGCCTGTCCTCCACACTGACCCTGTCTAAGGCCGACTAC GAGAAGCACAAGGTGTACGCCTGTGAAGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGTCTTT CAACAGAGGCGAGTGCTGATAGAgnOl:MVLQTQVFISLLLWISGAYGDIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPP KLLIYDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFGGGTKLEIKRTVAA PSVFI FPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGS QVQLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKA TLTADESSSTAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSASTKGPSVFPLA PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVS VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK..Agn02:MVLQTQVFISLLLWISGAYGDIQMTQSPSSLSASVGDRVTITCRSSQSLVHSNGNTYLHWYQQKPGKA PKFLIYKVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIKRTVA APSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGG SQVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQPPGKGLEWIGYISYDGSNNYNPSLKSR094669.0103PATENT VTISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGQGTLVTVSSASTKGPSVFPLAPSS KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSH EDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI SKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF FLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGK..Agn03:MVLQTQVFISLLLWISGAYGDIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPP KLLIYDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFGGGTKLEIKGGGGS GGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIWPGDGDT NYNGKFKGKATLTADESSSTAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSGG GGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGLEWIGYINPSRGYTNYNQKFK DKATLTTDKSSSTAYMQLSSLTSEDSAVYYCARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGS GGVDDIQLTQSPAIMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPYRFSGS GSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKHHHHHH..Agn07:MVLQTQVFISLLLWISGAYGQTVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQAPRG LIGGTNKRAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNLWVFGGGTKLTVLGQPKAAP SVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLT PEQWKSHRSYSCQVTHEGSTVEKTVAPTECSGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYAASVKGRFT ISRDDSKNSLYLQMNSLKTEDTAVYYCARHGNFGNSYVSWFAYWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVS HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS FFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGK..Agnl4:MVLQTQVFISLLLWISGAYGDIVMTQSPDSLAVSLGERATINCRASQSVDNGISYMHWYQQKPGQPPK LLIYAASNPESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQIIEDPWTFGQGTKVEIKRTVAAP SVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGSQ ITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGMGVSWIRQPPGKALEWLAHIYWDDDKRYNPSLKSRL TITKDTSKNQVVLTMTNMDPVDTATYYCARLYGFTYGFAYWGQGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK..Agnl7:MVLQTQVFISLLLWISGAYGEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLL IYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRFTFGPGTKVDIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGSQVQ LVQSGAEVKKPGSSVKVSCKDSGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTTNYAQQFQGRVTIT ADESTSTAYMELSSLRSEDTAVYYCAREAVAADWLDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSG GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK PSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG QPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.094669.0103PATENTAgn19:MVLQTQVFISLLLWISGAYGAIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLI YDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPYTFGQGTKLEIKRTVAAPSVF I FPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGSEVQL VQSGAEVKKPGESLKISCKGSGYSFSSSWIGWVRQMPGKGLEWMGIIYPDDSDTRYSPSFQGQVTISA DKSIRTAYLQWSSLKASDTAMYYCARHVTMIWGVIIDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.Agn30:MVLQTQVFISLLLWISGAYGDIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGCPP KLLIYDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFGGGTKLEIKGGGSG GSGGCPPCGGSGGQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIWPGD GDTNYNGKFKGKATLTADESSSTAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGCGTTVTVS SEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT LPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK.Agn31:MVLQTQVFISLLLWISGAYGDIVMTQSPDSLAVSLGERATINCRASQSVDNGISYMHWYQQKPGCPPK LLIYAASNPESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQIIEDPWTFGQGTKVEIKGGGSGG SGGCPPCGGSGGQITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGMGVSWIRQPPGKALEWLAHIYWD DDKRYNPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARLYGFTYGFAYWGCGTLVTVSSEPKS SDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNA KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGKAgn32:MVLQTQVFISLLLWISGAYGDIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPP KLLIYDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFGGGTKLEIKGGGGS GGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIWPGDGDT NYNGKFKGKATLTADESSSTAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSEP KSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK.Agn33:MVLQTQVFISLLLWISGAYGDIQMTQSPSSLSASVGDRVTITCRSSQSLVHSNGNTYLHWYQQKPGCA PKFLIYKVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIKGGGS GGSGGCPPCGGSGGQVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQPPGKGLEWIGYISY DGSNNYNPSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGCGTLVTVSSEP KSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK.Agn35:MVLQTQVFISLLLWISGAYGEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGCAPRLL IYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRFTFGPGTKVDIKGGGSGGSG094669.0103PATENT GCPPCGGSGGQVQLVQSGAEVKKPGSSVKVSCKDSGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTT NYAQQFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAVAADWLDPWGCGTLVTVSSEPKSSDK THTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS VMHEALHNHYTQKSLSLSPGK.Agn36:MVLQTQVFISLLLWISGAYGAIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGCAPKLLI YDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPYTFGQGTKLEIKGGGSGGSGG CPPCGGSGGEVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWIGWVRQMPGKGLEWMGI IYPDDSDTR YSPSFQGQVTISADKSIRTAYLQWSSLKASDTAMYYCARHVTMIWGVIIDFWGCGTLVTVSSEPKSSD KTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC S VMHEALHNHYTQKSLSLSPGK.Agn37:MVLQTQVFISLLLWISGAYGEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLL IYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRFTFGPGTKVDIKGGGGSGGG GSGGGGSQVQLVQSGAEVKKPGSSVKVSCKDSGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTTNYA QQFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAVAADWLDPWGQGTLVTVSSEPKSSDKTHT CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN QVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH EALHNHYTQKSLSLSPGK.Agn38:MVLQTQVFISLLLWISGAYGAIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLI YDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPYTFGQGTKLEIKGGGGSGGGG SGGGGSEVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWIGWVRQMPGKGLEWMGIIYPDDSDTRYSP SFQGQVTISADKSIRTAYLQWSSLKASDTAMYYCARHVTMIWGVIIDFWGQGTLVTVSSEPKSSDKTH TCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPR EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK NQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM HEALHNHYTQKSLSLSPGK.Agn39:MVLQTQVFISLLLWISGAYGQTVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQAPRG LIGGTNKRAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNLWVFGGGTKLTVLGGGGSGG GGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYAT YYAASVKGRFTISRDDSKNSLYLQMNSLKTEDTAVYYCARHGNFGNSYVSWFAYWGQGTLVTVSSEPK SSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS REEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK.pIGS000169:MAWVWTLLFLMAAAQSIQAQVQLQESGPGLVKPSETLSLTCTVSGYSITSGYFWNWIRQPPGKGLEWI GYISYDGSNNYNPSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCASPSPGTGYAVDYWGQGTLVT VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDT LMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQ PENNY KTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMH EALHNRFTQKSLSLSPGK.094669.0103PATENTpIGS000171:MAWVWTLLFLMAAAQSIQADIQMTQSPSSLSASVGDRVTITCRSSQSLVHSSGNTYLHWYQQKPGKAP KFLIYKVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCSQSTHVPFTFGQGTKLEIKRTVAA PSVFI FPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECpIGS000131:MAWVWTLLFLMAAAQSIQAQITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGMGVSWIRQPPGKALEW LAHIYWDDDKRYNPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARLYGFTYGFAYWGQGTLVT VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDT LMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQ PENNY KTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGK PBD000105996_vDR363:MAWVWTLLFLMAAAQSIQADIVMTQSPDSLAVSLGERATINCRASQSVDNGISYMHWYQQKPGQPPKL LIYAASNPESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQIIEDPWTFGQGTKVEIKRTVAAPS VFI FPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGECpIGS000237:MAWVWTLLFLMAAAQSIQAQVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEW LADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTTVT VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDT LMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQ PENNY KTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMH EALHNRFTQKSLSLSPGK. pIGS000223:MAWVWTLLFLMAAAQSIQADIQMTQSPSTLSASVGDRVTITCSASSRVGYMHWYQQKPGCAPKLLIYD TSKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCFQGSGYPFTFGGGTKVEIKGGGSGGSGGCP PCGGSGGQVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALEWLADIWWDDKKHY NPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGCGTTVTVSSEPKSSDKTH TCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAKTKPR EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK NQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM HEALHNHYTQKSLSLSPGK.pIGS000238:MAWVWTLLFLMAAAQSIQADIQMTQSPSTLSASVGDRVTITCSASSRVGYMHWYQQKPGKAPKLLIYD TSKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCFQGSGYPFTFGGGTKVEIKRTVAAPSVFIF PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY EKHKVYACEVTHQGLSSPVTKSFNRGECExample 2The present example measures the binding of Vβ17xCD19 bispecific antibodies as compared to CD19 x CD3 BiTE Antibody and Vβ17x null antibody on target cell lines, isolated Pan-T cells, and isolated and expanded Vβ17 T cells from human PBMCs. In addition, the present example measures the cytotoxic potency of Vβ17XCD19 bispecific antibodies as094669.0103PATENTcompared to CD 19 x CD3 BiTE Antibody and Vβ17x null antibody using WIL2-S / GFP cell lines as target cell lines and isolated and expanded Vβ17 T cells and isolated Pan-T cells as effector cells.Briefly, antibodies were cloned and obtained as described in Example 1 above. A list of the different tested antibodies in provided in Table 7 below.Table 7Antibody DesignationAGNAB1.001 HD37 CD19 x CD3-BiTeAGNAB2.001 Vβ17 x HD37 CD19AGNAB3.001 Vβ17 X47G4 CD19AGNAB4.001 Vβ17 X 21D4 CD19AGNAB5.001 Vβ17 X NULLAGNAB6.001 B219 CD3 scFab x HD37CD19 scFabAGNAB7.001 B219 CD3 scFab x 47G4 CD19 scFabAGNAB8.001 B219 CD3 scFab X 21D4 CD19 scFabAGNAB9.001 B219 CD3_scFab X NULL_scFabAGNAB10 Vβ17 Fab X HD37 CD19 spFvAGNAB11 Vβ17 Fab X 47G4 CD19 spFvAGNAB12 Vβ17 Fab X 21D4 CD19 spFvAGNAB14 Vβ17 Fab X HD37 CD19 scFvAGNAB15 Vβ17 Fab X47G4 CD19 scFvAGNAB16 Vβ17 Fab X 21D4 CD19 scFvAGNAB34 Null Fab X Null SpFv (NuMAX)Next, target cells were cultured in RPMI + 10% FBS. Cells were passaged every 3 days. Briefly, cells were collected from the flask and centrifuged at 1000 rpm for 5 min. Supernatant was discarded and the cells were seeded back in fresh media at a density of 5x105cells / ml.For binding of antibodies on target cell lines, target cells were seeded at a density of 0.1 million cells / well in 96 well plates. Live / Dead stain (zombie green) in PBS was added and incubated at 4°C for 15 minutes. The cell pellet was washed twice with FACS buffer (PBS+2%FBS). Antibodies in decided concentrations were added to the designated wells. Incubated the plate at 37°C for 40 minutes and washed the cell pellet twice with FACS buffer (PBS+2%FBS). Secondary antibody (Alexa Fluor® 647 AffmiPure™ F(ab’) 2 Fragment Goat094669.0103PATENTAnti-Human IgG, Fey fragment specific) was added to the wells at 1:500 dilution. Incubated the plate at 4°C for 30 minutes and washed the cell pellet twice with FACS buffer (PBS+2%FBS). Finally, data acquisition was done by NovoCyte flow cytometer.For binding of antibodies on isolated pan-T cells, frozen PBMCs was removed from LN2 tank. Quickly thaw PBMC vial was added to 49 mL of warm media (RPMI+10% FBS) in a 50 mL falcon to dilute freezing medium. PBMCs were centrifuged at 1200RPM for 5 minutes. Next, the cell pellet was resuspended in media and the cells were counted. T cell isolation using EasySep Human T cell isolation kit was performed. According to the kit protocol, take 50x106cells suspended in 1ml EasySep buffer in 5ml polypropylene glass tubes. Enrichment cocktail and microbeads were added as per manufacturer’s instructions. Next, the volume was made up to 2.5ml with the EasySep buffer and the tubes placed on the magnet for 5 mins. The supernatant was transferred to new 5ml polypropylene tubes and placed on the magnet for 5 mins. Finally, the supernatant (isolated T cells) was collected in fresh falcon tubes, spinned for 5mins at 1200rpm and resuspended in RPMI media with 10% FBS. An operator counted the cells and took aliquots for phenotyping to check the CD3+ and Vb17 expression. The binding protocol outlined above was further followed.Protocols for binding of antibodies on enriched Vb17 T cells are provided below. For isolation and expansion of VB17 T cells from frozen PBMCs, T cells were isolated using EasySep Human T cell isolation kit. The T cells were stained using TCR Vβ17- APC antibody for Ih at 4°C, in the dark. After Ih, 10ml of sort buffer was added and cells were centrifuged at 400g, for 5 min at 4°C. Discarded the supernatant, the wash was repeated one more time. Next, cells were resuspended in 100 pl of sorting buffer (e.g., 100 pl for up to 10e6 cells). 20pl of anti-APC beads were added for up to 10e6 cells and cells were incubated for 15 minutes in the dark, at 4°C. Once 10ml of sorting buffer was added, cells were spinned for 5 minutes at 400g. Next, the cell pellet was resuspended in 600pl of sorting buffer (500 pl for up to 100e6 cells) and loaded onto LS column. Flow through was collected into a 50ml conical tube (this is the negative fraction) and washed with sorting buffer. Next, using a MACS separator, cells adhered to the columns were collected (positive fraction- Vβ17+ cells). After further washing and centrifugation steps, the pellet was resuspended in 10% RPMI media. Finally, cells were dispersed at a density of 1.5 million / ml of media. Culture volumes did not exceed 55 mL / T175 flask.For preparation of anti-Biotin MACSi Bead Particles (for activation of T cells), the following protocol was followed. Briefly, 100 pL CD2-Biotin, 100 pL CD3 -Biotin and 100 pL CD28 Biotin were pipetted into a sealable 2 mL tube and mix. Anti-Biotin MACS iBeads094669.0103PATENTwere mixed with antibody. Next, bead buffer was added and incubated for 2 hours at 40C under constant rotation.For T cell activation with beads (Day-0), 2.5×106loaded Anti-Biotin MACSiBead Particles were admixed with 5×106Pan T cell / PBMCs in 10% RPMI (without IL-2) and incubated at 37°C in CO2 incubator for 3 days. If media without IL-2 were used, cells were prepared at a density of 1.5 million / ml.For T cell stimulation and expansion with IL2, cells were counter after three days of culture, count cells. Concentration of culture was adjusted to 0.75-1.5 cells / ml with RPMI + 10% FBS supplemented with IL-2 (20IU / ml of media).The results of binding of antibodies to specific cells are depicted in Figures 1 A-6D. Figures 7A-8F illustrate the cytotoxicity activities of the tested antibodies.Incorporation By ReferenceDiscussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is for the purpose of providing context for the present disclosure. Such discussion is not an admission that any or all of these matters form part of the prior art with respect to any inventions disclosed or claimed.All publications, patents, and patent applications herein are incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. In the event of a conflict between a term herein and a term in an incorporated reference, the term herein controls.

Claims

094669.0103PATENT CLAIMS1. A bispecific antibody comprising:(a) a first binding domain that binds Vβ17 comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 26, and a second binding domain that binds CD 19 comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 30;(b) a first binding domain that binds Vβ17 comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 26, and a second binding domain that binds CD 19 comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 33; or(c) a first binding domain that binds Vβ17 comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 26, and a second binding domain that binds CD 19 comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain094669.0103PATENTcomplementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) of the amino acid sequence set forth in SEQ ID NO: 36.

2. The bispecific antibody of claim 1, wherein each CDR is designated by a method selected from Kabat, Clothia, AbM, or IMGT.

3. The bispecific antibody of claim 1 or 2, wherein the first binding domain comprises a single chain Fab.

4. The bispecific antibody of any one of claims 1-3, wherein the first binding domain comprises the amino acid sequence set forth in SEQ ID NO: 26.

5. The bispecific antibody of any one of claims 1-4, wherein the second binding domain comprises a single chain Fab.

6. The bispecific antibody of any one of claims 1-5, wherein the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 30.

7. The bispecific antibody of any one of claims 1-5, wherein the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 33.

8. The bispecific antibody of any one of claims 1-5, wherein the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 36.

9. The bispecific antibody of claim 1 or 2, wherein the first binding domain comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28.

10. The bispecific antibody of claim 1 or 2, wherein the first binding domain comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29.

11. The bispecific antibody of claim 1 or 2, wherein the first binding domain comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 29.

12. The bispecific antibody of any one of claims 9-11, wherein the second binding domain comprises an spFv.

13. The bispecific antibody of claim 12, wherein the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 31.

14. The bispecific antibody of claim 12, wherein the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 34.094669.0103PATENT15. The bispecific antibody of claim 12, wherein the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 37.

16. The bispecific antibody of any one of claims 9-11, wherein the second binding domain comprises an scFv.

17. The bispecific antibody of claim 16, wherein the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 32.

18. The bispecific antibody of claim 16, wherein the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 35.

19. The bispecific antibody of claim 16, wherein the second binding domain comprises the amino acid sequence set forth in SEQ ID NO: 38.

20. A bispecific antibody comprising:(a) a single chain Fab binding Vβ17 comprising the amino acid sequence set forth in SEQ ID NO: 26, and(b) a single chain Fab binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 30.

21. Abispecific antibody comprising:(a) a single chain Fab binding Vβ17 comprising the amino acid sequence set forth in SEQ ID NO: 26, and(b) a single chain Fab binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 33.

22. A bispecific antibody comprising:(a) a single chain Fab binding Vβ17 comprising the amino acid sequence set forth in SEQ ID NO: 26, and(b) a single chain Fab binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 36.

23. Abispecific antibody comprising:(a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29; and (b) an spFv binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 31.

24. A bispecific antibody comprising:(a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29; and094669.0103PATENT(b) an spFv binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 34.

25. Abispecific antibody comprising:(a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29; and (b) an spFv binding CD19 comprising the amino acid sequence set forth in SEQ ID NO: 37.

26. A bispecific antibody comprising:(a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29; and (b) an scFv binding CD 19 comprising the amino acid sequence set forth in SEQ ID NO: 32.

27. A bispecific antibody comprising:(a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29; and (b) an scFv binding CD 19 comprising the amino acid sequence set forth in SEQ ID NO: 35.

28. Abispecific antibody comprising:(a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29; and (b) an scFv binding CD 19 comprising the amino acid sequence set forth in SEQ ID NO: 38.

29. A nucleic acid encoding the bispecific antibody of any one of claims 1-29.

30. The nucleic acid of claim 29 comprising a first polynucleotide encoding the first binding domain that binds Vβ17.

31. The nucleic acid of claim 29 or 30 comprising a second polynucleotide encoding the second binding domain that binds CD 19.

32. A vector comprising the nucleic acid of any one of claims 29-31.

33. A host cell comprising the nucleic acid of any one of claims 29-31 or the vector of claim 32.

34. A composition comprising the bispecific antibody of any one of claims 1-28, the nucleic acid of any one of claims 29-31, the vector of claim 32, or the host cell of claim 33.

35. The composition of claim 34, which is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.094669.0103PATENT36. A method for treating an autoimmune disease in a subject in need thereof, the method comprising administering an effective amount of the bispecific antibody of any one of claims 1-28 or the composition of claim 34 or 35.

37. The method of claim 36, wherein the autoimmune disease is selected from lupus, lupus erythematosus, systemic lupus erythematosus, refractory systemic lupus erythematosus, or external lupus (cutaneous lupus erythematosus).

38. The method of claim 36, wherein the autoimmune disease is selected from nephritis, lupus nephritis, goodpasture’s syndrome, membranous nephropathy, ANCA-associated renal vasculitis, Henoch–Schönlein purpura, polyarteritis nodosa (PAN), sarcoidosis, scleroderma nephritis, or immune nephritis.

39. The method of claim 36, wherein the autoimmune disease is selected from systemic sclerosis, limited cutaneous systemic sclerosis (IcSSc), diffuse cutaneous systemic sclerosis (dcSSc), systemic sclerosis sine scleroderma, scleroderma, localized scleroderma, systemic scleroderma, limited cutaneous scleroderma, or diffuse cutaneous scleroderma.

40. The method of claim 36, wherein the autoimmune disease is selected from arthritis, rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis (JIA), lupus arthritis, reactive arthritis, lyme arthritis, or gout.

41. The method of claim 36, wherein the autoimmune disease is selected from multiple sclerosis, clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS).

42. The method of claim 36, wherein the autoimmune disease is selected from atopic dermatitis, psoriasis, pemphigus, bullous pemphigoid, dermatitis herpetiformis, Behcet's disease, or vasculitis.

43. The method of claim 36, wherein the autoimmune disease is selected from asthma, interstitial lung disease (ILD), pulmonary hypertension, bronchiectasis, lung nodules, or Sjogren’s syndrome.

44. The method of claim 36, wherein the autoimmune disease is selected from antiphospholipid syndrome45. The method of claim 36, wherein the autoimmune disease is selected from myositis, idiopathic inflammatory myopathies (IIMs), polymyositis, dermatomyositis, sporadic inclusion body myositis, inclusion body myositis, or dermatomyositis.

46. The method of claim 36, wherein the autoimmune disease is selected from generalized myasthenia gravis.094669.0103PATENT47. The method of claim 36, wherein the autoimmune disease is selected from neuromyelitis optica, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), or acute disseminated encephalomyelitis (ADEM).

48. A method for depleting B cells in a subject in need thereof, the method comprising administering an effective amount of the bispecific antibody of any one of claims 1-28 or the composition of claim 34 or 35.

49. A method of promoting T cell mediated killing of B cells expressing CD 19 in a subject in need thereof, the method comprising administering an effective amount of the bispecific antibody of any one of claims 1-28 or the composition of claim 34 or 35.

50. A method of directing a Vβ17-expressing T cell to a B cell in a subject in need thereof, the method comprising administering an effective amount of the bispecific antibody of any one of claims 1-28 or the composition of claim 34 or 35.

51. The method of claim 50, wherein the T cell is a CD8 T cell or a CD4 T cell.

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