Monoclonal antibody or antigen-binding fragment thereof that specifically binds to TRBV5-1 segment of variable domain of beta chain of human t-cell receptor and its use

Abstract

FIELD: biotechnology.SUBSTANCE: antibodies that specifically bind to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor, used in medicine for the treatment of diseases or disorders mediated by the said segment, such as type 1 diabetes mellitus, delaying the transition of type 1 diabetes mellitus stage 2 to stage 3, high blood glucose, impaired glucose tolerance, prediabetes, rejection of nickel implants or prostheses, sarcoidosis, berylliosis, celiac disease and dermatitis herpetiformis. Monoclonal antibodies to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor and their antigen-binding fragments, as well as means and methods for their recombinant production and use in therapy are proposed.EFFECT: production of antibodies that have high parameters of binding affinity to the said segment and antibody-dependent cell-mediated cytotoxicity (ADCC), and are also humanized, stable in human serum and thermostable.17 cl, 16 dwg, 8 tbl, 18 ex

Description

[0001] Field of technology to which the invention relates

[0002] The present invention relates to the field of biotechnology and medicine, namely to a monoclonal antibody or an antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor.The invention also relates to nucleic acids encoding said antibody, expression vectors, host cells and methods for their production, methods for producing antibodies of the invention, pharmaceutical compositions containing an antibody of the invention, pharmaceutical compositions containing an antibody of the invention and other therapeutically active compounds, methods for treating or preventing diseases or disorders mediated by the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor, uses of antibodies or their pharmaceutical compositions for treating or preventing diseases or disorders mediated by the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor, and uses of antibodies of the invention and other therapeutically active compounds for treating or preventing diseases or disorders mediated by the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor.

[0003] Technology Level

[0004] Monoclonal antibodies in the form of chimeric, humanized or fully human molecules have proven their value as effective drugs for the treatment of a number of disorders and diseases.

[0005] One of the causes of autoimmune diseases are autoreactive T lymphocytes (Haroon N et al., Arthritis Rheum. 2013 Oct; 65(10):2645-54., Duarte J. et al., PloS One 2010 May 10; 5(5):e10558; Konig M. et al., Front Immunol 2016 Jan 25; 7:11). A key role in the emergence of autoreactive T lymphocyte clones is played by the interaction of the antigen-recognizing T-cell receptor (T-cell receptor, TCR) with proteins of the major histocompatibility complex (MHC, HLA), which present processed peptides of intracellular proteins or proteins of pathogenic organisms on their surface.

[0006] It is known from the prior art that the T-cell receptor sequence is a marker for identifying the T-lymphocyte clone involved in the pathogenesis of an autoimmune disease. T-cell receptor subunits structurally belong to the immunoglobulin superfamily and are formed from several gene segments. The variable regions of the TCR form the antigen-binding center of the TCR. This means that they are clone-specific, i.e., they differ in T-lymphocytes that respond to different antigens.

[0007] T lymphocytes (T cells) are stimulated when antigens bind to their T cell receptors. The TCR, the defining structure of T cells, is a transmembrane heterodimer consisting of either alpha and beta chains or delta and gamma chains linked by a disulfide bond. Within these chains are complementarity-determining regions (CDRs), which determine the antigen that the TCR will bind. TCR development occurs through a lymphocyte-specific process of gene recombination, which assembles a final sequence from a large number of potential segments. This genetic recombination of TCR gene segments in somatic T cells occurs early in thymus development. The TCR α gene locus contains the variable (V) and joining (J) gene segments (Va and Ja), whereas the TCR β locus contains the D gene segment in addition to the Vβ and Jβ segments.Accordingly, the α-chain is generated as a result of VJ recombination, and the β-chain is involved in VDJ recombination.

[0008] The TCR α chain gene locus consists of 46 variable segments (TRAV), 8 joining segments (TRAJ), and a constant region. The TCR β chain gene locus consists of 48 variable segments (TRBV), followed by two diversity segments (TRBD), 12 joining segments (TRBJ), and two constant regions (Bio-Rad. Mini-review | An overview of T cell receptors [Electronic resource] / / Bio-Rad. URL: https: / / www.bio-rad-antibodies.com / t-cell-receptor-minireview.html).

[0009] The T-cell receptor interacts with an antigen noncovalently bound to the MHC molecule through six complementarity-determining regions (CDRs): three regions of the alpha chain and three of the beta chain. These CDRs are the variable regions, loops of the variable domains of the T-cell receptor—Valpha (TRAV) and Vbeta (TRBV).

[0010] The relationship between the TCR of CD4+ T cells and the development of type 1 diabetes mellitus is known in the prior art (Mai T. Tran ET ALL., T cell receptor recognition of hybrid insulin peptides bound to HLA-DQ8, NATURE COMMUNICATIONS, 2021, 12:5110, https: / / doi.org / 10.1038 / s41467-021-25404-x, Maki Nakayama ET ALL., Using the T Cell Receptor as a Biomarker in Type 1 Diabetes, Front. Immunol., 17 November 2021, Sec. Immunological Tolerance and Regulation, https: / / doi.org / 10.3389 / fimmu.2021.777788).

[0011] Patent document WO2020010250 describes an antibody that specifically binds to the variable chain region of the T lymphocyte receptor beta (TCRβV).

[0012] Patent documents WO2019132738 and WO2020139171 describe an antibody that specifically binds to a portion of the variable domain of the beta chain of the human T cell receptor belonging to the TRBV9 family.

[0013] In connection with the above, it is relevant to create antibodies that specifically bind to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor.

[0014] Disclosure of the essence of the invention (detailed description of the invention)

[0015] The authors of this group of inventions developed antibodies that specifically bind to the TRBV5-1 segment of the human T-cell receptor beta chain variable domain and exhibit high binding affinity. Furthermore, the antibodies according to the invention are humanized, stable in human serum, and heat-stable, and exhibit antibody-dependent cell-mediated cytotoxicity (ADCC).

[0016] Definitions and General Methods

[0017] Unless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those skilled in the art.

[0018] Furthermore, unless the context otherwise requires, singular terms include plural terms, and plural terms include singular terms. The generally used classification and methods of cell culture, molecular biology, immunology, microbiology, genetics, analytical chemistry, organic synthetic chemistry, medicinal and pharmaceutical chemistry, as well as hybridization and protein and nucleic acid chemistry described herein are well known to those skilled in the art and are widely used in this field. Enzymatic reactions and purification methods are carried out in accordance with the manufacturer's instructions, as commonly practiced in the art, or as described herein.

[0019] The term “KD” in this specification refers to the affinity constant (or equilibrium constant) which is obtained from the ratio of Kd to Ka (i.e., Kd / Ka), and is expressed as a molar concentration (M).

[0020] "Binding affinity" typically refers to the strength of the combined non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless otherwise specified, "binding affinity" refers to the intrinsic (characteristic, true) binding affinity, which reflects the 1:1 interaction between the members of a binding pair (e.g., an antibody and an antigen). The affinity of molecule X for its partner Y can typically be represented by the affinity constant (KD). It is desirable that the KD value is approximately 200 nM, 150 nM, 100 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 8 nM, 6 nM, 4 nM, 2 nM, 1 nM or less. The affinity can be measured by conventional methods known in the art, including the methods described herein.Low-affinity antibodies typically bind to antigen slowly and tend to dissociate easily, whereas high-affinity antibodies typically bind to antigen more quickly and tend to remain bound longer. Various methods for measuring binding affinity are known in the art, and any of these methods can be used for the purposes of the present invention.

[0021] The term "Kd," "koff," or "kdis" refers to the dissociation rate constant of a specific interaction between a binding molecule and an antigen. The dissociation rate constant koff can be measured using biolayer interferometry, such as the Octet™ system.

[0022] The term "Ka", "kon" or "on-rate" refers to the association rate constant.

[0023] The term "R 2 » refers to the coefficient of determination.

[0024] The term “Response” refers to the binding signal of an antibody to an antigen.

[0025] The term "in vitro" refers to a biological object, biological process, or biological reaction outside the body, simulated under artificial conditions. For example, in vitro cell growth should be understood as cell growth in an environment outside the body, such as a test tube, culture flask, or microplate.

[0026] Term ED 50 (EC 50 ) (50% effective dose / concentration, half-maximal effective concentration) refers to the drug concentrations at which 50% of the measurable biological effect is achieved (may include cytotoxicity).

[0027] The human T-cell receptor is a heterodimeric protein complex located on the surface of T lymphocytes. This receptor is present only on T lymphocytes. The primary function of the T-cell receptor is the specific recognition of processed antigens bound to major histocompatibility complex (MHC) molecules.

[0028] The terms "anti-TRBV5-1 antibody", "antibody to TRBV5-1", "antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor", "antibody that specifically binds to the TRBV5-1 segment" are interchangeable in the context of the present application and refer to an antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor.

[0029] ADCC - antibody-dependent cell-mediated cytotoxicity.

[0030] ADCP - antibody-dependent cellular phagocytosis.

[0031] NFAT - nuclear factor of activated T cells.

[0032] Luc - luciferase.

[0033] FBS - fetal bovine serum.

[0034] CD3 - cluster of differentiation 3.

[0035] CD16 - cluster of differentiation 16.

[0036] CD20 - cluster of differentiation 20.

[0037] CD64 - cluster of differentiation 64.

[0038] PBMC - peripheral blood mononuclear cells.

[0039] PE - phycoerythrin.

[0040] In the present description and in the following claims, unless the context otherwise requires, the words "include" and "comprise" or variations thereof such as "includes," "including," "comprises," or "containing" are to be understood as including the stated whole or group of wholes, but not excluding any other whole or group of wholes.

[0041] Antibody

[0042] The present invention relates to a monoclonal antibody or an antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor.

[0043] The term "monoclonal antibody" or "mAb" refers to an antibody that is synthesized and secreted by a distinct clonal population of cells.

[0044] The antibody of the invention is a recombinant antibody.

[0045] The term "recombinant antibody" means an antibody that is expressed in a cell or cell line containing a nucleotide sequence(s) that encodes the antibody, wherein said nucleotide sequence(s) is(are) not associated with the cell in nature.

[0046] In one aspect, the present invention relates to a monoclonal antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor, comprising:

[0047] (a) a light chain variable domain comprising:

[0048] (i) CDR1 with an amino acid sequence selected from the group: SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3;

[0049] (ii) CDR2 with the amino acid sequence EIX1KLX2S, where

[0050] X1=T or S

[0051] X2=A, F or M; And

[0052] (iii) CDR3 with the amino acid sequence QQWNYPX3LX4, where

[0053] X3=L, R or Y;

[0054] X4=S or T;

[0055] and

[0056] (b) a heavy chain variable domain comprising:

[0057] (i) CDR1 with the amino acid sequence of SEQ ID NO: 12;

[0058] (ii) CDR2 with the amino acid sequence YINPX5X6GRTGYNQKX7QX8, where

[0059] X5= Y or W;

[0060] X6= Q or N;

[0061] X7= F or L;

[0062] X8= A or G;

[0063] and

[0064] (iii) CDR3 with the amino acid sequence of SEQ ID NO: 18.

[0065] In one embodiment of the invention, the antibody of the invention is an isolated antibody.

[0066] The term "isolated" used to describe various antibodies in this specification means an antibody that has been identified and separated and / or recovered from the cell or cell culture in which it is expressed. Contaminants (impurities) from the natural environment are materials that typically interfere with the diagnostic or therapeutic use of the polypeptide and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. Typically, an isolated polypeptide is obtained through at least one purification step.

[0067] In one embodiment of the invention, the antibody of the invention is a humanized antibody.

[0068] A humanized antibody is an antibody whose amino acid sequence has at least 95% homology to human immunoglobulin reference sequences (according to the IMGT database). The use of humanized antibodies reduces the risk of an immune response in the human body when administered.

[0069] The term "antibody" or "immunoglobulin" (Ig), as used herein, includes whole antibodies. The term "antibody" refers to a glycoprotein comprising at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each heavy chain comprises a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. Each light chain consists of a light chain variable region (abbreviated herein as VL) and a light chain constant region. The light chain constant domain can be CK (light chain kappa constant domain) or CL (light chain lambda constant domain). Preferably, the light chain is a light kappa (κ) chain, and the light chain constant domain is preferably CK.

[0070] The antibodies of the invention may be antibodies of any class (e.g., IgA, IgD, IgE, IgG and IgM, preferably IgG) or subclass (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2, preferably IgG1).

[0071] The VH and VL regions can be further subdivided into regions of hypervariability, called complementarity-determining regions (CDRs), interspersed with more conserved regions, called framework regions (FRs). Each VH and VL consists of three CDRs and four FRs, arranged from amino terminus to carboxy terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain the binding domain that interacts with the antigen.

[0072] The constant regions of antibodies can mediate the binding of immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system.

[0073] The term "antigen-binding portion" of an antibody or "antigen-binding fragment," as used herein, refers to one or more fragments of an antibody that retain the ability to specifically bind to an antigen. It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody. Examples of binding fragments included within the term "antigen-binding portion" of an antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL, and CH1 domains; (ii) an F(ab')2 fragment, a divalent fragment comprising two Fab fragments linked by a disulfide bridge in the hinge region; (iii) an Fd fragment, consisting of the VH and CH1 domains; (iv) the Fv fragment, which consists of the VL and VH domains in a single arm of the antibody, (v) the dAb fragment (Ward et al., (1989) Nature 341:544-546), which consists of the VH / VHH domain.Furthermore, the two regions of the Fv fragment, VL and VH, are encoded by different genes and can be joined recombinantly using a synthetic linker that allows them to be produced as a single protein chain in which the VL and VH regions are paired to form monovalent molecules (known as single-chain Fv (scFv); see, e.g., Bird et al. (1988) Science 242:423–426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879–5883). Such single-chain molecules are also intended to be included within the term "antigen-binding portion" of an antibody. Such antibody fragments are produced using conventional methods known to those skilled in the art and are screened in the same manner as intact antibodies.

[0074] “Kabat nomenclature” or “Kabat nomenclature” is used in this application to refer to a system of numbering amino acid residues that are more variable (i.e., hypervariable) than the rest of the amino acid residues in the variable regions of the heavy and light chains of an antibody (Kabat et al. Ann. NY Acad. Sci., 190:382-93 (1971); Kabat et al. Sequences of Proteins of Immunological Interest, Fifth Edition, US Department of Health and Human Services, NIH Publication No. 91-3242 (1991)).

[0075] The antibody of the present invention, "which specifically binds" to a target antigen, is an antibody that binds the antigen with sufficient affinity such that the antibody can be used as a diagnostic and / or therapeutic agent by targeting a protein or a cell or tissue expressing the antigen, and does not significantly cross-react with other proteins.

[0076] The term "specifically binds to" a particular polypeptide or epitope on a particular target polypeptide can be characterized by an example of a molecule having a KD to the target of at least about 200 nM, or at least about 150 nM, or at least about 100 nM, or at least about 60 nM, or at least about 50 nM, or at least about 40 nM, or at least about 30 nM, or at least about 20 nM, or at least about 10 nM, or at least about 8 nM, or at least about 6 nM, or at least about 4 nM, or at least about 2 nM, or at least about 1 nM or less.

[0077] In one embodiment of the invention, the term "specific binding" refers to binding in which a molecule binds to a particular polypeptide or epitope on a particular polypeptide without substantially binding to any other polypeptide or epitope on the polypeptide.

[0078] In some embodiments of the invention, a monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain that comprises a CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7.

[0079] In some embodiments of the invention, a monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain that comprises a CDR3 with an amino acid sequence selected from the group: SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11.

[0080] In some embodiments of the invention, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain that comprises:

[0081] (i) CDR1 with an amino acid sequence selected from the group: SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3;

[0082] (ii) CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7;

[0083] and

[0084] (iii) CDR3 with an amino acid sequence selected from the group: SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11.

[0085] In some embodiments of the invention, the monoclonal antibody or antigen-binding fragment thereof comprises:

[0086] (i) a light chain variable domain comprising:

[0087] CDR1 with the amino acid sequence SEQ ID NO: 1,

[0088] CDR2 with the amino acid sequence of SEQ ID NO: 4 and

[0089] CDR3 with the amino acid sequence of SEQ ID NO: 8; or

[0090] (ii) a light chain variable domain comprising:

[0091] CDR1 with the amino acid sequence SEQ ID NO: 2,

[0092] CDR2 with the amino acid sequence of SEQ ID NO: 5 and

[0093] CDR3 with the amino acid sequence of SEQ ID NO: 9; or

[0094] (iii) a light chain variable domain comprising:

[0095] CDR1 with the amino acid sequence SEQ ID NO: 1,

[0096] CDR2 with the amino acid sequence of SEQ ID NO: 5 and

[0097] CDR3 with the amino acid sequence of SEQ ID NO: 8; or

[0098] (iv) a light chain variable domain comprising:

[0099] CDR1 with the amino acid sequence of SEQ ID NO: 2,

[0100] CDR2 with the amino acid sequence of SEQ ID NO: 4 and

[0101] CDR3 with the amino acid sequence of SEQ ID NO: 9; or

[0102] (v) light chain variable domain comprising:

[0103] CDR1 with the amino acid sequence SEQ ID NO: 2,

[0104] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0105] CDR3 with the amino acid sequence of SEQ ID NO: 8; or

[0106] (vi) a light chain variable domain comprising:

[0107] CDR1 with the amino acid sequence SEQ ID NO: 1,

[0108] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0109] CDR3 with the amino acid sequence of SEQ ID NO: 9; or

[0110] (vii) a light chain variable domain comprising:

[0111] CDR1 with the amino acid sequence of SEQ ID NO: 3,

[0112] CDR2 with the amino acid sequence of SEQ ID NO: 7 and

[0113] CDR3 with the amino acid sequence of SEQ ID NO: 10; or

[0114] (viii) a light chain variable domain comprising:

[0115] CDR1 with the amino acid sequence of SEQ ID NO: 2,

[0116] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0117] CDR3 with the amino acid sequence of SEQ ID NO: 11; or

[0118] (ix) a light chain variable domain comprising:

[0119] CDR1 with the amino acid sequence of SEQ ID NO: 2,

[0120] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0121] CDR3 with the amino acid sequence of SEQ ID NO: 10; or

[0122] (x) light chain variable domain comprising:

[0123] CDR1 with the amino acid sequence of SEQ ID NO: 2,

[0124] CDR2 with the amino acid sequence of SEQ ID NO: 7 and

[0125] CDR3 with the amino acid sequence SEQ ID NO: 9.

[0126] In some embodiments of the invention, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable domain that comprises a CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, or SEQ ID NO: 17.

[0127] In some embodiments of the invention, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable domain that comprises:

[0128] (i) CDR1 with the amino acid sequence of SEQ ID NO: 12;

[0129] (ii) CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16 or SEQ ID NO: 17;

[0130] and

[0131] (iii) CDR3 with the amino acid sequence of SEQ ID NO: 18.

[0132] In some embodiments of the invention, the monoclonal antibody or antigen-binding fragment thereof comprises:

[0133] (i) a heavy chain variable domain comprising:

[0134] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0135] CDR2 with the amino acid sequence of SEQ ID NO: 13 and

[0136] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0137] (ii) a heavy chain variable domain comprising:

[0138] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0139] CDR2 with the amino acid sequence of SEQ ID NO: 14 and

[0140] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0141] (iii) a heavy chain variable domain comprising:

[0142] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0143] CDR2 with the amino acid sequence of SEQ ID NO: 15 and

[0144] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0145] (iv) a heavy chain variable domain comprising:

[0146] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0147] CDR2 with the amino acid sequence of SEQ ID NO: 16 and

[0148] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0149] (v) heavy chain variable domain comprising:

[0150] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0151] CDR2 with the amino acid sequence of SEQ ID NO: 17 and

[0152] CDR3 with the amino acid sequence SEQ ID NO: 18.

[0153] In some embodiments of the invention, the monoclonal antibody or antigen-binding fragment thereof comprises:

[0154] (a) a light chain variable domain comprising:

[0155] (i) CDR1 with an amino acid sequence selected from the group: SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3;

[0156] (ii) CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7;

[0157] and

[0158] (iii) CDR3 with an amino acid sequence selected from the group: SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11; and

[0159] (b) a heavy chain variable domain comprising:

[0160] (i) CDR1 with the amino acid sequence of SEQ ID NO: 12;

[0161] (ii) CDR2 with an amino acid sequence selected from the group: SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16 or SEQ ID NO: 17;

[0162] and

[0163] (iii) CDR3 with the amino acid sequence of SEQ ID NO: 18.

[0164] In some embodiments of the invention, the monoclonal antibody or antigen-binding fragment thereof comprises:

[0165] (i) (a) a light chain variable domain comprising:

[0166] CDR1 with the amino acid sequence of SEQ ID NO: 1,

[0167] CDR2 with the amino acid sequence of SEQ ID NO: 4 and

[0168] CDR3 with the amino acid sequence of SEQ ID NO: 8; and

[0169] (b) a heavy chain variable domain comprising:

[0170] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0171] CDR2 with the amino acid sequence of SEQ ID NO: 13 and

[0172] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0173] (ii) (a) a light chain variable domain comprising:

[0174] CDR1 with the amino acid sequence of SEQ ID NO: 2,

[0175] CDR2 with the amino acid sequence of SEQ ID NO: 5 and

[0176] CDR3 with the amino acid sequence of SEQ ID NO: 9; and

[0177] (b) a heavy chain variable domain comprising:

[0178] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0179] CDR2 with the amino acid sequence of SEQ ID NO: 13 and

[0180] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0181] (iii) (a) a light chain variable domain comprising:

[0182] CDR1 with the amino acid sequence SEQ ID NO: 1,

[0183] CDR2 with the amino acid sequence of SEQ ID NO: 5 and

[0184] CDR3 with the amino acid sequence of SEQ ID NO: 8; and

[0185] (b) a heavy chain variable domain comprising:

[0186] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0187] CDR2 with the amino acid sequence of SEQ ID NO: 14 and

[0188] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0189] (iv) (a) a light chain variable domain comprising:

[0190] CDR1 with the amino acid sequence of SEQ ID NO: 2,

[0191] CDR2 with the amino acid sequence of SEQ ID NO: 4 and

[0192] CDR3 with the amino acid sequence of SEQ ID NO: 9; and

[0193] (b) a heavy chain variable domain comprising:

[0194] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0195] CDR2 with the amino acid sequence of SEQ ID NO: 14 and

[0196] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0197] (v) (a) a light chain variable domain comprising:

[0198] CDR1 with the amino acid sequence of SEQ ID NO: 2,

[0199] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0200] CDR3 with the amino acid sequence of SEQ ID NO: 8; and

[0201] (b) a heavy chain variable domain comprising:

[0202] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0203] CDR2 with the amino acid sequence of SEQ ID NO: 14 and

[0204] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0205] (vi) (a) a light chain variable domain comprising:

[0206] CDR1 with the amino acid sequence of SEQ ID NO: 2,

[0207] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0208] CDR3 with the amino acid sequence of SEQ ID NO: 8; and

[0209] (b) a heavy chain variable domain comprising:

[0210] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0211] CDR2 with the amino acid sequence of SEQ ID NO: 13 and

[0212] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0213] (vii) (a) a light chain variable domain comprising:

[0214] CDR1 with the amino acid sequence SEQ ID NO: 1,

[0215] CDR2 with the amino acid sequence of SEQ ID NO: 4 and

[0216] CDR3 with the amino acid sequence of SEQ ID NO: 8; and

[0217] (b) a heavy chain variable domain comprising:

[0218] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0219] CDR2 with the amino acid sequence of SEQ ID NO: 15 and

[0220] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0221] (viii) (a) a light chain variable domain comprising:

[0222] CDR1 with the amino acid sequence SEQ ID NO: 2,

[0223] CDR2 with the amino acid sequence of SEQ ID NO: 4 and

[0224] CDR3 with the amino acid sequence of SEQ ID NO: 9; and

[0225] (b) a heavy chain variable domain comprising:

[0226] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0227] CDR2 with the amino acid sequence of SEQ ID NO: 15 and

[0228] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0229] (ix) (a) a light chain variable domain comprising:

[0230] CDR1 with the amino acid sequence SEQ ID NO: 1,

[0231] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0232] CDR3 with the amino acid sequence of SEQ ID NO: 9; and

[0233] (b) a heavy chain variable domain comprising:

[0234] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0235] CDR2 with the amino acid sequence of SEQ ID NO: 15 and

[0236] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0237] (x) (a) a light chain variable domain comprising:

[0238] CDR1 with the amino acid sequence SEQ ID NO: 2,

[0239] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0240] CDR3 with the amino acid sequence of SEQ ID NO: 11; and

[0241] (b) a heavy chain variable domain comprising:

[0242] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0243] CDR2 with the amino acid sequence of SEQ ID NO: 15 and

[0244] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0245] (xi) (a) a light chain variable domain comprising:

[0246] CDR1 with the amino acid sequence SEQ ID NO: 1,

[0247] CDR2 with the amino acid sequence of SEQ ID NO: 5 and

[0248] CDR3 with the amino acid sequence of SEQ ID NO: 8; and

[0249] (b) a heavy chain variable domain comprising:

[0250] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0251] CDR2 with the amino acid sequence of SEQ ID NO: 16 and

[0252] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0253] (xii) (a) a light chain variable domain comprising:

[0254] CDR1 with the amino acid sequence of SEQ ID NO: 1,

[0255] CDR2 with the amino acid sequence of SEQ ID NO: 4 and

[0256] CDR3 with the amino acid sequence of SEQ ID NO: 8; and

[0257] (b) a heavy chain variable domain comprising:

[0258] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0259] CDR2 with the amino acid sequence of SEQ ID NO: 16 and

[0260] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0261] (xiii) (a) a light chain variable domain comprising:

[0262] CDR1 with the amino acid sequence of SEQ ID NO: 3,

[0263] CDR2 with the amino acid sequence of SEQ ID NO: 7 and

[0264] CDR3 with the amino acid sequence of SEQ ID NO: 10; and

[0265] (b) a heavy chain variable domain comprising:

[0266] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0267] CDR2 with the amino acid sequence of SEQ ID NO: 17 and

[0268] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0269] (xiv) (a) a light chain variable domain comprising:

[0270] CDR1 with the amino acid sequence of SEQ ID NO: 2,

[0271] CDR2 with the amino acid sequence of SEQ ID NO: 5 and

[0272] CDR3 with the amino acid sequence of SEQ ID NO: 9; and

[0273] (b) a heavy chain variable domain comprising:

[0274] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0275] CDR2 with the amino acid sequence of SEQ ID NO: 16 and

[0276] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0277] (xv) (a) a light chain variable domain comprising:

[0278] CDR1 with the amino acid sequence SEQ ID NO: 2,

[0279] CDR2 with the amino acid sequence of SEQ ID NO: 4 and

[0280] CDR3 with the amino acid sequence of SEQ ID NO: 9; and

[0281] (b) a heavy chain variable domain comprising:

[0282] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0283] CDR2 with the amino acid sequence of SEQ ID NO: 16 and

[0284] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0285] (xvi) (a) a light chain variable domain comprising:

[0286] CDR1 with the amino acid sequence SEQ ID NO: 1,

[0287] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0288] CDR3 with the amino acid sequence of SEQ ID NO: 9; and

[0289] (b) a heavy chain variable domain comprising:

[0290] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0291] CDR2 with the amino acid sequence of SEQ ID NO: 16 and

[0292] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0293] (xvii) (a) a light chain variable domain comprising:

[0294] CDR1 with the amino acid sequence of SEQ ID NO: 2,

[0295] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0296] CDR3 with the amino acid sequence of SEQ ID NO: 11; and

[0297] (b) a heavy chain variable domain comprising:

[0298] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0299] CDR2 with the amino acid sequence of SEQ ID NO: 16 and

[0300] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0301] (xviii) (a) a light chain variable domain comprising:

[0302] CDR1 with the amino acid sequence SEQ ID NO: 2,

[0303] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0304] CDR3 with the amino acid sequence of SEQ ID NO: 8; and

[0305] (b) a heavy chain variable domain comprising:

[0306] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0307] CDR2 with the amino acid sequence of SEQ ID NO: 16 and

[0308] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0309] (ixx) (a) a light chain variable domain comprising:

[0310] CDR1 with the amino acid sequence of SEQ ID NO: 2,

[0311] CDR2 with the amino acid sequence of SEQ ID NO: 6 and

[0312] CDR3 with the amino acid sequence of SEQ ID NO: 10; and

[0313] (b) a heavy chain variable domain comprising:

[0314] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0315] CDR2 with the amino acid sequence of SEQ ID NO: 17 and

[0316] CDR3 with the amino acid sequence of SEQ ID NO: 18; or

[0317] (xx) (a) a light chain variable domain comprising:

[0318] CDR1 with the amino acid sequence SEQ ID NO: 2,

[0319] CDR2 with the amino acid sequence of SEQ ID NO: 7 and

[0320] CDR3 with the amino acid sequence of SEQ ID NO: 9; and

[0321] (b) a heavy chain variable domain comprising:

[0322] CDR1 with the amino acid sequence of SEQ ID NO: 12,

[0323] CDR2 with the amino acid sequence of SEQ ID NO: 17 and

[0324] CDR3 with the amino acid sequence SEQ ID NO: 18.

[0325] In some embodiments of the invention, the monoclonal antibody or antigen-binding fragment thereof comprises a light chain variable domain that comprises an amino acid sequence selected from the group: SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28.

[0326] In some embodiments of the invention, the monoclonal antibody or antigen-binding fragment thereof comprises a heavy chain variable domain that comprises an amino acid sequence selected from the group: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, or SEQ ID NO: 34.

[0327] In some embodiments of the invention, the monoclonal antibody or antigen-binding fragment thereof comprises:

[0328] (a) a light chain variable domain that comprises an amino acid sequence selected from the group: SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27 or SEQ ID NO: 28; and

[0329] (b) a heavy chain variable domain that comprises an amino acid sequence selected from the group: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33 or SEQ ID NO: 34.

[0330] In some embodiments of the invention, the monoclonal antibody or antigen-binding fragment thereof comprises:

[0331] (i) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 19 and

[0332] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 29; or

[0333] (ii) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 20 and

[0334] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 29; or

[0335] (iii) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 21 and

[0336] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 30; or

[0337] (iv) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 22 and

[0338] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 30; or

[0339] (v) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 23 and

[0340] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 30; or

[0341] (vi) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 23 and

[0342] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 31; or

[0343] (vii) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 19 and

[0344] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 32; or

[0345] (viii) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 22 and

[0346] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 32; or

[0347] (ix) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 24 and

[0348] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 32; or

[0349] (x) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 26 and

[0350] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 32; or

[0351] (xi) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 21 and

[0352] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33; or

[0353] (xii) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 19 and

[0354] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33; or

[0355] (xiii) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 25 and

[0356] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 34; or

[0357] (xiv) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 20 and

[0358] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33; or

[0359] (xv) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 22 and

[0360] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33; or

[0361] (xvi) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 24 and

[0362] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33; or

[0363] (xvii) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 26 and

[0364] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33; or

[0365] (xviii) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 23 and

[0366] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33; or

[0367] (ixx) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 27 and

[0368] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 34; or

[0369] (xx) (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 28 and

[0370] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 34.

[0371] In some embodiments of the invention, a monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of a human T cell receptor is a full-length IgG antibody.

[0372] In some embodiments of the invention, a monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of a human T cell receptor is a full-length IgG antibody that is of the human IgG1, IgG2, IgG3 or IgG4 isotype.

[0373] In some embodiments of the invention, a monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of a human T cell receptor is a full-length IgG antibody that belongs to the human IgG1 isotype.

[0374] In some embodiments of the invention, the monoclonal antibody comprises mutations S239D and I332E in the Fc region according to the amino acid numbering of EU antibodies in the CH2 region (Edelman GM et al., Proc. Natl. Acad. Sci. USA 63, 1969, pp. 78-85; Kabat EA et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD, 1991).

[0375] In some embodiments of the invention, the monoclonal antibody comprises mutations G236A, S239D and I332E according to the amino acid numbering of EU antibodies in the CH2 region.

[0376] In some embodiments, the monoclonal antibody comprises a deletion of 446G and 447K according to the amino acid numbering of EU antibodies in the CH3 region.

[0377] In some embodiments, the monoclonal antibody comprises a light chain comprising an amino acid sequence selected from the group: SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, or SEQ ID NO: 44.

[0378] In some embodiments, the monoclonal antibody comprises a heavy chain comprising an amino acid sequence selected from the group: SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, or SEQ ID NO: 52.

[0379] In some embodiments, the monoclonal antibody comprises:

[0380] (i) (a) a light chain comprising an amino acid sequence selected from the group: SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43 or SEQ ID NO: 44, and

[0381] (b) a heavy chain comprising an amino acid sequence selected from the group: SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52.

[0382] In some embodiments, the monoclonal antibody comprises:

[0383] (i) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 35, and

[0384] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 45; or

[0385] (ii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 36, and

[0386] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 46; or

[0387] (iii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 37, and

[0388] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 47; or

[0389] (iv) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 38, and

[0390] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 47; or

[0391] (v) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 39, and

[0392] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 48; or

[0393] (vi) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 39, and

[0394] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 49; or

[0395] (vii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 35, and

[0396] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50; or

[0397] (viii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 38, and

[0398] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50; or

[0399] (ix) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 40, and

[0400] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50; or

[0401] (x) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 42, and

[0402] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50; or

[0403] (xi) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 37, and

[0404] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or

[0405] (xii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 35, and

[0406] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or

[0407] (xiii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 41, and

[0408] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 52; or

[0409] (xiv) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 36, and

[0410] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or

[0411] (xv) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 38, and

[0412] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or

[0413] (xvi) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 40, and

[0414] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or

[0415] (xvii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 42, and

[0416] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or

[0417] (xviii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 39, and

[0418] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or

[0419] (ixx) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 43, and

[0420] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 52; or

[0421] (xx) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 44, and

[0422] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 52.

[0423] In some embodiments, a monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of a human T cell receptor is an antibody selected from the group: 04-002, 04-004, 04-009, 04-013, 04-016, 04-024, 04-042, 04-045, 04-046, 04-047, 03-008, 03-010, 03-015, 03-023, 03-024, 03-026, 03-027, 03-028, 03-036 or 03-038.

[0424] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 04-002.

[0425] Antibody 04-002 includes:

[0426] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 35; and

[0427] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 45.

[0428] Antibody 04-002 includes:

[0429] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 19;

[0430] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 29.

[0431] Antibody 04-002 includes:

[0432] (a) a light chain variable domain comprising:

[0433] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 1,

[0434] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 4,

[0435] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 8, and

[0436] (b) a heavy chain variable domain comprising:

[0437] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0438] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 13,

[0439] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0440] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 04-004.

[0441] Antibody 04-004 includes:

[0442] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 36; and

[0443] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 46.

[0444] Antibody 04-004 includes:

[0445] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 20;

[0446] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 29.

[0447] Antibody 04-004 includes:

[0448] (a) a light chain variable domain comprising:

[0449] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0450] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 5,

[0451] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 9, and

[0452] (b) a heavy chain variable domain comprising:

[0453] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0454] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 13,

[0455] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0456] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 04-009.

[0457] Antibody 04-009 includes:

[0458] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 37; and

[0459] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 47.

[0460] Antibody 04-009 includes:

[0461] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 21;

[0462] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 30.

[0463] Antibody 04-009 includes:

[0464] (a) a light chain variable domain comprising:

[0465] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 1,

[0466] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 5,

[0467] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 8, and

[0468] (b) a heavy chain variable domain comprising:

[0469] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0470] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 14,

[0471] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0472] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 04-013.

[0473] Antibody 04-013 includes:

[0474] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 38; and

[0475] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 47.

[0476] Antibody 04-013 includes:

[0477] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 22;

[0478] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 30.

[0479] Antibody 04-013 includes:

[0480] (a) a light chain variable domain comprising:

[0481] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0482] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 4,

[0483] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 9, and

[0484] (b) a heavy chain variable domain comprising:

[0485] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0486] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 14,

[0487] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0488] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 04-016.

[0489] Antibody 04-016 includes:

[0490] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 39; and

[0491] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 48.

[0492] Antibody 04-016 includes:

[0493] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 23;

[0494] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 30.

[0495] Antibody 04-016 includes:

[0496] (a) a light chain variable domain comprising:

[0497] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0498] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 6,

[0499] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 8, and

[0500] (b) a heavy chain variable domain comprising:

[0501] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0502] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 14,

[0503] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0504] In some embodiments of the invention, a monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 04-024.

[0505] Antibody 04-024 includes:

[0506] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 39; and

[0507] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 49.

[0508] Antibody 04-024 includes:

[0509] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 23;

[0510] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 31.

[0511] Antibody 04-024 includes:

[0512] (a) a light chain variable domain comprising:

[0513] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0514] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 6,

[0515] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 8, and

[0516] (b) a heavy chain variable domain comprising:

[0517] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0518] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 13,

[0519] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0520] In some embodiments of the invention, a monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is the antibody 04-042.

[0521] Antibody 04-042 includes:

[0522] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 35; and

[0523] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50.

[0524] Antibody 04-042 includes:

[0525] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 19;

[0526] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 32.

[0527] Antibody 04-042 includes:

[0528] (a) a light chain variable domain comprising:

[0529] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 1,

[0530] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 4,

[0531] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 8, and

[0532] (b) a heavy chain variable domain comprising:

[0533] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0534] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 15,

[0535] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0536] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is the antibody 04-045.

[0537] Antibody 04-045 includes:

[0538] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 38; and

[0539] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50.

[0540] Antibody 04-045 includes:

[0541] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 22;

[0542] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 32.

[0543] Antibody 04-045 includes:

[0544] (a) a light chain variable domain comprising:

[0545] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0546] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 4,

[0547] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 9, and

[0548] (b) a heavy chain variable domain comprising:

[0549] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0550] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 15,

[0551] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0552] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is the antibody 04-046.

[0553] Antibody 04-046 includes:

[0554] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 40; and

[0555] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50.

[0556] Antibody 04-046 includes:

[0557] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 24;

[0558] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 32.

[0559] Antibody 04-046 includes:

[0560] (a) a light chain variable domain comprising:

[0561] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 1,

[0562] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 6,

[0563] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 9, and

[0564] (b) a heavy chain variable domain comprising:

[0565] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0566] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 15,

[0567] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0568] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 04-047.

[0569] Antibody 04-047 includes:

[0570] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 42; and

[0571] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50.

[0572] Antibody 04-047 includes:

[0573] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 26;

[0574] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 32.

[0575] Antibody 04-047 includes:

[0576] (a) a light chain variable domain comprising:

[0577] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0578] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 6,

[0579] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 11, and

[0580] (b) a heavy chain variable domain comprising:

[0581] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0582] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 15,

[0583] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0584] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 03-008.

[0585] Antibody 03-008 includes:

[0586] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 37; and

[0587] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51.

[0588] Antibody 03-008 includes:

[0589] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 21;

[0590] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33.

[0591] Antibody 03-008 includes:

[0592] (a) a light chain variable domain comprising:

[0593] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 1,

[0594] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 5,

[0595] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 8, and

[0596] (b) a heavy chain variable domain comprising:

[0597] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0598] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 16,

[0599] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0600] In some embodiments of the invention, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is the antibody 03-010.

[0601] Antibody 03-010 includes:

[0602] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 35; and

[0603] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51.

[0604] Antibody 03-010 includes:

[0605] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 19;

[0606] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33.

[0607] Antibody 03-010 includes:

[0608] (a) a light chain variable domain comprising:

[0609] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 1,

[0610] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 4,

[0611] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 8, and

[0612] (b) a heavy chain variable domain comprising:

[0613] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0614] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 16,

[0615] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0616] In some embodiments of the invention, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 03-015.

[0617] Antibody 03-015 includes:

[0618] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 41; and

[0619] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 52.

[0620] Antibody 03-015 includes:

[0621] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 25;

[0622] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 34.

[0623] Antibody 03-015 includes:

[0624] (a) a light chain variable domain comprising:

[0625] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 3,

[0626] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 7,

[0627] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 10, and

[0628] (b) a heavy chain variable domain comprising:

[0629] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0630] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 17,

[0631] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0632] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 03-023.

[0633] Antibody 03-023 includes:

[0634] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 36; and

[0635] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51.

[0636] Antibody 03-023 includes:

[0637] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 20;

[0638] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33.

[0639] Antibody 03-023 includes:

[0640] (a) a light chain variable domain comprising:

[0641] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0642] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 5,

[0643] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 9, and

[0644] (b) a heavy chain variable domain comprising:

[0645] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0646] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 16,

[0647] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0648] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 03-024.

[0649] Antibody 03-024 includes:

[0650] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 38; and

[0651] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51.

[0652] Antibody 03-024 includes:

[0653] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 22;

[0654] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33.

[0655] Antibody 03-024 includes:

[0656] (a) a light chain variable domain comprising:

[0657] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0658] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 4,

[0659] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 9, and

[0660] (b) a heavy chain variable domain comprising:

[0661] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0662] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 16,

[0663] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0664] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 03-026.

[0665] Antibody 03-026 includes:

[0666] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 40; and

[0667] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51.

[0668] Antibody 03-026 includes:

[0669] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 24;

[0670] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33.

[0671] Antibody 03-026 includes:

[0672] (a) a light chain variable domain comprising:

[0673] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 1,

[0674] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 6,

[0675] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 9, and

[0676] (b) a heavy chain variable domain comprising:

[0677] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0678] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 16,

[0679] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0680] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 03-027.

[0681] Antibody 03-027 includes:

[0682] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 42; and

[0683] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51.

[0684] Antibody 03-027 includes:

[0685] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 26;

[0686] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33.

[0687] Antibody 03-027 includes:

[0688] (a) a light chain variable domain comprising:

[0689] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0690] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 6,

[0691] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 11, and

[0692] (b) a heavy chain variable domain comprising:

[0693] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0694] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 16,

[0695] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0696] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 03-028.

[0697] Antibody 03-028 includes:

[0698] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 39; and

[0699] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51.

[0700] Antibody 03-028 includes:

[0701] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 23;

[0702] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 33.

[0703] Antibody 03-028 includes:

[0704] (a) a light chain variable domain comprising:

[0705] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0706] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 6,

[0707] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 8, and

[0708] (b) a heavy chain variable domain comprising:

[0709] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0710] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 16,

[0711] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0712] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 03-036.

[0713] Antibody 03-036 includes:

[0714] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 43; and

[0715] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 52.

[0716] Antibody 03-036 includes:

[0717] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 27;

[0718] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 34.

[0719] Antibody 03-036 includes:

[0720] (a) a light chain variable domain comprising:

[0721] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0722] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 6,

[0723] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 10, and

[0724] (b) a heavy chain variable domain comprising:

[0725] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0726] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 17,

[0727] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0728] In some embodiments, the monoclonal antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor is antibody 03-038.

[0729] Antibody 03-038 includes:

[0730] (a) a light chain comprising the amino acid sequence of SEQ ID NO: 44; and

[0731] (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 52.

[0732] Antibody 03-038 includes:

[0733] (a) a light chain variable domain that comprises the amino acid sequence of SEQ ID NO: 28;

[0734] (b) a heavy chain variable domain that comprises the amino acid sequence of SEQ ID NO: 34.

[0735] Antibody 03-038 includes:

[0736] (a) a light chain variable domain comprising:

[0737] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 2,

[0738] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 7,

[0739] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 9, and

[0740] (b) a heavy chain variable domain comprising:

[0741] (i) CDR1 (Kabat) with the amino acid sequence of SEQ ID NO: 12,

[0742] (ii) CDR2 (Kabat) with the amino acid sequence of SEQ ID NO: 17,

[0743] (iii) CDR3 (Kabat) with the amino acid sequence of SEQ ID NO: 18.

[0744] The hypervariable regions of the variable domains of the light and heavy chains (LCDR1, 2, 3 and HCDR1, 2, 3) of all the above-mentioned antibodies are indicated in accordance with the Kabat nomenclature. It is obvious to those skilled in the art that the hypervariable regions of the variable domains of the light and heavy chains (LCDR1, 2, 3 and HCDR1, 2, 3) can also be represented in accordance with other well-known nomenclature, for example, IMGT, Chothia or AbM. Thus, all the above-mentioned antibodies, which are characterized by the hypervariable regions of the variable domains of the light and heavy chains (LCDR1, 2, 3 and HCDR1, 2, 3) in accordance with the IMGT, Chothia or AbM nomenclature, are also the subject of the present invention.

[0745] Antibodies of the invention that specifically bind to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor exhibit high binding affinity parameters for the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor. Furthermore, the antibodies of the invention are humanized, stable in human serum and heat-stable, and also exhibit antibody-dependent cell-mediated cytotoxicity (ADCC).

[0746] Nucleic acid molecule

[0747] In one aspect, the present invention relates to a nucleic acid that encodes any of the above-mentioned antibodies or antigen-binding fragments thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor.

[0748] In any of the embodiments of the invention, the nucleic acid molecules may be isolated.

[0749] The terms "nucleic acid," "nucleic sequence" or "nucleic acid sequence," "polynucleotide," "oligonucleotide," "polynucleotide sequence," and "nucleotide sequence," which are used interchangeably in this specification, mean a distinct sequence of nucleotides, whether modified or not modified, defining a fragment or section of nucleic acid, whether or not containing non-natural nucleotides, and being either double-stranded DNA or RNA, or single-stranded DNA or RNA, or transcription products of said DNA.

[0750] The term "nucleotide sequence" encompasses its complement unless otherwise specified. Thus, a nucleic acid having a certain sequence should be understood as encompassing its complementary strand with its complementary sequence.

[0751] An "isolated" nucleic acid molecule is a nucleic acid molecule that has been identified and separated from at least one contaminating nucleic acid molecule. An isolated nucleic acid molecule is distinct from the form or composition in which it is naturally found. Thus, an isolated nucleic acid molecule is distinct from a nucleic acid molecule naturally occurring in cells.

[0752] In one aspect, the present invention relates to a nucleic acid molecule comprising a nucleotide sequence that encodes an amino acid sequence selected from SEQ ID NO: 53-86. The nucleic acid molecule may also comprise any combination of said nucleotide sequences.

[0753] It will be apparent to those skilled in the art that the amino acid sequence of the light or heavy chain of the antibody of the invention or fragments thereof (VH, VL, CDR, etc.) can be encoded by a wide range of different DNA sequences, given the degeneracy of the genetic code. Those skilled in the art are well-versed in obtaining such alternative DNA sequences encoding the same amino acid sequences. Such variant DNA sequences are within the scope of the present invention.

[0754] In some embodiments of the invention, the nucleic acid is DNA.

[0755] The nucleic acid molecule of the present invention can be isolated from any source that produces a monoclonal antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the human T-cell receptor beta chain variable domain. In certain embodiments, the nucleic acid molecule of the present invention can be synthesized by chemical synthesis rather than isolated.

[0756] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibodies 04-002, 04-042, 03-010, and includes the nucleotide sequence of SEQ ID NO: 53.

[0757] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibodies 04-004, 03-023, and includes the nucleotide sequence of SEQ ID NO: 54.

[0758] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibodies 04-009, 03-008, and includes the nucleotide sequence of SEQ ID NO: 55.

[0759] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibodies 04-013, 04-045, 03-024, and includes the nucleotide sequence of SEQ ID NO: 56.

[0760] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibodies 04-016, 04-024, 03-028, and includes the nucleotide sequence of SEQ ID NO: 57.

[0761] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibodies 04-046, 03-026, and includes the nucleotide sequence of SEQ ID NO: 58.

[0762] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 03-015, and includes the nucleotide sequence of SEQ ID NO: 59.

[0763] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibodies 03-027, 04-047, and includes the nucleotide sequence of SEQ ID NO: 60.

[0764] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 03-036, and includes the nucleotide sequence of SEQ ID NO: 61.

[0765] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain variable domain of antibody 03-038, and includes the nucleotide sequence of SEQ ID NO: 62.

[0766] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibodies 04-002, 04-004, and includes the nucleotide sequence of SEQ ID NO: 63.

[0767] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibodies 04-009, 04-013, 04-016, and includes the nucleotide sequence of SEQ ID NO: 64.

[0768] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibody 04-024, and includes the nucleotide sequence of SEQ ID NO: 65.

[0769] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibodies 04-042, 04-045, 04-046, 04-047, and includes the nucleotide sequence of SEQ ID NO: 66.

[0770] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibodies 03-008, 03-010, 03-023, 03-024, 03-026, 03-027, 03-028, and includes the nucleotide sequence of SEQ ID NO: 67.

[0771] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain variable domain of antibodies 03-015, 03-036, 03-038, and includes the nucleotide sequence of SEQ ID NO: 68.

[0772] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibodies 04-002, 04-042, 03-010, and includes the nucleotide sequence of SEQ ID NO: 69.

[0773] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibodies 04-004, 03-023, and includes the nucleotide sequence of SEQ ID NO: 70.

[0774] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibodies 04-009, 03-008, and includes the nucleotide sequence of SEQ ID NO: 71.

[0775] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibodies 04-013, 04-045, 03-024, and includes the nucleotide sequence of SEQ ID NO: 72.

[0776] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibodies 04-016, 04-024, 03-028, and includes the nucleotide sequence of SEQ ID NO: 73.

[0777] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibodies 04-046, 03-026, and includes the nucleotide sequence of SEQ ID NO: 74.

[0778] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 03-015 and includes the nucleotide sequence of SEQ ID NO: 75.

[0779] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibodies 03-027, 04-047, and includes the nucleotide sequence of SEQ ID NO: 76.

[0780] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 03-036, and includes the nucleotide sequence of SEQ ID NO: 77.

[0781] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the light chain of antibody 03-038, and includes the nucleotide sequence of SEQ ID NO: 78.

[0782] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 04-002 and includes the nucleotide sequence of SEQ ID NO: 79.

[0783] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 04-004 and includes the nucleotide sequence of SEQ ID NO: 80.

[0784] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibodies 04-009, 04-013, and includes the nucleotide sequence of SEQ ID NO: 81.

[0785] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 04-016, and includes the nucleotide sequence of SEQ ID NO: 82.

[0786] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibody 04-024 and includes the nucleotide sequence of SEQ ID NO: 83.

[0787] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibodies 04-042, 04-045, 04-046, 04-047, and includes the nucleotide sequence of SEQ ID NO: 84.

[0788] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibodies 03-008, 03-010, 03-023, 03-024, 03-026, 03-027, 03-028, and includes the nucleotide sequence of SEQ ID NO: 85.

[0789] In some embodiments of the invention, the nucleic acid is a nucleic acid that encodes the amino acid sequence of the heavy chain of antibodies 03-015, 03-036, 03-038, and includes the nucleotide sequence of SEQ ID NO: 86.

[0790] The nucleic acid molecules can be used to express a recombinant monoclonal antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor.

[0791] Vector

[0792] In one aspect, the present invention relates to an expression vector comprising any of the above nucleic acid molecules that encode the corresponding amino acid sequences of an antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor, or a portion thereof (e.g., the sequences of the binding domains of the heavy chain and / or light chain). The present invention relates to a vector suitable for expressing any of the nucleotide sequences described herein.

[0793] The term "vector" as used herein means a nucleic acid molecule capable of transporting another nucleic acid to which it is linked.

[0794] As used herein, the term "expression" is defined as the transcription and / or translation of a particular nucleotide sequence driven by its promoter.

[0795] In some embodiments of the invention, the vector is a plasmid, i.e., a circular double-stranded piece of DNA into which additional DNA segments can be inserted.

[0796] In some embodiments of the invention, the vector is a viral (expression) vector in which additional DNA segments can be inserted into the viral genome.

[0797] In some embodiments, vectors are capable of autonomous replication in the host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal vectors). In other embodiments, vectors (e.g., non-episomal vectors) can be integrated into the host cell genome upon introduction into the host cell and thus replicate along with the host genome. Moreover, some vectors are capable of directing the expression of genes to which they are operably linked. Such vectors are referred to herein as "recombinant expression vectors" (or simply "expression vectors" ("expression vector" or "expression vector")).

[0798] In some embodiments, expression vectors include plasmids, retroviruses, adenoviruses, adeno-associated viruses (AAV), plant viruses such as cauliflower mosaic virus, tobacco mosaic virus, cosmids, YAC, and the like. DNA molecules can be inserted into the vector such that transcription and translation control sequences in the vector perform the intended function of regulating DNA transcription and translation. The expression vector and expression control sequences can be selected to be compatible with the expression host cell used.

[0799] In one embodiment of the invention, DNA molecules encoding part or all of the heavy and light chain sequences may be introduced into separate vectors.

[0800] In one embodiment of the invention, any combination of the above DNA molecules is introduced into the same expression vector.

[0801] In one embodiment of the invention, DNA molecules can be introduced into an expression vector by standard methods (e.g., by ligating complementary restriction sites on the antibody gene fragment and the vector, or by blunt-end ligation if restriction sites are absent).

[0802] In some embodiments, a suitable vector includes restriction sites such that any VH or VL sequence can be readily incorporated and expressed as described above. The recombinant expression vector can also encode a signal peptide that facilitates production of the antibody chain by the host cell. The antibody chain gene can be cloned into the vector such that the signal peptide is linked to the reading frame of the amino terminus of the immunoglobulin chain. The signal peptide can be an immunoglobulin signal peptide or a heterologous signal peptide (i.e., a signal peptide of a non-immunoglobulin protein).

[0803] In some embodiments, the vector may include an expression control sequence. The term "expression control sequence" as used herein refers to polynucleotide sequences that are necessary to affect the expression and processing of the coding sequences into which they are inserted. Those skilled in the art will appreciate that the design of an expression vector, including the choice of expression control sequences, may depend on factors such as the choice of host cell type for transformation, the desired level of antibody expression, etc. Expression control sequences include appropriate transcription initiation, termination, promoter, and enhancer sequences; efficient RNA processing signals such as splicing and polyadenylation signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (i.e.,Kozak consensus sequence); sequences that enhance protein stability; and, optionally, sequences that enhance protein secretion. The nature of such expression control sequences varies depending on the host organism; in prokaryotes, such expression control sequences typically include a promoter, a ribosome binding site, and transcription termination sequences; in eukaryotes, such expression control sequences typically include promoters and transcription termination sequences.Preferred expression control sequences for the mammalian expression host cell include viral elements that provide high-level protein expression in mammalian cells, such as promoters and / or enhancers derived from the retroviral long terminal repeat (LTR), cytomegalovirus (CMV) (e.g., the CMV enhancer / promoter), simian virus 40 (SV40) (e.g., the SV40 promoter / enhancer), adenovirus (e.g., the adenovirus large late promoter (AdMLP)), polyoma virus, and strong mammalian promoters such as the TTR promoter, the native immunoglobulin promoter, or the actin promoter. The expression control sequences include, at a minimum, all components whose presence is essential for expression and processing.

[0804] In some embodiments, in addition to antibody chain genes and expression control sequences, the recombinant expression vectors of the invention may carry additional sequences, such as sequences that regulate vector replication in host cells (e.g., origins of replication) and selectable marker genes. A selectable marker gene facilitates selection of host cells into which the vector has been introduced.

[0805] Host cell

[0806] In one aspect, the present invention relates to a method for producing a host cell for producing any of the above-mentioned antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor, and comprises transforming the cell with the above-mentioned vector.

[0807] In one aspect, the present invention relates to a host cell for producing any of the above-mentioned antibodies or antigen-binding fragments thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T cell receptor, which comprises any of the above-mentioned nucleic acids.

[0808] The term "host cell," as used herein, means a cell into which a recombinant expression vector has been introduced. The present invention relates to host cells that may comprise, for example, a vector according to the present invention described above. The present invention also relates to host cells that comprise, for example, a nucleotide sequence encoding a heavy chain or its antigen-binding portions, a nucleotide sequence encoding a light chain or its antigen-binding portions, or both. It should be understood that "host cell" refers not only to the specific cell claimed, but also to the progeny of such a cell. Because modifications may occur in subsequent generations due to mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but such cells are still included within the scope of the term "host cell" as used herein.

[0809] Nucleic acid molecules encoding a monoclonal antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the human T-cell receptor beta chain variable domain, according to the invention, and vectors containing these nucleic acid molecules can be used to transfect mammalian cells, plant cells, bacterial cells, or yeast cells. Transfection can occur by any known method for introducing polynucleotides into a host cell. Methods for introducing heterologous polynucleotides into mammalian cells are well known in the art and include dextran-mediated transfection, transfection with a complex of nucleic acid and a positively charged polymer, transfection by electroporation, transfection with a precipitate of nucleic acid and calcium phosphate, polybrene-mediated transfection, protoplast fusion, transfection with liposome-encapsulated polynucleotides, and direct microinjection of DNA into nuclei.In addition, nucleic acid molecules can be introduced into mammalian cells by viral (expression) vectors.

[0810] Mammalian cell lines used as transformation hosts are well known in the art and include a variety of immortalized cell lines available. These include, for example, Chinese hamster ovary (CHO) cells, NS0 cells, SP2 cells, HEK-293T cells, 293 Freestyle cells (Invitrogen), NIH-3T3 cells, HeLa cells, hamster kidney (BHK) cells, African green monkey kidney (COS) cells, human hepatocellular carcinoma cells (e.g., Hep G2), A549, SK-HEP1, HUH7, Hep-RG cells, and a number of other cell lines. Cell lines are selected by determining which cell lines have high expression levels and provide the desired characteristics of the produced protein. Other cell lines that can be used are insect cell lines such as Sf9 or Sf21 cells.When recombinant expression vectors encoding a monoclonal antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the human T-cell receptor beta chain variable domain are introduced into mammalian host cells, the antibodies or fragments thereof are produced by culturing the host cells for a time sufficient to express the antibodies or fragments thereof in the host cells or, preferably, by isolating the antibodies or fragments thereof into the growth medium in which the host cells are grown. The monoclonal antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the human T-cell receptor beta chain variable domain can be isolated from the growth medium using standard protein purification methods. Plant host cells, for example, include Nicotiana, Arabidopsis, duckweed, corn, wheat, potato, etc.Bacterial host cells include Escherichia and Streptomyces species. Yeast host cells include Schizosaccharomyces pombe, Saccharomyces cerevisiae, and Pichia pastoris.

[0811] Furthermore, the production level of a monoclonal antibody or its antigen-binding fragment that specifically binds to the TRBV5-1 segment of the human T-cell receptor beta chain variable domain can be enhanced from a producing cell line using a number of known methods. For example, the glutamine synthetase gene expression system (GS system) is widely used for enhancing expression under certain conditions.

[0812] It is likely that a monoclonal antibody or an antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor of different cell lines will differ from each other in the glycosylation profile. However, a monoclonal antibody or an antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor, encoded by the nucleic acid molecules described herein or comprising the amino acid sequences set forth herein, is part of the present invention, regardless of the glycosylation state of the binding molecules and, in general, regardless of the presence or absence of post-translational modifications.

[0813] The above host cell does not refer to the host cell obtained using human embryos.

[0814] The above host cell does not refer to a host cell obtained by modifying the genetic integrity of human germline cells.

[0815] Method for producing antibodies

[0816] In one aspect, the present invention relates to a method for producing an antibody or an antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor, which comprises culturing the above-described host cell in a culture medium under conditions sufficient to produce said antibody or fragment thereof, followed by isolating and purifying the obtained antibody or fragment thereof.

[0817] Pharmaceutical compositions

[0818] Another aspect of the invention is a pharmaceutical composition comprising as an active ingredient (or as the only active ingredient) a monoclonal antibody of the present invention or an antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor.

[0819] In one aspect, the present invention relates to a pharmaceutical composition that comprises any of the above-mentioned antibodies or antigen-binding fragments thereof in combination with one or more pharmaceutically acceptable excipients.

[0820] In one aspect, the present invention relates to a pharmaceutical composition for the treatment or prevention of a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor, which comprises any of the above-mentioned antibodies or antigen-binding fragments thereof in combination with one or more pharmaceutically acceptable excipients.

[0821] In one aspect, the present invention relates to a pharmaceutical composition for the treatment or prevention of a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor, which comprises any of the above-mentioned antibodies or antigen-binding fragments thereof in a therapeutically effective amount in combination with one or more pharmaceutically acceptable excipients.

[0822] “Pharmaceutical composition” means a composition comprising an antibody according to the invention and at least one component selected from the group consisting of pharmaceutically acceptable and pharmacologically compatible fillers, solvents, diluents, carriers, auxiliary, distributing and receiving means, delivery means.

[0823] The term "pharmaceutically acceptable" means one or more compatible liquid or solid components that are suitable for administration to a mammal, preferably a human.

[0824] The term "excipient" or "auxiliary substance" is used herein to describe any component other than the antibody of the present invention. These are substances of inorganic or organic origin used in the manufacturing process of medicinal products to impart the necessary physicochemical properties.

[0825] In some embodiments, the compositions are for ameliorating, preventing, or treating diseases or disorders that may be mediated by the TRBV5-1 segment of the human T cell receptor beta chain variable domain.

[0826] The term "disease or disorder mediated by the TRBV5-1 segment of the human T-cell receptor beta chain variable domain" means all diseases or disorders that are either directly or indirectly related to the TRBV5-1 segment of the human T-cell receptor beta chain variable domain, including the etiology, development, progression, persistence, or pathology of the disease or disorder.

[0827] "Treat," "treatment," and "therapy" refer to a method of alleviating or eliminating a biological disorder and / or at least one of its associated symptoms. Furthermore, references to "treatment" in this document include references to curative, palliative, and preventive therapy.

[0828] "Prevention" according to the present invention is a set of measures aimed at preventing diseases or disorders mediated by the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor.

[0829] The term "disorder" means any condition that can be ameliorated by the treatment or prevention provided by the present invention. This term is defined to include chronic and acute disorders or diseases, including pathological conditions that predispose a mammal to developing the disorder.

[0830] A "therapeutically effective amount" is the amount of a therapeutic agent administered during treatment or prophylaxis that will relieve, to a certain extent, one or more symptoms of the disease being treated or prevented. The therapeutically effective amount may vary depending on factors such as the specific condition being treated or prevented, the age, sex, and weight of the patient, and whether the administration of a monoclonal antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor is a stand-alone treatment or prophylaxis or is carried out in combination with one or more additional drugs, treatments, or prophylaxis methods.

[0831] In one aspect, the subject of treatment or prevention, or patient, is a human subject. The said subject may be male or female of any age.

[0832] The pharmaceutical compositions of the present invention and the methods for their manufacture will be readily apparent to those skilled in the art. The manufacture of the pharmaceutical compositions should preferably comply with GMP (good manufacturing practice) requirements.

[0833] In some embodiments of the pharmaceutical composition, it may include a buffer composition, tonic agents (osmolytic or osmotic agent), stabilizers and / or solubilizers.

[0834] The pharmaceutical composition of the invention is stable.

[0835] A pharmaceutical composition is considered "stable" if the active ingredient retains its physical stability and / or chemical stability and / or biological activity throughout the stated shelf life at a storage temperature of, for example, 2-8°C. Preferably, the active ingredient retains both physical and chemical stability, as well as biological activity. The shelf life is determined based on the results of stability studies under accelerated and natural storage.

[0836] In some embodiments, the pharmaceutical composition is an injectable dosage form.

[0837] In some embodiments, the injectable dosage form is an infusion solution.

[0838] In some embodiments, the injectable dosage form is a solution for subcutaneous administration.

[0839] Injectable dosage forms can be manufactured in unit dosage form, such as, but not limited to, ampoules, vials, polymer containers, pre-filled syringes, autoinjector devices.

[0840] In some embodiments, the pharmaceutical composition is a pharmaceutical composition provided in dry form, i.e., a powder or granules for reconstitution in a suitable solvent (e.g., sterile, pyrogen-free water) prior to administration. Such a drug can be obtained, for example, by lyophilization, i.e., a process known in the art as freeze-drying, which involves freezing the drug and then removing the solvent from the frozen contents.

[0841] In some embodiments, the pharmaceutical composition is a lyophilisate for the preparation of an infusion solution.

[0842] In some embodiments, the pharmaceutical composition is a lyophilisate for the preparation of a solution for subcutaneous administration.

[0843] In some embodiments, the pharmaceutical composition is a concentrate for the preparation of an infusion solution.

[0844] In some embodiments, the pharmaceutical composition is a concentrate for the preparation of a solution for subcutaneous administration.

[0845] In one aspect, the present invention relates to a pharmaceutical composition that comprises a monoclonal antibody of the present invention or an antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor, and at least one other therapeutically active compound.

[0846] In one aspect, the present invention relates to a pharmaceutical composition for the treatment or prevention of a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor, which comprises any of the above-mentioned antibodies or antigen-binding fragments thereof and at least one other therapeutically active compound.

[0847] In one aspect, the present invention relates to a pharmaceutical that comprises any of the above-mentioned antibodies or antigen-binding fragments thereof and, additionally, at least one other therapeutically active compound.

[0848] In one aspect, the present invention relates to a pharmaceutical composition for the treatment or prevention of a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor, which comprises any of the above-mentioned antibodies or antigen-binding fragments thereof and, additionally, at least one other therapeutically active compound.

[0849] In one aspect, the present invention relates to a pharmaceutical composition for the treatment or prevention of a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor, which comprises any of the above-mentioned antibodies or antigen-binding fragments thereof and at least one other therapeutically active compound, which is an antibody, insulin preparations, a small molecule, a hormonal therapy agent, or any combination thereof.

[0850] In some embodiments of the pharmaceutical composition, the other therapeutically active compound is selected from the group: insulin preparations, glucocorticoids, β2-adrenergic receptor agonists, M-cholinergic receptor antagonists, budesonide, azathioprine, methotrexate, dapsone, or any combination thereof.

[0851] In some embodiments of the pharmaceutical composition, the disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor is selected from the group: type 1 diabetes mellitus, delay in the transition of type 1 diabetes mellitus stage 2 to stage 3, high blood glucose, impaired glucose tolerance, prediabetes, rejection of nickel implants or prostheses, sarcoidosis, berylliosis, celiac disease or dermatitis herpetiformis.

[0852] Therapeutic use of a monoclonal antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor

[0853] In one aspect, an antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor is used in the treatment or prevention of diseases or disorders mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor.

[0854] In one aspect, the subject of treatment or prevention, or patient, is a human subject. The said subject may be male or female and of any age.

[0855] In one aspect, the present invention relates to a method for treating or preventing a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor, which comprises administering to a subject in need of such treatment or prevention any of the above-mentioned antibody or antigen-binding fragment thereof or the above-mentioned pharmaceutical composition in a therapeutically effective amount.

[0856] In one aspect, the present invention relates to a method for treating or preventing a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor, which comprises administering to a subject in need of such treatment or prevention any of the above-mentioned antibodies or antigen-binding fragments thereof and at least one other therapeutically active compound in a therapeutically effective amount.

[0857] In some embodiments of the method for treating or preventing, the disease or disorder mediated by the TRBV5-1 segment of the beta chain variable domain of the human T-cell receptor is selected from the group: type 1 diabetes mellitus, delay in the transition of type 1 diabetes mellitus stage 2 to stage 3, high blood glucose, impaired glucose tolerance, prediabetes, rejection of nickel implants or prostheses, sarcoidosis, berylliosis, celiac disease, or dermatitis herpetiformis.

[0858] In some embodiments of the method of treatment or prevention, the other therapeutically active compound is an antibody, insulin preparations, a small molecule, a hormonal therapy agent, or a combination thereof.

[0859] In one aspect, the present invention relates to the use of the above-mentioned antibody or antigen-binding fragment thereof or the above-mentioned pharmaceutical composition for the treatment or prevention, in a subject in need of such treatment or prevention, of a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T cell receptor.

[0860] In one aspect, the present invention relates to the use of the above-mentioned antibody or antigen-binding fragment thereof and at least one other therapeutically active compound for the treatment or prevention, in a subject in need of such treatment or prevention, of a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T cell receptor.

[0861] In some embodiments of the use, the disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor is selected from the group: type 1 diabetes mellitus, delay in the transition of type 1 diabetes mellitus stage 2 to stage 3, high blood glucose, impaired glucose tolerance, prediabetes, rejection of nickel implants or prostheses, sarcoidosis, berylliosis, celiac disease or dermatitis herpetiformis.

[0862] In some embodiments of the use, the other therapeutically active compound is an antibody, insulin preparations, a small molecule, a hormonal therapy agent, or a combination thereof.

[0863] As used herein, uses or methods relating to an antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor, with one or more other therapeutic agents are intended to mean, refer to, or include:

[0864] 1) the simultaneous administration of such a combination of an antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor and a therapeutic agent to a patient in need of treatment or prophylaxis, when such components are formulated together in a single dosage form from which said components are released substantially simultaneously to said patient,

[0865] 2) the simultaneous administration of such a combination of an antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor and a therapeutic agent to a patient in need of treatment or prophylaxis, when such components are formulated separately in different dosage forms, the administration of which occurs at substantially the same time to said patient, after which said components are released substantially simultaneously to said patient,

[0866] 3) sequential administration of such combination of an antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor and a therapeutic agent to a patient in need of treatment or prophylaxis, wherein such components are formulated separately from each other in separate dosage forms that are administered sequentially in time to said patient with a significant time interval between each administration, whereupon said components are released at substantially different times to said patient; and

[0867] 4) sequential administration of such a combination of an antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor and a therapeutic agent to a patient in need of treatment or prevention, when such components are formulated together in a single dosage form from which the release of said components occurs in a controlled manner, after which they are simultaneously, sequentially or jointly released at the same time and / or different times to said patient, where each part can be administered by the same or different routes.

[0868] An antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor can be administered without additional therapeutic treatment or prophylaxis, i.e., as an independent therapy.

[0869] In some embodiments of the method of treatment or prevention or use of an antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor, it can be administered in combination with another therapeutically active compound that is selected from the group: insulin preparations, glucocorticoids, β2-adrenergic receptor agonists, M-cholinergic receptor antagonists, budesonide, azathioprine, methotrexate, dapsone or any combination thereof.

[0870] In some embodiments, the method of treatment or prevention or use will require premedication, which is selected from the group: histamine receptor blockers, glucocorticoids, antiemetics, paracetamol or any combination thereof.

[0871] The antibody or antigen-binding fragment thereof that specifically binds to a segment of TRBV5-1 and the pharmaceutical composition of the present invention are suitable for parenteral administration in the form of sterile medicinal products intended for administration into the body of a subject with disruption of the integrity of the skin or mucous membranes, bypassing the gastrointestinal tract by injection, infusion or implantation. In particular, it is contemplated that parenteral administration includes, but is not limited to, subcutaneous, intraperitoneal, intramuscular, intravenous, intraarterial, intrathecal, intraventricular, intraurethral, ​​intracranial, intra-articular, transdermal injection or infusion; and renal dialysis infusion techniques.

[0872] In some embodiments of the method of treatment or prevention or use, the antibody or antigen-binding fragment thereof that specifically binds to a segment of TRBV5-1, or the pharmaceutical composition is administered intravenously.

[0873] In some embodiments, intravenous administration is carried out by infusion, prolonged infusion, or long-term continuous infusion.

[0874] In some embodiments of the method of treatment or prevention or use, the antibody or antigen-binding fragment thereof that specifically binds to a segment of TRBV5-1, or the pharmaceutical composition is administered subcutaneously.

[0875] In some embodiments, subcutaneous administration is performed by subcutaneous injection.

[0876] In some embodiments of the method of treatment or prevention or use, a suitable dose of the monoclonal antibody or antigen-binding fragment thereof that specifically binds to a segment of TRBV5-1 according to the present invention will be in the range of 0.1-200 mg / kg.

[0877] Brief description of drawings

[0878] Figure 1 is a map of a vector carrying the genetic sequence of the light chain of an anti-TRBV5-1 antibody.

[0879] Figure 2 is a map of a vector carrying the genetic sequence of the heavy chain of the anti-TRBV5-1 antibody.

[0880] For figures 1-2.

[0881] Name Transcript EBV ori Epstein-Barr virus replication origin site AmpR A beta-lactamase gene that confers resistance to ampicillin. Allows for selection of E. coli cell cultures. hCMV promoter Eukaryotic promoter of human cytomegalovirus Cmv enhancer Human cytomegalovirus enhancer sequence Intron A Acceptor site Cossack Kozak consensus sequence for translation initiation START Start codon Leader IgK Mouse IgK signal leader peptide aTRBV51-VH Sequence of the heavy chain variable domain of the anti-TRBV5-1 antibody HC Sequence of the constant domain of the heavy chain of the IgG1 antibody HC. aTRBV51-VL Sequence of the light chain variable domain of the anti-TRBV5-1 antibody CK Sequence of the constant domain of the light chain of the IgG1 antibody k STOP Stop codon SV40 PA term Transcription terminator, polyadenylation signal of the SV40 virus

[0882] Figure 3 is an electropherogram of antibodies containing no (reducing conditions) additional disulfide bonds between the heavy and light chains in 4-15% PAGE.

[0883] 1) Molecular protein markers; molecular weights (kDa) corresponding to the bands; 2) 04-002; 3) 04-004; 4) 04-009; 5) 04-013; 6) 04-016; 7) 04-024; 8) 04-042; 9) 04-045; 10) 04-046; 11) 04-047.

[0884] Figure 4 is an electropherogram of antibodies containing (non-reducing conditions) additional disulfide bonds between the heavy and light chains in 4-15% PAGE.

[0885] 1) Molecular protein markers; molecular weights (kDa) corresponding to the bands; 2) 04-002; 3) 04-004; 4) 04-009; 5) 04-013; 6)04-016; 7) 04-024; 8) 04-042; 9) 04-045; 10) 04-046; 11) 04-047.

[0886] Figure 5 is a graph showing the lack of ability of antibodies 04-002 and 03-010 to induce antibody-dependent cellular phagocytosis (ADCP) in a reporter cell assay.

[0887] Figure 6 is a graph showing the absence of non-specific activation of NFAT signaling cascade by antibodies 04-002, 04-016, and 04-024 in a reporter cell assay.

[0888] Figure 7 is a graph showing the absence of non-specific activation of NFAT signaling cascade by antibodies 03-010 and 03-015 in a reporter cell assay.

[0889] Figure 8 is a graph showing the ability of antibodies 04-002, 04-016, 04-024, and 03-010 to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in peripheral blood mononuclear cell (PBMC) suspension.

[0890] Figure 9 is a histogram showing the change in the relative expression level of the TRBV5-1 gene in human peripheral blood mononuclear cells (PBMC) in the presence of anti-TRBV5-1 antibody.

[0891] Figure 10 is a graph showing the absence of complement-dependent cytotoxicity (CDC) of antibodies 04-002 and 03-010.

[0892] Figure 11 is a graph showing the lack of ability of antibody 04-002 to deplete NK cell populations in human PBMCs.

[0893] Figure 12 is a graph showing the lack of ability of antibody 04-002 to deplete B cell populations in human PBMCs.

[0894] Figure 13 is a graph showing the lack of ability of antibody 04-002 to deplete the total T cell population in human PBMCs.

[0895] Figure 14 is a graph showing the lack of ability of antibody 04-002 to deplete monocyte populations in human PBMCs.

[0896] Figure 15 is a graph showing the percentage of TRBV5-1-positive cells in the presence of anti-TRBV5-1 antibody in mouse blood samples among the population of cells positive for human CD45 and CD3 markers on day 18.

[0897] ** - p-value ≤ 0.01

[0898] Statistical analysis was performed using the Kruskal-Wallis test and Dunn's test for multiple comparisons.

[0899] Figure 16 is a graph showing the percentage of TRBV5-1-positive cells in mouse spleen samples among the human CD45 and CD3 positive cell population at day 18.

[0900] *** - p-value ≤ 0.001

[0901] Statistical analysis was performed using the Kruskal-Wallis test and Dunn's test for multiple comparisons.

[0902] Examples

[0903] For a better understanding of the invention, the following examples are provided. These examples are provided for illustrative purposes only and should not be construed as limiting the scope of the invention in any way.

[0904] Materials and General Methods

[0905] General information concerning the nucleotide sequences of the light and heavy chains of human immunoglobulin is given in: Kabat EA et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD, 1991. The amino acids of the antibody chains are numbered according to the EU numbering (Edelman GM et al., Proc. Natl. Acad. Sci. USA 63, 1969, ee. 78-85; Kabat EA et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD, 1991).

[0906] Recombinant DNA methods

[0907] DNA manipulations were performed using standard methods described in Sambrook J. et al., Molecular cloning: A laboratory manual; Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1989. Molecular biology reagents were used according to the manufacturers' instructions.

[0908] Gene synthesis

[0909] The desired gene segments were obtained from oligonucleotides created by chemical synthesis. Gene segments ranging from 300 to 1400 bp in length, flanked by unique restriction sites, were assembled by annealing and ligation of the oligonucleotides, including PCR amplification and subsequent cloning through the restriction sites. The DNA sequences of the subcloned gene fragments were confirmed by DNA sequencing.

[0910] DNA Sequencing

[0911] DNA sequences were determined by Sanger sequencing.

[0912] DNA and protein sequence analysis and sequence data processing

[0913] Unipro UGENE version 1.29 and SnapGene version 6.1 software packages were used to generate, map, analyze, annotate, and illustrate sequences.

[0914] Expression vectors

[0915] For expression of the antibodies described in the application materials, variants of expression plasmids designed for antibody expression in prokaryotic cells (E. coli) and short-term expression in eukaryotic cells (e.g., CHO cells) were used. In addition to the antibody expression cassette, the vectors contained a replication origin site, ensuring replication of the specified plasmid in E. coli, and genes conferring resistance to various antibiotics (e.g., ampicillin and kanamycin) in E. coli.

[0916] Fusions of genes containing the described antibody chains, as described below, were accomplished by PCR and / or gene synthesis and assembly using known recombination methods and procedures by joining corresponding nucleic acid segments, for example, by using unique restriction sites in the corresponding vectors. Subcloned nucleotide sequences were confirmed by DNA sequencing. For short-term transfections, large quantities of plasmids were generated by obtaining plasmids from transformed E. coli cultures.

[0917] Example 1. Selection of anti-TRBV5-1 antibody sequences.

[0918] The anti-TRBV5-1 antibody molecules were created using in silico structural data. In silico scaffolding was performed using an internal algorithm at BIOCAD. The PrepWizard tool from Schrodinger Suite 2021-3 was used to prepare the structures. Folding was then performed using Schrodinger Prime 2021-3.

[0919] An approach of sequentially changing the amino acid composition of variable domains was used.

[0920] The amino acid sequences of the antibodies were optimized in silico, and the antibodies shown in Table 1 were obtained.

[0921] Table 1. Anti-TRBV5-1 antibodies.

[0922] Name of the antibody 04-002 04-004 04-009 04-013 04-016 04-024 04-042 04-045 04-046 04-047 03-008 03-010 03-015 03-023 03-024 03-026 03-027 03-028 03-036 03-038

[0923] Example 2. Humanization analysis of the variable fragments of the heavy and light chains of anti-TRBV5-1 antibodies.

[0924] Table 2 shows the result of the humanization analysis of the variable fragments of the heavy and light chains of anti-TRBV5-1 antibodies in comparison with the control drug 01-010, the sequences of which are known from the international application WO2020142672.

[0925] Table 2. Degree of humanization of antibody variable fragments.

[0926] Name of the antibody Humanization of VH, % Humanization of VL, % 04-002 85,7 85,7 04-004 85,7 86,8 04-009 85,7 86,8 04-013 85,7 85,7 04-016 85,7 86,8 04-024 85,7 86,8 04-042 85,7 85,7 04-045 85,7 85,7 04-046 85,7 86,8 04-047 85,7 86,8 03-008 85,7 86,8 03-010 85,7 85,7 03-015 86,7 85,7 03-023 85,7 86,8 03-024 85,7 85,7 03-026 85,7 86,8 03-027 85,7 86,8 03-028 85,7 86,8 03-036 86,7 85,7 03-038 86,7 85,7 01-010 82,7 84,6

[0927] Thus, the variable fragments of the heavy and light chains of the developed anti-TRBV5-1 antibodies of the invention have a humanization degree of more than 85%.

[0928] Example 3. Obtaining anti-TRBV5-1 antibody sequences.

[0929] The genes of the heavy and light chain variable domains of the anti-TRBV5-1 antibodies of the invention, which are selected from the group in Table 1, were assembled by de novo synthesis from oligonucleotides. The nucleotide sequences were selected based on the amino acid sequences, and the codon composition was optimized for CHO cell line expressor cells. Partially complementary primers with a 20 bp overlap region were selected for each variable fragment sequence, and PCR was performed. The resulting fragments were combined by PCR with the CK constant domain sequence for the light chain variable domain and the CH1-CH2-CH3 constant domain sequences of the heavy chain for the heavy chain variable domain and cloned into the pintA expression vector (Figures 1-2). Restriction-ligation or ligation-free cloning methods were used to assemble the plasmids. The gene's nucleotide sequences were confirmed by Sanger DNA sequencing.A plasmid DNA preparation was obtained by purification using a commercial Qiagen kit from an E. coli cell culture. The resulting DNA was used for transient protein production in a CHO cell line.

[0930] Example 4. Modification of the constant domain of the heavy chain Fc of anti-TRBV5-1 antibodies 04-002, 04-016, 04-024.

[0931] To obtain antibodies with improved properties, the heavy chain constant domain was modified by deleting the C-terminal amino acids glycine and lysine (delGK). This modification improves the homogeneity of the protein preparation.

[0932] Genetic constructs were assembled by cloning the variable fragment sequences of the heavy chains of antibodies 04-002, 04-016, and 04-024 into the pintA vector, merging them with the CH1-CH2-CH3 constant domain sequences of the heavy chain with the delGK modification. Cloning was performed using restriction ligation, and the resulting sequences were confirmed by Sanger sequencing.

[0933] The plasmid DNA preparation was obtained by purification using a commercial kit from Qiagen from a culture of E. coli cells. The resulting DNA was used for transient protein production in the CHO cell line.

[0934] Example 5. Production of antibody preparations and determination of the functional activity of antibodies.

[0935] To generate antibodies, CHO cells cultured for 24 hours with a fucose analog to a density of 1.8-2.2 million / mL were transfected with plasmid DNA complexed with polyethyleneamine. One day after transfection, the cells were cultured with growth supplements at lower temperatures. Antibody titers were measured using OctetRed96 (Pall) according to the manufacturer's standard recommendations on proA biosensors 4-7 days after cell transfection. The culture fluid containing the antibodies was then diluted to 3-10 μg / mL and incubated with J.RT3-T3.5-TRBV5-1 cells. After incubation with secondary fluorescently labeled a-hFc-PE antibodies (Jackson ImmunoResearch), cell fluorescence was measured on a flow cytometer to confirm binding of anti-TRBV5-1 antibodies to the TRBV5-1 antigen, indicating functional activity of the antibodies. J.RT3-T3 cells were used as a negative binding control.5-TRBV5-1 cells stained with secondary antibodies only, and J.RT3-T3.5-TRBV5-1 cells stained with a commercial anti-TRBV5-1 antibody (Beckman Coulter IM2285) served as a positive control.

[0936] Table 3 shows that 20 anti-TRBV5-1 antibodies generated bind to the TRBV5-1 antigen expressed on the cell surface as part of the multiprotein TRC-CD3 complex.

[0937] Table 3. Data on the concentration and functional activity of anti-TRBV5-1 antibodies produced in a transient expression system based on Chinese hamster CHO cells.

[0938] Antibody Antibody concentration, mg / l Binding to the J.RT3-T3.5-TRBV5-1 cell line, average fluorescence value 04-002 98,6 540 04-004 46,7 490 04-009 48,3 521 04-013 63,9 418 04-016 141,6 447 04-024 116 547 04-042 53,2 473 04-045 66 400 04-046 65,7 361 04-047 65,9 397 03-008 80,1 775 03-010 110,7 810 03-015 121,3 663 03-023 87,2 730 03-024 56 1124 03-026 69,1 585 03-027 66 1064 03-028 121,7 796 03-036 127,4 658 03-038 108,1 633 Negative control - 81 Positive control - 441

[0939] Example 6. Purification of antibodies from mammalian cell suspension culture.

[0940] Antibodies were purified from the CHO cell growth medium. The cell culture fluid was clarified after 7 days of growth by centrifugation at 8000g and subsequent filtration through a 0.22 μm filter. Proteins were isolated using 5 ml Thermo Scientific gravity chromatography columns packed with 0.5-1 ml of Protein A sorbent. The clarified culture fluid was passed through the column, then the sorbent was washed with phosphate-buffered saline (PBS) pH 7.4, and the antibodies were eluted with 0.1 M glycine buffer pH 3.0. The eluted antibody solutions were brought to neutrality with 1 M TrisHCl buffer (pH 8.0). The antibodies were then dialyzed into PBS (pH 7.4), concentrated if necessary, and purified by gel filtration on a Superdex 200 Increase 10 / 300 GL column equilibrated with PBS. The target peaks were collected, filtered through a 0.22 μm filter, and stored at -80°C. The purity of the resulting protein solution was assessed by SDS gel electrophoresis (Figures 3-4) and analytical HPLC.

[0941] Example 7. Measurement of the affinity constants of interaction of anti-TRBV5-1 antibodies with the target antigen (TRBV5-1 segment).

[0942] Affinity studies of antibodies to the human TRAV1-2 / TRBV5-1 antigen were performed on a ForteBio Octet RED 384 instrument using Protein A sensors (ForteBio). The assay was carried out at 30°C in a kinetic buffer solution (4.3 mM Na2HPO4; 136.9 mM NaCl, 1.5 mM KH2PO4; 2.7 mM KCl; the volume fraction of the added Tween 20 was 0.1%; the mass fraction of the added BSA was 0.1%; pH 7.4). Before measurements, the sensors were regenerated using a 10 mM glycine solution with added HCl (pH 2.0). The regeneration process consisted of three repetitions of the following steps: 5 s in the regeneration solution and 5 s neutralization in the kinetic buffer solution. Antibodies were immobilized on the sensor surface in a kinetic buffer solution for 300 s. The antibody concentration for immobilization was 10 μg / ml. After immobilization, a baseline was recorded in the kinetic buffer solution (120 s).During the association step (duration 60 s), sensors loaded with antibodies were immersed in wells containing an analyte solution (TRAV1-2 / TRBV5-1 antigen) prepared in a kinetic buffer solution. For each antibody tested, sensograms were recorded with analyte concentrations of 10 μg / mL (217.4 nM) and 2.5 μg / mL (54.4 nM). A kinetic buffer solution without antigen was used as a reference signal (reference sensogram). After the association step, the dissociation of the antibody-antigen complex was recorded for 300 seconds. During the dissociation step, the sensors were immersed in wells containing a kinetic buffer solution, in which the baseline was recorded. Sensors not loaded with antibodies were used to test for nonspecific interaction of the analyte with the sensors (negative control). During the loading step, negative control sensors were immersed in a kinetic buffer solution that did not contain antibodies; all other steps were similar to antibody-loaded sensors.

[0943] Reference-subtracted binding curves were analyzed using Octet Data Analysis. Fitting was performed using two sensorgrams and a 1:1 interaction model. The affinities of the presented antibodies ranged from 8.4 to 69.4 nM.

[0944] Table 4. Data on the measurement of the kinetic constant of the interaction of antibodies with the TRAV1-2 / TRBV5-1 antigen.

[0945] Antibody c***, nm Response*, nm KD, M Kon, M-1s-1 Kdis, s-1 R2 03-008 217,4 0,835 8,44E-09 1,31E+05 1,11E-03 0,9991 54,4 0,3006 03-010 217,4 0,8362 1,38E-08 1,26E+05 1,75E-03 0,9982 54,4 0,3295 03-015 217,4 0,5342 3,58E-08 8,76E+04 3,13E-03 0,9982 54,4 0,1918 03-023 217,4 0,8078 1,91E-08 1,16E+05 2,22E-03 0,9992 54,4 0,2983 03-024 217,4 0,7988 2,78E-08 1,16E+05 3,23E-03 0,9981 54,4 0,2867 03-026 217,4 0,748 3,91E-08 9,94E+04 3,89E-03 0,9981 54,4 0,2526 03-027 217,4 0,8223 2,18E-08 1,52E+05 3,32E-03 0,9951 54,4 0,3201 03-028 217,4 0,7749 2,03E-08 1,16E+05 2,35E-03 0,999 54,4 0,2952 03-036 217,4 0,3893 4,26E-08 1,37E+05 5,84E-03 0,9952 54,4 0,1469 03-038 217,4 0,7606 3,03E-08 1,11E+05 3,35E-03 0,9976 54,4 0,2816 04-002 217,4 0,8309 2,81E-08 8,74E+04 2,46E-03 0,9986 54,4 0,2866 04-004 217,4 0,859 2,20E-08 1,38E+05 3,03E-03 0,9957 54,4 0,3522 04-009 217,4 0,8347 1,30E-08 1,17E+05 1,51E-03 0,9991 54,4 0,3278 04-013 217,4 0,8322 3,26E-08 1,34E+05 4,35E-03 0,9967 54,4 0,313 04-016 217,4 0,8699 2,31E-08 1,31E+05 3,03E-03 0,9979 54,4 0,3303 04-024 217,4 0,8888 1,97E-08 1,31E+05 2,57E-03 0,9985 54,4 0,344 04-042 217,4 0,7618 1,46E-08 1,13E+05 1,66E-03 0,9986 54,4 0,2805 04-045 217,4 0,7081 2,72E-08 1,09E+05 2,95E-03 0,9981 54,4 0,2577 04-046 217,4 0,7196 2,90E-08 1,26E+05 3,65E-03 0,9978 54,4 0,2572 04-047 217,4 0,7226 2,00E-08 1,36E+05 2,73E-03 0,9964 54,4 0,2673 01-010 217,4 0,6916 6,94E-08 1,45E+05 1,00E-02 0,9893 54,4 0,2157 Negative control** 217,4 -0,0072 n / a n / a n / a n / a 54,4 -0,0121 Response* - signal level achieved at the end of the association step; negative control** - testing for non-specific interaction of the analyte (TRAV1-2 / TRBV5-1 antigen) with sensors not loaded with antibodies; c*** - analyte concentration (TRAV1-2 / TRBV5-1 antigen)

[0946] Conclusion: The anti-TRBV5-1 antibody of the invention specifically binds to the human TRBV5-1 antigen. The affinity of the resulting antibodies exceeds that of antibody 01-010.

[0947] Example 8. Analysis of the affinity constants of interaction of anti-TRBV5-1 antibodies with Fcgamma and FcRn receptors.

[0948] Measurements were performed according to the manufacturer's method for streptavidin sensors (SA Biosensors) and the instructions for the OctetRed96 (Pall) instrument. Sensors were prepared as for the target antigen affinity constant analysis.

[0949] The sensors were then bound to the corresponding biotinylated receptor in 1x kinetic buffer, then the sensors were transferred to solutions of anti-TRBV5-1 antibodies in kinetic buffer with different concentrations, and finally the sensors were immersed in wells with kinetic buffer.

[0950] The resulting data were processed in Octet Data Analysis 8.2, 1:1 or 2:1 model. The calculated affinity constants are presented in Table 5.

[0951] Table 5. The values ​​of the affinity constant of the interaction of anti-TRBV5-1 antibody 04-002 with Fcgamma and FcRn receptors. The data were obtained on an Octet Red96 instrument and the constants were calculated in the Octet Data Analysis 8.2 program.

[0952] Name of the receptor Antibody 04-002 FcγRIa, KD, M-1 1,4E-09 FcγRIIa-131R, KD, M-1 2E-07 FcγRIIa-131H, KD, M-1 2E-07 FcγRIIb, KD, M-1 2E-07 FcγRIIIa-158V, KD, M-1 2E-08 FcγRIIIa-158F, KD, M-1 3E-08 FcRn, KD, M-1 1,7E-08

[0953] Conclusion: The antibody 04-002 shows high affinity for FcγR IIIa158V and IIIa158F receptors, which potentially improves the effector properties of this antibody.

[0954] Example 9. Stability of anti-TRBV5-1 antibodies during storage in human serum.

[0955] In this study, stability was defined as the preservation of full-length antibody molecules in human serum at +37°C in vitro. To determine stability, antibody samples were diluted in human serum to a concentration of 25 μg / mL and stored at +37°C in a thermostat for 14 days in 150 μL microtubes supplemented with sodium thiolate to 0.1%. Pure human serum samples were stored under similar conditions to subsequently determine the background concentrations of the test samples. After storage, antibody concentrations in the samples were determined by enzyme-linked immunosorbent assay (ELISA) using a calibration titration of the antibody from 250 to 3.9 ng / mL. Calibration and comparison samples were diluted to the desired concentration immediately before the experiment.

[0956] To perform the ELISA, the antigen containing the target segment of human TRBV5-1 was adsorbed on the plate at a concentration of 2.5 μg / ml in 0.1 M carbonate buffer pH 9.5. The plate was washed, then the wells were blocked with a 0.5% solution of dry milk in the wash buffer for 1 hour. The wash buffer was 0.1% Tween-20 solution in PBS. After blocking, solutions of the studied antibodies and calibration solutions were added to the plate, all samples were diluted in the blocking solution, and incubated at 37°C for 1 hour on a plate shaker. The plate was washed, and a solution of goat antibodies to the Fc portion of human IgG conjugate with horseradish peroxidase (a-hFc-HRP) was added to the wells and incubated at 37°C for 1 hour on a plate shaker. The wells were then washed, TMB solution was added, and after staining, the reaction was stopped with 10% sulfuric acid. Staining in the wells was recorded by absorbance at 450 nm using a Tecan plate fluorometer.

[0957] Prior to ELISA, samples removed from storage and comparison samples were diluted 500-fold with buffer to a calculated concentration of 50 ng / mL. The concentration of the studied antibodies was determined based on ELISA results. Antibody stability was expressed as the ratio of the concentration of samples removed from storage to the concentration of the original samples, multiplied by 100%. A concentration reduction of no more than 60% in the incubated samples was considered sufficient for further analysis (Table 6).

[0958] Table 6. Relative stability values ​​of antibodies when stored in human serum for 14 days at +37°C.

[0959] Name of the antibody Antibody concentration in freshly prepared human serum sample (μg / ml) Antibody concentration after 14 days of storage in human serum at 37°C (μg / ml) Proportion of full-length antibody molecules remaining in the sample after storage in serum (%) 04-002 18,8 17 90 04-016 19,2 19,9 100 04-024 25,3 20,9 82

[0960] The table shows the percentage of remaining full-length antibody molecules in serum after incubation compared to the antibody content in the samples before incubation, as well as antibody concentration values. The anti-TRBV5-1 antibodies according to the invention are shown to be stable during storage in human serum.

[0961] Example 10. Antibody stability test.

[0962] Using HPLC, we assessed the difference between antibody samples before and after heating at 50°C for 48 hours. Peak area and peak area ratio data for each sample were evaluated pairwise. The comparison criteria were changes in peak area and peak area ratios between the sample stored at 4°C and the same sample incubated at 50°C for 48 hours.

[0963] The results of peak area change of target molecules are shown in Table 7.

[0964] Table 7. Change in the proportion of monomer in antibody preparations subjected to thermal stress.

[0965] Name of the antibody % peak ratio Σ aggregates, % monomer, % Σfragments, % 01-010 before warming up 3,4 96,4 0,2 after warming up 1,1 92 6,9 04-002 before warming up 1,2 98 0,8 after warming up 1 95,4 3,6

[0966] Thus, antibody 04-002 has higher thermal stability compared with antibody 01-010.

[0967] Example 11. Ability of antibodies to induce ADCC in a reporter cell assay.

[0968] The test utilized the Jurkat-NFAT-Luc-CD16 cell line, which stably expresses CD16 on the surface and contains the firefly luciferase gene, the expression of which is under the control of the NFAT promoter; the target cells were the J.RT3-T3.5-TRBV5-1 cell line, which stably expresses the variable domain of the T cell receptor β-chain, including the TRBV5-1 segment.

[0969] The assay was performed in a white 96-well culture plate for luminescence work. The suspension in each well contained 25,000 Jurkat-NFAT-Luc-CD16 effector cells, 8,000 J.RT3-T3.5-TRBV5-1 target cells, and the analyzed antibodies at the concentrations indicated in the graph. The final volume of cell suspension and antibodies in a well was 100 μl, all suspension components were prepared in RPMI-1640 medium containing 5% FBS and 2 mM glutamine. After adding all components, the plates were incubated for 5 hours at +37°C, 5% CO2. Then, using the One-Glo Lucifer Assay Kit (Promega), the luminescence intensity in the wells was measured. Measurements were performed on a plate reader.

[0970] Antibodies 04-002, 04-004, 04-009, 04-013, 04-016, 04-024, 04-042, 04-045, 04-046, 04-047, 03-028, 03-015, 03-036, 03-038, 03-026, 03-008, 03-010, 03-023, 03-024, 03-027 were shown to cause antibody-dependent cell-mediated cytotoxicity in the reporter assay, the half-maximal effective concentration of antibodies (EC50) is shown in Table 8.

[0971] Table 8. Antibody-dependent cell-mediated cytotoxicity of the antibodies of the invention in a reporter test.

[0972] Antibody half-maximal effective concentration of antibodies (EC50), ng / ml 04-002 55,2 04-004 77,5 04-009 38,5 04-013 96,7 04-016 41,1 04-024 45,3 04-042 44,9 04-045 64,2 04-046 71 04-047 73,1 03-008 62,8 03-010 45,3 03-015 44,2 03-023 27,7 03-024 19 03-026 30,8 03-027 36,3 03-028 52,1 03-036 77,3 03-038 62,1 01-010 170,6

[0973] Example 12. Ability of antibodies to induce ADCP in a reporter cell assay.

[0974] In the reporter cell assay to test the ADCP-inducing ability of antibodies, the Jurkat-NFAT-Luc-CD64 cell line, which stably expresses CD64 on the surface and contains the firefly luciferase gene, the expression of which is under the control of the NFAT promoter, was used; J.RT3-T3.5-TRBV5-1 cells, which stably expresses the variable domain of the T cell receptor β-chain, including the TRBV5-1 segment, were used as target cells.

[0975] The assay was performed in a white 96-well culture plate for luminescence analysis. The suspension in each well contained 30,000 Jurkat-NFAT-Luc-CD64 effector cells, 30,000 J.RT3-T3.5-TRBV5-1 target cells, and the antibodies to be analyzed. The anti-CD20 antibody Rituximab, which has ADCP activity, was used as a positive control. The final volume of cell suspension and antibodies in a well was 100 μl; all suspension components were prepared in RPMI-1640 medium containing 5% FBS. After adding all components, the plates were incubated for 16 hours at 37°C, 5% CO2, and then the luminescence intensity in the wells was measured using the One-Glo Lucifer Assay Kit (Promega). Luminescence was measured on a plate reader.

[0976] Antibodies 04-002 and 03-010 were shown not to induce ADCP in a reporter cell assay. Mean values ​​with standard deviations for two replicates are shown (Figure 5).

[0977] Example 13. Analysis of non-specific activation of the NFAT signaling cascade by antibodies 03-010, 03-015, 04-002, 04-016 and 04-024.

[0978] The J.RT3-T3.5-TRBV5-1-NFAT-Luc cell line was used in a reporter cell assay to test the activating properties of antibodies. The cell line stably expresses the variable domain of the T-cell receptor β-chain, including the TRBV5-1 segment, on its surface and contains the firefly luciferase gene, whose expression is controlled by the NFAT promoter. The assay was conducted in a white 96-well luminescence culture plate. Each well contained 50,000 J.RT3-T3.5-TRBV5-1-NFAT-Luc cells suspended in a suspension, along with the antibodies being analyzed. The anti-CD3 antibody OKT3, pre-incubated with cross-linking antibodies against the Fc portion of the antibody, served as a control. The final volume of cell suspension and antibodies in the well was 100 μl, all suspension components were prepared in RPMI-1640 medium containing 5% FBS and 2 mM glutamine.After adding all components, the plates were incubated for 16 hours at 37°C, 5% CO2, and then the luminescence intensity in the wells was measured using the One-Glo luciferase assay kit (Promega). Luminescence was measured using a plate reader.

[0979] Antibodies 03-010, 03-015, 04-002, 04-016, and 04-024 were shown to not significantly activate the J.RT3-T3.5-TRBV5-1-NFAT-Luc reporter cell line. Mean values ​​with standard deviations are shown (Figures 6 and 7).

[0980] Example 14. Analysis of ADCC activity of antibodies 04-002, 04-016, 04-024 and 03-010 in a suspension of peripheral blood mononuclear cells.

[0981] To evaluate the ability of antibodies to induce ADCC under conditions similar to real-life conditions, a cell-based assay was performed with human PBMC. The assay was conducted in a 96-well culture plate designed for suspension cultures. The suspension in each well contained 500,000 freshly isolated PBMC from a healthy donor and the biotinylated antibody indicated in the graph at the indicated concentration. The final volume of the cell suspension per well was 200 μl. All suspension components were prepared in RPMI-1640 medium containing 5% FBS and 2 mM glutamine. After mixing the PBMC and antibodies, the plate was incubated for 24 hours at 37°C, 5% CO2. The proportion of TRBV5-1-positive T cells in the suspensions was then assessed. For this purpose, cell pellets from each well of the plate were stained with the corresponding biotinylated anti-TRBV5-1 antibody at a concentration of 1 μg / ml, followed by fluorescently labeled streptavidin (PE). The proportion of T cells in the suspensions was determined by direct staining with a fluorescently labeled anti-CD3 antibody.The analysis was performed using a flow cytometer.

[0982] Antibodies 04-002, 04-016, 04-024 and 03-010 were shown to induce antibody-dependent cell-mediated cytotoxicity in human PBMC, and the half-maximal effective concentration (EC50) of the antibodies was shown in Figure 8.

[0983] Example 15. Analysis of depletion of native TRBV5-1 T cells in human PBMCs by RT-PCR.

[0984] To analyze the depletion of T cells expressing the variable domain of the T cell receptor β-chain, including the TRBV5-1 segment, one million cells were collected by real-time PCR (RT-PCR) from samples incubated in the presence of candidate 04-002 and from intact samples, the preparation of which is described in Example 14. Cell pellets were placed in RLT buffer (Qiagen), and RNA was isolated from them using the Qiagen RNeasy mini kit according to the manufacturer's protocol. Spectrometric assessment of the amount of isolated RNA was performed on a NanoDrop 8000 instrument (Themo Scientific). The qualitative analysis of the obtained RNA was assessed using denaturing RNA gel electrophoresis. Residual genomic DNA was removed using DNase (New England Biolabs). cDNA synthesis on an RNA template was performed using the SuperScript IV First-Strand Synthesis System (Invitrogen) according to the manufacturer's protocol. 1 μg of RNA was used for each reverse transcription reaction.For quantitative PCR, the "Reagent Kit for Real-Time PCR with SYBR Green I Dye" (Synthol) was used. Three technical replicates were run for each sample. The glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was used as a reference for normalizing the obtained quantitative evaluation parameters. Real-time PCR was performed using the StepOne™ Real-Time PCR System (Applied Bioscience). TRBV5-1 expression levels were calculated using the Pfaffl method, with amplification efficiency adjusted.

[0985] Thus, it is shown (Figure 9) that antibody 04-002 causes antibody-dependent cell-mediated cytotoxicity by eliminating a population of T cells carrying on their surface the variable domain of the β-chain of the T-cell receptor, including the TRBV5-1 segment.

[0986] Example 16. Ability of antibodies to induce CDC in a reporter cell assay.

[0987] The J.RT3-T3.5-TRBV5-1 cell line was used in the CDC detection test. The test was conducted in a 96-well culture plate. The suspension in each well contained 50,000 J.RT3-T3.5-TRBV5-1 cells, as well as the analyzed antibodies at the specified concentration and human serum complement diluted 1:4. The final volume of the cell suspension in the well was 150 μl, all components of the suspension were prepared in RPMI-1640 medium containing 0.1% BSA. Then the plate was incubated for 4 hours at +37°C, 5% CO2. 15 μl of AlamarBlue reagent was added to each well and incubated for 16 hours at +37°C, 5% CO2.

[0988] The fluorescence value was measured at an excitation wavelength of 544 nm and an emission wavelength of 590 nm using a plate reader.

[0989] Antibodies 04-002 and 03-010 were shown not to induce complement-dependent cytotoxicity in the assay (Figure 10). The graph shows mean values ​​with standard deviations.

[0990] Example 17. Analysis of autocytotoxic activity mediated by anti-TRBV5-1 antibodies.

[0991] The autocytotoxicity test was performed in a 96-well culture plate for suspension cultures. Each well contained 300,000 freshly isolated PBMCs from healthy donors and the antibody indicated in the graph at the indicated concentration; the final volume of the cell suspension per well was 150 μl. All suspension components were prepared in RPMI-1640 medium containing 5% FBS and 2 mM glutamine. After mixing the PBMCs and antibodies, the plate was incubated for 16 hours at 37°C and 5% CO2. The proportion of CD56+, CD19+, CD3+, and CD14+ PBMC subsets was then assessed by direct staining of the suspensions with fluorescently labeled antibodies against the corresponding CDs and subsequent cell analysis on a flow cytometer. Anti-CD20 antibody (GA101), which induces B cell depletion in the concentration range of 1 to 100 μg / mL, was used as a positive control.

[0992] The graphs show the mean values ​​and standard deviations for two replicates (Figures 11-14).

[0993] Conclusion: The antibody 04-002 lacks the ability to deplete populations of NK cells, B cells, and it also does not affect the total number of T cells, except for those carrying TRBV5-1, which follows from the results (Figure 13), where in the concentration range from 1 to 100 μg / ml of the antibody 04-002, the number of T cells decreases by about 5%.

[0994] Example 18. Study of the effector properties of the antibody in an in vivo model on NSIG mice in blood and spleen samples.

[0995] Two groups of NSIG mice were injected with human peripheral blood mononuclear cells from a healthy donor (injection into the retroorbital sinus, 10 7cells per mouse; injection volume - 200 μl). The next day, on day 7 and on day 16, one group of mice was injected with anti-TRBV5-1 antibody 04-002 (n=9) (intraperitoneal injection, dosage 10 μg / kg; injection volume - 200 μl). The control group of animals (n=8) did not receive the antibody. On day 18 after cell injection, the percentage of TRBV5-1-positive cells in blood and spleen samples of animals was assessed by flow cytometry. TRBV5-1 positive cells were detected among the population of cells positive for human CD45 and CD3 markers. Figures 15 (blood samples) and 16 (spleen samples) show the percentage of TRBV5-1-positive cells for each animal, median ± interquartile range.It was shown that in NSIG mice, in whose blood human peripheral mononuclear cells circulate, after the introduction of the monoclonal antibody 04-002, a reliable depletion of the population of CD3-positive cells expressing the variable domain of the β-chain of the T-cell receptor, including the TRBV5-1 segment, is observed in blood and spleen samples.

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[0997] <?xml version="1.0" encoding="UTF-8"?>

[0998] <!DOCTYPE ST26SequenceListing PUBLIC "- / / WIPO / / DTD Sequence Listing

[0999] 1.3 / / EN" "ST26SequenceListing_V1_3.dtd">

[1000] <st26sequencelisting dtdversion="V1_3" filename="lseq TRBV5-1.xml"

[1001] softwarename="WIPO Sequence" softwareversion="2.3.0"

[1002] productiondate="2023-08-24">

[1003] <applicationidentification>

[1004] <ipofficecode> RU< / ipofficecode>

[1005] <applicationnumbertext>< / applicationnumbertext>

[1006] <filingdate>< / filingdate>

[1007] < / applicationidentification>

[1008] <applicantfilereference> TRBV5-1< / applicantfilereference>

[1009] <applicantname languagecode="ru">JOINT-STOCK COMPANY

[1010] "BIOCAD"< / applicantname>

[1011] <applicantnamelatin> JOINT STOCK COMPANY BIOCAD< / applicantnamelatin>

[1012] <inventiontitle languagecode="ru">Monoclonal antibody or its

[1013] An antigen-binding fragment that specifically binds to

[1014] TRBV5-1 segment of the variable domain of the beta chain of T-cell

[1015] human receptor and its application< / inventiontitle>

[1016] <sequencetotalquantity> 86< / sequencetotalquantity>

[1017] <sequencedata sequenceidnumber="1">

[1018] <insdseq>

[1019] <INSDSeq_length> 10< / INSDSeq_length>

[1020] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1021] <INSDSeq_division> PAT< / INSDSeq_division>

[1022] <INSDSeq_feature-table>

[1023] <insdfeature>

[1024] <INSDFeature_key>source< / INSDFeature_key>

[1025] <INSDFeature_location>1..10< / INSDFeature_location>

[1026] <INSDFeature_quals>

[1027] <insdqualifier>

[1028] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1029] <INSDQualifier_value>protein< / INSDQualifier_value>

[1030] < / insdqualifier>

[1031] <insdqualifier id="q2">

[1032] <INSDQualifier_name>organism< / INSDQualifier_name>

[1033] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1034] < / insdqualifier>

[1035] < / INSDFeature_quals>

[1036] < / insdfeature>

[1037] < / INSDSeq_feature-table>

[1038] <INSDSeq_sequence> SASSTVSYMH< / INSDSeq_sequence>

[1039] < / insdseq>

[1040] < / sequencedata>

[1041] <sequencedata sequenceidnumber="2">

[1042] <insdseq>

[1043] <INSDSeq_length>10< / INSDSeq_length>

[1044] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1045] <INSDSeq_division>PAT< / INSDSeq_division>

[1046] <INSDSeq_feature-table>

[1047] <insdfeature>

[1048] <INSDFeature_key>source< / INSDFeature_key>

[1049] <INSDFeature_location>1..10< / INSDFeature_location>

[1050] <INSDFeature_quals>

[1051] <insdqualifier>

[1052] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1053] <INSDQualifier_value>protein< / INSDQualifier_value>

[1054] < / insdqualifier>

[1055] <insdqualifier id="q4">

[1056] <INSDQualifier_name>organism< / INSDQualifier_name>

[1057] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1058] < / insdqualifier>

[1059] < / INSDFeature_quals>

[1060] < / insdfeature>

[1061] < / INSDSeq_feature-table>

[1062] <INSDSeq_sequence>SASSSVSYMH< / INSDSeq_sequence>

[1063] < / insdseq>

[1064] < / sequencedata>

[1065] <sequencedata sequenceidnumber="3">

[1066] <insdseq>

[1067] <INSDSeq_length> 10< / INSDSeq_length>

[1068] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1069] <INSDSeq_division> PAT< / INSDSeq_division>

[1070] <INSDSeq_feature-table>

[1071] <insdfeature>

[1072] <INSDFeature_key>source< / INSDFeature_key>

[1073] <INSDFeature_location>1..10< / INSDFeature_location>

[1074] <INSDFeature_quals>

[1075] <insdqualifier>

[1076] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1077] <INSDQualifier_value>protein< / INSDQualifier_value>

[1078] < / insdqualifier>

[1079] <insdqualifier id="q6">

[1080] <INSDQualifier_name>organism< / INSDQualifier_name>

[1081] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1082] < / insdqualifier>

[1083] < / INSDFeature_quals>

[1084] < / insdfeature>

[1085] < / INSDSeq_feature-table>

[1086] <INSDSeq_sequence> SASSEVSYMH< / INSDSeq_sequence>

[1087] < / insdseq>

[1088] < / sequencedata>

[1089] <sequencedata sequenceidnumber="4">

[1090] <insdseq>

[1091] <INSDSeq_length> 7< / INSDSeq_length>

[1092] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1093] <INSDSeq_division> PAT< / INSDSeq_division>

[1094] <INSDSeq_feature-table>

[1095] <insdfeature>

[1096] <INSDFeature_key>source< / INSDFeature_key>

[1097] <INSDFeature_location>1..7< / INSDFeature_location>

[1098] <INSDFeature_quals>

[1099] <insdqualifier>

[1100] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1101] <INSDQualifier_value>protein< / INSDQualifier_value>

[1102] < / insdqualifier>

[1103] <insdqualifier id="q8">

[1104] <INSDQualifier_name>organism< / INSDQualifier_name>

[1105] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1106] < / insdqualifier>

[1107] < / INSDFeature_quals>

[1108] < / insdfeature>

[1109] < / INSDSeq_feature-table>

[1110] <INSDSeq_sequence> EITCLASS< / INSDSeq_sequence>

[1111] < / insdseq>

[1112] < / sequencedata>

[1113] <sequencedata sequenceidnumber="5">

[1114] <insdseq>

[1115] <INSDSeq_length> 7< / INSDSeq_length>

[1116] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1117] <INSDSeq_division> PAT< / INSDSeq_division>

[1118] <INSDSeq_feature-table>

[1119] <insdfeature>

[1120] <INSDFeature_key>source< / INSDFeature_key>

[1121] <INSDFeature_location>1..7< / INSDFeature_location>

[1122] <INSDFeature_quals>

[1123] <insdqualifier>

[1124] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1125] <INSDQualifier_value>protein< / INSDQualifier_value>

[1126] < / insdqualifier>

[1127] <insdqualifier id="q10">

[1128] <INSDQualifier_name>organism< / INSDQualifier_name>

[1129] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1130] < / insdqualifier>

[1131] < / INSDFeature_quals>

[1132] < / insdfeature>

[1133] < / INSDSeq_feature-table>

[1134] <INSDSeq_sequence> EISCLFS< / INSDSeq_sequence>

[1135] < / insdseq>

[1136] < / sequencedata>

[1137] <sequencedata sequenceidnumber="6">

[1138] <insdseq>

[1139] <INSDSeq_length> 7< / INSDSeq_length>

[1140] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1141] <INSDSeq_division> PAT< / INSDSeq_division>

[1142] <INSDSeq_feature-table>

[1143] <insdfeature>

[1144] <INSDFeature_key>source< / INSDFeature_key>

[1145] <INSDFeature_location>1..7< / INSDFeature_location>

[1146] <INSDFeature_quals>

[1147] <insdqualifier>

[1148] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1149] <INSDQualifier_value>protein< / INSDQualifier_value>

[1150] < / insdqualifier>

[1151] <insdqualifier id="q12">

[1152] <INSDQualifier_name>organism< / INSDQualifier_name>

[1153] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1154] < / insdqualifier>

[1155] < / INSDFeature_quals>

[1156] < / insdfeature>

[1157] < / INSDSeq_feature-table>

[1158] <INSDSeq_sequence> ESKLAS< / INSDSeq_sequence>

[1159] < / insdseq>

[1160] < / sequencedata>

[1161] <sequencedata sequenceidnumber="7">

[1162] <insdseq>

[1163] <INSDSeq_length> 7< / INSDSeq_length>

[1164] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1165] <INSDSeq_division> PAT< / INSDSeq_division>

[1166] <INSDSeq_feature-table>

[1167] <insdfeature>

[1168] <INSDFeature_key>source< / INSDFeature_key>

[1169] <INSDFeature_location>1..7< / INSDFeature_location>

[1170] <INSDFeature_quals>

[1171] <insdqualifier>

[1172] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1173] <INSDQualifier_value>protein< / INSDQualifier_value>

[1174] < / insdqualifier>

[1175] <insdqualifier id="q14">

[1176] <INSDQualifier_name>organism< / INSDQualifier_name>

[1177] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1178] < / insdqualifier>

[1179] < / INSDFeature_quals>

[1180] < / insdfeature>

[1181] < / INSDSeq_feature-table>

[1182] <INSDSeq_sequence> EISKLMS< / INSDSeq_sequence>

[1183] < / insdseq>

[1184] < / sequencedata>

[1185] <sequencedata sequenceidnumber="8">

[1186] <insdseq>

[1187] <INSDSeq_length> 9< / INSDSeq_length>

[1188] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1189] <INSDSeq_division> PAT< / INSDSeq_division>

[1190] <INSDSeq_feature-table>

[1191] <insdfeature>

[1192] <INSDFeature_key>source< / INSDFeature_key>

[1193] <INSDFeature_location>1..9< / INSDFeature_location>

[1194] <INSDFeature_quals>

[1195] <insdqualifier>

[1196] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1197] <INSDQualifier_value>protein< / INSDQualifier_value>

[1198] < / insdqualifier>

[1199] <insdqualifier id="q16">

[1200] <INSDQualifier_name>organism< / INSDQualifier_name>

[1201] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1202] < / insdqualifier>

[1203] < / INSDFeature_quals>

[1204] < / insdfeature>

[1205] < / INSDSeq_feature-table>

[1206] <INSDSeq_sequence> QQWNYPLLS< / INSDSeq_sequence>

[1207] < / insdseq>

[1208] < / sequencedata>

[1209] <sequencedata sequenceidnumber="9">

[1210] <insdseq>

[1211] <INSDSeq_length> 9< / INSDSeq_length>

[1212] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1213] <INSDSeq_division> PAT< / INSDSeq_division>

[1214] <INSDSeq_feature-table>

[1215] <insdfeature>

[1216] <INSDFeature_key>source< / INSDFeature_key>

[1217] <INSDFeature_location>1..9< / INSDFeature_location>

[1218] <INSDFeature_quals>

[1219] <insdqualifier>

[1220] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1221] <INSDQualifier_value>protein< / INSDQualifier_value>

[1222] < / insdqualifier>

[1223] <insdqualifier id="q18">

[1224] <INSDQualifier_name>organism< / INSDQualifier_name>

[1225] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1226] < / insdqualifier>

[1227] < / INSDFeature_quals>

[1228] < / insdfeature>

[1229] < / INSDSeq_feature-table>

[1230] <INSDSeq_sequence> QQWNYPLLT< / INSDSeq_sequence>

[1231] < / insdseq>

[1232] < / sequencedata>

[1233] <sequencedata sequenceidnumber="10">

[1234] <insdseq>

[1235] <INSDSeq_length> 9< / INSDSeq_length>

[1236] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1237] <INSDSeq_division> PAT< / INSDSeq_division>

[1238] <INSDSeq_feature-table>

[1239] <insdfeature>

[1240] <INSDFeature_key>source< / INSDFeature_key>

[1241] <INSDFeature_location>1..9< / INSDFeature_location>

[1242] <INSDFeature_quals>

[1243] <insdqualifier>

[1244] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1245] <INSDQualifier_value>protein< / INSDQualifier_value>

[1246] < / insdqualifier>

[1247] <insdqualifier id="q20">

[1248] <INSDQualifier_name>organism< / INSDQualifier_name>

[1249] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1250] < / insdqualifier>

[1251] < / INSDFeature_quals>

[1252] < / insdfeature>

[1253] < / INSDSeq_feature-table>

[1254] <INSDSeq_sequence> QQWNYPRLT< / INSDSeq_sequence>

[1255] < / insdseq>

[1256] < / sequencedata>

[1257] <sequencedata sequenceidnumber="11">

[1258] <insdseq>

[1259] <INSDSeq_length> 9< / INSDSeq_length>

[1260] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1261] <INSDSeq_division> PAT< / INSDSeq_division>

[1262] <INSDSeq_feature-table>

[1263] <insdfeature>

[1264] <INSDFeature_key>source< / INSDFeature_key>

[1265] <INSDFeature_location>1..9< / INSDFeature_location>

[1266] <INSDFeature_quals>

[1267] <insdqualifier>

[1268] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1269] <INSDQualifier_value>protein< / INSDQualifier_value>

[1270] < / insdqualifier>

[1271] <insdqualifier id="q22">

[1272] <INSDQualifier_name>organism< / INSDQualifier_name>

[1273] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1274] < / insdqualifier>

[1275] < / INSDFeature_quals>

[1276] < / insdfeature>

[1277] < / INSDSeq_feature-table>

[1278] <INSDSeq_sequence> QQWNYPYLT< / INSDSeq_sequence>

[1279] < / insdseq>

[1280] < / sequencedata>

[1281] <sequencedata sequenceidnumber="12">

[1282] <insdseq>

[1283] <INSDSeq_length>5< / INSDSeq_length>

[1284] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1285] <INSDSeq_division>PAT< / INSDSeq_division>

[1286] <INSDSeq_feature-table>

[1287] <insdfeature>

[1288] <INSDFeature_key>source< / INSDFeature_key>

[1289] <INSDFeature_location>1..5< / INSDFeature_location>

[1290] <INSDFeature_quals>

[1291] <insdqualifier>

[1292] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1293] <INSDQualifier_value>protein< / INSDQualifier_value>

[1294] < / insdqualifier>

[1295] <insdqualifier id="q24">

[1296] <INSDQualifier_name>organism< / INSDQualifier_name>

[1297] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1298] < / insdqualifier>

[1299] < / INSDFeature_quals>

[1300] < / insdfeature>

[1301] < / INSDSeq_feature-table>

[1302] <INSDSeq_sequence>DYNIH< / INSDSeq_sequence>

[1303] < / insdseq>

[1304] < / sequencedata>

[1305] <sequencedata sequenceidnumber="13">

[1306] <insdseq>

[1307] <INSDSeq_length> 17< / INSDSeq_length>

[1308] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1309] <INSDSeq_division> PAT< / INSDSeq_division>

[1310] <INSDSeq_feature-table>

[1311] <insdfeature>

[1312] <INSDFeature_key>source< / INSDFeature_key>

[1313] <INSDFeature_location>1..17< / INSDFeature_location>

[1314] <INSDFeature_quals>

[1315] <insdqualifier>

[1316] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1317] <INSDQualifier_value>protein< / INSDQualifier_value>

[1318] < / insdqualifier>

[1319] <insdqualifier id="q26">

[1320] <INSDQualifier_name>organism< / INSDQualifier_name>

[1321] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1322] < / insdqualifier>

[1323] < / INSDFeature_quals>

[1324] < / insdfeature>

[1325] < / INSDSeq_feature-table>

[1326] <INSDSeq_sequence> YINPYQGRTGYNQKFQA< / INSDSeq_sequence>

[1327] < / insdseq>

[1328] < / sequencedata>

[1329] <sequencedata sequenceidnumber="14">

[1330] <insdseq>

[1331] <INSDSeq_length> 17< / INSDSeq_length>

[1332] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1333] <INSDSeq_division> PAT< / INSDSeq_division>

[1334] <INSDSeq_feature-table>

[1335] <insdfeature>

[1336] <INSDFeature_key>source< / INSDFeature_key>

[1337] <INSDFeature_location>1..17< / INSDFeature_location>

[1338] <INSDFeature_quals>

[1339] <insdqualifier>

[1340] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1341] <INSDQualifier_value>protein< / INSDQualifier_value>

[1342] < / insdqualifier>

[1343] <insdqualifier id="q28">

[1344] <INSDQualifier_name>organism< / INSDQualifier_name>

[1345] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1346] < / insdqualifier>

[1347] < / INSDFeature_quals>

[1348] < / insdfeature>

[1349] < / INSDSeq_feature-table>

[1350] <INSDSeq_sequence> YINPYQGRTGYNQKFQG< / INSDSeq_sequence>

[1351] < / insdseq>

[1352] < / sequencedata>

[1353] <sequencedata sequenceidnumber="15">

[1354] <insdseq>

[1355] <INSDSeq_length> 17< / INSDSeq_length>

[1356] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1357] <INSDSeq_division> PAT< / INSDSeq_division>

[1358] <INSDSeq_feature-table>

[1359] <insdfeature>

[1360] <INSDFeature_key>source< / INSDFeature_key>

[1361] <INSDFeature_location>1..17< / INSDFeature_location>

[1362] <INSDFeature_quals>

[1363] <insdqualifier>

[1364] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1365] <INSDQualifier_value>protein< / INSDQualifier_value>

[1366] < / insdqualifier>

[1367] <insdqualifier id="q30">

[1368] <INSDQualifier_name>organism< / INSDQualifier_name>

[1369] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1370] < / insdqualifier>

[1371] < / INSDFeature_quals>

[1372] < / insdfeature>

[1373] < / INSDSeq_feature-table>

[1374] <INSDSeq_sequence> YINPWNGRTGYNQKFQG< / INSDSeq_sequence>

[1375] < / insdseq>

[1376] < / sequencedata>

[1377] <sequencedata sequenceidnumber="16">

[1378] <insdseq>

[1379] <INSDSeq_length> 17< / INSDSeq_length>

[1380] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1381] <INSDSeq_division> PAT< / INSDSeq_division>

[1382] <INSDSeq_feature-table>

[1383] <insdfeature>

[1384] <INSDFeature_key>source< / INSDFeature_key>

[1385] <INSDFeature_location>1..17< / INSDFeature_location>

[1386] <INSDFeature_quals>

[1387] <insdqualifier>

[1388] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1389] <INSDQualifier_value>protein< / INSDQualifier_value>

[1390] < / insdqualifier>

[1391] <insdqualifier id="q32">

[1392] <INSDQualifier_name>organism< / INSDQualifier_name>

[1393] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1394] < / insdqualifier>

[1395] < / INSDFeature_quals>

[1396] < / insdfeature>

[1397] < / INSDSeq_feature-table>

[1398] <INSDSeq_sequence> YINPYNGRTGYNQKFQA< / INSDSeq_sequence>

[1399] < / insdseq>

[1400] < / sequencedata>

[1401] <sequencedata sequenceidnumber="17">

[1402] <insdseq>

[1403] <INSDSeq_length> 17< / INSDSeq_length>

[1404] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1405] <INSDSeq_division> PAT< / INSDSeq_division>

[1406] <INSDSeq_feature-table>

[1407] <insdfeature>

[1408] <INSDFeature_key>source< / INSDFeature_key>

[1409] <INSDFeature_location>1..17< / INSDFeature_location>

[1410] <INSDFeature_quals>

[1411] <insdqualifier>

[1412] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1413] <INSDQualifier_value>protein< / INSDQualifier_value>

[1414] < / insdqualifier>

[1415] <insdqualifier id="q34">

[1416] <INSDQualifier_name>organism< / INSDQualifier_name>

[1417] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1418] < / insdqualifier>

[1419] < / INSDFeature_quals>

[1420] < / insdfeature>

[1421] < / INSDSeq_feature-table>

[1422] <INSDSeq_sequence> YINPYNGRTGYNQKLQG< / INSDSeq_sequence>

[1423] < / insdseq>

[1424] < / sequencedata>

[1425] <sequencedata sequenceidnumber="18">

[1426] <insdseq>

[1427] <INSDSeq_length> 9< / INSDSeq_length>

[1428] <INSDSeq_moltype> AA< / INSDSeq_moltype>

[1429] <INSDSeq_division> PAT< / INSDSeq_division>

[1430] <INSDSeq_feature-table>

[1431] <insdfeature>

[1432] <INSDFeature_key>source< / INSDFeature_key>

[1433] <INSDFeature_location>1..9< / INSDFeature_location>

[1434] <INSDFeature_quals>

[1435] <insdqualifier>

[1436] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1437] <INSDQualifier_value>protein< / INSDQualifier_value>

[1438] < / insdqualifier>

[1439] <insdqualifier id="q36">

[1440] <INSDQualifier_name>organism< / INSDQualifier_name>

[1441] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1442] < / insdqualifier>

[1443] < / INSDFeature_quals>

[1444] < / insdfeature>

[1445] < / INSDSeq_feature-table>

[1446] <INSDSeq_sequence> WDGSSYFDY< / INSDSeq_sequence>

[1447] < / insdseq>

[1448] < / sequencedata>

[1449] <sequencedata sequenceidnumber="19">

[1450] <insdseq>

[1451] <INSDSeq_length>106< / INSDSeq_length>

[1452] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1453] <INSDSeq_division>PAT< / INSDSeq_division>

[1454] <INSDSeq_feature-table>

[1455] <insdfeature>

[1456] <INSDFeature_key>source< / INSDFeature_key>

[1457] <INSDFeature_location>1..106< / INSDFeature_location>

[1458] <INSDFeature_quals>

[1459] <insdqualifier>

[1460] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1461] <INSDQualifier_value>protein< / INSDQualifier_value>

[1462] < / insdqualifier>

[1463] <insdqualifier id="q38">

[1464] <INSDQualifier_name>organism< / INSDQualifier_name>

[1465] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1466] < / insdqualifier>

[1467] < / INSDFeature_quals>

[1468] < / insdfeature>

[1469] < / INSDSeq_feature-table>

[1470] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSTVSYMHWYQQKPAKAPKLFIYE

[1471] ITKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLSFGQGTKLEIK< / INSDSeq_seq

[1472] uence>

[1473] < / insdseq>

[1474] < / sequencedata>

[1475] <sequencedata sequenceidnumber="20">

[1476] <insdseq>

[1477] <INSDSeq_length>106< / INSDSeq_length>

[1478] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1479] <INSDSeq_division>PAT< / INSDSeq_division>

[1480] <INSDSeq_feature-table>

[1481] <insdfeature>

[1482] <INSDFeature_key>source< / INSDFeature_key>

[1483] <INSDFeature_location>1..106< / INSDFeature_location>

[1484] <INSDFeature_quals>

[1485] <insdqualifier>

[1486] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1487] <INSDQualifier_value>protein< / INSDQualifier_value>

[1488] < / insdqualifier>

[1489] <insdqualifier id="q40">

[1490] <INSDQualifier_name>organism< / INSDQualifier_name>

[1491] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1492] < / insdqualifier>

[1493] < / INSDFeature_quals>

[1494] < / insdfeature>

[1495] < / INSDSeq_feature-table>

[1496] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[1497] ISKLFSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLTFGQGTKLEIK< / INSDSeq_seq

[1498] uence>

[1499] < / insdseq>

[1500] < / sequencedata>

[1501] <sequencedata sequenceidnumber="21">

[1502] <insdseq>

[1503] <INSDSeq_length>106< / INSDSeq_length>

[1504] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1505] <INSDSeq_division>PAT< / INSDSeq_division>

[1506] <INSDSeq_feature-table>

[1507] <insdfeature>

[1508] <INSDFeature_key>source< / INSDFeature_key>

[1509] <INSDFeature_location>1..106< / INSDFeature_location>

[1510] <INSDFeature_quals>

[1511] <insdqualifier>

[1512] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1513] <INSDQualifier_value>protein< / INSDQualifier_value>

[1514] < / insdqualifier>

[1515] <insdqualifier id="q42">

[1516] <INSDQualifier_name>organism< / INSDQualifier_name>

[1517] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1518] < / insdqualifier>

[1519] < / INSDFeature_quals>

[1520] < / insdfeature>

[1521] < / INSDSeq_feature-table>

[1522] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSTVSYMHWYQQKPAKAPKLFIYE

[1523] ISKLFSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLSFGQGTKLEIK< / INSDSeq_seq

[1524] uence>

[1525] < / insdseq>

[1526] < / sequencedata>

[1527] <sequencedata sequenceidnumber="22">

[1528] <insdseq>

[1529] <INSDSeq_length>106< / INSDSeq_length>

[1530] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1531] <INSDSeq_division>PAT< / INSDSeq_division>

[1532] <INSDSeq_feature-table>

[1533] <insdfeature>

[1534] <INSDFeature_key>source< / INSDFeature_key>

[1535] <INSDFeature_location>1..106< / INSDFeature_location>

[1536] <INSDFeature_quals>

[1537] <insdqualifier>

[1538] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1539] <INSDQualifier_value>protein< / INSDQualifier_value>

[1540] < / insdqualifier>

[1541] <insdqualifier id="q44">

[1542] <INSDQualifier_name>organism< / INSDQualifier_name>

[1543] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1544] < / insdqualifier>

[1545] < / INSDFeature_quals>

[1546] < / insdfeature>

[1547] < / INSDSeq_feature-table>

[1548] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[1549] ITKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLTFGQGTKLEIK< / INSDSeq_seq

[1550] uence>

[1551] < / insdseq>

[1552] < / sequencedata>

[1553] <sequencedata sequenceidnumber="23">

[1554] <insdseq>

[1555] <INSDSeq_length>106< / INSDSeq_length>

[1556] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1557] <INSDSeq_division>PAT< / INSDSeq_division>

[1558] <INSDSeq_feature-table>

[1559] <insdfeature>

[1560] <INSDFeature_key>source< / INSDFeature_key>

[1561] <INSDFeature_location>1..106< / INSDFeature_location>

[1562] <INSDFeature_quals>

[1563] <insdqualifier>

[1564] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1565] <INSDQualifier_value>protein< / INSDQualifier_value>

[1566] < / insdqualifier>

[1567] <insdqualifier id="q46">

[1568] <INSDQualifier_name>organism< / INSDQualifier_name>

[1569] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1570] < / insdqualifier>

[1571] < / INSDFeature_quals>

[1572] < / insdfeature>

[1573] < / INSDSeq_feature-table>

[1574] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[1575] ISKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLSFGQGTKLEIK< / INSDSeq_seq

[1576] uence>

[1577] < / insdseq>

[1578] < / sequencedata>

[1579] <sequencedata sequenceidnumber="24">

[1580] <insdseq>

[1581] <INSDSeq_length>106< / INSDSeq_length>

[1582] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1583] <INSDSeq_division>PAT< / INSDSeq_division>

[1584] <INSDSeq_feature-table>

[1585] <insdfeature>

[1586] <INSDFeature_key>source< / INSDFeature_key>

[1587] <INSDFeature_location>1..106< / INSDFeature_location>

[1588] <INSDFeature_quals>

[1589] <insdqualifier>

[1590] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1591] <INSDQualifier_value>protein< / INSDQualifier_value>

[1592] < / insdqualifier>

[1593] <insdqualifier id="q48">

[1594] <INSDQualifier_name>organism< / INSDQualifier_name>

[1595] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1596] < / insdqualifier>

[1597] < / INSDFeature_quals>

[1598] < / insdfeature>

[1599] < / INSDSeq_feature-table>

[1600] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSTVSYMHWYQQKPAKAPKLFIYE

[1601] ISKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLTFGQGTKLEIK< / INSDSeq_seq

[1602] uence>

[1603] < / insdseq>

[1604] < / sequencedata>

[1605] <sequencedata sequenceidnumber="25">

[1606] <insdseq>

[1607] <INSDSeq_length>106< / INSDSeq_length>

[1608] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1609] <INSDSeq_division>PAT< / INSDSeq_division>

[1610] <INSDSeq_feature-table>

[1611] <insdfeature>

[1612] <INSDFeature_key>source< / INSDFeature_key>

[1613] <INSDFeature_location>1..106< / INSDFeature_location>

[1614] <INSDFeature_quals>

[1615] <insdqualifier>

[1616] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1617] <INSDQualifier_value>protein< / INSDQualifier_value>

[1618] < / insdqualifier>

[1619] <insdqualifier id="q50">

[1620] <INSDQualifier_name>organism< / INSDQualifier_name>

[1621] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1622] < / insdqualifier>

[1623] < / INSDFeature_quals>

[1624] < / insdfeature>

[1625] < / INSDSeq_feature-table>

[1626] <INSDSeq_sequence>AIRLTQSPFSLSASVGDRVTITCSASSEVSYMHWYQQKPAKAPKLFIYE

[1627] ISKLMSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPRLTFGQGTKLEIK< / INSDSeq_seq

[1628] uence>

[1629] < / insdseq>

[1630] < / sequencedata>

[1631] <sequencedata sequenceidnumber="26">

[1632] <insdseq>

[1633] <INSDSeq_length>106< / INSDSeq_length>

[1634] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1635] <INSDSeq_division>PAT< / INSDSeq_division>

[1636] <INSDSeq_feature-table>

[1637] <insdfeature>

[1638] <INSDFeature_key>source< / INSDFeature_key>

[1639] <INSDFeature_location>1..106< / INSDFeature_location>

[1640] <INSDFeature_quals>

[1641] <insdqualifier>

[1642] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1643] <INSDQualifier_value>protein< / INSDQualifier_value>

[1644] < / insdqualifier>

[1645] <insdqualifier id="q52">

[1646] <INSDQualifier_name>organism< / INSDQualifier_name>

[1647] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1648] < / insdqualifier>

[1649] < / INSDFeature_quals>

[1650] < / insdfeature>

[1651] < / INSDSeq_feature-table>

[1652] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[1653] ISKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPYLTFGQGTKLEIK< / INSDSeq_seq

[1654] uence>

[1655] < / insdseq>

[1656] < / sequencedata>

[1657] <sequencedata sequenceidnumber="27">

[1658] <insdseq>

[1659] <INSDSeq_length>106< / INSDSeq_length>

[1660] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1661] <INSDSeq_division>PAT< / INSDSeq_division>

[1662] <INSDSeq_feature-table>

[1663] <insdfeature>

[1664] <INSDFeature_key>source< / INSDFeature_key>

[1665] <INSDFeature_location>1..106< / INSDFeature_location>

[1666] <INSDFeature_quals>

[1667] <insdqualifier>

[1668] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1669] <INSDQualifier_value>protein< / INSDQualifier_value>

[1670] < / insdqualifier>

[1671] <insdqualifier id="q54">

[1672] <INSDQualifier_name>organism< / INSDQualifier_name>

[1673] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1674] < / insdqualifier>

[1675] < / INSDFeature_quals>

[1676] < / insdfeature>

[1677] < / INSDSeq_feature-table>

[1678] <INSDSeq_sequence>AIRLTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[1679] ISKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPRLTFGQGTKLEIK< / INSDSeq_seq

[1680] uence>

[1681] < / insdseq>

[1682] < / sequencedata>

[1683] <sequencedata sequenceidnumber="28">

[1684] <insdseq>

[1685] <INSDSeq_length>106< / INSDSeq_length>

[1686] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1687] <INSDSeq_division>PAT< / INSDSeq_division>

[1688] <INSDSeq_feature-table>

[1689] <insdfeature>

[1690] <INSDFeature_key>source< / INSDFeature_key>

[1691] <INSDFeature_location>1..106< / INSDFeature_location>

[1692] <INSDFeature_quals>

[1693] <insdqualifier>

[1694] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1695] <INSDQualifier_value>protein< / INSDQualifier_value>

[1696] < / insdqualifier>

[1697] <insdqualifier id="q56">

[1698] <INSDQualifier_name>organism< / INSDQualifier_name>

[1699] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1700] < / insdqualifier>

[1701] < / INSDFeature_quals>

[1702] < / insdfeature>

[1703] < / INSDSeq_feature-table>

[1704] <INSDSeq_sequence>AIRLTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[1705] ISKLMSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLTFGQGTKLEIK< / INSDSeq_seq

[1706] uence>

[1707] < / insdseq>

[1708] < / sequencedata>

[1709] <sequencedata sequenceidnumber="29">

[1710] <insdseq>

[1711] <INSDSeq_length>118< / INSDSeq_length>

[1712] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1713] <INSDSeq_division>PAT< / INSDSeq_division>

[1714] <INSDSeq_feature-table>

[1715] <insdfeature>

[1716] <INSDFeature_key>source< / INSDFeature_key>

[1717] <INSDFeature_location>1..118< / INSDFeature_location>

[1718] <INSDFeature_quals>

[1719] <insdqualifier>

[1720] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1721] <INSDQualifier_value>protein< / INSDQualifier_value>

[1722] < / insdqualifier>

[1723] <insdqualifier id="q58">

[1724] <INSDQualifier_name>organism< / INSDQualifier_name>

[1725] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1726] < / insdqualifier>

[1727] < / INSDFeature_quals>

[1728] < / insdfeature>

[1729] < / INSDSeq_feature-table>

[1730] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWMG

[1731] YINPYQGRTGYNQKFQARVTLTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSS<

[1732] / INSDSeq_sequence>

[1733] < / insdseq>

[1734] < / sequencedata>

[1735] <sequencedata sequenceidnumber="30">

[1736] <insdseq>

[1737] <INSDSeq_length>118< / INSDSeq_length>

[1738] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1739] <INSDSeq_division>PAT< / INSDSeq_division>

[1740] <INSDSeq_feature-table>

[1741] <insdfeature>

[1742] <INSDFeature_key>source< / INSDFeature_key>

[1743] <INSDFeature_location>1..118< / INSDFeature_location>

[1744] <INSDFeature_quals>

[1745] <insdqualifier>

[1746] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1747] <INSDQualifier_value>protein< / INSDQualifier_value>

[1748] < / insdqualifier>

[1749] <insdqualifier id="q60">

[1750] <INSDQualifier_name>organism< / INSDQualifier_name>

[1751] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1752] < / insdqualifier>

[1753] < / INSDFeature_quals>

[1754] < / insdfeature>

[1755] < / INSDSeq_feature-table>

[1756] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWVG

[1757] YINPYQGRTGYNQKFQGRVTLTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSS<

[1758] / INSDSeq_sequence>

[1759] < / insdseq>

[1760] < / sequencedata>

[1761] <sequencedata sequenceidnumber="31">

[1762] <insdseq>

[1763] <INSDSeq_length>118< / INSDSeq_length>

[1764] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1765] <INSDSeq_division>PAT< / INSDSeq_division>

[1766] <INSDSeq_feature-table>

[1767] <insdfeature>

[1768] <INSDFeature_key>source< / INSDFeature_key>

[1769] <INSDFeature_location>1..118< / INSDFeature_location>

[1770] <INSDFeature_quals>

[1771] <insdqualifier>

[1772] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1773] <INSDQualifier_value>protein< / INSDQualifier_value>

[1774] < / insdqualifier>

[1775] <insdqualifier id="q62">

[1776] <INSDQualifier_name>organism< / INSDQualifier_name>

[1777] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1778] < / insdqualifier>

[1779] < / INSDFeature_quals>

[1780] < / insdfeature>

[1781] < / INSDSeq_feature-table>

[1782] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWVG

[1783] YINPYQGRTGYNQKFQARVTMTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSS<

[1784] / INSDSeq_sequence>

[1785] < / insdseq>

[1786] < / sequencedata>

[1787] <sequencedata sequenceidnumber="32">

[1788] <insdseq>

[1789] <INSDSeq_length>118< / INSDSeq_length>

[1790] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1791] <INSDSeq_division>PAT< / INSDSeq_division>

[1792] <INSDSeq_feature-table>

[1793] <insdfeature>

[1794] <INSDFeature_key>source< / INSDFeature_key>

[1795] <INSDFeature_location>1..118< / INSDFeature_location>

[1796] <INSDFeature_quals>

[1797] <insdqualifier>

[1798] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1799] <INSDQualifier_value>protein< / INSDQualifier_value>

[1800] < / insdqualifier>

[1801] <insdqualifier id="q64">

[1802] <INSDQualifier_name>organism< / INSDQualifier_name>

[1803] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1804] < / insdqualifier>

[1805] < / INSDFeature_quals>

[1806] < / insdfeature>

[1807] < / INSDSeq_feature-table>

[1808] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWVG

[1809] YINPWNGRTGYNQKFQGRVTLTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSS<

[1810] / INSDSeq_sequence>

[1811] < / insdseq>

[1812] < / sequencedata>

[1813] <sequencedata sequenceidnumber="33">

[1814] <insdseq>

[1815] <INSDSeq_length>118< / INSDSeq_length>

[1816] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1817] <INSDSeq_division>PAT< / INSDSeq_division>

[1818] <INSDSeq_feature-table>

[1819] <insdfeature>

[1820] <INSDFeature_key>source< / INSDFeature_key>

[1821] <INSDFeature_location>1..118< / INSDFeature_location>

[1822] <INSDFeature_quals>

[1823] <insdqualifier>

[1824] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1825] <INSDQualifier_value>protein< / INSDQualifier_value>

[1826] < / insdqualifier>

[1827] <insdqualifier id="q66">

[1828] <INSDQualifier_name>organism< / INSDQualifier_name>

[1829] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1830] < / insdqualifier>

[1831] < / INSDFeature_quals>

[1832] < / insdfeature>

[1833] < / INSDSeq_feature-table>

[1834] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWVG

[1835] YINPYNGRTGYNQKFQARVTLTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSS<

[1836] / INSDSeq_sequence>

[1837] < / insdseq>

[1838] < / sequencedata>

[1839] <sequencedata sequenceidnumber="34">

[1840] <insdseq>

[1841] <INSDSeq_length>118< / INSDSeq_length>

[1842] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1843] <INSDSeq_division>PAT< / INSDSeq_division>

[1844] <INSDSeq_feature-table>

[1845] <insdfeature>

[1846] <INSDFeature_key>source< / INSDFeature_key>

[1847] <INSDFeature_location>1..118< / INSDFeature_location>

[1848] <INSDFeature_quals>

[1849] <insdqualifier>

[1850] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1851] <INSDQualifier_value>protein< / INSDQualifier_value>

[1852] < / insdqualifier>

[1853] <insdqualifier id="q68">

[1854] <INSDQualifier_name>organism< / INSDQualifier_name>

[1855] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1856] < / insdqualifier>

[1857] < / INSDFeature_quals>

[1858] < / insdfeature>

[1859] < / INSDSeq_feature-table>

[1860] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWVG

[1861] YINPYNGRTGYNQKLQGRVTLTVDKSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSS<

[1862] / INSDSeq_sequence>

[1863] < / insdseq>

[1864] < / sequencedata>

[1865] <sequencedata sequenceidnumber="35">

[1866] <insdseq>

[1867] <INSDSeq_length>213< / INSDSeq_length>

[1868] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1869] <INSDSeq_division>PAT< / INSDSeq_division>

[1870] <INSDSeq_feature-table>

[1871] <insdfeature>

[1872] <INSDFeature_key>source< / INSDFeature_key>

[1873] <INSDFeature_location>1..213< / INSDFeature_location>

[1874] <INSDFeature_quals>

[1875] <insdqualifier>

[1876] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1877] <INSDQualifier_value>protein< / INSDQualifier_value>

[1878] < / insdqualifier>

[1879] <insdqualifier id="q70">

[1880] <INSDQualifier_name>organism< / INSDQualifier_name>

[1881] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1882] < / insdqualifier>

[1883] < / INSDFeature_quals>

[1884] < / insdfeature>

[1885] < / INSDSeq_feature-table>

[1886] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSTVSYMHWYQQKPAKAPKLFIYE

[1887] ITKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLSFGQGTKLEIKRTVAAPSVFIFPP

[1888] SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

[1889] VYACEVTHQGLSSPVTKSFNRGEC< / INSDSeq_sequence>

[1890] < / insdseq>

[1891] < / sequencedata>

[1892] <sequencedata sequenceidnumber="36">

[1893] <insdseq>

[1894] <INSDSeq_length>213< / INSDSeq_length>

[1895] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1896] <INSDSeq_division>PAT< / INSDSeq_division>

[1897] <INSDSeq_feature-table>

[1898] <insdfeature>

[1899] <INSDFeature_key>source< / INSDFeature_key>

[1900] <INSDFeature_location>1..213< / INSDFeature_location>

[1901] <INSDFeature_quals>

[1902] <insdqualifier>

[1903] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1904] <INSDQualifier_value>protein< / INSDQualifier_value>

[1905] < / insdqualifier>

[1906] <insdqualifier id="q72">

[1907] <INSDQualifier_name>organism< / INSDQualifier_name>

[1908] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1909] < / insdqualifier>

[1910] < / INSDFeature_quals>

[1911] < / insdfeature>

[1912] < / INSDSeq_feature-table>

[1913] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[1914] ISKLFSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLTFGQGTKLEIKRTVAAPSVFIFPP

[1915] SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

[1916] VYACEVTHQGLSSPVTKSFNRGEC< / INSDSeq_sequence>

[1917] < / insdseq>

[1918] < / sequencedata>

[1919] <sequencedata sequenceidnumber="37">

[1920] <insdseq>

[1921] <INSDSeq_length>213< / INSDSeq_length>

[1922] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1923] <INSDSeq_division>PAT< / INSDSeq_division>

[1924] <INSDSeq_feature-table>

[1925] <insdfeature>

[1926] <INSDFeature_key>source< / INSDFeature_key>

[1927] <INSDFeature_location>1..213< / INSDFeature_location>

[1928] <INSDFeature_quals>

[1929] <insdqualifier>

[1930] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1931] <INSDQualifier_value>protein< / INSDQualifier_value>

[1932] < / insdqualifier>

[1933] <insdqualifier id="q74">

[1934] <INSDQualifier_name>organism< / INSDQualifier_name>

[1935] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1936] < / insdqualifier>

[1937] < / INSDFeature_quals>

[1938] < / insdfeature>

[1939] < / INSDSeq_feature-table>

[1940] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSTVSYMHWYQQKPAKAPKLFIYE

[1941] ISKLFSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLSFGQGTKLEIKRTVAAPSVFIFPP

[1942] SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

[1943] VYACEVTHQGLSSPVTKSFNRGEC< / INSDSeq_sequence>

[1944] < / insdseq>

[1945] < / sequencedata>

[1946] <sequencedata sequenceidnumber="38">

[1947] <insdseq>

[1948] <INSDSeq_length>213< / INSDSeq_length>

[1949] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1950] <INSDSeq_division>PAT< / INSDSeq_division>

[1951] <INSDSeq_feature-table>

[1952] <insdfeature>

[1953] <INSDFeature_key>source< / INSDFeature_key>

[1954] <INSDFeature_location>1..213< / INSDFeature_location>

[1955] <INSDFeature_quals>

[1956] <insdqualifier>

[1957] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1958] <INSDQualifier_value>protein< / INSDQualifier_value>

[1959] < / insdqualifier>

[1960] <insdqualifier id="q76">

[1961] <INSDQualifier_name>organism< / INSDQualifier_name>

[1962] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1963] < / insdqualifier>

[1964] < / INSDFeature_quals>

[1965] < / insdfeature>

[1966] < / INSDSeq_feature-table>

[1967] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[1968] ITKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLTFGQGTKLEIKRTVAAPSVFIFPP

[1969] SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

[1970] VYACEVTHQGLSSPVTKSFNRGEC< / INSDSeq_sequence>

[1971] < / insdseq>

[1972] < / sequencedata>

[1973] <sequencedata sequenceidnumber="39">

[1974] <insdseq>

[1975] <INSDSeq_length>213< / INSDSeq_length>

[1976] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[1977] <INSDSeq_division>PAT< / INSDSeq_division>

[1978] <INSDSeq_feature-table>

[1979] <insdfeature>

[1980] <INSDFeature_key>source< / INSDFeature_key>

[1981] <INSDFeature_location>1..213< / INSDFeature_location>

[1982] <INSDFeature_quals>

[1983] <insdqualifier>

[1984] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[1985] <INSDQualifier_value>protein< / INSDQualifier_value>

[1986] < / insdqualifier>

[1987] <insdqualifier id="q78">

[1988] <INSDQualifier_name>organism< / INSDQualifier_name>

[1989] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[1990] < / insdqualifier>

[1991] < / INSDFeature_quals>

[1992] < / insdfeature>

[1993] < / INSDSeq_feature-table>

[1994] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[1995] ISKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLSFGQGTKLEIKRTVAAPSVFIFPP

[1996] SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

[1997] VYACEVTHQGLSSPVTKSFNRGEC< / INSDSeq_sequence>

[1998] < / insdseq>

[1999] < / sequencedata>

[2000] <sequencedata sequenceidnumber="40">

[2001] <insdseq>

[2002] <INSDSeq_length>213< / INSDSeq_length>

[2003] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2004] <INSDSeq_division>PAT< / INSDSeq_division>

[2005] <INSDSeq_feature-table>

[2006] <insdfeature>

[2007] <INSDFeature_key>source< / INSDFeature_key>

[2008] <INSDFeature_location>1..213< / INSDFeature_location>

[2009] <INSDFeature_quals>

[2010] <insdqualifier>

[2011] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2012] <INSDQualifier_value>protein< / INSDQualifier_value>

[2013] < / insdqualifier>

[2014] <insdqualifier id="q80">

[2015] <INSDQualifier_name>organism< / INSDQualifier_name>

[2016] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2017] < / insdqualifier>

[2018] < / INSDFeature_quals>

[2019] < / insdfeature>

[2020] < / INSDSeq_feature-table>

[2021] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSTVSYMHWYQQKPAKAPKLFIYE

[2022] ISKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLTFGQGTKLEIKRTVAAPSVFIFPP

[2023] SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

[2024] VYACEVTHQGLSSPVTKSFNRGEC< / INSDSeq_sequence>

[2025] < / insdseq>

[2026] < / sequencedata>

[2027] <sequencedata sequenceidnumber="41">

[2028] <insdseq>

[2029] <INSDSeq_length>213< / INSDSeq_length>

[2030] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2031] <INSDSeq_division>PAT< / INSDSeq_division>

[2032] <INSDSeq_feature-table>

[2033] <insdfeature>

[2034] <INSDFeature_key>source< / INSDFeature_key>

[2035] <INSDFeature_location>1..213< / INSDFeature_location>

[2036] <INSDFeature_quals>

[2037] <insdqualifier>

[2038] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2039] <INSDQualifier_value>protein< / INSDQualifier_value>

[2040] < / insdqualifier>

[2041] <insdqualifier id="q82">

[2042] <INSDQualifier_name>organism< / INSDQualifier_name>

[2043] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2044] < / insdqualifier>

[2045] < / INSDFeature_quals>

[2046] < / insdfeature>

[2047] < / INSDSeq_feature-table>

[2048] <INSDSeq_sequence>AIRLTQSPFSLSASVGDRVTITCSASSEVSYMHWYQQKPAKAPKLFIYE

[2049] ISKLMSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPRLTFGQGTKLEIKRTVAAPSVFIFPP

[2050] SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

[2051] VYACEVTHQGLSSPVTKSFNRGEC< / INSDSeq_sequence>

[2052] < / insdseq>

[2053] < / sequencedata>

[2054] <sequencedata sequenceidnumber="42">

[2055] <insdseq>

[2056] <INSDSeq_length>213< / INSDSeq_length>

[2057] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2058] <INSDSeq_division>PAT< / INSDSeq_division>

[2059] <INSDSeq_feature-table>

[2060] <insdfeature>

[2061] <INSDFeature_key>source< / INSDFeature_key>

[2062] <INSDFeature_location>1..213< / INSDFeature_location>

[2063] <INSDFeature_quals>

[2064] <insdqualifier>

[2065] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2066] <INSDQualifier_value>protein< / INSDQualifier_value>

[2067] < / insdqualifier>

[2068] <insdqualifier id="q84">

[2069] <INSDQualifier_name>organism< / INSDQualifier_name>

[2070] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2071] < / insdqualifier>

[2072] < / INSDFeature_quals>

[2073] < / insdfeature>

[2074] < / INSDSeq_feature-table>

[2075] <INSDSeq_sequence>AIRMTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[2076] ISKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPYLTFGQGTKLEIKRTVAAPSVFIFPP

[2077] SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

[2078] VYACEVTHQGLSSPVTKSFNRGEC< / INSDSeq_sequence>

[2079] < / insdseq>

[2080] < / sequencedata>

[2081] <sequencedata sequenceidnumber="43">

[2082] <insdseq>

[2083] <INSDSeq_length>213< / INSDSeq_length>

[2084] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2085] <INSDSeq_division>PAT< / INSDSeq_division>

[2086] <INSDSeq_feature-table>

[2087] <insdfeature>

[2088] <INSDFeature_key>source< / INSDFeature_key>

[2089] <INSDFeature_location>1..213< / INSDFeature_location>

[2090] <INSDFeature_quals>

[2091] <insdqualifier>

[2092] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2093] <INSDQualifier_value>protein< / INSDQualifier_value>

[2094] < / insdqualifier>

[2095] <insdqualifier id="q86">

[2096] <INSDQualifier_name>organism< / INSDQualifier_name>

[2097] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2098] < / insdqualifier>

[2099] < / INSDFeature_quals>

[2100] < / insdfeature>

[2101] < / INSDSeq_feature-table>

[2102] <INSDSeq_sequence>AIRLTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[2103] ISKLASGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPRLTFGQGTKLEIKRTVAAPSVFIFPP

[2104] SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

[2105] VYACEVTHQGLSSPVTKSFNRGEC< / INSDSeq_sequence>

[2106] < / insdseq>

[2107] < / sequencedata>

[2108] <sequencedata sequenceidnumber="44">

[2109] <insdseq>

[2110] <INSDSeq_length>213< / INSDSeq_length>

[2111] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2112] <INSDSeq_division>PAT< / INSDSeq_division>

[2113] <INSDSeq_feature-table>

[2114] <insdfeature>

[2115] <INSDFeature_key>source< / INSDFeature_key>

[2116] <INSDFeature_location>1..213< / INSDFeature_location>

[2117] <INSDFeature_quals>

[2118] <insdqualifier>

[2119] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2120] <INSDQualifier_value>protein< / INSDQualifier_value>

[2121] < / insdqualifier>

[2122] <insdqualifier id="q88">

[2123] <INSDQualifier_name>organism< / INSDQualifier_name>

[2124] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2125] < / insdqualifier>

[2126] < / INSDFeature_quals>

[2127] < / insdfeature>

[2128] < / INSDSeq_feature-table>

[2129] <INSDSeq_sequence>AIRLTQSPFSLSASVGDRVTITCSASSSVSYMHWYQQKPAKAPKLFIYE

[2130] ISKLMSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQWNYPLLTFGQGTKLEIKRTVAAPSVFIFPP

[2131] SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

[2132] VYACEVTHQGLSSPVTKSFNRGEC< / INSDSeq_sequence>

[2133] < / insdseq>

[2134] < / sequencedata>

[2135] <sequencedata sequenceidnumber="45">

[2136] <insdseq>

[2137] <INSDSeq_length>446< / INSDSeq_length>

[2138] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2139] <INSDSeq_division>PAT< / INSDSeq_division>

[2140] <INSDSeq_feature-table>

[2141] <insdfeature>

[2142] <INSDFeature_key>source< / INSDFeature_key>

[2143] <INSDFeature_location>1..446< / INSDFeature_location>

[2144] <INSDFeature_quals>

[2145] <insdqualifier>

[2146] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2147] <INSDQualifier_value>protein< / INSDQualifier_value>

[2148] < / insdqualifier>

[2149] <insdqualifier id="q90">

[2150] <INSDQualifier_name>organism< / INSDQualifier_name>

[2151] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2152] < / insdqualifier>

[2153] < / INSDFeature_quals>

[2154] < / insdfeature>

[2155] < / INSDSeq_feature-table>

[2156] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWMG

[2157] YINPYQGRTGYNQKFQARVTLTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSSA

[2158] STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTV

[2159] PSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

[2160] VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

[2161] PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

[2162] DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP< / INSDSeq_sequence>

[2163] < / insdseq>

[2164] < / sequencedata>

[2165] <sequencedata sequenceidnumber="46">

[2166] <insdseq>

[2167] <INSDSeq_length>448< / INSDSeq_length>

[2168] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2169] <INSDSeq_division>PAT< / INSDSeq_division>

[2170] <INSDSeq_feature-table>

[2171] <insdfeature>

[2172] <INSDFeature_key>source< / INSDFeature_key>

[2173] <INSDFeature_location>1..448< / INSDFeature_location>

[2174] <INSDFeature_quals>

[2175] <insdqualifier>

[2176] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2177] <INSDQualifier_value>protein< / INSDQualifier_value>

[2178] < / insdqualifier>

[2179] <insdqualifier id="q92">

[2180] <INSDQualifier_name>organism< / INSDQualifier_name>

[2181] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2182] < / insdqualifier>

[2183] < / INSDFeature_quals>

[2184] < / insdfeature>

[2185] < / INSDSeq_feature-table>

[2186] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWMG

[2187] YINPYQGRTGYNQKFQARVTLTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSSA

[2188] STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTV

[2189] PSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

[2190] VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

[2191] PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

[2192] DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK< / INSDSeq_sequence>

[2193] < / insdseq>

[2194] < / sequencedata>

[2195] <sequencedata sequenceidnumber="47">

[2196] <insdseq>

[2197] <INSDSeq_length>448< / INSDSeq_length>

[2198] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2199] <INSDSeq_division>PAT< / INSDSeq_division>

[2200] <INSDSeq_feature-table>

[2201] <insdfeature>

[2202] <INSDFeature_key>source< / INSDFeature_key>

[2203] <INSDFeature_location>1..448< / INSDFeature_location>

[2204] <INSDFeature_quals>

[2205] <insdqualifier>

[2206] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2207] <INSDQualifier_value>protein< / INSDQualifier_value>

[2208] < / insdqualifier>

[2209] <insdqualifier id="q94">

[2210] <INSDQualifier_name>organism< / INSDQualifier_name>

[2211] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2212] < / insdqualifier>

[2213] < / INSDFeature_quals>

[2214] < / insdfeature>

[2215] < / INSDSeq_feature-table>

[2216] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWVG

[2217] YINPYQGRTGYNQKFQGRVTLTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSSA

[2218] STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTV

[2219] PSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

[2220] VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

[2221] PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

[2222] DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK< / INSDSeq_sequence>

[2223] < / insdseq>

[2224] < / sequencedata>

[2225] <sequencedata sequenceidnumber="48">

[2226] <insdseq>

[2227] <INSDSeq_length>446< / INSDSeq_length>

[2228] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2229] <INSDSeq_division>PAT< / INSDSeq_division>

[2230] <INSDSeq_feature-table>

[2231] <insdfeature>

[2232] <INSDFeature_key>source< / INSDFeature_key>

[2233] <INSDFeature_location>1..446< / INSDFeature_location>

[2234] <INSDFeature_quals>

[2235] <insdqualifier>

[2236] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2237] <INSDQualifier_value>protein< / INSDQualifier_value>

[2238] < / insdqualifier>

[2239] <insdqualifier id="q96">

[2240] <INSDQualifier_name>organism< / INSDQualifier_name>

[2241] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2242] < / insdqualifier>

[2243] < / INSDFeature_quals>

[2244] < / insdfeature>

[2245] < / INSDSeq_feature-table>

[2246] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWVG

[2247] YINPYQGRTGYNQKFQGRVTLTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSSA

[2248] STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTV

[2249] PSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

[2250] VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

[2251] PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

[2252] DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP< / INSDSeq_sequence>

[2253] < / insdseq>

[2254] < / sequencedata>

[2255] <sequencedata sequenceidnumber="49">

[2256] <insdseq>

[2257] <INSDSeq_length>446< / INSDSeq_length>

[2258] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2259] <INSDSeq_division>PAT< / INSDSeq_division>

[2260] <INSDSeq_feature-table>

[2261] <insdfeature>

[2262] <INSDFeature_key>source< / INSDFeature_key>

[2263] <INSDFeature_location>1..446< / INSDFeature_location>

[2264] <INSDFeature_quals>

[2265] <insdqualifier>

[2266] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2267] <INSDQualifier_value>protein< / INSDQualifier_value>

[2268] < / insdqualifier>

[2269] <insdqualifier id="q98">

[2270] <INSDQualifier_name>organism< / INSDQualifier_name>

[2271] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2272] < / insdqualifier>

[2273] < / INSDFeature_quals>

[2274] < / insdfeature>

[2275] < / INSDSeq_feature-table>

[2276] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWVG

[2277] YINPYQGRTGYNQKFQARVTMTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSSA

[2278] STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTV

[2279] PSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

[2280] VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

[2281] PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

[2282] DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP< / INSDSeq_sequence>

[2283] < / insdseq>

[2284] < / sequencedata>

[2285] <sequencedata sequenceidnumber="50">

[2286] <insdseq>

[2287] <INSDSeq_length>448< / INSDSeq_length>

[2288] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2289] <INSDSeq_division>PAT< / INSDSeq_division>

[2290] <INSDSeq_feature-table>

[2291] <insdfeature>

[2292] <INSDFeature_key>source< / INSDFeature_key>

[2293] <INSDFeature_location>1..448< / INSDFeature_location>

[2294] <INSDFeature_quals>

[2295] <insdqualifier>

[2296] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2297] <INSDQualifier_value>protein< / INSDQualifier_value>

[2298] < / insdqualifier>

[2299] <insdqualifier id="q100">

[2300] <INSDQualifier_name>organism< / INSDQualifier_name>

[2301] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2302] < / insdqualifier>

[2303] < / INSDFeature_quals>

[2304] < / insdfeature>

[2305] < / INSDSeq_feature-table>

[2306] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWVG

[2307] YINPWNGRTGYNQKFQGRVTLTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSSA

[2308] STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTV

[2309] PSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

[2310] VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

[2311] PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

[2312] DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK< / INSDSeq_sequence>

[2313] < / insdseq>

[2314] < / sequencedata>

[2315] <sequencedata sequenceidnumber="51">

[2316] <insdseq>

[2317] <INSDSeq_length>448< / INSDSeq_length>

[2318] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2319] <INSDSeq_division>PAT< / INSDSeq_division>

[2320] <INSDSeq_feature-table>

[2321] <insdfeature>

[2322] <INSDFeature_key>source< / INSDFeature_key>

[2323] <INSDFeature_location>1..448< / INSDFeature_location>

[2324] <INSDFeature_quals>

[2325] <insdqualifier>

[2326] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2327] <INSDQualifier_value>protein< / INSDQualifier_value>

[2328] < / insdqualifier>

[2329] <insdqualifier id="q102">

[2330] <INSDQualifier_name>organism< / INSDQualifier_name>

[2331] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2332] < / insdqualifier>

[2333] < / INSDFeature_quals>

[2334] < / insdfeature>

[2335] < / INSDSeq_feature-table>

[2336] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWVG

[2337] YINPYNGRTGYNQKFQARVTLTVDTSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSSA

[2338] STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTV

[2339] PSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

[2340] VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

[2341] PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

[2342] DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK< / INSDSeq_sequence>

[2343] < / insdseq>

[2344] < / sequencedata>

[2345] <sequencedata sequenceidnumber="52">

[2346] <insdseq>

[2347] <INSDSeq_length>448< / INSDSeq_length>

[2348] <INSDSeq_moltype>AA< / INSDSeq_moltype>

[2349] <INSDSeq_division>PAT< / INSDSeq_division>

[2350] <INSDSeq_feature-table>

[2351] <insdfeature>

[2352] <INSDFeature_key>source< / INSDFeature_key>

[2353] <INSDFeature_location>1..448< / INSDFeature_location>

[2354] <INSDFeature_quals>

[2355] <insdqualifier>

[2356] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2357] <INSDQualifier_value>protein< / INSDQualifier_value>

[2358] < / insdqualifier>

[2359] <insdqualifier id="q104">

[2360] <INSDQualifier_name>organism< / INSDQualifier_name>

[2361] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2362] < / insdqualifier>

[2363] < / INSDFeature_quals>

[2364] < / insdfeature>

[2365] < / INSDSeq_feature-table>

[2366] <INSDSeq_sequence>QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNIHWVRQAPGQGLEWVG

[2367] YINPYNGRTGYNQKLQGRVTLTVDKSTSTAYMELRSLRSDDMAVYYCARWDGSSYFDYWGQGTTVTVSSA

[2368] STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTV

[2369] PSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

[2370] VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

[2371] PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

[2372] DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK< / INSDSeq_sequence>

[2373] < / insdseq>

[2374] < / sequencedata>

[2375] <sequencedata sequenceidnumber="53">

[2376] <insdseq>

[2377] <INSDSeq_length>318< / INSDSeq_length>

[2378] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2379] <INSDSeq_division>PAT< / INSDSeq_division>

[2380] <INSDSeq_feature-table>

[2381] <insdfeature>

[2382] <INSDFeature_key>source< / INSDFeature_key>

[2383] <INSDFeature_location>1..318< / INSDFeature_location>

[2384] <INSDFeature_quals>

[2385] <insdqualifier>

[2386] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2387] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2388] < / insdqualifier>

[2389] <insdqualifier id="q106">

[2390] <INSDQualifier_name>organism< / INSDQualifier_name>

[2391] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2392] < / insdqualifier>

[2393] < / INSDFeature_quals>

[2394] < / insdfeature>

[2395] < / INSDSeq_feature-table>

[2396] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2397] accgcgtgaccatcacctgtagcgccagctctaccgtgagctacatgcactggtaccagcagaagccagc

[2398] caaggctcccaagctgttcatctacgagatcaccaagctggctagcggcgtgccttccaggtttagtggc

[2399] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2400] gtcagcagtggaactaccccctgctcagcttcggccaggggaccaaactggaaatcaag< / INSDSeq_s

[2401] equence>

[2402] < / insdseq>

[2403] < / sequencedata>

[2404] <sequencedata sequenceidnumber="54">

[2405] <insdseq>

[2406] <INSDSeq_length>318< / INSDSeq_length>

[2407] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2408] <INSDSeq_division>PAT< / INSDSeq_division>

[2409] <INSDSeq_feature-table>

[2410] <insdfeature>

[2411] <INSDFeature_key>source< / INSDFeature_key>

[2412] <INSDFeature_location>1..318< / INSDFeature_location>

[2413] <INSDFeature_quals>

[2414] <insdqualifier>

[2415] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2416] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2417] < / insdqualifier>

[2418] <insdqualifier id="q108">

[2419] <INSDQualifier_name>organism< / INSDQualifier_name>

[2420] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2421] < / insdqualifier>

[2422] < / INSDFeature_quals>

[2423] < / insdfeature>

[2424] < / INSDSeq_feature-table>

[2425] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2426] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[2427] caaggctcccaagctgttcatctacgagatctccaagctgttcagcggcgtgccttccaggtttagtggc

[2428] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2429] gtcagcagtggaactaccccctgctcaccttcggccaggggaccaaactggaaatcaag< / INSDSeq_s

[2430] equence>

[2431] < / insdseq>

[2432] < / sequencedata>

[2433] <sequencedata sequenceidnumber="55">

[2434] <insdseq>

[2435] <INSDSeq_length>318< / INSDSeq_length>

[2436] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2437] <INSDSeq_division>PAT< / INSDSeq_division>

[2438] <INSDSeq_feature-table>

[2439] <insdfeature>

[2440] <INSDFeature_key>source< / INSDFeature_key>

[2441] <INSDFeature_location>1..318< / INSDFeature_location>

[2442] <INSDFeature_quals>

[2443] <insdqualifier>

[2444] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2445] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2446] < / insdqualifier>

[2447] <insdqualifier id="q110">

[2448] <INSDQualifier_name>organism< / INSDQualifier_name>

[2449] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2450] < / insdqualifier>

[2451] < / INSDFeature_quals>

[2452] < / insdfeature>

[2453] < / INSDSeq_feature-table>

[2454] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2455] accgcgtgaccatcacctgtagcgccagctctaccgtgagctacatgcactggtaccagcagaagccagc

[2456] caaggctcccaagctgttcatctacgagatctccaagctgttcagcggcgtgccttccaggtttagtggc

[2457] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2458] gtcagcagtggaactaccccctgctcagcttcggccaggggaccaaactggaaatcaag< / INSDSeq_s

[2459] equence>

[2460] < / insdseq>

[2461] < / sequencedata>

[2462] <sequencedata sequenceidnumber="56">

[2463] <insdseq>

[2464] <INSDSeq_length>318< / INSDSeq_length>

[2465] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2466] <INSDSeq_division>PAT< / INSDSeq_division>

[2467] <INSDSeq_feature-table>

[2468] <insdfeature>

[2469] <INSDFeature_key>source< / INSDFeature_key>

[2470] <INSDFeature_location>1..318< / INSDFeature_location>

[2471] <INSDFeature_quals>

[2472] <insdqualifier>

[2473] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2474] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2475] < / insdqualifier>

[2476] <insdqualifier id="q112">

[2477] <INSDQualifier_name>organism< / INSDQualifier_name>

[2478] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2479] < / insdqualifier>

[2480] < / INSDFeature_quals>

[2481] < / insdfeature>

[2482] < / INSDSeq_feature-table>

[2483] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2484] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[2485] caaggctcccaagctgttcatctacgagatcaccaagctggctagcggcgtgccttccaggtttagtggc

[2486] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2487] gtcagcagtggaactaccccctgctcaccttcggccaggggaccaaactggaaatcaag< / INSDSeq_s

[2488] equence>

[2489] < / insdseq>

[2490] < / sequencedata>

[2491] <sequencedata sequenceidnumber="57">

[2492] <insdseq>

[2493] <INSDSeq_length>318< / INSDSeq_length>

[2494] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2495] <INSDSeq_division>PAT< / INSDSeq_division>

[2496] <INSDSeq_feature-table>

[2497] <insdfeature>

[2498] <INSDFeature_key>source< / INSDFeature_key>

[2499] <INSDFeature_location>1..318< / INSDFeature_location>

[2500] <INSDFeature_quals>

[2501] <insdqualifier>

[2502] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2503] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2504] < / insdqualifier>

[2505] <insdqualifier id="q114">

[2506] <INSDQualifier_name>organism< / INSDQualifier_name>

[2507] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2508] < / insdqualifier>

[2509] < / INSDFeature_quals>

[2510] < / insdfeature>

[2511] < / INSDSeq_feature-table>

[2512] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2513] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[2514] caaggctcccaagctgttcatctacgagatctccaagctggctagcggcgtgccttccaggtttagtggc

[2515] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2516] gtcagcagtggaactaccccctgctcagcttcggccaggggaccaaactggaaatcaag< / INSDSeq_s

[2517] equence>

[2518] < / insdseq>

[2519] < / sequencedata>

[2520] <sequencedata sequenceidnumber="58">

[2521] <insdseq>

[2522] <INSDSeq_length>318< / INSDSeq_length>

[2523] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2524] <INSDSeq_division>PAT< / INSDSeq_division>

[2525] <INSDSeq_feature-table>

[2526] <insdfeature>

[2527] <INSDFeature_key>source< / INSDFeature_key>

[2528] <INSDFeature_location>1..318< / INSDFeature_location>

[2529] <INSDFeature_quals>

[2530] <insdqualifier>

[2531] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2532] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2533] < / insdqualifier>

[2534] <insdqualifier id="q116">

[2535] <INSDQualifier_name>organism< / INSDQualifier_name>

[2536] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2537] < / insdqualifier>

[2538] < / INSDFeature_quals>

[2539] < / insdfeature>

[2540] < / INSDSeq_feature-table>

[2541] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2542] accgcgtgaccatcacctgtagcgccagctctaccgtgagctacatgcactggtaccagcagaagccagc

[2543] caaggctcccaagctgttcatctacgagatctccaagctggctagcggcgtgccttccaggtttagtggc

[2544] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2545] gtcagcagtggaactaccccctgctcaccttcggccaggggaccaaactggaaatcaag< / INSDSeq_s

[2546] equence>

[2547] < / insdseq>

[2548] < / sequencedata>

[2549] <sequencedata sequenceidnumber="59">

[2550] <insdseq>

[2551] <INSDSeq_length>318< / INSDSeq_length>

[2552] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2553] <INSDSeq_division>PAT< / INSDSeq_division>

[2554] <INSDSeq_feature-table>

[2555] <insdfeature>

[2556] <INSDFeature_key>source< / INSDFeature_key>

[2557] <INSDFeature_location>1..318< / INSDFeature_location>

[2558] <INSDFeature_quals>

[2559] <insdqualifier>

[2560] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2561] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2562] < / insdqualifier>

[2563] <insdqualifier id="q118">

[2564] <INSDQualifier_name>organism< / INSDQualifier_name>

[2565] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2566] < / insdqualifier>

[2567] < / INSDFeature_quals>

[2568] < / insdfeature>

[2569] < / INSDSeq_feature-table>

[2570] <INSDSeq_sequence>gccatcagactgacccagagcccctttagcttatctgcaagcgtgggag

[2571] accgcgtgaccatcacctgtagcgccagctctgaggtgagctacatgcactggtaccagcagaagccagc

[2572] caaggctcccaagctgttcatctacgagatctccaagctgatgagcggcgtgccttccaggtttagtggc

[2573] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2574] gtcagcagtggaactacccccggctcaccttcggccaggggaccaaactggaaatcaag< / INSDSeq_s

[2575] equence>

[2576] < / insdseq>

[2577] < / sequencedata>

[2578] <sequencedata sequenceidnumber="60">

[2579] <insdseq>

[2580] <INSDSeq_length>318< / INSDSeq_length>

[2581] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2582] <INSDSeq_division>PAT< / INSDSeq_division>

[2583] <INSDSeq_feature-table>

[2584] <insdfeature>

[2585] <INSDFeature_key>source< / INSDFeature_key>

[2586] <INSDFeature_location>1..318< / INSDFeature_location>

[2587] <INSDFeature_quals>

[2588] <insdqualifier>

[2589] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2590] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2591] < / insdqualifier>

[2592] <insdqualifier id="q120">

[2593] <INSDQualifier_name>organism< / INSDQualifier_name>

[2594] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2595] < / insdqualifier>

[2596] < / INSDFeature_quals>

[2597] < / insdfeature>

[2598] < / INSDSeq_feature-table>

[2599] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2600] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[2601] caaggctcccaagctgttcatctacgagatctccaagctggctagcggcgtgccttccaggtttagtggc

[2602] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2603] gtcagcagtggaactacccctacctcaccttcggccaggggaccaaactggaaatcaag< / INSDSeq_s

[2604] equence>

[2605] < / insdseq>

[2606] < / sequencedata>

[2607] <sequencedata sequenceidnumber="61">

[2608] <insdseq>

[2609] <INSDSeq_length>318< / INSDSeq_length>

[2610] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2611] <INSDSeq_division>PAT< / INSDSeq_division>

[2612] <INSDSeq_feature-table>

[2613] <insdfeature>

[2614] <INSDFeature_key>source< / INSDFeature_key>

[2615] <INSDFeature_location>1..318< / INSDFeature_location>

[2616] <INSDFeature_quals>

[2617] <insdqualifier>

[2618] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2619] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2620] < / insdqualifier>

[2621] <insdqualifier id="q122">

[2622] <INSDQualifier_name>organism< / INSDQualifier_name>

[2623] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2624] < / insdqualifier>

[2625] < / INSDFeature_quals>

[2626] < / insdfeature>

[2627] < / INSDSeq_feature-table>

[2628] <INSDSeq_sequence>gccatcagactgacccagagcccctttagcttatctgcaagcgtgggag

[2629] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[2630] caaggctcccaagctgttcatctacgagatctccaagctggctagcggcgtgccttccaggtttagtggc

[2631] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2632] gtcagcagtggaactacccccggctcaccttcggccaggggaccaaactggaaatcaag< / INSDSeq_s

[2633] equence>

[2634] < / insdseq>

[2635] < / sequencedata>

[2636] <sequencedata sequenceidnumber="62">

[2637] <insdseq>

[2638] <INSDSeq_length>318< / INSDSeq_length>

[2639] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2640] <INSDSeq_division>PAT< / INSDSeq_division>

[2641] <INSDSeq_feature-table>

[2642] <insdfeature>

[2643] <INSDFeature_key>source< / INSDFeature_key>

[2644] <INSDFeature_location>1..318< / INSDFeature_location>

[2645] <INSDFeature_quals>

[2646] <insdqualifier>

[2647] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2648] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2649] < / insdqualifier>

[2650] <insdqualifier id="q124">

[2651] <INSDQualifier_name>organism< / INSDQualifier_name>

[2652] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2653] < / insdqualifier>

[2654] < / INSDFeature_quals>

[2655] < / insdfeature>

[2656] < / INSDSeq_feature-table>

[2657] <INSDSeq_sequence>gccatcagactgacccagagcccctttagcttatctgcaagcgtgggag

[2658] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[2659] caaggctcccaagctgttcatctacgagatctccaagctgatgagcggcgtgccttccaggtttagtggc

[2660] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2661] gtcagcagtggaactaccccctgctcaccttcggccaggggaccaaactggaaatcaag< / INSDSeq_s

[2662] equence>

[2663] < / insdseq>

[2664] < / sequencedata>

[2665] <sequencedata sequenceidnumber="63">

[2666] <insdseq>

[2667] <INSDSeq_length>354< / INSDSeq_length>

[2668] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2669] <INSDSeq_division>PAT< / INSDSeq_division>

[2670] <INSDSeq_feature-table>

[2671] <insdfeature>

[2672] <INSDFeature_key>source< / INSDFeature_key>

[2673] <INSDFeature_location>1..354< / INSDFeature_location>

[2674] <INSDFeature_quals>

[2675] <insdqualifier>

[2676] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2677] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2678] < / insdqualifier>

[2679] <insdqualifier id="q126">

[2680] <INSDQualifier_name>organism< / INSDQualifier_name>

[2681] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2682] < / insdqualifier>

[2683] < / INSDFeature_quals>

[2684] < / insdfeature>

[2685] < / INSDSeq_feature-table>

[2686] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[2687] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[2688] tcctggccaaggactggaatggatgggctacatcaacccctaccagggccgaaccggctacaaccagaag

[2689] tttcaggctcgcgtgaccctgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[2690] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[2691] gggcaccactgtgaccgtgtcttct< / INSDSeq_sequence>

[2692] < / insdseq>

[2693] < / sequencedata>

[2694] <sequencedata sequenceidnumber="64">

[2695] <insdseq>

[2696] <INSDSeq_length>354< / INSDSeq_length>

[2697] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2698] <INSDSeq_division>PAT< / INSDSeq_division>

[2699] <INSDSeq_feature-table>

[2700] <insdfeature>

[2701] <INSDFeature_key>source< / INSDFeature_key>

[2702] <INSDFeature_location>1..354< / INSDFeature_location>

[2703] <INSDFeature_quals>

[2704] <insdqualifier>

[2705] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2706] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2707] < / insdqualifier>

[2708] <insdqualifier id="q128">

[2709] <INSDQualifier_name>organism< / INSDQualifier_name>

[2710] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2711] < / insdqualifier>

[2712] < / INSDFeature_quals>

[2713] < / insdfeature>

[2714] < / INSDSeq_feature-table>

[2715] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[2716] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[2717] tcctggccaaggactggaatgggtgggctacatcaacccctaccagggccgaaccggctacaaccagaag

[2718] tttcagggccgcgtgaccctgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[2719] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[2720] gggcaccactgtgaccgtgtcttct< / INSDSeq_sequence>

[2721] < / insdseq>

[2722] < / sequencedata>

[2723] <sequencedata sequenceidnumber="65">

[2724] <insdseq>

[2725] <INSDSeq_length>354< / INSDSeq_length>

[2726] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2727] <INSDSeq_division>PAT< / INSDSeq_division>

[2728] <INSDSeq_feature-table>

[2729] <insdfeature>

[2730] <INSDFeature_key>source< / INSDFeature_key>

[2731] <INSDFeature_location>1..354< / INSDFeature_location>

[2732] <INSDFeature_quals>

[2733] <insdqualifier>

[2734] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2735] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2736] < / insdqualifier>

[2737] <insdqualifier id="q130">

[2738] <INSDQualifier_name>organism< / INSDQualifier_name>

[2739] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2740] < / insdqualifier>

[2741] < / INSDFeature_quals>

[2742] < / insdfeature>

[2743] < / INSDSeq_feature-table>

[2744] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[2745] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[2746] tcctggccaaggactggaatgggtgggctacatcaacccctaccagggccgaaccggctacaaccagaag

[2747] tttcaggctcgcgtgaccatgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[2748] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[2749] gggcaccactgtgaccgtgtcttct< / INSDSeq_sequence>

[2750] < / insdseq>

[2751] < / sequencedata>

[2752] <sequencedata sequenceidnumber="66">

[2753] <insdseq>

[2754] <INSDSeq_length>354< / INSDSeq_length>

[2755] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2756] <INSDSeq_division>PAT< / INSDSeq_division>

[2757] <INSDSeq_feature-table>

[2758] <insdfeature>

[2759] <INSDFeature_key>source< / INSDFeature_key>

[2760] <INSDFeature_location>1..354< / INSDFeature_location>

[2761] <INSDFeature_quals>

[2762] <insdqualifier>

[2763] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2764] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2765] < / insdqualifier>

[2766] <insdqualifier id="q132">

[2767] <INSDQualifier_name>organism< / INSDQualifier_name>

[2768] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2769] < / insdqualifier>

[2770] < / INSDFeature_quals>

[2771] < / insdfeature>

[2772] < / INSDSeq_feature-table>

[2773] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[2774] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[2775] tcctggccaaggactggaatgggtgggctacatcaacccctggaacggccgaaccggctacaaccagaag

[2776] tttcagggccgcgtgaccctgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[2777] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[2778] gggcaccactgtgaccgtgtcttct< / INSDSeq_sequence>

[2779] < / insdseq>

[2780] < / sequencedata>

[2781] <sequencedata sequenceidnumber="67">

[2782] <insdseq>

[2783] <INSDSeq_length>354< / INSDSeq_length>

[2784] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2785] <INSDSeq_division>PAT< / INSDSeq_division>

[2786] <INSDSeq_feature-table>

[2787] <insdfeature>

[2788] <INSDFeature_key>source< / INSDFeature_key>

[2789] <INSDFeature_location>1..354< / INSDFeature_location>

[2790] <INSDFeature_quals>

[2791] <insdqualifier>

[2792] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2793] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2794] < / insdqualifier>

[2795] <insdqualifier id="q134">

[2796] <INSDQualifier_name>organism< / INSDQualifier_name>

[2797] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2798] < / insdqualifier>

[2799] < / INSDFeature_quals>

[2800] < / insdfeature>

[2801] < / INSDSeq_feature-table>

[2802] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[2803] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[2804] tcctggccaaggactggaatgggtgggctacatcaacccctacaacggccgaaccggctacaaccagaag

[2805] tttcaggctcgcgtgaccctgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[2806] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[2807] gggcaccactgtgaccgtgtcttct< / INSDSeq_sequence>

[2808] < / insdseq>

[2809] < / sequencedata>

[2810] <sequencedata sequenceidnumber="68">

[2811] <insdseq>

[2812] <INSDSeq_length>354< / INSDSeq_length>

[2813] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2814] <INSDSeq_division>PAT< / INSDSeq_division>

[2815] <INSDSeq_feature-table>

[2816] <insdfeature>

[2817] <INSDFeature_key>source< / INSDFeature_key>

[2818] <INSDFeature_location>1..354< / INSDFeature_location>

[2819] <INSDFeature_quals>

[2820] <insdqualifier>

[2821] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2822] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2823] < / insdqualifier>

[2824] <insdqualifier id="q136">

[2825] <INSDQualifier_name>organism< / INSDQualifier_name>

[2826] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2827] < / insdqualifier>

[2828] < / INSDFeature_quals>

[2829] < / insdfeature>

[2830] < / INSDSeq_feature-table>

[2831] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[2832] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[2833] tcctggccaaggactggaatgggtgggctacatcaacccctacaacggccgaaccggctacaaccagaag

[2834] ctgcagggccgcgtgaccctgaccgtagacaagagcacctcgaccgcgtacatggagctgcggtccctga

[2835] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[2836] gggcaccactgtgaccgtgtcttct< / INSDSeq_sequence>

[2837] < / insdseq>

[2838] < / sequencedata>

[2839] <sequencedata sequenceidnumber="69">

[2840] <insdseq>

[2841] <INSDSeq_length>639< / INSDSeq_length>

[2842] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2843] <INSDSeq_division>PAT< / INSDSeq_division>

[2844] <INSDSeq_feature-table>

[2845] <insdfeature>

[2846] <INSDFeature_key>source< / INSDFeature_key>

[2847] <INSDFeature_location>1..639< / INSDFeature_location>

[2848] <INSDFeature_quals>

[2849] <insdqualifier>

[2850] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2851] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2852] < / insdqualifier>

[2853] <insdqualifier id="q138">

[2854] <INSDQualifier_name>organism< / INSDQualifier_name>

[2855] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2856] < / insdqualifier>

[2857] < / INSDFeature_quals>

[2858] < / insdfeature>

[2859] < / INSDSeq_feature-table>

[2860] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2861] accgcgtgaccatcacctgtagcgccagctctaccgtgagctacatgcactggtaccagcagaagccagc

[2862] caaggctcccaagctgttcatctacgagatcaccaagctggctagcggcgtgccttccaggtttagtggc

[2863] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2864] gtcagcagtggaactaccccctgctcagcttcggccaggggaccaaactggaaatcaagcgtacggtggc

[2865] tgcaccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgc

[2866] ctgctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggta

[2867] actcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccctgacgct

[2868] gagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgccc

[2869] gtcacaaagagcttcaacaggggagagtgt< / INSDSeq_sequence>

[2870] < / insdseq>

[2871] < / sequencedata>

[2872] <sequencedata sequenceidnumber="70">

[2873] <insdseq>

[2874] <INSDSeq_length>639< / INSDSeq_length>

[2875] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2876] <INSDSeq_division>PAT< / INSDSeq_division>

[2877] <INSDSeq_feature-table>

[2878] <insdfeature>

[2879] <INSDFeature_key>source< / INSDFeature_key>

[2880] <INSDFeature_location>1..639< / INSDFeature_location>

[2881] <INSDFeature_quals>

[2882] <insdqualifier>

[2883] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2884] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2885] < / insdqualifier>

[2886] <insdqualifier id="q140">

[2887] <INSDQualifier_name>organism< / INSDQualifier_name>

[2888] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2889] < / insdqualifier>

[2890] < / INSDFeature_quals>

[2891] < / insdfeature>

[2892] < / INSDSeq_feature-table>

[2893] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2894] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[2895] caaggctcccaagctgttcatctacgagatctccaagctgttcagcggcgtgccttccaggtttagtggc

[2896] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2897] gtcagcagtggaactaccccctgctcaccttcggccaggggaccaaactggaaatcaagcgtacggtggc

[2898] tgcaccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgc

[2899] ctgctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggta

[2900] actcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccctgacgct

[2901] gagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgccc

[2902] gtcacaaagagcttcaacaggggagagtgt< / INSDSeq_sequence>

[2903] < / insdseq>

[2904] < / sequencedata>

[2905] <sequencedata sequenceidnumber="71">

[2906] <insdseq>

[2907] <INSDSeq_length>639< / INSDSeq_length>

[2908] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2909] <INSDSeq_division>PAT< / INSDSeq_division>

[2910] <INSDSeq_feature-table>

[2911] <insdfeature>

[2912] <INSDFeature_key>source< / INSDFeature_key>

[2913] <INSDFeature_location>1..639< / INSDFeature_location>

[2914] <INSDFeature_quals>

[2915] <insdqualifier>

[2916] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2917] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2918] < / insdqualifier>

[2919] <insdqualifier id="q142">

[2920] <INSDQualifier_name>organism< / INSDQualifier_name>

[2921] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2922] < / insdqualifier>

[2923] < / INSDFeature_quals>

[2924] < / insdfeature>

[2925] < / INSDSeq_feature-table>

[2926] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2927] accgcgtgaccatcacctgtagcgccagctctaccgtgagctacatgcactggtaccagcagaagccagc

[2928] caaggctcccaagctgttcatctacgagatctccaagctgttcagcggcgtgccttccaggtttagtggc

[2929] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2930] gtcagcagtggaactaccccctgctcagcttcggccaggggaccaaactggaaatcaagcgtacggtggc

[2931] tgcaccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgc

[2932] ctgctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggta

[2933] actcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccctgacgct

[2934] gagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgccc

[2935] gtcacaaagagcttcaacaggggagagtgt< / INSDSeq_sequence>

[2936] < / insdseq>

[2937] < / sequencedata>

[2938] <sequencedata sequenceidnumber="72">

[2939] <insdseq>

[2940] <INSDSeq_length>639< / INSDSeq_length>

[2941] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2942] <INSDSeq_division>PAT< / INSDSeq_division>

[2943] <INSDSeq_feature-table>

[2944] <insdfeature>

[2945] <INSDFeature_key>source< / INSDFeature_key>

[2946] <INSDFeature_location>1..639< / INSDFeature_location>

[2947] <INSDFeature_quals>

[2948] <insdqualifier>

[2949] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2950] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2951] < / insdqualifier>

[2952] <insdqualifier id="q144">

[2953] <INSDQualifier_name>organism< / INSDQualifier_name>

[2954] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2955] < / insdqualifier>

[2956] < / INSDFeature_quals>

[2957] < / insdfeature>

[2958] < / INSDSeq_feature-table>

[2959] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2960] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[2961] caaggctcccaagctgttcatctacgagatcaccaagctggctagcggcgtgccttccaggtttagtggc

[2962] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2963] gtcagcagtggaactaccccctgctcaccttcggccaggggaccaaactggaaatcaagcgtacggtggc

[2964] tgcaccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgc

[2965] ctgctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggta

[2966] actcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccctgacgct

[2967] gagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgccc

[2968] gtcacaaagagcttcaacaggggagagtgt< / INSDSeq_sequence>

[2969] < / insdseq>

[2970] < / sequencedata>

[2971] <sequencedata sequenceidnumber="73">

[2972] <insdseq>

[2973] <INSDSeq_length>639< / INSDSeq_length>

[2974] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[2975] <INSDSeq_division>PAT< / INSDSeq_division>

[2976] <INSDSeq_feature-table>

[2977] <insdfeature>

[2978] <INSDFeature_key>source< / INSDFeature_key>

[2979] <INSDFeature_location>1..639< / INSDFeature_location>

[2980] <INSDFeature_quals>

[2981] <insdqualifier>

[2982] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[2983] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[2984] < / insdqualifier>

[2985] <insdqualifier id="q146">

[2986] <INSDQualifier_name>organism< / INSDQualifier_name>

[2987] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[2988] < / insdqualifier>

[2989] < / INSDFeature_quals>

[2990] < / insdfeature>

[2991] < / INSDSeq_feature-table>

[2992] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[2993] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[2994] caaggctcccaagctgttcatctacgagatctccaagctggctagcggcgtgccttccaggtttagtggc

[2995] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[2996] gtcagcagtggaactaccccctgctcagcttcggccaggggaccaaactggaaatcaagcgtacggtggc

[2997] tgcaccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgc

[2998] ctgctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggta

[2999] actcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccctgacgct

[3000] gagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgccc

[3001] gtcacaaagagcttcaacaggggagagtgt< / INSDSeq_sequence>

[3002] < / insdseq>

[3003] < / sequencedata>

[3004] <sequencedata sequenceidnumber="74">

[3005] <insdseq>

[3006] <INSDSeq_length>639< / INSDSeq_length>

[3007] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3008] <INSDSeq_division>PAT< / INSDSeq_division>

[3009] <INSDSeq_feature-table>

[3010] <insdfeature>

[3011] <INSDFeature_key>source< / INSDFeature_key>

[3012] <INSDFeature_location>1..639< / INSDFeature_location>

[3013] <INSDFeature_quals>

[3014] <insdqualifier>

[3015] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3016] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3017] < / insdqualifier>

[3018] <insdqualifier id="q148">

[3019] <INSDQualifier_name>organism< / INSDQualifier_name>

[3020] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3021] < / insdqualifier>

[3022] < / INSDFeature_quals>

[3023] < / insdfeature>

[3024] < / INSDSeq_feature-table>

[3025] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[3026] accgcgtgaccatcacctgtagcgccagctctaccgtgagctacatgcactggtaccagcagaagccagc

[3027] caaggctcccaagctgttcatctacgagatctccaagctggctagcggcgtgccttccaggtttagtggc

[3028] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[3029] gtcagcagtggaactaccccctgctcaccttcggccaggggaccaaactggaaatcaagcgtacggtggc

[3030] tgcaccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgc

[3031] ctgctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggta

[3032] actcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccctgacgct

[3033] gagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgccc

[3034] gtcacaaagagcttcaacaggggagagtgt< / INSDSeq_sequence>

[3035] < / insdseq>

[3036] < / sequencedata>

[3037] <sequencedata sequenceidnumber="75">

[3038] <insdseq>

[3039] <INSDSeq_length>639< / INSDSeq_length>

[3040] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3041] <INSDSeq_division>PAT< / INSDSeq_division>

[3042] <INSDSeq_feature-table>

[3043] <insdfeature>

[3044] <INSDFeature_key>source< / INSDFeature_key>

[3045] <INSDFeature_location>1..639< / INSDFeature_location>

[3046] <INSDFeature_quals>

[3047] <insdqualifier>

[3048] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3049] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3050] < / insdqualifier>

[3051] <insdqualifier id="q150">

[3052] <INSDQualifier_name>organism< / INSDQualifier_name>

[3053] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3054] < / insdqualifier>

[3055] < / INSDFeature_quals>

[3056] < / insdfeature>

[3057] < / INSDSeq_feature-table>

[3058] <INSDSeq_sequence>gccatcagactgacccagagcccctttagcttatctgcaagcgtgggag

[3059] accgcgtgaccatcacctgtagcgccagctctgaggtgagctacatgcactggtaccagcagaagccagc

[3060] caaggctcccaagctgttcatctacgagatctccaagctgatgagcggcgtgccttccaggtttagtggc

[3061] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[3062] gtcagcagtggaactacccccggctcaccttcggccaggggaccaaactggaaatcaagcgtacggtggc

[3063] tgcaccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgc

[3064] ctgctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggta

[3065] actcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccctgacgct

[3066] gagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgccc

[3067] gtcacaaagagcttcaacaggggagagtgt< / INSDSeq_sequence>

[3068] < / insdseq>

[3069] < / sequencedata>

[3070] <sequencedata sequenceidnumber="76">

[3071] <insdseq>

[3072] <INSDSeq_length>639< / INSDSeq_length>

[3073] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3074] <INSDSeq_division>PAT< / INSDSeq_division>

[3075] <INSDSeq_feature-table>

[3076] <insdfeature>

[3077] <INSDFeature_key>source< / INSDFeature_key>

[3078] <INSDFeature_location>1..639< / INSDFeature_location>

[3079] <INSDFeature_quals>

[3080] <insdqualifier>

[3081] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3082] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3083] < / insdqualifier>

[3084] <insdqualifier id="q152">

[3085] <INSDQualifier_name>organism< / INSDQualifier_name>

[3086] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3087] < / insdqualifier>

[3088] < / INSDFeature_quals>

[3089] < / insdfeature>

[3090] < / INSDSeq_feature-table>

[3091] <INSDSeq_sequence>gccatcagaatgacccagagcccctttagcttatctgcaagcgtgggag

[3092] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[3093] caaggctcccaagctgttcatctacgagatctccaagctggctagcggcgtgccttccaggtttagtggc

[3094] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[3095] gtcagcagtggaactacccctacctcaccttcggccaggggaccaaactggaaatcaagcgtacggtggc

[3096] tgcaccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgc

[3097] ctgctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggta

[3098] actcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccctgacgct

[3099] gagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgccc

[3100] gtcacaaagagcttcaacaggggagagtgt< / INSDSeq_sequence>

[3101] < / insdseq>

[3102] < / sequencedata>

[3103] <sequencedata sequenceidnumber="77">

[3104] <insdseq>

[3105] <INSDSeq_length>639< / INSDSeq_length>

[3106] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3107] <INSDSeq_division>PAT< / INSDSeq_division>

[3108] <INSDSeq_feature-table>

[3109] <insdfeature>

[3110] <INSDFeature_key>source< / INSDFeature_key>

[3111] <INSDFeature_location>1..639< / INSDFeature_location>

[3112] <INSDFeature_quals>

[3113] <insdqualifier>

[3114] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3115] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3116] < / insdqualifier>

[3117] <insdqualifier id="q154">

[3118] <INSDQualifier_name>organism< / INSDQualifier_name>

[3119] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3120] < / insdqualifier>

[3121] < / INSDFeature_quals>

[3122] < / insdfeature>

[3123] < / INSDSeq_feature-table>

[3124] <INSDSeq_sequence>gccatcagactgacccagagcccctttagcttatctgcaagcgtgggag

[3125] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[3126] caaggctcccaagctgttcatctacgagatctccaagctggctagcggcgtgccttccaggtttagtggc

[3127] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[3128] gtcagcagtggaactacccccggctcaccttcggccaggggaccaaactggaaatcaagcgtacggtggc

[3129] tgcaccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgc

[3130] ctgctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggta

[3131] actcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccctgacgct

[3132] gagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgccc

[3133] gtcacaaagagcttcaacaggggagagtgt< / INSDSeq_sequence>

[3134] < / insdseq>

[3135] < / sequencedata>

[3136] <sequencedata sequenceidnumber="78">

[3137] <insdseq>

[3138] <INSDSeq_length>639< / INSDSeq_length>

[3139] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3140] <INSDSeq_division>PAT< / INSDSeq_division>

[3141] <INSDSeq_feature-table>

[3142] <insdfeature>

[3143] <INSDFeature_key>source< / INSDFeature_key>

[3144] <INSDFeature_location>1..639< / INSDFeature_location>

[3145] <INSDFeature_quals>

[3146] <insdqualifier>

[3147] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3148] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3149] < / insdqualifier>

[3150] <insdqualifier id="q156">

[3151] <INSDQualifier_name>organism< / INSDQualifier_name>

[3152] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3153] < / insdqualifier>

[3154] < / INSDFeature_quals>

[3155] < / insdfeature>

[3156] < / INSDSeq_feature-table>

[3157] <INSDSeq_sequence>gccatcagactgacccagagcccctttagcttatctgcaagcgtgggag

[3158] accgcgtgaccatcacctgtagcgccagctcttccgtgagctacatgcactggtaccagcagaagccagc

[3159] caaggctcccaagctgttcatctacgagatctccaagctgatgagcggcgtgccttccaggtttagtggc

[3160] tctggtagcgggacggactacaccctgacaatcagcagcctgcagcccgaggacttcgccacctactact

[3161] gtcagcagtggaactaccccctgctcaccttcggccaggggaccaaactggaaatcaagcgtacggtggc

[3162] tgcaccatctgtcttcatcttcccgccatctgatgagcagttgaaatctggaactgcctctgttgtgtgc

[3163] ctgctgaataacttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggta

[3164] actcccaggagagtgtcacagagcaggacagcaaggacagcacctacagcctcagcagcaccctgacgct

[3165] gagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgccc

[3166] gtcacaaagagcttcaacaggggagagtgt< / INSDSeq_sequence>

[3167] < / insdseq>

[3168] < / sequencedata>

[3169] <sequencedata sequenceidnumber="79">

[3170] <insdseq>

[3171] <INSDSeq_length>1338< / INSDSeq_length>

[3172] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3173] <INSDSeq_division>PAT< / INSDSeq_division>

[3174] <INSDSeq_feature-table>

[3175] <insdfeature>

[3176] <INSDFeature_key>source< / INSDFeature_key>

[3177] <INSDFeature_location>1..1338< / INSDFeature_location>

[3178] <INSDFeature_quals>

[3179] <insdqualifier>

[3180] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3181] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3182] < / insdqualifier>

[3183] <insdqualifier id="q158">

[3184] <INSDQualifier_name>organism< / INSDQualifier_name>

[3185] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3186] < / insdqualifier>

[3187] < / INSDFeature_quals>

[3188] < / insdfeature>

[3189] < / INSDSeq_feature-table>

[3190] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[3191] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[3192] tcctggccaaggactggaatggatgggctacatcaacccctaccagggccgaaccggctacaaccagaag

[3193] tttcaggctcgcgtgaccctgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[3194] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[3195] gggcaccactgtgaccgtgtcttctgctagcaccaagggcccatcggtcttccccctggcaccctcctcc

[3196] aagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaaccggtgacgg

[3197] tgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggact

[3198] ctactccctcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgtg

[3199] aatcacaagcccagcaacaccaaggtggacaagagagttgagcccaaatcttgtgacaaaactcacacat

[3200] gcccaccgtgcccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaagga

[3201] caccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgag

[3202] gtcaagttcaactggtacgtggacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagt

[3203] acaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaaggagta

[3204] caagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcag

[3205] ccccgagaaccacaggtgtacaccctgcccccatcccgggacgagctgaccaagaaccaggtcagcctga

[3206] cctgcctggtcaaaggcttctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggagaa

[3207] caactacaagaccacgcctcccgtgctggactccgacggctccttcttcctctatagcaagctcaccgtg

[3208] gacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccact

[3209] acacgcagaaaagcctctccctgtccccg< / INSDSeq_sequence>

[3210] < / insdseq>

[3211] < / sequencedata>

[3212] <sequencedata sequenceidnumber="80">

[3213] <insdseq>

[3214] <INSDSeq_length>1344< / INSDSeq_length>

[3215] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3216] <INSDSeq_division>PAT< / INSDSeq_division>

[3217] <INSDSeq_feature-table>

[3218] <insdfeature>

[3219] <INSDFeature_key>source< / INSDFeature_key>

[3220] <INSDFeature_location>1..1344< / INSDFeature_location>

[3221] <INSDFeature_quals>

[3222] <insdqualifier>

[3223] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3224] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3225] < / insdqualifier>

[3226] <insdqualifier id="q160">

[3227] <INSDQualifier_name>organism< / INSDQualifier_name>

[3228] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3229] < / insdqualifier>

[3230] < / INSDFeature_quals>

[3231] < / insdfeature>

[3232] < / INSDSeq_feature-table>

[3233] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[3234] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[3235] tcctggccaaggactggaatggatgggctacatcaacccctaccagggccgaaccggctacaaccagaag

[3236] tttcaggctcgcgtgaccctgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[3237] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[3238] gggcaccactgtgaccgtgtcttctgctagcaccaagggcccatcggtcttccccctggcaccctcctcc

[3239] aagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaaccggtgacgg

[3240] tgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggact

[3241] ctactccctcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgtg

[3242] aatcacaagcccagcaacaccaaggtggacaagagagttgagcccaaatcttgtgacaaaactcacacat

[3243] gcccaccgtgcccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaagga

[3244] caccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgag

[3245] gtcaagttcaactggtacgtggacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagt

[3246] acaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaaggagta

[3247] caagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcag

[3248] ccccgagaaccacaggtgtacaccctgcccccatcccgggacgagctgaccaagaaccaggtcagcctga

[3249] cctgcctggtcaaaggcttctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggagaa

[3250] caactacaagaccacgcctcccgtgctggactccgacggctccttcttcctctatagcaagctcaccgtg

[3251] gacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccact

[3252] acacgcagaaaagcctctccctgtccccgggtaaa< / INSDSeq_sequence>

[3253] < / insdseq>

[3254] < / sequencedata>

[3255] <sequencedata sequenceidnumber="81">

[3256] <insdseq>

[3257] <INSDSeq_length>1344< / INSDSeq_length>

[3258] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3259] <INSDSeq_division>PAT< / INSDSeq_division>

[3260] <INSDSeq_feature-table>

[3261] <insdfeature>

[3262] <INSDFeature_key>source< / INSDFeature_key>

[3263] <INSDFeature_location>1..1344< / INSDFeature_location>

[3264] <INSDFeature_quals>

[3265] <insdqualifier>

[3266] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3267] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3268] < / insdqualifier>

[3269] <insdqualifier id="q162">

[3270] <INSDQualifier_name>organism< / INSDQualifier_name>

[3271] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3272] < / insdqualifier>

[3273] < / INSDFeature_quals>

[3274] < / insdfeature>

[3275] < / INSDSeq_feature-table>

[3276] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[3277] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[3278] tcctggccaaggactggaatgggtgggctacatcaacccctaccagggccgaaccggctacaaccagaag

[3279] tttcagggccgcgtgaccctgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[3280] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[3281] gggcaccactgtgaccgtgtcttctgctagcaccaagggcccatcggtcttccccctggcaccctcctcc

[3282] aagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaaccggtgacgg

[3283] tgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggact

[3284] ctactccctcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgtg

[3285] aatcacaagcccagcaacaccaaggtggacaagagagttgagcccaaatcttgtgacaaaactcacacat

[3286] gcccaccgtgcccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaagga

[3287] caccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgag

[3288] gtcaagttcaactggtacgtggacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagt

[3289] acaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaaggagta

[3290] caagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcag

[3291] ccccgagaaccacaggtgtacaccctgcccccatcccgggacgagctgaccaagaaccaggtcagcctga

[3292] cctgcctggtcaaaggcttctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggagaa

[3293] caactacaagaccacgcctcccgtgctggactccgacggctccttcttcctctatagcaagctcaccgtg

[3294] gacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccact

[3295] acacgcagaaaagcctctccctgtccccgggtaaa< / INSDSeq_sequence>

[3296] < / insdseq>

[3297] < / sequencedata>

[3298] <sequencedata sequenceidnumber="82">

[3299] <insdseq>

[3300] <INSDSeq_length>1338< / INSDSeq_length>

[3301] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3302] <INSDSeq_division>PAT< / INSDSeq_division>

[3303] <INSDSeq_feature-table>

[3304] <insdfeature>

[3305] <INSDFeature_key>source< / INSDFeature_key>

[3306] <INSDFeature_location>1..1338< / INSDFeature_location>

[3307] <INSDFeature_quals>

[3308] <insdqualifier>

[3309] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3310] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3311] < / insdqualifier>

[3312] <insdqualifier id="q164">

[3313] <INSDQualifier_name>organism< / INSDQualifier_name>

[3314] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3315] < / insdqualifier>

[3316] < / INSDFeature_quals>

[3317] < / insdfeature>

[3318] < / INSDSeq_feature-table>

[3319] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[3320] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[3321] tcctggccaaggactggaatgggtgggctacatcaacccctaccagggccgaaccggctacaaccagaag

[3322] tttcagggccgcgtgaccctgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[3323] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[3324] gggcaccactgtgaccgtgtcttctgctagcaccaagggcccatcggtcttccccctggcaccctcctcc

[3325] aagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaaccggtgacgg

[3326] tgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggact

[3327] ctactccctcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgtg

[3328] aatcacaagcccagcaacaccaaggtggacaagagagttgagcccaaatcttgtgacaaaactcacacat

[3329] gcccaccgtgcccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaagga

[3330] caccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgag

[3331] gtcaagttcaactggtacgtggacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagt

[3332] acaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaaggagta

[3333] caagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcag

[3334] ccccgagaaccacaggtgtacaccctgcccccatcccgggacgagctgaccaagaaccaggtcagcctga

[3335] cctgcctggtcaaaggcttctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggagaa

[3336] caactacaagaccacgcctcccgtgctggactccgacggctccttcttcctctatagcaagctcaccgtg

[3337] gacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccact

[3338] acacgcagaaaagcctctccctgtccccg< / INSDSeq_sequence>

[3339] < / insdseq>

[3340] < / sequencedata>

[3341] <sequencedata sequenceidnumber="83">

[3342] <insdseq>

[3343] <INSDSeq_length>1338< / INSDSeq_length>

[3344] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3345] <INSDSeq_division>PAT< / INSDSeq_division>

[3346] <INSDSeq_feature-table>

[3347] <insdfeature>

[3348] <INSDFeature_key>source< / INSDFeature_key>

[3349] <INSDFeature_location>1..1338< / INSDFeature_location>

[3350] <INSDFeature_quals>

[3351] <insdqualifier>

[3352] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3353] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3354] < / insdqualifier>

[3355] <insdqualifier id="q166">

[3356] <INSDQualifier_name>organism< / INSDQualifier_name>

[3357] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3358] < / insdqualifier>

[3359] < / INSDFeature_quals>

[3360] < / insdfeature>

[3361] < / INSDSeq_feature-table>

[3362] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[3363] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[3364] tcctggccaaggactggaatgggtgggctacatcaacccctaccagggccgaaccggctacaaccagaag

[3365] tttcaggctcgcgtgaccatgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[3366] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[3367] gggcaccactgtgaccgtgtcttctgctagcaccaagggcccatcggtcttccccctggcaccctcctcc

[3368] aagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaaccggtgacgg

[3369] tgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggact

[3370] ctactccctcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgtg

[3371] aatcacaagcccagcaacaccaaggtggacaagagagttgagcccaaatcttgtgacaaaactcacacat

[3372] gcccaccgtgcccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaagga

[3373] caccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgag

[3374] gtcaagttcaactggtacgtggacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagt

[3375] acaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaaggagta

[3376] caagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcag

[3377] ccccgagaaccacaggtgtacaccctgcccccatcccgggacgagctgaccaagaaccaggtcagcctga

[3378] cctgcctggtcaaaggcttctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggagaa

[3379] caactacaagaccacgcctcccgtgctggactccgacggctccttcttcctctatagcaagctcaccgtg

[3380] gacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccact

[3381] acacgcagaaaagcctctccctgtccccg< / INSDSeq_sequence>

[3382] < / insdseq>

[3383] < / sequencedata>

[3384] <sequencedata sequenceidnumber="84">

[3385] <insdseq>

[3386] <INSDSeq_length>1344< / INSDSeq_length>

[3387] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3388] <INSDSeq_division>PAT< / INSDSeq_division>

[3389] <INSDSeq_feature-table>

[3390] <insdfeature>

[3391] <INSDFeature_key>source< / INSDFeature_key>

[3392] <INSDFeature_location>1..1344< / INSDFeature_location>

[3393] <INSDFeature_quals>

[3394] <insdqualifier>

[3395] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3396] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3397] < / insdqualifier>

[3398] <insdqualifier id="q168">

[3399] <INSDQualifier_name>organism< / INSDQualifier_name>

[3400] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3401] < / insdqualifier>

[3402] < / INSDFeature_quals>

[3403] < / insdfeature>

[3404] < / INSDSeq_feature-table>

[3405] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[3406] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[3407] tcctggccaaggactggaatgggtgggctacatcaacccctggaacggccgaaccggctacaaccagaag

[3408] tttcagggccgcgtgaccctgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[3409] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[3410] gggcaccactgtgaccgtgtcttctgctagcaccaagggcccatcggtcttccccctggcaccctcctcc

[3411] aagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaaccggtgacgg

[3412] tgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggact

[3413] ctactccctcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgtg

[3414] aatcacaagcccagcaacaccaaggtggacaagagagttgagcccaaatcttgtgacaaaactcacacat

[3415] gcccaccgtgcccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaagga

[3416] caccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgag

[3417] gtcaagttcaactggtacgtggacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagt

[3418] acaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaaggagta

[3419] caagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcag

[3420] ccccgagaaccacaggtgtacaccctgcccccatcccgggacgagctgaccaagaaccaggtcagcctga

[3421] cctgcctggtcaaaggcttctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggagaa

[3422] caactacaagaccacgcctcccgtgctggactccgacggctccttcttcctctatagcaagctcaccgtg

[3423] gacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccact

[3424] acacgcagaaaagcctctccctgtccccgggtaaa< / INSDSeq_sequence>

[3425] < / insdseq>

[3426] < / sequencedata>

[3427] <sequencedata sequenceidnumber="85">

[3428] <insdseq>

[3429] <INSDSeq_length>1344< / INSDSeq_length>

[3430] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3431] <INSDSeq_division>PAT< / INSDSeq_division>

[3432] <INSDSeq_feature-table>

[3433] <insdfeature>

[3434] <INSDFeature_key>source< / INSDFeature_key>

[3435] <INSDFeature_location>1..1344< / INSDFeature_location>

[3436] <INSDFeature_quals>

[3437] <insdqualifier>

[3438] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3439] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3440] < / insdqualifier>

[3441] <insdqualifier id="q170">

[3442] <INSDQualifier_name>organism< / INSDQualifier_name>

[3443] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3444] < / insdqualifier>

[3445] < / INSDFeature_quals>

[3446] < / insdfeature>

[3447] < / INSDSeq_feature-table>

[3448] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[3449] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[3450] tcctggccaaggactggaatgggtgggctacatcaacccctacaacggccgaaccggctacaaccagaag

[3451] tttcaggctcgcgtgaccctgaccgtagacaccagcacctcgaccgcgtacatggagctgcggtccctga

[3452] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[3453] gggcaccactgtgaccgtgtcttctgctagcaccaagggcccatcggtcttccccctggcaccctcctcc

[3454] aagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaaccggtgacgg

[3455] tgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggact

[3456] ctactccctcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgtg

[3457] aatcacaagcccagcaacaccaaggtggacaagagagttgagcccaaatcttgtgacaaaactcacacat

[3458] gcccaccgtgcccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaagga

[3459] caccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgag

[3460] gtcaagttcaactggtacgtggacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagt

[3461] acaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaaggagta

[3462] caagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcag

[3463] ccccgagaaccacaggtgtacaccctgcccccatcccgggacgagctgaccaagaaccaggtcagcctga

[3464] cctgcctggtcaaaggcttctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggagaa

[3465] caactacaagaccacgcctcccgtgctggactccgacggctccttcttcctctatagcaagctcaccgtg

[3466] gacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccact

[3467] acacgcagaaaagcctctccctgtccccgggtaaaa< / INSDSeq_sequence>

[3468] < / insdseq>

[3469] < / sequencedata>

[3470] <sequencedata sequenceidnumber="86">

[3471] <insdseq>

[3472] <INSDSeq_length>1344< / INSDSeq_length>

[3473] <INSDSeq_moltype>DNA< / INSDSeq_moltype>

[3474] <INSDSeq_division>PAT< / INSDSeq_division>

[3475] <INSDSeq_feature-table>

[3476] <insdfeature>

[3477] <INSDFeature_key>source< / INSDFeature_key>

[3478] <INSDFeature_location>1..1344< / INSDFeature_location>

[3479] <INSDFeature_quals>

[3480] <insdqualifier>

[3481] <INSDQualifier_name>mol_type< / INSDQualifier_name>

[3482] <INSDQualifier_value>other DNA< / INSDQualifier_value>

[3483] < / insdqualifier>

[3484] <insdqualifier id="q172">

[3485] <INSDQualifier_name>organism< / INSDQualifier_name>

[3486] <INSDQualifier_value>synthetic construct< / INSDQualifier_value>

[3487] < / insdqualifier>

[3488] < / INSDFeature_quals>

[3489] < / insdfeature>

[3490] < / INSDSeq_feature-table>

[3491] <INSDSeq_sequence>caggtgcagctggtgcagtctggcgctgaagtgaaaaagcctggcgctt

[3492] ccgtgaaggtgtcatgcaaggcctctggctacaccttcaccgactacaacatccactgggtaagacaggc

[3493] tcctggccaaggactggaatgggtgggctacatcaacccctacaacggccgaaccggctacaaccagaag

[3494] ctgcagggccgcgtgaccctgaccgtagacaagagcacctcgaccgcgtacatggagctgcggtccctga

[3495] gatctgacgatatggctgtgtactattgcgcccgctgggacggcagctcttacttcgactactggggcca

[3496] gggcaccactgtgaccgtgtcttctgctagcaccaagggcccatcggtcttccccctggcaccctcctcc

[3497] aagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaaccggtgacgg

[3498] tgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggact

[3499] ctactccctcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgtg

[3500] aatcacaagcccagcaacaccaaggtggacaagagagttgagcccaaatcttgtgacaaaactcacacat

[3501] gcccaccgtgcccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaagga

[3502] caccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgag

[3503] gtcaagttcaactggtacgtggacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagt

[3504] acaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaaggagta

[3505] caagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcag

[3506] ccccgagaaccacaggtgtacaccctgcccccatcccgggacgagctgaccaagaaccaggtcagcctga

[3507] cctgcctggtcaaaggcttctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggagaa

[3508] caactacaagaccacgcctcccgtgctggactccgacggctccttcttcctctatagcaagctcaccgtg

[3509] gacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccact

[3510] acacgcagaaaagcctctccctgtccccgggataaa< / INSDSeq_sequence>

[3511] < / insdseq>

[3512] < / sequencedata>

[3513] < / st26sequencelisting>

[3514] <---

Claims

1. A monoclonal antibody or antigen-binding fragment thereof that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor, comprising: (i) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 1, CDR2 with the amino acid sequence of SEQ ID NO: 4 and CDR3 with the amino acid sequence of SEQ ID NO: 8; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 13 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (ii) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 5 and CDR3 with the amino acid sequence of SEQ ID NO: 9; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 13 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (iii) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 1, CDR2 with the amino acid sequence of SEQ ID NO: 5 and CDR3 with the amino acid sequence of SEQ ID NO: 8; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 14 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (iv) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 4 and CDR3 with the amino acid sequence of SEQ ID NO: 9; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 14 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (v) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 6 and CDR3 with the amino acid sequence of SEQ ID NO: 8; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 14 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (vi) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 6 and CDR3 with the amino acid sequence of SEQ ID NO: 8; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 13 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (vii) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 1, CDR2 with the amino acid sequence of SEQ ID NO: 4 and CDR3 with the amino acid sequence of SEQ ID NO: 8; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 15 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (viii) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 4 and CDR3 with the amino acid sequence of SEQ ID NO: 9; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 15 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (ix) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 1, CDR2 with the amino acid sequence of SEQ ID NO: 6 and CDR3 with the amino acid sequence of SEQ ID NO: 9; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 15 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (x) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 6 and CDR3 with the amino acid sequence of SEQ ID NO: 11; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 15 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (xi) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 1, CDR2 with the amino acid sequence of SEQ ID NO: 5 and CDR3 with the amino acid sequence of SEQ ID NO: 8; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 16 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (xii) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 1, CDR2 with the amino acid sequence of SEQ ID NO: 4 and CDR3 with the amino acid sequence of SEQ ID NO: 8; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 16 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (xiii) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 3, CDR2 with the amino acid sequence of SEQ ID NO: 7 and CDR3 with the amino acid sequence of SEQ ID NO: 10; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 17 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (xiv) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 5 and CDR3 with the amino acid sequence of SEQ ID NO: 9; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 16 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (xv) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 4 and CDR3 with the amino acid sequence of SEQ ID NO: 9; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 16 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (xvi) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 1, CDR2 with the amino acid sequence of SEQ ID NO: 6 and CDR3 with the amino acid sequence of SEQ ID NO: 9; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 16 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (xvii) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 6 and CDR3 with the amino acid sequence of SEQ ID NO: 11; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 16 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (xviii) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 6 and CDR3 with the amino acid sequence of SEQ ID NO: 8; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 16 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (ixx) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 6 and CDR3 with the amino acid sequence of SEQ ID NO: 10; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 17 and CDR3 with the amino acid sequence of SEQ ID NO: 18; or (xx) (a) a light chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 2, CDR2 with the amino acid sequence of SEQ ID NO: 7 and CDR3 with the amino acid sequence of SEQ ID NO: 9; and (b) a heavy chain variable domain comprising: CDR1 with the amino acid sequence SEQ ID NO: 12, CDR2 with the amino acid sequence of SEQ ID NO: 17 and CDR3 with the amino acid sequence SEQ ID NO:

18.

2. A monoclonal antibody or antigen-binding fragment thereof according to claim 1, where: (i) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 19 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 29; or (ii) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 20 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 29; or (iii) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 21 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 30; or (iv) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 22 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 30; or (v) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 23 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 30; or (vi) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 23 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 31; or (vii) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 19 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 32; or (viii) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 22 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 32; or (ix) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 24 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 32; or (x) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 26 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 32; or (xi) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 21 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 33; or (xii) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 19 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 33; or (xiii) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 25 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 34; or (xiv) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 20 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 33; or (xv) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 22 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 33; or (xvi) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 24 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 33; or (xvii) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 26 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 33; or (xviii) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 23 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 33; or (ixx) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 27 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 34; or (xx) (a) the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 28 and (b) the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:

34.

3. A monoclonal antibody according to any one of claims 1, 2, wherein the antibody that specifically binds to the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor is a full-length IgG antibody.

4. The monoclonal antibody of claim 3, wherein the full-length IgG antibody is of the human IgG1, IgG2, IgG3 or IgG4 isotype.

5. The monoclonal antibody of claim 4, wherein the full-length IgG antibody is of the human IgG1 isotype.

6. A monoclonal antibody according to claim 5, wherein the antibody comprises a deletion of 446G and 447K according to the amino acid numbering of EU antibodies in the CH3 region.

7. A monoclonal antibody according to claim 5, wherein the antibody comprises the mutations S239D and I332E according to the amino acid numbering of EU antibodies.

8. A monoclonal antibody according to claim 5, wherein the antibody comprises the mutations G236A, S239D and I332E according to the amino acid numbering of EU antibodies.

9. A monoclonal antibody according to claim 1, comprising: (i) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 35, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 45; or (ii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 36, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 46; or (iii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 37, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 47; or (iv) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 38, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 47; or (v) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 39, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 48; or (vi) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 39, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 49; or (vii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 35, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50; or (viii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 38, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50; or (ix) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 40, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50; or (x) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 42, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50; or (xi) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 37, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or (xii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 35, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or (xiii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 41, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 52; or (xiv) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 36, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or (xv) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 38, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or (xvi) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 40, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or (xvii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 42, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or (xviii) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 39, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 51; or (ixx) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 43, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 52; or (xx) (a) a light chain comprising the amino acid sequence of SEQ ID NO: 44, and (b) a heavy chain comprising the amino acid sequence of SEQ ID NO:

52.

10. A nucleic acid that encodes an antibody or antigen-binding fragment thereof according to any one of claims 1-9.

11. The nucleic acid of claim 10, wherein the nucleic acid is DNA.

12. A mammalian host cell for producing an antibody or antigen-binding fragment thereof according to any one of claims 1-9, containing a nucleic acid according to any one of claims 10, 11 and an expression control sequence.

13. A method for producing an antibody or an antigen-binding fragment thereof according to any one of claims 1-9, comprising culturing a mammalian host cell according to claim 12 in a culture medium under conditions sufficient to produce said antibody, followed by isolating and purifying the resulting antibody.

14. A pharmaceutical composition for the treatment or prevention of a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor, comprising an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 9 in a therapeutically effective amount in combination with one or more pharmaceutically acceptable excipients, wherein the disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor is selected from the group: type 1 diabetes mellitus, delay in the transition of type 1 diabetes mellitus stage 2 to stage 3, high blood glucose, impaired glucose tolerance, prediabetes, rejection of nickel implants or prostheses, sarcoidosis, berylliosis, celiac disease or dermatitis herpetiformis.

15. A pharmaceutical composition for the treatment or prevention of a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor, comprising an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 9 and an insulin preparation, wherein the disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of a human T-cell receptor is selected from the group: type 1 diabetes mellitus, delay in the transition of type 1 diabetes mellitus stage 2 to stage 3, elevated blood glucose, impaired glucose tolerance, prediabetes, rejection of nickel implants or prostheses, sarcoidosis, berylliosis, celiac disease or dermatitis herpetiformis.

16. The use of an antibody or antigen-binding fragment thereof according to any one of claims 1-9 or a pharmaceutical composition according to any one of claims 14-15 for the treatment or prevention in a subject in need of such treatment or prevention of a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor, wherein the disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor is selected from the group: type 1 diabetes mellitus, delay in the transition of type 1 diabetes mellitus stage 2 to stage 3, elevated blood glucose, impaired glucose tolerance, prediabetes, rejection of nickel implants or prostheses, sarcoidosis, berylliosis, celiac disease or dermatitis herpetiformis.

17. The use of an antibody or antigen-binding fragment thereof according to any one of claims 1 to 9 and an insulin preparation for the treatment or prevention of a disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor, in a subject in need of such treatment or prevention, wherein the disease or disorder mediated by the TRBV5-1 segment of the variable domain of the beta chain of the human T-cell receptor is selected from the group: type 1 diabetes mellitus, delay in the transition of type 1 diabetes mellitus stage 2 to stage 3, elevated blood glucose, impaired glucose tolerance, prediabetes, rejection of nickel implants or prostheses, sarcoidosis, berylliosis, celiac disease or dermatitis herpetiformis.

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