# US 2019/0169261 A1 · T cell receptors and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0169261 A1 - Document ID: US20190169261A1 - Status: Published application - Kind: A1 - Application number: 16/309,902 - Filed: 2017-06-16 - Published: 2019-06-06 - Earliest claimed: 2016-06-17 - Assignees: Medigene Immunotherapies GmbH - Applicants: Medigene Immunotherapies GmbH - Inventors: Christian ELLINGER; Carina WEHNER; Manon WEIS; Susanne WILDE; Dolores SCHENDEL - Web page: https://patentgrep.com/patent/US20190169261A1 ## CPC - C07K 14/7051: {T-cell receptor (TcR)-CD3 complex} - A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00) - A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells - A61K 40/19: Dendritic cells - A61K 40/24: Antigen-presenting cells [APC] - A61K 40/32: T-cell receptors [TCR] - A61K 40/427: {PRAME} - A61P 35/00: Antineoplastic agents - C07K 14/4748: {Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE} - C07K 14/70539: {MHC-molecules, e.g. HLA-molecules} - C07K 16/3053: {Skin, nerves, brain} - C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to the field of biotechnology. Specifically, the invention provides antigen-specific T-cell receptors (TCRs). Further, the invention encompasses polynucleotides encoding the same and vectors comprising said polynucleotides. Host cells comprising the molecules of the invention are also provided. Moreover, the invention provides means and methods for diagnostics and therapy, in particular of cancer. ## Claims ### Claim 1 A T-cell receptor (TCR) comprising: (i) a CDR3 of the TCR alpha chain variable region comprising or consisting of the amino acid sequence of CAVHSTAQAGTALIF (SEQ ID NO: 1) or an amino acid sequence having at least 80% identity to SEQ ID NO: 1, more preferably at least 85% identity, more preferably 90% or 95% and/or (ii) a CDR3 of the TCR beta chain variable region comprising or consisting of the amino acid sequence of CASSTHRGQTNYGYTF (SEQ ID NO. 2) or an amino acid sequence having at least 80% identity to SEQ ID NO: 2, more preferably at least 85% identity, more preferably 90% or 95% identity, said TCR being capable of binding to the epitope comprised within the amino acid sequence of X1LX2GLDX3LL (SEQ ID NO:31) or its MHC-bound form, preferably to the epitope comprised within the amino acid sequence of VLDGLDVLL (SEQ ID NO:32) or its MHC-bound form. ### Claim 2 (depends on 1) The TCR according to claim 1, comprising (i) a TCR alpha chain variable region comprising or consisting of the amino acid sequence depicted in SEQ ID NO: 15, and/or (ii) a TCR beta chain variable region comprising or consisting of the amino acid sequence depicted in SEQ ID NO: 16. ### Claim 3 (depends on 1, 2) The TCR according to any one of claim 1 or 2, further comprising (i) a TCR alpha chain constant region and/or (ii) a TCR beta chain constant region. ### Claim 4 The TCR according to any one of the preceding claims, comprising (i) a TCR alpha chain comprising or consisting of an amino acid sequence selected from SEQ ID NO: 7; SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, or an amino acid sequence having at least 80% identity, more preferably at least 85% identity, more preferably 90% or 95% to SEQ ID NO: 7, 11, 9 or 13; and/or (ii) a TCR beta-chain comprising or consisting of an amino acid sequence selected from of SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, or SEQ ID NO: 14 or an amino acid sequence having at least 80% identity, more preferably at least 85% identity, more preferably 90% or 95% to SEQ ID NO: 8, 10, 12 or 14. ### Claim 5 The TCR according to any one of the preceding claims, said TCR being selected from a native TCR, a TCR variant, a TCR fragment, or a TCR construct. ### Claim 6 (depends on 5) The TCR construct according to claim 5, comprising at least one TCR alpha-chain(s) and at least one TCR beta-chain(s) covalently linked to each other to form TCR heterodimers or multimers. ### Claim 7 The TCR according to any of the preceding claims, further comprising one or more fusion component(s) optionally selected from Fc receptors; Fc domains, including IgA, IgD, IgG, IgE, and IgM; cytokines, including IL-2 or IL-15; toxins; antibodies or antigen-binding fragments thereof, including anti-CD3, anti-CD28, anti-CDS, anti-CD 16 or anti-CD56 antibodies or antigen-binding fragments thereof; CD247 (CD3-zeta), CD28, CD137, CD134 domain, or combinations thereof, optionally further comprising at least one linker. ### Claim 8 (depends on 1, 2, 3) The TCR according to any one of the preceding claims, comprising (i) at least one TCR alpha-chain as defined in any one of claims 1 to 3; and (ii) at least one TCR beta-chain as defined in any one of claims 1 to 3 (iii) an antibody or a single chain antibody fragment (scFv) which is directed against an antigen or epitope on the surface of lymphocytes. wherein the TCR alpha-chain(s) and TCR beta-chain(s) are linked to each other and fused, optionally via a linker, to said antibody or scFv. ### Claim 9 (depends on 8) The TCR according to claim 8, wherein said antigen is selected from CD3, CD28, CD5, CD16 or CD56. ### Claim 10 The TCR according to any one of the preceding claims, further comprising at least one label. ### Claim 11 The TCR according to any one of the preceding claims which is soluble. ### Claim 12 A nucleic acid encoding the TCR according to any one of the preceding claims. ### Claim 13 (depends on 12) The nucleic acid according to claim 12, comprising the nucleic acid sequence of SEQ ID NO: 23, 24, 25, 26, 27, 28, 29 or 30. ### Claim 14 (depends on 12, 13) A vector comprising the nucleic acid according to any one of claim 12 or 13. ### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14) A host cell comprising the TCR according to any one of claims 1 to 11, the nucleic acid sequence according to claim 12 or 13 or the vector according to claim 14. ### Claim 16 (depends on 15) The host cell according to claim 15 which is selected from lymphocytes including but not limited to cytotoxic T lymphocytes (CTLs), CD8+ T cells, CD4+ T cells, natural killer (NK) cells, natural killer T (NKT) cells, gamma/ delta-T-cells. ### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 16) A method for obtaining a TCR according to any one of claims 1 to 11, comprising (i) incubating a host cell according to claim 15 or 16 under conditions causing expression of said TCR (ii) purifying said TCR. ### Claim 18 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) A pharmaceutical or diagnostic composition comprising one or more of: (i) the TCR according to any one of claims 1 to 11; (ii) the nucleic acid according to any one of claim 12 or 13 (iii) the vector according to claim 14; and/or (iv) the host cell according to any one of claim 15 or 16, and, optionally, pharmaceutically excipient(s). ### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) The TCR according to any one of claims 1 to 11, the nucleic acid according to claim 12 or 13, the vector according to claim 14 and/or the host cell according to claim 15 or 16 for use as a medicament. ### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) The TCR according to any one of claims 1 to 11, the nucleic acid according to claim 12 or 13, the vector according to claim 14 and/or the host cell according to claim 15 or 16 for use in detection, diagnosis, prognosis, prevention and/or treatment of cancer. ### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20) The TCR, nucleic acid, vector and/or host cell for the use of claim 20, wherein prevention and/or treatment of cancer comprises (a) providing or more of (i) the TCR according to any one of claims 1 to 11; (ii) the nucleic acid according to any one of claim 12 or 13 (iii) the vector according to claim 14; and/or (iv) the host cell according to any one of claim 15 or 16, (v) the pharmaceutical composition according to claim 18; and (b) administering at least one of (i) to (v) to a subject in need thereof. ### Claim 22 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20) The TCR, nucleic acid, vector and/or host cell for the use of claim 20, wherein prevention and/or treatment of cancer comprises (a) providing a sample of a subject, said sample comprising lymphocytes; (b) providing one or more of (i) the TCR according to any one of claims 1 to 11; (ii) the nucleic acid according to any one of claim 12 or 13 (iii) the vector according to claim 14; and/or (iv) the host cell according to any one of claim 15 or 16, (v) the pharmaceutical composition according to claim 18; (c) introducing of one or more of (i) to (v) of step (b) into the lymphocytes of step (a) and, thereby, obtaining modified lymphocytes, (d) administering the modified lymphocytes of step (c) to a subject or patient in need thereof. ### Claim 23 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 15, 16, 18) A method of detecting the presence of a cancer in a subject in vitro, comprising: (a) providing a sample of a subject, said sample comprising one or more cells; (b) contacting said sample with (i) the TCR according to any one of claims 1 to 11; (ii) the host cell according to any one of claim 15 or 16, and/or (iii) the pharmaceutical composition according to claim 18; thereby forming a complex, and (c) detecting the complex, wherein detection of the complex is indicative of the presence of the cancer in the subject. ### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14) Use of a TCR according to any one of claims 1 to 11, a nucleic acid according to claim 12 or 13 and/or a vector according to claim 14 for generating modified lymphocytes.