# US 11,440,956 B2 · Anti-thyroglobulin T cell receptors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,440,956 B2 - Document ID: US11440956B2 - Status: Granted - Kind: B2 - Application number: 16/586,310 - Filed: 2019-09-27 - Published: 2020-04-02 - Granted: 2022-09-13 - Earliest claimed: 2014-11-14 - Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services - Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Services - Inventors: Kenichi Hanada; Qiong J. Wang; James C. Yang; Zhiya Yu - Web page: https://patentgrep.com/patent/US11440956B2 ## CPC - C07K 16/26: against hormones {; against hormone releasing or inhibiting factors} - A61K 39/001144: {Hormones, e.g. calcitonin} - A61P 35/00: Antineoplastic agents - A61P 35/04: specific for metastasis - C07K 14/7051: {T-cell receptor (TcR)-CD3 complex} - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K 2039/5156: {expressing foreign proteins} - 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 2317/565: Complementarity determining region [CDR] - C07K 2317/70: characterized by effect upon binding to a cell or to an antigen - C07K 2318/20: Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics - C07K 2319/00: Fusion polypeptide - 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 Disclosed is a synthetic T cell receptor (TCR) having antigenic specificity for an HLA-A2-restricted epitope of thyroglobulin (TG), TG470-478. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells are also provided. Antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal. ## Claims ### Claim 1 A method of treating cancer in a mammal in need thereof, comprising administering to the mammal (a) one or more host cells expressing at least one of (i)-(vi): (i) a T cell receptor (TCR) having antigenic specificity for the amino acid sequence of SEQ ID NO: 2 and comprising an α chain complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO: 3, an α chain CDR2 comprising the amino acid sequence of SEQ ID NO: 4, an α chain CDR3 comprising the amino acid sequence of SEQ ID NO: 5, a β chain CDR1 comprising the amino acid sequence of SEQ ID NO: 6, a β chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a β chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, (ii) a polypeptide comprising a functional portion of the TCR of (i), wherein the functional portion comprises the amino acid sequences of SEQ ID NOs: 3-8, (iii) a polypeptide comprising a functional portion of the TCR of (i), wherein the functional portion comprises the amino acid sequence of both SEQ ID NOs: 9 and 10, (iv) a polypeptide comprising a functional portion of the TCR of (i), wherein the functional portion comprises the amino acid sequence of both SEQ ID NOs: 11 and 12, (v) a protein comprising at least one of the polypeptides of any one of (ii)-(iv), and (vi) a protein comprising a first polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 3-5 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 6-8, or (b) a pharmaceutical composition comprising the one or more cells of (a) and a pharmaceutically acceptable carrier in an amount effective to treat the cancer in the mammal, wherein the cancer expresses a human thyroglobulin (hTG) peptide comprising an amino acid sequence of SEQ ID NO: 2. ### Claim 2 (depends on 1) The method of claim 1, wherein the cancer is thyroid cancer or neuroblastoma. ### Claim 3 (depends on 1) The method of claim 1, wherein the TCR comprises an α chain variable region comprising the amino acid sequence of SEQ ID NO: 9 and a β chain variable region comprising the amino acid sequence of SEQ ID NO: 10. ### Claim 4 (depends on 1) The method of claim 1, wherein the TCR further comprises an α chain constant region comprising the amino acid sequence of SEQ ID NO: 13 and a β chain constant region comprising the amino acid sequence of SEQ ID NO: 14. ### Claim 5 (depends on 1) The method of claim 1, wherein the TCR comprises an α chain comprising the amino acid sequence of SEQ ID NO: 11 and a β chain comprising the amino acid sequence of SEQ ID NO: 12. ### Claim 6 (depends on 1) The method of claim 1, wherein the polypeptide comprises a TCR α chain, a TCR β chain, and a self-cleaving, viral linker peptide, wherein the linker peptide is positioned between the TCR α and β chains. ### Claim 7 (depends on 1) The method of claim 1, wherein the protein of (vi) comprises a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 9 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 10. ### Claim 8 (depends on 1) The method of claim 1, wherein the protein of (vi) comprises a first polypeptide chain comprising the amino acid sequence of SEQ ID NO: 11 and a second polypeptide chain comprising the amino acid sequence of SEQ ID NO: 12. ### Claim 9 (depends on 1) The method of claim 1, wherein the protein of (vi) is a fusion protein. ### Claim 10 (depends on 1) The method of claim 1, wherein the protein of (vi) is a recombinant antibody. ### Claim 11 (depends on 1) The method of claim 1, wherein the one or more host cells is/are human. ### Claim 12 (depends on 1) The method of claim 1, wherein the method comprises administering to the mammal a host cell expressing the TCR of (i). ### Claim 13 (depends on 1) The method of claim 1, wherein the method comprises administering to the mammal a population of cells comprising at least one host cell expressing the TCR of (i).