# US 11,993,662 B2 · General sequence of chimeric antigen receptor, chimeric antigen receptor and an application thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,993,662 B2 - Document ID: US11993662B2 - Status: Granted - Kind: B2 - Application number: 17/027,856 - Filed: 2020-09-22 - Published: 2021-04-08 - Granted: 2024-05-28 - Earliest claimed: 2019-08-06 - Assignees: Fudan University - Applicants: Fudan University - Inventors: Yiwei Chu; Yuedi Wang; Feifei Luo - Web page: https://patentgrep.com/patent/US11993662B2 ## CPC - C07K 16/32: against translation products of oncogenes - A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells - A61K 40/31: Chimeric antigen receptors [CAR] - A61K 40/4205: {Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4} - A61K 40/4211: {CD19 or B4} - A61K 40/4261: {Proteoglycans, e.g. glypican, brevican or CSPG4} - A61P 35/00: Antineoplastic agents - C07K 14/7051: {T-cell receptor (TcR)-CD3 complex} - C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies - C07K 16/2803: {against the immunoglobulin superfamily} - C07K 16/303: {Liver or Pancreas} - C12N 5/0636: {T lymphocytes} - C12N 5/0646: {Natural killers cells [NK], NKT cells} - A61K 2239/28: Expressing multiple CARs, TCRs or antigens - C07K 2317/53: Hinge - C07K 2317/622: Single chain antibody (scFv) - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2319/03: containing a transmembrane segment - 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 - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract The present invention provides a general sequence of chimeric antigen receptor (CAR) and an application thereof, The hinge domain in the general sequence includes hinge domain V-5, hinge domain V-4-5, hinge domain V-3-4-5, hinge domain V-2-3-4-5 or hinge domain V-1-2-3-4-5. The CAR constructed by using the general sequence of the chimeric antigen receptor of the present invention can significantly improve the antigen-specific immune response of CAR-T cells, enhance the sensitivity of CAR-T cells and resist exhaustion, so as to enhance the therapeutic effect of CAR-T cells and enhance the therapeutic effect of anti-tumor agents. At the same time, the CAR containing the general sequence of the present invention is suitable for transfection of immune cells such as T cells and NK cells, and can be broadly applied to tumor therapy. ## Claims ### Claim 1 A general sequence of chimeric antigen receptor, wherein a hinge domain comprises a general sequence selected from the group consisting of a hinge domain V-5, a hinge domain V-4-5, a hinge domain V-3-4-5, a hinge domain V-2-3-4-5 or a hinge domain V-1-2-3-4-5; wherein the nucleotide sequence of the hinge domain V-5 is set forth in SEQ ID NO.1; the nucleotide sequence of the hinge domain V-4-5 is set forth in SEQ ID NO.2; the nucleotide sequence of the hinge domain V-3-4-5 is set forth in SEQ ID NO.3; the nucleotide sequence of the hinge domain V-2-3-4-5 is set forth in SEQ ID NO.4; the nucleotide sequence of the hinge domain V-1-2-3-4-5 is set forth in SEQ ID NO.5; the nucleotide sequence of the general sequence comprising the hinge domain V-5 is set forth in SEQ ID NO.6; the nucleotide sequence of the general sequence comprising the hinge domain V-4-5 is set forth in SEQ ID NO.7; the nucleotide sequence of the general sequence comprising the hinge domain V-3-4-5 is set forth in SEQ ID NO.8; the nucleotide sequence of the general sequence comprising the hinge domain V-2-3-4-5 is set forth in SEQ ID N0.9; and the nucleotide sequence of the general sequence comprising the hinge domain V-1-2-3-4-5 is set forth in SEQ ID NO.10. ### Claim 2 (depends on 1) A chimeric antigen receptor comprising the general sequence of claim 1, wherein the chimeric antigen receptor is obtained by connecting a single chain antibody and the general sequence in series; wherein the single chain antibody is selected from the group consisting of HER2, CD19, and GPC; wherein the single chain antibody is HER2, and the chimeric antigen receptors are selected from the group consisting of HER2-V-5, HER2-V-4-5, HER2 V-3-4-5, HER2-2-3-4-5 and HER2-V-1-2-3-4-5; wherein the nucleotide sequence of HER2-V-5 is set forth in SEQ ID NO:11; the nucleotide sequence of HER2-V-4-5 is set forth in SEQ ID NO:12; the nucleotide sequence of HER2-V-3-4-5 is set forth in SEQ ID NO:13; the nucleotide sequence of HER2-V-2-3-4-5 is set forth in SEQ ID NO:14; the nucleotide sequence of HER2-V-1-2-3-4-5 is set forth in SEQ ID NO:15; wherein the single chain antibody is CD19, and the chimeric antigen receptors are selected from the group consisting of CD19-V-5, CD19-V-4-5, CD19 V-3-4-5, CD19-2-3-4-5 and CD19-V-1-2-3-4-5; wherein the nucleotide sequence of CD19-V-5 is set forth in SEQ ID NO:16; the nucleotide sequence of CD19-V-4-5 is set forth in SEQ ID NO:17; the nucleotide sequence of CD19-V-3-4-5 is set forth in SEQ ID NO:18; the nucleotide sequence of CD19-V-2-3-4-5 is set forth in SEQ ID NO:19; the nucleotide sequence of CD19-V-1-2-3-4-5 is set forth in SEQ ID NO: 20; or wherein the single chain antibody is GPC3, and the chimeric antigen receptors are selected from the group consisting of GPC3-V-5, GPC3-V-4-5, GPC3 V-3-4-5, GPC3-2-3-4-5 and GPC3-V-1-2-3-4-5; wherein the nucleotide sequence of GPC3-V-5 is set forth in SEQ ID NO:21; the nucleotide sequence of GPC3-V-4-5 is set forth in SEQ ID NO:22; the nucleotide sequence of GPC3-V-3-4-5 is set forth in SEQ ID NO:23; the nucleotide sequence of GPC3-V-2-3-4-5 is set forth in SEQ ID NO:24; the nucleotide sequence of GPC3-V-1-2-3-4-5 is set forth in SEQ ID NO:25. ### Claim 3 (depends on 1) A drug for improving the antigen-specific immune response of immune cells and promoting an anti-tumor effect, wherein the active components of the drug comprise the general sequence of the chimeric antigen receptor of claim 1.