# US 10,869,911 B2 · Chimeric protein > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,869,911 B2 - Document ID: US10869911B2 - Status: Granted - Kind: B2 - Application number: 15/565,914 - Filed: 2016-04-12 - Published: 2018-06-21 - Granted: 2020-12-22 - Earliest claimed: 2015-04-13 - Assignees: Autolus Limited - Applicants: Ucl Business PLC - Inventors: Martin Pulé; Brian Philip - Web page: https://patentgrep.com/patent/US10869911B2 ## CPC - A61K 38/191: {Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta} - 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 39/39558: {against tumor tissues, cells, antigens} - A61P 35/00: Antineoplastic agents - C07K 14/7051: {T-cell receptor (TcR)-CD3 complex} - C07K 16/2887: {against CD20} - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - C07K 2317/734: Complement-dependent cytotoxicity [CDC] - C07K 2319/00: Fusion polypeptide - C07K 2319/03: containing a transmembrane segment - 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 - 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) ## Abstract The present invention provides a chimeric protein which comprises a multi-spanning transmembrane protein fused to a FAS endodomain, wherein the multi-spanning transmembrane protein binds an extracellular ligand, leading to activation of the FAS endodomain. The chimeric protein is useful as a suicide gene. The invention also provides a cell, such as a T cell comprising such a chimeric protein, which is useful in adoptive T cell immunotherapy approaches. ## Claims ### Claim 1 A chimeric protein comprising a multi-spanning transmembrane protein fused to a FAS endodomain, wherein the multi-spanning transmembrane protein comprises CD20 truncated at the amino-terminus so that it lacks up to 41 amino acids from the CD20 amino-terminus, or at the carboxy-terminus so that it lacks up to 61 amino acids from the CD20 carboxy-terminus, and wherein the multi-spanning transmembrane protein binds at least one extracellular ligand selected from Rituxumab, Ofatumumab or Veltuzumab, leading to activation of the FAS endodomain. ### Claim 2 (depends on 1) The chimeric protein according to claim 1, which comprises a FAS endodomain fused to the carboxy-terminus of a truncated version of CD20, lacking up to 41 amino acids from the CD20 amino-terminus. ### Claim 3 (depends on 1) The chimeric protein according to claim 1, wherein the FAS endodomain comprises the sequence shown in SEQ ID NO: 20. ### Claim 4 (depends on 1) The chimeric protein according to claim 1, wherein the FAS endodomain comprises the amino acid sequence of SEQ ID NO: 29. ### Claim 5 A chimeric protein comprising a multi-spanning transmembrane protein that consists of the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6 fused to a FAS endodomain, wherein the multi-spanning transmembrane protein binds at least one extracellular ligand selected from Rituxumab, Ofatumumab or Veltuzumab, leading to activation of the FAS endodomain. ### Claim 6 (depends on 5) The chimeric protein according to claim 5, wherein the FAS endodomain comprises the sequence shown in SEQ ID NO: 20. ### Claim 7 (depends on 5) The chimeric protein according to claim 5, wherein the FAS endodomain comprises the amino acid sequence of SEQ ID NO: 29. ### Claim 8 A chimeric protein comprising: a multi-spanning transmembrane protein fused to a FAS endodomain, wherein the multi-spanning transmembrane protein comprises the amino acid sequence of SEQ ID NO: 3 truncated at the amino terminus so that it lacks up to 41 amino acids from the amino-terminus of SEQ ID NO: 3, or truncated at the carboxy-terminus so that it lacks up to 61 amino acids from the carboxy-terminus of SEQ ID NO: 3, and optionally has one or both of the following substitution mutations: (a) an amino acid substitution at position A170 of SEQ ID NO: 3; (b) an amino acid substitution at position P172 of SEQ ID NO: 3; and wherein the multi-spanning transmembrane protein binds at least one extracellular ligand selected from Rituxumab, Ofatumumab or Veltuzumab, leading to activation of the FAS endodomain. ### Claim 9 (depends on 8) The chimeric protein according to claim 8 that comprises the mutation P172W, with position 172 defined with reference to the full length CD20 sequence shown as SEQ ID NO: 3. ### Claim 10 (depends on 8) The chimeric protein according to claim 8, wherein the FAS endodomain comprises the amino acid sequence of SEQ ID NO: 29. ### Claim 11 (depends on 8) The chimeric protein according to claim 8, wherein the FAS endodomain comprises the sequence shown in SEQ ID NO: 20. ### Claim 12 (depends on 1) An isolated cell which expresses the chimeric protein according to claim 1. ### Claim 13 (depends on 5) An isolated cell which expresses the chimeric protein according to claim 5. ### Claim 14 (depends on 6) An isolated cell which expresses the chimeric protein according to claim 6. ### Claim 15 (depends on 3) An isolated cell which expresses the chimeric protein according to claim 3. ### Claim 16 (depends on 4) An isolated cell which expresses the chimeric protein according to claim 4. ### Claim 17 (depends on 7) An isolated cell which expresses the chimeric protein according to claim 7. ### Claim 18 (depends on 8) An isolated cell which expresses the chimeric protein according to claim 8. ### Claim 19 (depends on 9) An isolated cell which expresses the chimeric protein according to claim 9. ### Claim 20 (depends on 10) An isolated cell which expresses the chimeric protein according to claim 10. ### Claim 21 (depends on 11) An isolated cell which expresses the chimeric protein according to claim 11.