# US 10,308,697 B2 · Fusion proteins for treating cancer and related methods > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,308,697 B2 - Document ID: US10308697B2 - Status: Granted - Kind: B2 - Application number: 15/307,646 - Filed: 2015-04-30 - Published: 2017-02-23 - Granted: 2019-06-04 - Earliest claimed: 2014-04-30 - Assignees: President and Fellows of Harvard College - Applicants: President and Fellows of Harvard College - Inventors: Jeffrey Charles Way; Avram Lev Robinson-Mosher - Web page: https://patentgrep.com/patent/US10308697B2 ## CPC - C07K 14/56: IFN-alpha - A61K 38/212: {IFN-alpha} - A61K 39/39558: {against tumor tissues, cells, antigens} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - C07K 16/2863: {against receptors for growth factors, growth regulators} - C07K 16/32: against translation products of oncogenes - A61K 2039/505: {comprising antibodies} - 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 2317/56: variable (Fv) region, i.e. VH and/or VL - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2319/00: Fusion polypeptide - C07K 2319/01: containing a localisation/targetting motif - 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 Aspects of the disclosure provide fusion proteins that bind cells expressing one or more target molecules including, for example, one or more cell surface multisubunit signaling receptors (e.g., EGFRvIII-expressing cells that also express interferon receptors) and that induce anti-proliferative effects, and related compositions and methods for the treatment of cancer. ## Claims ### Claim 1 A fusion protein comprising a Type 1 interferon protein domain comprising the sequence of SEQ ID NO: 18 or a sequence with one or two mutations relative to SEQ ID NO:18, the mutations selected from the group consisting of: L30A, R145A, M149A, E59A, H58A, and R150A; an antibody variable region element comprising a heavy chain variable region comprising the amino acid sequence provided by SEQ ID NO: 15 and a light chain variable region comprising the amino acid sequence provided by SEQ ID NO: 16, wherein the antibody variable region element binds to EGFRvIII; and a linker that connects the protein domain and the antibody variable region element. ### Claim 2 (depends on 1) The fusion protein of claim 1, wherein the fusion protein comprises one polypeptide chain. ### Claim 3 (depends on 1) The fusion protein of claim 1, wherein the Type 1 interferon protein domain comprises mutations H58A and R150A. ### Claim 4 (depends on 1) The fusion protein of claim 1, wherein the Type 1 interferon comprises mutations E59A and M149A. ### Claim 5 (depends on 1) The fusion protein of claim 1, wherein the linker connects the C-terminal end of the antibody variable region element to the N-terminal end of the protein domain. ### Claim 6 (depends on 1) The fusion protein of claim 1, wherein the linker connects the C-terminal end of the protein domain to the N-terminal end of the antibody or antibody variable region element. ### Claim 7 (depends on 1) The fusion protein of claim 1, wherein the linker is a peptide linker and has a net charge. ### Claim 8 (depends on 1) The fusion protein of claim 1, wherein the net charge of the linker is negative. ### Claim 9 (depends on 1) The fusion protein of claim 1, wherein the net charge of the linker is positive. ### Claim 10 (depends on 8) The fusion protein of claim 8, wherein the linker comprises amino acids selected from the group consisting of glycine, serine, glutamate, and aspartate. ### Claim 11 (depends on 9) The fusion protein of claim 9, wherein the linker comprises amino acids selected from the group consisting of lysine, arginine, and histidine. ### Claim 12 (depends on 1) The fusion protein of claim 1, comprising the amino acid sequence of SEQ ID NO: 1 [MR1-1 IFNα2-lb WT]. ### Claim 13 (depends on 1) The fusion protein of claim 1, comprising the amino acid sequence of SEQ ID NO: 2 [MR1-1 IFNα2-1B L30A]. ### Claim 14 (depends on 1) The fusion protein of claim 1, comprising the amino acid sequence of SEQ ID NO: 3 [MR1-1 IFNα2-1B R145A]. ### Claim 15 (depends on 1) The fusion protein of claim 1, comprising the amino acid sequence of SEQ ID NO: 4 [MR1-1 IFNα2-lb E59A M149A]. ### Claim 16 An isolated fusion protein comprising the amino acid sequence of SEQ ID NO: 5 [MR1-1 IFNα2-lb H58A R150A].