# US 11,026,996 B2 · Human Notch1 based fusion proteins as decoy inhibitors of jagged-notch signaling and DLL-notch signaling > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,026,996 B2 - Document ID: US11026996B2 - Status: Granted - Kind: B2 - Application number: 16/304,595 - Filed: 2017-05-25 - Published: 2019-06-20 - Granted: 2021-06-08 - Earliest claimed: 2016-05-25 - Assignees: The Trustees of Columbia University in the City of New York - Applicants: The Trustees of Columbia University in the City of New York - Inventors: Jan Kitajewski; Reyhaan Ali Chaudhri - Web page: https://patentgrep.com/patent/US11026996B2 ## CPC - A61K 38/1866: {Vascular endothelial growth factor [VEGF]} - A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants} - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 27/02: Ophthalmic agents - A61P 35/00: Antineoplastic agents - C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} - C07K 16/283: {against Fc-receptors, e.g. CD16, CD32, CD64 (CD23 C07K16/2851)} - C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes} - C12N 15/62: DNA sequences coding for fusion proteins - C12N 15/85: for animal cells - C07K 2319/02: containing a signal sequence - C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract This invention provides a fusion protein, the sequence of which, commencing at the N-terminus of the fusion protein, is identical to the sequence of amino acids in: (a) an extracellular domain of a human Notch1 receptor protein, followed by (b) an Fc portion of an antibody, wherein the extracellular domain of the human Notch1 receptor protein (i) commences with the amino acid present at the N-terminus of EGF-like repeat 10 and (ii) extends to and includes the C-terminal amino acid of EGF-like repeat 18 or 20. Also provided is a composition comprising the any of the fusion proteins of this invention and a pharmaceutically acceptable carrier, a method of treating a subject suffering from age-related macular degeneration (AMD), diabetic retinopathy, or cancer which comprises administering to the subject any of the compositions of this invention in an amount effective to treat the subject's cancer. ## Claims ### Claim 1 A fusion protein, the sequence of which, commencing at the N-terminus of the fusion protein, is identical to the sequence of amino acids in: (a) an extracellular domain of a human Notch1 receptor protein, followed by (b) an Fc portion of an antibody, wherein the extracellular domain of the human Notch1 receptor protein (i) commences with the amino acid present at the N-terminus of EGF-like repeat 10 and (ii) extends to and includes the C-terminal amino acid of EGF-like repeat 18 as the C-terminal amino acid of the extracellular domain. ### Claim 2 (depends on 1) The fusion protein of claim 1, wherein the Fc portion of the antibody is the Fc portion of a human antibody. ### Claim 3 (depends on 1) A composition comprising the fusion protein of claim 1 and a pharmaceutically acceptable carrier. ### Claim 4 (depends on 3) The composition of claim 3, wherein the fusion protein is present in an amount effective to inhibit Jagged-Notch signaling. ### Claim 5 (depends on 3) The composition of claim 3, wherein the fusion protein is present in an amount effective to inhibit Delta-like-Notch signaling. ### Claim 6 (depends on 3) A method of treating a subject suffering from cancer which comprises administering to the subject the composition of claim 3 in an amount effective to treat the subject's cancer. ### Claim 7 (depends on 6) The method of claim 6, wherein the cancer is pancreatic cancer. ### Claim 8 (depends on 6) The method of claim 6, wherein the cancer is breast cancer. ### Claim 9 A fusion protein, the sequence of which, commencing at the N-terminus of the fusion protein, is identical to the sequence of amino acids in: (a) an extracellular domain of a human Notch1 receptor protein, followed by (b) an Fc portion of an antibody, wherein the extracellular domain of the human Notch1 receptor protein (i) commences with the amino acid present at the N-terminus of EGF-like repeat 10 and (ii) extends to and includes the C-terminal amino acid of EGF-like repeat 20 as the C-terminal amino acid of the extracellular domain. ### Claim 10 A fusion protein, the sequence of which, commencing at the N-terminus of the fusion protein, is identical to the sequence of amino acids in: (a) an extracellular domain of a human Notch1 receptor protein, followed by (b) a linker sequence, followed by (c) an Fc portion of an antibody, wherein the extracellular domain of the human Notch1 receptor protein (i) commences with the amino acid present at the N-terminus of EGF-like repeat 10 and (ii) extends to and includes the C-terminal amino acid of EGF-like repeat 18 as the C-terminal amino acid of the extracellular domain. ### Claim 11 A fusion protein, the sequence of which, commencing at the N-terminus of the fusion protein, is identical to the sequence of amino acids in: (a) an extracellular domain of a human Notch1 receptor protein, followed by (b) a linker sequence, followed by (c) an Fc portion of an antibody, wherein the extracellular domain of the human Notch1 receptor protein (i) commences with the amino acid present at the N-terminus of EGF-like repeat 10 and (ii) extends to and includes the C-terminal amino acid of EGF-like repeat 20 as the C-terminal amino acid of the extracellular domain.