# US 9,518,117 B2 · Therapeutic CD47 antibodies > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,518,117 B2 - Document ID: US9518117B2 - Status: Granted - Kind: B2 - Application number: 14/940,755 - Filed: 2015-11-13 - Published: 2016-05-19 - Granted: 2016-12-13 - Earliest claimed: 2012-12-12 - Assignees: Tioma Therapeutics, Inc. - Applicants: Vasculox Inc. - Inventors: William A. Frazier; Pamela T. Manning; Gerhard Frey; Hwai Wen Chang - Web page: https://patentgrep.com/patent/US9518117B2 ## CPC - C07K 16/2803: {against the immunoglobulin superfamily} - 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 - C07K 16/30: from tumour cells - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - 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) ## Abstract Provided are monoclonal antibodies and antigen-binding fragments thereof that bind to, and inhibit the activity of, CD47, as well as monoclonal antibodies and antigen binding fragments thereof that compete with the former for binding to CD47. Also provided are combinations of any of the foregoing. Such antibody compounds are variously effective in 1) treating tissue ischemia and ischemia-reperfusion injury (IRI) in the setting of organ preservation and transplantation, pulmonary hypertension, sickle cell disease, myocardial infarction, stroke, and other instances of surgery and/or trauma in which IRI is a component of pathogenesis; 2) in treating autoimmune and inflammatory diseases; and 3) as anti-cancer agents that are toxic to susceptible cancer cells, promoting their phagocytic uptake and clearance, or directly killing such cells. ## Claims ### Claim 1 A method of treating ischemia or ischemia-reperfusion injury in a patient in need thereof, comprising administering to said patient an effective amount of a monoclonal antibody, or antigen-binding fragment thereof, that specifically binds CD47, wherein said monoclonal antibody, or antigen-binding fragment thereof, comprises three light chain complementarity determining regions (LCDRs 1-3) and three heavy chain complementarity determining regions (HCDRs 1-3), wherein: LCDR 1 comprises the amino acid sequence RSSQSLVHSNGNTYLH (SEQ ID NO:1) LCDR 2 comprises the amino acid sequence KVSYRFS (SEQ ID NO:2); and LCDR 3 comprises the amino acid sequence SQNTHVPRT (SEQ ID NO:3); HCDR1 comprises the amino acid sequence (SEQ ID NO:4); HCDR 2 comprises the amino acid sequence DINPVNGDTNFNEKFKN (SEQ ID NO:5); and HCDR 3 comprises the amino acid sequence GGYTMDY (SEQ ID NO:6). ### Claim 2 (depends on 1) The method of claim 1, wherein said monoclonal antibody, or antigen-binding fragment thereof, specifically binds human, rat, mouse, and pig CD47. ### Claim 3 (depends on 1) The method of claim 1, wherein said monoclonal antibody, or antigen-binding fragment thereof, comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein said LCVR and said HCVR comprise, respectively, amino acid sequences selected from the group consisting of: SEQ ID NO:7 and SEQ ID NO:57; SEQ ID NO:8 and SEQ ID NO:58; SEQ ID NO:9 and SEQ ID NO:59; SEQ ID NO:10 and SEQ ID NO:60; SEQ ID NO:11 and SEQ ID NO:61; SEQ ID NO:12 and SEQ ID NO:62; SEQ ID NO:13 and SEQ ID NO:63; SEQ ID NO:14 and SEQ ID NO:64; SEQ ID NO:15 and SEQ ID NO:65; SEQ ID NO:16 and SEQ ID NO:66; SEQ ID NO:17 and SEQ ID NO:67; SEQ ID NO:18 and SEQ ID NO:68; SEQ ID NO:19 and SEQ ID NO:69; SEQ ID NO:20 and SEQ ID NO:70; SEQ ID NO:21 and SEQ ID NO:71; SEQ ID NO:22 and SEQ ID NO:72; SEQ ID NO:23 and SEQ ID NO:73; SEQ ID NO:24 and SEQ ID NO:74; SEQ ID NO:25 and SEQ ID NO:75; SEQ ID NO:26 and SEQ ID NO:76; SEQ ID NO:27 and SEQ ID NO:77; SEQ ID NO:28 and SEQ ID NO:78; SEQ ID NO:29 and SEQ ID NO:79; SEQ ID NO:30 and SEQ ID NO:80; and SEQ ID NO:31 and SEQ ID NO:81. ### Claim 4 (depends on 1) The method of claim 1, further comprising administering to said patient an effective amount of a nitric oxide donor, precursor, or both. ### Claim 5 (depends on 4) The method of claim 4, wherein said nitric oxide donor or precursor is selected from the group consisting of NO gas, isosorbide dinitrite, nitrite, nitroprusside, nitroglycerin, 3-Morpholinosydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP), Diethylenetriamine/NO (DETA/NO), S-nitrosothiols, and arginine. ### Claim 6 (depends on 1) The method of claim 1, wherein said monoclonal antibody, or antigen-binding fragment thereof, is chimeric or humanized.