# US 5,346,991 A · Tissue factor mutants useful for the treatment of myocardial infarction and coagulopathic disorders > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,346,991 A - Document ID: US5346991A - Status: Granted - Kind: A - Application number: 07/714,819 - Filed: 1991-06-13 - Granted: 1994-09-13 - Earliest claimed: 1991-06-13 - Assignees: Genentech, Inc. - Inventors: Soumitra Roy; Gordon A. Vehar - Web page: https://patentgrep.com/patent/US5346991A ## CPC - C07K 14/745: Blood coagulation or fibrinolysis factors - C07K 14/475: Growth factors; Growth regulators - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - Y10S 530/829: Blood - 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) - Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS ## Abstract A tissue factor protein mutant capable of neutralizing the ability of endogenous tissue factor to induce coagulation is provided. A representative tissue factor mutant designated K165A, K166A TF is useful in a method for inhibiting thrombin-induced platelet aggregation in a mammal, either separately or in combination with a thrombolytic agent, an anticoagulant, or a GPII.sub.b III.sub.a inhibitor. ## Claims ### Claim 1 A tissue factor protein mutant capable of inhibiting the ability of endogenous tissue factor to induce coagulation, wherein either or both the positively charged amino acid residues 165 and 166 are substituted with an .alpha.-amino acid other than one bearing a substantially positively charged side chain at physiological pH. ### Claim 2 (depends on 1) The tissue factor protein mutant of claim 1 selected from the group: mature human tissue factor protein, human tissue factor protein with amino acid residues from about 243 to 263 deleted, and human tissue factor protein with amino acid residues from about 220 to 263 deleted. ### Claim 3 (depends on 2) The mutant of claim 2 wherein both positively charged amino acid residues 165 and 166 are substituted with an .alpha.-amino acid other than one bearing a positively charged sidechain at physiological pH. ### Claim 4 (depends on 2) The mutant of claim 2 wherein either or both positively charged amino acid residues 165 and 166 are substituted with glutamic acid or aspartic acid. ### Claim 5 (depends on 3) The mutant of claim 3 wherein the .alpha.-amino acid is other than lysine or arginine. ### Claim 6 (depends on 3) The mutant of claim 3 wherein the .alpha.-amino acid is selected from amino acids bearing an uncharged side chain. ### Claim 7 (depends on 6) The mutant of claim 6 wherein the .alpha.-amino acid is alanine. ### Claim 8 (depends on 7) The mutant of claim 7 wherein the amino acid residues from about 243 to 263 are deleted. ### Claim 9 (depends on 7) The mutant of claim 7 wherein the amino acid residues from about 220 to 263 are deleted. ### Claim 10 (depends on 2, 7) The mutant of claims 2, 7, or 8 that is not glycosylated. ### Claim 11 (depends on 1) An isolated polypeptide comprising the tissue factor protein mutant of claim 1 fused to a heterologous polypeptide. ### Claim 12 (depends on 1) A composition comprising the tissue factor protein mutant of claim 1 and a pharmaceutically acceptable carrier. ### Claim 13 (depends on 12) The composition of claim 12 wherein the pharmaceutically acceptable carrier comprises a phospholipid.