# US 5,350,578 A · Inhibition of arterial thrombotic occlusion or thromboembolism > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,350,578 A - Document ID: US5350578A - Status: Granted - Kind: A - Application number: 07/782,817 - Filed: 1991-10-25 - Granted: 1994-09-27 - Earliest claimed: 1987-11-17 - Assignees: Scripps Clinic and Research Foundation - Inventors: John H. Griffin; Andras Gruber; Stephen R. Hanson; Lawrence A. Harker - Web page: https://patentgrep.com/patent/US5350578A ## CPC - C12N 9/6464: {Protein C (3.4.21.69)} - A61K 38/166: {Streptokinase} - A61K 38/49: Urokinase; Tissue plasminogen activator - A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors - C12Y 304/21069: Protein C activated (3.4.21.69) - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - 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 - C12Y: ENZYMES ## Abstract The method of preventing arterial thrombotic occlusion or thromboembolism by administering plasma-derived or recombinant produced protein C alone or in combination with a thrombolytic agent or combinations of thrombolytic agents. ## Claims ### Claim 1 A pharmaceutical composition for inhibiting arterial platelet deposition, acute arterial thrombotic occlusion, thromboembolism, or stenosis in coronary, cerebral or peripheral arteries or in vascular grafts the composition comprising an effective amount of isolated and purified activated protein C obtained from a plasma source, to inhibit arterial platelet deposition, acute arterial thrombotic occlusion, thromboembolism or stenosis in coronary, cerebral or peripheral arteries or in vascular grafts in a pharmaceutically acceptable carrier. ### Claim 2 (depends on 1) A composition as claimed in claim 1 wherein the composition further comprises an effective amount of a thrombolytic agent or combination of thrombolytic agents to inhibit arterial platelet deposition, arterial thrombotic occlusion, thromboembolism, or stenosis in coronary, cerebral or peripheral arteries or in vascular grafts. ### Claim 3 (depends on 2) A composition as claimed in claim 2 wherein the thrombolytic agent is selected from the group consisting of tissue plasminogen activator, urokinase, prourokinase, streptokinase, an acylated form of plasminogen, plasmin, and acylated streptokinase-plasminogen complex. ### Claim 4 A pharmaceutical composition for inhibiting arterial platelet deposition, acute arterial thrombotic occlusion, thromboembolism, or stenosis in coronary, cerebral or peripheral arteries or in vascular grafts comprising an effective amount of isolated and purified activated protein C in an amount that provides a dose of 0.2 mg/kg-hr. to 1.1 mg/kg-hr. of activated protein C in a pharmaceutically acceptable carrier. ### Claim 5 (depends on 4) A composition as claimed in claim 4 wherein the activated protein C is selected from the group consisting of plasma-derived activated protein C or recombinantly-derived activated protein C. ### Claim 6 (depends on 4) A composition as claimed in claim 4 wherein the composition further comprises an effective amount of a thrombolytic agent or combination of thrombolytic agents to inhibit arterial platelet deposition, arterial thrombotic occlusion, thromboembolism, a stenosis in coronary, cerebral or peripheral arteries or in vascular grafts. ### Claim 7 (depends on 6) A composition as claimed in claim 6 wherein the thrombolytic agent is selected from the group consisting of tissue plasminogen activator, urokinase, prourokinase, streptokinase, acylated form of plasminogen, acylated form of plasmin, and acylated streptokinase-plasminogen complex. ### Claim 8 (depends on 6) A composition as claimed in claim 6 wherein the thrombolytic agent consists essentially of an effective amount of tissue plasminogen activator, said composition capable of providing a dose of 0.1 to 0.4 mg/kg-hr tissue plasminogen activator. ### Claim 9 A pharmaceutical composition for inhibiting acute arterial thrombotic occlusion, thromboembolism, or stenosis in coronary, cerebral or peripheral arteries or in vascular grafts comprising an effective amount of isolated and purified activated protein C in a pharmaceutically acceptable carrier that provides an activated protein C plasma level in the range of 0.1 to 1.6 .mu.g/ml. ### Claim 10 (depends on 9) A composition as claimed in claim 9 wherein the activated protein C is selected from the group consisting of plasma-derived activated protein C and recombinantly-derived activated protein C. ### Claim 11 (depends on 9) A composition as claimed in claim 9 wherein the composition further comprises an effective amount of a thrombolytic agent or combination of thrombolytic agents to inhibit arterial platelet deposition, acute arterial thrombotic occlusion, thromboembolism, or stenosis in coronary, cerebral or peripheral arteries or in vascular grafts. ### Claim 12 (depends on 11) A composition as claimed in claim 11 wherein the thrombolytic agent is selected from the group consisting of tissue plasminogen activator, urokinase, prourokinase, streptokinase, acylated form of plasminogen, acylated form of plasmin, and acylated streptokinase-plasminogen complex. ### Claim 13 (depends on 12) A composition as claimed in claim 12 wherein the thrombolytic agent consists essentially of an effective amount of tissue plasminogen activator said composition capable of providing a dose of 0.1 to 0.4 mg/kg-hr tissue plasminogen activator. ### Claim 14 (depends on 1) The composition as claimed in claim 1 wherein the isolated and purified activated protein C is at least 95% pure.