Method for treatment of indwelling catheter occlusion using fibrinolytic metalloproteinases

• US 7,033,776 B2
• Filed: 06/21/2002
• Issued: 04/25/2006
• Est. Priority Date: 12/17/1999
• Status: Expired due to Fees

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Toombs, Christopher F.
• Primary Examiner(s): GITOMER, RALPH J
• Application Number:
  US10/177,916
• Publication Number:
  US 20020197246A1
• Time in Patent Office: 1,404 Days
• Field of Search: 435/13, 435/23, 435/69.2, 435/212, 435/217, 424/94.64, 424/94.67, 424/145.1, 514/822, 530/324
• US Class Current: 435/13
• CPC Class Codes: 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
• CPC Class Codes: A61K 38/4886 Metalloendopeptidases (3.4.24), e.g. collagenase
• CPC Class Codes: A61L 2300/254 Enzymes, proenzymes
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 29/048 Other specific proteins or polypeptides not covered by A61L29/045 - A61L29/047
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C12Q 1/56 involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors

Abstract

A method is provided for the localized intravascular administration of a fibrinolytic metalloproteinase to a human subject in amounts that are both safe and effective to lyse an occluding fibrin-containing blood clot, while also avoiding the neutralizing effects of α₂-macroglobulin in the circulating blood. A method is also provided for the treatment of a blood clot in, around or attached to an indwelling vascular access device. A method for restoring patency and function of an indwelling vascular access device is also provided.

Claims

1. A method for the therapeutic treatment of a blood clot in, around or attached to an indwelling vascular access device comprising administering through said vascular access device 0.025 to 1.7 milligrams of fibrinolytic metalloproteinase per kilogram of body weight of the human subject being treated, in a pharmaceutically acceptable solution.

3. The method of claim 1 or 2 wherein the fibrinolytic metalloproteinase is at a concentration ranging from 0.1 to 80 mg/ml.

4. The method of claim 1 or 2 wherein the fibrinolytic metalloproteinase is at a concentration ranging from 0.1 to 50 mg/ml.

5. The method of claim 1 or 2 wherein said vascular access device is a catheter.

6. The method of claim 1 or 2 wherein said vascular access device is a shunt.

7. The method of claim 1 or 2 wherein said vascular access device is an access graft.

8. The method of claim 1 or 2 wherein said vascular access device is a needle.

9. The method of claim 1 or 2 wherein the vascular access device is used to introduce a liquid composition into a human artery or vein.

10. The method of claim 1 or 2 wherein the vascular access device is used to remove blood from a human artery or vein.

11. The method of claim 1 or 2 wherein the vascular access device is used in connection with a hemodialysis procedure.

12. The method of claim 1 or 2 wherein the vascular access device is used in connection with a blood transfusion procedure.

13. The method of claim 1 or 2 wherein the vascular access device is used in connection with chemotherapy.

14. The method of claim 1 or 2 which is used to treat peripheral arterial occlusions.

15. The method of claim 1 or 2 wherein the vascular access device is used in connection with blood removal.

16. The method of claim 1 or 2 wherein said blood clot is located on an interior surface of the indwelling vascular access device.

17. The method of claim 1 or 2 wherein said blood clot is located on an exterior surface of the indwelling vascular access device.

18. The method of claim 1 or 2 wherein said blood clot is attached to the indwelling vascular access device.

19. The method of claim 1 or 2 wherein said vascular access device is located in an artery of the human subject.

20. The method of claim 1 or 2 in which said vascular access device is located in a vein of the human subject.

21. The method of claim 1 or 2 in which said vascular access device comprises a “

side hole”

catheter device.

22. The method of claim 1 or 2 in which said vascular access device comprises a “

pressure response outlet”

(PRO) catheter delivery device.

23. The method of claim 1 or 2 in which the solution of fibrinolytic metalloproteinase is administered by bolus injection.

24. The method of claim 1 or 2 in which the fibrinolytic metalloproteinase comprises Novel Acting Thrombolytic (NAT).

25. The method of claim 1 or 2 in which the fibrinolytic metalloproteinase comprises fibrolase.

2. A method for proteolytically degrading a blood clot in, around, or attached to an indwelling vascular access device in a human subject comprising administering through said vascular access device a quantity of fibrinolytic metalloproteinase that complexes with alpha-two macroglobulin, in an amount sufficient to facilitate lysing of the clot while not exceeding a level significantly above saturable level of alpha-two macroglobulin in the human subject, in a pharmaceutically acceptable solution.

26. A method for restoring patency to an indwelling vascular access device having a fibrin-based occlusion in a human subject comprising administering through said vascular access device a quantity of a fibrinolytic metalloproteinase that complexes with alpha-two macroglobulin, wherein said quantity is 0.025 to 1.7 milligrams of the fibrinolytic metalloproteinase per kilogram of body weight of the human subject being treated.

27. A method of restoring function to an indwelling vascular access device having fibrin-based occlusion in a human subject comprising administering through said vascular access device a quantity of a fibrinolytic metalloproteinase that complexes with alpha-two macroglobulin in a pharmaceutically acceptable solution, wherein said quantity is 0.025 to 1.7 milligrams of the fibrinolytic metalloproteinase per kilogram of body weight of the human subject being treated.

28. A method of lysing a clot associated with an implanted medical device in a human subject comprising administering through said medical device 0.025 to 1.7 milligrams of fibrinolytic metalloproteinase per kilogram of body weight of the human subject being treated, in a pharmaceutically acceptable solution.

29. The method of claim 28, wherein the medical device is an indwelling catheter.

30. The method of claim 28, wherein the medical device is a hemodialysis access graft.

31. The method of claim 28, wherein the fibrinolytic metalloproteinase binds covalently to alpha-2-macroglobulin.