Methods of treating peripheral arterial occlusions

• US 7,314,728 B2
• Filed: 10/13/2005
• Issued: 01/01/2008
• 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:
  US11/249,696
• Publication Number:
  US 20060029592A1
• Time in Patent Office: 810 Days
• Field of Search: 435/13, 514/822
• 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 treating a peripheral arterial occlusion in a subject in need thereof, comprising delivering to the occlusion through an indwelling vascular access device, a pharmaceutical composition comprising a quantity of fibrinolytic metalloproteinase that complexes with alpha-two macroglobulin, in an amount sufficient to facilitate lysing of the occlusion while not exceeding a level significantly above saturable level of alpha-two macroglobulin in the subject.

2. The method of claim 1, wherein 0.025 to 1.7 milligrams per kilogram of body weight of said subject, of the fibrinolytic metalloproteinase are delivered.

3. The method of claim 1, wherein 0.1 to 0.5 milligrams per kilogram of body weight of said subject, of the fibrinolytic metalloproteinase are delivered.

4. The method of claim 1, wherein said vascular access device is a catheter device.

5. The method of claim 4, wherein said catheter device is a “

side hole”

catheter device.

6. The method of claim 4, wherein said catheter device is a pressure response outlet (PRO) catheter device.

7. The method of claim 1, wherein said composition is delivered by bolus injection.

8. The method of claim 1, wherein said fibrinolytic metalloproteinase is Novel Acting Thrombolytic (NAT).

9. The method of claim 8, wherein said NAT comprises the amino acid sequence of SEQ ID NO:

1.

10. The method of claim 1, wherein said fibrinolytic metalloproteinase is a fibrolase.

11. The method of claim 10, wherein said fibrolase comprises the amino acid sequence of SEQ ID NO:

3.

13. The method of claim 1, wherein 0.1 to 0.5 milligrams per kilogram of body weight of the NAT are delivered.

12. A method for treating a peripheral arterial occlusion in a human subject in need thereof, said method comprising delivering to the occlusion through a catheter device located in an artery of said subject, Novel Acting Thrombolytic (NAT) comprising the amino acid sequence of SEQ ID NO:

1, wherein 0.025 to 1.7 milligrams of said NAT per kilogram of body weight of said subject are delivered.

14. The method of claim 12, wherein said catheter device is a side hole catheter device.

15. The method of claim 12, wherein said catheter device is a pressure response outlet (PRO) catheter device.