Tissue plasminogen activator variant uses

• US 8,916,148 B2
• Filed: 10/30/2007
• Issued: 12/23/2014
• Est. Priority Date: 11/07/2006
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Blaney, Martha E.
• Primary Examiner(s): FOX, ALLISON M
• Application Number:
  US12/447,838
• Publication Number:
  US 20120270299A1
• Time in Patent Office: 2,611 Days
• Field of Search: 424/93.64
• US Class Current: 424/94.64
• CPC Class Codes: A61K 38/49 Urokinase; Tissue plasminogen activator
• 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 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 1/285 Catheters therefor
• CPC Class Codes: A61M 2025/0019 Cleaning catheters or the like, e.g. for reuse of the device, for avoiding replacement
• 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: C12N 9/6459 t-plasminogen activator (3.4.21.68), i.e. tPA
• CPC Class Codes: C12Y 304/21069 Protein C activated (3.4.21.69)

Abstract

A method is disclosed for using tenecteplase to restore function in dysfunctional hemodialysis catheters, which have a blood flow rate of less than 300 mL/minute. Kits are also provided with instructions to direct the user to administer tenecteplase in a total dose of about 3 to 4 mg locally into all catheter lumens and allow the tenecteplase to dwell in the catheter for from about one hour to about 72 hours.

Claims

1. A method for restoring function in a dysfunctional hemodialysis catheter indwelling in a mammal, which catheter has a blood flow rate (BFR) of less than 300 mL/minute, which method comprises administering tenecteplase in a total dose of about 2 to 4 mg locally into all catheter lumens and allowing the tenecteplase to dwell in the catheter for from about one hour to about 72 hours, such that the BFR of the catheter is equal to or greater than 300 mL/minute, wherein the catheter is not an implantable port.

2. The method of claim 1 wherein the dysfunctional hemodialysis catheter additionally has a BFR at least 25 mL/minute below the prescribed BFR at an arterial pressure of −

250 mmHg during the first 30 minutes of the hemodialysis.

3. The method of claim 1 wherein the tenecteplase is in a solution of sterile water for injection or bacteriostatic water for injection.

4. The method of claim 1 wherein the tenecteplase dwells in the catheter until the BFR of the catheter is improved over the BFR before administration of tenecteplase and the improvement maintained for at least 48 hours.

5. The method of claim 1 wherein the tenecteplase is in sterile water for injection.

6. The method of claim 1 wherein the total dose of tenecteplase is about 4 mg.

7. The method of claim 1 wherein the tenecteplase is instilled into the catheter for about one hour.

8. The method of claim 1 wherein the tenecteplase is instilled into the catheter and allowed to dwell for a period of from over about one hour to about 72 hours.

9. The method of claim 8 wherein the period the tenecteplase is allowed to dwell is from about 2 to about 48 hours.

10. The method of claim 1 wherein the tenecteplase is administered more than once.

11. The method of claim 10 wherein the tenecteplase is administered at each hemodialysis session that the mammal undergoes.

12. The method of claim 1 wherein the tenecteplase is administered once or twice.

13. The method of claim 12 wherein the tenecteplase is administered once.

14. The method of claim 1 wherein the mammal undergoes hemodialysis after administration of the tenecteplase.

15. The method of any one of claims 1-6 and 14 wherein the mammal is a human.