METHODS FOR PREVENTING AND TREATING TISSUE DAMAGE ASSOCIATED WITH ISCHEMIA-REPERFUSION INJURY

• US 20090017031A1
• Filed: 06/13/2008
• Published: 01/15/2009
• Est. Priority Date: 02/21/2003
• Status: Abandoned Application

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Fung, Sek Chung
• Application Number:
  US12/139,192
• Publication Number:
  US 20090017031A1
• Time in Patent Office: Days
• US Class Current: 424/139.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/18 against material from animals or humans

Abstract

A method for preventing or treating tissue damage associated with ischemia-reperfusion injury and thoraco-abdominal aortic aneurysm (TAAA) repair by administering a tissue damage preventing or treating amount of a complement inhibitor to a patient likely to suffer from or suffering from tissue damage associated with ischemia-reperfusion injury or TAAA repair. The complement inhibitors are preferably antibodies that bind to and inhibit complement proteins involved in the formation of the membrane attach complex, preferably antibodies that inhibit MBL, MASP1, MASP2, and MASP3 in the lectin pathway. The complement inhibitors can be used alone or in combination to decrease the morbidity and mortality caused by tissue damage associated with ischemia-reperfusion injury or TAAA repair.

Claims

1. A method for preventing or treating tissue damage associated with ischemia-reperfusion injury comprising administering a tissue damaging preventing or treating amount of one or more complement inhibitors to a patient likely to suffer from or suffering from tissue damage associated with ischemia-reperfusion injury.

2. The method of claim 1 wherein the complement inhibitor is selected from the group consisting of compstatin and its functional analogs, C1 Inhibitor, sCR1 and its analogues, anti-C5 antibodies and their functionally equivalent fragments, anti-C5a antibodies and their functionally equivalent fragments, anti-Ca receptor antibodies and their functionally equivalent fragments, anti-C3a antibodies and their functionally equivalent fragments, anti-C3a receptor antibodies and their functionally equivalent fragments, anti-6 antibodies and their functionally equivalent fragments, anti-C7 antibodies and their functionally equivalent fragments anti-C8 antibodies and their functionally equivalent fragment;

anti-C9 antibodies and their functionally equivalent fragments, anti-properdin antibodies and their functionally equivalent fragment, fusion protein Membrane Cofactor Protein (MCP), Decay Accelerating Factor (DAF), cluster, CD59, C4 bp, Factor H, Factor L, Carboxypeptidase N, vitronectin (S Protein), SP-40, CD59, and Homologous Restriction Factor (HRF).

3. The method of claim 1 wherein the complement inhibitor inhibits a component of the lectin pathway.

4. The method of claim 3 wherein the complement inhibitor is selected from the group consisting of anti-MBL antibodies and their functionally equivalent fragments, anti-MASP1 antibodies and their functionally equivalent fragments, anti-MASP2 antibodies and their functionally equivalent fragments, anti-MASP3 antibodies and their functionally equivalent fragments, anti-MBL complex antibodies and their functionally equivalent fragments, mannan binding lectin receptor antagonists, keratin binding molecules, anti-keratin antibodies and their functionally equivalent fragments, MASP1 binding peptides, MASP2 biding peptides, and MASP3 binding peptides.

5. The method of claim 1 wherein the complement inhibitor is administered to the patient in dosages of from about 2 to 50 milligrams per kilogram of body weight.

6. The method of claim 1 wherein the complement inhibitor is an antibody or a functionally equivalent fragment thereof.

7. The method of claim 1 wherein the antibody inhibits a component of the lectin complement pathway.

8. The method of claim 7 wherein the antibody is selected from the group consisting of anti-MBL antibodies and their functionally equivalent fragments, anti-MASP1 antibodies and their functionally equivalent fragments, anti-MASP2 antibodies and their functionally equivalent fragments, anti-MASP3 antibodies and their functionally equivalent fragments, and anti-MBL complex antibodies and their functionally equivalent fragments.

9. The method of claim 7 wherein the antibody is an anti-MBL antibody or functionally equivalent fragments thereof.

10. The method of claim 1 wherein at least two complement inhibitors are administered to the patient.

11. The method of claim 10 wherein the complement inhibitors are administered in conjunction to the patient.

12. The method of claim 10 wherein one complement inhibitor is an anti-MBL antibody.

13. The method of claim 1 wherein the complement inhibitor is administered within 24 hours before or within 72 hours after a patient suffers an ischemia-reperfusion injury.

14. The method of claim 1 wherein the complement inhibitor is administered periodically after a patient suffers an ischemia-reperfusion injury.

15. A method for preventing or treating tissue damage associated with thoraco-abdominal aortic aneurysm repair comprising administering a tissue damaging preventing or treating amount of one or more complement inhibitors to a patient likely to suffer from or suffering from tissue damage associated with thoraco-abdominal aortic aneurysm repair.

16. The method of claim 15 wherein the complement inhibitor is selected from the group consisting of compstatin and its functional analogs, C1 inhibitor, sCR1 and its analogues, anti-C5 antibodies and their functionally equivalent fragments, anti-C5a antibodies and their functionally equivalent fragments, anti-C5a receptor antibodies and their functionally equivalent fragments, anti-C3a antibodies and their functionally equivalent fragments, anti-C3a receptor antibodies and their functionally equivalent fragments, anti-C6 antibodies and their functionally equivalent fragments, anti-C7 antibodies and their functionally equivalent fragments, anti-C8 antibodies and their functionally equivalent fragments, anti C9 antibodies and their functionally equivalent fragments, anti-properdin antibodies and their functionally equivalent fragments, fusion protein Membrane Cofactor Protein (MCP), Decay Accelerating Factor (OAF), clusterin, CD59, C4 bp, Factor H, Factor I, Carboxypeptidase N, vitronectin (S Protein), SP40, CD59, and Homologous Restriction Factor (HRF).

17. The method of claim 15 wherein the complement inhibitor inhibits a component of the lectin pathway.

18. The method of claim 17 wherein the complement inhibitor is selected from the group consisting of anti-MBL antibodies and their functionally equivalent fragments, anti-MASP1 antibodies and their functionally equivalent fragments, anti-MASP2 antibodies and their functionally equivalent fragments, anti-MASP3 antibodies and their functionally equivalent fragments, anti-MBL complex antibodies and their functionally equivalent fragments, mannan binding lectin receptor antagonists, keratin binding molecules, anti-keratin antibodies and their functionally equivalent fragments, MASP1 binding peptides, MASP2 binding peptides, and MASP3 binding peptides.

19. The method of claim 15 wherein the complement inhibitor is administered to the patient in dosages of from about 2 to 50 milligrams per kilogram of body weight.

20. The method of claim 15 wherein the complement inhibitor is an antibody or a functionally equivalent fragment thereof.

21. The method of claim 15 wherein the antibody inhibits a component of the lectin complement pathway.

22. The method of claim 21 wherein the antibody is selected from the group consisting of anti-MBL antibodies and their functionally equivalent fragments, anti-MASP1 antibodies and their functionally equivalent fragments, anti-MASP2 antibodies and their functionally equivalent fragments, anti-MASP3 antibodies and their functionally equivalent fragments, and anti-MBL complex antibodies and their functionally equivalent fragments.

23. The method of claim 21 wherein the antibody is an anti-MBL antibody or functionally equivalent fragments thereof.

24. The method of claim 15 wherein at least two complement inhibitors are administered to the patient.

25. The method of claim 24 wherein the complement inhibitors are administered in conjunction to the patient.

26. The method of claim 24 wherein one complement inhibitor is an anti-MBL antibody.

27. The method of claim 15 wherein the complement inhibitor is administered within 24 hours before or within 72 hours after a patient suffers an ischemia-reperfusion injury.

28. The method of claim 15 wherein the complement inhibitor is administered periodically after a patient suffers an ischemia-reperfusion injury.

29. A composition useful for the prevention and treatment of tissue damage associated with an ischemia-reperfusion injury or a thoraco-abdominal aortic aneurysm repair comprising one or more complement inhibitors and one or more pharmaceutically acceptable adjuvants, carriers, excipients, and diluents.

30. The composition of claim 29 comprising two or more complement inhibitors.

31. The composition of claim 30 wherein one of the complement inhibitors is an antibody or functionally equivalent fragment thereof.

32. The composition of claim 30 wherein a first complement inhibitor is selected from the group consisting of anti-MBL antibodies and their functionally equivalent fragments, anti-MASP antibodies and their functionally equivalent fragments, anti-MBL antibodies and their functionally equivalent fragments, anti-MASP3 antibodies and their functionally equivalent fragments, and anti-MBL complex antibodies and their functionally equivalent fragments and a second antibody different from the first antibody is selected from the group consisting of anti-MBL antibodies and their functionally equivalent fragments, anti-MASP antibodies and their functionally equivalent fragments, anti-MASP2 antibodies and their functionally equivalent fragments, anti-MASP3 antibodies and their functionally equivalent fragments, anti-MBL complex antibodies and their functionally equivalent fragments, and other complement inhibitors.

33. The composition of claim 31 comprising an anti-MBL antibody or functionally equivalent fragment thereof and one or more different complement inhibitors.