Methods of therapy with thrombin derived peptides

1. A method for promoting cardiac tissue repair in a patient, said method comprising administering to the patient a therapeutically effective amount of an angiogenic thrombin derivative peptide, wherein said peptide comprises a serine esterase conserved sequence, and a thrombin receptor binding domain having the sequence Arg-Gly-Asp-Ala (SEQ ID NO:1).

2. The method of claim 1 wherein the serine esterase conserved sequence comprises Asp-Ala-Cys-Glu-Gly-Asp-Ser-Gly-Gly-Pro-Phe-Val (SEQ ID NO: 2).

3. The method of claim 1 wherein the thrombin derivative peptide comprises the amino acid sequence: Ala-Gly-Tyr-Lys-Pro-Asp-Glu-Gly-Lys-Arg-Gly-Asp-Ala-Cys-Glu-Gly-Asp-Ser-Gly-Gly-Pro-Phe-Val (SEQ ID NO: 3).

4. The method of claim 1 wherein the thrombin derivative peptide consists of the amino acid sequence Ala-Gly-Tyr-Lys-Pro-Asp-Glu-Gly-Lys-Arg-Gly-Asp-Ala-Cys-Glu-Gly-Asp-Ser-Gly-Gly-Pro-Phe-Val (SEQ ID NO: 3).

5. The method of claim 1 , wherein the patient is administered a therapeutically effective amount of a thrombin derivative peptide comprising a C-terminal amide.

6. The method of claim 1 , wherein the patient is administered a therapeutically effective amount of a thrombin derivative peptide comprising SEQ ID NO:4.

7. The method of claim 1 , wherein the patient is administered a therapeutically effective amount of a thrombin derivative peptide consisting of SEQ ID NO:4.

8. The method of claim 1 wherein the peptide is administered during or following cardiac surgery.

9. The method of claim 1 wherein the peptide is administered by injection into the cardiac tissue.

10. The method of claim 1 wherein a sustained release formulation comprising the angiogenic thrombin derivative peptide is administered to the patient.

11. The method of claim 10 wherein the sustained release formulation comprises polylactic acid/polyglycolic acid microparticles comprising the angiogenic thrombin derivative peptide.

12. A method of stimulating revascularization in cardiac tissue of a patient, said method comprising administering to the patient a therapeutically effective amount of an angiogenic thrombin derivative peptide, wherein said peptide comprises a serine esterase conserved sequence, and a thrombin receptor binding domain having the sequence Arg-Gly-Asp-Ala (SEQ ID NO:1).

13. A method of stimulating vascular endothelial cell proliferation in a patient in need of such treatment, said method comprising administering to the patient a therapeutically effective amount of an angiogenic thrombin derivative peptide, wherein said peptide comprises a serine esterase conserved sequence, and a thrombin receptor binding domain having the sequence Arg-Gly-Asp-Ala (SEQ ID NO:1).

14. A method of inhibiting restenosis in a patient following balloon angioplasty, said method comprising administering to the patient a therapeutically effective amount of an angiogenic thrombin derivative peptide, wherein the peptide comprises a serine esterase conserved sequence and a thrombin receptor binding domain having the sequence Arg-Gly-Asp-Ala (SEQ ID NO:1).

15. The method of claim 14 wherein the peptide is coated onto a balloon angioplasty catheter.

16. The method of claim 14 wherein the peptide is administered systemically.

17. The method of claim 14 wherein the peptide is administered locally to an area of a blood vessel damaged by balloon angioplasty.

18. The method of claim 14 wherein a stent coated with the peptide is inserted into a blood vessel at an area damaged by balloon angioplasty.

19. The method of claim 14 wherein the serine esterase conserved sequence comprises Asp-Ala-Cys-Glu-Gly-Asp-Ser-Gly-Gly-Pro-Phe-Val (SEQ ID NO: 2).

20. The method of claim 14 wherein the thrombin derivative peptide comprises the amino acid sequence: Ala-Gly-Tyr-Lys-Pro-Asp-Glu-Gly-Lys-Arg-Gly-Asp-Ala-Cys-Glu-Gly-Asp-Ser-Gly-Gly-Pro-Phe-Val (SEQ ID NO: 3).

21. The method of claim 14 wherein the thrombin derivative peptide consists of the amino acid sequence Ala-Gly-Tyr-Lys-Pro-Asp-Glu-Gly-Lys-Arg-Gly-Asp-Ala-Cys-Glu-Gly-Asp-Ser-Gly-Gly-Pro-Phe-Val (SEQ ID NO: 3).

22. The method of claim 14 , wherein the patient is administered a therapeutically effective amount of a thrombin derivative peptide comprising a C-terminal amide.

23. The method of claim 14 , wherein the patient is administered a therapeutically effective amount of a thrombin derivative peptide comprising SEQ ID NO:4.

24. The method of claim 14 , wherein the patient is administered a therapeutically effective amount of a thrombin derivative peptide consisting of SEQ ID NO:4.

25. A stent coated with an angiogenic thrombin derivative peptide, wherein said peptide comprises a serine esterase conserved sequence, and a thrombin receptor binding domain having the sequence Arg-Gly-Asp-Ala (SEQ ID NO:1).

26. A method of inhibiting vascular occlusion in a patient, said method comprising administering to the patient a therapeutically effective amount of a thrombin derivative peptide, wherein said peptide comprises a serine esterase conserved sequence, and a thrombin receptor binding domain having the sequence Arg-Gly-Asp-Ala (SEQ ID NO:1).

27. The method of claim 12 wherein the serine esterase conserved sequence comprises SEQ ID NO:2.

28. The method of claim 13 wherein the serine esterase conserved sequence comprises SEQ ID NO:2.

29. The method of claim 13 wherein the peptide comprises SEQ ID NO:3.

30. The method of claim 13 wherein the peptide consists of SEQ ID NO:4.

31. The method of claim 25 wherein the serine esterase conserved sequence comprises SEQ ID NO:2.

32. The method of claim 26 wherein the serine esterase conserved sequence comprises SEQ ID NO:2.