Antiangiogenic peptides
The present invention provides an antiangiogenic polypeptide having the amino acid sequence set forth in SEQ ID NO: 1, or a fragment thereof, which is effective to inhibit endothelial cell proliferation as determined by the capillary EC proliferation assay. Preferably, the fragment has at least 50% inhibition of bFGF-stimulated EC proliferation at 5 μg/ml-20 μg/ml, more preferably 75% inhibition, most preferably 95% inhibition.
1. A polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1.
2. A pharmaceutical composition comprising the polypeptide of claim 1 in a therapeutically effective amount capable of inhibiting endothelial cell proliferation.
3. A method of inhibiting angiogenesis in a subject having an angiogenic disease or disorder, or at risk for developing an angiogenic disease or disorder, which comprises administering to the subject the pharmaceutical composition of claim 2 , wherein angiogenesis is inhibited.
4. The method of claim 3 , wherein the angiogenesis disease or disorder is restenosis.
5. The method of claim 3 , wherein the angiogenesis disease or disorder is cancer.
6. The method of claim 5 , wherein the cancer is a solid tumor.
7. The method of claim 5 , wherein the cancer is medullary thyroid cancer.
8. The method of claim 5 , wherein the tumor is a tumor of the central nervous system.
9. The method according to claim 3 , wherein the angiogenesis disease or disorder is an ophthalmologic disease or disorder.
10. The method of claim 9 , wherein the ophthalmologic disease or disorder is retinopathy, diabetic retinopathy or macular degeneration.
11. The method of 3 , wherein said administering is conducted in conjunction with chemotherapy.
12. A method of treating a subject having a tissue remodeling-associated condition comprising administering to the subject the pharmaceutical composition of claim 2 .
13. The method of claim 12 , wherein the tissue remodeling-associated condition is arthritis or rheumatoid arthritis.
14. The method of claim 3 , wherein said administering is conducted in conjunction with other known angiogenesis inhibitors.
15. The method of claim 3 , wherein said administering comprises intravenous, transdermal, intrasynovial, intramuscular, or oral administration.
16. The method of claim 3 , wherein said administering comprises therapeutic administration.
17. The method of claim 3 , wherein said risk for developing an angiogenic disease or disorder is determined by measuring levels of cancer marker protein.
18. The method of claim 17 , wherein the cancer marker protein is selected from the group consisting of calcitonin, PSA, thymosin β-15, thymosin β-16, or matrix metalloproteinase (MMP).
19. An article of manufacture comprising packaging material and a pharmaceutical composition contained within said packaging material, wherein said pharmaceutical composition is capable of inhibiting angiogenesis in a tissue associated with a disease condition, wherein said packaging material comprises a label which indicates that said pharmaceutical composition can be used for treating disease conditions by inhibiting angiogenesis, and wherein said pharmaceutical composition comprises a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, in a therapeutically effective amount capable of inhibiting endothelial cell proliferation.