Methods and compositions useful for inhibition of αvβ5mediated angiogenesis

• US 7,053,041 B1
• Filed: 05/30/1997
• Issued: 05/30/2006
• Est. Priority Date: 05/31/1996
• Status: Expired due to Fees

• Current Assignee: The Scripps Research Institute
• Original Assignee: The Scripps Research Institute
• Inventors: Friedlander, Martin, Brooks, Peter C., Cheresh, David A.
• Primary Examiner(s): DENT, ALANA HARRIS
• Application Number:
  US09/194,552
• Time in Patent Office: 3,287 Days
• Field of Search: 530/321, 530/326, 530/385, 530/386, 530/387.1, 530/300, 530/317, 530/350, 514/9, 514/11, 514/14, 424/184.1, 424/185.1, 436/64, 436/86
• US Class Current: 514/13.3
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/57 from animals; from humans A61K38/553, A61K38/556 take precedence
• CPC Class Codes: C07K 16/2839 against the integrin superfamily
• CPC Class Codes: C07K 16/2848 against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present invention describes methods for inhibiting angiogenesis in tissues using vitronectin α_vβ₅ antagonists. The α_vβ₅-mediated angiogenesis is correlated with exposure to cytokines including vascular endothelial growth factor, transforming growth factor-α and epidermal growth factor. Inhibition of α_vβ₅-mediated angiogenesis is particularly preferred in vascular endothelial ocular neovascular diseases, in tumor growth and in inflammatory conditions, using therapeutic compositions containing α_vβ₅ antagonists.

Claims

1. A method for inhibiting α

_vβ

₅ mediated angiogenesis in a tissue comprising administering to said tissue a composition comprising an angiogenesis-inhibiting amount of an α

_vβ

₅ antagonist, wherein said antagonist is a matrix metalloproteinase polypeptide consisting of;

SEQ ID NO 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22.

2. The method of claim 1 wherein said tissue is human tissue.

3. The method of claim 2 wherein said tissue is inflamed and said angiogenesis is inflamed tissue angiogenesis.

4. The method of claim 1 wherein said tissue is arthritic.

5. The method of claim 4 wherein said arthritic tissue is present in a mammal with rheumatoid arthritis.

6. The method of claim 1 wherein said tissue is the retinal tissue and said angiogenesis is retinal angiogenesis.

7. The method of claim 6 wherein said retinal tissue is in a patient with diabetic retinopathy or macular degeneration.

8. The method of claim 1 wherein said tissue is a solid tumor or a solid tumor metastasis and said angiogenesis is tumor angiogenesis.

9. The method of claim 8 wherein said tissue is a carcinoma.

10. The method of claim 8 wherein said solid tumor is a tumor of lung, pancreas, breast, colon, larynx or ovary.

11. The method of claim 8 wherein said administering is conducted in conjunction with chemotherapy.

12. The method of claim 1 wherein said administering comprises intravenous, transdermal, intrasynovial, intramuscular, or oral administration.

13. The method of claim 1 wherein said angiogenesis-inhibiting amount is from about 0.1 mg/kg to about 300 mg/kg.

14. The method of claim 1 wherein said therapeutically effective amount is from about 0.1 mg/kg to about 300 mg/kg.

15. The method of claim 1 wherein said administering comprises a single dose intravenously.

16. The method of claim 1 wherein said administering comprises one or more dose administrations daily for one or more days.

17. The method of claim 1 wherein said angiogenesis is present in a patient having an eye disease selected from the group of eye diseases consisting of diabetic retinopathy, age-related macular degeneration, presumed ocular histoplasmosis, retinopathy of prematurity and neovascular glaucoma.

18. The method of claim 1 wherein said angiogenesis is present in a patient having a corneal neovascular disorder selected from the group of disorders consisting of corneal transplantation, herpetic keratitis, luetic keratitis, pterygium and neovascular pannus associated with contact lens use.

19. The method of claim 1 wherein said angiogenesis is induced by a cytokine.

20. The method of claim 19 wherein said cytokine is selected from the group consisting of vascular endothelial growth factor, transforming growth factor-α

and epidermal growth factor.

21. The method of claim 19 wherein said cytokine is vascular endothelial growth factor and said angiogenesis is selected from the group consisting of retinal angiogenesis, corneal angiogenesis, tumor angiogenesis and inflamed tissue angiogenesis.

22. A method for inhibiting α

_vβ

₅ mediated angiogenesis in a tissue comprising administering to said tissue a composition comprising an angiogenesis-inhibiting amount of an α

_vβ

₅ antagonist, wherein said antagonist is an organic compound selected from the group consisting of compounds represented by the following structures;

23. The method of claim 22 wherein said tissue is human tissue.

24. The method of claim 23 wherein said tissue is inflamed and said angiogenesis is inflamed tissue angiogenesis.

25. The method of claim 22 wherein said tissue is arthritic.

26. The method of claim 25 wherein said arthritic tissue is present in a mammal with rheumatoid arthritis.

27. The method of claim 22 wherein said tissue is the retinal tissue and said angiogenesis is retinal angiogenesis.

28. The method of claim 27 wherein said retinal tissue is in a patient with diabetic retinopathy or macular degeneration.

29. The method of claim 22 wherein said tissue is a solid tumor or a solid tumor metastasis and said angiogenesis is tumor angiogenesis.

30. The method of claim 29 wherein said tissue is a carcinoma.

31. The method of claim 29 wherein said solid tumor is a tumor of lung, pancreas, breast, colon, larynx or ovary.

32. The method of claim 29 wherein said administering is conducted in conjunction with chemotherapy.

33. The method of claim 22 wherein said administering comprises intravenous, transdermal, intrasynovial, intramuscular, or oral administration.

34. The method of claim 22 wherein said angiogenesis-inhibiting amount is from about 0.1 mg/kg to about 300 mg/kg.

35. The method of claim 22 wherein said therapeutically effective amount is from about 0.1 mg/kg to about 300 mg/kg.

36. The method of claim 22 wherein said administering comprises a single dose intravenously.

37. The method of claim 22 wherein said administering comprises one or more dose administrations daily for one or more days.

38. The method of claim 22 wherein said angiogenesis is present in a patient having an eye disease selected from the group of eye diseases consisting of diabetic retinopathy, age-related macular degeneration, presumed ocular histoplasmosis, retinopathy of prematurity and neovascular glaucoma.

39. The method of claim 22 wherein said angiogenesis is present in a patient having a corneal neovascular disorder selected from the group of disorders consisting of corneal transplantation, herpetic keratitis, luetic keratitis, pterygium and neovascular pannus associated with contact lens use.

40. The method of claim 22 wherein said angiogenesis is induced by a cytokine.

41. The method of claim 40 wherein said cytokine is selected from the group consisting of vascular endothelial growth factor, transforming growth factor-α

and epidermal growth factor.

42. The method of claim 40 wherein said cytokine is vascular endothelial growth factor and said angiogenesis is selected from the group consisting of retinal angiogenesis, corneal angiogenesis, tumor angiogenesis and inflamed tissue angiogenesis.