COMBINATION TREATMENT FOR OCULAR DISEASES

• US 20110110932A1
• Filed: 04/27/2010
• Published: 05/12/2011
• Est. Priority Date: 05/07/2009
• Status: Abandoned Application

• Current Assignee: Ophthotech Corporation (Astellas Pharma Incorporated)
• Original Assignee: Ophthotech Corporation (Astellas Pharma Incorporated)
• Inventors: Patel, Samir
• Application Number:
  US12/768,605
• Publication Number:
  US 20110110932A1
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/2842 against integrin beta1-subunit-containing molecules, e.g. CD29, CD49
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Abstract

The invention provides compositions and methods for treating ocular disorders, such as angiogenesis-associated disorders, by administering a combination of an inhibitor of VEGF activity and an inhibitor of α₅β₁ integrin activity.

Claims

1. A method of treating an ocular disease comprising administering to a subject in need thereof a therapeutically effective amount of an inhibitor of VEGF activity in combination with a therapeutically effective amount of an inhibitor of α

₅β

₁ integrin activity.

2. The method of claim 1, wherein the ocular disease is an angiogenesis-associated ocular disease.

3. The method of claim 2, wherein the ocular disease is selected from the group consisting of macular degeneration, diabetic retinopathy, and choroidal neovascularization.

4. The method of claim 3, wherein the ocular disease is wet macular degeneration.

5. The method of claim 3, wherein the ocular disease is dry macular degeneration.

6. The method of claim 1, wherein administering comprises intravitreal injection.

7. The method of claim 1, wherein administering comprises intravenous injection.

8. The method of claim 1, wherein the inhibitor of VEGF activity is an antibody or functional fragment thereof.

9. The method of claim 8, wherein the inhibitor of VEGF activity is bevacizumab or ranibizumab.

10. The method of claim 1, wherein the inhibitor of VEGF activity is a peptide, peptidomimetic, small molecule, chemical or nucleic acid.

11. The method of claim 10, wherein the inhibitor of VEGF activity is pegaptanib sodium, aflibercept, bevasiranib, rapamycin, AGN-745, vitalanib, pazopanib, NT-502, NT-503, or PLG101.

12. The method of claim 1, wherein the inhibitor of α

₅β

₁ integrin activity is an antibody or functional fragment thereof.

13. The method of claim 12, wherein the inhibitor of α

₅β

₁ integrin activity is volociximab.

14. The method of claim 1, wherein the inhibitor of α

₅β

₁ integrin activity is a peptide, peptidomimetic, small molecule, chemical or nucleic acid.

15. The method of claim 14, wherein the inhibitor of α

₅β

₁ integrin activity is 3-(2-{1-alkyl-5-[(pyridine-2-ylamino)-methyl]-pyrrolidin-3-yloxy}-acetylamino)-2-(alkyl-amino)-propionic acid, (S)-2-[(2,4,6-trimethylphenyl)sulfonyl]amino-3-[7-benzyloxycarbonyl-8-(2-pyridinylaminomethyl)-1-oxa-2,7-diazaspiro-(4,4)-non-2-en-3-yl]carbonylamino propionic acid, EMD478761, or RC*D(ThioP)C*.

16. The method of claim 1, wherein the inhibitor of VEGF activity and the inhibitor of α

₅β

₁ integrin activity are administered simultaneously.

17. The method of claim 1, wherein the inhibitor of VEGF activity and the inhibitor of α

₅β

₁ integrin activity are administered sequentially.

18. The method of claim 1, wherein the inhibitor of VEGF activity is administered daily.

19. The method of claim 1, wherein the inhibitor of VEGF activity is administered monthly.

20. The method of claim 1, wherein the inhibitor of α

₅β

₁ integrin activity is administered daily.

21. The method of claim 1, wherein the inhibitor of α

₅β

₁ integrin activity is administered monthly.

22. The method of claim 1, wherein about 0.1 mg to about 6.0 mg of the inhibitor VEGF activity is administered per month.

23. The method of claim 22, wherein about 0.5 mg of the inhibitor VEGF activity is administered per month.

24. The method of claim 1, wherein about 0.1 mg to about 2.5 mg of the inhibitor of α

₅β

₁ integrin activity is administered per month.

25. The method of claim 24, wherein about 0.5 mg, 1.25 mg, or 2.5 mg of the inhibitor of α

₅β

₁ integrin activity is administered per month.

26. The method of claim 1, wherein treatment duration is up to three months.

27. The method of claim 1, wherein treatment duration is six months to a year.

28. The method of claim 1, wherein the subject is a mammal.

29. The method of claim 28, wherein the subject is human.

30. A method of treating macular degeneration comprising administering to a subject in need thereof a therapeutically effective amount of ranibizumab or bevacizumab in combination with a therapeutically effective amount of volociximab.

31. The method of claim 30, wherein the volociximab is administered monthly via intravitreal injection.

32. The method of claim 31, wherein about 0.1 mg to about 2.5 mg of volociximab is administered in each injection.

33. The method of claim 32, wherein about 0.5 mg, 1.25 mg, or 2.5 mg of volociximab is administered in each injection.

34. The method of claim 30, wherein the ranibizumab or bevacizumab is administered monthly via intravitreal injection.

35. The method of claim 34, wherein about 0.1 mg to about 6.0 mg of ranibizumab or bevacizumab is administered in each injection.

36. The method of claim 35, wherein about 0.5 mg of ranibizumab or bevacizumab is administered in each injection.

37. The method of claim 30, wherein the subject is a mammal.

38. The method of claim 37, wherein the subject is human.

39. A composition comprising an inhibitor of VEGF activity and an inhibitor of α

₅β

₁ integrin activity in a pharmaceutically acceptable carrier.

40. The composition of claim 39, wherein the inhibitor of VEGF activity is bevacizumab, ranibizumab, pegaptanib sodium, aflibercept, bevasiranib, rapamycin, AGN-745, vitalanib, pazopanib, NT-502, NT-503, or PLG101.

41. The composition of claim 39, wherein the inhibitor of α

₅β

₁ integrin activity is volociximab, 3-(2-{1-alkyl-5-[(pyridine-2-ylamino)-methyl]pyrrolidin-3-yloxy}-acetylamino)-2-(alkyl-amino)-propionic acid, (S)-2-[(2,4,6-trimethylphenyl)sulfonyl]amino-3-[7-benzyloxycarbonyl-8-(2-pyridinylaminomethyl)-1-oxa-2,7-diazaspiro-(4,4)-non-2-en-3-yl]carbonylamino propionic acid, EMD478761, or RC*D(ThioP)C*.

42. A composition comprising a therapeutically effective amount of ranibizumab or bevacizumab and a therapeutically effective amount of volociximab in a pharmaceutically acceptable carrier.

43. The composition of claim 42, wherein the therapeutically effective amount of ranibizumab or bevacizumab is about 0.1 mg to about 6.0 mg.

44. The composition of claim 42, wherein the therapeutically effective amount of volociximab is about 0.1 mg to about 2.5 mg.

45. The composition of claim 44, wherein the therapeutically effective amount of volociximab is about 1.0 mg or about 2.5 mg.

46. The composition of claim 42, wherein the therapeutically effective amount of ranibizumab or bevacizumab is about 0.1 mg to about 6.0 mg.

47. The composition of claim 42, wherein the therapeutically effective amount of ranibizumab or bevacizumab is about 1.0 mg.

48. A composition comprising about 0.1 mg to about 6.0 mg ranibizumab or bevacizumab and about 0.1 mg to about 2.5 mg volociximab in a pharmaceutically acceptable carrier.

49. A composition comprising about 0.5 mg of ranibizumab or bevacizumab and about 0.5 mg, 1.25 mg, or 2.5 mg of volociximab in a pharmaceutically acceptable carrier.

50. A composition comprising a therapeutically effective amount of about 1.0 mg ranibizumab or bevacizumab and a therapeutically effective amount of about 1.0 mg or about 2.5 mg volociximab.