Methods and compositions for inhibition of angiogenesis

• US 5,712,291 A
• Filed: 06/06/1995
• Issued: 01/27/1998
• Est. Priority Date: 03/01/1993
• Status: Expired

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: D'Amato, Robert
• Primary Examiner(s): Ivy, C. Warren
• Assistant Examiner(s): DAHLEN, GARTH
• Application Number:
  US08/468,792
• Time in Patent Office: 966 Days
• Field of Search: 514/323
• US Class Current: 514/323
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/4035 Isoindoles, e.g. phthalimide
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/535 having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/10 for accommodation disorders, e.g. myopia
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• 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: C07D 403/02 : containing two hetero rings

Abstract

The present invention comprises a group of compounds that effectively inhibit angiogenesis. More specifically, thalidomide and various related compounds such as thalidomide precursors, analogs, metabolites and hydrolysis products have been shown to inhibit angiogenesis. Importantly, these compounds can be administered orally.

Claims

1. A method of treating undesired angiogenesis in a human or animal comprising the step of administering to the human or animal with the undesired angiogenesis a composition comprising an effective amount of an angiogenesis-inhibiting compound selected from the group consisting of 3-aminothalidomide, and 3-hydroxythalidomide, and metabolites or hydrolysis products of 3-aminothalidomide and metabolites or hydrolysis products of 3-hydroxythalidomide, and mixtures thereof.

2. The method of claim 1, wherein the undesired angiogenesis is associated with retinal neovascularization.

3. The method of claim 1, wherein the undesired angiogenesis is associated with choroidal neovascularization.

4. The method of claim 1 wherein the undesired angiogenesis is associated with diabetic retinopathy.

5. The method of claim 1, wherein the undesired angiogenesis is associated with macular degeneration.

6. The method of claim 1, wherein the undesired angiogenesis is associated with corneal neovascularization.

7. The method of claim 1 wherein the undesired angiogenesis occurs in retinopathy of prematurity.

8. The method of claim 1 wherein the undesired angiogenesis occurs in corneal graft rejection.

9. The method of claim 1 wherein the undesired angiogenesis occurs in neovascular glaucoma.

10. The method of claim 1 wherein the undesired angiogenesis occurs in retrolental fibroplasia.

11. The method of claim 1 wherein the undesired angiogenesis occurs in epidemic keratoconjunctivitis.

12. The method of claim 1 wherein the undesired angiogenesis occurs due to Vitamin A deficiency.

13. The method of claim 1 wherein the undesired angiogenesis occurs due to contact lens overwear.

14. The method of claim 1 wherein the undesired angiogenesis occurs in atopic keratitis.

15. The method of claim 1 wherein the undesired angiogenesis occurs in superior limbic keratitis.

16. The method of claim 1 wherein the undesired angiogenesis occurs in pterygium keratitis sicca.

17. The method of claim 1 wherein the undesired angiogenesis occurs in sogrens.

18. The method of claim 1 wherein the undesired angiogenesis occurs in acne rosacea.

19. The method of claim 1 wherein the undesired angiogenesis occurs in phylectenulosis.

20. The method of claim 1 wherein the undesired angiogenesis occurs in syphilis.

21. The method of claim 1 wherein the undesired angiogenesis occurs in Mycobacteria infections other than leprosy.

22. The method of claim 1 wherein the undesired angiogenesis occurs in lipid degeneration.

23. The method of claim 1 wherein the undesired angiogenesis occurs in chemical burns.

24. The method of claim 1 wherein the undesired angiogenesis occurs in bacterial ulcers.

25. The method of claim 1 wherein the undesired angiogenesis occurs in fungal ulcers.

26. The method of claim 1 wherein the undesired angiogenesis occurs in Herpes simplex infections.

27. The method of claim 1 wherein the undesired angiogenesis occurs in Herpes zoster infections.

28. The method of claim 1 wherein the undesired angiogenesis occurs in protozoan infections.

29. The method of claim 1 wherein the undesired angiogenesis occurs in Kaposi'"'"'s sarcoma.

30. The method of claim 1 wherein the undesired angiogenesis occurs in Mooren ulcer.

31. The method of claim 1 wherein the undesired angiogenesis occurs in Terrien'"'"'s marginal degeneration.

32. The method of claim 1 wherein the undesired angiogenesis occurs in marginal keratolysis.

33. The method of claim 1 wherein the undesired angiogenesis is caused by trauma.

34. The method of claim 1 wherein the undesired angiogenesis occurs in rheumatoid arthritis.

35. The method of claim 1 wherein the undesired angiogenesis occurs in systemic lupus.

36. The method of claim 1 wherein the undesired angiogenesis occurs in polyarteritis.

37. The method of claim 1 wherein the undesired angiogenesis occurs in Wegeners sarcoidosis.

38. The method of claim 1 wherein the undesired angiogenesis occurs in scleritis.

39. The method of claim 1 wherein the undesired angiogenesis occurs in Steven'"'"'s Johnson disease.

40. The method of claim 1 wherein the undesired angiogenesis occurs in radial keratotomy.

41. The method of claim 1 wherein the undesired angiogenesis occurs in sickle cell anemia.

42. The method of claim 1 wherein the undesired angiogenesis occurs in sarcoid.

43. The method of claim 1 wherein the undesired angiogenesis occurs in pseudoxanthoma elasticum.

44. The method of claim 1 wherein the undesired angiogenesis occurs in Pagets disease.

45. The method of claim 1 wherein the undesired angiogenesis occurs in vein occlusion.

46. The method of claim 1 wherein the undesired angiogenesis occurs in artery occulsion.

47. The method of claim 1 wherein the undesired angiogenesis occurs in carotid obstructive disease.

48. The method of claim 1 wherein the undesired angiogenesis occurs in chronic uveitis.

49. The method of claim 1 wherein the undesired angiogenesis occurs in chronic vitritis.

50. The method of claim 1 wherein the undesired angiogenesis occurs in Lyme'"'"'s disease.

51. The method of claim 1 wherein the undesired angiogenesis occurs in Eales disease.

52. The method of claim 1 wherein the undesired angiogenesis occurs in Bechets disease.

53. The method of claim 1 wherein the undesired angiogenesis occurs in myopia.

54. The method of claim 1 wherein the undesired angiogenesis occurs in optic pits.

55. The method of claim 1 wherein the undesired angiogenesis occurs in Stargarts disease.

56. The method of claim 1 wherein the undesired angiogenesis occurs in pars planitis.

57. The method of claim 1 wherein the undesired angiogenesis occurs in chronic retinal detachment.

58. The method of claim 1 wherein the undesired angiogenesis occurs in hyperviscosity syndromes.

59. The method of claim 1 wherein the undesired angiogenesis occurs in toxoplasmosis.

60. The method of claim 1 wherein the undesired angiogenesis occurs in post-laser complications.

61. The method of claim 1 wherein the undesired angiogenesis occurs in abnormal proliferation of fibrovascular tissue.

62. The method of claim 1 wherein the undesired angiogenesis occurs in hemangiomas.

63. The method of claim 1 wherein the undesired angiogenesis occurs in Osler-Weber-Rendu.

64. The method of claim 1 wherein the undesired angiogenesis occurs in solid tumors.

65. The method of claim 1 wherein the undesired angiogenesis occurs in blood borne tumors.

66. The method of claim 1 wherein the undesired angiogenesis occurs in acquired immune deficiency syndrome.

67. The method of claim 1 wherein the undesired angiogenesis occurs in ocular neovascular disease.

68. The method of claim 1 wherein the undesired angiogenesis occurs in osteoarthritis.

69. The method of claim 1 wherein the undesired angiogenesis occurs in diseases caused by chronic inflammation.

70. The method of claim 1 wherein the undesired angiogenesis occurs in Crohn'"'"'s disease.

71. The method of claim 1 wherein the undesired angiogenesis occurs in ulceritive colitis.

72. The method of claim 1 wherein the undesired angiogenesis occurs in the tumors of rhabdomyosarcoma.

73. The method of claim 1 wherein the undesired angiogenesis occurs in the tumors of retinoblastoma.

74. The method of claim 1 wherein the undesired angiogenesis occurs in the tumors of Ewing sarcoma.

75. The method of claim 1 wherein the undesired angiogenesis occurs in the tumors of neuroblastoma.

76. The method of claim 1 wherein the undesired angiogenesis occurs in the tumors of osteosarcoma.

77. The method of claim 1 wherein the undesired angiogenesis occurs in leukemia.

78. The method of claim 1 wherein the undesired angiogenesis occurs in psoriasis.

79. The method of claim 1 wherein the undesired angiogenesis occurs in atherosclerosis.

80. The method of claim 1 wherein the undesired angiogenesis occurs in pemphigoid.