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Details for Patent: 6,469,045

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Details for Patent: 6,469,045

Title: Methods and compositions for inhibition of angiogenesis with EM-138
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 and to treat disease states resulting from angiogenesis. Importantly, these compounds can be administered orally.
Inventor(s): D'Amato; Robert (Lancaster, PA)
Assignee: The Children's Medical Center Corporation (Boston, MA)
Filing Date:Apr 07, 2000
Application Number:09/545,139
Claims:1. A method of treating an eye condition associated with angiogenesis in a human or animal comprising administering to said human or animal an angiogenesis inhibiting amount of EM-138, ##STR19##

2. The method of claim 1 wherein the amount administered is between approximately 0.1 and approximately 300 mg/kg/day.

3. The method of claim 2 wherein the amount administered is between approximately 0.5 and approximately 50 mg/kg/day.

4. The method of claim 3 wherein the amount administered is between approximately 1 and approximately 10 mg/kg/day.

5. The method of claim 1 wherein the compound is administered in the form of a tablet or capsule.

6. The method of claim 1 wherein the compound is administered in the form of a lozenge, a cachet, a solution, a suspension, an emulsion, a powder, an aerosol, a suppository, a spray, a pastille, an ointment, a cream, a paste, a foam, a gel, a tamport, or a pessary.

7. The method of claim 1 wherein the administration is oral, parenteral, transdermal, or topical.

8. The method of claim 1 wherein the administration is sublingual, buccal, rectal, vaginal, or nasal.

9. The method of claim 1 wherein the eye condition is diabetic retinopathy.

10. The method of claim 1 wherein the eye condition is retinopathy of prematurity.

11. The method of claim 1 wherein the eye condition is corneal graft rejection.

12. The method of claim 1 wherein the eye condition is neovascular glaucoma.

13. The method of claim 1 wherein the eye condition is retrolental fibroplasias.

14. The method of claim 1 wherein the eye condition is epidemic keratoconjunctivitis.

15. The method of claim 1 wherein the eye condition is Vitamin A deficiency.

16. The method of claim 1 wherein the eye condition is contact lens overwear.

17. The method of claim 1 wherein the eye condition is atopic keratitis.

18. The method of claim 1 wherein the eye condition is superior limbic keratitis.

19. The method of claim 1 wherein the eye condition is pterygium keratitis sicca.

20. The method of claim 1 wherein the eye condition is myopia.

21. The method of claim 1 wherein the eye condition is Terrien's marginal degeneration.

22. The method of claim 1 wherein the eye condition is mariginal keratolysis.

23. The method of claim 1 wherein the eye condition is radial keratotomy.

24. The method of claim 1 wherein the eye condition is macular degeneration.

25. The method of claim 1 wherein the eye condition is post-laser complications.

26. The method of claim 1 wherein the eye condition is chronic retinal detachment.

27. The method of claim 1 wherein the eye condition is optic pits.

28. The method of claim 1 wherein the eye condition is a hyperviscosity syndrome.

29. The method of claim 1 wherein the eye condition is chronic uveitis.

30. The method of claim 1 wherein the eye condition is chronic vitritis.

31. The method of claim 1 wherein the eye condition is ocular neovascular disease.

32. The method of claim 1 wherein the eye condition is age-related macular degeneration.

33. The method of claim 1 wherein the eye condition is presumed ocular histoplasmosis.

34. The method of claim 1 wherein the eye condition is an infection causing retinitis or choroiditis.

35. The method of claim 1 wherein the eye condition is proliferative vitreoretinopathy.

36. The method of claim 1 wherein the eye condition is scleritis.

37. The method of claim 1 wherein the eye condition is Eales' disease.

38. The method of claim 1 wherein the eye condition is Best's disease.

39. The method of claim 1 wherein the eye condition is trachoma.

40. A method of treating an ulcerative disease associated with angiogenesis in a human or animal comprising administering to said human or animal an angiogenesis inhibiting amount of EM-138, ##STR20##

41. The method of claim 40 wherein the ulcerative disease is a bacterial ulcer.

42. The method of claim 40 wherein the ulcerative disease is a fungal ulcer.

43. The method of claim 40 wherein the ulcerative disease is Mooren's ulcer.

44. The method of claim 40 wherein the ulcerative disease is Wegener's sarcoidosis.

45. The method of claim 40 wherein the ulcerative disease is Stevens-Johnson disease.

46. The method of claim 40 wherein the ulcerative disease is Behcet's disease.

47. The method of claim 40 wherein the ulcerative disease is pemphigoid.

48. The method of claim 40 wherein the ulcerative disease is ulceritive colitis.

49. The method of claim 40 wherein the amount administered is between approximately 0.1 and approximately 300 mg/kg/day.

50. The method of claim 49 wherein the amount administered is between approximately 0.5 and approximately 50 mg/kg/day.

51. The method of claim 50 wherein the amount administered is between approximately 1 and approximately 10 mg/kg/day.

52. The method of claim 40 wherein the compound is administered in the form of a tablet or capsule.

53. The method of claim 40 wherein the compound is administered in the form of a lozenge, a cachet, a solution, a suspension, an emulsion, a powder, an aerosol, a suppository, a spray, a pastille,an ointment, a cream, a paste, a foam, a gel, a tamport, or a pessary.

54. The method of claim 40 wherein the administration is oral, parenteral, transdermal, or topical.

55. The method of claim 40 wherein the administration is sublingual, buccal, rectal, vaginal, or nasal.

56. A method of treating a skin condition associated with angiogenesis in a human or animal comprising administering to said human or animal an angiogenesis inhibiting amount of EM-138, ##STR21##

57. The method of claim 56 wherein the skin condition is acne.

58. The method of claim 56 wherein the skin condition is rosacea.

59. The method of claim 56 wherein the skin condition is a chemical burn.

60. The method of claim 56 wherein the skin condition is psoriasis.

61. The method of claim 56 wherein the amount administered is between approximately 0.1 and approximately 300 mg/kg/day.

62. The method of claim 61 wherein the amount administered is between approximately 0.5 and approximately 50 mg/kg/day.

63. The method of claim 62 wherein the amount administered is between approximately 1 and approximately 10 mg/kg/day.

64. The method of claim 56 wherein the compound is administered in the form of a tablet or capsule.

65. The method of claim 56 wherein the compound is administered in the form of a lozenge, a cachet, a solution, a suspension, an emulsion, a powder, an aerosol, a suppository, a spray, a pastille, an ointment, a cream, a paste, a foam, a gel, a tamport, or a pessary.

66. The method of claim 56 wherein the administration is oral, parenteral, transdermal, or topical.

67. The method of claim 56 wherein the administration is sublingual, buccal, rectal, vaginal, or nasal.

68. A method for inhibiting undesired angiogenesis in a human or animal wherein the angiogenesis is associated with a condition selected from the group consisting of trauma, sjogren's syndrome, phylectenulosis, sarcoid, pseudoxanthoma elasticum, Stargardt's disease, Paget's disease, Lyme's disease, par planitis, pyogenic granulomas, lipid degeneration, Crohn's disease, chronic inflammation, acoustic neuroma, and abnormal proliferation of fibrovascular or fibrous tissue comprising administering to the human or animal an angiogenesis inhibiting amount of EM-138, ##STR22##

69. The method of claim 68 wherein the condition is trauma.

70. The method of claim 68 wherein the condition is sjogren's syndrome.

71. The method of claim 68 wherein the condition is phylectenulosis.

72. The method of claim 68 wherein the condition is sarcoid.

73. The method of claim 68 wherein the condition is pseudoxanthoma elasticum.

74. The method of claim 68 wherein the condition is Stargardt's disease.

75. The method of claim 68 wherein the condition is Paget's disease.

76. The method of claim 68 wherein the condition is Lyme's disease.

77. The method of claim 68 wherein the condition is par planitis.

78. The method of claim 68 wherein the condition is pyogenic granulomas.

79. The method of claim 68 wherein the condition is lipid degeneration.

80. The method of claim 68 wherein the condition is Crohn's disease.

81. The method of claim 68 wherein the condition is chronic inflammation.

82. The method of claim 68 wherein the condition is acoustic neuroma.

83. The method of claim 68 wherein the condition is abnormal proliferation of fibrovascular or fibrous tissue.

84. The method of claim 68 wherein the amount administered is between approximately 0.1 and approximately 300 mg/kg/day.

85. The method of claim 84 wherein the amount administered is between approximately 0.5 and approximately 50 mg/kg/day.

86. The method of claim 85 wherein the amount administered is between approximately 1 and approximately 10 mg/kg/day.

87. The method of claim 68 wherein the compound is administered in the form of a tablet or capsule.

88. The method of claim 68 wherein the compound is administered in the form of a lozenge, a cachet, a solution, a suspension, an emulsion, a powder, an aerosol, a suppository, a spray, a pastille, an ointment, a cream, a paste, a foam, a gel, a tamport, or a pessary.

89. The method of claim 68 wherein the administration is oral, parenteral, transdermal, or topical.

90. The method of claim 68 wherein the administration is sublingual, buccal, rectal, vaginal, or nasal.
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