Oromucosal cytokine compositions and uses thereof

• US 6,660,258 B1
• Filed: 10/09/1998
• Issued: 12/09/2003
• Est. Priority Date: 05/09/1997
• Status: Expired due to Fees

• Current Assignee: Pharma Pacific Pty., Ltd. (Nufarm Ltd.)
• Original Assignee: Pharma Pacific Pty., Ltd. (Nufarm Ltd.)
• Inventors: Tovey, Michael Gerard
• Primary Examiner(s): Eyler, Yvonne
• Assistant Examiner(s): ANDRES, JANET L
• Application Number:
  US09/169,844
• Time in Patent Office: 1,887 Days
• Field of Search: 519/2, 424/85.2, 424/198.1, 530/351
• US Class Current: 424/85.2
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays

Abstract

Pharmaceutical compositions for oromucosal; contact to stimulate host defense mechanisms in a mammal, having an effective amount of Th1 or Th2 stimulating cytokine, and methods of treatment with such compositions are provided.

Claims

1. A method for treating diseases that would benefit from TH1 stimulation, comprising stimulating the host defense mechanisms in a mammal having such a disease by oromucosally administering an effective amount of a TH1-stimulating cytokine selected from the group consisting of IL-12, IL-18, TNF-β

and GM-CSF, wherein said oromucosal administration is accomplished in a manner that provides contact of the cytokine with the oromucosal cavity of the recipient for a period of time sufficient to obtain the desired stimulation.

2. A method in accordance with claim 1, wherein said disease that would benefit from TH1 stimulation is selected from the group consisting of neoplastic conditions, viral conditions, allergic disorders, asthma and atopic dermatitis.

3. A method in accordance with claim 1, wherein said effective amount is large enough to generate a pathological response if said cytokine were administered parenterally in that amount.

4. A method in accordance with claim 2, wherein said disease is selected from the group consisting of neoplastic conditions and viral conditions.

5. A method in accordance with claim 4, wherein said disease is a viral condition.

6. A method in accordance with claim 4, wherein said disease is a neoplastic condition.

7. A method of claim 6, wherein the effective amount of cytokine is from about 0.01 μ

g to about 150 μ

g of cytokine per kg body weight.

8. A method of claim 6, in which the effective amount of cytokine is administered in a single amount.

9. A method of claim 6, in which the effective amount of cytokine is administered in a plurality of amounts, each smaller than the effective amount, over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

10. A method of claim 6, in which the effective amount of cytokine is administered continuously over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

11. A method in accordance with claim 2, wherein said disease is selected from the group consisting of allergic disorders, asthma, and atopic dermatitis.

12. A method of claim 11, wherein the effective amount of cytokine is from about 0.01 μ

g to about 150 μ

g of cytokine per kg body weight.

13. A method of claim 11, in which the effective amount of cytokine is administered in a single amount.

14. A method of claim 11, in which the effective amount of cytokine is administered in a plurality of amounts, each smaller than the effective amount, over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

15. A method of claim 11, in which the effective amount of cytokine is administered continuously over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

16. A method in accordance with claim 11, wherein said disease is an allergic disorder.

17. A method in accordance with claim 11, wherein said disease is asthma.

18. A method in accordance with claim 11, wherein said disease is atopic dermatitis.

19. A method for treating diseases that would benefit from TH1 stimulation, comprising stimulating the host defense mechanisms in a mammal having such a disease by oromucosally administering, in a single dose, an effective amount of a TH1-stimulating cytokine selected from the group consisting of IL-2, IL-12, IL-15, IL-18, TNF-β

and GM-CSF, wherein said oromucosal administration is accomplished in a manner that provides contact of the cytokine with the oromucosal cavity of the recipient for a period of time sufficient to obtain the desired stimulation.

20. A method in accordance with claim 19, wherein said disease that would benefit from TH1 stimulation is selected from the group consisting of neoplastic conditions, viral conditions, allergic disorders, asthma and atopic dermatitis.

21. A method in accordance with claim 20, wherein said disease is selected from the group consisting of neoplastic conditions and viral conditions.

22. A method in accordance with claim 21, wherein said disease is a neoplastic condition.

23. A method of claim 19, wherein the effective amount of cytokine is from about 0.01 μ

g to about 150 μ

g of cytokine per kg body weight.

24. A method in accordance with claim 21, wherein said disease is a viral condition.

25. A method in accordance with claim 20, wherein said disease is selected from the group consisting of allergic disorders, asthma, and atopic dermatitis.

26. A method in accordance with claim 25, wherein said disease is an allergic disorder.

27. A method in accordance with claim 25, wherein said disease is asthma.

28. A method in accordance with claim 25, wherein said disease is atopic dermatitis.

29. A method of claim 25, wherein the effective amount of cytokine is from about 0.01 μ

g to about 150 μ

g of cytokine per kg body weight.

30. A method in accordance with claim 19, wherein said effective amount is large enough to generate a pathological response if said cytokine were administered parenterally in that amount.

31. A method for treating allergic disorders, asthma or atopic dermatitis, comprising stimulating the host defense mechanisms in a mammal having such a disease by oromucosally administering an effective amount of a TH1-stimulating cytokine selected from the group consisting of IL-2, IL-12, IL-15, IL-18, TNF-β

and GM-CSF, wherein said oromucosal administration is accomplished in a manner that provides contact of the cytokine with the oromucosal cavity of the recipient for a period of time sufficient to obtain the desired stimulation.

32. A method of claim 31, wherein the effective amount of cytokine is from about 0.01 μ

g to about 150 μ

g of cytokine per kg body weight.

33. A method of claim 31, in which the effective amount of cytokine is administered in a single amount.

34. A method of claim 31, in which the effective amount of cytokine is administered in a plurality of amounts, each smaller than the effective amount, over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

35. A method of claim 31, in which the effective amount of cytokine is administered continuously over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

36. A method in accordance with claim 31, wherein said disease is an allergic disorder.

37. A method in accordance with claim 31, wherein said disease is asthma.

38. A method in accordance with claim 31, wherein said disease is atopic dermatitis.

39. A method in accordance with claim 31, wherein said effective amount is large enough to generate a pathological response if said cytokine were administered parenterally in that amount.

40. A method for treating diseases that would benefit from TH1 stimulation, comprising stimulating the host defense mechanisms in a mammal having such a disease by oromucosally administering IL-2 or IL-15 in an effective amount that is great enough to generate a pathological response if administered parenterally, wherein said oromucosal administration is accomplished in a manner that provides contact of the cytokine with the oromucosal cavity of the recipient for a period of time sufficient to obtain the desired stimulation.

41. A method in accordance with claim 40, wherein said disease that would benefit from TH1 stimulation is selected from the group consisting of neoplastic conditions, viral conditions, allergic disorders, asthma and atopic dermatitis.

42. A method in accordance with claim 41, wherein said disease is selected from the group consisting of neoplastic conditions and viral conditions.

43. A method in accordance with claim 42, wherein said disease is a neoplastic condition.

44. A method of claim 43, in which the effective amount of cytokine is administered in a single amount.

45. A method of claim 43, in which the effective amount of cytokine is administered in a plurality of amounts, each smaller than the effective amount, over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

46. A method of claim 43, in which the effective amount of cytokine is administered continuously over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

47. A method in accordance with claim 42, wherein said disease is a viral condition.

48. A method in accordance with claim 41, wherein said disease is selected from the group consisting of allergic disorders, asthma, and atopic dermatitis.

49. A method in accordance with claim 48, wherein said disease is an allergic disorder.

50. A method in accordance with claim 48, wherein said disease is asthma.

51. A method in accordance with claim 48, wherein said disease is atopic dermatitis.

52. A method of claim 48, in which the effective amount of cytokine is administered in a single amount.

53. A method of claim 48, in which the effective amount of cytokine is administered in a plurality of amounts, each smaller than the effective amount, over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

54. A method of claim 48, in which the effective amount of cytokine is administered continuously over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

55. A method for treating diseases that would benefit from TH2 stimulation, comprising stimulating the host defense mechanisms in a patient having such a disease by oromucosally administering an effective amount of a TH2-stimulating cytokine selected from the group consisting of IL-4, IL-5 and IL-13, wherein said oromucosal administration is accomplished in a manner that provides contact of the cytokine with the oromucosal cavity of the recipient for a period of time sufficient to obtain the desired stimulation.

56. A method in accordance with claim 55, wherein said disease that would benefit from TH2 stimulation is an autoimmune disease.

57. A method of claim 56, in which the effective amount of cytokine is from about 0.01 μ

g to about 150 μ

g of cytokine per kg body weight.

58. A method of claim 56, in which the effective amount of cytokine is administered in a single amount.

59. A method of claim 56, in which the effective amount of cytokine is administered in a plurality of amounts, smaller than the effective amount, over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

60. A method of claim 56, in which the effective amount of cytokine is administered continuously over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

61. A method in accordance with claim 55, wherein said effective amount is large enough to generate a pathological response if said cytokine were administered parenterally in that amount.

62. A method for treating diseases that would benefit from TH2 stimulation, comprising stimulating the host defense mechanism in a patient having such a disease by oromucosally administering IL-10 in an effective amount that is great enough to generate a pathological response if administered parenterally, wherein said oromucosal administration is accomplished in a manner that provides contact of the cytokine with the oromucosal cavity of the recipient for a period of time sufficient to obtain the desired stimulation.

63. A method in accordance with claim 62, wherein said disease that would benefit from TH2 stimulation is an autoimmune disease.

64. A method of claim 63, in which the effective amount of cytokine is administered in a single amount.

65. A method of claim 63, in which the effective amount of cytokine is administered in a plurality of amounts, smaller than the effective amount, over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.

66. A method of claim 63, in which the effective amount of cytokineis administered continuously over a period of time sufficient to elicit stimulation equivalent to that of a single effective amount.