Use of IL-12 and IFN.alpha. for the treatment of infectious diseases

• US 5,928,636 A
• Filed: 04/30/1997
• Issued: 07/27/1999
• Est. Priority Date: 05/13/1996
• Status: Expired due to Fees

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Carr, Jacqueline Anne, Palmer, Kathrin, Mattner, Frank Albert, Mulqueen, Michael John, Rogerson, Jane Andre Louise, Alber, Gottfried
• Primary Examiner(s): MERTZ, PREMA MARIA
• Application Number:
  US08/845,973
• Time in Patent Office: 818 Days
• Field of Search: 424/85.1, 424/85.2, 424/85.4, 424/85.7, 514/2, 514/8, 514/12, 514/885, 514/895
• US Class Current: 424/85.2
• 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 38/212 IFN-alpha
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/06 for tuberculosis
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 33/12 Schistosomicides
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides a combination of IL-12 and IFNα together with a pharmaceutically acceptable carrier useful for treatment and prophylaxis of infectious diseases, preferably chronic infectious diseases and more preferably viral infections, e.g. HSV, HIV, Hepatitis B, Hepatitis C, papilloma etc., bacterial infections, e.g. tuberculosis, salmonellosis, listeriosis, etc., and parasite infections, e.g. malaria, leishmaniasis, and schistosomiasis. These compositions are characterized by the synergistic interaction of IL-12 and IFNα. The present invention also provides the use of the above combination for the treatment and prophylaxis of infectious diseases.

Claims

1. A pharmaceutical composition in unit dosage form for parenteral administration to a human patient said composition comprising:

Interleukin-12 in an amount from about 10 to about 1000 nanograms/kilogram of body weight of said human patient; and

Interferon-α

in an amount from about 0.1 to about 50 micrograms/kilogram of body weight of said human patient;

together with a pharmaceutically acceptable carrier.

2. The composition of claim 1, wherein said amount of Interleukin-12 is from about 30 to about 300 nanograms/kilogram of body weight of said human patient.

3. The composition of claim 2, wherein said amount of Interferon-α

is from about 1 to about 15 micrograms/kilogram of body weight of said human patient.

4. A method of treating a viral infection in a human patient in need of such treatment comprising administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of Interleukin-12 for such treatment;

and a therapeutically effective amount of Interferon-α

for such treatment;

together with a pharmaceutically acceptable carrier;

wherein said viral infection is selected from the group consisting of herpes (HSV), hepatitis B, hepatitis C and papilloma.

5. The method of claim 4, wherein said amount of Interleukin-12 is from about 10 to about 1000 nanograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

6. The method of claim 5, wherein said amount of Interferon-α

is from about 0.1 to about 50 micrograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

7. The method of claim 6, wherein said amount of Interleukin-12 is from about 30 to about 300 nanograms/kilogram of body weight of said human patient.

8. The method of claim 7, wherein amount of Interferon-α

is from about 1 to about 15 micrograms/kilogram of body weight of said human patient.

9. A method of treating a bacterial infection in a human patient in need of such treatment comprising administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of Interleukin-12 for such treatment;

and a therapeutically effective amount of Interferon-α

for such treatment;

together with a pharmaceutically acceptable carrier.

10. The method of claim 9, wherein the bacterial infection is selected from the group consisting of tuberculosis, salmonellosis and listerosis.

11. The method of claim 9, wherein said amount of Interleukin-12 is from about 10 to about 1000 nanograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

12. The method of claim 11, wherein said amount of Interferon-α

is from about 0.1 to about 50 micrograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

13. The method of claim 12, wherein said amount of Interleukin-12 is from about 30 to about 300 nanograms/kilogram of body weight of said human patient.

14. The method of claim 13, wherein said amount of Interferon-α

is from about 1 to about 15 micrograms/kilogram of body weight of said human patient.

15. A method of treating a parasitic infection in a human patient in need of such treatment comprising administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of Interleukin-12 for such treatment;

and a therapeutically effective amount of Interferon-α

for such treatment;

together with a pharmaceutically acceptable carrier.

16. The method of claim 15, wherein the parasitic infection is selected from the group consisting of malaria, leishmaniosis and schistosomiasis.

17. The method of claim 15 wherein said amount of Interleukin-12 is from about 10 to about 1000 nanograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

18. The method of claim 17, wherein said amount of Interferon-α

is from about 0.1 to about 50 micrograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

19. The method of claim 18, wherein said amount of Interleukin-12 is from about 30 to about 300 nanograms/kilogram of body weight of said human patient.

20. The method of claim 19 wherein said amount of Interferon-α

is from about 1 to about 15 micrograms/kilogram of body weight of said human patient.

21. A method of preventing a viral infection in a human patient susceptible to viral infections comprising administering to the patient a pharmaceutical composition comprising:

an amount of Interleukin-12 and an amount of Interferon-α

, wherein said amounts of Interleukin-12 and Interferon-α

are effective for preventing said viral infection in said patient;

together with a pharmaceutically acceptable carrier;

wherein said viral infection is selected from the group consisting of herpes (HSV), hepatitis B, hepatitis C and papilloma.

22. The method of claim 21, wherein said amount of Interleukin-12 is from about 10 to about 1000 nanograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

23. The method of claim 22, wherein said amount of Interferon-α

is from about 0.1 to about 50 micrograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

24. The method of claim 23, wherein said amount of Interleukin-12 is from about 30 to about 300 micrograms/kilogram of body weight of said human patient.

25. The method of claim 24, wherein said amount of Interferon-α

is from about 1 to about 15 micrograms/kilogram of body weight of said human patient.

26. A method of preventing a bacterial infection in a human patient in need of such treatment comprising administering to the patient a pharmaceutical composition comprising an amount of Interleukin-12 and an amount of Interferon-α

, wherein said amounts of Interleukin-12 and Interferon-α

are effective for preventing said bacterial infection in said patient;

together with a pharmaceutically acceptable carrier.

27. The method of claim 26, wherein the bacterial infection is selected from the group consisting of tuberculosis, salmonellosis and listerosis.

28. The method of claim 26 wherein said amount of Interleukin-12 is from about 10 to about 1000 nanograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

29. The method of claim 28, wherein said amount of Interferon-α

is from about 0.1 to about 50 micrograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

30. The method of claim 29, wherein said amount of Interleukin-12 is from about 30 to about 300 nanograms/kilogram of body weight of said human patient.

31. The method of claim 30, wherein said amount of Interferon-α

is from about 1 to about 15 micrograms/kilogram of body weight of said human patient.

32. A method of preventing a parasitic infection in a human patient in need of such treatment comprising administering to the patient a pharmaceutical composition comprising an amount of Interleukin-12 and an amount of Interferon-α

, wherein said amounts of Interleukin-12 and Interferon-α

are effective for preventing said parasitic infection in said patient;

together with a pharmaceutically acceptable carrier.

33. The method of claim 32, wherein the parasitic infection is selected from the group consisting of malaria, leishmaniosis and schistosomiasis.

34. The method of claim 32 wherein said amount of Interleukin-12 is from about 10 to about 1000 nanograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

35. The method of claim 34, wherein said amount of Interferon-α

is from about 0.1 to about 50 micrograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

36. The method of claim 35, wherein said amount of Interleukin-12 is from about 30 to about 300 nanograms/kilogram of body weight of said human patient.

37. The method of claim 36, wherein said amount of Interferon-α

is from about 1 to about 15 micrograms/kilogram of body weight of said human patient.

38. A method of stimulating T cells in a human patient infected with HIV comprising parenterally administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of Interleukin-12;

and a therapeutically effective amount of Interferon-α

;

together with a pharmaceutically acceptable carrier.

39. The method of claim 38, wherein said amount of Interleukin-12 for such treatment is from about 10 to about 1000 nanograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

40. The method of claim 39, wherein said amount of Interferon-α

is from about 0.1 to about 50 micrograms/kilogram of body weight of said human patient administered 1 to 3 times per week.

41. The method of claim 40, wherein said amount of Interleukin-12 is from about 30 to about 300 nanograms/kilogram of body weight of said human patient.

42. The method of claim 41, wherein said amount of Interferon-α

is from about 1 to about 15 micrograms /kilogram of body weight of said human patient.