METHOD FOR TREATING DEFICIENCY IN HEMATOPOIESIS

• US 20100278777A1
• Filed: 04/08/2010
• Published: 11/04/2010
• Est. Priority Date: 07/03/2003
• Status: Active Grant

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Zhao, Yi, Anderson, W. French, Chen, Tingchao
• Granted Patent: US 9,023,337 B2
• Time in Patent Office: Days
• 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 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/208 IL-12
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61N 2005/1098 Enhancing the effect of the particle by an injected agent or implanted device
• CPC Class Codes: A61N 5/10 X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07K 14/53 Colony-stimulating factor [CSF]
• CPC Class Codes: C07K 14/5434 IL-12

Abstract

Methods for enhancing or stimulating hematopoiesis including the step of administering Interleukin-12 (IL-12) to yield hematopoietic recovery in a mammal in need. Preferred methods include the step of administering IL-12 as an adjuvant therapy to alleviate the hematopoietic toxicities associated with one or more treatment regimens used to combat a disease state. Other methods include administering IL-12 to ameliorate various hematopoietic deficiencies. Still other methods are directed to uses of IL-12 for in-vivo proliferation of hematopoietic repopulating cells, hematopoietic progenitor cells and hematopoietic stem cells. Other disclosed methods are directed to uses of IL-12 for bone marrow preservation or recovery.

Claims

1. A method for treating a mammal for a deficiency in hematopoiesis comprising:

administering one or more therapeutically effective dose(s) of IL-12 as needed to ameliorate the deficiency.

2. The method of claim 1, wherein the deficiency in hematopoiesis comprises a deficiency in one or more hematopoietic cell types or lineages.

3. The method of claim 1, wherein the mammal is a human.

4. The method of claim 1, wherein the dose of IL-12 is less than about 2000 ng/kg.

5. The method of claim 1, wherein the dose of IL-12 is less than about 500 ng/kg.

6. The method of claim 1, wherein the dose of IL-12 is less than about 100 ng/kg.

7. The method of claim 1, wherein the dose of IL-12 is less than about 10 ng/kg.

8. The method of claim 1, wherein the deficiency is ameliorated by the IL-12 facilitated proliferation of one or more types of bone marrow cells.

9. The method of claim 1, wherein the deficiency is ameliorated by the IL-12 facilitated proliferation of hematopoietic repopulating cells, hematopoietic stem cells or hematopoietic progenitor cells.

10. The method of claim 1, wherein the deficiency is exacerbated by chemotherapy.

11. The method of claim 1, wherein the deficiency is exacerbated by radiation therapy.

12. The method of claim 1, wherein the deficiency is substantially the result of a disease state.

13. The method of claim 1, wherein the deficiency comprises a lymphopenia.

14. The method of claim 1, wherein the deficiency comprises a myelopenia.

15. The method of claim 1, wherein the deficiency comprises a leukopenia.

16. The method of claim 1, wherein the leukopenia is neutropenia.

17. The method of claim 1, wherein the deficiency comprises erythropenia.

18. The method of claim 1, wherein the deficiency comprises megakaryopenia.

19. The method of claim 1, wherein the deficiency comprises a deficiency in platelets.

20. The method of claim 1, wherein the deficiency comprises a deficiency in monocytes.

21. The method of claim 1, wherein the deficiency comprises a deficiency in lymphocyctes.

22. The method of claim 1, wherein the deficiency comprises a deficiency in erythrocytes.

23. The method of claim 1, wherein the deficiency comprises a deficiency in neutrophils.

24. The method of claim 1, wherein the deficiency comprises a deficiency in T cells.

25. The method of claim 1, wherein the deficiency comprises a deficiency in granulocytes.

26. The method of claim 1, wherein the deficiency comprises a deficiency in dendritic cells.

27. A method for stimulating or enhancing hematopoiesis in a mammal comprising administering one or more therapeutically effective dose(s) of IL-12 for a duration to achieve a therapeutic effect comprising the stimulation or enhancement of hematopoiesis.

28. The method of claim 27, wherein the stimulation or enhancement of hematopoiesis involves the Il-12 facilitated proliferation of bone marrow cells.

29. The method of claim 27, wherein the stimulation or enhancement of hematoapoiesis involves the IL-12 facilitated proliferation of hematopoietic repopulating cells, hematopoietic progenitor cells or hematopoietic stem cells.

30. The method of claim 27, wherein the dose of IL-12 is less than about 2000 ng/kg.

31. The method of claim 27, wherein the dose of IL-12 is less than about 500 ng/kg.

32. The method of claim 27, wherein the dose of IL-12 is less than about 100 ng/kg.

33. The method of claim 27, wherein the dose of IL-12 is less than about 10 ng/kg.

34. The method of claim 29, wherein the hematopoietic repopulating cells comprise long-term repopulating cells.

35. The method of claim 27 further comprising the administration of radiation therapy.

36. The method of claim 27 further comprising the administration of chemotherapy.

37. The method of claim 27, wherein the mammal has a deficiency in one or more hematopoietic cell types or lineages.

38. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising lymphopenia.

39. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising myelopenia.

40. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising leukopenia.

41. The method of claim 40, wherein the leukopenia is neutropenia.

42. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising a erythropenia.

43. The method of claim 27, wherein the mammal has a deficiency comprising megakaryopenia.

44. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising a deficiency in platelets.

45. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising a deficiency in monocytes.

46. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising a deficiency in lymphocyctes.

47. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising a deficiency in erythrocytes.

48. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising a deficiency in neutrophils.

49. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising a deficiency in T cells.

50. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising a deficiency in granulocytes.

51. The method of claim 27, wherein the mammal has a hematopoietic deficiency comprising a deficiency in dendritic cells.