Methods of Using Interleukin-10 for Treating Diseases and Disorders

• US 20170246252A1
• Filed: 10/20/2015
• Published: 08/31/2017
• Est. Priority Date: 10/22/2014
• Status: Active Grant

• Current Assignee: Armo BioSciences Inc.
• Original Assignee: Armo BioSciences Inc.
• Inventors: OFT, Martin
• Granted Patent: US 10,143,726 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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

Abstract

Methods of treating subjects having a disease or disorder responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided.

Claims

1. A method of treating or preventing a disease, disorder or condition in a subject, comprising administering to the subject a therapeutically effective amount of an IL-10 agent, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least 6.0 ng/mL.

2. The method of claim 1, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least 8.0 ng/mL.

3. The method of claim 1, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least 10.0 ng/mL.

4. The method of claim 1, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least 12.0 ng/mL.

5. The method of claim 1, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least 14.0 ng/mL.

6. The method of claim 1, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least 16.0 ng/mL.

7. The method of claim 1, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least 18.0 ng/mL.

8. The method of claim 1, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least 20.0 ng/mL

32. The method of any one of claims 1-31, wherein the IL-10 agent is mature human IL-10.

33. The method of any one of claims 1-31, wherein the IL-10 agent is a variant of mature human IL-10, and wherein the variant exhibits activity comparable to the activity of mature human IL-10.

34. The method of any one of claims 1-33, wherein the disease, disorder or condition is a proliferative disorder.

35. The method of claim 34, wherein the proliferative disorder is a cancer.

36. The method of claim 35, wherein the cancer is a solid tumor or a hematological disorder.

37. The method of any one of claims 1-33, wherein the disease, disorder or condition is an immune or inflammatory disorder.

38. The method of claim 37, wherein immune or inflammatory disorder is selected from the group consisting of inflammatory bowel disease, psoriasis, rheumatoid arthritis, multiple sclerosis, and Alzheimer'"'"'s disease.

39. The method of any one of claims 1-33, wherein the disease, disorder or condition is thrombosis or a thrombotic condition.

40. The method of any one of claims 1-33, wherein the disease, disorder or condition is a fibrotic disorder.

41. The method of any one of claims 1-33, wherein the disease, disorder or condition is a viral disorder.

42. The method of claim 41, wherein the viral disorder is selected from the group consisting of human immunodeficiency virus, hepatitis B virus, hepatitis C virus and cytomegalovirus.

43. The method of any one of claims 1-33, wherein the disease, disorder or condition is a cardiovascular disorder.

44. The method of claim 43, wherein the cardiovascular disorder is atherosclerosis.

45. The method of claim 43 or 44, wherein the subject has elevated cholesterol.

46. The method of any one of claims 1-45, wherein the IL-10 agent comprises at least one modification to form a modified IL-10 agent, wherein the modification does not alter the amino acid sequence of the IL-10 agent.

47. The method of claim 46, wherein the modified IL-10 agent is a PEG-IL-10 agent.

48. The method of claim 47, wherein the PEG-IL-10 agent comprises at least one PEG molecule covalently attached to at least one amino acid residue of at least one subunit of IL-10.

49. The method of claim 47 or 48, wherein the PEG-IL-10 agent comprises a mixture of mono-pegylated and di-pegylated IL-10.

50. The method of any one of claims 47-49, wherein the PEG component of the PEG-IL-10 agent has a molecular mass from about 5 kDa to about 20 kDa.

51. The method of any one of claims 47-49, wherein the PEG component of the PEG-IL-10 agent has a molecular mass greater than about 20 kDa.

52. The method of any one of claims 47-49, wherein the PEG component of the PEG-IL-10 agent has a molecular mass of at least about 30 kD.

53. The method of claim 46, wherein the modified IL-10 agent is an Fc fusion molecule.

54. The method of claim 46, wherein the modified IL-10 agent comprises a serum albumin.

55. The method of claim 46, wherein the modified IL-10 agent is glycosylated.

56. The method of any one of claims 46-55, wherein the modification is site-specific.

57. The method of claim 46, wherein the modification comprises a linker.

58. The method of any one of claims 1-57, wherein the IL-10 agent is administered to the subject at least twice daily.

59. The method of any one of claims 1-57, wherein the IL-10 agent is administered to the subject at least once daily.

60. The method of any one of claims 1-57, wherein the IL-10 agent is administered to the subject at least every 72 hours.

61. The method of any one of claims 1-57, wherein the IL-10 agent is administered to the subject at least once weekly.

62. The method of any one of claims 1-57, wherein the IL-10 agent is administered to the subject at least every 2 weeks.

63. The method of any one of claims 1-57, wherein the IL-10 agent is administered to the subject at least once monthly.

64. The method of any one of claims 1-63, further comprising administering at least one additional prophylactic or therapeutic agent.

65. The method of any one of claims 1-64, wherein the subject is a human.

66. The method of any one of claims 1-65, wherein the administering is by parenteral injection.

67. The method of claim 66, wherein the parenteral injection is subcutaneous.

68. The method of any one of claims 1-67, wherein the treating or preventing is mediated by CD8+ T cells.

69. A pharmaceutical composition, comprising an amount of an IL-10 agent of any one of claims 1-56, and a pharmaceutically acceptable diluent, carrier or excipient.

70. The pharmaceutical composition of claim 69, wherein the excipient is an isotonic injection solution.

71. The pharmaceutical composition of claim 69, wherein the composition is suitable for human administration.

72. The pharmaceutical composition of any one of claims 69-71, further comprising at least one additional prophylactic or therapeutic agent.

73. A sterile container comprising the pharmaceutical composition of any one of claims 69-72.

74. The sterile container of claim 73, wherein the sterile container is a syringe.

75. A kit comprising the sterile container of claim 73 or claim 74.

76. The kit of claim 75, further comprising a second sterile container comprising at least one additional prophylactic or therapeutic agent.

9. A method of treating or preventing a disease, disorder or condition in a subject, comprising administering to the subject a therapeutically effective amount of an IL-10 agent, wherein the amount is sufficient to maintain a mean IL-10 serum trough concentration over a period of time;

wherein the mean IL-10 serum trough concentration is at least 6.0 ng/mL, and

wherein the mean IL-10 serum trough concentration is maintained for at least 90% of the period of time.

10. The method of claim 9, wherein the mean IL-10 serum trough concentration is at least 8.0 ng/mL.

11. The method of claim 9, wherein the mean IL-10 serum trough concentration is at least 10.0 ng/mL.

12. The method of claim 9, wherein the mean IL-10 serum trough concentration is at least 12.0 ng/mL.

13. The method of claim 9, wherein the mean IL-10 serum trough concentration is at least 14.0 ng/mL.

14. The method of claim 9, wherein the mean IL-10 serum trough concentration is at least 16.0 ng/mL.

15. The method of claim 9, wherein the mean IL-10 serum trough concentration is at least 18.0 ng/mL.

16. The method of claim 9, wherein the mean IL-10 serum trough concentration is at least 20.0 ng/mL.

17. The method of any one of claims 9-16, wherein the period of time is at least 12 hours.

18. The method of claim 17, wherein the period of time is at least 24 hours.

19. The method of claim 18, wherein the period of time is at least 48 hours.

20. The method of claim 19, wherein the period of time is at least 72 hours.

21. The method of claim 20, wherein the period of time is at least 1 week.

22. The method of claim 21, wherein the period of time is at least 2 weeks.

23. The method of claim 22, wherein the period of time is at least 1 month.

24. The method of any one of claims 9-23, wherein the mean IL-10 serum trough concentration is maintained for at least 95% of the period of time.

25. The method of claim 24, wherein the mean IL-10 serum trough concentration is maintained for at least 98% of the period of time.

26. The method of claim 25, wherein the mean IL-10 serum trough concentration is maintained for 100% of the period of time.

27. A method of treating or preventing a disease, disorder or condition in a subject, comprising administering to the subject a therapeutically effective amount of an IL-10 agent, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least the EC50 of the IL-10 agent.

28. The method of claim 27, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least the EC60 of the IL-10 agent.

29. The method of claim 27, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least the EC70 of the IL-10 agent.

30. The method of claim 27, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least the EC80 of the IL-10 agent.

31. The method of claim 27, wherein the amount is sufficient to achieve a mean IL-10 serum trough concentration of at least the EC90 of the IL-10 agent.