METHODS OF USING INTERLEUKIN-10 FOR TREATING DISEASES AND DISORDERS

• US 20190307849A1
• Filed: 05/26/2016
• Published: 10/10/2019
• Est. Priority Date: 05/29/2015
• Status: Abandoned Application

• Current Assignee: Armo BioSciences Inc. (Eli Lilly and Company)
• Original Assignee: Armo BioSciences Inc. (Eli Lilly and Company)
• Inventors: Oft, Martin
• Application Number:
  US15/576,239
• Publication Number:
  US 20190307849A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 38/2046 IL-7
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61K 38/385 Serum albumin
• CPC Class Codes: A61K 39/39541 against normal tissues, cells
• 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: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/5418 IL-7
• CPC Class Codes: C07K 14/5428 IL-10
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: G01N 2333/5418 IL-7
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/57496 involving intracellular compounds

Abstract

Methods of treating subjects having a cancer-related, immune-related, or viral-related disease, disorder or condition via administration of an IL-10 agent, including pegylated IL-10, and an IL-7 agent are provided, as are methods of identifying subjects that may be responsive to treatment with an IL-10 agent.

Claims

1. A method of treating or preventing a disease, disorder or condition in a subject, comprising administering to the subject:

a) a therapeutically effective amount of an IL-7 agent, and

b) a therapeutically effective amount of an IL-10 agent; and

wherein the disease disorder or condition is a cancer-related disease, disorder or condition;

an immune-related disease, disorder or condition;

or a viral-related disease, disorder or condition.

10. The method of claim 1, wherein the IL-10 agent is mature human IL-10.

11. The method of claim 1, 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.

12. The method of claim 1, wherein the disease, disorder or condition is a cancer-related disease, disorder or condition.

13. The method of claim 12, wherein the cancer-related disease, disorder or condition is a solid tumor or a hematological disorder.

14. The method of claim 12, wherein the cancer-related disease, disorder or condition is selected from the group consisting of melanoma, lung cancer, renal cancer colon cancer, head and neck cancer and breast cancer.

15. The method of claim 12, wherein the cancer-related disease, disorder or condition is leukemia or lymphoma.

16. The method of claim 1, wherein the disease, disorder or condition is an immune-related disease, disorder or condition.

17. The method of claim 1, wherein the disease, disorder or condition is a viral-related disease, disorder or condition.

18. The method of claim 1, 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.

19. The method of claim 18, wherein the modified IL-10 agent is a PEG-IL-10 agent.

20. The method of claim 19, 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.

21. The method of claim 19, wherein the PEG-IL-10 agent comprises a mixture of mono-pegylated and di-pegylated IL-10.

22. The method of claim 19, wherein the PEG component of the PEG-IL-10 agent has a molecular mass from about 5 kDa to about 20 kDa.

23. The method of claim 19, wherein the PEG component of the PEG-IL-10 agent has a molecular mass greater than about 20 kDa.

24. The method of claim 19, wherein the modification comprises a linker.

25. The method of claim 18, wherein the modified IL-10 agent is an Fc fusion molecule.

26. The method of claim 18, wherein the modified IL-10 agent comprises a serum albumin or an albumin binding domain (ABD).

27. The method of claim 18, wherein the modified IL-10 agent is glycosylated or hesylated.

28. The method of claim 19, wherein the modification is site-specific.

29. The method of claim 1, wherein the administering of the IL-7 agent and the IL-10 agent is by parenteral injection.

30. The method of claim 29, wherein the administering of the IL-10 agent is by subcutaneous injection.

31. The method of claim 1, wherein the IL-7 agent and the IL-10 agent are administered simultaneously.

32. The method of claim 1, wherein the IL-7 agent and the IL-10 agent are administered sequentially.

33. The method of claim 1, further comprising administering at least one additional prophylactic or therapeutic agent.

34. The method of claim 33, wherein the prophylactic or therapeutic agent is a chemotherapeutic agent.

35. The method of claim 1, wherein the subject is a human.

36. A pharmaceutical composition, comprising

a) a therapeutically effective amount of an IL-7 agent of claim 1, and a pharmaceutically acceptable diluent, carrier or excipient;

and

b) a therapeutically effective amount of an IL-10 agent of any onc of claims 1 35, and a pharmaceutically acceptable diluent, carrier or excipient.

37. The pharmaceutical composition of claim 36, wherein the excipient is an isotonic injection solution.

38. The pharmaceutical composition of claim 36 or 37, wherein the composition is suitable for human administration.

39. The pharmaceutical composition of claim 36, further comprising at least one additional prophylactic or therapeutic agent.

40. The pharmaceutical composition of claim 36, wherein the prophylactic or therapeutic agent is a chemotherapeutic agent.

89. The pharmaceutical composition of claim 36, wherein the IL-10 agent comprises a PEG-IL-10 agent.

90. The pharmaceutical composition of claim 89, wherein the IL-10 agent the PEG-IL-10 agent comprises a mixture of mono-pegylated and di-pegylated IL-10.

91. The method of claim 33, wherein the additional prophylactic or therapeutic agent is an immune checkpoint inhibitor.

92. The method of claim 91, wherein the immune checkpoint inhibitor is a monoclonal antibody.

93. The method of claim 92, wherein the monoclonal antibody is selected from the group consisting of anti-PD1 antibodies, anti-PDL1 antibodies, anti-LAG3 antibodies, anti-CTLA4 antibodies, anti-PDL1 antibodies, anti-IM3 antibodies.

94. The method of claim 93, wherein the anti-PD1 antibody is selected from the group consisting of nivolumab and lambrolizumab.

2. A method of treating or preventing a disease, disorder or condition in a subject, comprising administering to the subject:

a) a therapeutically effective amount of an IL-7 agent, and

b) 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 of at least one week; and

wherein the mean IL-10 serum trough concentration is at least 1.0 ng/mL,

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

wherein the disease disorder or condition is a cancer-related disease, disorder or condition;

an immune-related disease, disorder or condition;

or a viral-related disease, disorder or condition.

3. The method of claim 2, wherein the mean IL-10 serum trough concentration is at least 1.5 ng/mL.

4. The method of claim 3, wherein the mean IL-10 serum trough concentration is at least 2.0 ng/ml.

8. The method of claim 2, wherein the mean IL-10 serum trough concentration is maintained for at least 95% of the period of time.

9. The method of claim 8, wherein the mean IL-10 serum trough concentration is maintained for 100% of the period of time.

5-7. -7. (canceled)

41-88. -88. (canceled)