Methods of treating cancer metastasis by using interleukin-10

• US 10,653,751 B2
• Filed: 10/23/2018
• Issued: 05/19/2020
• Est. Priority Date: 10/22/2014
• Status: Active Grant

• Current Assignee: Armo BioSciences Inc. (Eli Lilly and Company)
• Original Assignee: Armo BioSciences Inc. (Eli Lilly and Company)
• Inventors: Oft, Martin
• Primary Examiner(s): Stoica, Elly-Gerald
• Application Number:
  US16/168,345
• Publication Number:
  US 20190046613A1
• Time in Patent Office: 574 Days
• Field of Search: None
• 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 metastasis or inhibiting metastasis of a primary tumor in a human subject, the method comprising administering to the subject a therapeutically effective amount of an IL-10 agent, wherein the amount of IL-10 agent administered daily is in a range of about 20 μ

g/kg to about 40 μ

g/kg wherein the administering is effective to treat metastasis or inhibit metastasis of the primary tumor in the subject, and wherein the primary tumor is a cancer selected from the group consisting of pancreatic cancer, colon cancer, kidney cancer, breast cancer, lung cancer, prostate cancer and melanoma.

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

3. The method of claim 1, wherein the IL-10 agent is a variant of human IL-10, and wherein the variant exhibits activity comparable to the activity of human IL-10.

4. The method of claim 1, wherein the IL-10 agent is a PEG-IL-10 agent.

5. The method of claim 4, 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.

6. The method of claim 4, wherein the PEG component of the PEG-IL-10 agent has a molecular mass from about 5 kDa and about 50 kDa.

7. The method of claim 6, wherein the PEG component of the PEG-IL-10 agent has a molecular mass from about 10 kDa to about 30 kDa.

8. The method of claim 6, wherein the PEG component of the PEG-IL-10 agent has a molecular mass from about 5 kDa to about 20 kDa.

9. The method of claim 6, wherein the PEG-IL-10 agent comprises a mixture of mono-pegylated and di-pegylated IL-10.

10. The method of claim 9, wherein the PEG component of the PEG-IL-10 has a molecular mass of about 5 kDa.

11. The method of claim 9, wherein the PEG component of the PEG-IL-10 agent has a molecular mass of about 20 kDa.

12. The method of claim 11, wherein the PEG is a branched PEG.

13. The method of claim 11, wherein the PEG is a linear PEG.

14. The method of claim 9, wherein the PEG component of the PEG-IL-10 agent has a molecular mass of about 40 kDa.

15. The method of claim 14, wherein the PEG is a branched PEG.

16. The method of claim 5, wherein the covalent attachment of the PEG to at least one amino acid residue of at least one subunit of IL-10 comprises a linker.

17. The method of claim 1, wherein the IL-10 agent is administered subcutaneously to the subject.

18. The method of claim 1, wherein the method results in an improvement in Immune-Related Response Criteria (irRC) in the subject.

19. The method of claim 1, wherein the method further comprises administering a therapeutically effective amount of one or more chemotherapeutic agents.

20. The method of claim 19, wherein the one or more chemotherapeutic agents is selected from the group consisting of platinum coordination complexes, folic acid analogs and purine analogs.

21. The method of claim 20, wherein the folic acid analog is folinic acid and the purine analog is 5-FU.

22. The method of claim 20, wherein the method results in an improvement in Immune-Related Response Criteria (irRC) in the subject.

23. The method of claim 1, wherein the method comprises further comprises administering a therapeutically effective amount of one or more monoclonal antibodies against a tumor antigen.

24. The method of claim 1, wherein the administering reduces the frequency or size of metastatic lesions of the primary tumor in the subject.