Methods of using pegylated interleukin-10 for treating hyperlipidemia

• US 10,010,588 B2
• Filed: 08/26/2014
• Issued: 07/03/2018
• Est. Priority Date: 08/30/2013
• Status: Active Grant

• Current Assignee: Armo BioSciences Inc.
• Original Assignee: Armo BioSciences Inc.
• Inventors: Mumm, John Brian, Chan, Ivan Ho
• Primary Examiner(s): Stoica, Elly-Gerald
• Application Number:
  US14/908,992
• Publication Number:
  US 20160193300A1
• Time in Patent Office: 1,407 Days
• Field of Search: None
• 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 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• 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
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

Methods of treating subjects having diseases, disorders, or conditions, including disorders associated with cholesterol homeostasis, responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided, More particularly, the present disclosure relates to optimized dosing parameters to achieve and maintain efficacy in the treatment and/or prevention of metabolic diseases, disorders and conditions in a subject, while minimizing the adverse effects associated therewith. Particular embodiments are directed to the treatment and/or prevention of abnormally high levels of cholesterol and/or manifestation(s) of hypercholesterolemia in as subject.

Claims

1. A method of treating hyperlipidemia in a subject suffering therefrom, said method comprising administering to the subject a therapeutically effective amount of a PEG-IL-10 agent, wherein the amount is sufficient to maintain an IL-10 serum trough concentration of 1.0 pg/mL to 10.0 ng/mL over a period of time of at least 24 hours.

2. The method of claim 1, wherein the IL-10 serum trough concentration is in the range of from 1.0 pg/mL to 1.0 ng/mL.

3. The method of claim 1, wherein the PEG-IL-10 agent comprises mature human IL-10.

4. The method of claim 1, wherein the PEG-IL-10 agent comprises a variant of mature human IL-10, and wherein the variant exhibits activity comparable to the activity of mature human IL-10.

5. The method of claim 1, wherein the disease is hypercholesterolemia.

6. The method of claim 1, 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 mature human IL-10.

7. The method of claim 1, wherein the PEG-IL-10 agent comprises a mixture of mono-pegylated and di-pegylated IL-10.

8. The method of claim 1, 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 1, wherein the PEG component of the PEG-IL-10 agent has a molecular mass greater than about 20 kDa.

10. The method of claim 6, wherein at least one PEG molecule is covalently attached to the at least one IL-10 subunit via a linker.

11. The method of claim 1, wherein the PEG-IL-10 agent is administered to the subject at least once daily.

12. The method of claim 1, wherein the method comprises administering at least one additional prophylactic or therapeutic agent.

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

14. The method of claim 1, wherein the administering is by parenteral injection.

15. The method of claim 14, wherein the parenteral injection is subcutaneous.