Pegylated interleukin-10

• US 10,471,126 B2
• Filed: 02/06/2018
• Issued: 11/12/2019
• Est. Priority Date: 09/29/2000
• Status: Expired due to Term

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Merck Sharp & Dohme Limited (Merck & Co., Inc.)
• Inventors: Lee, Seoju, Wylie, David C., Cannon-Carlson, Susan V.
• Primary Examiner(s): Bunner, Bridget E
• Assistant Examiner(s): Hamud, Fozia
• Application Number:
  US15/889,953
• Publication Number:
  US 20180250363A1
• Time in Patent Office: 644 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: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07K 14/5428 IL-10
• CPC Class Codes: C07K 2319/31 fusions, other than Fc, for prolonged plasma life, e.g. albumin
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Interleukin-10 (IL-10) conjugated via a linker to one or more polyethylene glycol (PEG) molecules at a single amino acid residue of the IL-10, and a method for preparing the same, are provided. The method produces a stable mono-pegylated IL-10, which retains IL-10 activity, where pegylation is selective for the N-terminus on one subunit of IL-10 with little or no formation of monomeric IL-10. The method also provides a substantially homogenous population of mono-PEG-IL-10.

Claims

1. A method of treating an inflammatory disease in a human subject comprising administering to said human subject a therapeutically effective amount of pharmaceutical composition comprising a monopegylated PEG-IL10 (mono-PEG-IL-10), the mono-PEG-IL-10 comprising one or more polyethylene glycol (PEG) molecules covalently attached via a linker to the alpha amino group of the N-terminal amino acid residue of a single subunit of IL-10, and a pharmaceutically acceptable carrier.

2. The method of claim 1, wherein the inflammatory disease is selected from the group consisting of autoimmune diseases, organ and bone marrow transplant rejection, graft-versus-host disease, parasitic infections, granulomas, Crohn'"'"'s disease, colitis, pancreatitis, inflammatory lung disease, inflammatory eye diseases, allergic conditions, asthma, atopic dermatitis, and rhinitis.

3. The method of claim 1, wherein the IL-10 is human IL-10 (hIL10).

4. The method of claim 3, wherein the hIL10 is recombinant hIL-10.

5. The method of claim 3, wherein the therapeutically effective amount is from about 0.1 to about 20 μ

g protein per kg of body weight per day.

6. The method of claim 3, wherein the therapeutically effective amount is from about 0.5 to about 10 μ

g protein per kg of body weight per day.

7. The method of claim 1, wherein the pharmaceutical composition is administered by injection.

8. The method of claim 7, wherein the injection is subcutaneous.

9. The method of claim 7, wherein the injection is intradermal.

10. The method of claim 7, wherein the injection is intravenous.

11. The method of claim 1, wherein the pharmaceutically acceptable carrier is an aqueous carrier selected from the group consisting of normal saline, Ringer'"'"'s solution, dextrose solution, and Hank'"'"'s solution.

12. The method of claim 11 wherein the pharmaceutical composition comprises one or more additives selected from the group consisting of stabilizers, isotonicity agents, buffers and preservatives.

13. The mono-PEG-IL-10 according to claim 1, wherein the one or more PEG molecules has a combined molecular mass of from about 1,000 daltons to 100,000 daltons.

14. The mono-PEG-IL-10 according to claim 1, wherein the combined molecular mass of the one or more PEG molecules is from about 10,000 daltons to 36,000 daltons.

15. The mono-PEG-IL-10 according to claim 1, wherein the one or more PEG molecules is a single PEG molecule having a molecular mass of about 5,000 daltons.