Stabilization and storage of biological pharmaceutical compositions

Patent metadata

Field	Value
Publication number	US-9289381-B2
Application number	US-201013392784-A
Country	US
Kind code	B2
Filing date	Dec 3, 2010
Priority date	Dec 3, 2009
Publication date	Mar 22, 2016
Grant date	Mar 22, 2016

Abstract

The present invention relates to compositions and methods for the preparation, stabilization, and/or storage of active agents, particularly therapeutic proteins and polypeptides such as Interleukin-2.

First claim

That which is claimed is:

1. A parenterally injectable pharmaceutical composition comprising:
(a) from 0.01 to 40 weight percent choline dihydrogen phosphate;
(b) an added base included in an amount not greater than 40 weight percent, wherein said added base is choline hydroxide;
(c) at least 60 weight percent water; and
(d) from 0.01 to 10 weight percent active compound selected from the group consisting of Interleukin-2, gelsolin, antibodies, erythropoietin, interferon, human growth hormone, follicle stimulating hormone, and granulocyte colony stimulating factor;
said composition having a pH of from 6 up to 8;
said composition packaged in a sterile container.

2. The composition of claim 1 , wherein said active compound is included in an amount of not more than 5 weight percent.

3. The composition of claim 1 , wherein said water is included in an amount up to 99 weight percent.

4. The composition of claim 1 , wherein said choline dihydrogen phosphate is included in an amount of not more than 40 weight percent.

5. The composition of claim 1 , wherein said base and said choline dihydrogen phosphate are included together in a combined amount not more than 50 weight percent.

6. The composition of claim 1 , wherein said composition is a single phase liquid solution.

7. The composition of claim 1 , wherein said composition has an osmolality of 100 to 3,000 milliOsmoles per kilogram of water.

8. The composition of claim 1 , wherein said active compound is Interleukin-2.

9. The composition of claim 8 , wherein said Interleukin-2 is human Interleukin-2.

10. The composition of claim 8 , wherein said Interleukin-2 is aldesleukin.

11. The composition of claim 1 , wherein said active compound is gelsolin.

12. The composition of claim 11 , wherein said gelsolin is human gelsolin.

13. The composition of claim 1 , wherein said active compound is recombinant.

14. The composition of claim 1 , wherein said active compound is non-glycosylated.

15. The composition of claim 1 having a shelf life of from 2 days to 2 years at 37° C.

16. The composition of claim 1 , wherein said active compound is Interleukin-2 and said composition has a shelf life of 2 days to 2 months at 37° C.

17. A method comprising administering a composition of claim 1 to a subject in need thereof.

18. The composition of claim 1 , wherein:
said active compound is included in an amount of not more than 5 weight percent;
said water is included in an amount up to 99 weight percent;
said choline dihydrogen phosphate is included in an amount of not more than 40 weight percent;
said base and said choline dihydrogen phosphate are included together in a combined amount not more than 50 weight percent;
said composition is a single phase liquid solution;
said composition has an osmolality of 100 to 3,000 milliOsmoles per kilogram of water; and
said active agent is Interleukin-2.

19. The composition of claim 1 having a shelf life of from 2 weeks to 2 years at 37° C.

20. The composition of claim 1 having a shelf life of at least 2 weeks at 37° C.

21. The composition of claim 1 having a shelf life of at least 1 month at 37° C.

22. The composition of claim 1 having a shelf life of at least 1 year at 37° C.

23. The composition of claim 1 , further comprising from 0.01 to 50 weight percent of at least one osmolyte.

Assignees

• Elliott Gloria
• Macfarlane Douglas
• Foureau David M
• Mckillop Iain
• Univ North Carolina
• Charlotte Mecklenburg Hospital
• Univ Monash

Inventors

• Elliott Gloria
• Macfarlane Douglas
• Foureau David M
• Mckillop Iain

Classifications

• A61K38/2013

  IL-2 · CPC title

• A61K38/47

  acting on glycosyl compounds (3.2), e.g. cellulases, lactases · CPC title

• A61K47/24

  containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids · CPC title

• A61K9/0019 Primary

  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 title