Gamma interferon formulation

• US 5,151,265 A
• Filed: 04/25/1990
• Issued: 09/29/1992
• Est. Priority Date: 11/03/1987
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Hwang-Felgner, Jiin-Yu, Jones, Richard E., Maher, James F.
• Primary Examiner(s): Wax, Robert A.
• Assistant Examiner(s): BAKER, R KEITH
• Application Number:
  US07/514,392
• Time in Patent Office: 888 Days
• Field of Search: 424/85.5, 530/351
• US Class Current: 424/85.5
• CPC Class Codes: A61K 38/217 IFN-gamma
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• 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

Abstract

A liquid pharmaceutical composition comprising an effective amount of non-lyophilized gamma-interferon. The liquid pharmaceutical composition which additionally includes a buffer capable of maintaining the pH of the liquid composition within the range of 4.0 to 6.0, a stabilizing agent and a non-ionic detergent.

Claims

1. A stable liquid pharmaceutical composition consisting essentially of an effective amount of gamma-interferon not subjected to prior lyophilization, a buffer maintaining the pH within the range of 4.0 to 6.0, a stabilizing agent, a non-ionic detergent and water, in which said gamma-interferon essentially retains its physical stability and biological activity during storage at a temperature of between about 2°

and about 8°

C. for a period of at least 14 months.

2. The liquid pharmaceutical composition of claim 1 wherein the buffer is an organic acid buffer.

3. The liquid pharmaceutical composition of claim 2 wherein the organic acid buffer is selected from the group consisting of citrate, succinate, tartrate, fumarate, gluconate, oxalate, lactate and acetate.

4. The liquid pharmaceutical composition of claim 1 wherein the stabilizing agent is a polyhydric sugar alcohol.

5. The liquid pharmaceutical composition of claim 4 wherein the polyhydric sugar alcohol is selected from the group consisting of glycerin, erythritol, arabitol, xylitol, sorbitol and mannitol.

6. The liquid pharmaceutical composition of claim 5 wherein the sugar alcohol is added in an amount of about 1% to 25% by weight based on the composition.

7. The liquid pharmaceutical composition of claim 5 wherein the sugar alcohol is added in an amount of about 2% to 5% by weight based on the composition.

8. The liquid pharmaceutical composition of claim 1 wherein the non-ionic detergent is selected from the group consisting of polysorbate 20 and polysorbate 80.

9. The liquid pharmaceutical composition of claim 1 wherein the pH of the liquid composition is in the range of 4.5 to 5.5.

10. The liquid pharmaceutical composition of claim 1 wherein the pH of the liquid composition is at a pH of 5.0.

11. The liquid pharmaceutical composition of claim 1 which is sterile.

12. The liquid pharmaceutical composition of claim 1 which is isotonic to blood.

13. The liquid pharmaceutical composition of claim 1 wherein the gamma-interferon is human recombinant gamma-interferon.

14. The liquid pharmaceutical composition of claim 13 wherein the activity of the human recombinant gamma-interferon is in the range of 1×

10⁶ to 2×

10⁷ U/mg protein.

15. The liquid pharmaceutical composition of claim 14 wherein comprising a succinate buffer, and mannitol as a stabilizing agent.

16. The liquid pharmaceutical composition of claim 13 comprising 0.2 mg/ml human recombinant gamma-interferon.

17. A process for stabilizing gamma-interferon in liquid pharmaceutical compositions so that it essentially retains its physical stability and biological activity during storage at a temperature of between about 2°

and about 8°

C. for a period of at least 14 months, consisting essentially of admixing an effective amount of previously not lyophilized gamma-interferon with a buffer maintaining the pH within the range of 4.0 to 6.0, a stabilizing agent, a non-ionic detergent and water.