STABLE LIQUID INTERFERON FORMULATIONS

• US 20100239531A1
• Filed: 06/04/2010
• Published: 09/23/2010
• Est. Priority Date: 12/24/1996
• Status: Active Grant

• Current Assignee: Biogen MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen Idec MA Inc. (Biogen, Inc.)
• Inventors: Chung, Wen-Li, DiBiase, Mary D., Staples, Mark, Scharin, Eric
• Granted Patent: US 8,512,692 B2
• Time in Patent Office: Days
• US Class Current: 424/85.600
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 38/215 IFN-beta
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• 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: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/565 IFN-beta

Abstract

Liquid interferon compositions having a pH between 4.0 and 7.2 are described. The compositions comprise interferon-beta and a stabilizing agent at between about 0.3% and 5% by weight which is an amino acid selected from the group consisting of acidic amino acids, arginine and glycine. If needed, salt is added to provide sufficient ionic strength. The liquid composition has not been previously lyophilized or previously cavitated. The liquid is preferably contained within a vessel having at least one surface in contract with the liquid that is coated with a material inert to adsorption of interferon-beta. A kit for parenteral administration of a liquid interferon formulation and a method for stabilizing liquid interferon compositions are also described.

Claims

1. A method of treating multiple sclerosis in a patient, comprising administering to said patient a liquid composition, wherein said liquid composition comprises:

(i) an interferon-beta and (ii) between about 0.3% and 5% by weight of an amino acid selected from the group consisting of acidic amino acids, arginine and glycine, wherein the composition does not comprise serum albumin and;

wherein the liquid composition has not been previously lyophilized.

44. The method of claim 1, wherein the multiple sclerosis is relapsing multiple sclerosis.

45. The method of claim 1, wherein the composition has a pH of between about 4.0 and 7.2.

46. The method of claim 1, wherein the composition has a pH of between about 4.0 and 5.0.

47. The method of claim 1, wherein the composition has a pH of between about 4.5 and 5.5.

48. The method of claim 1, wherein the composition has a pH of between about 4.8 and 5.2.

49. The method of claim 1, wherein the arginine is arginine-HCl.

50. The method of claim 1, wherein the interferon-beta is present at between 6 MIU/ml and 50 MIU/ml.

51. The method of claim 1, wherein the composition further comprises a solution of weak acid comprising acetate and acetate salt.

52. The method of claim 51, wherein the acetate buffer is present at 20 mM.

53. The method of claim 1, further comprising a surfactant.

54. The method of claim 53, wherein the surfactant is 0.1% (w/v) PLURONIC F-68.

55. The method of claim 1, wherein said liquid composition has a dissolved oxygen level that is less than 30% of atmospheric equilibrium levels.

56. The method of claim 55, wherein said liquid composition has a dissolved oxygen level that is less than or equal to 10% of atmospheric equilibrium levels.

2-43. -43. (canceled)