Stable liquid interferon beta formulations

• US 9,522,174 B2
• Filed: 12/09/2014
• Issued: 12/20/2016
• Est. Priority Date: 12/24/1996
• Status: Expired due to Fees

• Current Assignee: Biogen MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen MA Inc. (Biogen, Inc.)
• Inventors: DiBiase, Mary D., Chung, Wen-Li, Staples, Mark, Scharin, Eric
• Primary Examiner(s): Landsman, Robert
• Assistant Examiner(s): Hissong, Bruce D
• Application Number:
  US14/564,637
• Publication Number:
  US 20150093359A1
• Time in Patent Office: 742 Days
• US Class Current: 1/1
• 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 for preparing an interferon-beta formulation, comprising the step of mixing a liquid composition comprising interferon-beta with a sterile diluent, wherein the liquid composition further comprises a stabilizing agent at between about 0.3% and 5% by weight, wherein the liquid composition has not been previously lyophilized, wherein the formulation does not comprise serum albumin, and wherein the stabilizing agent is either arginine or glycine.

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

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

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

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

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

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

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

9. The method of claim 8, wherein the acetate or acetate salt is present at 20 mM.

10. The method of claim 1, wherein the formulation further comprises a surfactant.

11. The method of claim 1, wherein the liquid formulation has a dissolved oxygen level that is less than 30% of atmospheric equilibrium levels.

12. The method of claim 11, wherein the liquid formulation has a dissolved oxygen level that is less than or equal to 10% of atmospheric equilibrium levels.

13. The method of claim 1, wherein the diluent is a buffer having a pH of between about 4.0 and 7.2.

14. The method of claim 1 or 13, wherein the method further comprises the step of filter sterilizing the formulation.

15. The method of claim 1 or 13, wherein the method further comprises the step of transferring the formulation to a sterile syringe.