Etanercept formulations stabilized with sodium chloride

• US 10,493,151 B2
• Filed: 10/18/2012
• Issued: 12/03/2019
• Est. Priority Date: 10/18/2011
• Status: Expired due to Fees

• Current Assignee: Coherus BioSciences Inc.
• Original Assignee: Coherus BioSciences Inc.
• Inventors: Manning, Mark, Murphy, Brian
• Primary Examiner(s): Ford, Vanessa L.
• Assistant Examiner(s): Dillahunt, Sandra E
• Application Number:
  US13/654,795
• Publication Number:
  US 20130101583A1
• Time in Patent Office: 2,602 Days
• Field of Search: None
• CPC Class Codes: A61K 38/1793 for cytokines; for lymphokines; for interferons
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The invention provides stabilized aqueous pharmaceutical etanercept compositions suitable for long-term storage of etanercept, methods of manufacture of these compositions, methods of administration, and kits containing same.

Claims

1. A stable aqueous etanercept formulation comprising 25 to 75 mg/ml of etanercept, up to 150 mM sodium chloride, 1 to 30 mM sodium phosphate, and 3 to 5 wt. % sucrose, wherein the formulation is free of arginine.

2. The formulation of claim 1 wherein the formulation elicits long term storage stability as characterized by at least one of:

SEC analysis at M3 or T2 or T4 of;

monomer content greater than 90%;

aggregates content of less than 3 wt. %; and

fragment 3 content less than 5 wt. %.

3. The aqueous etanercept formulation of claim 1, wherein the amount of sodium phosphate is 25 mM.

4. The formulation of claim 3 wherein etanercept is at a concentration of 50 mg/ml and sodium chloride is at a concentration of 75 mM.

5. The formulation of claim 1 wherein sodium phosphate is at a concentration of 10 mM.

8. The formulation of claim 1 wherein the formulation elicits long term storage stability as characterized by at least one of:

HIC analysis at M3 or T2 or T4 wherein the amount of the composition represented by peak 1 of the HIC chromatogram is less than 3 wt. %;

the amount of the composition represented by peak 2 of the HIC chromatogram is greater than 80 wt. %; and

the amount of the composition represented by peak 3 of the HIC chromatogram is less than 20 wt. %.

9. The formulation of claim 1 wherein the formulation, at M3 or T2 or T4, elicits long term storage stability that meets the following criteria:

(A) an SEC analysis of;

monomer content greater than 90%;

aggregates content of less than 3 wt. %; and

fragment 3 content less than 5 wt. %; and

(B) an HIC analysis wherein the amount of the composition represented by peak 1 of the HIC chromatogram is less than 3 wt. %;

the amount of the composition represented by peak 2 of the HIC chromatogram is greater than 80 wt. %; and

the amount of the composition represented by peak 3 of the HIC chromatogram is less than 20 wt. %.

10. The formulation of claim 1, wherein the formulation has a pH of 6.0 to 6.6.

6. A stable aqueous etanercept formulation comprising 25 to 75 mg/ml of etanercept, up to 150 mM sodium chloride, 10 to 25 mM sodium phosphate, and 3 to 5 wt. % trehalose, wherein the formulation is free of arginine.

7. The formulation of claim 6 wherein etanercept is at a concentration of 50 mg/ml, sodium chloride is at a concentration of 75 mM and sodium phosphate is at a concentration of 25 mM.

11. The formulation of claim 6, wherein the formulation has a pH of 6.0 to 6.6.