Etanercept formulations stabilized with amino acids

Patent metadata

Field	Value
Publication number	US-10293049-B2
Application number	US-201213654735-A
Country	US
Kind code	B2
Filing date	Oct 18, 2012
Priority date	Oct 18, 2011
Publication date	May 21, 2019
Grant date	May 21, 2019

Abstract

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

First claim

What is claimed is:

1. A stable aqueous pharmaceutical composition comprising about 50 mg/ml etanercept, and 100-120 mM glutamate, wherein the composition has a pH of about 6.0 to 6.6, and wherein the composition is free or essentially free of arginine.

2. The composition of claim 1 , further comprising one or more additional components selected from: a buffer; a tonicity modifier, and an excipient.

3. The composition of claim 2 wherein the formulation comprises less than 6 wt. % sucrose; optionally up to about 100 mM NaCl; and about 1 to about 30 mM sodium phosphate buffer.

4. The composition of claim 1 eliciting long term storage stability as characterized by: an HIC analysis at M 3 or T 2 or T 4 wherein the amount of the composition represented by peak 2 of the HIC chromatogram is greater than or equal to 95 wt. %; and wherein, if peak 3 is present on the HIC chromatogram, the amount of the composition represented by peak 3 is less than or equal to 3 wt. %.

5. The composition of claim 1 having no more than, on average, about 10,000 subvisible particles per mL having a size greater than 5 μm.

6. The composition of claim 1 further comprising about 0 to 3 wt. % sucrose.

7. The composition of claim 1 further comprising less than 4 wt. % sucrose, and about 10 to 30 mM sodium phosphate buffer; and having a pH of about 6.3 to 6.5.

8. The composition of claim 1 further comprising 100 mM glutamate; less than 2 wt. % sucrose, about 100 mM NaCl; about 10-30 mM sodium phosphate buffer; and having a pH of about 6.3 to 6.5.

9. The composition of claim 1 , wherein the composition elicits long term storage stability as characterized by an HIC chromatogram, at M 3 or T 2 or T 4 , in which (i) peak 3 is absent, or essentially absent and (ii) peak 2 represents greater than 95 weight % of the composition; and peak 1 represents less than 3 wt. %.

10. The composition of claim 1 , wherein the composition elicits long term storage stability as characterized by an SEC chromatogram, at M 3 or T 2 or T 4 , containing essentially no peak corresponding to aggregate(s) and a monomer content of at least 95 wt % of the composition and fragment 3 content less than 5 wt. % of the composition.

11. The composition of claim 1 , wherein the composition elicits long term storage stability as characterized by SEC analysis at M 3 or T 2 or T 4 of: monomer content greater than 90%; aggregates content of less than 3 wt %; and fragment 3 content less than 5 wt %.

12. The composition of claim 1 , wherein the composition elicits long term storage stability as characterized by HIC analysis at M 3 or T 2 or T 4 , 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. %.

13. The composition of claim 6 , having no more than, on average, about 10,000 subvisible particles per mL having a size greater than 5 μm.

14. The composition of claim 7 , having no more than, on average, about 10,000 subvisible particles per mL having a size greater than 5 μm.

15. The composition of claim 8 , having no more than, on average, about 10,000 subvisible particles per mL having a size greater than 5 μm.

Assignees

• Coherus Biosciences Inc

Inventors

• Manning Mark
• Murphy Brian

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P37/02

  Immunomodulators · CPC title