Claims for Patent: 9,943,601

Summary for Patent: 9,943,601

Title:	Etanercept formulations stabilized with combinations of sugars and polyols
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.
Inventor(s):	Manning; Mark (Johnstown, CO), Murphy; Brian (Fort Collins, CO)
Assignee:	Coherus Biosciences, Inc. (Redwood City, CA)
Application Number:	15/078,755
Patent Claims:	1. A stable aqueous pharmaceutical composition comprising about 25 to about 75 mg/ml of etanercept; about 1 to about 10 wt. % sucrose, trehalose or dextrose; up to 10 wt. % mannitol or sorbitol; and about 1 mM to about 30 mM sodium phosphate; wherein said composition is free or essentially free of arginine; has a pH of about 6.0 to 6.6; and is characterized by SEC analysis at M.sub.3 or T.sub.2 or T.sub.4 in which: the monomer content is greater than about 80 wt. %; aggregates content is less than about 3 wt. %, and fragment 3 content less than about 10 wt. %. 2. A stable aqueous pharmaceutical composition comprising about 25 to about 75 mg/ml of etanercept; about 1 to about 10 wt. % sucrose, trehalose or dextrose; up to about 10 wt. % mannitol or sorbitol; and about 1 mM to about 30 mM sodium phosphate; wherein said composition is free or essentially free of arginine; has a pH of about 6.0 to 6.6; and is characterized by HIC analysis at M.sub.3 or T.sub.2 or T.sub.4 wherein the amount of the composition represented by peak 1 of the HIC chromatogram is less than about 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 about 20 wt. %. 3. The composition of claim 2 having an HIC analysis at M.sub.3 or T.sub.2 or T.sub.4 wherein the amount of the composition represented by peak 1 of the HIC chromatogram is less than about 1 wt. %; the amount of the composition represented by peak 2 of the HIC chromatogram is greater than about 95 wt. %; and the amount of the composition represented by peak 3 of the HIC chromatogram is less than about 3 wt. %. 4. The composition of claim 2 comprising: about 50 mg/ml of etanercept; about 1 to 5 wt. % sucrose, trehalose or dextrose; about 1-2 wt. % mannitol or sorbitol, about 10-30 mM sodium phosphate, said composition having pH of about 6.3 to 6.5. 5. The composition of claim 2 eliciting long term storage stability as characterized by: an HIC analysis at M.sub.3 or T.sub.2 or T.sub.4 wherein the amount of the composition represented by peak 2 of the HIC chromatogram is greater than or equal to about 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 about 3 wt. %. 6. The composition of claim 2 having, at M.sub.3 or T.sub.2 or T.sub.4 no more than, on average, about 10,000 subvisible particles per mL having a size greater than 5 .mu.m. 7. The composition of claim 1 comprising about 50 mg/ml of etanercept; about 1 to 5 wt. % sucrose, trehalose or dextrose; about 1-2 wt. % mannitol or sorbitol, about 10-30 mM sodium phosphate, said composition having pH of about 6.3 to 6.5. 8. The composition of claim 1 having, at M3 or T2 or T4 no more than, on average, about 10,000 subvisible particles per mL having a size greater than 5 .mu.m.

Details for Patent 9,943,601

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2039-02-26
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2039-02-26
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2039-02-26