Claims for Patent: 10,258,689

Summary for Patent: 10,258,689

Title:	Stable liquid formulation of etanercept
Abstract:	The present invention relates to a stable liquid formulation of etanercept (recombinant p75 sTNFR:Fc fusion protein), and more particularly, to a liquid formulation comprising one or more stabilizers selected from the group consisting of methionine, lysine, histidine, and pharmaceutically acceptable salts thereof in an amount sufficient to reduce by-product formation of etanercept during storage. The liquid formulation according to the present invention effectively reduces production of etanercept by-products and to stably maintain its pharmaceutical efficacies for long-term storage. Therefore, the reconstitution procedure is not required before administration, and the sterile formulation can be administered to patients to ensure patient safety. Thus, it can be applied to the fields in need of etanercept treatment.
Inventor(s):	Choi; Suk Young (Daejeon, KR), Ko; Youn Kyung (Daejeon, KR), So; Jin Eon (Daejeon, KR)
Assignee:	LG CHEM, LTD. (Seoul, KR)
Application Number:	14/123,704
Patent Claims:	1. A liquid formulation of etanercept, consisting of 1 to 100 mg/mL of etanercept, 0.1 to 250 mM of methionine or pharmaceutically acceptable salts thereof as a stabilizer, 0.1 to 100 mM of phosphate buffer, and 1 to 1000 mM of sodium chloride; wherein the liquid formulation has an increased storage stability of etanercept compared to the formulation comprising arginine as a stabilizer, by reducing etanercept by products that are produced due to denaturation during storage. 2. A liquid formulation of etanercept, consisting of 1 to 100 mg/mL of etanercept, 0.1 to 250 mM of histidine or pharmaceutically acceptable salts thereof and 0.1 to 250 mM of methionine or pharmaceutically acceptable salts thereof as stabilizers, 0.1 to 100 mM of phosphate buffer, and 1 to 1000 mM of sodium chloride; wherein the liquid formulation has an increased storage stability of etanercept compared to the formulation comprising arginine as a stabilizer, by reducing etanercept by products that are produced due to denaturation during storage. 3. A liquid formulation of etanercept, consisting of 1 to 100 mg/mL of etanercept, 0.1 to 250 mM of methionine or pharmaceutically acceptable salts thereof and 0.1 to 250 mM of lysine or pharmaceutically acceptable salts thereof as stabilizers, 0.1 to 100 mM of phosphate buffer, and 1 to 1000 mM of sodium chloride; wherein the liquid formulation has an increased storage stability of etanercept compared to the formulation comprising arginine as a stabilizer, by reducing etanercept by products that are produced due to denaturation during storage.

Details for Patent 10,258,689

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2031-06-03
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2031-06-03
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2031-06-03