Stable liquid formulation of etanercept

Patent metadata

Field	Value
Publication number	US-10258689-B2
Application number	US-201214123704-A
Country	US
Kind code	B2
Filing date	Jun 1, 2012
Priority date	Jun 3, 2011
Publication date	Apr 16, 2019
Grant date	Apr 16, 2019

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.

First claim

What is claimed is:

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.

Assignees

• Choi Suk Young
• Ko Youn Kyung
• So Jin Eon
• Lg Chemical Ltd

Inventors

• Choi Suk Young
• Ko Youn Kyung
• So Jin Eon

Classifications

• A61P43/00

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

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title