Etanercept Formulations Stabilized with Sodium Chloride

a technology of sodium chloride and etanercept, which is applied in the field of aqueous pharmaceutical compositions stabilized with sodium chloride, can solve the problems of unstable polypeptides in solution, inactive polypeptides, and less convenient use of lyophilized pharmaceutical compositions, so as to reduce instability and reduce aggregation and/or fragmentation

Inactive Publication Date: 2019-11-07
COHERUS BIOSCI
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about a new way to make etanercept, which is a drug used to treat rheumatoid arthritis and other autoimmune diseases. The new way involves making a drug that is stabilized to prevent it from breaking down and becoming less effective over time. The stabilizers used in the new formulation of etanercept include sodium chloride and sucrose or trehalose, which help keep the etanercept stable and safe for storage. The new formulation also results in reduced formation of harmful particles and does not require the use of another substance called arginine, which can increase the cost of the drug. Overall, this new formulation of etanercept is more stable and safer than currently available versions, and it can potentially save money for patients and healthcare providers.

Problems solved by technology

When stored for extended periods, polypeptides are frequently unstable in solution (Manning et al., 1989, Pharm. Res. 6:903-918).
However, lyophilized pharmaceutical compositions are less convenient to use.
However, the use of additives can still result in inactive polypeptides.
Aggregation of polypeptides is undesirable, as it may result in immunogenicity (Cleland et al., 1993, Crit. Rev. Therapeutic Drug Carrier Systems, 10:307-377; and Robbins et al., 1987, Diabetes, 36:838-845).

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

example

Etanercept Stabilized with NaCl

[0108]Etanercept formulations stabilized with NaCl, alone, or NaCl in combination with sucrose, trehalose and / or arginine, may be prepared and tested using the procedures generally described below.

[0109]Each solid formulation component is weighed to the amount required for a given volume of formulation buffer. These components are combined into a beaker or vessel capable of carrying and measuring the given volume of formulation buffer. A volume of deionized water equal to approximately ¾ of the target given formulation buffer is added to the beaker, and the components are then solublized. The pH of the buffer is adjusted to the target formulation pH using 1 M sodium hydroxide and / or 1 M hydrogen chloride. The final formulation buffer volume is then raised to the target volume through the addition of deionized water. Etanercept protein solution is placed in dialysis material housing (such as Thermo Scientific Slide-A-Lyzer® MINI Dialysis Unit 10,000 MWC...

example 2

Preparation of Etanercept

[0113]Step 1. Cell Expansion.

[0114]In a manner known in the art, cell expansion necessary to generate a sufficient number of cells for inoculation of a production bioreactor is performed using a clone of CHO cells expressing the etanercept fusion protein. The product of this expression process (a harvested cell culture fluid) results in a mixture of correctly folded etanercept, as well as incorrectly folded and / or aggregated etanercept, along with additional impurities. The harvested cell culture fluid comprising such protein mixture is subjected to detergent viral inactivation.

[0115]Step 2. Affinity Chromatography.

[0116]Affinity chromatography is performed on the harvested cell culture obtain in Step 1 above using a conventional Protein A affinity column in a well known manner. Product recovery is approximately 85%. The product obtained is a complex protein mixture comprising correctly folded etanercept, incorrectly folded etanercept, and / or aggregates of c...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

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.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. application Ser. No. 13 / 654,795, filed Oct. 18, 2012, which claims priority benefit of U.S. provisional Appl. Ser. No. 61 / 669,480, filed Jul. 9, 2012, and 61 / 548,518, filed Oct. 18, 2011, the disclosures of which are incorporated herein by reference in their entireties.FIELD OF THE INVENTION[0002]The present invention relates to aqueous pharmaceutical compositions stabilized with sodium chloride for long-term storage of etanercept, methods of manufacture of the compositions, methods of their administration, and kits containing the same. The invention includes etanercept formulations that do not require arginine for stabilization.BACKGROUND OF THE INVENTION[0003]Polypeptides must often be stored prior to their use. When stored for extended periods, polypeptides are frequently unstable in solution (Manning et al., 1989, Pharm. Res. 6:903-918). To extend their shelf life, additional processing steps...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61K38/17
CPCC07K2319/30A61K39/39591A61K38/1793
Inventor MANNING, MARKMURPHY, BRIAN
Owner COHERUS BIOSCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap