Proteins with Improved Solubility and Methods for Producing and Using Same

US20090269358A1Inactive Publication Date: 2009-10-29THE UK SEC FOR HEALTH & HER BRITANNIC MAJESTYS GOVERNMENT OF THE UK OF GREAT BRITAIN & NORTHERN IRELAND +1

Patent Information

Authority / Receiving Office
US · United States
Current Assignee / Owner
THE UK SEC FOR HEALTH & HER BRITANNIC MAJESTYS GOVERNMENT OF THE UK OF GREAT BRITAIN & NORTHERN IRELAND
Publication Date
2009-10-29
Estimated Expiration
Not applicable · inactive patent

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Abstract

A method is provided for improving the solubility of proteins, for example, bacterial toxins. In one embodiment, solubility is improved by introducing point mutations that replace cysteine residues capable of forming intermolecular disulfide bonds with other amino acid residues that do not form such bonds. By abrogating the ability of the cysteine residues to form inter-molecular disulfide bonds, aggregation of the protein is reduced, thereby improving the solubility of the protein. In another embodiment, solubility of the protein is improved by producing truncated forms of the protein that express the LHN domain and a fragment of the Hc domain. Proteins made according to the method of the invention are useful, for example, as immunodiagnostic agents and vaccine components.
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Description

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the benefit of U.S. provisional application Nos. 60 / 724,274, filed Oct. 7, 2005, and 60 / 742,900, filed Dec. 7, 2005, the entire disclosures of which are incorporated by reference.DESCRIPTION OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to methods for producing recombinant proteins that exhibit improved utility and process characteristics, such as solubility, compared to the corresponding native proteins. The invention also relates to proteins made according to the present methods, nucleic acids encoding the proteins, and the use of the proteins for prophylactic and therapeutic applications.

[0004] 2, Background of the Invention

[0005] Proteins produced by organisms, and in particular microorganisms such as bacteria, are of interest because of their potential to serve as immunodiagnostic reagents, therapeutic agents, and vaccine components. Toxins are one group of proteins th...

Claims

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