Single chain fc fusion proteins

Abstract

The present invention provides novel, single chain Fc fusion proteins having improved properties. The invention provides single chain fusions of soluble proteins fused to the Fc region of an immunoglobulin via a novel linker comprising a constant region of an immunoglobulin light chain linked to a CH1 constant region of an immunoglobulin heavy chain. This novel linker confers favorable properties on the Fc fusion proteins of the invention such as improved bioactivity and increased half-life as compared to non-Fc fusion counterparts or as compared to prior art Fc fusion proteins. The novel Fc fusion protein scaffold as described herein may be designed to include soluble proteins of interest capable of binding or interacting with any target of interest. Preferably, the Fc fusion protein of the invention is a dimer. The dimer preferably forms via a disulfide bond between free cysteine residues in the hinge region of two monomeric Fc fusion proteins of the invention.

Description

RELATED APPLICATION[0001]This application claims the benefit of U.S. Provisional Application No. 62 / 094,242, filed on Dec. 19, 2014. The entire teachings of the above application are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]One strategy for increasing serum half-life of a therapeutic protein is to attach the protein to an Fc (fragment crystallizable) domain of an antibody. Many such fusion proteins are capable of forming homodimers or heterodimers thereby forming antibody-like fusion protein molecules. However, many prior art approaches to Fc fusion protein engineering have limitations including, but not limited to, immunogenicity and poor pharmacokinetic properties.[0003]The present invention provides monomers and dimers of Fc fusion proteins comprising novel linkers having single chain constant light (CL) and constant heavy (CH1) immunoglobulin domains. Such novel linkers are also referred to herein as scCLCH1 linkers.[0004]Without limitation to a particul...

AI Technical Summary

Benefits of technology

[0005]The present invention provides novel, single chain Fc fusion proteins having improved properties. The invention provides single chain fusions of soluble proteins fused to the Fc region of an immunoglobulin via a novel linker comprising a constant region of an immunoglobulin light chain (CL) linked to a CH1 constant region of an immunoglobulin heavy chain (scCLCH1 or scCH1CL linkers). This novel linker confers favorable properties on the Fc fusion proteins of the invention such as improved bioactivity and increased half-life as compared to non-Fc fusion counterparts or as compared to prior art Fc fusion proteins. The novel Fc fusion proteins as described herein may be designed to include soluble proteins of interest capable of binding or interacting with any target of interest with high specificity and affinity.

Problems solved by technology

However, many prior art approaches to Fc fusion protein engineering have limitations including, but not limited to, immunogenicity and poor pharmacokinetic properties.

Steric hindrance can result in losses in bioactivity, inefficient dimerization or reduction in the half-life of the dimer molecule for example, due to reduced binding to the FcRn.

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