Patent ID: 8956847
Filing Date: 2015-02-17
Classification: A61K,A61P,C07K,C12N

Abstract:
1. A single chain, polypeptide fusion protein, comprising: a) a non-cytotoxic protease that cleaves a protein of the exocytic fusion apparatus of a target cell; b) a Targeting Moiety that binds to a Binding Site on the target cell, which Binding Site undergoes endocytosis to be incorporated into an endosome within the target cell; c) a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease and the Targeting Moiety; and d) a translocation domain that translocates the non-cytotoxic protease from within an endosome, across the endosomal membrane and into the cytosol of the target cell; wherein the Targeting Moiety is located between the protease cleavage site and the translocation domain; and wherein the non-cytotoxic protease forms a disulphide bond with the translocation domain of the fusion protein, wherein the amino acid residue of the non-cytotoxic protease that forms the first part of the disulphide bond is located within the last 20 C-terminal amino acid residues of the non-cytotoxic protease, and the amino acid residue of the translocation domain that forms the second part of the disulphide bond is located within the first 20 N-terminal amino acid residues of the translocation domain.