Keith Foster;Patrick Stancombe;Kei Roger Aoki;Joseph Francis;John Chaddock;Lance Steward;Philip Marks
发明人:
Keith Foster,John Chaddock,Philip Marks,Patrick Stancombe,Kei Roger Aoki,Joseph Francis,Lance Steward
申请号：
US13419381
公开号：
US20120230975A1
申请日:
2012.03.13
申请国别(地区):
US
年份:
2012
代理人:
摘要：
A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment can cleave a protein of the exocytic fusion apparatus of a nociceptive sensory afferent； a Targeting Moiety that can bind to a Binding Site on the nociceptive sensory afferent, which Binding Site can undergo endocytosis to be incorporated into an endosome within the nociceptive sensory afferent； a protease cleavage site at which site the fusion protein is cleavable by a protease, which is located between the non-cytotoxic protease and the Targeting Moiety； and a translocation domain that can translocate the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent； wherein the Targeting Moiety is BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin. Nucleic acid sequences encoding the fusion proteins, methods of preparing same and uses thereof are also described.
