Keith Foster;Kei Roger Aoki;Joseph Francis;Charles Penn;John Chaddock;Lance Steward
发明人:
Keith Foster,John Chaddock,Charles Penn,Kei Roger Aoki,Joseph Francis,Lance Steward
申请号：
US13072865
公开号：
US09139635B2
申请日:
2011.03.28
申请国别(地区):
US
年份:
2015
代理人:
摘要：
The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell； (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell； and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.
