Patent ID: 8778634

Claim:
A non-cytotoxic protein conjugate for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell, comprising: (i) a Targeting Moiety (TM), wherein said TM binds to a Binding site on a nociceptive sensory afferent cell, wherein said Binding site undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell, and wherein the TM is nociceptin; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment cleaves a protein of the exocytic fusion apparatus of said nociceptive sensory afferent cell and wherein the non-cytotoxic protease or fragment thereof is selected from a clostridial neurotoxin; 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 and wherein the Translocation Domain is a botulinum H N domain; wherein said conjugate comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:137, 138, 142, and 163-168.