Patent ID: 8309686
Filing Date: 2012-11-13
Classification: A61K,C07K,Y02A

Abstract:
1. A modified Clostridial neurotoxin comprising: a) a botulinum neurotoxin A binding domain comprising a first heavy chain portion able to interact with a surface receptor present in a target cell, wherein said first heavy chain portion comprises a mammalian blood protease cleavage site, said mammalian blood protease cleavage site comprising a modification in one or more regions selected from the group consisting of amino acids 930-935 of SEQ ID NO: 1, amino acids 1060-1063 of SEQ ID NO: 1, amino acids 1136-1144 of SEQ ID NO: 1 and amino acids 1165-1171 of SEQ ID NO: 1; b) a Clostridial neurotoxin translocation domain comprising a second heavy chain portion able to mediate the escape of a light chain portion of said neurotoxin from an endosome to the cytoplasm of said target cell, wherein said Clostridial neurotoxin translocation domain is a BoNT/B translocation domain, a BoNT/C c) a Clostridial neurotoxin enzymatic domain comprising said light chain portion able to cleave a SNARE-protein present in said target cell, wherein said Clostridial neurotoxin enzymatic domain is a BoNT/B enzymatic domain, a BoNT/C