Patent ID: 8563691
Filing Date: 2013-10-22
Classification: A61K,A61P,C07K,C12N,C12Y

Abstract:
1. A therapeutic fusion protein comprising an amino acid sequence at least 70% identical to wild type human α-N-acetylglucosaminidase (Naglu); a lysosomal targeting moiety; and wherein, once administered, the therapeutic fusion protein is targeted to lysosomes and is therapeutically active in vivo, wherein the lysosomal targeting moiety is an IGF-II mutein comprising an amino acid sequence at least 70% identical to mature human IGF-II (SEQ ID NO:1), with a mutation within a region corresponding to amino acids 30-40 of SEQ ID NO:1 such that said mutation abolishes at least one furin protease cleavage site, wherein said mutation comprises a deletion of amino acids 30-40 of SEQ ID NO:1 or an amino acid substitution at a position corresponding to Arg37 of SEQ ID NO: 1, and wherein the IGF-II mutein is (a) resistant to furin cleavage, (b) has diminished binding affinity for the insulin receptor relative to the affinity of naturally-occurring human IGF-II for the insulin receptor, and (c) binds to the human cation-independent mannose-6-phosphate receptor in a mannose-6-phosphate-independent manner.