Patent ID: 6423513
Filing Date: 2002-07-23
Classification: A61K,A61P,C07K

Abstract:
A recombinant polynucleotide comprising a nucleotide sequence encoding a protease-activatable Pseudomonas exotoxin A-like (â€œPE-likeâ€ ) proprotein comprising:(a) a cell recognition domain of between 10 and 1500 amino acids that binds to an exterior surface of a targeted cell; (b) a modified PE translocation domain comprising an amino acid sequence with 80% or greater sequence identity to amino acids 280 to 344 of SEQ ID NO:2 and which effects translocation to a cell cytosol upon proteolytic cleavage, wherein the translocation domain comprises a cysteine-cysteine loop that comprises a protease activatable sequence cleavable by a protease and wherein the protease activatable sequence is refractory to cleavage by furin when incubated with furin at a 1:10 enzyme:substrate molar ratio at 25Â° C. for 16 hours; (c) a cytotoxicity domain comprising an amino acid sequence with 80% or greater sequence identity to amino acids 400 to 613 of SEQ ID NO:2, the cytotoxicity domain having ADP-ribosylating activity; and (d) an endoplasmic reticulum (â€œERâ€ ) retention sequence.