IDENTIFICATION, PRODUCTION AND USE OF STAPHYLOKINASE DERIVATIVES WITH REDUCED IMMUNOGENICITY AND/OR REDUCED CLEARANCE

摘要

Methods for the identification, production and use of staphylokinase derivatives characterized by a reduced immunogenicity after administration in patients and that can be administered by a single bolus injection. The derivatives of the invention are obtained by preparing a DNA fragment comprising at least part of the coding sequence of staphylokinase; performing in vitro site-directed mutagenesis on the DNA fragment; cloning the mutated DNA fragment in a suitable vector; transforming a suitable host cell with the vector; culturing the host cell under conditions suitable for expressing the DNA fragment; purifying the staphylokinase derivative and chemically modifying Cys residues with thiol-directed polyethylene glycol. The invention also relates to pharmaceutical compositions comprising at least one of the staphylokinase derivatives according to the invention together with a suitable excipient, for treatment of arterial thrombosis.