SITE SPECIFIC PEGYLATION OF BROADLY-NEUTRALIZING ANTIBODIES AGAINST HEPATITIS C VIRUS AND THEIR USE IN THE TREATMENT OF CHRONIC HCV INFECTIONS

摘要

The present invention provides for the pegylation of therapeutic antibodies to treat HCV infections. More specifically, the invention relates to site-specific pegylation of E2 antibody fragments at specifically defined amino acid residue(s) that is optionally engineered away from the antigen binding sites. The pegylated-MAb derivatives show substantially improved pharmacokinetic and pharmacodynamic properties, and they are broadly-neutralizing against several HCV clinical isolates by selectively binding to broadly-conserved neutralization epitope(s) of HCV E2 glycoprotein.