Polymer Fusions to Increase Antibody Half-Lives: PEGylation and Other Modifications

PEGylation of proteins has been performed for over 30 years (Abuchowski et al., 1977a,b). Although the details such as polyethylene glycol (PEG) size, structure, synthesis, purification, and reactive chemistries have changed, the basic aims of the method remain the same. These aims are to improve the biophysical and pharmaceutical characteristics of proteins by modifying pharmacokinetics (circulating serum half-life); increasing resistance to proteolysis; reducing antigenicity and immunogenicity; and in some instances, increasing solubility and reducing propensity to aggregate. These improvements have been demonstrated successfully in the clinic with a variety of proteins including enzymes, cytokines, and antibodies. In this chapter we will introduce the aspects of PEGylation common to all proteins before dealing with their specific application to antibodies and antibody fragments.