The therapeutic value of poly(ethylene glycol)-modified proteins

The field of protein therapy has flourished in the past few years, mainly due to the advent of recombinant DNA techniques and large-scale manufacturing processes. It was believed that human-derived proteins would eliminate the problems of short circulating lives, low stability and immunogenicity associated with the use of non-human proteins as drugs. Unfortunately, it has been demonstrated that many human proteins still suffer from short circulating lives and low stability, and often require the use of large doses to maintain therapeutic efficacy. This in turn increases the chances for the development of an adverse immune response, or at least for the development of clearing antibodies. The discovery that the modification of proteins with poly(ethylene glycol) (PEGNOLOGY^SM) results in an adduct with decreased to non-existent immunogenicity increased circulating life, increased stability and opened the way for the development of protein pharmaceuticals that would realize the promise of protein therapy. In this paper, we will review the clinical value of PEGNOLOGY^SM as researched by Enzon Inc. and discuss the future for this technology.