PEGylation of therapeutic proteins

Abstract

International audiencePEGylation has been widely used as a post-production modification methodology for improving biomedical efficacy and physicochemical properties of therapeutic proteins since the first PEGylated product was approved by Food and Drug Administration in 1990. Applicability and safety of this technology have been proven by use of various PEGylated pharmaceuticals for many years. It is expected that PEGylation as the most established technology for extension of drug residence in the body will play an important role in the next generation therapeutics, such as peptides, protein nanobodies and scaffolds, which due to their diminished molecular size need half-life extension. This review focuses on several factors important in the production of PEGylated biopharmaceuticals enabling efficient preparation of highly purified PEG-protein conjugates that have to meet stringent regulatory criteria for their use in human therapy. Areas addressed are PEG properties, the specificity of PEGylation reactions, separation and large-scale purification, the availability and analysis of PEG reagents, analysis of PEG-protein conjugates, the consistency of products and processes and approaches used for rapid screening of pharmacokinetic properties of PEG-protein conjugates

PK/PD modelling of comb-shaped PEGylated salmon calcitonin conjugates of differing molecular weights

“…Several efficacious and safe PEGylated products have been on the market for over 15 years, and ten PEGylated products have been approved to date [29]. Although PEG is an approved biocompatible polymer, individual components of the methacrylate-based PEG, (poly(poly(ethylene glycol) methyl ether methacrylate) are not.…”

PEGylated protein separations: Challenges and opportunities

“…This is especially the case when proteins are PEGylated with large PEG. The DBC drops dramatically especially for the PEGylation, the covalent attachment of polyethylene glycol (PEG) chains to protein, is a promising method for making an efficient protein drug [1,2]. Several PEGylated protein drugs, such as PEGylated interferons, are already on the market and others are presently in their clinical trials [1,2].…”

“…The DBC drops dramatically especially for the PEGylation, the covalent attachment of polyethylene glycol (PEG) chains to protein, is a promising method for making an efficient protein drug [1,2]. Several PEGylated protein drugs, such as PEGylated interferons, are already on the market and others are presently in their clinical trials [1,2]. However, the PEGylation reaction is very product specific so that generalized or platform processes for both reaction and purification have not yet been established [3].…”

Successful treatment of a hemodialyzed patient with pure red cell aplasia associated with epoetin beta pegol therapy with cyclosporine

“…Although all ESAs contain various versions of glycoproteins, only epoetin beta pegol contains a pegylated glycoprotein. The pegylation method is also widely used for other drugs, such as granulocyte-colony stimulating factor, factor VIII, and interferon alfa [15]. Thus far, PRCA caused by pegylated interferon has previously been reported [16][17][18].…”