“
“PEGylation is
the technology involving the covalent attachment of polyethylene glycol (PEG) to a protein-, peptide- or small-molecule drug to improve their pharmacokinetic, pharmacodynamic and immunological profiles, and thus, enhance the therapeutic effect. Today, PEGylation of proteins is a well-established technology and is being used in the treatment of a variety of clinical disorders. Several PEGylated coagulation proteins for haemophilia A and B are under development with the goal of prolonging the circulation half-life of factor VIII (FVIII) or factor IX. The prolongation of half-life, resulting in less frequent injections can provide significant benefits in improving the quality of life BMN 673 price of subjects with haemophilia and improvement in adherence to treatment. A review of published literature on PEGylated therapeutic products currently approved for human use and a discussion of a PEGylated recombinant FVIII molecule (BAY 94–9027, Bayer HealthCare, Berkeley, CA, USA) currently MLN0128 mouse being investigated in the pivotal clinical trial prior to registration is provided. Available safety information of PEGylated proteins containing high molecular weight PEG does not indicate any safety concerns to
date, following long-term (chronic) use in animal models or patients. Chronic use of currently available PEGylated products has been shown to be safe, paving the way for chronic use of PEGylated coagulation products in persons with haemophilia. PEGylation is the technology involving the covalent attachment of polyethylene glycol (PEG) to a protein-, peptide- or small-molecule drug to improve their pharmacokinetics, pharmacodynamic and/or immunological profiles, and thus, enhance its therapeutic effect [1]. As early as 1977, PEGylation was introduced to bovine serum albumin to reduce the immunogenicity
[2]. The initial technology used random PEGylation of the proteins with relatively small PEG molecules in the range of up to 5 kDa. This resulted in several PEG molecules 上海皓元 per protein and sometimes a variation in number of PEGs per protein [3]. Random PEGylation may result in a loss or change of protein activity due to binding of the PEG at undesirable sites and interaction with target receptor or binding molecules [3]. More recently targeted PEGylation with considerably larger PEG molecules has been developed with the goal of mono- or di-PEGylation, reproducibly attaching one or two PEGs per protein molecule at specific amino acid sites. Site-specific PEGylation is now a well-established technology and it offers substantial advantage over random PEGylated proteins [4]. Site-specific PEGylation with high molecular weight PEG molecules is used to alter the pharmacokinetic properties of several marketed proteins and to improve pharmacological properties and immunogenicity [4, 5].