New generation PEG launched
polyethylene glycol (PEG) to improve the half-life of biologic
drugs in the body.
The new PEG, which goes under the POLY PEG tradename, is in fact a range of polymers that can be used as bioconjugates for the PEGylation of proteins, peptides and biomolecular therapeutics.
The attachment of PEG to therapeutic proteins or small molecules to enhance their delivery, for example by reducing the number of doses required, has traditionally been based on linear and branched structures, using polyether as the backbone of the polymer.
POLY PEG is different because it features a unique 'comb' structure, whereby the backbone is a methacrylic polymer and the teeth of the comb are PEG. WEP's process grows the terminally functional polymer onto the active terminal initiator in a controlled way, permitting a wide range of structures and sizes to be produced.
"The polymers are ... principally PEG and use the same active terminals as the technology currently familiar to the pharmaceutical industry," said the company.
PEGylation has already been used to improve the delivery of interferons used in the treatment of hepatitis and drugs to support blood function in patients undergoing cancer chemotherapy, and is being evaluated for use with a number of experimental therapies.
However, PEGylation has been available for years, and the relatively low take-up of the technology reflects the fact that it can be difficult to bind PEG to the active molecule without limiting the latter's activity.
WEP believes that because the structure of its POLY PEG can be varied in three ways - by a choice of active end group; by the PEG chain length, determining the amount of PEG on each 'tooth'; or by the methacrylic spine which determines the 'length' of the comb - it represents a new generation of PEG that could overcome the limitations of its predecessors.
So while PEGylation has mostly been used to date with recombinant proteins, advances in the technology, from WEP and others such as Avantium, Celltech, PolyMASC, could expand its use into antibodies, oligonucleotides and small molecules.
WEP's chief executive Fergal O'Brien, said that POLY PEG has all the benefits of conventional pegylation technology but offers 'supreme versatility of structure and hence application'.
"Use of the POLY PEG conjugates allows pharmaceutical producers to synthesise pure monofunctionalised polymers, with zero contamination from disubstituted polymer and the by-products experienced with conventional, linear PEGylating reagents," he said.
"Additionally, the unique comb structure allows greater control of size and weight in solution as the primary architecture can be varied along the backbone and length of the teeth."
Within the structure of the POLY PEG range, WEP has designed a hydrolysable ester linkage, which attaches the PEG to the polymer backbone. These links cleave over time, releasing low molecular weight and non-toxic PEG, facilitating renal clearance from the body.
Available in batches from grams to kilos, the POLY PEG family incorporates WEP's patented polymerisation technology and features terminal groups suitable for conjugation with lysine, terminal amino and cysteine residues.
