In vivo evaluation of PolyPEG® in a pharmacodynamic study demonstrated that a protein conjugated to two different PolyPEGs® shows an increased biological activity compared to a linear PEG conjugate control.
Biological activity of PolyPEG® conjugates in vivo
There are numerous published reports that certain larger, conventional linear and branched PEGs can accumulate in tissues and organs, specifically in the kidneys, thereby resulting in vacuolisation in the renal epithelium. WEP has carried out a meta-analysis of reported repeat dose toxicology studies with PEGylated biologics, looking specifically at renal vacuolisation as a marker for tissue accumulation. This shows a cumulative dose-dependent increase in renal vacuolisation for products conjugated with linear PEGs, but illustrates the absence of any accumulation for PolyPEG®-conjugates. This is consistent with all the components of PolyPEG® being small enough to be readily excreted from the body thereby avoiding tissue accumulation.
