Reversible PEGylation is a synthetic chemistry based technology for extending the half-life of injectable therapeutic peptides and small molecules, exclusively licensed from the Weizmann Institute. The technology is based on the formation of a conjugate between a drug that contains a primary amine group and a polyethylene glycol (PEG) chain through a proprietary bi-functional hydrolysable linker. Once the conjugate enters the bloodstream, the linker hydrolyses in a controlled manner and the authentic intact drug is gradually released. The drug product released after hydrolysis is identical to the native protein. Using a hydrolysable linker bypasses the disadvantages of using a standard PEGylated molecule, i.e. the potential for steric hindrance that limits its function, and the limited ability to cross cellular membranes. This technology is especially suitable for drugs with a short half-life which are required to cross the blood-brain barrier.
