Polymer selection impacts the pharmaceutical profile of site-specifically conjugated Interferon-?2a

Conjugation of poly(ethylene glycol) (PEG) to biologics is a successful strategy to favorably impact the pharmacokinetics and efficacy of the resulting bioconjugate. We compare bioconjugates synthesized by strainpromoted azide-alkyne cycloaddition (SPAAC) using PEG and linear polyglycerol (LPG) of about 20 kDa or 40 kDa, respectively, with an azido functionalized human Interferon-alpha 2a (IFN-alpha 2a) mutant. Site-specific PEGylation and LPGylation resulted in IFN-alpha 2a bioconjugates with improved in vitro potency compared to commercial Pegasys. LPGylated bioconjugates had faster disposition kinetics despite comparable hydrodynamic radii to their PEGylated analogues. Overall exposure of the PEGylated IFN-alpha 2a with a 40 kDa polymer exceeded Pegasys, which, in return, was similar to the 40 kDa LPGylated conjugates. The study points to an expanded polymer design space through which the selected polymer class may result in a different distribution of the studied bioconjugates.

Automated summary

Conjugation of poly(ethylene glycol) (PEG) and linear polyglycerol (LPG) with biologics can improve their pharmacokinetics and efficacy. The study shows that bioconjugates synthesized by specific site PEGylation and LPGylation have better in vitro potency compared to commercial Pegasys, and the overall exposure of 40 kDa PEGylated IFN-α-2a exceeds that of Pegasys.