Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters

The purpose of making a biobetter biologic is to improve on the salient characteristics of a known biologic for which there is, minimally, clinical proof of concept or, maximally, marketed product data. There already are several examples in which second-generation or biobetter biologics have been generated by improving the pharmacokinetic properties of an innovative drug, including Neulasta (R) [a PEGylated, longer-half-life version of Neupogen (R) (filgrastim)] and Aranesp (R) [a longer-half-life version of Epogen (R) (epoetin-alpha)]. This review describes the use of protein fusion technologies such as Fc fusion proteins, fusion to human serum albumin, fusion to carboxy-terminal peptide, and other polypeptide fusion approaches to make biobetter drugs with more desirable pharmacokinetic profiles.