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

BioDrugs. 2015 Aug;29(4):215-39. doi: 10.1007/s40259-015-0133-6.


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(®) [a PEGylated, longer-half-life version of Neupogen(®) (filgrastim)] and Aranesp(®) [a longer-half-life version of Epogen(®) (epoetin-α)]. 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Products / chemistry
  • Biological Products / pharmacokinetics*
  • Chemistry, Pharmaceutical / methods
  • Drug Design*
  • Half-Life
  • Humans
  • Peptides / chemistry
  • Peptides / pharmacokinetics
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / pharmacokinetics*
  • Serum Albumin / metabolism


  • Biological Products
  • Peptides
  • Recombinant Fusion Proteins
  • Serum Albumin