Strategies for extended serum half-life of protein therapeutics

► New biodegradable polymers, for example, flexible polypeptide chains, are being developed as a substitute for PEGylation. ► Fusion to the IgG Fc region is an established method to prolong half-life of small-sized protein therapeutics. ► The half-life of antibodies has been extended by increasing the pH-dependent interaction with the neonatal Fc receptor. ► Fusion to albumin is increasingly used for half-life extension also implementing recycling by the neonatal Fc receptor. ► Fusion to albumin-binding moieties has emerged as half-life extension strategy utilizing noncovalent interaction with albumin.