Basic research on neonatal Fc receptor (FcRn) affinity to establish half-life extension technology of therapeutic antibodies

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08087
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Suzuki Takuo 国立医薬品食品衛生研究所, 生物薬品部, 主任研究官 (10415466)
• Co-Investigator(Kenkyū-buntansha): 橋井 則貴 国立医薬品食品衛生研究所, 生物薬品部, 室長 (20425672)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: FcRn / 抗体医薬品 / 表面プラズモン共鳴 / Fcγ受容体 / 半減期延長 / アミノ酸改変 / HDX/MS

Outline of Final Research Achievements

Therepeutic antibodies are protected from degradation by binding to neonatal Fc receptor (FcRn) in endosome and are recycled into plasma, thereby having long half-lives. To prolong the half-lives additionally with the aim of reducing dose and frequency, amino acids-substituted antibodies having high affinity to FcRn are being developed. However, there are cases that the half-lives of the antibodies are not prolonged. As basic researches on neonatal Fc receptor (FcRn) affinity to establish half-life extension technology of therapeutic antibodies, we performed the studies on the binding between FcRn and amino acids-substituted antibodies, and investigated the changes of the conformation and function of IgG (i.e. binding to Fc gamma receptors) by amino acids substitution for raising the affinity to FcRn.

Free Research Field

医療系薬学