Event Details

Jun 23 – Jun 23, 2016

Predicting Human IgG Half-Life with an In Vitro Assay

  • Webinars

Colby Souders, Ph.D.
Kanyos Bio
10 AM EST New York/3 PM BST London

Immunoglobulin G (IgG) has an unusually long serum half-life in comparison to proteins of similar size due to IgG’s ability to bind the neonatal Fc receptor (FcRn) in a pH-dependent manner. FcRn binding properties can vary among IgGs, resulting in altered in vivo half-lives, making it beneficial to accurately predict the FcRn binding properties of therapeutic IgG monoclonal antibodies (mAbs). This webinar will describe the development of an in vitro model capable of predicting the in vivo half-life of human IgG. Using a high-throughput Bio-Layer Interferometry (BLI) Octet® platform, the human FcRn association rate at acidic pH and subsequent dissociation rate at physiological pH was determined for 5 human IgG1 mAbs. Comparing the combined FcRn association and dissociation rates to the Phase 1 clinical study half-lives of the mAbs resulted in a strong correlation. The correlation was also verified in vivo using mice transgenic for human FcRn.

The model was used to characterize various factors that may influence the FcRn-mAb binding, including mAb variable region sequence differences and constant region glycosylation patterns.