Influence of FcRn binding properties on the gastrointestinal absorption and exposure profile of Fc molecules

Abstract

The neonatal Fc receptor (FcRn) represents a transport system with the potential to facilitate absorption of biologics across the gastrointestinal barrier. How biologics interact with FcRn to enable their gastrointestinal absorption, and how these interactions might be optimized in a biological therapeutic are not well understood. Thus, we studied the absorption of Fc molecules from the intestine using three IgG₄-derived Fc variants with different, pH-dependent FcRn binding and release profiles. Using several different intestinal models, we consistently observed that FcRn binding affinity correlated with transcytosis. Our findings support targeting FcRn to enable intestinal absorption of biologics and highlight additional strategic considerations for future work.

Keywords: Biologics; Caco-2 cells; Fc; FcRn; Half-life; Intestinal FcRn Gene Expression; Intestinal absorption; Oral delivery; Peptides; Pharmacokinetics; Rat Intrajejunal Closed Loop Model; Transcytosis.