Stian Foss, Siri A Sakya, Leire Aguinagalde, Marta Lustig, Jutamas Shaughnessy, Ana Rita Cruz, Lisette Scheepmaker, Line Mathiesen, Fulgencio Ruso-Julve, Aina Karen Anthi, Torleif Tollefsrud Gjølberg, Simone Mester, Malin Bern, Mitchell Evers, Diane B Bratlie, Terje E Michaelsen, Tilman Schlothauer, Devin Sok, Jayanta Bhattacharya, Jeanette Leusen, Thomas Valerius, Sanjay Ram, Suzan H M Rooijakkers, Inger Sandlie, Jan Terje Andersen
Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice...
March 7, 2024: Nature Communications