A strategy for risk mitigation of antibodies with fast clearance

• DOI: 10.4161/mabs.22189
• Publication Date: 2012-11-01T15:43:23Z
• Authors: Isidro Hötzel; Frank-Peter Theil; Lisa J. Bernstein; Saileta Prabhu; Rong Deng; Leah Quintana; Jeff Lutman; Renuka Sibia; Pamela Chan; Daniela Bumbaca; Paul Fielder; Paul J. Carter; Robert F. Kelley
• Keywords: Neonatal Fc receptor; Clearance; Clearance rate; Plasma clearance

A majority of human therapeutic antibody candidates show pharmacokinetic properties suitable for clinical use, but an unexpectedly fast clearance is sometimes observed that may limit the utility. Pharmacokinetic data in cynomolgus monkeys collected a panel 52 antibodies showed broad distribution target-independent values (2.4–61.3 mL/day/kg), with 15 (29%) having > 10 mL/day/kg. Alteration interaction recycling FcRn receptor did not account faster than expected antibodies; off-target binding was presumed to clearance. We developed assay based on ELISA detection non-specific baculovirus particles can identify increased risk This be used during lead generation or optimization both humans and monkeys, thus increase likelihood obtaining drug candidate.