title: AFIR: A Dimensionless Potency Metric for Characterizing the Activity of Monoclonal Antibodies.
abstract: For monoclonal antibody (mAb) drugs, soluble targets may accumulate several thousand fold after binding to the drug. Time course data of mAb and total target is often collected and, although free target is more closely related to clinical effect, it is difficult to measure. Therefore, mathematical models of this data are used to predict target engagement. In this article, a "potency factor" is introduced as an approximation for the model-predicted target inhibition. This potency factor is defined to be the time-Averaged Free target concentration to Initial target concentration Ratio (AFIR), and it depends on three key quantities: the average drug concentration at steady state; the binding affinity; and the degree of target accumulation. AFIR provides the intuition for how changes in dosing regimen and binding affinity affect target capture and AFIR can be used to predict the druggability of new targets and the expected benefits of more potent, second-generation mAbs.
authors.affiliation: Novartis Institute for BioMedical Research, Cambridge, Massachusetts, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Stein
authors.affiliation: Novartis Institute for BioMedical Research, Cambridge, Massachusetts, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ramakrishna
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy
chemical_list: D000911:Antibodies, Monoclonal