Author:
Jain Tushar,Sun Tingwan,Durand Stéphanie,Hall Amy,Houston Nga Rewa,Nett Juergen H.,Sharkey Beth,Bobrowicz Beata,Caffry Isabelle,Yu Yao,Cao Yuan,Lynaugh Heather,Brown Michael,Baruah Hemanta,Gray Laura T.,Krauland Eric M.,Xu Yingda,Vásquez Maximiliano,Wittrup K. Dane
Abstract
Antibodies are a highly successful class of biological drugs, with over 50 such molecules approved for therapeutic use and hundreds more currently in clinical development. Improvements in technology for the discovery and optimization of high-potency antibodies have greatly increased the chances for finding binding molecules with desired biological properties; however, achieving drug-like properties at the same time is an additional requirement that is receiving increased attention. In this work, we attempt to quantify the historical limits of acceptability for multiple biophysical metrics of “developability.” Amino acid sequences from 137 antibodies in advanced clinical stages, including 48 approved for therapeutic use, were collected and used to construct isotype-matched IgG1 antibodies, which were then expressed in mammalian cells. The resulting material for each source antibody was evaluated in a dozen biophysical property assays. The distributions of the observed metrics are used to empirically define boundaries of drug-like behavior that can represent practical guidelines for future antibody drug candidates.
Publisher
Proceedings of the National Academy of Sciences
Cited by
461 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献