title: Biophysical properties of the clinical-stage antibody landscape.
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.
authors.affiliation: Department of Computational Biology, Adimab LLC, Lebanon, NH 03766.
authors.forename: Tushar
authors.initials: T
authors.lastname: Jain
authors.affiliation: Department of Protein Analytics, Adimab LLC, Lebanon, NH 03766.
authors.forename: Tingwan
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Molecular Biology, Adimab LLC, Lebanon, NH 03766.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Durand
authors.affiliation: Department of Molecular Biology, Adimab LLC, Lebanon, NH 03766.
authors.forename: Amy
authors.initials: A
authors.lastname: Hall
authors.affiliation: Department of Molecular Biology, Adimab LLC, Lebanon, NH 03766.|Department of Antibody Discovery, Adimab LLC, Lebanon, NH 03766.
authors.forename: Nga Rewa
authors.initials: NR
authors.lastname: Houston
authors.affiliation: Department of High-Throughput Expression, Adimab LLC, Lebanon, NH 03766.
authors.forename: Juergen H
authors.initials: JH
authors.lastname: Nett
authors.affiliation: Department of High-Throughput Expression, Adimab LLC, Lebanon, NH 03766.
authors.forename: Beth
authors.initials: B
authors.lastname: Sharkey
authors.affiliation: Department of High-Throughput Expression, Adimab LLC, Lebanon, NH 03766.
authors.forename: Beata
authors.initials: B
authors.lastname: Bobrowicz
authors.affiliation: Department of Protein Analytics, Adimab LLC, Lebanon, NH 03766.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Caffry
authors.affiliation: Department of Protein Analytics, Adimab LLC, Lebanon, NH 03766.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Protein Analytics, Adimab LLC, Lebanon, NH 03766.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Protein Analytics, Adimab LLC, Lebanon, NH 03766.
authors.forename: Heather
authors.initials: H
authors.lastname: Lynaugh
authors.affiliation: Department of Protein Analytics, Adimab LLC, Lebanon, NH 03766.
authors.forename: Michael
authors.initials: M
authors.lastname: Brown
authors.affiliation: Department of Antibody Discovery, Adimab LLC, Lebanon, NH 03766.
authors.forename: Hemanta
authors.initials: H
authors.lastname: Baruah
authors.affiliation: Department of Antibody Discovery, Adimab LLC, Lebanon, NH 03766.
authors.forename: Laura T
authors.initials: LT
authors.lastname: Gray
authors.affiliation: Department of Antibody Discovery, Adimab LLC, Lebanon, NH 03766.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Krauland
authors.affiliation: Department of Protein Analytics, Adimab LLC, Lebanon, NH 03766; yingda.xu@adimab.com max.vasquez@adimab.com dane.wittrup@adimab.com.
authors.forename: Yingda
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Computational Biology, Adimab LLC, Lebanon, NH 03766; yingda.xu@adimab.com max.vasquez@adimab.com dane.wittrup@adimab.com.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Vásquez
authors.affiliation: Department of Computational Biology, Adimab LLC, Lebanon, NH 03766; yingda.xu@adimab.com max.vasquez@adimab.com dane.wittrup@adimab.com.|Department of Protein Analytics, Adimab LLC, Lebanon, NH 03766.|Department of Molecular Biology, Adimab LLC, Lebanon, NH 03766.|Department of Antibody Discovery, Adimab LLC, Lebanon, NH 03766.|Department of High-Throughput Expression, Adimab LLC, Lebanon, NH 03766.
authors.forename: K Dane
authors.initials: KD
authors.lastname: Wittrup
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry; D055592:Biophysical Phenomena; D017277:Drug Approval; D055808:Drug Discovery / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G
keywords: biophysical properties; developability; manufacturability; monoclonal antibody; nonspecificity