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.
Submitter: Stephanie Contreras
Submission Date: Dec. 11, 2019, 2:51 p.m.
|Number of data points||1644|
|Proteins||Immunoglobulin kappa light chain ; Immunoglobulin gamma-1 heavy chain|
|Assays/Quantities/Protocols||Experimental Assay: salt-gradient affinity-capture self-interaction nanoparticle spectroscopy (SGAC-SINS) ; Experimental Assay: Tm ; Experimental Assay: Affinity-Capture Self-Interaction Nanoparticle Spectroscopy (AC-SINS) ; Experimental Assay: HEK titer ; Experimental Assay: Baculovirus particle ELISA (BVP ELISA) ; Experimental Assay: ELISA ; Experimental Assay: clone self-interaction by biolayer interferometry (CSI-BLI) ; Experimental Assay: cross-interaction chromatography (CIC) ; Experimental Assay: polyspecificity reagent (PSR) ; Experimental Assay: size-exclusion chromatography (SEC) ; Experimental Assay: standup monolayer adsorption chromatography (SMAC) ; Experimental Assay: hydrophobic interaction chromatography (HIC)|
|Libraries||biophysical properties of the clinical-stage antibody landscape|
|Percent Identity||Matching Chains||Protein||Accession||Entry Name|
|100.0||Immunoglobulin kappa light chain||P0DOX7||IGK_HUMAN|
|100.0||Immunoglobulin kappa light chain||P01834||IGKC_HUMAN|
|94.7||Immunoglobulin kappa light chain||P01602||KV105_HUMAN|
|100.0||Immunoglobulin gamma-1 heavy chain||P0DOX5||IGG1_HUMAN|
|100.0||Immunoglobulin gamma-1 heavy chain||P01857||IGHG1_HUMAN|
|90.9||Immunoglobulin gamma-1 heavy chain||P01859||IGHG2_HUMAN|
|90.9||Immunoglobulin gamma-1 heavy chain||P01861||IGHG4_HUMAN|