A single molecular descriptor to predict solution behavior of therapeutic antibodies.
Sci Adv
; 6(32): eabb0372, 2020 08.
Article
in English
| MEDLINE | ID: covidwho-827120
ABSTRACT
Despite the therapeutic success of monoclonal antibodies (mAbs), early identification of developable mAb drug candidates with optimal manufacturability, stability, and delivery attributes remains elusive. Poor solution behavior, which manifests as high solution viscosity or opalescence, profoundly affects the developability of mAb drugs. Using a diverse dataset of 59 mAbs, including 43 approved products, and an array of molecular descriptors spanning colloidal, conformational, charge-based, hydrodynamic, and hydrophobic properties, we show that poor solution behavior is prevalent (>30%) in mAbs and is singularly predicted (>90%) by the diffusion interaction parameter (k D), a dilute-solution measure of colloidal self-interaction. No other descriptor, individually or in combination, was found to be as effective as k D. We also show that well-behaved mAbs, a substantial subset of which bear high positive charge and pI, present no disadvantages with respect to pharmacokinetics in humans. Here, we provide a systematic framework with quantitative thresholds for selecting well-behaved therapeutic mAbs during drug discovery.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antibodies, Monoclonal
Type of study:
Prognostic study
/
Systematic review/Meta Analysis
Limits:
Humans
Language:
English
Journal:
Sci Adv
Year:
2020
Document Type:
Article
Affiliation country:
Sciadv.abb0372
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