Rationalizing mAb Candidate Screening Using a Single Holistic Developability Parameter.

Autor:	Willis LF; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K., Trayton I; The Discovery Centre─AstraZeneca PLC, Cambridge CB2 0AA, U.K., Saunders JC; The Discovery Centre─AstraZeneca PLC, Cambridge CB2 0AA, U.K., Brùque MG; The Discovery Centre─AstraZeneca PLC, Cambridge CB2 0AA, U.K., Davis Birch W; School of Mechanical Engineering, Faculty of Engineering and Physical Sciences, University of Leeds, Leeds LS2 9JT, U.K., Westhead DR; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K., Day K; The Discovery Centre─AstraZeneca PLC, Cambridge CB2 0AA, U.K., Bond NJ; The Discovery Centre─AstraZeneca PLC, Cambridge CB2 0AA, U.K., Devine PWA; The Discovery Centre─AstraZeneca PLC, Cambridge CB2 0AA, U.K., Lloyd C; The Discovery Centre─AstraZeneca PLC, Cambridge CB2 0AA, U.K., Kapur N; School of Mechanical Engineering, Faculty of Engineering and Physical Sciences, University of Leeds, Leeds LS2 9JT, U.K., Radford SE; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K., Darton NJ; The Discovery Centre─AstraZeneca PLC, Cambridge CB2 0AA, U.K., Brockwell DJ; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K.
Jazyk:	angličtina
Zdroj:	Molecular pharmaceutics [Mol Pharm] 2024 Dec 16. Date of Electronic Publication: 2024 Dec 16.
DOI:	10.1021/acs.molpharmaceut.4c00829
Abstrakt:	A framework for the rational selection of a minimal suite of nondegenerate developability assays (DAs) that maximize insight into candidate developability or storage stability is lacking. To address this, we subjected nine formulation:mAbs to 12 mechanistically distinct DAs together with measurement of their accelerated and long-term storage stability. We show that it is possible to identify a reduced set of key variables from this suite of DAs by using orthogonal statistical methods. We exemplify our approach by predicting the rank formulation:mAb degradation rate at 25 °C (determined over 6 months) using just five DAs that can be measured in less than 1 day, spanning a range of physicochemical features. Implementing such approaches focuses on resources, thus increasing sustainability and decreasing development costs.
Databáze:	MEDLINE
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