Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical properties

Antibody drugs should exhibit not only high-binding affinity for their target antigens but also favorable physicochemical drug-like properties. Such drug-like biophysical properties are essential for the successful development of antibody drug products. The traditional approaches used in antibody dr...

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Main Authors: Hristo L. Svilenov, Paolo Arosio, Tim Menzen, Peter Tessier, Pietro Sormanni
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:mAbs
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Online Access:https://www.tandfonline.com/doi/10.1080/19420862.2022.2164459
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author Hristo L. Svilenov
Paolo Arosio
Tim Menzen
Peter Tessier
Pietro Sormanni
author_facet Hristo L. Svilenov
Paolo Arosio
Tim Menzen
Peter Tessier
Pietro Sormanni
author_sort Hristo L. Svilenov
collection DOAJ
description Antibody drugs should exhibit not only high-binding affinity for their target antigens but also favorable physicochemical drug-like properties. Such drug-like biophysical properties are essential for the successful development of antibody drug products. The traditional approaches used in antibody drug development require significant experimentation to produce, optimize, and characterize many candidates. Therefore, it is attractive to integrate new methods that can optimize the process of selecting antibodies with both desired target-binding and drug-like biophysical properties. Here, we summarize a selection of techniques that can complement the conventional toolbox used to de-risk antibody drug development. These techniques can be integrated at different stages of the antibody development process to reduce the frequency of physicochemical liabilities in antibody libraries during initial discovery and to co-optimize multiple antibody features during early-stage antibody engineering and affinity maturation. Moreover, we highlight biophysical and computational approaches that can be used to predict physical degradation pathways relevant for long-term storage and in-use stability to reduce the need for extensive experimentation.
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institution Kabale University
issn 1942-0862
1942-0870
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publishDate 2023-12-01
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series mAbs
spelling doaj-art-375ca2578f7d4343a49f80dafa044d392025-08-20T03:25:59ZengTaylor & Francis GroupmAbs1942-08621942-08702023-12-0115110.1080/19420862.2022.2164459Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical propertiesHristo L. Svilenov0Paolo Arosio1Tim Menzen2Peter Tessier3Pietro Sormanni4Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Gent, BelgiumDepartment of Chemistry and Applied Biosciences, ETH Zürich, Zürich, SwitzerlandCoriolis Pharma Research GmbH, Martinsried, 82152, GermanyDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USACentre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UKAntibody drugs should exhibit not only high-binding affinity for their target antigens but also favorable physicochemical drug-like properties. Such drug-like biophysical properties are essential for the successful development of antibody drug products. The traditional approaches used in antibody drug development require significant experimentation to produce, optimize, and characterize many candidates. Therefore, it is attractive to integrate new methods that can optimize the process of selecting antibodies with both desired target-binding and drug-like biophysical properties. Here, we summarize a selection of techniques that can complement the conventional toolbox used to de-risk antibody drug development. These techniques can be integrated at different stages of the antibody development process to reduce the frequency of physicochemical liabilities in antibody libraries during initial discovery and to co-optimize multiple antibody features during early-stage antibody engineering and affinity maturation. Moreover, we highlight biophysical and computational approaches that can be used to predict physical degradation pathways relevant for long-term storage and in-use stability to reduce the need for extensive experimentation.https://www.tandfonline.com/doi/10.1080/19420862.2022.2164459AntibodiesmAbsdevelopabilitymanufacturabilitydrug-like propertiesearly-stage screening
spellingShingle Hristo L. Svilenov
Paolo Arosio
Tim Menzen
Peter Tessier
Pietro Sormanni
Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical properties
mAbs
Antibodies
mAbs
developability
manufacturability
drug-like properties
early-stage screening
title Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical properties
title_full Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical properties
title_fullStr Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical properties
title_full_unstemmed Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical properties
title_short Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical properties
title_sort approaches to expand the conventional toolbox for discovery and selection of antibodies with drug like physicochemical properties
topic Antibodies
mAbs
developability
manufacturability
drug-like properties
early-stage screening
url https://www.tandfonline.com/doi/10.1080/19420862.2022.2164459
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