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Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics

The effect of hydrophobicity on antibody aggregation is well understood, and it has been shown that charge calculations can be useful for high-concentration viscosity and pharmacokinetic (PK) clearance predictions. In this work, structure-based charge descriptors are evaluated for their predictive p...

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Detalles Bibliográficos
Autores principales: Thorsteinson, Nels, Gunn, John R., Kelly, Kenneth, Long, Will, Labute, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510563/
https://www.ncbi.nlm.nih.gov/pubmed/34632944
http://dx.doi.org/10.1080/19420862.2021.1981805
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author Thorsteinson, Nels
Gunn, John R.
Kelly, Kenneth
Long, Will
Labute, Paul
author_facet Thorsteinson, Nels
Gunn, John R.
Kelly, Kenneth
Long, Will
Labute, Paul
author_sort Thorsteinson, Nels
collection PubMed
description The effect of hydrophobicity on antibody aggregation is well understood, and it has been shown that charge calculations can be useful for high-concentration viscosity and pharmacokinetic (PK) clearance predictions. In this work, structure-based charge descriptors are evaluated for their predictive performance on recently published antibody pI, viscosity, and clearance data. From this, we devised four rules for therapeutic antibody profiling which address developability issues arising from hydrophobicity and charged-based solution behavior, PK, and the ability to enrich for those that are approved by the U.S. Food and Drug Administration. Differences in strategy for optimizing the solution behavior of human IgG1 antibodies versus the IgG2 and IgG4 isotypes and the impact of pH alterations in formulation are discussed.
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spelling pubmed-85105632021-10-13 Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics Thorsteinson, Nels Gunn, John R. Kelly, Kenneth Long, Will Labute, Paul MAbs Report The effect of hydrophobicity on antibody aggregation is well understood, and it has been shown that charge calculations can be useful for high-concentration viscosity and pharmacokinetic (PK) clearance predictions. In this work, structure-based charge descriptors are evaluated for their predictive performance on recently published antibody pI, viscosity, and clearance data. From this, we devised four rules for therapeutic antibody profiling which address developability issues arising from hydrophobicity and charged-based solution behavior, PK, and the ability to enrich for those that are approved by the U.S. Food and Drug Administration. Differences in strategy for optimizing the solution behavior of human IgG1 antibodies versus the IgG2 and IgG4 isotypes and the impact of pH alterations in formulation are discussed. Taylor & Francis 2021-10-10 /pmc/articles/PMC8510563/ /pubmed/34632944 http://dx.doi.org/10.1080/19420862.2021.1981805 Text en © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Report
Thorsteinson, Nels
Gunn, John R.
Kelly, Kenneth
Long, Will
Labute, Paul
Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics
title Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics
title_full Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics
title_fullStr Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics
title_full_unstemmed Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics
title_short Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics
title_sort structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510563/
https://www.ncbi.nlm.nih.gov/pubmed/34632944
http://dx.doi.org/10.1080/19420862.2021.1981805
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