Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1784582601080569856 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8510563 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT thorsteinsonnels structurebasedchargecalculationsforpredictingisoelectricpointviscosityclearanceandprofilingantibodytherapeutics AT gunnjohnr structurebasedchargecalculationsforpredictingisoelectricpointviscosityclearanceandprofilingantibodytherapeutics AT kellykenneth structurebasedchargecalculationsforpredictingisoelectricpointviscosityclearanceandprofilingantibodytherapeutics AT longwill structurebasedchargecalculationsforpredictingisoelectricpointviscosityclearanceandprofilingantibodytherapeutics AT labutepaul structurebasedchargecalculationsforpredictingisoelectricpointviscosityclearanceandprofilingantibodytherapeutics |