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Developing a medium combination to attain similar glycosylation profile to originator by DoE and cluster analysis method
Glycosylation is critical for monoclonal antibody production because of its impact on pharmacokinetics and pharmacodynamics. Modulation of glycan profile is frequently needed in biosimilar development. However, glycosylation profile is not a single value like that of cell culture titer, hence making...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007809/ https://www.ncbi.nlm.nih.gov/pubmed/33782463 http://dx.doi.org/10.1038/s41598-021-86447-0 |
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author | Xu, Jian Shao, Zhihui Wang, Zhanqing Huang, Yingfeng Zou, Xun Shen, Yaling |
author_facet | Xu, Jian Shao, Zhihui Wang, Zhanqing Huang, Yingfeng Zou, Xun Shen, Yaling |
author_sort | Xu, Jian |
collection | PubMed |
description | Glycosylation is critical for monoclonal antibody production because of its impact on pharmacokinetics and pharmacodynamics. Modulation of glycan profile is frequently needed in biosimilar development. However, glycosylation profile is not a single value like that of cell culture titer, hence making it challenging for the Design of Experiment (DoE) methodology to be directly applied. In this study, a Her2-binding antibody was developed as a biosimilar to Herceptin. Cluster analysis was introduced to demonstrate the similarity of glycan profiles between the samples and the reference with specific value—distance. The glycosylation was subsequently optimized with the DoE method. Basal medium and feed medium were found to be the significant factors to the glycosylation pattern. Moreover, a combination of medium and feed strategy was developed to attain the most similar glycoprotein molecule to that of the originator biologic drug. This study may provide an additional option to evaluate multivariable factors and assess biosimilarity and/or comparability in monoclonal antibody production. |
format | Online Article Text |
id | pubmed-8007809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80078092021-03-30 Developing a medium combination to attain similar glycosylation profile to originator by DoE and cluster analysis method Xu, Jian Shao, Zhihui Wang, Zhanqing Huang, Yingfeng Zou, Xun Shen, Yaling Sci Rep Article Glycosylation is critical for monoclonal antibody production because of its impact on pharmacokinetics and pharmacodynamics. Modulation of glycan profile is frequently needed in biosimilar development. However, glycosylation profile is not a single value like that of cell culture titer, hence making it challenging for the Design of Experiment (DoE) methodology to be directly applied. In this study, a Her2-binding antibody was developed as a biosimilar to Herceptin. Cluster analysis was introduced to demonstrate the similarity of glycan profiles between the samples and the reference with specific value—distance. The glycosylation was subsequently optimized with the DoE method. Basal medium and feed medium were found to be the significant factors to the glycosylation pattern. Moreover, a combination of medium and feed strategy was developed to attain the most similar glycoprotein molecule to that of the originator biologic drug. This study may provide an additional option to evaluate multivariable factors and assess biosimilarity and/or comparability in monoclonal antibody production. Nature Publishing Group UK 2021-03-29 /pmc/articles/PMC8007809/ /pubmed/33782463 http://dx.doi.org/10.1038/s41598-021-86447-0 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Xu, Jian Shao, Zhihui Wang, Zhanqing Huang, Yingfeng Zou, Xun Shen, Yaling Developing a medium combination to attain similar glycosylation profile to originator by DoE and cluster analysis method |
title | Developing a medium combination to attain similar glycosylation profile to originator by DoE and cluster analysis method |
title_full | Developing a medium combination to attain similar glycosylation profile to originator by DoE and cluster analysis method |
title_fullStr | Developing a medium combination to attain similar glycosylation profile to originator by DoE and cluster analysis method |
title_full_unstemmed | Developing a medium combination to attain similar glycosylation profile to originator by DoE and cluster analysis method |
title_short | Developing a medium combination to attain similar glycosylation profile to originator by DoE and cluster analysis method |
title_sort | developing a medium combination to attain similar glycosylation profile to originator by doe and cluster analysis method |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007809/ https://www.ncbi.nlm.nih.gov/pubmed/33782463 http://dx.doi.org/10.1038/s41598-021-86447-0 |
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