A multiscale modeling method for therapeutic antibodies in ion exchange chromatography
| العنوان: | A multiscale modeling method for therapeutic antibodies in ion exchange chromatography |
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| المؤلفون: | David Saleh, Rudger Hess, Michelle Ahlers‐Hesse, Federico Rischawy, Gang Wang, Jan‐Hendrik Grosch, Thomas Schwab, Simon Kluters, Joey Studts, Jürgen Hubbuch |
| المصدر: | Biotechnology and Bioengineering, 120 (1), 125-138 |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Antibodies, Monoclonal, biopharmaceutical downstream processing, mechanistic chromatography modeling, ion exchange chromatography, Bioengineering, Chromatography, Ion Exchange, multiscale modeling, Applied Microbiology and Biotechnology, Chemical engineering, Immunoglobulin G, ddc:660, Thermodynamics, Adsorption, quantitative structure–property relationships, Biotechnology |
| الوصف: | The development of biopharmaceutical downstream processes relies on exhaustive experimental studies. The root cause is the poorly understood relationship between the protein structure of monoclonal antibodies (mAbs) and their macroscopic process behavior. Especially the development of preparative chromatography processes is challenged by the increasing structural complexity of novel antibody formats and accelerated development timelines. This study introduces a multiscale in silico model consisting of homology modeling, quantitative structure-property relationships (QSPR), and mechanistic chromatography modeling leading from the amino acid sequence of a mAb to the digital representation of its cation exchange chromatography (CEX) process. The model leverages the mAbs' structural characteristics and experimental data of a diverse set of 21 therapeutic antibodies to predict elution profiles of two mAbs that were removed from the training data set. QSPR modeling identified mAb-specific protein descriptors relevant for the prediction of the thermodynamic equilibrium and the stoichiometric coefficient of the adsorption reaction. The consideration of two discrete conformational states of IgG4 mAbs enabled prediction of split-peak elution profiles. Starting from the sequence, the presented multiscale model allows in silico development of chromatography processes before protein material is available for experimental studies. |
| وصف الملف: | application/pdf |
| تدمد: | 1097-0290 0006-3592 |
| DOI: | 10.1002/bit.28258 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bed6c100d140e058f34c0ac110d66431 https://doi.org/10.1002/bit.28258 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bed6c100d140e058f34c0ac110d66431 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970290 00063592 |
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| DOI: | 10.1002/bit.28258 |