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A multiscale modeling method for therapeutic antibodies in ion exchange chromatography

Saleh, David 1; Hess, Rudger ORCID iD icon 1; Ahlers-Hesse, Michelle; Rischawy, Federico 1; Wang, Gang; Grosch, Jan-Hendrik; Schwab, Thomas; Kluters, Simon; Studts, Joey; Hubbuch, Jürgen ORCID iD icon 1
1 Institut für Bio- und Lebensmitteltechnik (BLT), Karlsruher Institut für Technologie (KIT)

Abstract:

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. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000152333
Veröffentlicht am 07.11.2022
Originalveröffentlichung
DOI: 10.1002/bit.28258
Scopus
Zitationen: 14
Web of Science
Zitationen: 9
Dimensions
Zitationen: 15
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Bio- und Lebensmitteltechnik (BLT)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2022
Sprache Englisch
Identifikator ISSN: 0006-3592, 1097-0290
KITopen-ID: 1000152333
Erschienen in Biotechnology and Bioengineering
Verlag John Wiley and Sons
Band 120
Heft 1
Seiten 125-138
Vorab online veröffentlicht am 13.10.2022
Schlagwörter biopharmaceutical downstream processing, ion exchange chromatography, mechanistic chromatography modeling, multiscale modeling, quantitative structure–property relationships
Nachgewiesen in Web of Science
Scopus
Dimensions
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