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Antibodies 2018, 7(1), 1; https://doi.org/10.3390/antib7010001

Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation

1
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA
2
Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, LA 70118, USA
*
Author to whom correspondence should be addressed.
Received: 16 October 2017 / Revised: 23 November 2017 / Accepted: 15 December 2017 / Published: 21 December 2017
(This article belongs to the Special Issue Monoclonal Antibodies)
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Abstract

In order to meet desired drug product quality targets, the glycosylation profile of biotherapeutics such as monoclonal antibodies (mAbs) must be maintained consistently during manufacturing. Achieving consistent glycan distribution profiles requires identifying factors that influence glycosylation, and manipulating them appropriately via well-designed control strategies. Now, the cell culture media supplement, MnCl2, is known to alter the glycosylation profile in mAbs generally, but its effect, particularly when introduced at different stages during cell growth, has yet to be investigated and quantified. In this study, we evaluate the effect of time-dependent addition of MnCl2 on the glycan profile quantitatively, using factorial design experiments. Our results show that MnCl2 addition during the lag and exponential phases affects the glycan profile significantly more than stationary phase supplementation does. Also, using a novel computational technique, we identify various combinations of glycan species that are affected by this dynamic media supplementation scheme, and quantify the effects mathematically. Our experiments demonstrate the importance of taking into consideration the time of addition of these trace supplements, not just their concentrations, and our computational analysis provides insight into what supplements to add, when, and how much, in order to induce desired changes. View Full-Text
Keywords: cell culture; glycosylation; media supplementation; MnCl2; controllability analysis cell culture; glycosylation; media supplementation; MnCl2; controllability analysis
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Radhakrishnan, D.; Robinson, A.S.; Ogunnaike, B.A. Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation. Antibodies 2018, 7, 1.

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