Predictive glycoengineering of biosimilars using a Markov chain glycosylation model

Philipp N. Spahn, Anders Holmgaard Hansen, Stefan Kol, Bjørn Gunnar Voldborg, Nathan E. Lewis

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Abstract

Biosimilar drugs must closely resemble the pharmacological attributes of innovator products to ensure safetyand efficacy to obtain regulatory approval. Glycosylation is one critical quality attribute that must be matched, but it is inherently difficult to control due to the complexity of its biogenesis. This usually implies that costly and time-consuming experimentation is required for clone identification and optimization of biosimilar glycosylation. Here, we describe a computational method that utilizes a Markov model of glycosylation to predict optimal glycoengineering strategies to obtain a specific glycosylation profile with desired properties. The approach uses a genetic algorithm to find the required quantities to perturb glycosylation reaction rates that lead to the best possible match with a given glycosylation profile. Furthermore, the approach can be used to identify cell lines and clones that will require minimal intervention while achieving a glycoprofile that is most similar to the desired profile. Thus, this approach can facilitate biosimilar design by providing computational glycoengineering guidelines that can be generated with a minimal time and cost.
Original languageEnglish
Article number1600489
JournalBiotechnology Journal
Volume12
Issue number2
Number of pages10
ISSN1860-6768
DOIs
Publication statusPublished - 2017

Keywords

  • CHO cells
  • Markov model
  • Biosimilars
  • Erythropoietin
  • Glycoengineering

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