In the biopharmaceutical industry, glycosylation is a critical protein quality attribute that can modulate the efficacy of a therapeutic glycoprotein. Obtaining a consistent glycoform profile in production is desired due to regulatory concerns because a molecule can be defined by its carbohydrate structures. Specifically, the fucose content of oligosaccharides in glycoproteins is one of the most important attributes which can significantly affect antibody-dependent cellular cytotoxicity (ADCC) activity, and it is therefore important to control when matching a biosimilar to an innovator molecule. Several strategies were explored in this study and a reagent addition was found to be able to manipulate the fucose content with the least undesired side effects. However, the response was significantly different between cell lines. Further experiments were then performed for deeper understanding of the mechanism of fucosylation in different CHO cell lines. Results show that the fucosylation related nucleotide pool changes after the reagent dosing are the main cause for the difference in fucosylation level response in different CHO cell lines and the reagent metabolism is also different between cell lines.

Controlling fucose content of glycoproteins expressed in different CHO cell lines

249th National Meeting (2015)

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