The Assessment of MAb Quality and Quantity

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Drouillard, Gerald
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University of Guelph

Monoclonal Antibodies (MAbs) make up a large portion of the therapeutic protein industry. A major component of MAb biosynthesis is the post-translational process whereby glycan chains are enzymatically attached to the protein side chain. The specific configuration of the glycan chains, which have been shown to have an effect on MAb efficacy and safety, are a measure of MAb quality. This work develops and explores a newly defined metric, titer quality (TQ), which is capable of quantifying both product quantity and product quality with respect to glycosylation. Optimization studies based on manipulating the culture environment were undertaken. Product quantity was improved by transitioning from 37 °C to hypothermic conditions (33 °C) between 24 and 48 hours post-inoculation. As compared with the proprietary medium BIOGRO CHO, product quality was improved with a medium formulation, named Mixture 6 (M6), which contained high levels of SITE and the soy hydrolysate HYPEP™ 1510, and low levels of the lipid mixture LM1 and a uridine, manganese, and galactose cocktail UMG supplements. M6 simultaneously promoted glycosylation, population growth and productivity. When a temperature shift strategy was employed, while both BIOGRO CHO and M6 were capable of achieving high final protein concentrations, the TQ was best in M6 due to the improved glycan profile.

monoclonal antibodies, chinese hamster ovary cells, media development, glycoprotein, productivity, glycosylation