An improved model framework linking the extracellular environment to antibody glycosylation

Abstract

Background Glycoproteins make up the bulk of biologically-derived medicines, and are taking up an ever increasing share of the prescription pharmaceuticals market. As opposed to small molecule drugs, glycoproteins are large complex molecules with heterogeneity arising from a multitude of glycan moieties. Glycans are complex post-translation modifications, which result from a number of enzymatic reactions in the ER and Golgi collectively known as glycosylation and play an important role in pharmacokinetics such as drug safety, efficacy and half-life. It is known that the availability of the nucleotide sugar donors (NSDs), which are the co-substrates to the enzymatic glycosylation reactions of the Golgi, can be affected by a number of process conditions such as culture mode, temperature, dissolved oxygen and nutrient availability, as well as the addition of precursor molecules to the culture medium [1]. Consequently, feeding strategies of nucleotide and nucleotide sugar precursors have been explored to exert control over the glycoform [2,3]. In this work, a mathematical model platform is presented to quantify the impact of nutrient availability and feeding strategies on the glycosylation process with the aim to enable the design of feeding strategies to optimise the product glycoform.