Methods to control protein heterogeneity

摘要

The instant invention relates to the field of protein production, and in particular to compositions and processes for controlling and limiting the heterogeneity of proteins expressed in host cells.

主权项

1. A method for controlling the oligosaccharide distribution of a recombinantly-expressed immunoglobulin comprising
supplementing during a production stage a cell culture media used in the recombinant expression of said immunoglobulin with a yeast hydrolysate supplement and/or a plant hydrolysate supplement to achieve a yeast hydrolysate concentration in the media of at least 11 g/L and/or a plant hydrolysate concentration of at least 7 g/L and assessing the oligosaccharide distribution of the recombinantly-expressed immunoglobulin, thereby controlling the oligosaccharide distribution of the recombinantly-expressed immunoglobulin, wherein the level of agalactosyl fucosylated biantennary oligosaccharides (sum of NGA2F and NGA2F-G1cNac) present on the recombinantly-expressed immunoglobulin is decreased as compared to the level of agalactosyl fucosylated biantennary oligosaccharides (sum of NGA2F and NGA2F-G1cNac) of the immunoglobulin recombinantly-expressed in cell culture media which is not supplemented with said yeast hydrolysate supplement and/or said plant hydrolysate supplement during the production stage; and/or wherein the level of galactose containing fucosylated biantennary oligossacharides (sum of NA1F and NA2F) present on the recombinantly-expressed immunoglobulin is increased as compared to the level of galactose containing fucosylated biantennary oligossacharides (sum of NA1F and NA2F) of the immunoglobulin recombinantly-expressed in cell culture media which is not supplemented with said yeast hydrolysate supplement and/or said plant hydrolysate supplement during the production stage.