Methods to control protein heterogeneity

摘要

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

主权项

1. A process for producing a recombinantly-expressed immunoglobulin comprising a heavy chain variable region comprising the sequence of SEQ ID NO: 2 and a light chain variable region comprising the sequence of SEQ ID NO: 7, comprising
culturing a mammalian cell which recombinantly expresses the immunoglobulin in a cell culture media comprising a yeast hydrolysate and/or a plant hydrolysate, thereby producing the recombinantly-expressed immunoglobulin, wherein the level of agalactosyl fucosylated biantennary oligosaccharides (sum of NGA2F and NGA2F-GlcNac) present on the produced immunoglobulin is decreased as compared to the level of agalactosyl fucosylated biantennary oligosaccharides (sum of NGA2F and NGA2F-GlcNac) of immunoglobulin produced in cell culture media which does not comprise said yeast hydrolysate, and/or said plant hydrolysate; and/or wherein the level of galactose containing fucosylated biantennary oligosaccharides (sum of NA1F and NA2F) present on the produced immunoglobulin is increased as compared to the level of galactose containing fucosylated biantennary oligosaccharides (sum of NA1F and NA2F) of immunoglobulin produced in cell culture media which does not comprise said yeast hydrolysate and/or said plant hydrolysate; and wherein the level of agalactosyl fucosylated biantennary oligosaccharides (sum of NGA2F and NGA2F-GlcNAc) present on the produced immunoglobulin is 66%-69%; and/or wherein the level of fucosylated biantennary oligosaccharides (sum of NA1F and NA2F) present on the produced immunoglobulin is 29%-31%.