Improved fermentation processes for NS0 cell lines expressing human antibodies and XXXX synthetase.

@entity1522 @entity1160 @entity68 @entity535 @entity69 @entity36475 @entity36251 @entity165
To meet the increasing requirement for therapeutic antibodies to conduct clinical trials, an enhanced culture medium and fed-batch process was developed for GS-NS0 cell lines. This process was shown to produce high concentrations of monoclonal antibodies for several cell lines expressing different antibodies. Cells were adapted to growth in a @entity1160 - and serum-free medium containing bovine serum albumin (BSA), @entity165 , and @entity69 . A number of @entity1522 were found to be depleted during cell culture. The concentrations of these @entity1522 were increased, and further cell culture analyses were performed. This process of cell growth and analysis was repeated over multiple cycles until no depletion was detected. This resulted in an @entity535 supplement that was shown to be generic and enhanced antibody productivity up to 5-fold for the three cell lines tested. @entity69 was replaced using @entity36251 , a lipophilic @entity68 chelator and @entity36475 . Cell growth was equivalent to that in @entity69 -containing medium over the wide ranges tested. A concentrated feed solution, based on the @entity535 supplement and the components of the serum- and protein-free supplements, was formulated. Addition of this feed in response to metabolic requirements resulted in a harvest titer a further 2-fold higher than the enhanced culture medium. Harvest antibody titers of up to 600 mg/L were achieved for three cell lines expressing different antibodies, representing an increase of 10-fold over the starting concentrations.
