The present invention describes a method for producing an antibody in Pichia pastoris, such as by fed-batch fermentation. The method includes the addition of about 2.0 - 5.0 g/L of hydroxyurea during the fermentation process to sustain a constant cell density and enhance the whole broth titer of the antibody. The method may also include a strategy of increasing the ethanol concentration to about 18-22 g/L and then maintaining the ethanol level at about 5-17 g/L to stabilize the cell mass and enhance the production rate of the antibody. The method may further include a respiratory quotient control for monitoring the ethanol profile and to improve the quality of the antibody by, for example, eliminating clipping of the heavy chain.
申请公布号
WO2014152100(A1)
申请公布日期
2014.09.25
申请号
WO2014US26949
申请日期
2014.03.14
申请人
BRISTOL-MYERS SQUIBB COMPANY
发明人
XING, ZIZHUO;CAMPBELL, GEORGE S.;EAGAN, BRUCE E.;QIAN, YUEMING;XU, XUANKUO;YOU, LI;LI, ZHENGJIAN;QIAN, NAN-XIN