RATIONALLY DESIGNED MEDIA FOR CELL CULTURE

摘要

This invention relates to methods for rationally designing cell culture media for use in cell cultures, e.g., cell cultures employed in polypeptide production; cell culture media designed with the disclosed methods; methods of producing a polypeptide of interest, e.g., an antibody, using such media; polypeptides produced using the methods and media disclosed herein; and pharmaceuticals compositions containing such polypeptides. The rationally designed media contain a concentration of an amino acid that is calculated for use in cell mass, a concentration of the amino acid that is calculated for use in cell maintenance, and a concentration of the amino acid that is calculated for incorporation into the polypeptide of interest. The rationally designed media may contain a baseline- adjusted concentration, A, of at least one amino acid that is calculated according to the formula A=[(M_*X)+(N_*P)+(Y_*M_*X)]_*F, wherein X is the concentration of the amino acid that is used per unit of cell mass, P is the concentration of the amino acid that is used for incorporation into the polypeptide of interest per unit of polypeptide titer, M is the multiplier for the desired peak cell density of the cell culture, N is the multiplier for the desired concentration of the polypeptide of interest, Y is the cell maintenance factor; and F is the baseline factor. This rationally designed media may also be used to produce a starting cell culture medium comprising a concentration, B, of at least one amino acid according to the formula B=[A- (Z_*V)]/(1-V), wherein Z is a concentration of the amino acid in the feeding cell culture medium, and V is a volume of the feeding culture medium as a proportion of the desired cell culture medium volume.