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.