Methods of improving protein production in animal cell cultures are
provided. Cell culture methods are presented wherein glucose is fed in a
restricted manner to cell culture; this restricted feeding of glucose to
the cell culture results in lactate production being controlled to a low
level. The restricted feeding of glucose in a fed-batch process is not
accomplished through a constant-rate feeding of glucose, and the
restricted feeding need not depend on sampling. Instead, restricted
feeding of glucose to the culture is accomplished through feeding of
glucose to the culture at a rate that is a function of an expected or a
premodeled rate of glucose consumption by the animal cells when exposed
to medium containing a high level of glucose. Because lactate production
is controlled to low levels, recombinant protein production is increased.