Abstract: A method of improving expression of polypeptides in mammalian cell culture systems is provided. In particular, the invention is directed to methods of culturing mammalian cells under conditions such as, for example, high levels of glucose, where environmental and nutritional conditions are controlled and adjusted so as to improve process robustness and to promote superior expression of polypeptides having desired qualities, e.g., biological activity. The invention also relates to polypeptides, especially antibodies, produced by the methods, and to methods of using such antibodies, and to pharmaceutical compositions containing the polypeptides. The invention also relates to methods of culturing animal cells in a fed batch cell culture to maximize production capacity, viability of the cell culture, and overall enhancement of yield from such cultures.