ETANERCEPT PRODUCTION PROCESS IN CROP LARGE SCALE PRODUCTION CELLS

摘要

The present invention relates to an improved system for large-scale production of proteins and / or proteins in cell cultures, particularly in media characterized by one or more of: 1) a concentration cumulative amino acid greater than about 70 mm; ii) a cumulative glutamine to asparagine molar ratio of less than about 2; iii) a cumulative glutamine to total amino acid molar ratio of less than about 0.2; iv) a cumulative inorganic ion to total amino acid molar ratio of about 0.4 to 1; or v) a combined cumulative concentration of asparagine and glutamine between about 16 and 36 mm is provided. The use of such a system allows the production of high protein levels and less accumulation of certain undesirable factors such as ammonium and / or lactate. Additionally, culture processes including a temperature shift, typically including a decrease in temperature when the culture has reached about 20-80% of its maximum cell density, are provided. alternatively or additionally, the present invention provides processes such that upon reaching a peak, lactate and / or ammonium levels in the culture decrease over time.