Cell cultivation process

摘要

This invention relates to a cell culture process for the production of polypeptides in mammalian CHO cells characterized by one or more temperature and pH shifts which are adjusted in respect to their timing and step size to reduce cell death, increase product yield and improve product quality.

主权项

1. A process for the production of a recombinant polypeptide comprising culturing CHO cells in a medium under conditions comprising at least one temperature shift and at least one pH shift and expressing the recombinant polypeptide, wherein
the cells are grown at a first temperature for at least 3 days after inoculation of the bioreactor and the temperature is then shifted to a second temperature which is between about 1 and about 8° C. lower than the first temperature and the cells are maintained at said second temperature for a period of at least another 2 days; the cells are grown at a first pH value for at least 2 days after inoculation of the bioreactor and the pH is then shifted to a second pH value which is between about 0.05 and about 1 pH units lower than the first pH and the cells are grown at said second pH for at least 1 day.