Cell culture improvements

A fed-batch production method of making a human anti-TNFα antibody which comprises (1) a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:1 and (2) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:2, said method comprising culturing Chinese Hamster Ovary (CHO) cells comprising a nucleic acid encoding said anti-TNFα antibody in a cell culture production medium, wherein the glucose concentration in said medium is monitored and glucose is added to said medium if the glucose concentration in said medium decreases to below 2 g/L, or the glucose concentration in said medium is monitored and glucose is added to said medium to maintain the glucose concentration in said medium at a concentration of at least 2 g/L, such that said anti-TNFα antibody is produced at a titer of at least 2 g/L in said cell culture production medium.

A fed-batch production method of making adalimumab, comprising culturing Chinese Hamster Ovary (CHO) cells comprising a nucleic acid encoding adalimumab in a cell culture production medium, wherein glucose concentration in said medium is monitored and glucose is added to said medium if the glucose concentration in said medium decreases to below 2 g/L, or the glucose concentration in said medium is monitored and glucose is added to said medium to maintain the glucose concentration in said medium at a concentration of at least 2 g/L, such that adalimumab is produced at a titer of at least 2 g/L in said cell culture production medium.

An improved fed-batch large scale cell culture process for producing an anti-TNFα antibody which comprises (1) a light chain variable region comprising the amino acid sequence of SEQ ID NO:1 and (2) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:2, said method comprising culturing Chinese Hamster Ovary (CHO) cells comprising a nucleic acid encoding the anti-TNFα antibody in a cell culture production medium at a temperature between 32° C. to 38° C. wherein glucose concentration in said medium is monitored and glucose is added to said medium if the glucose concentration in said medium decreases to below 2 g/L, or the glucose concentration in said medium is monitored and glucose is added to said medium to maintain the glucose concentration in said medium at a concentration of at least 2 g/L, such that said anti TNFα-antibody is produced at a titer of at least 2 g/L in said cell culture production medium.