Fed-batch method of making human anti-TNF-alpha antibody
OwnerItzcoatl A. Pla, Joseph G. Matuck +7inventors
InventorsItzcoatl A. Pla, Joseph G. Matuck, John C. Fann, Christof Schulz, Nichole A. Roy, David F. Bruton, James McIntire, Yu-Hsiang David Chang, Thomas Seewoester
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Abstract
The invention describes improved methods and compositions for producing a recombinant protein, e.g., an antibody, in mammalian cell culture. In addition, the invention provides improved cell culture media, including improved production media, feed solutions, and combination feeds, which may be used to improve protein productivity in mammalian cell culture.
Claims30
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 in large-scale, wherein the glucose concentration in said medium is monitored, the glucose concentration in said medium decreases to below 2 g/L, and glucose is added to said medium when 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 but no greater than 7 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 in large-scale, wherein glucose concentration in said medium is monitored, the glucose concentration in said medium decreases to below 2 g/L, and glucose is added to said medium when 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 but no greater than 7 g/L, such that adalimumab is produced at a titer of at least 2 g/L in said cell culture production medium.
A fed-batch method of producing adalimumab, comprising expressing adalimumab in large-scale in Chinese Hamster Ovary (CHO) cells in a cell culture production medium, wherein said CHO cells comprise an expression vector encoding adalimumab, wherein glucose concentration in said medium is monitored, the glucose concentration in said medium drops to a level between 1 and 5 g/L, and then glucose is added to said medium to maintain the glucose concentration in said medium at no less than 1-5 g/L, and wherein adalimumab is produced at a titer of at least 2 g/L in said cell culture production medium.
Dependencies are inferred from the claim text.