Novel strategy to reduce lactic acid production and control ph in animal cell culture

Abstract

The present disclosure provides a method for culturing cells in exogenous lactic acid. Certain aspects of the present disclosure include the production of recombinant proteins, such as antibodies and fragments thereof. Certain aspects of the present disclosure also relate to methods of controlling lactic acid production, pH stability and osmolality in cell culture.

1 . A method for culturing an animal cell, comprising the steps of:
 (a) selecting a sufficient concentration of exogenous lactate to reduce lactic acid production by the cell, wherein said selecting comprises culturing the cell at various concentrations of lactate and measuring cell density; and   (b) culturing the cell in the sufficient concentration of exogenous lactate.   
     
     
         2 . The method according to  claim 1 , further comprising adapting the cell to the sufficient concentration of exogenous lactate prior to said culturing step, thereby producing an adapted cell capable of growing in the sufficient concentration of exogenous lactate. 
     
     
         3 . The method according to  claim 1 , wherein said selecting step further comprises monitoring one or more of cell growth rate, pH, and osmolality. 
     
     
         4 . The method according to  claim 1 , further comprising measuring a concentration of one or more nutrients or metabolites. 
     
     
         5 . The method according to  claim 4 , wherein said one or more nutrients or metabolites is selected from the group consisting of glucose, glutamine, lactate and ammonium. 
     
     
         6 . The method according to  claim 1 , wherein said culturing step does not require an external pH control system to maintain optimum cell growth and viability. 
     
     
         7 . The method according to  claim 6 , wherein culturing the cell with the sufficient concentration of exogenous lactate maintains the pH at a range from about 7.0 to about 7.5. 
     
     
         8 . The method according to  claim 1 , further comprising infecting said cell with a viral vector in the sufficient concentration of lactate. 
     
     
         9 . The method according to  claim 8 , wherein the viral vector is for a gene therapy or a vaccine. 
     
     
         10 . The method according to  claim 2 , wherein the adapted cells express a recombinant polypeptide. 
     
     
         11 . The method according to  claim 10 , wherein the recombinant polypeptide is expressed transiently. 
     
     
         12 . The method according to  claim 1 , wherein said culturing step comprises a fed batch animal cell culture and the addition of a concentrated nutrient feed.