Method for increasing the specific production rate of eukaryotic cells

Abstract

The current invention reports the use of meta-tyrosine for increasing the specific productivity of a eukaryotic cell that produces/expresses a polypeptide. In the current method it is not necessary to perform a temperature-, osmolality- or pH shift or to add drugs like valproic acid or sodium butyrate to modulate the specific productivity of the cultivated cells. The method does not affect cell viability or product titer.

1 . A method for increasing specific productivity (qP) of a Chinese Hamster Ovary (CHO) cell, the method comprising culturing the cell in culture medium, wherein the culture medium contains meta-tyrosine. 
     
     
         2 - 9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the culture medium further comprises phenylalanine in a non-limiting concentration. 
     
     
         11 - 15 . (canceled) 
     
     
         16 . A method for producing an exogenous polypeptide in a Chinese Hamster Ovary (CHO) cell, wherein the CHO cell expresses a nucleic acid encoding the exogenous polypeptide, the method comprising culturing the CHO cell in a culture medium comprising meta-tyrosine. 
     
     
         17 . The method of  claim 16 , wherein the meta-tyrosine in the culture medium is at a concentration of from 0.2 mM to 0.7 mM. 
     
     
         18 . The method of  claim 16 , wherein the meta-tyrosine in the culture medium is at a concentration of from 0.25 mM to 0.6 mM. 
     
     
         19 . The method of  claim 16 , wherein the meta-tyrosine in the culture medium is at a concentration of from 0.3 mM to 0.5 mM. 
     
     
         20 . The method of  claim 16 , wherein the meta-tyrosine in the culture medium is at a concentration of from 0.3 mM to 0.4 mM. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . The method of  claim 16 , wherein the polypeptide is an immunoglobulin or a variant thereof or a fragment thereof or a fusion thereof. 
     
     
         24 . The method of  claim 16 , wherein the culture medium additionally comprises phenylalanine in a non-limiting concentration. 
     
     
         25 . The method of  claim 24 , wherein the molar ratio of meta-tyrosine/phenylalanine is lower than or equal to 1.25. 
     
     
         26 . The method of  claim 24 , wherein the molar ratio of meta-tyrosine/phenylalanine is lower than or equal to 0.25. 
     
     
         27 . The method of  claim 24 , wherein the molar ratio of meta-tyrosine/phenylalanine is lower than or equal to 0.125. 
     
     
         28 . The method of  claim 24 , wherein the molar ratio of meta-tyrosine/phenylalanine is lower than or equal to 0.025. 
     
     
         29 . The method of  claim 16 , wherein the culture medium temperature is kept constant during the process. 
     
     
         30 . A Chinese Hamster Ovary (CHO) cell culture medium comprising meta-tyrosine and phenylalanine in a molar ratio which is lower than or equal to 1.25. 
     
     
         31 . The cell culture medium of  claim 30 , wherein the culture medium is a chemically defined culture medium.