Cell Culture Performance with Betaine

Abstract

This invention relates generally to the field of cell culture. More particularly, the invention relates to improving viability of recombinant cell cultures and the yields of secreted polypeptides therefrom by the addition of betaine to the tissue culture medium.

What is claimed is: 
     
         1 . A method comprising culturing a recombinantly engineered animal cell line in tissue culture medium, wherein the cell line is recombinantly engineered to express an antibody to a human EGF receptor, the medium has an effective amount of betaine and the medium is not hyperosmotic, whereby cell survival is improved relative to cells grown without betaine. 
     
     
         2 . The method of  claim 1 , wherein the recombinantly engineered cell line is a mammalian cell line. 
     
     
         3 . The method of  claim 2 , wherein the mammalian cell line is selected from the group consisting of CHO, VERO, BHK, HeLa, Cos, MDCK, 293, 3T3, a myeloma cell line, a hybridoma cell line, and WI38 cells. 
     
     
         4 . The method of  claim 3 , wherein the tissue culture medium is serum free. 
     
     
         5 . The method of  claim 4 , wherein the cells are grown during a proliferative phase in the absence of betaine, and in the presence of betaine in an induction phase. 
     
     
         6 . The method of  claim 5 , wherein the betaine is selected from the group consisting of glycine betaine and betaine aldehyde. 
     
     
         7 . The method of  claim 6 , wherein cell survival is improved by about 20%. 
     
     
         8 . The method of  claim 4 , wherein the betaine is at a concentration in the medium of from about 1 mM to about 100 mM. 
     
     
         9 . The method of  claim 8 , wherein the cell line is cultured in a bioreactor. 
     
     
         10 . The method of  claim 9 , wherein the cell line is grown in suspension culture. 
     
     
         11 . The method of  claim 10 , further comprising collecting the antibody. 
     
     
         12 . A method comprising
 culturing a recombinantly engineered mammalian cell line in tissue culture medium, wherein the cell line is recombinantly engineered to express an antibody to a human EGF receptor, the medium contains betaine at a concentration of from about 1 mM to about 100 mM, and the tissue culture medium is not hyperosmotic, and   collecting the antibody.   
     
     
         13 . The method of  claim 12 , wherein the mammalian cell line is a CHO cell line or a hybridoma, and the tissue culture medium is serum free. 
     
     
         14 . A cell culture comprising a recombinantly engineered animal cell line in tissue culture medium, wherein the cell line is recombinantly engineered to express an antibody to a human EGF receptor, the medium contains betaine at a concentration of about 1 mM to about 100 mM, and the tissue culture medium is not hyperosmotic. 
     
     
         15 . The cell culture of  claim 14 , wherein the recombinantly engineered cell line is a mammalian cell line. 
     
     
         16 . The cell culture of  claim 15 , wherein the mammalian cell line is selected from the group consisting of CHO, VERO, BHK, HeLa, Cos, MDCK, 293, 3T3, a myeloma cell line, a hybridoma cell line, and WI38 cells. 
     
     
         17 . The cell culture of  claim 16 , wherein the tissue culture medium is serum free. 
     
     
         18 . The cell culture of  claim 17 , wherein the betaine is selected from the group consisting of glycine betaine and betaine aldehyde. 
     
     
         19 . The cell culture of  claim 17 , wherein the cell line is grown in suspension culture. 
     
     
         20 . The cell culture of  claim 14 , wherein the recombinantly engineered cell line is a CHO cell line or a hybridoma cell line, and the tissue culture medium is serum free.