Cell culture methods
AssigneeUcb Biopharma Srl
InventorsBASSEM BEN YAHIA, LAETITIA MALPHETTES, NADINE KOCHANOWSKI, GILL RENNER, SANDRINE DURRAN, ANDREW JEFFREY YATES
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Abstract
The present invention relates to the use of limited amounts of cysteine and tryptophan in the cell culture medium during production of recombinant proteins, and in particular antibodies. Proteins and antibodies produced under such controlled conditions exhibit reduced heterogeneity, in particular reduced charge variants heterogeneity.
Claims23
A method for reducing the heterogeneity of the population of recombinant proteins in a batch produced in production phase by recombinant host cells comprising limiting the total amount of
- a) cysteine or cystine;
- and
- b) tryptophan
- present in the cell culture medium during the production phase of the recombinant protein.
A process for producing a recombinant protein comprising:
- a) culturing host cells capable of producing a recombinant protein in a medium;
- b) progressing the culture through a production phase wherein the recombinant protein is produced by the cells and the cell culture medium is supplemented with cysteine or cystine and tryptophan, wherein
- the total amount of cysteine or cystine provided during the process is from 2.9 to 7 g/(1012 cells), wherein cells refer to the expected integral viable cell count at the end of the production phase, and
- the total amount of tryptophan provided during the process is from 2.5 to 3.5 g/(1012 cells), wherein cells refer to the expected integral viable cell count at the end of the production phase,
- c) and, optionally, recovering the recombinant protein from the cell culture medium.
Dependencies are inferred from the claim text.