Cell-controlled perfusion in continuous culture
AssigneeBoehringer Ingelheim International GmbH
InventorsGregory Walter HILLER, Matthew Paul GAGNON, Ana Maria OVALLE
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Abstract
Methods of protein production in continuous perfusion mammalian cell culture bioreactors are provided. Methods for continuous perfusion culture by allowing cells to self-regulate the rate of addition of perfusion medium to the bioreactor via a pH change are presented. Compositions comprising the perfusion medium as well as the process advantages of using hi-end pH control of perfusion or HIPCOP are also presented.
Claims20
A continuous perfusion culture process, comprising:
- (a) monitoring pH in a cell culture with a pH sensor;
- (b) delivering fresh medium and removing permeate when the pH is above a predetermined value;
- and
- (c) deactivating the medium delivery and the permeate removal when the pH is below the predetermined value.
A method for achieving rapid cell growth in a continuous perfusion culture process, comprising:
- (a) monitoring pH in a cell culture with a pH sensor;
- (b) delivering fresh medium and removing permeate when the pH is above a predetermined value;
- and
- (c) deactivating the medium delivery and the permeate removal when the pH is below the predetermined value.
A bioreactor for conducting a continuous perfusion culture process, wherein the continuous perfusion culture process comprises the steps of:
- (a) monitoring pH in a cell culture with a pH sensor;
- (b) delivering fresh medium and removing permeate when the pH is above a predetermined value;
- and
- (c) deactivating the medium delivery and the permeate removal when the pH is below the predetermined value.
A perfusion culture process, comprising:
- (d) monitoring pH in a cell culture in a perfusion bioreactor with a pH sensor;
- (e) delivering fresh medium to the perfusion bioreactor and removing permeate when the pH is above a predetermined value;
- and
- (f) deactivating the medium delivery and the permeate removal when the pH is below the predetermined value.
A method for achieving rapid cell growth in a perfusion culture process, comprising:
- (d) monitoring pH in a cell culture in a perfusion bioreactor with a pH sensor;
- (e) delivering fresh medium to the perfusion bioreactor and removing permeate when the pH is above a predetermined value;
- and
- (f) deactivating the medium delivery and the permeate removal when the pH is below the predetermined value.
A protein of interest produced by a method comprising:
- (a) culturing cells comprising a gene that encodes the protein of interest in a perfusion cell culture bioreactor under conditions that allow production of the protein of interest comprising:
- i. monitoring pH in the cell culture bioreactor with a pH sensor;
- ii. delivering fresh medium and removing permeate when the pH is above a predetermined value;
- and
- iii. deactivating the medium delivery and the permeate removal when the pH is below the predetermined value.
- (b) harvesting the protein of interest from the cell culture bioreactor.
Dependencies are inferred from the claim text.