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US 11,597,903 B2Granted
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.
Claims8
A continuous perfusion culture process, comprising:
- a) monitoring pH in a cell culture with a pH sensor, wherein the cell culture comprises mammalian cells;
- 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,
- wherein the fresh medium comprises glucose and L-lactate, and
- wherein the cells control their perfusion rate over the entire continuous perfusion period by taking up lactic acid when the glucose level in the cell culture becomes limiting, and excreting lactic acid when the glucose level in the cell culture becomes non-limiting.
3 more elements
Dependencies are inferred from the claim text.