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US 11,634,680 B2Granted
Process and system for propagating cell cultures while preventing lactate accumulation
AssigneeLonza Ltd.
InventorsBrandon John Downey, John Michael Schmitt, Jeffrey Francis Breit
Life of this patent
Estimating the term…
Abstract
A predictive model is described that can predict parameter concentrations in the future based on initial, measured concentrations and historical data. A plurality of multivariate techniques can be used to construct the predictive model capable of forecasting concentrations over multiple and diverse cell lines. The predictive model is also scalable. In one embodiment, a future lactate concentration trajectory is determined and at least one condition within a bioreactor is changed or modified to maintain lactate concentration within desired ranges.
Claims28
A process for propagating a cell culture comprising:
- determining a concentration of one or more quality attributes selected from the group consisting of lactate, a protein, glycan, a charge variant, an aggregate, disulfide oxidation, and a disulfide shuffling variant, in a cell culture;
- measuring a value of at least one attribute influencing parameter within the cell culture;
- sending the quality attribute concentration and the value of the at least one attribute influencing parameter measurement to a controller, the controller including a predictive model that is configured to calculate a future concentration of the quality attribute in the cell culture based at least in part on the value of the at least one attribute influencing parameter;
- running simulations on an optimizer to calculate future concentrations of the quality attribute based on manipulation of the attribute influencing parameter within the cell culture;
- and
- the controller selectively changing at least one condition within the cell culture based upon the simulations of the calculated future concentration of the quality attribute in the cell culture for maintaining the quality attribute concentration within preset limits.
3 more elements
A process for propagating a cell culture comprising:
- determining a concentration of lactate in a cell culture;
- measuring a value of at least one lactate influencing parameter within the cell culture;
- sending the lactate concentration and the value of the at least one lactate influencing parameter measurement to a controller, the controller including a predictive model that is configured to calculate a future concentration of lactate in the cell culture based at least in part on the value of the at least one attribute influencing parameter;
- running simulations on an optimizer to calculate future concentrations of lactate based on manipulation of the lactate influencing parameter within the cell culture;
- and
- the controller selectively changing at least one condition within the cell culture based upon the simulations of the calculated future concentration of lactate in the cell culture for maintaining lactate concentration within preset limits,
- wherein the cell culture has an incubation period prior to being harvested, and wherein the predictive model forecasts a final lactate concentration at the end of the incubation period.
4 more elements
A system for propagating a cell culture comprising:
- a bioreactor defining a hollow interior for receiving a cell culture, the bioreactor including a plurality of ports for feeding and/or removing materials from the hollow interior;
- a nutrient media feed for feeding a nutrient media to the hollow interior of the bioreactor, the nutrient media feed being in fluid communication with at least one of the ports on the bioreactor;
- a controller configured to receive lactate concentration measurements of a cell culture contained in the bioreactor, the controller also being configured to receive measurements of at least one lactate influencing parameter, the controller including a predictive model that is configured to calculate a future concentration of lactate in a cell culture contained in the bioreactor, the controller being configured to run simulations on an optimizer to calculate simulated future concentrations of the lactate concentrations based on manipulation of the nutrient media within the cell culture, the controller being configured to control the nutrient media feed for selectively increasing or decreasing flow of a nutrient media into the bioreactor based upon the simulations of the predicted lactate concentration for maintaining the lactate concentration within preset limits.
Dependencies are inferred from the claim text.