Abstract: The present invention is in the field of recombinant biotechnology, in particular in the field of protein expression. The invention generally relates to a method of expressing a protein of interest (POI) from a host cell. The invention relates particularly to improving a host cell's capacity to express and/or secrete a protein of interest and use of the host cell for protein expression. The invention also relates to cell culture technology, and more specifically to culturing cells to produce desired molecules for medical purposes or food products.

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.

Abstract: A customizable facility for manufacturing at least one product has at least one modular unit in communication with at least one central unit configured to provide utilities to the at least one modular unit. In some embodiments, the central unit(s) and modular unit(s) are positioned at least partially within a shell. Each modular unit can be a fermentation unit, a pre-viral unit, a post-viral unit, a utility space, a warehouse, a media buffer facility, an office, a personnel unit, or another unit. The modular units can be arranged to maximize a number of modular units within the shell while minimizing a footprint of the shell. A method of assembling a facility for manufacturing at least one product includes providing at least one central unit and providing at least one modular unit in communication with the central unit(s) such that utilities are provided by the central unit(s) to the modular unit(s).

Abstract: The monitoring and control of bioprocesses is provided. The present disclosure provides the ability to generate generic calibration models, independent of cell line, using inline Raman probes to monitor changes in glucose, lactate, glutamate, ammonium, viable cell concentration (VCC), total cell concentration (TCC) and product concentration. Calibration models were developed from cell culture using two different CHOK1SV GS-KO™ cell lines producing different monoclonal antibodies (mAbs). Developed predictive models, qualified using an independent CHOK1SV GS-KO™ cell line not used in calibration, measured changes in glucose, lactate, ammonium, VCC, and TCC with minor prediction errors over the course of cell culture with minimal cell line dependence. The development of these generic models allows the application of spectroscopic PAT techniques in a clinical manufacturing environment, where processes are typically run once or twice in GMP manufacturing based on a common platform process.

Abstract: A variable diameter bioreactor vessel is provided that includes a first vessel section having a first diameter configured to hold a liquid media and biologic material, and a second vessel section having a second diameter that is greater than the first diameter such that the liquid media can be increased from a first volume to a second volume within the vessel.

Abstract: The invention relates to methods of reducing the immunogenicity of CRISPR-associated (Cas) proteins and the modified Cas proteins produced therefrom. In addition, the invention relates to methods for cell and gene therapy, including any and all genetic modifications and alterations of gene expression (and/or genetic elements) made in-vivo or ex-vivo using Cas proteins with reduced immunogenicity.

Abstract: A process and system for efficiently producing reference data that can be fed into a predictive model for predicting quality attribute concentrations in cell culture processes. A perfusion bioreactor is operated at pseudo-steady-state conditions and one or more attribute influencing parameters are manipulated and changed over time. As the one or more attribute influencing parameters are manipulated, one or more quality attributes are monitored and measured. In one embodiment, multiple quality attributes are monitored and measured in parallel. The quality attribute information is recorded in conjunction with the changes in the attribute influencing parameters. This information is then fed to the predictive model for propagating cell cultures in commercial processes and maintaining the cell cultures within desired preset limits.

Abstract: A bioprocess system and a method for incubating, growing and harvesting cell cultures is described. Also disclosed is a bioprocess container that can be used with the system. In one aspect of the present disclosure, the bioprocess system includes bioprocess tubes and cell culture tubes having particular dimensions and being made from specific materials that allow the tubes to be welded together while preventing open connections and/or ruptures. In this manner, bioprocess containers can be connected and disconnected from a cell culture apparatus without having to perform the manipulation within a closed environment and without associated monitoring.

Abstract: A rupture disk includes a body including an internal wall extending from a first end of the body to a second end of the body. The internal wall defines an opening extending through the body. In some embodiments, the body further includes an internal flange formed on the internal wall, and the internal flange has a stepped surface. A rupture membrane is positioned within the body, and secured, for example, by cold welding. The rupture membrane may be secured to the stepped surface. The rupture membrane is positioned within the body such that the rupture membrane does not extend beyond the first end of the body. A process system including the rupture disk is also provided. A method of maintaining a process system that includes the rupture disk is also provided.

Abstract: The present invention is in the field of recombinant biotechnology, in particular in the field of protein expression. The invention generally relates to a method of expressing a protein of interest (POI) from a host cell. The invention relates particularly to improving a host cell's capacity to express and/or secrete a protein of interest and use of the host cell for protein expression. The invention also relates to cell culture technology, and more specifically to culturing cells to produce desired molecules for medical purposes or food products.

Abstract: The present disclosure features methods and compositions for modulating lipid metabolism to achieve improved production and quality of recombinant products, such as next generation biologics. Modulation of lipid metabolism as described herein includes, for example, introducing a lipid metabolism modulator described herein to a cell or a cell-free system. Also encompassed by the present disclosure are engineered cells with improved production capacity and improved product quality, methods for engineering such cells, and preparations and mixtures comprising the products from such cells.

Abstract: Disclosed herein are, inter alia, methods and compositions useful for detecting and/or quantifying host cell proteins during the production of a product, e.g., a recombinant protein, e.g., an antibody.

Abstract: Disclosed herein are, inter alia, methods and compositions useful for detecting and/or quantifying host cell proteins during the production of a product, e.g., a recombinant protein, e.g., an antibody.

Abstract: A method of producing a protein of interest (POI) by culturing a recombinant eukaryotic cell line comprising an expression construct comprising a regulatable promoter and a nucleic acid molecule encoding a POI under the transcriptional control of said promoter, comprising the steps a) cultivating the cell line with a basal carbon source repressing the promoter, b) cultivating the cell line with a limited amount of a supplemental carbon source de-repressing the promoter to induce production of the POI at a transcription rate of at least 15% as compared to the native pGAP promoter, and c) producing and recovering the POI; and further an isolated regulatable promoter and a respective expression system.

Abstract: A sampling system can include a cassette assembly coupled to a station base that has a plurality of actuators. The cassette assembly can include a cassette base, a cassette top, and an elastomer membrane disposed between the cassette base and cassette top. The cassette base can include a sample inlet, a reservoir for receiving a sample from the sample inlet, a sample outlet, and a fluid flow path extending between the sample inlet, the reservoir, and the sample outlet.

Abstract: The present invention relates to a displacement device, DD, for providing a displacement of a syringe closure system for a syringe relative to the syringe, a testing device, TD, and a method for leakage testing of a connection of a syringe closure system for a syringe with the syringe.

Abstract: A method for producing a recombinant protein of interest (POI) is provided, comprising the steps of (a) culturing cells in a cell culture medium to express said POI by adding a feed comprising at least one substrate to said cell culture, (b) applying a feeding strategy based on calculating, setting and optionally controlling the specific substrate uptake rate qs of the cells during the induction phase and/or production phase of the POI, wherein qs is set to be close to the maintenance rate of the cell culture; and (c) isolating said POI from the cell culture.

Abstract: A campus for fabricating at least one pharmaceutical product has one or more customizable facilities each configured to manufacture the at least one pharmaceutical product, a media/buffer plant, and a utility building connected by a utility line to the media/buffer plant and/or the one or more customizable facilities to provide at least one first utility to the media/buffer plant and/or the one or more customizable facilities via the utility line.

Abstract: A single-use bioreactor is provided. The single-use bioreactor may include a bioprocess container, a shell, at least one agitator, at least one sparger, at least one gas filter inlet port for the sparger(s) and headspace overlay, at least one fill port, at least one harvest port, at least one sample port, and at least one probe. In examples, at least one controller may monitor and control one or more parameters associated with the single-use bioreactor A method to cultivate and propagate mammalian cells is also provided. The method may include cultivating under suitable conditions and in a suitable culture medium in a first single-use bioreactor, transferring the medium containing the cells obtained by propagation from the at least one mammalian cell is into a second single-use bioreactor, transferring the medium containing the cells obtained by propagation from the at least one mammalian cell is into a third single-use bioreactor, and cultivating the cells in the third bioreactor.

Abstract: An isolated nucleic acid encoding a leader, which has a specific sequence, an isolated leader peptide encoded by such nucleic acid, an expression cassette comprising such nucleic acid encoding a leader operably linked to a nucleic acid sequence encoding a POI a recombinant yeast host cell or a vector comprising such expression cassette, a method of producing a POI in such yeast host cell, and further the use of the specific nucleic acid for the secretion of a POT from a host cell and/or to increase the secretion of a POT from a host cell.