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 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 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 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.

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: The invention concerns the field of container closure integrity (CCI) and the testing of CCI and relates to a device and a method for leakage testing of a connection between a rubber stopper and a corresponding drug container which can be used for storing drugs under sterile conditions and which is closed by said rubber stopper.

Abstract: Disclosed herein are methods and compositions useful for evaluating, selecting, identifying, or making a cell or cell line that has improved production capacity for generating higher yields of products and/or improved capacity to produce higher quality products. Products, as described herein, can include a polypeptide that is endogenously expressed by the cell, a recombinant polypeptide that is not endogenously expressed, or a non-naturally occurring recombinant polypeptide. The methods described herein include modulating, e.g., inhibiting, the protein degradation pathway by using a proteasome inhibitor, an ER-associated degradation (ERAD) inhibitor, or a ubiquitin pathway inhibitor.

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 invention discloses a method for preparation of 1,4-sorbitan by dehydration of D-sorbitol, wherein one equivalent of water is removed and a cyclization occurs, followed by a treatment with ethanol and isopropanol.

Abstract: The invention relates to an isolated nucleic acid sequence comprising a promoter, which is a native sequence of Pichia pastoris comprising the nucleic acid sequence of pCS1 of SEQ ID 1, or a functionally active variant thereof which is a size variant, a mutant or hybrid of SEQ ID 1, or a combination thereof, expression constructs and recombinant host cells comprising the promoter, and a method of producing a protein of interest under the control of the promoter. It further relates to a method to identify a constitutive promoter from eukaryotic cells, and an isolated nucleic acid sequence comprising a promoter which when operatively linked to a nucleotide sequence encoding a protein of interest directs the expression thereof in a host cell at an expression level that is higher than under control of the native pGAP promoter at high and low growth rates.

Abstract: Disclosed are methods and devices for the optimization of virus removal from solutions. A method of filtering a process fluid comprising a product includes allowing some of the process fluid to flow from a first reservoir to a viral filter; adding a chase fluid to the process fluid in the first reservoir to form a composite fluid; and allowing the composite fluid to flow from the first reservoir to the viral filter to produce eluent. In some embodiments, flow of fluid across the viral filter is sufficient to avoid significant impairment to viral removal until a preselected event, occurs. In some embodiments, flow of fluid from the first reservoir across the viral filter is maintained in the absence of an interruption or slowing of flow of duration or magnitude sufficient to impair viral removal to a level below a log-reduction value of the viral filter.

Abstract: A manufacturing facility for the continuous production of biopharmaceuticals integrated with single-use disposable technology.

Abstract: The disclosure is directed to a system, apparatus, and method for continuously monitoring data output from a wireless sensor on a mesh network at a frequency higher than mesh formation/propagation. For example, the system may include a wireless gateway, an amplifier coupled to the wireless gateway, a first antenna coupled to the amplifier, a second antenna coupled to the amplifier, and a wireless sensor. The wireless sensor may be a wireless temperature sensor configured to monitor the temperature of a cryopreserved material product. The wireless gateway forms the mesh network. The first antenna may be located on a first level of a building, and the second antenna may be located on a second level of the building, where the second level may be at an elevation higher than the first level.

Abstract: The invention discloses a method for preparation of 5-fluoro-2-methyl-3-nitrobenzoic acid and its methyl ester by conversion of 5-fluoro-2-methylbenzoic acid with fuming nitric acid and oleum and subsequent conversion with methanol.

Abstract: The present disclosure features methods and compositions for increasing the amount of products of cellular metabolism, e.g., proteins, by lowering the temperature of cells expressing the product at one or more steps while culturing the cells, expressing the product, and/or recovering the product.

Abstract: Antibodies having modified constant regions so as to permit conjugation of the antibody to a payload such as a therapeutic agent are described. Preferred antibodies include a mutation at light chain position 180 (positional numbering), most preferably the mutation is to a residue selected from C, K, Q, or a non-natural amino acid. Additional mutations may also be combined with a mutation at position 180; including one or more of light chain (LC) S208, LC S171, LC S182, LC A184, LC V191, LC S202, LC S203, LC T206, heavy chain (HC) S160, HC T190, HC S443, HC S447, HC S139, HC S168, HC V170, HC V176, HC T200, HC S445 according to a positional numbering convention.