Abstract: The present invention relates to a mammalian FGF21 responsive reporter cell line and method of using the same for detecting and optionally quantitating FGF21 activity in a test sample. The invention further relates to a method for detecting and optionally quantitating neutralizing antibodies against FGF21 present in a test sample using the reporter cell line of the present invention.

Abstract: The present invention relates to small secreted reporter-peptides 15 to 150 amino-acids in length comprising a response element, activated by one or more transcription factors induced by the pharmacology active substance to be analyzed following its interaction with a specific intracellular or cell surface molecule, functionally linked to a response element, a TATA box, a signal peptide, anchor and detection sequences to which antibodies can be raised, and a poy-A tail. The anchor sequence may differ from one peptide to another or may be common to multiple secreted reporter-peptides such that all the peptides can be analyzed simultaneously by ELISA using a detection antibody labelled with for example HRP, or by the use of a commonly available immuno-detection platform such MSD, Gyros, AlphaLisa, or Biacore.

Abstract: The activity of a number of therapeutic antibodies is mediated in part by antibody-dependent cell-mediated cytotoxicity (ADCC). An engineered effector cell line expressing the low affinity Fc receptor, Fc?R111a (CD16), that responds to ligation of the Fc moiety of antibody bound to the specific antigen expressed on target cells by activation of a NFAT responsive reporter gene is described. In this cell line the firefly luciferase (FL) reporter gene is regulated by a novel synthetic chimeric promoter containing binding sites for NF-AT, AP1, NFkB, and STAT5 that confers improved sensitivity, an improved dynamic range, an improved tolerance to human serum and a reduced incubation time, relative to engineered effector cell lines that express a NFAT regulated reporter-gene, when used in an ADCC assay together with engineered target cells.

Abstract: Cell based assays are required for the detection of biological activity and hence are required for use as potency assays, detection of neutralizing antibodies and detection and quantification of the effector cell function of therapeutic antibodies or the quantification of the potency or neutralizing antibody response to virus vectors such as AAV vectors used in gene therapy. Cell-based assay are also required for the quantification of antibody mediated effector functions including complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cell-mediated cytotoxicity (ADCC). Cell based assays are difficult to adapt for use on automated immuno-assay platforms.

Abstract: The present invention relates novel cells and their use in methods for determining the antibody-dependent cell-mediated cytotoxicity (ADCC) or antibody-dependent cell-mediated phagocytosis (ADCP) in a sample.

Abstract: The activity of a number of therapeutic antibodies is mediated in part by antibody-dependent cell-mediated cytotoxicity (ADCC). An engineered effector cell line expressing the low affinity Fc receptor, Fc?R111a (CD16), that responds to ligation of the Fc moiety of antibody bound to the specific antigen expressed on target cells by activation of a NFAT responsive reporter gene is described. In this cell line the firefly luciferase (FL) reporter gene is regulated by a novel synthetic chimeric promoter containing binding sites for NF-AT, AP1, NFkB, and STAT5 that confers improved sensitivity, an improved dynamic range, an improved tolerance to human serum and a reduced incubation time, relative to engineered effector cell lines that express a NFAT regulated reporter-gene, when used in an ADCC assay together with engineered target cells.

Abstract: The invention provides an assay-ready frozen eukaryotic cell (stored frozen) in a composition that includes a cryopreservative and an inhibitor of xanthine oxidase, a kit containing a plurality of the assay-ready frozen eukaryotic cell, and a method of preparation thereof to minimize the variability in the performance of the cell, particularly in terms of undesirable intra- and inter-assay variability.

Abstract: The present invention provides a cell for use in a one-step cell-based assay for an extracellular ligand (e.g., IFN?) that initiates a ligand-specific signal at the nucleus of the cell and for neutralizing antibodies against the extracellular ligand. The cell-based one-step assay allows both the extracellular ligand concentration and the neutralizing antibody titer to be quantified in a single sample (e.g., serum) without the need for sample dilution and addition of exogenous extracellular ligand.

Abstract: The invention provides an assay-ready frozen eukaryotic cell (stored frozen) in a composition that includes a cryopreservative and an inhibitor of xanthine oxidase, a kit containing a plurality of the assay-ready frozen eukaryotic cell, and a method of preparation thereof to minimize the variability in the performance of the cell, particularly in terms of undesirable intra- and inter-assay variability.

Abstract: The present invention relates to a commercializable cell and to a gene reporter assay method and a kit which use this cell to determine the presence and/or the level of a molecule that activates signal transduction activity of a cell surface protein. This cell is treated in such a manner that it will have a sufficiently long shelf life for its intended purpose, whereupon at the end of its useful shelf life or at the end of its use, i.e., in an assay, the cell undergoes cellular death.

Abstract: The present invention provides a reporter gene containing cell line with increased specificity and/or sensitivity for a particular extracellular signal of interest so that it can be used in a gene-reporter assay to accurately determine the presence and/or level of the extracellular signal of interest in the presence of other extracellular signals that are capable of activating the same signal transduction pathway as the extracellular signal of interest or that are capable of activating another signal transduction pathway capable of modulating the transcription of the reporter gene.

Abstract: A method for conducting a neutralization assay for the determination of the titer of antibodies in a sample is provided which is an improvement over existing neutralization assays because the sensitivity of the reporter gene assay to determine neutralization is increased by the use of a “one time use” cell line transformed with a reporter gene construct. The titer is determined for antibodies specific for a predetermined target molecule that activates the signal transduction activity of a cell surface protein or a pattern recognition receptor or are specific for an antagonist for the predetermined target molecule.

Abstract: The present invention relates to a commercializable cell and to a gene reporter assay method and a kit which use this cell to determine the presence and/or the level of a molecule that activates signal transduction activity of a cell surface protein. This cell is treated in such a manner that it will have a sufficiently long shelf life for its intended purpose, whereupon at the end of its useful shelf life or at the end of its use, i.e., in an assay, the cell undergoes cellular death.

Abstract: A method for conducting a neutralization assay for the determination of the titer of antibodies in a sample is provided which is an improvement over existing neutralization assays because the sensitivity of the reporter gene assay to determine neutralization is increased by the use of a “one time use” cell line transformed with a reporter gene construct. The titer is determined for antibodies specific for a predetermined target molecule that activates the signal transduction activity of a cell surface protein or a pattern recognition receptor or are specific for an antagonist for the predetermined target molecule.

Abstract: The present invention relates to a commercializable cell and to a gene reporter assay method and a kit which use this cell to determine the presence and/or the level of a molecule that activates signal transduction activity of a cell surface protein. This cell is treated in such a manner that it will have a sufficiently long shelf life for its intended purpose, whereupon at the end of its useful shelf life or at the end of its use, i.e., in an assay, the cell undergoes cellular death.

Abstract: The present invention relates to a commercializable cell and to a gene reporter assay method and a kit which use this cell to determine the presence and/or the level of a molecule that activates signal transduction activity of a cell surface protein. This cell is treated in such a manner that it will have a sufficiently long shelf life for its intended purpose, whereupon at the end of its useful shelf life or at the end of its use, i.e., in an assay, the cell undergoes cellular death.

Abstract: The present invention provides a reporter gene containing cell line with increased specificity and/or sensitivity for a particular extracellular signal of interest so that it can be used in a gene-reporter assay to accurately determine the presence and/or level of the extracellular signal of interest in the presence of other extracellular signals that are capable of activating the same signal transduction pathway as the extracellular signal of interest or that are capable of activating another signal transduction pathway capable of modulating the transcription of the reporter gene.

Abstract: In a method for eliminating voice signals from a stereo input signal stream a monophonic and a stereophonic signal stream is derived by adding (3) and subtracting, (4) respectively, the left and right signal content of the stereo input signal stream, where after the monophonic signal stream is filtered by means of a band stop filter device (5), and a stereo output signal stream is obtained by adding (6) the stereophonic signal stream and the filtered monophonic signal stream, and subtracting (7) the stereophonic signal stream and the filtered monophonic signal stream, respectively. The method may be applied for voice suppression in karaoke applications.

Abstract: The present invention relates to a commercializable cell and to a gene reporter assay method and a kit which use this cell to determine the presence and/or the level of a molecule that activates signal transduction activity of a cell surface protein. This cell is treated in such a manner that it will have a sufficiently long shelf life for its intended purpose, whereupon at the end of its useful shelf life or at the end of its use, i.e., in an assay, the cell undergoes cellular death.

Abstract: The invention relates to a method for at least two audio signals (A1, A2) each being impressed with a process function, particularly a transformation function. According to the invention, upper values (8) of a function-impressed audio signal (A3) are decreased after the function by a rate and subsequently all values (8, 9) of the partially decreased signal (A4) are increased.