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 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 present invention provides a cell for use in a one-step cell-based assay for an extracellular ligand (e.g., I FN?) 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: Ongoing pathogenic immune reactions and the severity of an incipient or prospective immune reaction may be downregulated or reduced by locally administering Type I interferon at a site remote from the ongoing, incipient or prospective immune reaction. The amount of interferon to be administered is that which is effective to induce trafficking of antigen-presenting cells to the site of interferon administration, and away from the site of the immune reaction. It is administered in the course of the ongoing immune reaction, or concurrently with the provocation of an immune reaction.

Abstract: A method for enhancing the immune response to an antigen or vaccine comprising administering an effective amount of a Th1 stimulatory cytokine, preferably interferon, oromucosally at substantially the same time as administration of an effective amount of an antigen or vaccine.

Abstract: The present invention relates to identification of a gene upregulated by interferon-a administration corresponding to the cDNA sequence set forth in SEQ. ID. NO. 1. Determination of expression products of this gene is proposed as having utility in predicting responsiveness to treatment with interferon-? and other interferons which act at the Type 1 interferon receptor. Therapeutic use of the protein encoded by the same geneis also envisaged.

Abstract: The invention relates to a monoclonal antibody directed against the human interferon class I receptor (IFN-R) characterized by the following properties: it recognizes the extracellular domain of the human IFN-R, and it has a neutralizing capacity against the biological properties of the human type I-IFN. It further concerns their use for the diagnosis.

Abstract: The present disclosure relates to identification of previously known genes as being genes upregulated by interferon-? administration, in particular the human genes corresponding to the cDNA sequence in GenBank designated g4758303, g5453897, g4505186, g2366751, g33917, g4504962, g3978516, g5924396, g4505656, g1504007, g3702446, g4001802, g292289, g4557226, g4507646 and g4507170. Determination of expression products of these genes is proposed as having utility in predicting responsiveness to treatment with interferon-? and other interferons which act at the Type 1 interferon receptor.

Abstract: The invention provides peptides of about 9-12 amino acids having a sequence derived from the interferon binding site of the IFNAR1 chain of the Type 1-interferon (Type 1-IFN) receptor for use as a Type 1-IFN antagonist. In particular, the invention provides peptides having the 9 mer sequence FSSLKLNVY (SEQ ID no. 1) and analogues thereof for use as Type 1-IFN antagonists. Particularly preferred for this purpose is the peptide of SEQ ID no. 1 and analogues thereof including SEQ ID no. 1 having an additional asparagine residue (N) at the C-terminus and/or additional glutamic acid residue (E) at the N-terminus.

Abstract: Oromucosal administration of antagonists of cytokines associated with stimulation or enhancement of T helper 1 cell responses, preferably for example a Type 1-interferon antibody, is disclosed for inhibition or prevention of auto immune diseases.

Abstract: The present invention relates to identification of a gene upregulated by interferon-? administration corresponding to the cDNA sequence set forth in SEQ. ID. NO. 1. Determination of expression products of this gene is proposed as having utility in predicting responsiveness to treatment with interferon-? and other interferons which act at the Type 1 interferon receptor. Therapeutic use of the protein encoded by the same gene is also envisaged.

Abstract: The present disclosure relates to identification of genes upregulated by interferon-? administration, in particular the human genes corresponding to the cDNA sequences in GenBank designated g4586459, g2342476, g3327161 and g4529886. Determination of expression products of these genes is proposed as having utility in predicting responsiveness to treatment with interferon-? and other interferons which act at the Type 1 interferon receptor. Therapeutic use of the proteins encoded by the same genes is also envisaged.

Abstract: The present invention relates to identification of a gene upregulated by interferon-administration corresponding to the cDNA sequence set forth in SEQ. ID. No. 1. Determination of expression products of this gene is proposed as having utility in predicting responsiveness to treatment with interferon- and other interferons which act at the Type 1 interferon receptor. Therapeutic use of the protein encoded by the same gene is also envisaged.

Abstract: The present invention relates to identification of a gene upregulated by interferon-? administration corresponding to the cDNA sequence set forth in SEQ. ID. No. 1. Determination of expression products of this gene is proposed as having utility in predicting responsiveness to treatment with interferon-? and other interferons which act at the Type 1 interferon receptor. Therapeutic use of the protein encoded by the same gene is also envisaged.

Abstract: The present invention relates to identification of a gene upregulated by interferon-? administration corresponding to the cDNA sequences set forth in SEQ. ID. No. 1 or in SEQ. ID. No. 3. Determination of expression products of this gene is proposed as having utility in predicting responsiveness to treatment with interferon-? and other interferons which act at the Type 1 interferon receptor. Therapeutic use of the protein encoded by the same gene is also envisaged.