Abstract: The present invention relates methods for making stable calibrators and controls that can be used in ligand-binding assays.

Abstract: Methods and compositions for delivering pharmaceutical agents into cells, in particular urothelial cells of the bladder, are provided. In the methods and compositions of the invention, a solubilized cholesterol composition is used to facilitate delivery of pharmaceutical agents. Preferably, the cholesterol is solubilized by a cyclodextrin (e.g., methyl-?-cyclodextrin) and the pharmaceutical agent comprises a polynucleotide and either a cationic lipid, a cationic polymer or a dendrimer. Improved methods for transfecting polynucleotides into cells thus are also provided, using cationic lipids, cationic polymers or dendrimers and solubilized cholesterol, wherein the transfection efficiency is enhanced compared to use of cationic lipids, cationic polymers or dendrimers alone.

Abstract: Mass tagging methods are provided that lead to mass spectrometer detection sensitivities and molecular discriminations that are improved over other methods. In particular the methods are useful for discriminating tagged molecules and fragments of molecules from chemical noise in the mass spectrum. These mass tagging methods are useful for oligomer sequencing, determining the relative abundances of molecules from different samples, and identifying individual molecules or chemical processing steps in combinatorial chemical libraries. The methods provided are useful for the simultaneous analysis of multiple molecules and reaction mixtures by mass spectrometric methods.

Abstract: The present invention relates to methods for making stable compositions, such as, but not limited to, test samples, that can be used in ligand-binding assays.

Abstract: The invention provides a method for assaying for troponin I in a sample such as serum, the method comprising a determination of the troponin I concentration in a sample using a standard preparation that comprises a complete native troponin complex. One exemplary assay for troponin I concentration according to the invention is an immunoassay. Further contemplated in the method is a step comprising contacting the sample with a Ca2+-binding agent. Another aspect of the invention is the standard preparation comprising a complete native troponin complex. Yet another aspect of the invention is a kit for use in the assay method comprising the standard preparation, a detectable label, and a troponin I binding partner, such as an anti-troponin I antibody. All aspects of the invention are usefully practiced using human materials, such as a human troponin complex, and/or human sources for samples.

Abstract: The invention provides monoclonal antibodies and other binding agents to human cytochrome P450 2C19 having advantageous properties, including capacity substantially to inhibit enzyme activity of human cytochrome P450 2C19 and lack of specific binding to other human cytochrome P450s. The binding agents of the invention are useful inter alia in methods for screening drugs for metabolism by cytochrome P450 2C19, and in methods of measuring P450 2C19 levels in individuals relative to P450 2C19 levels in a control population.

Abstract: Disclosed is a method for distinguishing between protein variants using high field asymmetric waveform ion mobility spectrometry (FAIMS). A method according to the instant invention includes the steps of providing a FAIMS analyzer region defined by a space between two spaced-apart electrodes, and providing predetermined conditions within said FAIMS analyzer region. Ions of an analyte protein are produced from a solution having predetermined properties and including the analyte protein, using a suitable ionization source. The ions are introduced into the FAIMS analyzer region, transmitted therethrough, and detected. An intensity of the detected ions is measured at a predetermined CV value. At least a difference is determined, between the detected intensity and a reference value, the reference value relating to an expected intensity at the predetermined CV value for a reference form of the analyte protein.

Abstract: Use of calcineurin B homologous protein (CHP) from body fluids or body tissues as a marker peptide for diagnosis, for prognosis and for monitoring the course of inflammations and infections and/or as a target for therapeutically influencing the course of inflammations and/or infections.

Abstract: Use of calibrant in extraction phase is described for quantification of components of interest in samples in laboratory application as well as in on-site monitoring. This approach is particularly useful for in-vivo investigation of living systems.

Abstract: The present invention provides methods for determining a ratio of an amount of a glycated form of a protein to a total amount of the protein in a sample containing the glycated protein, the glycosylated protein, or the glycoprotein. The method incorporates lateral flow test strip or vertical flow test strip devices having negatively charged carboxyl or carboxylate groups and hydroxyboryl groups immobilized and interspersed on a solid support matrix. The solid support matrix may include derivatives of cellulose (e.g., carboxy cellulose) derivatized with carboxylic acid (e.g., carboxylate, carboxyl) groups and hydroxyboryl compounds including phenylboronic acid (e.g., phenylborate), aminophenylboronic acid, boric acid (e.g., borate), or other boronic acid (e.g., boronate) compounds. The present invention is usefi.il for monitoring glycation or glycosylation of hemoglobin or albumin for monitoring glycemic control (e.g., glycemia in diabetes).

Abstract: A method of monitoring calibration of a spectrophotometric apparatus that includes one or more than one calibration algorithm for one or more than one analyte, involves measuring absorbance of a quality control material with the apparatus to obtain a measurement, calculating one or more than one value from the measurement using the one or more than one calibration algorithm, and comparing the one or more than one value with an assigned value given to the quality control material for each of the one or more than one analyte. The quality control material exhibits an absorbance spectrum having a negative slope for a continuous spectral segment from about 5 nm to about 200 nm in length, and the spectral segment includes a principal calibration wavelength for the one or more than one analyte. A reagentless method for determining the concentration of one or more than one analyte in a sample in a spectrophotometric apparatus having at least one primary calibration algorithm is also disclosed.

Abstract: The invention relates to a process for detecting or determining a C-peptide-containing impurity in a sample of recombinantly produced human insulin or a derivative thereof, by a non-radioactive assay, comprising the steps: (a) preparing a sample of recombinantly produced human insulin or a derivative thereof; (b) mixing the samples with dilution buffer; (c) adding a tracer to mixture (b); (d) adding antibody specific for the C-peptide impurity to mixture (c); (e) adding “C-peptide second antibody bead” having at least one label to mixture (d); and (f) detecting or determining the presence of the C-peptide-containing impurity.

Abstract: A method having clinically sufficient degree of diagnostic accuracy for detecting the presence of coronary artery disease in a human patient from the general population and for distinguishing between the stages of the disease in that patient is disclosed. The stages are, first, the non-acute stage, which is either asymptomatic coronary artery disease or stable angina, second, the acute stage known as unstable angina, and, third, the acute stage known as acute myocardial infarction. The diseased state (as opposed to the non-diseased state) is indicated by the clinically significant presence of a first marker in a sample from the patient. The presence of one of the two acute stages, unstable angina or acute myocardial infarction, is indicated by the clinically significant presence of a second marker in a sample from the patient. The presence of the more severe acute stage known as acute myocardial infarction is indicated by the clinically significant presence of a third marker in a sample from the patient.

Abstract: The present invention provides processes for determining the molecular weight of glatiramer acetate and other copolymers. The present invention further provides a plurality of molecular weight markers for determining the molecular weight of glatiramer acetate and other copolypmers which display linear relationships between molar ellipticity and molecular weight, and between retention time and the log of the molecular weight. The molecular weight markers also optimally demonstrate biological activity similar to glatiramer acetate or corresponding copolymers and can be used for treating or preventing various immune diseases. In addition, the subject invention provides pharmaceutical compositions for the treatment of immune diseases comprising a polypeptide having an identified molecular weight and an amino acid composition corresponding to glatiramer acetate or a terpolymer.

Abstract: A method of monitoring calibration of a spectrophotometric apparatus having one or more than one calibration algorithm for one or more than one analyte. This method involves measuring an absorbance of a quality control material to obtain a measurement, calculating one or more than one concentration value from the measurement using the one or more than one calibration algorithm, and comparing the one or more than one concentration value with an assigned value given to the quality control material for each of the one or more than one analyte. The quality control material exhibits an absorbance spectra having a negative slope for a continuous spectral segment from about 5 nm to about 400 nm in length, or a wavelength therebetween. A reagentless method for determining the concentration of one or more than one analyte in a sample in a spectrophotometric apparatus containing one or more than one primary calibration algorithm is also provided.

Abstract: A protein marker pellet for use in a gel electrophoresis system includes one or more protein markers including a protein of known molecular weight with ionic components to provide electrical conductance, and a non-protein, gel-forming material having a porosity sufficient to allow the one or more protein markers to migrate out of the protein marker pellet under the influence of an electrical field at the same rate as the ionic components.

Abstract: Heart and brain fatty acid binding proteins (H-FABP, B-FABP) are markers for stroke. The invention provides a diagnostic assay for either of these markers, preferably by ELISA using anti-H-FABP or B-FABP antibody. Since H-FABP is also a marker for acute myocardial infarction (AMI), to distinguish stroke from AMI requires an assay specific to AMI, e.g. using troponin-I or creatine kinase-MB as a marker, also to be carried out.

Abstract: Data acquisition and cataloging are used to classify polypeptides into a reference index or database. The database can be used to identify previously unidentified samples. New polypeptides are characterized and added to the database.

Abstract: The method of the invention provides novel compounds, termed acid-labile isotope-coded extractants (ALICE), for quantitative mass spectrometric analysis of protein mixtures. The compounds contain a thiol-reactive group that is used to capture cysteine-containing peptides from all peptide mixtures, an acid-labile linker, and a non-biological polymer. One of the two acid-labile linkers is isotopically labeled and therefore enables the direct quantitation of peptides/proteins through mass spectrometric analysis. Because no functional proteins are required to capture peptides, a higher percentage of organic solvent can be used to solubilize the peptides, particularly hydrophobic peptides, through the binding, washing and eluting steps, thus permitting much better recover of peptides. Moreover, since the peptides are covalently linked to the non-biological polymer (ALICE), more stringent washing is allowed in order to completely remove non-specifically bound species.

Abstract: A method for identifying and quantifying peptides resulting from enzyme cleavage of collagen type II by mass spectrometric analysis to detect characteristic peptide fragments of a carboxy-terminus having known mass to charge ratios to identify the peptide having that carboxy-terminus. Identification and quantification of the peptides in a biological sample is used to assess activity of proteolytic enzymes in diseases or physiological conditions such as osteoarthritis and rheumatoid arthritis and to assess the efficacy of enzyme blocking agents.

Abstract: The invention features a method of determining whether one or more members of an analyte family are present in a sample. The method makes use of a test zone binder, e.g., a receptor that can bind one or a plurality of analytes within an analyte family, the analytes family defined by similar structural binding sites. Members of an analyte family can have different detection level requirements and, therefore, additional analyte binders can be employed to adjust test sensitivity for a subset of the analytes in the analyte family individually, so that each analyte can be detected only if it is present in the sample above a predetermined threshold.

Abstract: This invention relates to single-chain polypeptides and their genetic sequences comprising human cardiac troponin I and troponin C. The single-chain polypeptide may be expressed recombinantly, and a linker peptide may be interposed between the troponin sequences. A linker peptide of about 6 to about 30 amino acids is preferred. The single-chain polypeptide has utility as a control or calibrator for troponin assays, for the purification of troponin subunits and as an antigen for the preparation of antibodies.

Abstract: The present invention provides processes for determining the molecular weight of glatiramer acetate and other copolymers using molecular weight markers. The present invention further provides a plurality of molecular weight markers for determining the molecular weight of glatiramer acetate and other copolymers which display linear relationships between molar ellipticity and molecular weight, and between retention time and the log of the molecular weight. The molecular weight markers also optimally demonstrate biological activity similar to glatiramer acetate or corresponding copolymers and can be used for treating or preventing various immune diseases.

Abstract: Several neurodegenerative diseases result from the aggregation of polyglutamine repeat proteins into insoluble neuronal intranuclear inclusions. The invention provides methods with which to study the processes of these diseases, including methods for solubilizing polypeptides containing a polyglutamine repeat sequence, for storing these polyglutamine polypeptides and inhibit their spontaneous aggregation, for making the aggregates of polyglutamine polypeptides, for assaying the extension of existing polyglutamine aggregates, for determining the ability of a chemical compound to inhibit aggregation, and for inhibiting aggregation of polyglutamine polypeptides. The invention further provides materials with which to study these diseases including a synthetic aggregate that have a capability to recruit additional monomeric polyglutamine polypeptides and chemical compounds that inhibit the formation and/or extension of polyglutamine aggregates.

Abstract: Novel bipyridyl-osmium complex conjugates and their use in electrochemical assays are described. The redox reversible-osmium complexes can be prepared to exhibit unique reversible redox potentials and can thus be used in combination with other electroactive redox reversible species having redox potentials differing by at least 50 millivolts in electrochemical assays designed for use of multiple electroactive species in the same cell and in the same sample without interference between the two or more redox coupled conjugate systems.

Abstract: The invention describes quality control devices for assays that measure analytes in cells and tissue samples, and methods of use thereof. In particular, the quality control device comprises a matrix affixed with synthetic controls in different concentrations, or different synthetic controls. The quality control device can be adhered to a microscope slide via an adhesive or chemically attached to a microscope slide and processed simultaneously with a tissue sample.

Abstract: A novel protein, enkurin, that is preferentially expressed in sperm has been discovered. Enkurin binds to TRPCs including TRPC2-S, a protein encoded by TRPC2 that is not predicted to be a calcium channel subunit. The invention includes methods of identifying compounds that affect enkurin expression or activity, and are useful, e.g., for contraception and treatment of infertility.

Abstract: An antibody is provided which specifically recognizes and binds to INGAP protein. The antibody is used in competitive binding assays for quantitation of INGAP in biological samples. The assay can be performed on a solid support or in a suspension.

Abstract: An improved reagent system for preparation of cells for flow cytometry having a physiologically compatible salt solution composition including a lysing agent, an agent for minimizing white blood cell lysis, and optionally a preservative.

Abstract: The present invention relates to a monoclonal antibody suitable for monitoring the activity of systems involving protein C inhibitor, a method for preparation of the monoclonal antibody, a method for monitoring the activity of systems involving protein C inhibitor and a method for diagnosis of e.g. venous thrombosis, wherein the monoclonal antibody is utilized. The monoclonal antibody is suitable for monitoring the activity of systems involving protein C inhibitor, and it has specific affinity for both i) a complex between a serine proteinase and an inhibitor thereof, and ii) a cleaved and uncomplexed form of the inhibitor, but has substantially no specific affinity for the inhibitor in its uncleaved and uncomplexed form; or a derivative thereof having the same biological activity.

Abstract: The present invention provides a method for determining expression levels of one or a multiplicity of target proteins in a tissue or cell sample.

Abstract: An artificial mixture which simulates human feces and its method of use for fecal occult blood testing as a control material or for proficiency testing are disclosed.

Abstract: Methods of determining Chronic Obstructive Pulmonary Disease (COPD) severity in patients which comprises measuring the concentration of soluble E-cadherin (sE-cadherin) in the patient's urine and/or blood serum and determining the extent of severity by reference to correlation graphs, a method of treating patients with COPD, methods for determining the responsiveness of said patients to said treatment and a prognostic product for detecting the concentration of sE-cadherin in urine and/or blood serum.

Abstract: Controls and standards for assays and method for manufacturing the controls and standards is described. The controls or standards comprise a porous carrier material which has quantitatively reversibly absorbed and dried thereon an analyte for the control or standard wherein the analyte is not degraded over time while it is absorbed to the porous carrier material. Preferably, the controls and standards are provided as a control strip (10) in which the porous carrier material (20) is adhered to the distal end (16) of a support member (12). To quantitatively elute the analyte from the carrier to a solvent for an assay, the carrier is contacted to the same solvent used for the samples in the assay. After the analyte has been eluted, the carrier is discarded and the assay is performed. The controls and standards are useful for assays which detect bacteria, fungi, viruses, and proteins.

Abstract: The invention provides monoclonal antibodies and other binding agents to human cytochrome P450 2C19 having advantageous properties, including capacity substantially to inhibit enzyme activity of human cytochrome P450 2C19 and lack of specific binding to other human cytochrome P450s. The binding agents of the invention are useful inter alia in methods for screening drugs for metabolism by cytochrome P450 2C19, and in methods of measuring P450 2C19 levels in individuals relative to P450 2C19 levels in a control population.

Abstract: This invention relates to preservative solutions for peptides, for example, parathyroid hormone, insulin-like growth factor binding protein 3 (IGFBP3), adrenocorticotropic hormone (ACTH) and mixtures thereof. Preferably, the peptides preserved by the solutions are non-reconstituted. In one embodiment, the preservative solutions comprise a polyvinyl alcohol, EDTA component and molybdic component.

Abstract: An aqueous control solution is disclosed for use with a spectrophotometer or photometric test strip that includes a predetermined amount of an analyte, a hydrophobic reference dye and a surfactant. In one embodiment, the aqueous control solution is applied to a photometric test strip having a chemical that oxidizes glucose and consequently forms hydrogen peroxide which reacts with an indicator dye that is also present on the strip. In this embodiment, the control solution includes a predetermined amount of glucose, an infrared reference dye, sodium dodecyl sulfate, and the indicator dye, such as sulforhodamine B.

Abstract: A method of emulating with a cyanide-free lyse solution, the measurement of hemoglobin in whole blood using a cyanide-containing lyse solution. Such an illustrative method includes: a) combining a predetermined amount of the whole blood sample with a predetermined amount of a cyanide-free lyse solution to form a mixture, b) developing the mixture to a molar absorbtivity (?) in the range of about 12.4 to 12.6 mM?1cm?1, and c) measuring a level of light absorbance of the mixture at a wavelength of about 540 nm. In one preferred illustrative embodiment, the cyanide-free lyse solution includes: a quaternary ammonium salt surfactant, an anionic surfactant, a hemoglobin binding agent selected from the group consisting of imidazole or hydroxylamine, and an aqueous medium. In one preferred embodiment, the molar absorbtivity is developed to a value of about 12.5 mM?1cm?1. That is to say to a level that is substantially identical to that of the prior art standard, cyanomethemoglobin.

Abstract: Methods of assessing the effect of a drug on long term memory and for screening a pharmaceutical agent for its ability to modulate long term memory are disclosed.

Abstract: A humanized antibody that binds to human 4-1BB and that allows binding of human 4-1BB to a human 4-1BB ligand. In one aspect, the antibody is an IgG4 antibody. Also provided is a method for treating cancer in a subject comprising administering a therapeutically effective amount of the antibody to said subject.

Abstract: The invention relates to synthetic biepitope compounds which can be used as standards in immunoassays, for the assay of troponin I, method for preparing them, compositions and kits containing such compounds as well as the immunoassay methods using such compounds.

Abstract: Multi-analyte reference solutions having a stable partial pressure of oxygen (pO2) in zero headspace packaging and methods for preparing such solutions are disclosed. The solutions have long shelf and use lives when stored at room temperature and are packaged in laminated foil containers having low or no oxygen reactivity. Access devices are also disclosed.

Abstract: The present invention relates to an isolated target sequence. The target sequence is a splice variant of PDE5 called a PDE5a1, a component of which is presented as SEQ ID No 1. The identified target sequence of the present invention may be used to as a target to identify agents (such as modulators) useful in the prevention and/or treatment of a disease associated with scarring and/or fibrosis or to selectively identify smooth muscle cells and myofibroblasts and myoepithelial cells in samples of normal and diseased tissue from individuals.

Abstract: An improved reagent system for preparation of cells for flow cytometry having a physiologically compatible salt solution composition including a lysing agent, an agent for minimizing white blood cell lysis, and optionally a preservative.

Abstract: An aqueous control solution is disclosed for use with a spectrophotometer or photometric test strip that includes a predetermined amount of an analyte, a hydrophobic reference dye and a surfactant. In one embodiment, the aqueous control solution is applied to a photometric test strip having a chemical that oxidizes glucose and consequently forms hydrogen peroxide which reacts with an indicator dye that is also present on the strip. In this embodiment, the control solution includes a predetermined amount of glucose, an infrared reference dye, sodium dodecyl sulfate, and the indicator dye, such as sulforhodamine B.

Abstract: The invention provides compositions and methods for treatment of amyloidogenic diseases. Such methods entail administering an agent that induces a beneficial immune response against an amyloid deposit in the patient. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In such methods, a suitable agent is A&bgr; peptide or an antibody thereto.

Abstract: The invention provides compositions and methods for treatment of amyloidogenic diseases. Such methods entail administering an agent that induces a beneficial immune response against an amyloid deposit in the patient. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In such methods, a suitable agent is A&bgr; peptide or an antibody thereto.

Abstract: The invention provides compositions and methods for treatment of amyloidogenic diseases. Such methods entail administering an agent that induces a beneficial immune response against an amyloid deposit in the patient. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In such methods, a suitable agent is A&bgr; peptide or an antibody thereto.

Abstract: Disclosed herein are aggregating amyloid A&bgr; peptides which are covalently bonded (for example, at a cysteine amino acid residue) to a fluorescent label, and methods for their use.

Abstract: A diagnostic assay, preferably immunoassay, is provided for the detection and determination of MGP in a human serum sample, which comprises the use of one or more antibodies, in particular monoclonal antibodies, specifically recognising epitopes on and/or conformations of human Matrix Gla-Protein. Also, a method is provided for using MGP-related antigens as biomarkers for certain diseases, for example, atherosclerosis and other vascular diseases, and angiogenesis/neogenesis in tumor development. Further, monoclonal antibodies of class IgG are provided for use in the assay, which are defined herein as mAb3-15 and mAb35-49.