Abstract: A method for the separation of at least one specific binding entity from a mixture of binding entities by the steps of contacting a mixture of binding entities with immobilized peptides in which the peptides specifically bind to the specific binding entities and the peptides contain an amino acid which facilitates removal of the binding entities from the peptides, and separating the immobilized peptide/specific binding entity complexes from the mixture of binding entities. A change in incubation conditions facilitates removal of the binding entities from the immobilized peptides.

Abstract: A method of preparing a homogeneous alkaline phosphatase-oligonucleotide probe conjugate having high specific enzyme activity for use in nucleic acid hybridization assays is disclosed. Indirect, competitive nucleic acid hybridization assay formats are also described.

Abstract: Methods are provided for substantially reducing background signals encountered in nucleic acid hybridization assays. The method is premised on the elimination or significant reduction of the phenomenon of nonspecific hybridization, so as to provide a detectable signal which is produced only in the presence the target polynucleotide of interest. In addition, a novel method for the chemical synthesis of isoguanosine or 2'-deoxy-isoguanosine is provided. The invention also has applications in antisense and aptamer therapeutics and drug discovery.

Abstract: Nucleic acid probes are immobilized on polystyrene surfaces such as the wells of microtiter plates for use in solution phase nucleic acid sandwich hybridization assays, particularly those using large branched DNA amplification multimers, by: (a) cleansing the surface by washing it sequentially with a strong acid, a strong base, and water, (b) passively adsorbing a polypeptide having primary amino groups onto the cleansed surface, and (c) covalently bonding the probe to the adsorbed polypeptide via a base-stable bifunctional crosslinking agent, and (d) subjecting the surface to conditions that simulate the hybridization conditions used in the assay.

Abstract: This invention provides a method of detecting or determining a binding oligonucleotide comprising a nucleotide sequence which binds within a known nucleotide sequence of a target nucleic acid using a technique called hybritope mapping. This invention also provides a method of using hybritope mapping to obtain discontinuous probes that bind to a target nucleic acid.

Abstract: Novel DNA probe sequences for detection of HBV in a sample in a solution phase sandwich hybridization assay are described. Amplified nucleic acid hybridization assays using the probes are exemplified.

Abstract: This invention provides a method of detecting or determining a binding oligonucleotide comprising a nucleotide sequence which binds within a known nucleotide sequence of a target nucleic acid using a technique called hybritope mapping. This invention also provides a method of using hybritope mapping to obtain discontinuous probes that bind to a target nucleic acid.

Abstract: A luminometer is described comprising a tray for receiving an array of sample wells, a photodetector assembly, and means for relatively moving the tray and photodetector assembly in one direction to align the sample wells received by the tray in a predetermined sequence with the photodetector assembly. The photodetector assembly of the luminometer includes a stage, a photodetection head having a detection aperture permitting passage of light therethrough, a means for mounting the photodetection head to the stage that permits movement of the head in a direction substantially normal to the direction of relative tray and photodetector assembly movement, and a means for biasing the photodetection head toward a selected sample well so that the detection aperture is substantially isolated from light emitted from adjacent wells. Internal and external photodetector calibration systems and a sample heater are also contemplated.

Abstract: A new virus, Hepatitis C virus (HCV), which has proven to be the major etiologic agent of blood-borne NANBH, was discovered by Applicant. Reagents for isolating, amplifying, and detecting HCV polynucleotides are provided. These reagents are oligomers comprised of polynucleotide sequences which are capable of forming hybrid structures with HCV target polynucleotide sequences.

Abstract: Compositions and methods are provided for increasing the serum half-life of a pharmacologically active agent. The novel compositions are covalent conjugates of the selected pharmacologically active agent and a transthyretin-binding ligand such as tetraiiodothyroacetic acid, 2,4,6-triiodophenol, flufenamic acid, or the like.

Abstract: The protease necessary for polyprotein processing in Hepatitis C virus is identified, cloned, and expressed. Proteases, truncated protease, and altered proteases are disclosed which are useful for cleavage of specific polypeptides, and for assay and design of antiviral agents specific for HCV.

Abstract: A new virus, Hepatitis C virus (HCV), which has proven to be the major etiologic agent of blood-borne NANBH, was discovered by Applicant. Reagents for isolating, amplifying, and detecting HCV polynucleotides are provided. These reagents are oligomers containing polynucleotide sequences which are capable of forming hybrid structures with HCV target polynucleotide sequences.

Abstract: Nucleic acid probes are immobilized on polystyrene surfaces such as the wells of microtiter plates for use in solution phase nucleic acid sandwich hybridization assays, particularly those using large branched DNA amplification multimers, by: (a) cleansing the surface by washing it sequentially with a strong acid, a strong base, and water, (b) passively adsorbing a polypeptide having primary amino groups onto the cleansed surface, and (c) covalently bonding the probe to the adsorbed polypeptide via a base-stable bifunctional crosslinking agent, and (d) subjecting the surface to conditions that simulate the hybridization conditions used in the assay.

Abstract: Large comb-type branched polynucleotides useful as amplifier molecules in nucleic acid hybridization assays are provided, the polynucleotides comprising: a polynucleotide backbone having at least about 15 multifunctional nucleotides, each of which defines a sidechain site and a first single-stranded oligonucleotide unit that is capable of binding specifically to a first single-stranded polynucleotide sequence of interest; and pendant polynucleotide sidechains extending from said multifunctional nucleotides each comprising iterations of a second single-stranded oligonucleotide unit that is capable of binding specifically to a second single-stranded polynucleotide sequence of interest, the total number of iterations in all sidechains being at least 20. Methods of making these polynucleotides are also provided.

Abstract: Novel DNA probe sequences for detection of HAV in a sample in a solution phase sandwich hybridization assay are described. Amplified nucleic acid hybridization assays using the probes are exemplified.

Abstract: A method for binding a target polynucleotide in a sample is provided. The method uses an assay reagent which is a substrate noncovalently bound to a hydrophobic moiety which is part of a polynucleotide capture probe. This assay reagent is contacted with the sample under conditions which permit hybridization between said capture probe and said target polynucleotide, thereby binding the target polynucleotide.

Abstract: New techniques are provided for substantially reducing background signals encountered in solution phase hybridization assays. The techniques are premised on eliminating or significantly reducing the phenomena of nonspecific hybridization and nonspecific binding, so as to provide a detectable signal which is produced only in the presence of the target polynucleotide of interest. In certain embodiments, methods are provided for increasing the signal which can otherwise be diminished in noise reduction. Kits for carrying out the novel assays are provided as well.