Producing Labeled Antigens Patents (Class 436/544)
  • Patent number: 6613583
    Abstract: Electrochemiluminescent label compounds containing multimetallic centers separated by bridging ligands are described. An example of a multimetallic electrochemiluminescent label suitable for use in electrochemiluminescence (ECL) methods, [(bpy)2Ru]2(bphb)4+, demonstrates ECL efficiencies 2 to 3 times greater than those for Ru(bpy)32+ in acetonitrile and aqueous media. Such multimetallic ECL compounds may be especially useful in the design of new labels for bioanalytical applications, such as immunoassays and DNA probes.
    Type: Grant
    Filed: June 26, 1998
    Date of Patent: September 2, 2003
    Assignee: IGEN International, Inc.
    Inventors: Mark M. Richter, Allen J. Bard, Russel H. Schmehl
  • Patent number: 6602987
    Abstract: A compound of the formula I: wherein R is H or —N═N-2-carboxyphenyl; A is (CH2)n or —CH═CH—, wherein n is an integer from 0 to 10, or A may also be —CH(COOH)— when R is —N═N-2-carboxyphenyl; and X is a radical selected from the group consisting of: (i) Cl; (ii) COOR1, wherein R1 is p-nitrophenyl or N-succinimidyl; (iii) CONH—NHR2, wherein R2 is H, COO(t-butyl) or COObenzyl; (iv) CONH—[B]—NHR3, wherein R3 is H, COOR1, or CO—[B′]—maleimido, wherein R1 is t-butyl, p-nitrophenyl or N-succinimidyl, and B and B′, the same or different, are (CH2)n wherein n is an integer from 2 to 10; (v) CONH—[B]—COOR4, wherein R4 is H, C1-C8 alkyl, N-succinimidyl; (vi) CONH—[B]—OH; (vii) CONH—[B]—CONH—NHR2, wherein R2 is H, COO(t-butyl) or COObenzyl; and (viii) NHR2, wherein R2 is H, COO(t-butyl) or COObenzyl, when A is —CH(C
    Type: Grant
    Filed: August 7, 2001
    Date of Patent: August 5, 2003
    Assignee: Yeda Research and Development Co., Ltd.
    Inventors: Meir Wilchek, Edward A. Bayer, Heike Hofstetter, Margherita Morpurgo
  • Patent number: 6551495
    Abstract: Disclosed is a component for a device for detecting the presence of an analyte of interest in a sample, the component comprising an electrically conducting solid support having immobilized thereon a chemical moiety, said chemical moiety comprising an electroactive portion with an electrochemical property capable of being directly modulated in a detectable manner by the binding thereto of a binding partner having a specific binding activity for the electroactive portion, together with apparatus comprising the component, and a method of detecting the presence of an analyte of interest.
    Type: Grant
    Filed: May 19, 2000
    Date of Patent: April 22, 2003
    Assignee: Inverness Medical Switzerland GmbH
    Inventors: Robert Andrew Porter, Robert Andrew Badley
  • Patent number: 6548645
    Abstract: To improve the detection of LSD, and LSD metabolites in biological samples, antibodies are raised to 2-oxo-3-hydroxy-LSD conjugated to a protein carrier. Selected antibodies are matched with an immunoassay reagent in which the 2-oxo-3-hydroxy-LSD is conjugated in the same position to a labeling or separation means. The set of reagents can be used in immunoassays for detecting or confirming the presence of LSD or LSD metabolites in a sample potentially containing interfering substances.
    Type: Grant
    Filed: June 16, 2000
    Date of Patent: April 15, 2003
    Assignee: Microgenetics Corporation
    Inventors: Anthony de Jesus Sanchez, David Davoudzadeh, William A. Coty
  • Patent number: 6509462
    Abstract: The present invention provides a highly sensitive immunoassay system for estrogens, which utilizes as a labeled compound a biotinylated estradiol derivative of the formula (1) wherein one of R1 and R2 is hydrogen and the other is a group represented by wherein R3s are the same or different and represent an arginine residue or a lysine residue, x is 0 or 1, y is an integer from 1 to 5, and z is an integer from 1 to 3.
    Type: Grant
    Filed: July 17, 2001
    Date of Patent: January 21, 2003
    Assignees: Otsuka Pharmaceutical Co., Ltd., Yanaihara Institute, Inc.
    Inventors: Noboru Yanaihara, Ikuo Kato, Kazuyuki Kitamura, Tsukasa Kodaira
  • Patent number: 6485982
    Abstract: Disclosed is a test cell and a method for detection of a preselected ligand in a liquid sample such as a body fluid. The test cell includes an elongate outer casing which houses an interior permeable material capable of transporting an aqueous solution and defining a sample inlet, a test volume, and a reservoir volume. The reservoir volume is disposed in a section of the test cell spaced apart from the inlet and is filled with sorbent material. The reservoir acts to receive liquid transported along a flow path defined by the permeable material and extending from the inlet and through the test volume. In the test volume is a test site which includes a first protein having a binding site specific to a first epitope of the ligand immobilized in fluid communication with the flow path. The test site can be observed through a window of the casing.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: November 26, 2002
    Assignee: Armkel, LLC
    Inventor: David E. Charlton
  • Publication number: 20020173053
    Abstract: A method of simultaneously identifying two different markers in a sample by contacting a sample suspected of containing the two different markers with an antibody solution having a first antibody or fragment thereof against a first marker and a second antibody or fragment thereof against a second marker. The first antibody is conjugated to a first enzyme and the second antibody is conjugated to a second enzyme. The first enzyme and the second enzyme are different. The sample is incubated with the antibody solution for a sufficient time to allow the first marker to bind with the first conjugated antibody and the second marker to bind with the second conjugated antibody. The sample is assayed for a change in enzymatic activity and the presence of the first marker and/or the second marker is determined. The present invention also includes a kit for the simultaneous detection of multiple target molecules.
    Type: Application
    Filed: September 6, 2001
    Publication date: November 21, 2002
    Inventors: Bassam Damaj, Ali-Samer Al-Assaad
  • Patent number: 6472228
    Abstract: This invention relates to novel tracers and their synthesis and use in an immunoassay for the detection of controlled drugs such as amphetamine (APM), methamphetamine (MAPM) and their derivatives, in a biological or aqueous sample. In particular, this invention provides methods for synthesizing novel tracers in which a non-controlled substance is both the starting material in tracer synthesis and the binding site on the resulting novel tracer for the antibody, thereby eliminating the necessity of using controlled substances as starting materials. In addition, the novel tracers of the present invention can be used as an analyte analog in an immunoassay, such as a continuous flow displacement immunoassay. It was unexpectedly discovered that the novel tracers of the present invention substantially improve the performance of the continuous flow displacement immunoassay as compared with conventionally designed tracers.
    Type: Grant
    Filed: December 4, 2000
    Date of Patent: October 29, 2002
    Assignee: Lifepoint, Inc.
    Inventors: Guohong Wang, Thomas Foley
  • Patent number: 6451545
    Abstract: Provided are a monoclonal antibody making it possible to detect a native fibrin monomer, which is produced at the initial state of blood coagulation, and soluble fibrin; a hybridoma; and an immunoassay for detecting the initial stage of blood coagulation with high sensitivity, quickly, using the monoclonal antibody. Using a fibrinogen analog in blood as an immune source, cell fusion is carried out to prepare a monoclonal antibody which is not reactive with fibrinogen and is specifically and simultaneously reactive with a native fibrin monomer (that is, a fibrin monomer which is present in a body fluid, in particular in blood, and is not solubilized) and soluble fibrin. The fibrin monomer analog is preferably fibrinogen treated with bathroxobin, which is a snake venom.
    Type: Grant
    Filed: February 17, 1999
    Date of Patent: September 17, 2002
    Assignee: Nissui Pharmaceutical Co., Ltd.
    Inventors: Seiji Tanaka, Akiei Hamano, Mamoru Umeda
  • Patent number: 6451543
    Abstract: The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis.
    Type: Grant
    Filed: August 26, 1999
    Date of Patent: September 17, 2002
    Assignee: Gryphon Sciences
    Inventors: Gerd. G. Kochendoerfer, Christie L. Hunter, Stephen B. H. Kent, Paolo Botti
  • Patent number: 6432722
    Abstract: The invention concerns the stabilization and amplification of electrochemiluminescence signals in detection methods.
    Type: Grant
    Filed: March 15, 1999
    Date of Patent: August 13, 2002
    Assignee: Roche Diagnostics GmbH
    Inventors: Gabriele Punzmann, Martin Egger, Hans-Peter Josel
  • Patent number: 6420168
    Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.
    Type: Grant
    Filed: October 30, 2001
    Date of Patent: July 16, 2002
    Assignee: Hitachi, Ltd.
    Inventors: Tomoko Takeshita, Jun Otomo
  • Patent number: 6410340
    Abstract: We have identified and purified to homogeneity from lymphatic tissues a 8.4 kDa immunophilin that specifically and avidly binds the immunosuppressant drugs FK-506 (Kd=0.8 nM) and rapamycin (Kd=0.08 nM) and their pharmacologically active metabolites and derivatives, but does not bind cyclosporin A. The isolated 8.4 kDa protein appears to be identical to authentic human and bovine ubiquitins in all measured respects (partial amino acid sequence, molecular weight, binding constants, binding specificity, biochemical aspects, and utility as the protein binding reagent in binding assays for immunosuppressant drugs in fluid samples, including patient blood). The availability of commercial quantities of human recombinant ubiguitin removes a supply barrier to the use of immunophilin protein binding assays for the estimation of FK-506, rapamycin and pharmacologically active metabolites and derivatives in the clinical setting.
    Type: Grant
    Filed: August 23, 2000
    Date of Patent: June 25, 2002
    Assignee: Children's Research Institute
    Inventor: Steven J. Soldin
  • Patent number: 6399318
    Abstract: The present invention provides an immunoassay for phthalic acid esters, which comprises measuring the phthalic acid esters contained in a sample using an antibody produced with a conjugate of a carrier protein and a phthalic acid ester derivative represented by the formula wherein R1 and R2 may be the same or different and are hydrogen, alkyl, cycloalkyl or phenylalkyl, with the proviso that both of R1 and R2 are not hydrogen; m is an integer from 1 to 5; and Y is amino or carboxyl.
    Type: Grant
    Filed: October 30, 2001
    Date of Patent: June 4, 2002
    Assignees: Otsuka Pharmaceutical Co., Ltd., Yanaihara Institute Inc.
    Inventors: Noboru Yanaihara, Ikuo Kato, Shingo Nagasawa, Tsukasa Kodaira
  • Patent number: 6368875
    Abstract: The present invention provides internally calibrated competitive assays for use on a solid support. Additionally, the invention provides a method of using such assays.
    Type: Grant
    Filed: May 24, 2000
    Date of Patent: April 9, 2002
    Inventor: Mark S. Geisberg
  • Publication number: 20020035325
    Abstract: A method is provided for immune corrective surgical removal of lymphoid tissues containing shed tumor antigen in an individual. A detector molecule, with binding specificity for shed tumor antigen, is administered to an individual, and detected in the individual is the presence of lymphoid tissue which contains shed tumor antigen, as detected by the signal emitted by the detector molecule bound to shed tumor antigen. The lymphoid tissue, detected as containing shed tumor antigen, may then be surgically removed, thereby removing B cells, shed tumor antigen, and follicular dendritic cells involved in a pro-tumor immune response that are contained in the removed lymphoid tissue.
    Type: Application
    Filed: August 27, 2001
    Publication date: March 21, 2002
    Inventor: Emilio Barbera-Guillem
  • Patent number: 6355803
    Abstract: This application relates to long-wavelength acridinium compounds having electron-donating groups, which may either be: (a) Part of an extended conjugation system attached by appropriate functional groups to the acridinium nucleus, with coplanarity of the attached functional group and the acridone moiety during light emission (geometry requirement), said functional group consisting of at least one aromatic ring and one electron-donating atom or group with an extra pair of electrons which can readily delocalize into the extended &pgr; system to which the heteroatom is directly attached or built into, and establish stable extended resonance with the electron-withdrawing carbonyl moiety of the light emitting acridone.
    Type: Grant
    Filed: August 10, 1999
    Date of Patent: March 12, 2002
    Assignee: Bayer Corporation
    Inventors: Anand Natrajan, Qingping Jiang, David Sharpe, Say-Jong Law
  • Patent number: 6355443
    Abstract: 4-(4-hydroxystyryl) pyridine-containing compounds are disclosed as substrates for use in assays. Also, a method for detecting or quantitating an analyte is provided which includes reacting an enzyme with a 4-(4-hydroxystyryl) pyridine-containing compound to form a reactive intermediate wherein the reactive intermediate deposits covalently on a surface by binding to a receptor, wherein deposited reactive intermediates either directly or indirectly through a label generate a signal which can be detected or quantitated.
    Type: Grant
    Filed: March 16, 2000
    Date of Patent: March 12, 2002
    Inventors: Mark Norman Bobrow, Kevin Aaron Roth
  • Patent number: 6352824
    Abstract: Novel bipyridyl-osmium complex conjugates, their preparation, 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.
    Type: Grant
    Filed: May 28, 1999
    Date of Patent: March 5, 2002
    Assignee: Roche Diagnostics Corporation
    Inventors: Harvey B. Buck, Jr., Zhi David Deng
  • Patent number: 6350579
    Abstract: A method and compositions for the detection and/or quantification of an analyte through the use of a plurality of labeled probes, with two or more said probes targeted to different regions of said analyte. In specific embodiments, the labels are separately distinguishable, and/or are present at different specific activities on the labels.
    Type: Grant
    Filed: August 28, 2000
    Date of Patent: February 26, 2002
    Assignee: Gen-Probe Incorporated
    Inventor: Norman C. Nelson
  • Patent number: 6344333
    Abstract: The present invention relates to an apparatus to perform reagent-free assays, which apparatus utilizes an all solid probe having an enzyme label that acts on a substrate by obtaining electrons directly from the electrode by bioelectrocatalysis.
    Type: Grant
    Filed: September 8, 1998
    Date of Patent: February 5, 2002
    Assignee: Synectig Corporation
    Inventor: Andrei L. Gindilis
  • Patent number: 6342352
    Abstract: The present invention relates to our discovery that the mxiM protein of Shigella flexneri is indispensable for the spread of Shigella from cell to cell. Thus, the invention provides the mxiM protein or peptides or portions thereof as antigens in vaccines to prevent Shigella infections and treat hosts infected with Shigella by inhibiting intercellular spread. In another aspect, the invention relates to antibodies generated against the mxiM proteins, peptides, or portions thereof to detect Shigella in contaminated food and water supplies as well as in infected hosts. The present invention also describes a method called the TIER (test of intracellular expression requirements) for determining the intracellular expression requirements of genes and therefore, permitting one to establish the role of genes in the pathogenesis of organisms. A method of detecting Shigella or Shigella mxiM DNA in a sample using a mxiM DNA probe is also described.
    Type: Grant
    Filed: April 22, 1999
    Date of Patent: January 29, 2002
    Assignee: The Henry M. Jackson Foundation for the Advancement of Military Medicine
    Inventors: Raymond Schuch, Robin C. Sandlin, Anthony T. Maurelli
  • Publication number: 20020009708
    Abstract: Immunoassay reagents, methods and test kits for the specific quantification of vancomycin in a test sample are disclosed. The reagent comprises antibodies prepared with immunogens of FIG. 6 wherein P is an immunogenic carrier material and X is a linking moiety.
    Type: Application
    Filed: October 16, 1998
    Publication date: January 24, 2002
    Inventors: MACIEJ ADAMCZYK, ELAINE M. BRATE, MARY M. PERKOWITZ, SUSHIL D. REGE
  • Patent number: 6338960
    Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.
    Type: Grant
    Filed: February 21, 2001
    Date of Patent: January 15, 2002
    Assignee: Hitachi, Ltd.
    Inventors: Tomoko Takeshita, Jun Otomo
  • Patent number: 6337178
    Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.
    Type: Grant
    Filed: April 30, 2001
    Date of Patent: January 8, 2002
    Assignee: Hitachi, Ltd.
    Inventors: Tomoko Takeshita, Jun Otomo
  • Patent number: 6329156
    Abstract: The protective antigen (PA) of Bacillus anthracis is integral to the mechanism of anthrax poisoning. The cloning, expression and purification of a 32 kDa B. anthracis PA fragment (PA32) is described. This fragment has also been expressed as a fusion construct to stabilized green fluorescent protein (EGFP-PA32). Both proteins were capable of binding to specific cell surface receptors as determined by fluorescent microscopy and a flow cytometric assay. To confirm binding specificity in the flow cytometric assay, non-fluorescent PA83 or PA32 was used to competitively inhibit fluorescent EGFP-PA32 binding to cell receptors. This assay can be employed as a rapid screen for compounds which disrupts binding of PA to cells. Additionally, the high intracellular expression levels and ease of purification make this recombinant protein an attractive vaccine candidate or therapeutic treatment for anthrax poisoning.
    Type: Grant
    Filed: March 22, 1999
    Date of Patent: December 11, 2001
    Assignee: The Regents of the University of California
    Inventors: Nick M. Cirino, Paul J. Jackson, Bruce E. Lehnert
  • Patent number: 6329154
    Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.
    Type: Grant
    Filed: February 21, 2001
    Date of Patent: December 11, 2001
    Assignee: Hitachi, Ltd.
    Inventors: Tomoko Takeshita, Jun Otomo
  • Patent number: 6329194
    Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.
    Type: Grant
    Filed: February 21, 2001
    Date of Patent: December 11, 2001
    Assignee: Hitachi, Ltd.
    Inventors: Tomoko Takeshita, Jun Otomo
  • Patent number: 6297015
    Abstract: A composition and method for detecting Crohn's disease include the use of serological testing as a rapid and simple way to diagnose Crohn's disease. The serological tests were based on the use of the two recombinant clones isolated from an M. paratuberculosis genomic library that expressed 35K and 36K MW antigens. Antigen p35 was isolated from Johne's disease sera (acid-fast bacilli form) and p36, from human CD sera (spheroplast form). The combined use of p35 and p36 recombinant antigens provides a highly specific and sensitive test to demonstrate the humoral immune response of CD patients to M. paratuberculosis. A serologic kit is disclosed including the composition including the combined p35 and p36 antigens. A treatment methodology utilizes antimycobacterial drugs, preferably upon patients prescreened for the presence of M para.
    Type: Grant
    Filed: September 23, 1999
    Date of Patent: October 2, 2001
    Inventor: Ira Shafran
  • Patent number: 6287875
    Abstract: The present invention provides internally calibrated competitive assays for use on a solid support. Additionally, the invention provides a method of using such assays.
    Type: Grant
    Filed: May 24, 2000
    Date of Patent: September 11, 2001
    Assignee: Silver Lake Corporation
    Inventor: Mark S. Geisberg
  • Patent number: 6287789
    Abstract: The subject invention provides methods and kits for detecting increased bone resorption in patients. These methods and kits use chondroitin sulfate, a glycosaminoglycan, as a marker for bone resorption. Levels of chondroitin sulfate are detected in samples of urine or serum taken from patients. Measurements of chondroitin sulfate levels are made by methods such as fluorophore-assisted carbohydrate electrophoresis (FACE). Knowledge of increased bone resorption rates is useful in diagnosis of bone disorders such as osteoporosis.
    Type: Grant
    Filed: February 8, 1999
    Date of Patent: September 11, 2001
    Assignee: BioMarin Pharmaceuticals
    Inventor: John C. Klock
  • Patent number: 6281021
    Abstract: The invention concerns methods for the detection of an analyte in a sample by chemiluminescence or electrochemiluminescence using derivatized test reagents. In addition new reagents and reagent kits for chemiluminescence and electrochemiluminescence detection methods are disclosed.
    Type: Grant
    Filed: June 18, 1999
    Date of Patent: August 28, 2001
    Assignee: Roche Diagnostics GmbH
    Inventors: Martin Egger, Hans-Peter Josel, Gabriele Punzmann
  • Patent number: 6277559
    Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.
    Type: Grant
    Filed: February 21, 2001
    Date of Patent: August 21, 2001
    Assignee: Hitachi, Ltd.
    Inventors: Tomoko Takeshita, Jun Otomo
  • Patent number: 6265227
    Abstract: The invention relates to the development of a method for assaying an antigen which is associated with disorders caused by mental stress in a human body fluid by way of an immunoassay technique which utilizes an antibody against a mental stress related protein having the following properties or a fragment thereof: (1) having a molecular weight of about 14 kDa (measured by SDS-PAGE); and (2) having the N-terminal partial sequence represented by SEQ ID NO: 1; and a kit for diagnosing disorders caused by mental stress which contains the above-mentioned antibody or a fragment thereof. Thus, the accumulation of mental stress can be easily estimated and judged and the results can be applied to the diagnosis of disorders caused by mental stress.
    Type: Grant
    Filed: July 21, 1998
    Date of Patent: July 24, 2001
    Assignee: Suntory Limited
    Inventors: Takako Inui, Masashi Nakagawa, Yoshitake Terano, Mamiko Ozaki
  • Patent number: 6262265
    Abstract: Novel chemical analogs are disclosed for the essential heroin metabolite 6-O-acetyl morphine (6MAM). The analogs optionally can be made to contain protein reactive groups, and can be used to form protein conjugates, fluorescently labeled compounds, and solid-phase adsorbants. The proteins conjugates can be used in turn to raise antibodies reactive with 6MAM and having a low cross-reactivity with the closely related opiates, morphine and codeine. The antibodies can be used in combination with labeled analogs in exquisitely sensitive immunoassays suitable for testing for heroin abuse.
    Type: Grant
    Filed: June 18, 1999
    Date of Patent: July 17, 2001
    Assignee: Microgenics Corporation
    Inventors: Riaz Rouhani, Gerald F. Sigler
  • Patent number: 6251584
    Abstract: The present invention relates to a method for improving the specificity of a specific binding assay by adding methyl orange to a coating solution in an amount sufficient for improving specificity of an immunoassay conducted using said coating. The present invention also relates to a method for the detection of antibodies to hepatitis C virus is performed by, i) providing a solid phase comprising a coating solution comprising methyl orange and at least one first binding ligand for antibodies to hepatitis C virus; ii) contacting the solid phase with a sample that may contain antibodies to hepatitis C virus; iii) contacting the solid phase with at least one second binding ligand for antibodies to hepatitis C virus, said second ligand labelled directly or indirectly with a detectable group and iv) measuring the amount of the detectable group bound to the solid phase.
    Type: Grant
    Filed: June 8, 1999
    Date of Patent: June 26, 2001
    Assignee: Ortho-Clinical Diagnostics
    Inventor: Pratul Unadkat
  • Patent number: 6225132
    Abstract: A method for detecting an analyte of interest present in a mixture at an ultralow concentration includes selecting a radioactive derivatizing agent comprising a multiphoton-emitting radioisotope moiety and a moiety reactive with the analyte of interest, the radioisotope moeity being bound to the derivatizing agent by a bond that is stable under the conditions employed in the other steps of the method, derivatizing the analyte of interest with the derivatizing agent, separating the analyte of interest from other components of the mixture by chromatography, and detecting the analyte of interest using multiphoton detection. The derivatizing step may be performed before or after fractionation. A radiophore for multiphoton emission enhanced chromatography has a first moeity bound to a multiphoton-emitting radioisotope, and a second moiety that is reactive with a functional group of an analyte of interest.
    Type: Grant
    Filed: December 10, 1998
    Date of Patent: May 1, 2001
    Assignee: BioTraces, Inc.
    Inventors: Andrzej K. Drukier, Roman Bielski
  • Patent number: 6207396
    Abstract: To improve the detection of LSD in biological samples, antibodies are raised to LSD conjugated to a protein carrier, preferably through the indole ring. Selected antibodies are matched with an immunoassay reagent in which the LSD is conjugated in the same position to a labeling or separation means. The set of reagents can be used in immunoassays with remarkably little cross-reactivity with potential interfering substances such as chlorpromazine and ergotamine, and a low false-positive rate in a panel of clinical test samples. Also provided is a set of reagents for measuring glucuronide metabolites of LSD by immunoassay, which permits exposure to LSD to be determined over a longer diagnostic window.
    Type: Grant
    Filed: February 20, 1998
    Date of Patent: March 27, 2001
    Assignee: Microgenics Corporation
    Inventors: Gerald F. Sigler, Riaz Rouhani, David Davoudzadeh, William A. Coty, Jeffrey E. Shindelman, Paul R. Morrill
  • Patent number: 6197522
    Abstract: Disclosed is a method for quantitatively identifying polymers in an aqueous system using immunoassay techniques, wherein at least a portion of the polymers contain a detectable terminus. This is particularly useful in water treatment systems. Also disclosed are new hybridoma cell lines which express MAbs which specifically recognize such a detectable terminus.
    Type: Grant
    Filed: January 16, 1997
    Date of Patent: March 6, 2001
    Assignee: Rohm and Haas Company
    Inventors: Lorraine Holowach Keller, Barry Weinstein
  • Patent number: 6197278
    Abstract: A method of imaging apoptosis in vivo, using radiolabeled annexin, is described.
    Type: Grant
    Filed: April 29, 1998
    Date of Patent: March 6, 2001
    Assignees: The Board of Trustees of the Leland Stanford Junior University, University of Washington
    Inventors: Francis G. Blankenberg, H. William Strauss, Jonathan F. Tait, Peter D. Katsikis
  • Patent number: 6180340
    Abstract: A method and compositions for the detection and/or quantification of an analyte through the use of a plurality of labeled probes, with two or more said probes targeted to different regions of said analyte. In specific embodiments, the labels are separately distinguishable, and/or are present at different specific activities on the labels.
    Type: Grant
    Filed: October 31, 1997
    Date of Patent: January 30, 2001
    Assignee: Gen-Probe Incorporated
    Inventor: Norman C. Nelson
  • Patent number: 6171807
    Abstract: Fluorescently labeled ENP as well as methods of preparation are disclosed. Also disclosed is a method of detecting endotoxin in a liquid sample suspected of containing endotoxin, comprising admixing said liquid sample with fluorescently labeled ENP for a time sufficient to form a complex between the labeled ENP and the endotoxin, and performing fluorescence polarization experiment on the sample, wherein a change in the fluorescence polarization indicates the presence of endotoxin.
    Type: Grant
    Filed: November 10, 1997
    Date of Patent: January 9, 2001
    Assignee: Associates of Cape Cod, Inc.
    Inventors: Thomas J. Novitsky, Richard J. Ridge, Jack L. Sloyer
  • Patent number: 6165800
    Abstract: A new class of chemiluminescent acridinium or benzacridinium compounds is disclosed by virtue of forming an intramolecular energy transfer conjugate (ETC) between the acridinium or benzacridinium compound and a luminophore. A method of extending the emission wavelengths of acridinium or benzacridinium esters in order to further reduce or eliminate the emission spectral overlap between the parent polysubstituted aryl Acridinium Esters (DMAE) and Benzacridinium Esters (LEAE) is disclosed. The ETC's retain the unique desired properties of acridinium or benzacridinium compounds including complete light emission in very short period of time, monophasic emission spectrum, simplicity of triggering mechanism, ability of labeling the biological molecules of interest to form a tracer, and good stability. Additionally, the range of the emission spectrum of an acridinium or benzacridinium compound can now be shifted at will and at longer leap through the choice of a luminophore as the integral part of an ETC molecule.
    Type: Grant
    Filed: May 27, 1998
    Date of Patent: December 26, 2000
    Assignee: Bayer Corporation
    Inventors: Qingping Jiang, Jun Xi, Anand Natrajan, David Sharpe, Marcus Baumann, Rolf Hilfiker, Erika Schmidt, Paul Senn, Fritz Thommen, Adrian Waldner, Alex Alder, Say-Jong Law
  • Patent number: 6159689
    Abstract: Methods of capturing and labeling a species, include attracting magnetically attractable particles to a solid support by magnetic forces, which particles have an affinity for the species, contacting the particles on the support with a sample containing the species to capture the species onto the particles on the support, and binding the species captured on the particles directly or indirectly to a detectable label before and/or whilst the species is captured on the particles on the support. The label may be bound to the captured species via an immunological binding partner which binds selectively to the species and may be a fluorescent label, luminescent label, enzyme label, dye label, phosphorescent label, metal-chelating label, radio label, spin label, heavy metal label, nucleic acid or nucleic acid analog hybridization label, avid or avid-like label suitably bound to or incorporated in particles which also bear a binding agent such as an antibody causing the particles to bind to the captured species.
    Type: Grant
    Filed: May 8, 1998
    Date of Patent: December 12, 2000
    Assignee: Genera Technologies Limited
    Inventor: Adrian Parton
  • Patent number: 6159749
    Abstract: An apparatus and method for chemical and biological analysis, the apparatus having an optical trapping means to manipulate the reaction substrate, and a measurement means. The optical trapping means is essentially a laser source capable of emitting a beam of suitable wavelength (e.g., Nd:YAG laser). The beam impinges upon a dielectric microparticle (e.g., a 5 micron polystyrene bead which serves as a reaction substrate), and the bead is thus confined at the focus of the laser beam by a radial component of the gradient force. Once "trapped," the bead can be moved, either by moving the beam focus, or by moving the reaction chamber. In this manner, the bead can be transferred among separate reaction wells connected by microchannels to permit reactions with the reagent affixed to the bead, and the reagents contained in the individual wells.
    Type: Grant
    Filed: July 21, 1998
    Date of Patent: December 12, 2000
    Assignee: Beckman Coulter, Inc.
    Inventor: Yagang Liu
  • Patent number: 6153442
    Abstract: The present invention relates to compounds that are bis-biotins. These compounds comprise two biotinyl radicals connected by a chain of atoms, usually at least 16 atoms in length. The bis-biotin is conjugated to a member of a specific binding pair ("sbp member") wherein the chain is not part of the sbp member. Also disclosed are compositions comprising a complex of avidin and a bis-biotin as described above. The compounds and compositions of the invention find use in an assay for an analyte wherein there is employed a reagent system comprising an avidin reagent and a biotin reagent. The improvement of the present invention comprises using as the biotin reagent a bis-biotin as described above. Also disclosed are kits comprising the present bis-biotins and methods of preparing a bis-biotinylated conjugate of a member of a specific binding pair ("sbp member") for use in a specific binding assay.
    Type: Grant
    Filed: May 20, 1998
    Date of Patent: November 28, 2000
    Assignee: Dade Behring Inc.
    Inventors: Marcel Rene Pirio, Dariush Davalian, Jacqueline Sadakan Ishkanian, Edwin F. Ullman
  • Patent number: 6150123
    Abstract: The present invention relates to a method for biotinylating a desired subset of a larger population of proteins, wherein the subset of proteins is first selectively bound to a solid phase, thereby separating it from undesired proteins of the population, and then, still bound to solid phase, it is biotinylated. Unreacted biotin may then be washed from the solid phase, and the biotinylated protein may be uncoupled from the solid phase.
    Type: Grant
    Filed: September 3, 1998
    Date of Patent: November 21, 2000
    Assignee: Centre Integre de Recherches Biocliniques sur le Sida (CIRBS)
    Inventor: Antonio Cosma
  • Patent number: 6143507
    Abstract: Disclosed is a high throughput compatible assay that is useful for the identification of specific antagonists of TRAF-receptor interactions. The modular flexibility of the assay makes it possible to introduce simple modifications in order to measure the interaction of any TNF receptor cytoplasmic domain (or TRAF-binding protein) with any of the six TRAF proteins, TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 and TRAF6.
    Type: Grant
    Filed: October 29, 1998
    Date of Patent: November 7, 2000
    Assignee: Boehringer Ingelheim Pharmaceuticals, Inc.
    Inventors: Marilyn R. Kehry, Steven S. Pullen, James J. Crute
  • Patent number: 6140138
    Abstract: A chemical moiety is disclosed which comprises a chemical, biochemical, or biological substance attached to one or more electrochemiluminescent organometallic compounds. In a preferred embodiment of the invention the substance is attached to one or more ruthenium-containing or osmium-containing luminescent organometallic compounds. Methods are disclosed for detecting low concentrations of the chemical moiety using chemiluminescent, electrochemiluminescent, and photoluminescent means. Compounds are disclosed which are useful for labeling substances of interest with ruthenium-containing and osmium-containing labels or other electrochemiluminescent labels. These labeled substances are useful in methods provided for detecting and quantifying analytes of interest in binding assays and competitive binding assays. The labeled substances are of particular use in homogeneous binding assays.
    Type: Grant
    Filed: May 4, 1994
    Date of Patent: October 31, 2000
    Assignee: IGEN International Inc.
    Inventors: Allen J. Bard, George M. Whitesides
  • Patent number: 6124430
    Abstract: The present invention provides reagents and assays for the quantification of hBNP in biological fluid samples such as plasma or serum. Antibodies are provided which are monospecific to epitopes comprising the amino acid sequences 5-13, 1-10 and 15-25 of hBNP. These antibodies, and peptide fragments containing these sequences, can be employed in the assays of the invention, which may be carried out in a sandwich format or a competition format.
    Type: Grant
    Filed: October 1, 1997
    Date of Patent: September 26, 2000
    Assignee: Scios Inc.
    Inventors: Ronald P. Mischak, Garrett A. Lim, Jan Marian Scardina