Producing Labeled Antigens Patents (Class 436/544)
  • Patent number: 6103536
    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 1, 1998
    Date of Patent: August 15, 2000
    Assignee: Silver Lake Research Corporation
    Inventor: Mark S. Geisberg
  • Patent number: 6078782
    Abstract: The invention relates to methods of performing a binding assay for an analyte of interest present in a sample based upon electrochemiluminescence at an electrode of interest. Particles are employed in the method, which are then collected in a zone at which electrochemiluminescence can be induced, wherein the amount of induced electrochemiluminescence is related to the amount of analyte in the sample.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: June 20, 2000
    Assignee: IGEN International Inc.
    Inventors: John K. Leland, Haresh P. Shah, John H. Kenten, Jack E. Goodman, George E. Lowke, Yuzaburo Namba, Gary F. Blackburn, Richard J. Massey
  • Patent number: 6071705
    Abstract: This invention relates to a method of detecting and diagnosing neurological disease or dysfunction using antibodies against a neurological form of Pancreatic Thread Protein (nPTP). Specifically, this invention is directed to a method of diagnosing Alzheimer's Disease, Down's Syndrome, and other neurological diseases or dysfunctions by using monoclonal antibodies, combination of those monoclonal antibodies or nucleic acid probes, to detect nPTP. The invention also relates to a recombinant DNA molecule encoding PTP and to the substantially pure form of nPTP. The invention additionally relates to a method of diagnosing pancreatic disease using antibodies against Pancreatic Thread Protein.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: June 6, 2000
    Assignee: The General Hospital Corporation
    Inventors: Jack R. Wands, Jerome Gross, Mehmet Ozturk, Suzanne de la Monte
  • Patent number: 6060260
    Abstract: The present invention relates to methods for substantially reducing adsorption of at least one positively charged molecule to a negatively charged surface upon contact therebetween, the method comprising combining the positively charged molecule with at least one blocking agent in an amount sufficient to substantially reduce the adsorption of the positively charged molecule to the negatively charged surface.
    Type: Grant
    Filed: February 27, 1998
    Date of Patent: May 9, 2000
    Assignee: Dade Behring Inc.
    Inventors: Joseph W. Amshey, Jr., Rosy Sheng Donn
  • Patent number: 6048703
    Abstract: Methods for the biochemical and immunohistochemical detection of cell apoptosis are described. The methods utilize the detection and measurement of polypeptide fragments generated during apoptosis. Conditions associated with apoptosis may be detected by the methods of this invention. Methods are also presented for the screening of potential therapeutic compounds which inhibit or stimulate apoptosis. Kits for detection of apoptosis and diagnosis of diseases are also provided.
    Type: Grant
    Filed: November 12, 1997
    Date of Patent: April 11, 2000
    Assignee: Cephalon, Inc.
    Inventors: Robert Siman, Donna Bozyczko-Coyne, Sheryl L. Meyer, Ratan Venkatraman Bhat
  • Patent number: 6037185
    Abstract: A non-competitive method for the determination of analytes. Initially the analyte is bound to a specific binding partner, after which the unoccupied binding sites of the binding partner are inactivated. The bound analyte is then dissociated from the binding partner and replaced by a labeled marker, after which the bound labeled marker is determined. The signal from the bound labeled marker is directly proportional to the initial amount of analyte in the sample, which makes the present method more favorable than the competitive assays.
    Type: Grant
    Filed: July 8, 1998
    Date of Patent: March 14, 2000
    Assignees: Wallac Oy, Orion-yhtyma Oy
    Inventor: Petri Saviranta
  • Patent number: 6017769
    Abstract: Methods of generating chemiluminescence rapidly without the use of enzymes are provided. The methods utilize chemiluminescent compounds comprising an acridan ring bearing an exocyclic double bond in a reaction with an acid, an oxidant and a base. The chemiluminescent methods are useful in assays to detect the amount of an analyte in a sample. The chemiluminescent compounds may be supplied as a label on an analyte or a specific binding partner or may be encapsulated within a liposome or latex particle.
    Type: Grant
    Filed: June 17, 1998
    Date of Patent: January 25, 2000
    Assignee: Lumigen, Inc.
    Inventor: Hashem Akhavan-Tafti
  • Patent number: 6010913
    Abstract: The invention deals with isolated human tau peptide epitopes of SEQ ID Nos: 1 to 4, 7 and 15 to 20 which have the capability of binding AT120 monoclonal antibody.
    Type: Grant
    Filed: January 19, 1995
    Date of Patent: January 4, 2000
    Assignee: N.V. Innogenetics S.A.
    Inventors: Marc Vandermeeren, Marc Mercken, Eugeen Vanmechelen, Andre Van De Voorde
  • Patent number: 6004824
    Abstract: The present invention provides hapten derivatives that are useful for the preparation of antigenic, antibody and label reagents having superior performance characteristics for use in immunoassays for the detection of d-propoxyphene and d-nor-propoxyphene. In the present invention the propoxyphene nucleus is derivatized out of the nitrogen center to form an aminoalkyl -carboxyl, or -hydroxyl haptenic derivative. The resulting hapten can then be further modified at the now functionalized position off the nitrogen for linking to an appropriate antigenic or labeling group to provide reagents for propoxyphene immunoassays having excellent sensitivity and selectivity for both d-propoxyphene and d-nor-propoxyphene.
    Type: Grant
    Filed: July 2, 1997
    Date of Patent: December 21, 1999
    Assignee: Roche Diagnostics Corporation
    Inventor: Robert Sundoro Wu
  • Patent number: 6001561
    Abstract: Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.
    Type: Grant
    Filed: May 9, 1995
    Date of Patent: December 14, 1999
    Assignee: Abbott Laboratories
    Inventors: Nai-Yi Wang, Roger C. Hu
  • Patent number: 6001659
    Abstract: Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.
    Type: Grant
    Filed: May 9, 1995
    Date of Patent: December 14, 1999
    Assignee: Abbott Laboratories
    Inventors: Nai-Yi Wang, Roger C. Hu
  • Patent number: 5989842
    Abstract: The invention is a method for the enzymatic labeling of biomolecules, such as immunoglobulin, peptide, hormone, or hapten, which involves oxidizing horseradishperoxidase (HRP) with a periodate, crosslinking the oxidized HRP with an .alpha.,.OMEGA.-diaminoalkane, and coupling the biomolecule with the crosslinked, oxidized HRP.
    Type: Grant
    Filed: June 26, 1998
    Date of Patent: November 23, 1999
    Assignee: Bio-Tez Berlin-Buch GmbH
    Inventors: Eberhard Schmidt, Christa Weiss
  • Patent number: 5989831
    Abstract: Method of assaying hapten in a sample, in which said sample is placed in contact with antibodies capable of recognizing hapten and with a predetermined quantity of a reagent capable of competing with said hapten-fixing antibodies. The reagent is a conjugate formed by a single-stranded fragment of nucleic acid with a compound capable of being recognized by said hapten-recognizing antibodies. The fixed or unfixed reactant is detected by antibodies capable of recognizing the nucleic acid fragment of said conjugate. Detection of said reactant by anti-fragment antibodies of said nucleic acid enhances, in particular, the sensitivity of the assay.
    Type: Grant
    Filed: July 8, 1997
    Date of Patent: November 23, 1999
    Assignee: Bio Merieux
    Inventors: Philippe Cros, Nicole Battail, Nadia Piga
  • Patent number: 5989921
    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: July 2, 1997
    Date of Patent: November 23, 1999
    Assignee: Carter Wallace, Inc.
    Inventors: David E. Charlton, Neal W. Miller
  • Patent number: 5972622
    Abstract: This invention relates to antibodies or fragments thereof that can be used as indicators of apoptosis. More specifically, this invention relates to antibodies and fragments thereof that selectively bind GP46, a protein whose levels increase significantly upon induction of apoptosis. This invention also relates to the hybridomas that produce anti-GP46 monoclonal antibodies. This invention also discloses a method of detecting cell death by apoptosis in vitro or in vivo by detecting and quantifying GP46 present in biological samples, comprising contacting the sample with the antibodies or fragments to form GP46 immunocomplexes, which may then be detected by the use of known methods. This detection method is useful for research into apoptosis and research relating to diseases in which apoptosis is involved. This method could also be used to diagnose the extent of damage caused by a particular disease or to evaluate the efficacy of drug treatments.
    Type: Grant
    Filed: February 6, 1997
    Date of Patent: October 26, 1999
    Inventor: Louise Desjardins
  • Patent number: 5962242
    Abstract: Diagnostic/prognostic methods are provided for screening for pathologies wherein an alteration in estrogen metabolism is indicative of a pathology or a susceptibility thereto which comprise detecting and/or quantifying directly in tissues and body fluids of mammals abnormal levels of estrone metabolites and their glucuronide conjugates. Particularly preferred methods involve the use of the 16OHE1-glucuronide fraction, i.e., the fraction which contains 16.alpha.-hydroxyestrone (16OHE1) and its conjugates, 16OHE1-3-glucuronide. Methods of preparing reagents to detect said 16OHE1-glucuronide fraction in tissues and body fluids are disclosed as well as test kits for performing the disclosed assays.
    Type: Grant
    Filed: August 22, 1997
    Date of Patent: October 5, 1999
    Assignee: Immuna Care Corporation
    Inventor: Thomas L. Klug
  • Patent number: 5962218
    Abstract: The invention relates to methods, apparatus, reagents, and kits for performing a binding assay for an analyte of interest present in a sample based upon electrochemiluminescence at an electrode of interest. In the method, reagents and kits particles can be employed; for instance, for settling upon the electrode surface by gravity, centrifugation or magnetic attraction. The apparatus can include a magnet for generating a magnetic field in a region proximate the electrode.
    Type: Grant
    Filed: November 24, 1993
    Date of Patent: October 5, 1999
    Assignee: IGEN International Inc.
    Inventors: Jonathan K. Leland, Haresh P. Shah, John H. Kenten, Jack E. Goodman, George E. Lowke, Gary F. Blackburn, Richard J. Massey
  • Patent number: 5935779
    Abstract: The invention relates to methods of performing a binding assay for an analyte of interest present in a sample based upon electrochemiluminescence at an electrode of interest. Particles are employed in the method, which are then collected in a zone at which electrochemiluminescence can be induced, wherein the amount of induced electrochemilurninescence is related to the amount of analyte in the sample.
    Type: Grant
    Filed: November 30, 1994
    Date of Patent: August 10, 1999
    Assignee: IGEN International Inc.
    Inventors: Richard J. Massey, Jonathan K. Leland, Haresh P. Shah, John H. Kenten, Jack E. Goodman, George E. Lowke, Yuzaburo Namba, Gary F. Blackburn
  • Patent number: 5936070
    Abstract: Methods are disclosed for determining an analyte in a medium suspected of containing the analyte. One method comprises providing (1) combining a medium suspected of containing the analyte and a novel chemiluminescent compound, (2) combining a means for chemically activating the chemiluminescent compound; and (3) detecting the amount of luminescence generated by the chemiluminescent compound. The amount of luminescence generated is related to the amount of analyte in the medium. The chemiluminescent compound can be chemically activated by hydrogen peroxide. Compositions and kits are also disclosed.
    Type: Grant
    Filed: June 11, 1996
    Date of Patent: August 10, 1999
    Assignee: Dade Behring Marburg GmbH
    Inventors: Sharat Singh, Rajendra Singh, Frank Meneghini, Edwin F. Ullman
  • Patent number: 5925526
    Abstract: An isolated nucleic acid sequence encoding major Yo paraneoplastic antigenic polypeptide is provided by this invention. This invention also provides a purified major Yo antigenic polypeptide and compositions containing the purified major Yo antigenic polypeptide. Further provided by this invention is a monoclonal antibody directed to an epitope on the major Yo paraneoplastic antigenic polypeptide. Compositions containing this monoclonal antibody also are provided by this invention. This invention also provides methods of diagnosis and treatment using the compositions described hereinabove.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: July 20, 1999
    Assignee: Sloan-Kettering Institute for Cancer Research
    Inventors: Jerome B. Posner, Henry M. Furneaux
  • Patent number: 5866335
    Abstract: The synthesis of 10,10'-substituted-9,9'-biacridine molecules and their derivatives is disclosed. These molecules are shown to catalyze the production of light by chemiluminescence in the presence of a signal solution having at a pH from about 10.0 to about 14.0, at a concentration effective for producing a chemiluminescent signal, a chelating agent, a sulfoxide, a reducing sugar, an oxidant or combination of oxidants, an alcohol and aqueous sodium tetraborate. These 10,10'-substituted-9,9'-biacridines are used alone or attached to haptens or macromolecules and are utilized as labels in the preparation of chemiluminescent, homogeneous or heterogeneous assays. They are also used in conjunction with other chemiluminescent label molecules to produce multiple analyte chemiluminescent assays.
    Type: Grant
    Filed: December 16, 1996
    Date of Patent: February 2, 1999
    Assignee: George W. Katsilometes
    Inventors: George W. Katsilometes, Pak T. Ho
  • Patent number: 5863401
    Abstract: Homogeneous competitive immunoassay methods for simultaneously detecting analytes using capillary electrophoresis and fluorescent detection systems are described. The methods are useful for detecting and/or quantitating the concentration of a plurality of drugs of abuse in a single urine sample using a single assay method.
    Type: Grant
    Filed: July 3, 1997
    Date of Patent: January 26, 1999
    Assignee: Beckman Instruments, Inc.
    Inventor: Fu-Tai A. Chen
  • Patent number: 5854009
    Abstract: Diagnostic/prognostic methods are provided for screening for pathologies wherein an alteration in estrogen metabolism is indicative of a pathology or a susceptibility thereto which comprise detecting and/or quantifying directly in tissues and body fluids of mammals abnormal levels of estrone metabolites and their glucuronide conjugates. Particularly preferred methods involve the use of the 16OHE1-, 2OHE1- or 2MeoE1-glucuronide fraction, i.e., the fraction which contains the metabolite and its 3-glucuronide conjugate. Methods of preparing reagents to detect said 16OHE1-, 2OHE1-, and 2MeoE1-glucuronide fraction in tissues and body fluids are disclosed as well as test kits for performing the disclosed assays.
    Type: Grant
    Filed: September 18, 1996
    Date of Patent: December 29, 1998
    Assignee: Immuna Care Corporation
    Inventor: Thomas L. Klug
  • Patent number: 5851781
    Abstract: The present invention discloses novel immunogens, antibodies prepared from such immunogens, and labeled reagents useful in immunoassays for the detection and quantification of testosterone in a test sample. Also disclosed are immunoassays using these reagents and methods for synthesizing these reagents. The immunoassays are preferably microparticle enzyme immunoassays (MEIAs) and fluorescence polarization immunoassays (FPIAs). Further disclosed are novel starting materials for making the above novel immunogens and labeled reagents. Methods for making the novel immunogens and labeled reagents from the novel starting materials are also disclosed.
    Type: Grant
    Filed: April 28, 1995
    Date of Patent: December 22, 1998
    Assignee: Abbott Laboratories
    Inventors: Maciej Adamczyk, Yon-Yih Chen, John A. Walling, Bryan D. James, Sharon G. Artrip
  • Patent number: 5851778
    Abstract: A trifunctional conjugate is provided having three chemical moieties attached through a spacer moeity. At least two of the chemical moieties are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected to impart certain steric properties to the conjugate. In one embodiment, the binding of a macromolecular specific binding partner to one of the chemical moieties sterically inhibits the binding of a different macromolecule to another chemical moiety. In another embodiment, the binding of a first chemical moiety to a macromolecule restricts the subsequent binding of a second chemical moiety to a proximate location on the same macromolecule. The three chemical moieties are preferably a nitrophenylazido residue, a phenyl boronic acid residue, and a solid support or a label such as biotin. The spacer is preferably cysteine, lysine, glutamic acid, pyroglutamic acid, S-acetylmercaptosuccinic anhydride or .omega.-carbobenzoxylysine.
    Type: Grant
    Filed: April 2, 1997
    Date of Patent: December 22, 1998
    Assignee: Beckman Instruments, Inc.
    Inventors: Chan S. Oh, James C. Sternberg
  • Patent number: 5851777
    Abstract: The present invention provides methods for detecting the presence of or determining the amount of a ligand in a fluid sample. The methods comprise providing a first reagent comprising a sol particle having a detectable physical property bound to the ligand or ligand analogue (in a competitive format) or a substance capable of specifically coupling with the ligand (in a sandwich format), providing a second reagent having a detectable physical property comprising a sol particle bound to a substance capable of specifically coupling with the ligand and/or ligand analogue, if present, combining the first reagent, second reagent and the fluid sample and detecting before, during or after the reaction, a change in the physical property of the sol particles, which provides a qualitative or quantitative indication of the ligand in the fluid sample.
    Type: Grant
    Filed: February 5, 1996
    Date of Patent: December 22, 1998
    Assignee: Dade Behring Inc.
    Inventors: Thomas J. Hunter, Ernest H. Pfadenhauer
  • Patent number: 5846737
    Abstract: The invention describes useful conjugates of sulforhodamine, wherein the conjugated substance and the fluorophore are separated by an alkanoic acid spacer that is attached to the fluorophore via a sulfonamide bond. The increased length of the covalent linkage due to the spacer results in dye-conjugates having a number of surprisingly advantageous properties relative to previous sulforhodamine-labeled conjugates, including increased fluorescence.
    Type: Grant
    Filed: July 26, 1996
    Date of Patent: December 8, 1998
    Assignee: Molecular Probes, Inc.
    Inventor: Hee Chol Kang
  • Patent number: 5843682
    Abstract: Novel derivatives of LSD having the formula ##STR1## wherein R.sub.1 is an alkyl, cycloalkyl or aryl group having 1 to 10 carbon atoms, preferably an alkyl group having 1 carbon atom;R.sub.2 is a bond or ##STR2## wherein R.sub.3 is alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms, preferably an alkyl group having 2 or 5 carbon atoms; Z is an immunogenic carrier substance, an enzyme donor polypeptide or a label selected from the group consisting of an enzyme, a substance having fluorescent or luminescent properties and a radioactive substance; and n is 1 to p where p equals MW of Z/1000. The derivatives include maleimide conjugates of an immunogenic poly(amino acid), an enzyme donor polypeptide or a labeling substance such as an enzyme, a fluorescent substance or a radioactive substance. Novel activated hapten intermediates useful in the preparation of the conjugates and methods for synthesis of the hapten intermediates and their conjugate derivatives are also disclosed.
    Type: Grant
    Filed: November 20, 1995
    Date of Patent: December 1, 1998
    Assignee: Boehringer Mannheim Corporation
    Inventors: Gerald F. Sigler, Riaz Rouhani, David Davoudzaheh
  • Patent number: 5817317
    Abstract: The present invention provides novel peptides and vaccines containing them capable of inducing production of antibodies directed against Clostridium perfringens alpha-toxin (CPa) in animals to which they are administered and thereby providing prophylaxis against infection by Clostridium perfringens and/or the alpha-toxin itself. Particularly the present invention provides such a vaccine that is relatively safe and simple to produce. e.g. by genetic engineering means. Preferred peptides comprise theo amino acid sequence of Clostridium perfringens alpha-toxin from amino acid 247 to 370 but lack the epitopes necessary for phospholipase C and/or sphingomyelin hydrolysing activity found between amino acids 1 to 240 of that sequence. Further provided are antisera and antibodies raised to the peptides and vaccines of the present invention, and particularly monoclonal antibodies and hybridoma cell lines for their production.
    Type: Grant
    Filed: November 28, 1994
    Date of Patent: October 6, 1998
    Assignee: The Secretary of State for Defense of Great Britian & Northern Ireland
    Inventors: Richard William Titball, Ethel Diane Williamson
  • Patent number: 5817529
    Abstract: The present invention provides hapten derivatives that are useful for the preparation of antigenic, antibody and label reagents having superior performance characteristics for use in immunoassays for the detection of d-propoxyphene and d-nor-propoxyphene. In the present invention the propoxyphene nucleus is derivatized out of the nitrogen center to form an aminoalkyl -carboxyl, -amino, -thiol or -hydroxyl haptenic derivative. The resulting hapten can then be further modified at the now functionalized position off the nitrogen for linking to an appropriate antigenic or labelling group to provide reagents for propoxyphene immunoassays having excellent sensitivity and selectivity for both d-propoxyphene and d-nor-propoxyphene.
    Type: Grant
    Filed: April 28, 1997
    Date of Patent: October 6, 1998
    Assignee: Roche Diagnostic Systems, Inc.
    Inventor: Robert Sundoro Wu
  • Patent number: 5786153
    Abstract: A method for substantially preventing coating of hydrophobic material on a probe of an automated analyzer during an assay is described. An automated analyzer having a probe is provided. A composition comprising a non-denaturing surfactant and a reagent for use in the assay is provided. The probe is contacted with the composition during the assay such that hydrophobic material is substantially prevented from coating the probe on the automated analyzer. Compositions for preventing such probe coating are also described. Methods and compositions comprising a non-denaturing surfactant for enhancing the stability of reagents used in an assay are also described.
    Type: Grant
    Filed: September 12, 1996
    Date of Patent: July 28, 1998
    Assignee: Chiron Diagnostics Corporation
    Inventors: Wei-Chao Ni, Anna Marie Detert, James Joseph Hughes
  • Patent number: 5773234
    Abstract: A lateral flow assay device for detecting the presence of Chlamydia antigen in patient's samples comprises a flow matrix including a labelling zone and a capture zone. Labelling complex comprising antibodies specific for an epitope on the lipopolysaccharide antigen of Chlamydia is present within the labelling zone. Immobilized antibody specific for the same or another epitope of the lipopolysaccharide antigen of Chlamydia is located in the capture zone. The sample containing the Chlamydia antigen will flow first through the labelling zone, where it complexes with the labelling complex, and then to the capture zone, where it is captured by the immobilized antibody. Chlamydia antigen may be extracted from a patient sample, such as a endocervical swab, by first extracting the antigen in a strong base followed by neutralization with a zwitterionic detergent and a blocking protein present in a zwitterionic buffer.
    Type: Grant
    Filed: August 7, 1995
    Date of Patent: June 30, 1998
    Assignee: Quidel Corporation
    Inventors: Allan D. Pronovost, Robert E. Klepper, Catherine Pawlak
  • Patent number: 5747047
    Abstract: The present invention is directed to novel purified and isolated mite allergens possessing mite allergen activity with a molecular weight of about 94,000, about 40,000, about 16,000 or about 14,000 as determined by SDS-PAGE, which can be isolated from extracts of mite, and to a process for producing such mite allergens. The purified and isolated mites allergens of the present invention are useful as a pharmaceutical and a diagnostic composition for mite allergic diseases.
    Type: Grant
    Filed: August 22, 1994
    Date of Patent: May 5, 1998
    Assignees: Fumakilla Ltd., Hiroshima University
    Inventors: Satoru Oka, Kazuhisa Ono, Seiko Shigeta, Takeshi Wada
  • Patent number: 5719064
    Abstract: It has been determined that HLA B27 is related to proteins of the Gram negative enteric bacteria. The hypervariable regions of the HLA B alleles were compared to the known sequenced proteins for short consecutive amino acid identities. It was found that, unique to the HLA B alleles,, HLA B27 shares an unexpected number of hexapeptides and pentapeptides with Gram negative bacteria proteins. The proteins from enteric organisms that share sequence with B27 tend to have sequences that satisfy protein sequence motifs which are thought to predict binding to B27. In addition, there is a sequence in B27, LRRYLENGK, which is predicted to bind as a peptide to B27. Binding of this peptide to B27 has been demonstrated. The disclosed peptides are useful for diagnostic and therapeutic purposes and can be used to design additional peptides from Gram negative enteric organisms can be identified to be important in the spondyloarthropathies.
    Type: Grant
    Filed: August 31, 1992
    Date of Patent: February 17, 1998
    Assignee: Oklahoma Medical Research Foundation
    Inventors: R. Hal Scofield, John B. Harley
  • Patent number: 5686244
    Abstract: This invention relates to a new electrochemiluminescent (ECL) label for oligonucleotides using phosphoramidite chemistry.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: November 11, 1997
    Assignee: IGEN Incorporated
    Inventors: Satyanarayana R. Gudibande, John H. Kenten
  • Patent number: 5669819
    Abstract: Acridinium sulfonylamides and isomers, such as phenanthridinium sulfonylamides, may be employed in applications including chemiluminmescent immunoassays. Methods for synthesis of these compounds include contacting an amine with a sulfonylhalide to form a sulfonamide and acylating with an activated carboxylic acid of an acridine or isomer thereof. The N-sulfonyl-9-acridinium carboxamide and isomers may be conjugated to antigens, haptens, antibodies, and nucleic acids for use in chemiluminescent assays.
    Type: Grant
    Filed: May 16, 1995
    Date of Patent: September 23, 1997
    Assignee: Abbott Laboratories
    Inventors: Phillip Gregory Mattingly, Larry Gene Bennett
  • Patent number: 5663074
    Abstract: This invention is directed to novel nucleophilic polysubstituted aryl acridinium conjugates and the methods for preparation thereof. The novel nucleophilic polysubstituted aryl acridinium conjugates are useful in biological assays, including novel assays for the determination of Vitamin B.sub.12, folate, cortisol, estradiol, and thromboxane B.sub.2.
    Type: Grant
    Filed: March 17, 1993
    Date of Patent: September 2, 1997
    Assignee: Chiron Diagnostics Corporation
    Inventor: Say-Jong Law
  • Patent number: 5660994
    Abstract: The invention relates to the identification of insoluble cytoskeletal proteins, or fragments thereof, which are characteristic of the origin of the tissue. The invention relates as well to the method for detecting such proteins by breaking down and solubilizing the protein for immunological detection and quantitation. The method allows detection of tissue lesions or other pathological foci and metastases.
    Type: Grant
    Filed: March 1, 1995
    Date of Patent: August 26, 1997
    Assignee: Progen Biotechnik GmbH
    Inventors: Gerda Bruder-Heid, Werner Wilhelm Franke
  • Patent number: 5661019
    Abstract: A trifunctional conjugate is providing having three chemical moieties attached through a spacer moiety. At least two of the chemical moieties are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected to impart certain steric properties to the conjugate. In one embodiment, the binding of a macromolecular specific binding partner to one of the chemical moieties sterically inhibits the binding of a different macromolecule to another chemical moieties. In another embodiment, the binding of a first chemical moiety to a macromolecule restricts the subsequent binding of a second tridentate member to a proximate location on the same macromolecule. The three chemical moieties are preferably a nitrophenylazido residue, a phenyl boronic acid residue, and a solid support or a label such as biotin. The spacer is preferably cysteine, lysine, glutamic acid, pyroglutamic acid, S-acetylmercaptosuccinic anhydride or .omega.-carbobenzoxylysine.
    Type: Grant
    Filed: March 22, 1995
    Date of Patent: August 26, 1997
    Assignee: Beckman Instruments, Inc.
    Inventors: Chan S. Oh, James C. Sternberg
  • Patent number: 5650270
    Abstract: Analytical reagents designated "release tags", for labeling molecular species with a highly detectable signal group which can be released in the form of a volatile compound at a desired point in an analytical procedure. In one embodiment, the release tags have the formula(SgCo).sub.x L(Rx).sub.rwherein each Sg is a signal group bearing one or more electronegative substituents, L is any of a wide variety of groups which when attached to a carbonyl group form a readily cleaved linkage, each COL moiety is a release group which upon scission releases signal group Sg in the form of a volative compound, and each Rx is a reactivity group for attaching the release tag compound to a molecular species to be labeled. In a second embodiment, the release tags have the formulaSgReRxwherein Sg and Rx are defined as above and Re is a release group which is an olefin, .alpha.-hydroxy ketone or vicinal diol. Conjugates of the release tag compounds and assay methods employing them are also disclosed.
    Type: Grant
    Filed: March 20, 1990
    Date of Patent: July 22, 1997
    Assignee: Northeastern University
    Inventors: Roger W. Giese, Samy Abdel-Baky, Kariman Allam
  • Patent number: 5650489
    Abstract: The instant invention provides a library of bio-oligomers of defined size and known composition, in which the library contains all of the possible sequences of the bio-oligomers, and a method of synthesis thereof. The bio-oligomers of the library may be peptides, nucleic acids, or a combination of the foregoing. The instant invention also provides methods to identify bio-oligomers from a library that demonstrate desired characteristics such as binding, bioactivity and catalytic activity. Thus the instant invention provides a unique and powerful method to identify a useful bio-oligomer sequences from a library more quickly than current state-of-the-art technology allows. Effector molecules for use in treatment or diagnosis of disease are also provided.
    Type: Grant
    Filed: June 19, 1991
    Date of Patent: July 22, 1997
    Assignee: The Arizona Board of Regents
    Inventors: Kit Sang Lam, Sydney E. Salmon
  • Patent number: 5643734
    Abstract: This invention relates to improved methods and novel compositions for enzyme complementation assays for qualitative and quantitative determination of a suspected analyte in a sample. The use of enzyme-acceptor and enzyme-donor polypeptides prepared by recombinant DNA techniques, DNA synthesis or chemical polypeptide synthesis techniques which are capable of interacting to form an active enzyme complex having catalytic activity characteristic of .beta.-galactosidase is described. Both homogeneous and heterogeneous assays utilizing these polypeptides are described.
    Type: Grant
    Filed: June 1, 1995
    Date of Patent: July 1, 1997
    Assignee: Microgenics Corporation
    Inventor: Daniel Robert Henderson
  • Patent number: 5637508
    Abstract: Polymer or copolymer coated catalytic colloidal metal particles bound to a biomolecule such as an antibody, avidin, or streptavidin and kits containing such polymer or copolymer coated catalytic metal particles are useful for detecting the presence of the biomolecule in an assay such as an immunoassay.
    Type: Grant
    Filed: January 23, 1995
    Date of Patent: June 10, 1997
    Assignees: Geo-Centers, Inc., The United States of America as represented by the Secretary of the Navy
    Inventors: David A. Kidwell, Susan M. Conyers
  • Patent number: 5631138
    Abstract: A method for the measurement of serum bile acids by ELISA comprising: preparing a bile acid active ester, reacting the ester with a bovine serum albumin solution, dialyzing, and immunizing a mammal other than human being with the dialyzate thus obtained as an antigen to thereby give an anti-bile acid antibody; reacting said active ester with an enzyme to thereby prepare an enzyme-labeled bile acid as an enzyme-labeled antigen; to a secondary antibody-coated plate, adding a dilution of the serum to be assayed, an anti-bile acid antibody solution and an enzyme-labeled antigen solution and reacting these substances followed by the addition of a substrate and the reaction therewith; measuring the absorbance of the reaction mixture and determining the concentration of each bile acid on the basis of the standard curve measured simultaneously; and referring the sum of the concentrations of these bile acids to the total bile acid concentration; and a method for the diagnosis of a liver disease comprising: calculating
    Type: Grant
    Filed: January 31, 1995
    Date of Patent: May 20, 1997
    Assignee: Yuugengaisha B.S.R.
    Inventors: Motonari Kano, Masaru Matsumoto
  • Patent number: 5620902
    Abstract: The stereochemistry of sialylation of an acceptor saccharide to obtain an .alpha. (2-3) or .alpha. (2-6) linkage is controlled to favor the .alpha. anomer by use of an aromatic ester of the sialyl reagent. The resulting intermediate .alpha. (2-3) and .alpha. (2-6) sialylated intermediate disaccharide blocks are useful in the synthesis of antigenic substances which can be used to raise antibodies useful in diagnosis and therapy, and can themselves be used as reagents in various applications. The preparation of the tetrasaccharide antigens corresponding to the 19-9 and sialyl-X antigens characteristic of malignant tissue illustrates the application of this method.
    Type: Grant
    Filed: May 19, 1995
    Date of Patent: April 15, 1997
    Assignee: Alberta Research Council
    Inventors: Robert M. Ratcliffe, Andre P. Venot, S. Zaheer Abbas
  • Patent number: 5614370
    Abstract: The invention is an assay, including a series of peptides, which allow screening for inhibitors of C5a binding targeted to the subsite on the C5a receptor occupied by the C-terminus of C5a. These peptides allow compound testing efforts to be targeted to this same subsite so that C5a agonists and antagonists can be identified. These peptides have much greater affinity (Ki<10 nM) than does the natural C-terminus of C5a (Ki=300 .mu.M) and have been labeled to allow for detection of molecules which inhibit binding of these peptides at this receptor subsite. The invention is useful to develop agonists, partial agonists, and antagonists of C5a, and the invention includes compounds identified according to the method of this invention and methods of their use.
    Type: Grant
    Filed: March 18, 1994
    Date of Patent: March 25, 1997
    Assignee: Merck & Co., Inc.
    Inventors: Zenon Konteatis, Salvatore J. Siciliano, Martin S. Springer
  • Patent number: 5604091
    Abstract: This invention relates to improved methods and novel compositions for enzyme complementation assays for qualitative and quantitative determination of a suspected analyte in a sample. The use of enzyme-acceptor and enzyme-donor polypeptides prepared by recombinant DNA techniques, DNA synthesis or chemical polypeptide synthesis techniques which are capable of interacting to form an active enzyme complex having catalytic activity characteristic of .beta.-galactosidase is described. Both homogeneous and heterogeneous assays utilizing these polypeptides are described.
    Type: Grant
    Filed: June 30, 1994
    Date of Patent: February 18, 1997
    Assignee: Microgenics Corporation
    Inventor: Daniel R. Henderson
  • Patent number: 5593897
    Abstract: A method of binding aggregated immunoglobulin or immune complexes comprising contacting them with modified forms of C-reactive protein. The method may be employed for diagnostic and therapeutic purposes and to deplete fluids of aggregated immunoglobulin or immune complexes. Further, a method of reducing the levels of immune complexes in a mammal comprising administering modified-CRP to the mammal, and a method of binding immunoglobulins comprising contacting them with modified C-reactive protein. Also, a method of binding aggregated immunoglobulin or immune complexes comprising contacting them with antibody to neo-CRP, and a method of modifying C-reactive protein. Finally, a test kit for detecting or quantitating immune complexes and a device for removing aggregated immunoglobulin or immune complexes from fluids are disclosed.
    Type: Grant
    Filed: July 6, 1994
    Date of Patent: January 14, 1997
    Assignee: Northwestern University
    Inventors: Lawrence A. Potempa, Byron E. Anderson
  • Patent number: 5585279
    Abstract: A time-resolved luminescence binding assay is described including a metal-labelled binding partner comprising a luminescent transition metal complex covalently attached to a binding partner such as an antigen or antibody. The metal-labelled binding partner, and a process for preparing said metal-labelled binding partner are described.
    Type: Grant
    Filed: August 8, 1994
    Date of Patent: December 17, 1996
    Inventor: Robert S. Davidson
  • Patent number: 5578500
    Abstract: Immunoassay methods and reagents for the specific quantification of imipramine or desipramine in a test sample are disclosed. The measurement of imipramine or desipramine is accomplished in a specific immunoassay employing antibodies prepared with imipramine or desipramine derivatives of the Formula III: ##STR1## wherein P is an immunogenic carrier material, X is two heteroatoms, Y is a linking group comprising from 1 to 6 carbon atoms and P is an immunogenic carrier material, and wherein for imipramine, R is CH.sub.3, and for desipramine, R is H.The present invention also describes the synthesis of unique labeled reagents of the structure of the Formula IV: ##STR2## wherein Z is a linking group comprising 1 to 4 carbon atoms and 0 to 2 heteroatoms and Q is a detectable moiety, preferably fluorescein or a fluorescein derivative, and wherein for imipramine, R.sub.1 is CH.sub.3, and for desipramine, R.sub.1 is H.
    Type: Grant
    Filed: August 5, 1994
    Date of Patent: November 26, 1996
    Assignee: Abbott Laboratories
    Inventors: Maciej Adamczyk, Charles A. Harrington, Donald Johnson