Thyroid Hormone Tests (e.g., T3, T4, Tbg, Tsh, Etc.) Patents (Class 436/500)
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Patent number: 6153442Abstract: 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: GrantFiled: May 20, 1998Date of Patent: November 28, 2000Assignee: Dade Behring Inc.Inventors: Marcel Rene Pirio, Dariush Davalian, Jacqueline Sadakan Ishkanian, Edwin F. Ullman
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Patent number: 6153440Abstract: The present invention provides methods for the simultaneous measurement of triiodothyronine (T.sub.3) and thyroxine (T.sub.4) in biological fluids such as serum by direct equilibrium dialysis and immunoassay. Specifically, the method comprises dialyzing the serum sample to equilibrium in a physiological buffer system so that the free T.sub.3 and the free T.sub.4 are separated from T.sub.3 and T.sub.4 bound to serum proteins. The method further comprises combining a measured quantity of the dialyzed serum sample having free T.sub.3 and free T.sub.4 with reagents comprising a measured quantity of T.sub.3 labelled with a detectable marker and a measured quantity of T.sub.4 labelled with a detectable marker; an anti-T.sub.3 antibody of sufficient specificity and in sufficient quantity to bind a measurable quantity of the free T.sub.3, and an anti-T.sub.4 antibody of sufficient specificity and in sufficient quantity to bind a measurable quantity of the free T.sub.4.Type: GrantFiled: September 23, 1998Date of Patent: November 28, 2000Assignee: The Regents of the University of CaliforniaInventor: Inder J. Chopra
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Patent number: 6154706Abstract: An apparatus for predicting a residual hormone concentration in a patient after a removal of a portion of the patient's glandular tissue which secretes the hormone, includes an input device constructed to receive a plurality of measured hormone concentrations corresponding to a plurality of human fluid samples taken from a patient at a plurality of sample times, respectively; and further includes a computer processor configured to iteratively calculate a residual hormone concentration. In accordance with one feature of the present invention, the computer processor is configured to generate data denoting a residual amount of glandular tissue that will remain in the patient after the removal of the portion of the patient's glandular tissue; and the apparatus further comprises an output device constructed to output the generated data denoting the residual amount of glandular tissue.Type: GrantFiled: April 9, 1999Date of Patent: November 28, 2000Inventors: Alan T. Remaley, Mark Ruddel, Phillip C. Miller
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Patent number: 6130037Abstract: A biosensor apparatus for detecting a binding event between a ligand and receptor. The apparatus includes an electrode substrate coated with a high-dielectric hydrocarbon-chain monolayer, and having ligands attached to the exposed monolayer surface. Binding of a receptor to the monolayer-bound ligand, and the resultant perturbation of the monolayer structure, causes ion-mediated electron flow across the monolayer. In one embodiment, the monolayers have a coil-coil heterodimer embedded therein, one subunit of which is attached to the substrate, and the second of which carries the ligand at the monolayer surface.Type: GrantFiled: April 24, 1997Date of Patent: October 10, 2000Assignee: PENCE and McGill UniversityInventors: R. Bruce Lennox, Robert S. Hodges, Randall T. Irvin
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Patent number: 6121056Abstract: Methods, compositions and articles of manufacture are provided for conducting specific binding assays to determine the concentration or presence of at least one analyte in a sample. At least two dendrimer-reagent preparations with different analyte specificities may be immobilized on a solid phase. Alternatively, at least one dendrimer-reagent preparation having multiple specificities may be immobilized on a solid phase. Immobilization is facilitated by coupling specific binding assay reagents such as polypeptide receptors or analytes with water soluble polymers. Such water soluble polymers, for example star polymers such as dendrimers, provide production advantages of lot-to-lot uniformity and homogeneity, and can enhance sensitivity due to low non-specific binding to the solid phase.Type: GrantFiled: April 12, 1994Date of Patent: September 19, 2000Assignee: Dade Behring Inc.Inventors: Fred Moll, III, Charles Ferzli, Spencer H. Lin, Pratap Singh
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Patent number: 6103486Abstract: A method for determining the concentration of the free fraction of an active compound, present in a biological fluid, in the presence of natural binders, the free and bound fractions of the active compound being in mutual equilibrium, bya) contacting a sample of the fluid with an unlabeled antibody,b) separating the sample from the unlabeled antibody,c) incubating the unlabeled antibody with a labeled substance (tracer) for cross-reaction with the antibody andd) measuring the amount of the tracer which is or is not bound to the antibody and calculating from this the concentration of the free fraction of the active compound,wherein the quantity of the unlabeled antibody and/or its affinity for the active compound are so small that they do not substantially effect the equilibrium between the free and bound fractions of the active compound, and the affinity of the tracer for the antibody is substantially higher or substantially lower than that of the active compound itself, and a test kit suitable for this methoType: GrantFiled: June 14, 1993Date of Patent: August 15, 2000Assignee: Dade Behring Marburg GmbHInventors: Guido Simons, Helmut Strecker, deceased, Peter Molz, Gerd Schnorr, Heinz Jurgen Skrzipczyk, Hans Wissmann
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Patent number: 6037185Abstract: 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: GrantFiled: July 8, 1998Date of Patent: March 14, 2000Assignees: Wallac Oy, Orion-yhtyma OyInventor: Petri Saviranta
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Patent number: 6017538Abstract: A molecule, protein or peptide characterized in that it is recognized by cytophilic antibodies from individuals who are immune to infection by Plasmodia, and recognized by non-cytophilic antibodies from individuals who are vulnerable to infection by Plasmodiae. The antibodies are capable of blocking the erythrocytic phase of the parasite by co-operating with accessory cells such as monocytes.Type: GrantFiled: August 8, 1995Date of Patent: January 25, 2000Assignee: Institut PasteurInventors: Pierre Druilhe, Hasnaq Bouharoun-Tayoun, Claude Oeuvray
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Patent number: 6013461Abstract: During routine screening of a patient with a family history of colorectal cancer for truncating APC mutations, a novel missense mutation was identified. Upon further evaluation, it was found that 6% of Ashkenazi Jews carry this mutation, and that it was present in .sup..about. 20% of Ashkenazis with a family history of CRC. Probes, methods, and kits for identifying individuals affected with this missense mutation are provided.Type: GrantFiled: February 13, 1998Date of Patent: January 11, 2000Assignee: The Johns Hopkins UniversityInventors: Steve Laken, Stephen Gruber, Gloria Petersen, Kenneth Kinzler, Bert Vogelstein
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Patent number: 5981296Abstract: Stabilized particle reagents suitable for use in turbidimetric immunoassays are disclosed. The stabilized particle reagents contain functionalized polymer particles in which the surface of the particle has been modified with a molecular surface modifier having the structure:R(OCH.sub.2 CH.sub.2).sub.n NH.sub.2in which: R is --H, --CH.sub.3 or --CH.sub.2 CH.sub.3, and n is an integer between 2 and 10, inclusive. The stabilized particle reagents are resistant to premature or spontaneous aggregation during preparation or storage.Type: GrantFiled: February 18, 1997Date of Patent: November 9, 1999Assignee: Dade Behring Inc.Inventor: Richard Wayne Stout
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Patent number: 5958789Abstract: A method of preventing false detection of signal due to splashing of reagent liquid used to produce such signal, when dispensing at least one such liquid from a metering tip into a second liquid, comprising the steps of: a) positioning the metering tip a predetermined distance above the upper level of the second liquid prior to dispensing the one liquid; andb) while maintaining the distance throughout the dispensing of the one liquid, dispensing the one liquid;wherein the predetermined distance is between about 1.0 mm and about 2.0 mm so that splashing during dispensing is reduced.Type: GrantFiled: July 29, 1997Date of Patent: September 28, 1999Assignee: Johnson & Johnson Clinical Diagnostics, Inc.Inventors: David Donald Hyde, Merrit Nyles Jacobs, James Daniel Riall
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Patent number: 5919632Abstract: Use of polyclonal human autoantibodies against thyroglobulin (anti-hTg autoantibodies), in particular in the form of an affinity-purified IgG fraction, as a specific binding reagent in an immunological assay for the clinical detection of autoantibodies against thyroglobulin (anti-hTg autoantibodies) in the serum of a patient, in particular in competitive assays in which the anti-hTg autoantibodies to be determined and present in the sample and the polyclonal human anti-hTg autoantibodies used as the specific binding reagent compete for the binding sites of a human thyroglobulin (hTg) used as a further reagent of the assay, one of the stated reagents in each case being labelled and the other component in each case being bound to a solid phase, and in which the presence of the anti-hTg autoantibodies to be determined and present in the sample is detected on the basis of the reduction of the binding of the labelled reagent to the solid phase.Type: GrantFiled: October 17, 1997Date of Patent: July 6, 1999Assignee: B.R.A.H.M.S. Diagnostica GmbHInventor: Andreas Bergmann
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Patent number: 5898005Abstract: Methods are provided for conducting specific binding assays to determine the concentration or presence of at least one analyte in a sample. Dendrimer-reagent preparations with particular analyte specificities are mixed in solution with a sample to form dendrimer-reagent-sample complexes. The complexes are then immobilized on a solid phase. Immobilization is facilitated by coupling specific binding assay reagents such as polypeptide receptors or analytes with water soluble polymers. Such water soluble polymers, for example star polymers such as dendrimers, provide production advantages of lot-to-lot uniformity and homogeneity, and can enhance sensitivity due to low non-specific binding to the solid phase.Type: GrantFiled: April 13, 1994Date of Patent: April 27, 1999Assignee: Dade Behring Inc.Inventors: Pratap Singh, Fred Moll, III, Peter Cronin, Spencer H. Lin, Charles Ferzli, Kent Koski, Richard Saul
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Patent number: 5879896Abstract: A human receptor protein capable of binding TRH, a DNA coding for said protein, use of the proetein and DNA, a method for preparing said protein, and antibodies to the protein are described.The human TRH receptor protein and the DNA coding for the protein of the present invention are useful as (1) a diagnostic composition for neuropathy (particularly, dementia), (2) a pharmaceutical composition for neuropathy and (3) a material used for screening a TRH receptor agonist or antagonist.Type: GrantFiled: August 9, 1994Date of Patent: March 9, 1999Assignee: Takeda Chemical Industries, Ltd.Inventors: Shuji Hinuma, Masaki Hosoya, Haruo Onda
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Patent number: 5879953Abstract: Chemiluminescent acridinium derivatives of the formula I ##STR1## in which R.sup.4 represents a radical of the formula II or III ##STR2## and A.sup..theta., X--, R.sup.1 -R.sup.3, R.sup.5 and R.sup.6 have the stated meanings, as well as processes for the preparation of the compounds of the formula (I) and the use thereof in chemiluminescence immunoassays.Type: GrantFiled: June 7, 1995Date of Patent: March 9, 1999Assignee: Hoechst AktiengesellschaftInventors: Tonio Kinkel, Peter Molz, Erwin Schmidt, Gerd Schnorr, Heinz Jurgen Skrzipczyk
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Patent number: 5861319Abstract: Methods and compositions are provided for specific binding assays in which specific binding reagents are immobilized on a solid phase. Immobilization is facilitated by covalently coupling specific binding assay reagents such as polypeptide receptors or analytes with water soluble polymers. Such water soluble polymers, for example star polymers such as dendrimers, provide production advantages of lot-to-lot uniformity and homogeneity, and can enhance sensitivity due to low non-specific binding to the solid phase.Type: GrantFiled: October 28, 1994Date of Patent: January 19, 1999Assignee: Dade Behring Inc.Inventors: Spencer H. Lin, Kwok Sum Yu, Pratap Singh, Steven E. Diamond
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Patent number: 5854008Abstract: Fluorogenic chelators for Eu.sup.3+ and Tb.sup.3+ are provided, they form highly fluorescent complexes with Eu.sup.3+ and Tb.sup.3+. In all cases, the fluorescence observed was lanthanide-specific, long-lived and it was monitored by microsecond time-resolved fluorometry. The fluorogenic chelators could be quantified, in the presence of excess lanthanide, at levels<10.sup.-8 mol/L. Fluorogenic chelators can form ternary complexes with Eu.sup.3+ and Tb.sup.3+, in the presence of EDTA. The structures of the identified chelators is such that enzyme substrates can be used for enzyme-labelled time-resolved fluorometric immunoassays.Type: GrantFiled: December 21, 1994Date of Patent: December 29, 1998Assignee: Nordion International, Inc.Inventor: Eleftherios P. Diamandis
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Patent number: 5851777Abstract: 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: GrantFiled: February 5, 1996Date of Patent: December 22, 1998Assignee: Dade Behring Inc.Inventors: Thomas J. Hunter, Ernest H. Pfadenhauer
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Patent number: 5851840Abstract: The invention concerns a binding matrix containing a carrier material with an oxidic surface and a solid phase reactant covalently bound thereto via anchor groups which is capable of binding to at least one free reaction partner, which is characterized in that the solid phase reactant forms a diluted and essentially laterally homogeneous binding layer on the surface of the carrier material and that the anchor groups are silane groups and are linked to the solid phase reactant via a spacer molecule.Type: GrantFiled: December 31, 1996Date of Patent: December 22, 1998Assignee: Boehringer Mannheim GmbHInventors: Peter Sluka, Hans-Georg Batz
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Patent number: 5847088Abstract: The present invention provides purified and isolated polynucleotide sequences encoding human plasma platelet-activating factor acetylhydrolase. Also provided are materials and methods for the recombinant production of platelet-activating factor acetylhydrolase products which are expected to be useful in regulating pathological inflammatory events.Type: GrantFiled: June 7, 1995Date of Patent: December 8, 1998Assignee: ICOS CorporationInventors: Lawrence S. Cousens, Christine D. Eberhardt, Patrick Gray, Hai Le Trong, Larry W. Tjoelker, Cheryl L. Wilder
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Patent number: 5811236Abstract: Electrochemiluminiscent moieties having the formula?Re(P).sub.m (L.sup.1).sub.n (L.sup.2).sub.o (L.sup.3).sub.p (L.sup.4).sub.q (L.sup.5).sub.r (L.sup.6).sub.s !.sub.t (B).sub.uwhereinP is a polydentate ligand of Re;L.sup.1, L.sup.2, L.sup.3, L.sup.4, L.sup.5 and L.sup.6 are ligands of Re, each of which may be the same as or different from each other ligand;B is a substance which is a ligand of Re or is conjugated to one or more of P, L.sup.1, L.sup.2, L.sup.3, L.sup.4, L.sup.5 or L.sup.6 ;m is an integer equal to or greater than 1;each of n, o, p, q, r and s is zero or an integer;t is an integer equal to or greater than 1; andu is an integer equal to or greater than 1;P, L.sup.1, L.sup.2, L.sup.3, L.sup.4, L.sup.5, L.sup.6 and B being of such composition and number that the chemical moiety can be induced to emit electromagnetic radiation and the total number of bonds to Re provided by the ligands of Re being equal to the coordination of Reare disclosed.Type: GrantFiled: June 6, 1995Date of Patent: September 22, 1998Assignee: IGEN International, Inc.Inventors: Richard J. Massey, Michael J. Powell, Walter J. Dressick, Jonathan K. Leland, Janel K. Hino, Mohindar S. Poonian, Leopoldo Della Ciana
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Patent number: 5795789Abstract: A stabilized liquid standard solution for use in calibrating assays of thyroid function containing albumin and known amounts of at least two analytes selected from a group consisting of total thyroxine, free thyroxine, total triiodothyronine, and free triiodothyronine, and optionally, thyroid stimulating hormone.Type: GrantFiled: June 4, 1997Date of Patent: August 18, 1998Assignee: Dade Behring Inc.Inventor: Dennis Jerome Dietzen
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Patent number: 5789219Abstract: The present invention provides crosslinking, conjugating and reducing agents which are functional with at least one phosphorothioate monoester group (--SPO.sub.3.sup.-2). Crosslinking and conjugation methods as well as solid phase reagents and conjugates which are useful in immunoassays are also provided.Crosslinking and conjugating agents of the invention generally comprise a compound corresponding to the formula (I), shown below, wherein n at least 1 and Q is a straight or branched monomer, polymer or oligomer having an average molecular weight between about 200 and about 1,000,000. Additionally, when n is 1, Q comprises at least 1 additional reactive functionality.Q--(S--PO.sub.3 .sup.-2)n (I)The reducing agents that are provided conform to a compound of the formula (Y), shown below, wherein (A) and (Z) can be independently selected from C.sub.1 -C.sub.5 alkyl and CONH(CH.sub.2)p wherein p is an integer between 1 and 5.Type: GrantFiled: May 29, 1996Date of Patent: August 4, 1998Assignee: Abbott LaboratoriesInventors: Christopher Bieniarz, Douglas F. Young, Michael J. Cornwell, Mazhar Husain, Zbigniew Skrzypczynski
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Patent number: 5786153Abstract: 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: GrantFiled: September 12, 1996Date of Patent: July 28, 1998Assignee: Chiron Diagnostics CorporationInventors: Wei-Chao Ni, Anna Marie Detert, James Joseph Hughes
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Patent number: 5776702Abstract: For the determination of an immunologically detectable substance based on a heterogeneous immunoassay by use of a solid phase on which one of the immunologically active reaction components is bound, a reaction vessel is used as the solid phase on the inner surface of which streptavidin or avidin is bound in such an amount that 0.1 to 2.5 .mu.g are present per ml reaction volume.A suitable reaction vessel for this has optically transparent wall areas which face one another and has avidin or streptavidin coated walls which are at least partially within the inner wall region intended as a receptacle for liquid, wherein the inner space of the container intended as a receptacle for liquid and the respective streptavidin or avidin content of the coating are so matched that 0.1 to 2.5 .mu.g streptavidin or avidin are present per ml reaction volume.Type: GrantFiled: July 7, 1994Date of Patent: July 7, 1998Assignee: Boehringer Mannheim GmbHInventors: Urban Schmitt, Eberhard Maurer, Wolfgang Rudinger, Rolf Deeg
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Patent number: 5773259Abstract: The invention relates to a method of diagnosing artherosclerosis by detecting mutation or altered expression of HC gp-39.Type: GrantFiled: March 10, 1997Date of Patent: June 30, 1998Assignee: SmithKline Beecham CorporationInventor: Robert B. Kirkpatrick
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Patent number: 5763164Abstract: The present invention relates to tumor specific antigens and functional proteins of a tumor cell preparable by identifying protein presents in the tumor cell that are selectively immunogenic for tumor patients. The present invention still further provides a process of making a peptide library of tumor specific humoral antigens, a process of increasing the immunogenic specificity of a tumor-associated antigen, an assay kit for detecting the presence of an antibody immunoreactive with a tumor-specific antigen, and a process of making T cells sensitized to a tumor-specific antigen.Type: GrantFiled: February 3, 1994Date of Patent: June 9, 1998Assignee: Northwestern UniversityInventor: Emanuel Calenoff
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Patent number: 5753441Abstract: The present invention relates generally to the field of human genetics. Specifically, the present invention relates to methods and materials used to isolate and detect a human breast and ovarian cancer predisposing gene (BRCA1), some mutant alleles of which cause susceptibility to cancer, in particular breast and ovarian cancer. More specifically, the invention relates to germline mutations in the BRCA1 gene and their use in the diagnosis of predisposition to breast and ovarian cancer. The present invention further relates to somatic mutations in the BRCA1 gene in human breast and ovarian cancer and their use in the diagnosis and prognosis of human breast and ovarian cancer. Additionally, the invention relates to somatic mutations in the BRCA1 gene in other human cancers and their use in the diagnosis and prognosis of human cancers. The invention also relates to the therapy of human cancers which have a mutation in the BRCA1 gene, including gene therapy, protein replacement therapy and protein mimetics.Type: GrantFiled: January 5, 1996Date of Patent: May 19, 1998Assignees: Myriad Genetics, Inc., University of Utah Research Foundation, The United States of America as represented by the Department of Health and Human ServicesInventors: Mark H. Skolnick, David E. Goldgar, Yoshio Miki, Jeff Swenson, Alexander Kamb, Keith D. Harshman, Donna M. Shattuck-Eidens, Sean V. Tavtigian, Roger W. Wiseman, P. Andrew Futreal
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Patent number: 5747260Abstract: A method of prognosing a head-injured subject or a subject who may be at risk of sustaining a head injury for the likelihood that a head injury might give rise to a chronic neurodegenerative pathology which could result in neuropsychological, psychiatric or neurological deficits, the method comprising detecting the presence or absence of ApoE isoforms or of DNA encoding ApoE isoforms in the subject.Type: GrantFiled: February 25, 1997Date of Patent: May 5, 1998Assignee: SmithKline Beecham p.l.c.Inventors: Gareth Wyn Roberts, David Ian Graham, James Alan Ramsey Nicoll
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Patent number: 5736624Abstract: The present invention provides crosslinking, conjugating and reducing agents which are functional with at least one phosphorothioate monoester group (--SPO.sub.3.sup.-2). Crosslinking and conjugation methods as well as solid phase reagents and conjugates which are useful in immunoassays are also provided. Crosslinking and conjugating agents of the invention generally comprise a compound corresponding to the formula (I), shown below, wherein n is at least 1 and Q is a straight or branched monomer, polymer or oligomer having an average molecular weight between about 200 and about 1,000,000. Additionally, when n is 1, Q comprises at least 1 additional reactive functionality.Q--(S--PO.sub.3.sup.-2)n (I)The reducing agents that are provided conform to a compound of the formula (Y), shown below, wherein (A) and (Z) can be independently selected from C.sub.1 -C.sub.5 alkyl and CONH(CH.sub.2).sub.p wherein p is an integer between 1 and 5.Type: GrantFiled: December 2, 1994Date of Patent: April 7, 1998Assignee: Abbott LaboratoriesInventors: Christopher Bieniarz, Douglas F. Young, Michael J. Cornwell, Mazhar Husain
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Patent number: 5731152Abstract: An apparatus for placing at least one biological reagent at a plurality of locations on a substrate includes a stamp member onto which the at least one biological reagent is applied. The stamp member defines a plurality of transfer elements patterned to correspond to the plurality of locations. The stamp member contacts the substrate to transfer the at least one biological reagent from the plurality of transfer elements to the plurality of locations. The transfer elements can be defined by reservoirs or projected portions of the stamp member. A method of using said apparatus is also disclosed.Type: GrantFiled: May 13, 1996Date of Patent: March 24, 1998Assignee: Motorola, Inc.Inventors: George N. Maracas, Donald E. Ackley, William L. Reber, Thomas B. Harvey, III
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Patent number: 5714336Abstract: A method for determining the concentration of the free fraction of an active compound, present in a biological fluid, in the presence of natural binders, the free and bound fractions of the active compound being in mutual equilibrium, bya) contacting a sample of the fluid with an unlabeled antibody,b) separating the sample from the unlabeled antibody,c) incubating the unlabeled antibody with a labeled substance (tracer) for cross-reaction with the antibody andd) measuring the amount of the tracer which is or is not bound to the antibody and calculating from this the concentration of the free fraction of the active compound,wherein the quantity of the unlabeled antibody and/or its affinity for the active compound are so small that they do not substantially effect the equilibrium between the free and bound fractions of the active compound, and the affinity of the tracer for the antibody is substantially higher or substantially lower than that of the active compound itself, and a test kit suitable for this methoType: GrantFiled: May 18, 1992Date of Patent: February 3, 1998Assignee: Hoechst AktiengesellschaftInventors: Guido Simons, Helmut Strecker, deceased, Peter Molz, Gerd Schnorr, Heinz Jurgen Skrzipczyk, Hans Wissmann
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Patent number: 5670380Abstract: Disclosed is an assay for fetal thyroid function involving determining the amount of fetal thyroid function indicator that is present in the maternal blood and maternal urine and then comparing the determined value to a known standard for the gestation age of the fetus. It is defined as below one standard deviation of the normal values. Also disclosed is a method of treating a fetus having hypothyroidism involving determining that the fetus is hypothyroid using the assay of the present invention and thereafter, administering supplemental thyroid hormone (T.sub.4, 500 ug/wk) into the amniotic sac. Also disclosed is a method of identifying euthyroid state using the assay of the present invention in hypothyroid fetuses receiving T.sub.4 therapy.Type: GrantFiled: July 8, 1994Date of Patent: September 23, 1997Inventor: Sing-Yung Wu
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Patent number: 5648272Abstract: Immunoassay methods and reagents for the specific quantification of thyroxine in a test sample are disclosed employing antibodies prepared with thyroxine derivatives of the formula: ##STR1## wherein P is an immunogenic carrier material and X is a linking moiety. The present invention also describes the synthesis of unique labelled reagent of the formula: ##STR2## wherein Q is a detectable moiety and W is a linking moiety, preferably fluorescein or a fluorescein derivative.Type: GrantFiled: May 18, 1995Date of Patent: July 15, 1997Assignee: Abbott LaboratoriesInventors: Maciej Adamczyk, Donald D. Johnson, Phillip G. Mattingly, Diana E. Clarisse, Joan D. Tyner, Mary M. Perkowitz
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Patent number: 5614367Abstract: Chimeric monoclonal antibodies or fragments thereof are used according to the present invention in diagnostic tests for the quantitative immunological determination of substances in the blood or serum of patients. For the diagnostic detection of substances in serum or blood of patients by binding of two monoclonal antibodies R.sub.1 and R.sub.2 directed against the substance, of which the first antibody R.sub.1 is capable of binding to a solid phase or is already bound and the second antibody R.sub.2 carries a label, binding of the antibody R.sub.1 to the solid phase if desired, separation of the complex formed of R.sub.1, substance and R.sub.2 which is bound to the solid phase and detection via the labelling of the antibody R.sub.2, a chimeric monoclonal antibody or a fragment thereof is used at least for one of the antibodies R.sub.1 or R.sub.2.Type: GrantFiled: November 17, 1993Date of Patent: March 25, 1997Assignee: Boehringer Mannheim GmbHInventors: Brigitte Kaluza, Helmut Lenz
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Patent number: 5601822Abstract: The present invention provides purified polypeptides which comprise at least a portion of a .delta. T cell receptor polypeptide, a .gamma. T cell receptor polypeptide, a .gamma., .delta. T cell receptor complex or a .gamma., .gamma. T cell receptor complex. Substances capable of forming complexes with these polypeptides are also provided.Additionally, methods for detecting T cells which have within them or on their surfaces a polypeptide of the present invention are provided. Moreover, methods for diagnosing immune system abnormalities are provided which comprise measuring in a sample from a subject the number of T cells which have within them or on their surfaces a polypeptide of the present invention.Type: GrantFiled: November 19, 1993Date of Patent: February 11, 1997Assignees: T Cell Sciences, Inc., President and Fellows of Harvard College, Dana Farber Cancer InstituteInventors: Michael B. Brenner, Jack L. Strominger, Johnathan Seidman, Stephen H. Ip, Michael S. Krangel
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Patent number: 5593896Abstract: Immunoassay methods and reagents for the specific quantification of thyroxine in a test sample are disclosed employing antibodies prepared with thyroxine derivatives of the formula: ##STR1## wherein P is an immunogenic carrier material and X is a linking moiety. The present invention also describes the synthesis of unique labelled reagent of the formula: ##STR2## wherein Q is a detectable moiety and W is a linking moiety, preferably fluorescein or a fluorescein derivative.Type: GrantFiled: July 13, 1994Date of Patent: January 14, 1997Assignee: Abbott LaboratoriesInventors: Maciej Adamczyk, Donald D. Johnson, Phillip G. Mattingly, Diana E. Clarisse, Joan D. Tyner, Mary M. Perkowitz
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Patent number: 5578445Abstract: An in vitro method of evaluating the antagonistic versus agonistic effects of a receptor-binding test substance on a selected type of cells containing endogenous intra-cellular hormone receptors, is disclosed. Said test substance, and separately a reference substance, known to be either an antagonist or an agonist, are incubated with said selected type of cells, and the magnitude of the selected cellular response resulting from hormone/receptor interaction, is analyzed. In case the method is performed on at least two selected types of cells which derive from different kinds of tissues, it is possible to evaluate the pattern of antagonistic versus agonistic effects of the selected test substance on said kinds of tissues.Type: GrantFiled: April 6, 1994Date of Patent: November 26, 1996Assignee: Karo Bio AktiebolagInventors: Stefan Nilsson, M.ang.rten Osterlund, Karin Heeroma
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Patent number: 5576219Abstract: The present invention provides a process for the determination of the thyroxine-binding capacity in serum, wherein, for the calibration, there are used at least two different standard solutions which contain substantially the same amount of thyroxine-binding globulin but a differing content of thyroxine.The present invention also provides a standard solution for the determination of the thyroxine-binding capacity containing thyroxine-binding globulin dissolved in a buffer system.Type: GrantFiled: February 2, 1994Date of Patent: November 19, 1996Assignee: Boehringer Mannheim GmbHInventors: Gerhard Bienhaus, Helmut Jering
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Patent number: 5538901Abstract: This invention is directed to the novel assay methods utilizing nucleophilic polysubstituted aryl acridinium ester conjugates as the tracers. Conjugates prepared by covalent coupling of novel nucleophilic polysubstituted aryl acridinium esters with biological compounds including small organic molecules such as Vitamin B12, folate, cortisol, estradiol, and thromboxane B2, were found useful in the development of highly sensitive assays for the analytes of diagnostic interest.Type: GrantFiled: August 18, 1994Date of Patent: July 23, 1996Assignee: Ciba Corning Diagnostics Corp.Inventors: Say-Jong Law, Steve C. S. Chang, Carol K. Klukas, Christine A. Vitkauskas
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Patent number: 5527709Abstract: The invention is directed to an immunoassay for a thyronine derivative comprising:A. contacting a liquid sample, containing a thyronine derivative, with a labeled thyronine hapten analogue of the derivative in the presence of antibodies for the thyronine derivative under conditions that promote the formation of antibody-thyronine immunocomplexes; andB. determining the bound or unbound quantity of the thyronine derivative in the liquid; characterized in that the labeled thyronine derivative comprises:(i) a label, of the type used in immunoassays, having an amine or sulfhydyl group;(ii) a thyronine nucleus and(iii) a linking chain linking the label to the thyronine nucleus.Type: GrantFiled: March 23, 1995Date of Patent: June 18, 1996Assignee: Johnson & Johnson Clinical Diagnostics, Inc.Inventors: Susan J. Danielson, Barbara A. Brummond, Patricia N. Tyminski, Ignazio S. Ponticello
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Patent number: 5476770Abstract: The invention relates to a process for the immunometric determination of an antigen or hapten.According to this process, contacting takes place (FIG. 1A) between the antigen or hapten (3) to be determined and the antibodies (2) fixed to a solid phase in order to immunologically bond the antigen or hapten with the antibody. This is followed (FIG. 1B) by immobilizing the antigen or hapten (3) by a covalent bond (4) to the solid phase (1) whilst releasing its epitope (FIG. 1C). This is followed by the contacting thereof (FIG. 1D) with labelled antibodies (5) and determination takes place (FIG. 1E) of the quantity of fixed labelled antibodies in order to deduce therefrom the initial hapten or antigen concentration.As a result of this stage of immobilizing and releasing the epitope, a high sensitivity is obtained using a single antibody.Type: GrantFiled: January 24, 1994Date of Patent: December 19, 1995Assignee: Commissariat A L'Energie AtomiqueInventor: Philippe Pradelles
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Patent number: 5464749Abstract: A method of determining free analyte level in a sample containing the analyte in free and bound portions is accomplished in sequential steps as follows. The sample is combined with a known first liquid volume containing soluble anti-analyte receptor in excess of the free analyte in the sample. The resultant mixture is incubated for a period of time sufficient to allow the binding reaction of the free analyte with the anti-analyte receptor to reach substantial completion to form a first incubation mixture. A known second liquid volume is added thereafter which contains soluble conjugate sufficient to reduce the sample proportion in the resultant mixture to no greater than 10% v/v, with the conjugate comprising a labeled analyte or labeled analog thereof, to allow the conjugate to bind with the anti-analyte receptor not bound in the first incubation mixture to form a second incubation mixture.Type: GrantFiled: July 22, 1991Date of Patent: November 7, 1995Assignee: Bayer CorporationInventors: Moshe Schwarzberg, Santosh Dayal
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Patent number: 5460975Abstract: The present invention concerns compounds having the general formula I ##STR1## in which R.sup.1 denotes hydrogen or hydroxy,R.sup.2 denotes hydrogen or hydroxy,R.sup.3 denotes hydrogen or alkoxy,R.sup.4 denotes hydrogen, CO.sub.2 H, SO.sub.3 H, PO.sub.3 H.sub.2 or a salt of the corresponding acid,R.sup.5 denotes CO.sub.2 H, SO.sub.3 H, PO.sub.3 H.sub.2 or a salt of the corresponding acid andR.sup.6 denotes alkoxy,their use for displacing iodothyronines from proteins binding them, as well as a method and reagent for the determination of iodothyronine in which such compounds are used.Type: GrantFiled: July 7, 1993Date of Patent: October 24, 1995Assignee: Boehringer Mannheim GmbHInventors: Helmut Freitag, Wolfgang-Reinhold Knappe, Heino Eikmeier, Wolfgang Weckerle
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Patent number: 5453356Abstract: 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 very small amounts of the chemical moiety using chemiluminescent, electrochemiluminescent, and photoluminescent means. Compounds are disclosed which are useful for labelling substances of interest with ruthenium-containing and osmium-containing labels or other electrochemiluminescent labels. These labelled substances are useful in methods provided for detecting and quantifying analytes of interest in binding assays and competitive binding assays. The labelled substances are of particular use in homogeneous binding assays.Type: GrantFiled: November 30, 1993Date of Patent: September 26, 1995Assignee: Igen, Inc.Inventors: Allen J. Bard, George M. Whitesides
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Patent number: 5449624Abstract: A method of assaying analytes using a rate procedure is described where the change in density over time has a variable rate. The method features the steps of depositing the sample onto a dried slide-like test element, making an initial rate reading during an early time window, using the initial rate readings in a comparison study with rates from known low and high concentration results to predict whether the sample rate will be sufficiently low as to be ascertainable during a later time window or not, and then calculating a rate of reaction and concentration during either the early time window or the early time window with a portion of the later time window, respectively.Type: GrantFiled: February 28, 1994Date of Patent: September 12, 1995Assignee: Eastman Kodak CompanyInventors: Paul A. Kildal-Brandt, Thomas A. Weber
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Patent number: 5439825Abstract: Disclosed herein are buffers and methodologies for the capillary zone electrophoretic analysis of hemoglobin and the variants of hemoglobin. In a particularly preferred embodiment, the buffer comprises at least about 100 mM of barbituric acid, derivatives of barbituric acid, combinations of barbituric acid and derivatives of barbituric acid, and combinations of the derivatives of barbituric acid, and has a pH of at least about 8.0.Type: GrantFiled: December 10, 1992Date of Patent: August 8, 1995Assignee: Beckman Instruments, Inc.Inventor: Fu-Tai A. Chen
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Patent number: 5434052Abstract: Compounds are evaluated for their binding to naturally occurring receptors, by employing the natural ligand conjugated to an enzyme donor fragment of .beta.-galactosidase for competing with the sample compound for the natural acceptor binding site or in the absence of competition where the sample compound binds to an allosteric site. By adding the enzyme acceptor fragment of the .beta.-galactosidase and substrate, the binding affinity of the sample compound may be evaluated as a measure of agonist or antagonist capability.Type: GrantFiled: July 21, 1993Date of Patent: July 18, 1995Assignee: Microgenics CorporationInventor: Pyare Khanna
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Patent number: 5399500Abstract: A process for coating an antibody on a substrate includes two steps. A secondary antibody to a primary antibody is coated on the substrate followed by a coating with primary antibody in the presence of blocking and stabilizer agents.Type: GrantFiled: June 26, 1992Date of Patent: March 21, 1995Assignee: Becton Dickinson and CompanyInventors: Leslie Oppenheimer, Lewis R. Pollack
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Patent number: 5382530Abstract: Disclosed is a method for the direct determination of the free fraction of analytes present in biological fluids in a free form and in a form bound to one or more endogenous ligands (said free and bound forms being in equilibrium with one another). This method provides for a (preferably substantially simultaneous) use:a first ligand L1 capable of sequestering an analyte quantity proportionate to the free-analyte concentration present in a biological fluid and to subsequently release it, after removal from the biological fluid of the specific endogenous ligand, as a result of the addition of an appropriate selective dissociating agent; a second ligand capable of binding both the previously released analyte and a labelled version of the analyte, even in the presence of the dissociating agent; a selective dissociating agent; and a quantity of labelled analyte.Type: GrantFiled: December 30, 1992Date of Patent: January 17, 1995Assignee: Technogenetics S.r.l.Inventors: Pier B. Romelli, Giovanni Chiodoni, Roberto Ringhini