Producing Labeled Antigens Patents (Class 436/544)
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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: 5532171Abstract: There is disclosed a novel phenothiazine derivative of the general formula (I): ##STR1## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are the same or different and are a C.sub.1-6 alkyl group and at least one of them has as a substituent a group which can react with amino group, thiol group or carboxyl group, and X.sup.- is a counter ion of the phenazathionium. Their production and the intermediates used in the production are also disclosed. The compound (I) is a derivative of methylene blue and is applicable to photodynamic therapy of cancer or immunoassays utilizing chemiluminescence.Type: GrantFiled: May 23, 1994Date of Patent: July 2, 1996Assignee: Takeda Chemical Industries, Ltd.Inventor: Marvin A. Motsenbocker
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Patent number: 5527901Abstract: 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: GrantFiled: December 22, 1993Date of Patent: June 18, 1996Assignee: Alberta Research CouncilInventors: Robert M. Ratcliffe, Andre P. Venot, S. Zaheer Abbas
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Patent number: 5527710Abstract: The rate of a biomolecular reaction, such as an enzymatic reaction or an affinity binding reaction, is measured using electrochemiluminescence ("ECL"). The reaction is conducted in an electrochemical cell with a mixture of reagents including a luminophore which will relate the concentration of a reactant, a reaction partner or the reaction product of a reaction partner to the ECL intensity. The reaction partner is a reagent which reacts with the reactant and which participates with the luminophore (or its reaction product participates with the luminophore) to cause the emission of ECL. The ECL intensity is modulated with a series of electrical pulses which are applied to the mixture of reagents at a preselected potential and for preselected intervals of time and duration. The ECL intensity is measured at the same intervals to provide a timed series of values (P).Type: GrantFiled: December 2, 1994Date of Patent: June 18, 1996Assignee: IGEN, Inc.Inventors: Laurette Nacamulli, Jonathan K. Leland, Stephanie A. Hayes
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Patent number: 5521103Abstract: New acridinium compounds are provided which comply with formula 1, whereinA is a divalent organic moiety, such as an alkylene chain,X is a group which can be transformed together with C-9 of the acridine into a dioxetane by reaction with hydrogen peroxide, such as an aryloxy group,Y is a counter ion, andZ is a functional group, such as a carboxyl derivative.These acridinium compounds are useful as chemiluminogenic labels for both heterogeneous and homogeneous immunoassays.Type: GrantFiled: June 24, 1991Date of Patent: May 28, 1996Assignee: Mochida Pharmaceutical Co., Ltd.Inventors: Gijsbert Zomer, Johannus F. C. Stavenuiter
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Patent number: 5496554Abstract: New purified mite allergens useful as pharmaceutical and diagnostic compositions for the treatment and diagnosis of mite allergic diseases are provided. Both allergens are contained in fecal extracts of mites in culture. The high molecular weight allergen has a weight average molecular weight of 70,000 to 80,000 as determined by sedimentation equilibrium. This is a glycoprotein containing more than about 70% sugar, and possesses allergen activity. The low molecular weight antigen has a molecular weight of 1,500 to 5,000 as determined by Sephadex G25 gel filtration. This is a glycoprotein containing more than about 40% sugar, and also possesses allergen activity.Type: GrantFiled: August 4, 1994Date of Patent: March 5, 1996Assignees: Fumakilla Limited, Hiroshima UniversityInventors: Satoru Oka, Kazuhisa Ono, Seiko Shigeta, Takeshi Wada
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Patent number: 5487977Abstract: The method for detecting the sulfidoleukotrienes sLT of the group LTC4, LTD4 and LTE4 by a single immunoenzymatic ELISA assay is based on the interaction between one or several monoclonal anti-sLT antibodies and a sLT conjugated to a revealing enzyme. A biological sample, wherein a content of sLT is assumed, is contacted with a monoclonal anti-sLT antibody bound to a carrier. After the sLTs present in the sample are bound to the said antibody, a conjugate of a sLT with a revealing enzyme is added to the charged carrier. Finally the amount of the conjugate bound to the carrier is evaluated, which amount is in an inverse correlation with the sLT bound to the carrier. The method is useful for in vitro-tests for the diagnosis of inflammatory diseases, as rheumatic diseases, immuno deficiencies, allergies or pseudo-allergies. With a priming of the biological samples with cytokines, e.g. with IL3, IL5 or GM-CSF as priming agents, the sensitivity of the method can be increased.Type: GrantFiled: June 1, 1993Date of Patent: January 30, 1996Inventor: Alain L. de Weck
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Patent number: 5470997Abstract: The present invention is directed to novel amphetamine derivatives which are synthesized for the covalent attachment to antigens (proteins or polypeptides) for the preparation of antibodies or receptors to amphetamine and amphetamine metabolites. The resulting novel antigens may be used for the production of antibodies or receptors using standard methods. Once generated, the antibodies or receptors and the novel derivatives which are covalently attached to proteins, polypeptides or labels may be used in the immunoassay process.Type: GrantFiled: April 6, 1992Date of Patent: November 28, 1995Assignee: Biosite Diagnostics IncorporatedInventors: Kenneth F. Buechler, Joseph B. Noar, Si S. Moi
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Patent number: 5468646Abstract: 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: GrantFiled: January 3, 1995Date of Patent: November 21, 1995Assignee: Abbott LaboratoriesInventors: Phillip G. Mattingly, Larry G. Bennett
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Patent number: 5464748Abstract: Immunoassay techniques for quantitating the amount of 3'-amido-3'-deoxythymidine (AMT) in body fluid samples, and antibodies useful in performing such immunoassays, are provided. The immunoassays use antibodies which are specific to AMT and have no cross-reactivity with 3'-azido-3'-deoxythymidine (AZT). Moreover, there is provided an improved method of conducting AZT therapy wherein the concentration of both AZT and AMT is monitored and the AZT dosage is adjusted to maintain rather low concentrations of AMT.Type: GrantFiled: September 7, 1993Date of Patent: November 7, 1995Assignee: The UAB Research FoundationInventor: Jean-Pierre Sommadossi
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Patent number: 5459080Abstract: The present invention includes novel assays employing a capture reagent, involving a first specific binding member conjugated to a polymeric anion such as carboxymethylamylose, and a solid phase material containing a reaction site comprising a polymeric cation substance. A test sample suspected of containing the analyte of interest may be contacted with the capture reagent to form a charged capture reagent/analyte complex. The complex is then contacted to/ the oppositely charged solid phase to attract, attach, and immobilize the capture reagent/analyte complex. The use of carboxymethylamylose to prepare a suitably charged capture reagent provides a superior capture reagent that is capable of binding and retaining the analyte on the solid phase even in the presence of polyanionic non-specific binding blockers.Type: GrantFiled: January 27, 1994Date of Patent: October 17, 1995Assignee: Abbott LaboratoriesInventors: Janina Adamczyk, Daniel S. Berry, Yi-Her Jou, Stephen D. Stroupe
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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: 5445972Abstract: A Raman label which, upon radiation, produces a detectable Raman scattering signal in a ligand-binding assay for an analyte in a test sample. A conjugate containing a Raman label attached to a specific binding member.Type: GrantFiled: July 22, 1993Date of Patent: August 29, 1995Assignee: Abbott LaboratoriesInventors: Peter J. Tarcha, Thomas E. Rohr, Therese Cotton, Gary E. Winter
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Patent number: 5441867Abstract: Pre-activated stable protein reagents are provided. The reagents can be made by reaction of the protein and a heterobifunctional linker and have extended stability especially after lyophilisation. The reagents can be used in assay kits to form conjugates with proteins e.g. antibodies or polynucleotides e.g. oligonucleotides probes.Type: GrantFiled: January 7, 1992Date of Patent: August 15, 1995Assignee: Zeneca LimitedInventors: Andrew J. Garman, John R. Parker
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Patent number: 5439798Abstract: Novel derivatives of procainamide and N-acetylprocainamide (NAPA) are disclosed having the following formula: ##STR1## wherein: X=hydrogen or acetyl;R.sub.1 =an alkyl group having 1 to 3 carbon atoms;m=an integer from 2 to 10;R.sub.2 =an alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms;Z=a poly(amino acid); andn=1 to p where p=MW of Z/1000.The derivatives include maleimide conjugates of proteins or poly(amino acids), enzymes, enzyme donor polypeptides and labeling substances. Novel activated hapten intermediates useful in the preparation of the conjugates and methods for synthesis of the hapten intermediates and derivatives are also disclosed.Type: GrantFiled: December 17, 1993Date of Patent: August 8, 1995Assignee: Boehringer Mannheim CorporationInventors: Gerald F. Sigler, Charles F. Walter, Charles E. Durant, Todd Glancy, Frank E. Klein, Allan R. Dorn
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Patent number: 5434050Abstract: The present invention provides: a labelled .beta.-amyloid peptide of active fragment; a composition including the labelled .beta.-amyloid peptide or active fragment thereof and a pharmaceutical carrier; a method for labelling the .beta.-amyloid peptide or an active fragment thereof, and methods of using the labelled peptide or peptide fragment for detecting or monitoring Alzheimer's disease in a patient.Type: GrantFiled: August 13, 1991Date of Patent: July 18, 1995Assignees: Regents of the University of Minnesota, President & Fellows of Harvard CollegeInventors: John E. Maggio, Patrick W. Mantyh
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Patent number: 5407835Abstract: Immunoassay methods and reagents for the specific quantification of amitriptyline or nortriptyline in a test sample are disclosed employing antibodies prepared with amitriptyline or nortriptyline derivatives of the Formula III: ##STR1## wherein for amitriptyline, R is CH.sub.3, and for nortriptyline, R is H. The present invention also describes the synthesis of unique fluorescein tracers of the structure of Formula IV and Formula V: ##STR2## wherein for a specific amitriptyline immunoassay, W.sub.1 is a heteroatom linked to the aromatic ring at the 2 or 3 position, and for a specific nortriptyline immunoassay, W.sub.2 is two heteroatoms linked together and attached to the aromatic ring at the 2 or 3 position, and wherein Q is a detectable moiety, preferably fluorescein or a fluorescein derivative.Type: GrantFiled: July 24, 1992Date of Patent: April 18, 1995Assignee: Abbott LaboratoriesInventors: Maciej Adamczyk, Jeffrey R. Fishpaugh, Donald Johnson, Daryl E. Hartter
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Patent number: 5399672Abstract: The invention relates to a novel process for preparing immunoconjugates consisting of haptens which are sparingly soluble or insoluble in aqueous solution and proteins/polypeptides using special solvents, in particular diethylene glycol monoalkyl ethers.Type: GrantFiled: November 23, 1993Date of Patent: March 21, 1995Assignee: Merck Patent Gesellschaft mit beschrankter HaftungInventors: Mohammad Jalalian, Arnulf Heubner, Bernd Reckmann
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Patent number: 5384265Abstract: Catalytic colloidal metal particles bound to a biomolecule such as an antibody, avidin, or streptavidin are useful for detecting the presence of the biomolecule in an assay such as an immunoassay.Type: GrantFiled: March 26, 1993Date of Patent: January 24, 1995Assignees: Geo-Centers, Inc., The United States of America as represented by the Secretary of the NavyInventors: David A. Kidwell, Susan M. Conyers
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Patent number: 5384241Abstract: Disclosed is an assay system including a compound comprising an analyte-specific moiety having substituted thereon a polymer comprising plurality of self-quenching emitter moieties and a plurality of isocharged functionality separating the emitter moieties. The present invention provides compounds that overcome the undesirable effects of self-quenching when multiple emitter moieties are used for labelling of assay reagents. Avoidance of this self-quenching phenomenon by the compounds of the invention makes it possible to introduce a more concentrated degree of labelling on to analyte-specific molecules such as oligo nucleotide probes, antibodies and other specific binding proteins and analyte-specific polysaccharides. Therefor, it is possible to effect greater assay sensitivity because the number of labels per recognition molecule(analyte-specific moiety) can be increased beyond the point previously possible without the reduction in signal caused by self-quenching.Type: GrantFiled: November 29, 1989Date of Patent: January 24, 1995Assignee: Enzo Diagnostics, Inc.Inventor: Stanley Kline
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Patent number: 5358851Abstract: The present invention provides methods, reagents and kits for determining the presence of aromatic ring-containing compounds by immunoassay techniques, including enzyme, fluorescent, chemiluminescent and biosensor immunoassay, as well as radioimmunoassay. Monoclonal and polyclonal antibodies may be used in the practice of the present invention.Type: GrantFiled: June 6, 1991Date of Patent: October 25, 1994Assignee: Quantix Systems, L.P.Inventor: Dana P. Peck
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Patent number: 5354554Abstract: Cross-linked labelled antibody conjugates are described which have at least one non-disulphide interchain bridge. The bridge may be the residue of a homo- or heterofunctional cross-linking reagent, and is located away from the antigen binding domains of the antibody. The antibody conjugates have an enhanced binding capacity and in vivo have good blood clearance and, in the presence of a tumour high tumour: blood and tumour: bone ratios. The conjugates are of use in the diagnosis and therapy of e.g. tumours and may be prepared by reaction of a cross-linking reagent with an antibody.Type: GrantFiled: January 22, 1992Date of Patent: October 11, 1994Assignee: Celltech LimitedInventor: Stephen K. Rhind
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Patent number: 5350574Abstract: This invention provides a molecule comprising cyclosporine A or a congener of cyclosporine A which is photochemically attached to a ligand containing a reactive group. This invention also provides a composition of matter which comprises a conjugate of a compound and the aforementioned molecule wherein the compound is bound to the molecule through the reactive group. This invention further provides an antibody directed to the aforementioned composition of matter specific for cyclosporine A or congener of cyclosporine A. This invention also provides methods for detecting the presence of cyclosporine A or congener thereof, methods for detecting the concentration of cyclosporine A or congener thereof, as well as a method of monitoring levels of cyclosporine A or congener of cyclosporine A in a subject.Type: GrantFiled: May 13, 1991Date of Patent: September 27, 1994Assignee: The Trustees of Columbia University in the City of New YorkInventors: Bernard F. Erlanger, William L. Cleveland, Nicholas A. Cacalano
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Patent number: 5346832Abstract: A method is described for measuring the amount of analyte present in a sample containing the analyte using a homogeneous amperometric immunoassay. The analyte is chemically bonded to a suitable carrier molecule, which is also chemically bonded to an electroactive molecule. The electroactive molecule, such as ferrocene carboxylic acid, contains a redox center which is capable of transferring a charge to an electrode. A preferred carrier molecule is bovine serum albumin (BSA), while suitable analytes include digoxin, theophylline and HCG. The immunoassay is conveniently performed by applying a voltage to a set of electrodes.Type: GrantFiled: December 18, 1992Date of Patent: September 13, 1994Assignee: Ciba Corning Diagnostics Corp.Inventors: Masuo Aizawa, Brenda D. Manning, Miki Hidaka, Laura S. Uretsky
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Patent number: 5342760Abstract: The present invention relates to the measurement of estradiol using competitive immunoassay methods. The inventors unexpectedly discovered that estrone and its derivatives conjugated to a label is a particularly effective tracer when used in conjunction with estradiol specific antibodies to determine estradiol levels in fluid samples. The present invention also utilizes 5.alpha.-dihydrotestosterone to enhance the assay performance.Type: GrantFiled: June 10, 1992Date of Patent: August 30, 1994Assignee: Abbott LaboratoriesInventors: Harold N. Baker, Katherine K. Eng, William D. Gurner, Michael K. Massei, Necklaws: Elizabeth C., Eugene W. Osikowicz, Sally K. Ramp, Paula Trach
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Patent number: 5340750Abstract: 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: GrantFiled: July 24, 1992Date of Patent: August 23, 1994Assignee: Abbott LaboratoriesInventors: Maciej Adamczyk, Charles A. Harrington, Donald Johnson
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Patent number: 5334504Abstract: An in vitro method of detecting a cell-mediated immune response to a specific antigen, comprising incubating a whole blood sample with the specific antigen and detecting the presence of gamma interferon released by sensitized lymphocytes in the whole blood sample as an indication of a cell-mediated immune response to the specific antigen.Type: GrantFiled: September 22, 1993Date of Patent: August 2, 1994Assignee: Commonwealth Scientific & Industrial Research OrganisationInventors: Paul R. Wood, Leigh A. Corner
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Patent number: 5332661Abstract: Immunoassay methods and reagents for the quantification of total doxepins (i.e., E-doxepin, Z-doxepin, E-desmethyldoxepin, and Z-desmethyldoxepin) in a test sample are disclosed. The quantification of total doxepins is accomplished in an immunoassay employing antibodies and labeled reagents prepared with doxepin derivatives of the Formula II: ##STR1## wherein Y--Z can be C.dbd.CH or N--CH.sub.2, R.sub.` is a linking group, R.sub.2 can be H or CH.sub.3, and Q can be a detectable moiety or an immunogenic carrier material. The antibody reagent comprises antibodies which are capable of binding to total doxepins and which are produced with one or more immunogens prepared from the doxepin derivative of Formula II, and the labeled reagent is also prepared from the doxepin derivative of Formula II.Type: GrantFiled: July 24, 1992Date of Patent: July 26, 1994Assignee: Abbott LaboratoriesInventors: Maciej Adamczyk, Jeffrey R. Fishpaugh, Donald Johnson, Robert E. Hruska
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Phencyclidine derivatives and protein and polypeptide phencyclidine derivative conjugates and labels
Patent number: 5331109Abstract: The present invention is directed to novel PCP derivatives which are synthesized for the covalent attachment to antigens or receptors (proteins or polypeptides) for the preparation of antibodies or receptors to PCP and PCP analogue metabolites. The resulting novel antigens may be used for the production of antibodies or receptors using standard methods. Once generated, the antibodies and the novel derivatives which are covalently attached to proteins, polypeptides or labels may be used in the immunoassay process.Type: GrantFiled: April 6, 1992Date of Patent: July 19, 1994Assignee: Biosite Diagnostics IncorporatedInventor: Kenneth F. Buechler -
Patent number: 5310687Abstract: 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: GrantFiled: November 4, 1991Date of Patent: May 10, 1994Assignee: Igen, Inc.Inventors: Allen J. Bard, George M. Whitesides
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Patent number: 5306622Abstract: The invention teaches a method for determining an analyte in a liquid sample via a heterogeneous assay. The sample is contacted to a carrier material which contains, in addition to one of a labelled analyte analogous substance or a labelled analyte specific substance, a detectable component which does not influence immunological reactions occurring during the course of the assay. A solid phase bound component, which is either an insufficient amount of analyte specific substance or an excess of analyte relative to analyte in the sample is contacted to the sample so as to accomplish formation of solid phase bound complexes. After separation of liquid and solid phase, label is measured in one of these, and the detectable substance is measured in the liquid. Correlation of the values obtained leads to determination of the analyte. Also described is a reagent used in the described method.Type: GrantFiled: November 5, 1991Date of Patent: April 26, 1994Assignee: Boehringer Mannheim GmbHInventor: Dieter Mangold
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Patent number: 5302703Abstract: The present invention is directed to novel THC derivatives which are synthesized for the covalent attachment to antigens (proteins or polypeptides) for the preparation of antibodies or receptors to the THC metabolites. The resulting novel antigens may be used for the production of antibodies or receptors using standard methods. Once generated, the antibodies or receptors and the novel derivatives which are covalently attached to proteins, polypeptides or labels may be used in the immunoassay process.Type: GrantFiled: March 17, 1993Date of Patent: April 12, 1994Assignee: Biosite Diagnostics IncorporatedInventors: Kenneth F. Buechler, Si S. Moi
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Patent number: 5296594Abstract: The stereochemistry of sialylation of an acceptor saccharide to obtain an .alpha. (2-3) or .alpha. (2-6) linkage is controlled to favor the a 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: GrantFiled: June 28, 1990Date of Patent: March 22, 1994Assignee: Alberta Research CouncilInventors: Robert M. Ratcliffe, Andre P. Venot, S. Zaheer Abbas
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Patent number: 5284778Abstract: This invention provides a quantitative assay for determining the amount of a biologically active ligand selected from the group consisting of human chorionic gonadotropin and luetinizing hormone present in a sample comprising contacting the sample with both the receptor to which the ligand naturally binds in order to effect its biologicaly activity and a monoclonal antibody directed to the ligand or to a complex of the ligand and the receptor so as to form a complex of the ligand bound to both the receptor, at the site to which the ligand naturally binds to the receptor, and the monoclonal antibody. In the complex so formed, either the receptor or the monoclonal antibody is labeled with a detectable marker and a determination is made of the amount of labeled receptor or of labeled monoclonal antibody bound to the ligand or the amount of labeled receptor or of labeled monoclonal antibody not bound to the ligand, or both such amounts.Type: GrantFiled: September 12, 1991Date of Patent: February 8, 1994Assignees: The Trustees of Columbia University in the City of New York, The University of Medicine & Dentistry of New JerseyInventors: Robert E. Canfield, E. Glenn Armstrong, William R. Moyle, Gordon J. MacDonald, Donna M. Anderson
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Patent number: 5283342Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described.Type: GrantFiled: June 9, 1992Date of Patent: February 1, 1994Assignee: NeoRx CorporationInventors: Linda M. Gustavson, Ananthachari Srinivasan, Alan R. Fritzberg, John M. Reno, Donald B. Axworthy
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Patent number: 5272257Abstract: A method for preparing phycobiliprotein/amine-reactive dye conjugates is disclosed in which the conjugates so prepared overcome the energy transfer/fluorescent quenching dilemma encountered in the use of prior art conjugates. A phycobiliprotein, for example, phycoerythrin or allophycocyanin, is conjugated with an amine-reactive dye, for example, Texas Red or carboxyfluorescein succinimidyl ester, in the presence of a selective salt which causes a hydrophobic intramolecular rearrangement of the phycobiliprotein thereby exposing more hydrophobic sites for binding to the amine-reactive dye. The conjugates prepared according to the invention are useful in multiple color fluorescence assays without requiring the use of multiple exciting sources.Type: GrantFiled: September 3, 1992Date of Patent: December 21, 1993Assignee: Coulter CorporationInventor: Ravinder K. Gupta
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Patent number: 5244816Abstract: A method for removing unbound labeling reagent from a composition comprising bound and unbound labeling reagent is described. Lilo-matrix conjugate capable of binding unbound labeling reagent is contacted with a biomolecule labeling reaction mixture and then the labeled biomolecule essentially free of unbound labeling reagent is removed.Type: GrantFiled: October 11, 1989Date of Patent: September 14, 1993Assignee: Akzo N.V.Inventor: Ramaswamy Subramanian
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Patent number: 5243074Abstract: An immunofluorescent assay method, characterized in using an immunodetective reagent, which is an antigen-like substance comprising a fluorescent substance and an antigen chemically bonded thereto with or without intervention of an additional chemical bond, said fluorescent substance being changed in the wavelength or intensity of the fluorescence when an antibody comes close thereto, and said antigen being specific to said antibody.Type: GrantFiled: November 21, 1990Date of Patent: September 7, 1993Assignee: Matsushita Electric Industrial Co., Ltd.Inventors: Tadayasu Mitsumata, Jinsei Miyazaki
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Patent number: 5234820Abstract: An auxiliary substance such as a label, support, or bioactive agent is attached to a protein at a site that is remote from the active site of the protein by the use of exopeptidase and a nucleophile which is an amino acid, amino acid derivative, amine or alcohol. In one embodiment, the nucleophile is attached to the carboxy terminus of a protein by catalysis with exopeptidase to form an adduct and then the adduct or its combination with a linker arm is bound to the auxiliary substance. In another embodiment, the auxiliary substance or its combination with a linker arm is bound to the nucleophile to form an intermediate substance which is then coupled by catalysis with exopeptidase to the carboxy terminus of a protein.Type: GrantFiled: June 28, 1990Date of Patent: August 10, 1993Assignees: Board of Regents of the University of Nebraska, BioNebraska, Inc.Inventors: Fred W. Wagner, Thomas R. Coolidge, Sheldon M. Schuster, Jay Stout, Dwane E. Wylie, Klaus Breddam, William Lewis
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Patent number: 5221611Abstract: This invention relates to a method for the immunoassay of ddI (2',3'-dideoxyinosine), also known as didanosine, in biological fluids such as serum, semen, plasma and urine, as well as other body fluids. The invention also includes (1) various novel analogs of ddI useful in preparing immunogens for antibodies to ddI and in preparing labeled ddI, (2) immunogens for antibodies to ddI, (3) antibodies to ddI, (4) labeled ddI analogs and (5) diagnostic test kits for the immunoassay.Type: GrantFiled: June 19, 1991Date of Patent: June 22, 1993Assignee: Sigma Chemical CompanyInventors: Kenneth J. Stenglein, Dennis M. Murray
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Patent number: 5221609Abstract: A method of assaying for the presence or quantity of a suspect nucleic acid in a suspect sample using a modified genetic probe in combination with an imaging procedure. The probe is modified by addition and provides an easy and very effective technique of modifying a genetic probe preparatory to its use in a kit. The genetic probe is then introduced into contact with DNA or RNA of the suspect sample and permitted to hybridize therewith. A kit for performing an assay using the modified probe is also disclosed.Type: GrantFiled: July 18, 1991Date of Patent: June 22, 1993Assignee: Orgenics Ltd.Inventor: Max Herzberg
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Patent number: 5219764Abstract: Hapten-biotin conjugates in which the hapten is linked with biotin via a spacer, which has 26 to 40 atoms in its chain and contains at least 5 heteroatoms, are novel and are suitable, in particular for use in a competitive homogeneous immunoassay in which the agglutination which occurs in the reaction is evaluated by turbidimetric or nephelometric measurements.Type: GrantFiled: April 10, 1991Date of Patent: June 15, 1993Assignee: Boehringer Mannheim GmbHInventors: Erasmus Huber, Dietmar Zdunek, Christian Klein, Roland Schenk
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Patent number: 5217881Abstract: Ligand reagents are disclosed which consist essentially of recombinant hyperglycosylated cytokines, expressed in yeast, which are purified and conjugated to various functional moieties, for example, biotin groups, via oligosaccharide residues.Type: GrantFiled: January 24, 1992Date of Patent: June 8, 1993Assignee: Immunex CorporationInventor: Linda S. Park
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Patent number: 5202423Abstract: The invention pertains to terpyridine compounds having structure (I). These compounds form fluorescent lanthanide chelates with the appropriate metal ions. The fluorescent metal chelates are useful as probes in time-resolved fluorescence spectroscopy.Type: GrantFiled: April 19, 1991Date of Patent: April 13, 1993Assignee: Wallac OyInventors: Jouko Kankare, Harri Takalo, Elina Hanninen, Matti Helenius, Veli-Matti Mukkala
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Patent number: 5198367Abstract: A method is described for measuring the amount of analyte present in a sample containing the analyte using a homogeneous amperometric immunoassay. The analyte is covalently bonded to a suitable carrier molecule, which is also covalently bonded to an electroactive molecule. The electroactive molecule, such as ferrocene carboxylic acid, contains a redox center which is capable of transferring a charge to an electrode. A preferred carrier molecule is bovine serum albumin (BSA), while suitable analytes include digoxin, theophylline and HCG. The immunoassay is conveniently performed by applying a voltage to a set of electrodes.Type: GrantFiled: June 9, 1989Date of Patent: March 30, 1993Inventors: Masuo Aizawa, Brenda D. Manning, Miki Hidaka, Laura S. Uretsky
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Patent number: 5169757Abstract: A device for immunological techniques is prepared containing a macroporous hydrophobic synthetic polymer cloth having antibodies or antigens directly adsorbed therein and directly absorbed and immobilized thereon. The cloth has a thickness of more than about 200 .mu.m and has spaces between fibres exceeding about 20 .mu.m in diameter, and preferably has a Frazier Air permeability, in CFM/ft.sup.2 at 0.5" H.sub.2 O of from about 215 to about 750 for thickness of from about 11 to about 40 mils such that it can accommodate a large volume of liquid per surface area, that it has a large surface area, and that it has minimum flow resistance. In immunoassays antibodies may be directly adsorbed therein and directly absorbed and immobilized thereon, and specific antigens from a selected test sample, may then be captured by the antibodies, to be detected conventionally.Type: GrantFiled: June 14, 1990Date of Patent: December 8, 1992Assignee: Carleton UniversityInventors: Hiroshi Yamazaki, Burton W. Blais
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Patent number: 5168057Abstract: A trifunctional conjugate is provided 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 mouths 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.Type: GrantFiled: September 30, 1991Date of Patent: December 1, 1992Assignee: Beckman Instruments, Inc.Inventors: Chan S. Oh, James C. Sternberg
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Patent number: 5162218Abstract: Polypeptide compositions are provided having a binding site specific for a particular target ligand and further having an active functionality proximate the binding site. The active functionality may be a reporter molecule, in which case the polypeptide compositions are useful in performing assays for the target ligand. Alternatively, the active functionality may be a chemotherapeutic agent, in which case the polypeptide compositions are useful for therapeutic treatment of various diseased states. A novel method for preparing such polypeptides having active functionalities proximate their binding site comprises combining the polypeptide specific for the target ligand with an affinity label including ligand having a reactive group attached thereto. The reactive group is then covalently attached to an amino acid side chain proximate the binding site and cleaved from the substrate. The substrate is eluted, leaving a moiety of the reactive group covalently attached to the polypeptide.Type: GrantFiled: June 10, 1991Date of Patent: November 10, 1992Assignee: The Regents of the University of CaliforniaInventor: Peter Schultz
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Patent number: 5128240Abstract: A quantitative immunoassay for a beta-lactam antibiotic in a sample, which may contain open and closed ring forms of the antibiotic, is disclosed. Closed-ring forms of the antibiotic in the sample are converted to open-ring protein conjugates and detected through immunospecific reaction with antibodies raised against the open-ring protein conjugate form of the beta-lactam antibiotic.Type: GrantFiled: January 12, 1989Date of Patent: July 7, 1992Assignee: International Immunoassay Laboratories, Inc.Inventor: Vipin D. Shah
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Patent number: RE34394Abstract: The performance of double receptor, specific binding assays is improved by use of a receptor complex having the structureA.sub.BL (BL).sub.n A.sub.1wherein BL is a binding ligand, A.sub.BL is a receptor specific for binding ligand, A.sub.1 is a receptor, BL is covalently bonded to A.sub.1 and A.sub.BL is reversibly bonded to BL. Generally A.sub.BL is absorbed onto an insoluble surface and A.sub.1 is an antibody to the substance being assayed. The complex has particular utility in coated tube and rechargeable radioimmunoassay systems.Type: GrantFiled: December 18, 1990Date of Patent: September 28, 1993Assignee: Baxter Diagnostics Inc.Inventor: James R. Bunting