Involving Esterase Patents (Class 435/19)
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Patent number: 5059526Abstract: A stable dry multi-layer analytical element for enzyme or triglyceride analysis in a fluid sample is prepared containing first and second layers on a support. The first layer contains a tetrazolium salt as a dye forming precursor. The second layer is adjacent the first layer and contains an electron-transmitting agent. Either layer contains a co-enzyme in oxidized form and either layer contains a reagent containing an enzyme substrate, enzyme or co-enzyme other than the oxidized co-enzyme. The analytical element has improved storage stability and low fog density before and after storage.Type: GrantFiled: March 14, 1990Date of Patent: October 22, 1991Assignee: Konishiroku Photo Industry Co., Ltd.Inventors: Kazumi Arai, Mario Kobayashi, Kenichiro Okaniwa
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Patent number: 5057412Abstract: A small enzymically inactive peptide fragment of an enzyme (e.g. ribonuclease S-peptide) is used as the label and conjugated with the complementary fragment (S-protein) to form an enzyme which catalyses a primary reaction whose product is, or leads to, an essential coenzyme or prosthetic group for a second enzyme which catalyses a secondary reaction leading to a detectable result indicating the presence of analyte. Also disclosed are novel synthetic substrates for the primary reaction. Substrates for ribonuclease S conjugate enzyme are of the formula R-X where R is pyrimidine 3'-phosphate moiety and X is a leaving group linked to R through the 3'-phosphate group and leads to said coenzyme or prosthetic group, e.g. via riboflavin, thiamine, pyridoxal, pyridoxine or pyridoxine phosphate.Type: GrantFiled: March 15, 1988Date of Patent: October 15, 1991Assignee: London Biotechnology LimitedInventors: Brian R. Rabin, Michael R. Hollaway, Christopher J. Taylorson
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Patent number: 5051358Abstract: The present invention relates to diagnostic methods for detecting or evaluating the presence of periodontal diseases, especially gingivitis, in humans or lower animals by measuring the presence of leukocyte esterase. These diagnostic methods comprise measuring the amount of leukocyte esterase present in the oral cavity of the human or lower aniaml being diagnosed.The present invention further relates to diagnostic products useful in vivo for detecting or evaluating the presence of periodontal diseases, especially gingivitis, in humans. These diagnostic products contain at least one agent useful in detecting the presence of leukocyte esterase, and a carrier material. These diagnostic products must be sterile and safe for in vivo contact with the tissue in the oral cavity of the human being diagnosed.Finally, the present invention further relates to diagnostic kits useful for detecting or evaluating the presence of periodontal diseases, especially gingivitis, in humans.Type: GrantFiled: May 7, 1987Date of Patent: September 24, 1991Assignee: The Procter & Gamble CompanyInventor: Jonathan J. Witt
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Patent number: 5047327Abstract: There is provided a stable cholesterol assay composition which comprises an aqueous solution of at least one bile acid or salt thereof being present in an amount of up to about 5 mM; a nonionic surfactant present in an amount of from about 0.15 to about 1.5 percent volume by volume; a buffer in a concentration of from 0 to about 65 mM; and cholesterol oxidase in a concentration of at least about 0.1 kIU/l. Solution pH is from about 5.5 to about 8.5. Addition of cholesterol esterase, phenol, peroxidase and 4-aminoantipyrine provides a total cholesterol chromogen system.Type: GrantFiled: January 3, 1989Date of Patent: September 10, 1991Assignee: Ivan E. ModrovichInventors: Karen R. Caris, Ivan E. Modrovich
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Patent number: 5047330Abstract: Compound labelled by the acetyl cholinesterase of Electrophorus electricus, its preparation process and its use in enzymoimmunology.This compound is constituted by a molecule chosen from among the antigens, haptens and antibodies, bonded by a covalent bond to an enzyme formed by the acetyl cholinesterase of Electrophorus electricus (electric eel).For example, the molecule is the substance P or a prostaglandin and the compound can be used for the enzymoimmunological determination of these molecules.Type: GrantFiled: January 6, 1988Date of Patent: September 10, 1991Assignee: Commissariat a l'Energie AtomiqueInventors: Jacques Grassi, Philippe Pradelles
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Patent number: 5035998Abstract: Reagents for the determination of hydrolase comprises compounds of the formula ##STR1## wherein Z is an organic or inorganic acid residue or a sugar residue, A is an organic or inorganic acid residue, and B is an organic acid residue. Each of R.sup.2 and R.sup.5, is hydrogen, halogen or lower alkyl. Each of R.sup.1, R.sup.3, R.sup.4 and R.sup.6, is hydrogen, halogen, cyano, lower alkyl, lower alkoxy, carboxyl, lower alkoxycarbonyl, carboxy lower alkyl or lower alkoxycarbonyl lower alkyl, or carboxamido groups optical substituted once or twice, or a radical of the formula--COO--(CH.sub.2 CH.sub.2 O).sub.n --R.sup.7in which R.sup.7 is hydrogen or lower alkyl and n is a number from 1 to 4. Additionally, R.sup.6 can be sulpho or nitro.Type: GrantFiled: November 13, 1989Date of Patent: July 30, 1991Assignee: Boehringer Mannheim GmbHInventors: Herbert von der Eltz, Hans-Joachim Guder, Klaus Muhlegger
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Patent number: 5034317Abstract: The present invention provides an enzyme controlled release system and prepared reactant by which an identifiable molecule may be released on demand through the action of an active enzyme. The controlled release system is useful for detection of an analyte of interest present in a test sample in picogram per liter quantities and may be employed in a variety of different modes of use including immunoassays, enzyme amplification systems and the release of pharmacologically active ligands.Type: GrantFiled: January 30, 1987Date of Patent: July 23, 1991Assignee: Polaroid CorporationInventors: Michael J. Arnost, Frank A. Meneghini, Paul S. Palumbo
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Patent number: 5030561Abstract: A method for assaying of Chlamydia includes adhering Chlamydia antigen to amidine modified latex particles, binding of adhered antigen to an anti-Chlamydia antibody conjugated to an enzyme, separating the particles from the liquid phase of the assay and detecting bound enzyme by color development when the separated particles are contacted with a substrate for the enzyme. The invention includes a kit of materials for preforming an assay in accordance with the method of the invention.Type: GrantFiled: December 27, 1988Date of Patent: July 9, 1991Assignee: Becton, Dickinson and CompanyInventors: James P. Mapes, Catherine S. Donahue
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Patent number: 5024936Abstract: A method for assessing whether the lungs of a fetus are mature comprising obtaining a sample of the amniotic fluid surrounding the fetus and determining the presence or absence of phosphatidyl glycerol in the sample. The presence of phosphatidyl glycerol indicates that the fetus lungs are mature, and the absence indicates that the fetus lungs are not mature. More particularly, in one embodiment of the present invention, the presence of phosphatidyl glycerol is determined by adding phospholipase C to the amniotic fluid to convert the phosphatidyl glycerol to glycerol-3-phosphate. Then adding glycerol-3-phosphate oxidase to convert the glyerol-3-phosphate to dihydroxyacetone phosphate and hydrogen peroxide and then reacting the hydrogen peroxide with a substrate and peroxidase to form a visually detectable reaction product.Type: GrantFiled: September 26, 1988Date of Patent: June 18, 1991Inventor: James Macri
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Patent number: 5015572Abstract: Carrier-bound multicomponent detection system for the colorimetric determination of esterolytically- and/or proteolytically-active ingredients of body fluids, wherein the components of the detection system are present in different reagent layers, and where a liquid exchange between the layers is possible.Type: GrantFiled: April 19, 1989Date of Patent: May 14, 1991Assignee: Boehringer Mannheim GmbHInventors: Jurgen Backhaus, Dieter Mangold, Wolfgang-Reinhold Knappe
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Patent number: 5011769Abstract: This invention provides a method for detecting a target nucleic acid which comprises forming a reaction mixture which includes the target nucleic acid and an amount of a complementary single-stranded nucleic acid probe which is greater than the target molecule, under conditions which allow the probe and the target nucleic acid to hybridize to each other and form a double stranded target-probe complex, nicking the hybridized probe at least once within a predetermined sequence so as to form at least two probe fragments hybridized to the target nucleic acid, resulting in the probe fragments to become single-stranded and allowing the target nucleic acid to become hybridized to another probe; and identifying probe fragments, thereby detecting the target nucleic acid. This invention also provides a method for detecting a target nucleic acid.Type: GrantFiled: April 29, 1988Date of Patent: April 30, 1991Assignee: Meiogenics U.S. Limited PartnershipInventors: Peter Duck, Robert Bender
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Patent number: 5006462Abstract: The diagnosis of schizophrenia through the detection of a phospholipase enzyme is disclosed. In this invention, a test sample from the patient can be combined with a test composition to measure phospholipase enzyme in the test sample. The sample can be read and the result compared with a scale of values found in nonschizophrenic controls.Type: GrantFiled: March 16, 1988Date of Patent: April 9, 1991Assignee: Abbott LaboratoriesInventor: Wagner F. Gattaz
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Patent number: 5004685Abstract: A dry-type multilayer analytical element containing a color reagent composition comprising an oxidase specifically reaction with an analyte or derived therefrom to produce hydrogen peroxide, hydrogen peroxide-decomposing enzyme, an alkali metal salt of ferrocyanide and a chromogen which is separated from the hydrogen peroxide-decomposing enzyme, the chromogen being incorporated in a layer nearer to the transparent support of the analytical element than the layer containing the hydrogen peroxide-decomposing enzyme. The analytical element exhibits excellent coloration, color stability, and accuracy and the results are minimally influenced by the presence of hemoglobin in the sample.Type: GrantFiled: August 18, 1987Date of Patent: April 2, 1991Assignee: Fuji Photo Film Co., Ltd.Inventors: Fuminori Arai, Asaji Kondo
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Patent number: 4999289Abstract: Lipase isolated from Penicillium characterized by the following properties:(1) Efficiently hydrolyzes triglycerides of fatty acids having 4-18 carbon atoms;(2) Hydrolysis of such triglycerides with such lipase produces at least 5 moles of glycerol per 100 moles of fatty acid;(3) Optimal pH range for said hydrolysis 5-7;(4) Stable in the pH range of 4.5-6;(5) Optimal temperature range for activity 35.degree.-40.degree. C.;(6) thermal stability up to about 35.degree. C.;(7) Activated by surface-active agents, but not substantially inhibited by such surface-active agents in concentration up to 5%;(8) Molecular weight about 1000,000 to 120,000;(9) Isoelectric point about pH 3.84.Type: GrantFiled: April 6, 1987Date of Patent: March 12, 1991Assignee: Amano Pharmaceutical Co. Ltd.,Inventors: Tetsunori Akiba, Shotaro Yamaguchi, Satoru Suzuki, Kimiyasu Isobe, Kuniyoshi Matsunaga
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Patent number: 4996145Abstract: A method for detecting the sensitivity of tumor cells to immune effector substances by using an assay that distinguishes living tumor cells from dead cells in mixed populations of cells. Acquired resistance to immune effectors used in therapy may be determined and used to identify methods to circumvent such resistance using the method.Type: GrantFiled: October 27, 1987Date of Patent: February 26, 1991Assignee: Oncotech IncorporatedInventor: Larry M. Weisenthal
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Patent number: 4990445Abstract: A stable reagent and kinetic assay for .alpha.-amylase is provided. The reagent comprises a substrate for the .alpha.-amylase and various enzymes and cofactors necessary to produce NADH as the end-product of a series of four reactions. The substrate, enzymes, and cofactors are provided in sufficient excess that the .alpha.-amylase from the test sample is the rate-limiting factor. The concentration of .alpha.-amylase in a test sample is determined by measuring the rate of increase in absorbance caused by the production of NADH. The use of the novel cofactor fructose-1,6-diphosphate has been found to impart improved stability to the reagent.Type: GrantFiled: January 20, 1988Date of Patent: February 5, 1991Assignee: Beckman Instruments, Inc.Inventors: Sandra M. Poudrier, Mark T. Oyen
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Patent number: 4988497Abstract: The present invention provides a lipase substrate of the general formula: ##STR1## wherein A is an alkalene or alkenylene radical containing up to 16 carbon atoms, R and R.sub.1, which can be the same or different, each signify an alkyl, alkenyl or acyl radical containing up to 20 carbon atoms or an optionally alkyl-substituted aryl or aralkyl radical containing up to 8 carbon atoms in the alkyl moiety and wherein one of R and R.sub.1 can also be a hydrogen atom, X is the residue of an aromatic hydroxy or thiol compound, and each Y and Z, independently from each other, is --S-- or --O--, Z also --CH.sub.2 --.The present invention also provides a process and a reagent for the optical determination of lipase.Type: GrantFiled: May 17, 1989Date of Patent: January 29, 1991Assignee: Boehringer Mannheim GmbHInventors: Ulrich Neumann, Martina Junius, Hans-Georg Batz
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Patent number: 4983514Abstract: The antiaggregatory effect of phosphodiesterase inhibitors (A) and/or of cyclooxygenase inhibitors (B) is detected outside the human or animal body bysampling blood,addition of (A) and/or (B) to the blood sample--if not already present therein, in unchanged or in metabolized form, as a consequence of previous administration,where appropriate removal of the erythrocytes and leukocytes andinitiation--preferably by addition of an aggregation inducer--and measurement of the platelet aggregation,the method comprises (A) also being added--if only (B) has been administered or added up till then--or (B) also being added--if only (A) has been administered or added up till then--and at least one prostaglandin (C) being added, before, or no later than at, the initiation of the platelet aggregation, so that the initiation and measurement of the platelet aggregation takes place in the presence of the ternary combination of (A), (B), each in the unchanged or in metabolized form, and (C).Type: GrantFiled: May 20, 1988Date of Patent: January 8, 1991Assignee: Hoechst AktiengesellschaftInventors: Klaus U. Weithmann, Dirk Seiffge
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Patent number: 4980280Abstract: The present invention relates to the synthesis of conjugated polyene sterol derivatives, the compounds obtained and to their use as fluorescent probes for cellular membranes. The fluorescent probes of the present invention resemble cholesterol both structurally and in amphipathic nature. The probes of the present invention have potential for use in determining cholesterol levels and cholesterol properties and cell membrane properties and can be applied to clinical assays and diagnoses involving cholesterol.Type: GrantFiled: May 31, 1989Date of Patent: December 25, 1990Assignee: University of Ottawa/Universite d'OttawaInventors: Peter Morand, Jacinta Drew, Arthur G. Szabo, Pierre R. Proulx
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Patent number: 4978614Abstract: In an assay method in which a member of a specific binding pair is detected by means of an optically detectable reaction, the improvement wherein the optically detectable reaction includes the reaction, with an enzyme, of a dioxetane having the formula ##STR1## where T is a cycloalkyl or polycycloalkyl group bonded to the 4-membered ring portion of the dioxetane by a spiro linkage; Y is a fluorescent chromophore; X is hydrogen, alkyl, aryl, aralkyl, alkaryl, heteroalkyl, heteroaryl, cycloalkyl, cycloheteroalkyl, or enzyme-cleavable group; and Z is hydrogen or an enzyme-cleavable group, provided that at least one of X or Z must be an enzyme-cleavable group, so that the enzyme cleaves the enzyme-cleavable group from the dioxetane to form a negatively charged substituent bonded to the dioxetane, the negatively charged substituent causing the dioxetane to decompose to form a luminescent substance that includes group Y of said dioxetane.Type: GrantFiled: July 20, 1989Date of Patent: December 18, 1990Assignee: Tropix, Inc.Inventor: Irena Y. Bronstein
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Patent number: 4970152Abstract: A reagent comprising a fraction obtained from plasma of an insect such as silkworm larvae and capable of reacting specifically with .beta.-1,3-glucan or peptidoglycan can be used for determining .beta.-1,3-glucan or peptidoglycan.Type: GrantFiled: December 2, 1987Date of Patent: November 13, 1990Assignee: Wako Pure Chemical Industries, Ltd.Inventors: Masaaki Ashida, Masakazu Tsuchiya, Yoshitsugu Sakata, Shuji Matsuura
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Patent number: 4962024Abstract: A method for assay for an unknown enzyme suspected to be present in a liquid includes signal amplification by use of a second enzyme and a blocked modulator for the second enzyme. Unknown enzyme in the liquid removes a blocking group from the blocked modulator. The resulting modulator activates or inhibits the second enzyme which catalyzes an indicator reaction in which a substrate is converted to a product. The presence or absence of the unknown enzyme in the liquid is indicated by a signal, such as a color change or a rate of color change, associated with the indicator reaction. The concentration of the enzyme in the sample may be determined by the measurement of the signal. The invention includes a kit of materials useful for performing the method of the invention. The method involves the hydrolyzing of a blocked fluoroketone inhibitor to facilitate the analytical method.Type: GrantFiled: August 11, 1988Date of Patent: October 9, 1990Assignee: Becton, Dickinson and CompanyInventor: Thomas H. Schulte
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Patent number: 4959182Abstract: A method and compositions including a 1,2-dioxetane and a fluorescent compound is described. In particular, enzymatic triggering of a triggerable 1,2-dioxetane admixed with a surfactant and the fluorescent compound attached to a hydrocarbon to provide a co-surfactant in a micelle or other structure providing close association of these molecules is described. The method and compositions are useful in immunoassays and in DNA probes used for various purposes.Type: GrantFiled: March 1, 1989Date of Patent: September 25, 1990Assignee: Board of Governors of Wayne State UniversityInventor: Arthur P. Schaap
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Patent number: 4954434Abstract: The present invention relates to a method of diagnosis of pathological pregnancy which relies on an evaluation of the amount of placental isoferritin (PLF) in the serum or amniotic fluid of a pregnant woman. Diagnosis may also be achieved by observation of percentages of PLF-bearing lymphocytes in the pregnant female. Detection of PLF levels is achieved by immunoassay with a PLF-specific anitbody. Also described is a method of treating or preventing pathological pregnancies and transplant or graft rejection by administration of effective amounts of PLF and/or a PLF-specific antibody in combination with immunization.Type: GrantFiled: June 23, 1988Date of Patent: September 4, 1990Inventor: Chaya Moroz
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Patent number: 4952495Abstract: Hydrolyzable substrates comprise blocked moieties which, when cleaved from the substrate during hydrolysis, provide electron transfer agents. The released electron transfer agents can be recycled between a reductant and a reducible compound that upon reduction provides a detectable species. Alternatively, they can be recycled between an oxidant and an oxidizable compound that upon oxidation provides a detectable species. These substrates are useful in analytical compositions, elements and methods for the determination of hydrolytic analytes, such as hydrolytic enzymes or biological cells containing such enzymes.Type: GrantFiled: June 8, 1987Date of Patent: August 28, 1990Assignee: Eastman Kodak CompanyInventors: Robert T. Belly, Patricia M. Scensny, Annie L. Wu, Chung-yuan Chen
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Patent number: 4948726Abstract: An enzyme immunoassay based on membrane separation of antigen-antibody complexes wherein human or animal body fluid specimens containing an antigen are mixed with an enzyme-conjugated antibody specific for the antigen under test. Following incubation the antigen-antibody-conjugate mixture is passed through a filter membrane having an electrostatic charge providing an affinity for retaining antigen-antibody-conjugate complexes while not retaining free antibody-conjugate. Following washing of the filter membrane to remove free antibody-conjugate remaining thereon an enzyme substrate-chromogen reagent solution is applied to the filter membrane, which reacts with filter-bound antibody-conjugate and develops a visible or fluorogenic color indicative of the presence of antibody-conjugate.Type: GrantFiled: March 20, 1989Date of Patent: August 14, 1990Inventor: Claude C. Longoria
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Patent number: 4940659Abstract: Disclosed is a screening assay for determining the amount of Superoxide Dismutase (SOD-1) in extra-cellular body fluids, for use in determining Trisomy 21 Down syndrome in a fetus. The assay can be done by any of a number of well known techniques including Radioimmunoassay, an Enzyme Linked Immunoassay, or a luminescence assay, single or tandem antibody type, carried out in solid or liquid phase. Polyclonal or monoclonal antibodies can be used. In the preferred embodiment, the assay is used to determine SOD-1 levels in amniotic fluid. A level above a threshold indicates a high probability of Trisomy 21 Down Syndrome for the fetus.Type: GrantFiled: February 20, 1987Date of Patent: July 10, 1990Assignee: Monoclonetics International, Inc.Inventors: Richard E. Warrington, Abbas A. Khan, Carl R. Merril
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Patent number: 4914020Abstract: An analytical element to measure a specific component in a fluid samples comprising support, a layer containing a reagent provided the support and a spreading layer provided on above the reagent containing layer. In the spreading layer, an emzyme necessary for the reaction to produce a product capable of being detected with said reagent from the specific component is contained. The enzyme is protected from deterioration of activity during a manufacturing and preservation of the analytical element by means of the enzyme is included in the spread layer as a dispersion mixture with a protein and/or polypeptide. An accurate analytical result is stably obtained by the analytical element.Type: GrantFiled: January 31, 1986Date of Patent: April 3, 1990Assignees: Konishiroku Photo Industry Co., Ltd., Chugai Seiyaku Kabushiki KaishaInventors: Kazumi Arai, Mikio Koyama, Morio Kobayashi, Kenichiro Okaniwa, Takasi Momose, Kunihiro Furukawa, Souichi Zanma
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Patent number: 4904583Abstract: A method for enzyme immunoassay includes contacting under binding conditions a liquid suspected of containing an analyte, an antianalyte affixed to a solid support and a tracer having an enzyme conjugated thereto. A bound fraction is separated from the liquid and incubated in a second liquid with a masked ligand. The masked ligand is converted by the enzyme on the bound fraction to give free lignad which binds to an antiligand. A signal system, such as a signal enzyme and substrate therefor, or a label-loaded vesicle and vesicle lysing agent, is added to generate a signal used to detect or measure the analyte in the liquid. The invention includes a kit of materials useful in performing the assay of the invention.Type: GrantFiled: May 26, 1987Date of Patent: February 27, 1990Assignee: Becton, Dickinson and CompanyInventors: James P. Mapes, Randal A. Hoke
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Patent number: 4898813Abstract: Test compositions and test devices are provided which are capable of generating different hues at different analyte concentrations. Visual results for clinically important analytes, such as glucose and cholesterol, are provided by use of compositions containing two independent catalytic systems which are reactive with a common substrate generated from the analyte of interest, to produce visual endpoints of different hues for different concentrations of analyte. Preferred formulations provide a RAINBOW of hues, the particular final hue produced depending on the concentration of the analyte.Type: GrantFiled: April 4, 1986Date of Patent: February 6, 1990Inventors: James P. Albarella, Steven C. Charlton, James W. Reinsch, Mary E. Warchal
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Patent number: 4892816Abstract: An enzymatic method for measurement of cholesterol comprises incubating:(a) a test sample;(b) a cholesterol dehydrogenase;(c) an oxidizing agent selected from the group consisting of nicotinamide - adenine dinucleotide (NAD) and nicotinamide - adenine dinucleotide phosphate (NADP); and(d) a surfactantand measuring the resulting detectable oxidized and reduced products kinetically.A composition for the kinetic measurement of cholesterol comprises:(a) a cholesterol dehydrogenase;(b) an oxidizing agent selected from the group consisting of nicotinamide - adenine dinucleotide (NAD) and nicotinamide - adenine dinucleotide phosphate (NADP); and(c) a surfactant.Type: GrantFiled: December 22, 1987Date of Patent: January 9, 1990Assignee: Amano Pharmaceutical Co., Ltd.Inventors: Tetsunori Akiba, Kuniyoshi Matsunaga
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Patent number: 4892815Abstract: The present invention provides a process for the specific determination of the cholesterol of the HDL fraction in the presence of the LDL fraction of serum lipoproteins. Pancreatic cholesterol esterase is used to liberate cholesterol, and the liberated cholesterol then reacts with cholesterol oxidase and oxygen to form hydrogen peroxide. The kinetics of either of hydrogen peroxide formation or oxygen consumption is measured within 2 to 15 minutes after the start of the reaction between cholesterol and the oxidase. The temperature is maintained within a range of 20.degree. C., during a predetermined time interval. Specific concentrations of reactants are maintained in the reaction solution, i.e., from 0.05 to 30 U/ml pancreatic cholesterol esterase; from 0.1 to 50 U/ml cholesterol oxidase; from 1.0 to 20 mMole/liter of a tenside of the bile acid group, and 0.1 to 10 g/liter of a non-ionic detergent. The pH is kept within a range of 5 to 9.Type: GrantFiled: October 6, 1987Date of Patent: January 9, 1990Assignee: Boehringer Mannheim GmbHInventors: Lorenz Kerscher, Brigitte Pautz, Gisela Trunk, Joachim Ziegenhorn
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Patent number: 4888288Abstract: Liposomes are formed from compounds including a phosphonate or phosphinate group instead of a phosphate group. The liposomes bind to enzymes, such as a phospholipase, and such liposomes containing a detectable marker may be used as a substrate in an enzyme immunoassay.Type: GrantFiled: January 30, 1986Date of Patent: December 19, 1989Assignee: Becton Dickinson and CompanyInventor: Daniel B. Wagner
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Patent number: 4874695Abstract: Rapid identification of different species of microorganism selected from fungi and yeast like algae is accomplished by culturing the microorganism for several hours under normal conditions on a non-inhibitory mycological medium which stimulates the microorganism to make characteristic enzymes by which the microorganism can be identified, distributing the culture (in suspension) onto several supports containing different substrates which are capable of reacting with the enzymes so produced by the different species of microorganisms; and rapidly incubating the admixture to produce a distinctly colored or colorable reaction product.Type: GrantFiled: February 21, 1985Date of Patent: October 17, 1989Assignee: American Home Products Corp.Inventor: David H. Pincus
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Patent number: 4861709Abstract: A method for determining the presence of microorganisms in a tests sample. Exogenous DNA containing a luminescent system or other genetic marker system derived from a suitable donor source is introduced by genetic means into a host microorganism which lacks or poorly expresses the donor DNA and whose presence it is desired to detect. Expression of the donor gene system allows the detection of the host microorganism. Compositions of bacteriophages and plasmids as well as a method for detection of antibiotics in a test sample are described.Type: GrantFiled: May 31, 1985Date of Patent: August 29, 1989Assignee: Technicon Research A.G.Inventors: Shimon Y. Ulitzur, Jonathan C. Kuhn
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Patent number: 4845028Abstract: A composition and method for lipase assay, comprising the use of an aqueous solution of a 1,2-diglyceride of a higher fatty acid, and a nonionic surface active agent. The higher fatty acid is a higher fatty acid of 8 or more and preferably 12 or more carbons, most preferably a higher unsaturated fatty acid of more than 16 carbons. The concentration of 1,2-diglyceride is more than 0.5 g per liter of solution. The nonionic surface active agent is a polyoxyethylene-type nonionic surface active agent, a polyhydric-alcohol-type nonionic surface active agent or a block-polymer-type nonionic surface active agent, whose concentration is more than 0.1% by weight in the composition and which has an HLB more than 10. The composition preferably contains 0.5-10 g of 1,2-diglyceride and 10-50 g of nonionic surface active agent per liter of solution.Type: GrantFiled: September 9, 1988Date of Patent: July 4, 1989Assignee: Toyo Jozo Kabushiki KaishaInventors: Shigeyuki Imamura, Hideo Misaki
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Patent number: 4845029Abstract: The present invention provides a method of use for a hydrogen peroxide-forming oxidase, wherein the enzyme is obtained from Streptomycetaceae and at 25.degree. C., in 0.15 mol/liter potassium phosphate (pH 7.9), in the presence of surface-active substances, still shows after 2 days an activity of at least 40% of the initial activity. This enzyme is useful in the determination of sarcosine, creatine and creatinine.Type: GrantFiled: February 9, 1988Date of Patent: July 4, 1989Assignee: Boehringer Mannheim GmbHInventors: Ulrich Mayr, Hans Mollering, Joachim Siedel, Hans Seidel
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Patent number: 4835099Abstract: A method for enzyme immunoassay for a ligand suspected to be present in a liquid sample includes signal amplification by use of at least two hydrolases and a blocked fluoroketone for one of the hydrolases. Ligand present in the liquid binds to an antiligand and a hydrolase-labeled tracer. The resulting bound fraction is separated and the hydrolase in the tracer removes the blocking group from the blocked fluoroketone. The fluoroketone activates or inhibits a second hydrolase which catalyzes the conversion of a substrate to a product. The presence or absence of the ligand in the liquid is indicated by a signal, such as a color change or a rate of color change, associated with the product. The invention includes a new class of hydrolase inhibitors and blocked fluoroketones and a kit of materials useful for performing the method of the invention.Type: GrantFiled: November 20, 1986Date of Patent: May 30, 1989Assignee: Becton, Dickinson and CompanyInventors: Patrick D. Mize, James P. O'Connell
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Patent number: 4828982Abstract: A sac is produced by use of a compound which includes a hydrophobic portion and a polar group which is hydrolyzable by an enzyme and which is spaced from the hydrophobic portion by a hydrophilic portion which does not have a polarity sufficient to form a vesicle. A detectable marker may be released from the sac by use of a hydrolase enzyme, whereby the sac may be used as a substrate in an enzyme assay.Type: GrantFiled: May 28, 1985Date of Patent: May 9, 1989Assignee: Becton, Dickinson & CompanyInventor: Daniel B. Wagner
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Patent number: 4826761Abstract: An integral multilayer analytical element for analysis of cholesterol which comprises a water-impermeable light-transmissive support, a hydrophilic layer and a spreading layer superposed in this order, and contains cholesterol esterase, cholesterol oxidase, peroxidase and a coloring reagent composition, which is characterized, in that the above coloring reagent composition is a combination of 4-aminoantipyrine or its derivative and 2-hydroxy-3,5-dichlorobenzene sulfonic acid, and in that pH of the layer where coloring reaction proceeds is kept in the range of 7.5 to 9.This analytical element is stable, and capable of preserving more than 8 months without fogging.Type: GrantFiled: July 8, 1986Date of Patent: May 2, 1989Assignee: Fuji Photo Film Co, Ltd.Inventors: Fuminori Arai, Takeshi Igarashi
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Patent number: 4820635Abstract: A kit for assaying the activation of terminal complement cascade is disclosed. The kit includes a plurality of containers which contain a first antibody having a specificity for poly C9 neoantigen. The containers further have a second antibody which is different from the first antibody and has a specificity for a constituent of terminal complement cascade. A third antibody is optionally present which recognizes the second antibody. The kit also includes a substrate splitting enzyme, a substrate for the enzyme which produces a color reaction when split, and a SCb-9 standard microtiter plate. Pipettes and instructions for performing the assay are also included.Type: GrantFiled: July 31, 1987Date of Patent: April 11, 1989Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Martin E. Sanders, Keith A. Joiner, Michael M. Frank, Carl H. Hammer
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Patent number: 4816411Abstract: A method for eliminating turbidity in a biological fluid by combining said fluid with a surfactant and an enzyme is disclosed as well as a diagnostic reagent formulation for that purpose.Type: GrantFiled: August 26, 1986Date of Patent: March 28, 1989Assignee: Technicon Instruments CorporationInventors: Shyun-long Yun, Luis P. Leon, Syed I. Ahmad
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Patent number: 4814271Abstract: The present invention relates to new chromogenic amino acid esters and peptide esters of hydroxyisoquinolines and hydroxyquinolines, processes for their preparation and the use of the new esters as substrates for the analytical detection of esterolytic and/or proteolytic enzymes, for example in body fluids, the esters being incorporated into test agents, in particular test strips, in a suitable manner. The new esters are particularly used for the detection of leukocytes, in particular in urine.Type: GrantFiled: August 10, 1987Date of Patent: March 21, 1989Assignee: Miles Inc.Inventors: Herbert Hugl, Hans-Volker Runzheimer, Eugen Schnabel, Gerhard Wolfrum
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Patent number: 4812409Abstract: Hydrolyzable substrates comprise blocked dye moieties which, when cleaved from the substrate during hydrolysis, provide fluorescent dyes having maximum absorptions above about 530 nm and maximum emissions at least about 580 nm at physiological pH. These substrates can be used in analytical determinations of hydrolytic substances including hydrolytic enzymes or biological cells containing such enzymes.Type: GrantFiled: January 31, 1986Date of Patent: March 14, 1989Assignee: Eastman Kodak CompanyInventors: Bruce E. Babb, Robert T. Belly, Patricia M. Scensny
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Patent number: 4810631Abstract: A method for immunoassay for a ligand suspected to be present in a fluid includes use of an enzyme, a metal ion catalyst for an indicator reaction and a blocked modulator for the catalyst. Ligand present in the fluid binds to an antiligand. The resulting bound fraction activates the enzyme to unblock the modulator. The free modulator activates or inhibits the catalyst thereby modulating the rate of an indicator reaction between a substrate and a redox reagent. The presence of absence of the ligand in the fluid is indicated by a signal, such as a color change or a rate of color change, consequent to the indicator reaction. The invention includes a kit of materials useful for performing the method of the invention.Type: GrantFiled: May 12, 1986Date of Patent: March 7, 1989Assignee: Becton, Dickinson and CompanyInventors: Michael E. Perlman, Susan A. Evans
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Patent number: 4810636Abstract: Chromogenic acridinone enzyme substrate compounds comprising 7-hydroxy-9H-acridin-2-one chromogens derivatized at the 7-hydroxy-position with an enzymatically-cleavable group and disubstituted at the 9-position with alkyl or aryl groups, which can be the same or different, preferably lower alkyl or phenyl, respectively, or together form a cyclohexa-2,5-diene-4-one residue or a 4-hydroxycycloxhexyl residue, and 7-hydroxy-1,3-dihalo-9,9-dimethyl-acridin-2-one intermediates useful for the preparation of the novel chromogenic acridinone enzyme substrate compounds and methods therefor.Type: GrantFiled: November 20, 1987Date of Patent: March 7, 1989Assignee: Miles Inc.Inventor: Paul F. Corey
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Patent number: 4806469Abstract: Lipase activity is determined in an improved process for determining the activity thereof by providing a triglyceride imbibed or absorbed in a triglyceride swellable triglyceride insoluble polymer having a predetermined particle size.Type: GrantFiled: March 20, 1985Date of Patent: February 21, 1989Assignee: The Dow Chemical CompanyInventor: Daniel H. Haigh
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Patent number: 4806423Abstract: The present invention relates to new chromogenic amino acid esters and peptide esters of hydroxybenzo(iso)thiazoles and hydroxybenzopyrazoles and the use of the new esters as substrates for the analytical detection of esterolytic and/or proteolytic enzymes, for example in body fluids, the esters being incorporated into test agents, in particular test strips, in a suitable manner. The new esters are preferably used for the detection of leukocytes, in particular in urine.Type: GrantFiled: August 27, 1987Date of Patent: February 21, 1989Assignee: Miles Inc.Inventors: Herbert Hugl, Eugen Schnabel
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Patent number: 4803156Abstract: A reagent for an ELISA determination of an antibody, the reagent comprising a peptide covalently linked to beta-lactamase. The reagent can be used in the following method to detect antibodies in a sample which involvesa. contacting the sample with protein A linked to a solid support,b. incubating the sample-protein A linked to the solid support,c. washing the incubated sample-protein A linked to the solid support,d. contacting the washed sample-protein A with the reagent,e. incubating the sample-protein A and reagent,f. washing the incubated sample-protein A-reagent, andg. determining the enzymatic activity of the resultant mass.Type: GrantFiled: September 11, 1985Date of Patent: February 7, 1989Assignees: New York Blood Center, California Institute of TechnologyInventors: Alexander R. Neurath, Stephen B. H. Kent, Nathan Strick
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Patent number: RE33635Abstract: A method for assaying a compound of the formula ##STR1## wherein R.sub.1 is hydroxyl or amino, or hydrogen if at least one of R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 is hydroxyl or amino, and R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are hydrogen, halogen, lower alkyl, lower alkoxy, amino, substituted amino, hydroxy, carboxyl or sulfo, or R.sub.5 and R.sub.6 together form a ring, comprises establishing a reaction system containing the compound to be assayed and a coupler and an enzyme capable of consuming oxygen and generating a pigment in the presence of the compound and the coupler. A detectable change in the reaction system is measured, to assay the compound in question. The measurement can comprise the measurement of consumed oxygen, as by an oxygen electrode. Or the measurement can comprise the measurement of the generated pigment, as by a colorimetric assay at a specific absorption wavelength thereof.Type: GrantFiled: June 6, 1988Date of Patent: July 9, 1991Assignee: Toyo Jozo Kabushiki KaishaInventors: Kunio Matsumoto, Tsutomu Hirata