Polysaccharide, Carrier (e.g., Dextran, Etc.) Patents (Class 436/529)
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Patent number: 5620845Abstract: An immunoassay process is provided for the detection of a target antigen in a fluid sample where an admixture of the target antigen and a labeled capture reagent against the target antigen is contacted by a solid polymeric carrier having bound to a portion of its surface a capture reagent against the target antigen and visual determination of a change in color of the bound labeled reaction product on the surface of the solid carrier member serves to readily detect the presence of the target antigen.Type: GrantFiled: September 14, 1994Date of Patent: April 15, 1997Assignee: Ampcor, Inc.Inventors: Martin Gould, Sudhakar Vulimiri
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Patent number: 5605806Abstract: The present invention provides a reagent for assaying an endotoxin which comprises limulus amoebocyte lysate and an antibody to (1 .fwdarw. 3)-.beta.-D-glucan sensitive factor or a reagent which comprises a lysate substantially free from (1 .fwdarw. 3)-.beta.-D-glucan sensitive factor. The reagent of the present invention makes it possible to assay an endotoxin originating from gram-negative bacteria contained in a biological sample such as blood, urine and cerebrospinal fluid at an extremely high sensitivity without being affected by (1 .fwdarw. 3)-.beta.-D-glucan.Type: GrantFiled: April 24, 1995Date of Patent: February 25, 1997Assignee: Seikagaku Kogyo Kabushiki Kaisha (Seikagaku Corporation)Inventors: Shigenori Tanaka, Hiroshi Tamura
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Patent number: 5591646Abstract: Method and apparatus for simple and rapid preparation of reusable, addressable surface-immobilized arrays of biomolecules (libraries) used for screening for interaction with any biologically significant target. A special plate having on its surface a plurality of discreet functionalized substrate areas, typically in arrays of 10.times.10 to 400.times.400, is provided for chemical synthesis or bonding thereon of desired families of biomolecules (e.g. peptides, DNA, RNA, oligosaccharides). In the case of peptides, such as hexapeptides, the resulting permanently hexapeptide-loaded plate is a reusable Addressable Synthetic Peptide Combinatorial Library (ASPCL), in which 1 to 3 (typically two) of the positions in the sequence are uniquely identified by the address location. Plate embodiments include substrates of physically bonded (e.g.Type: GrantFiled: September 2, 1992Date of Patent: January 7, 1997Assignee: Arris PharmaceuticalInventors: Derek Hudson, Charles R. Johnson, Lutz Giebel
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Patent number: 5587291Abstract: Method for the quantitative determination of plasmin-.alpha.2-antiplasmin complexes, using a specific monoclonal antibody directed against the neoantigene in the plasmin-.alpha.2-antiplasmin complex, and use of such a method of determining PAP-complexes in plasma and serum to assess changes in the fibrinolytic potential.Type: GrantFiled: December 10, 1993Date of Patent: December 24, 1996Assignee: Berbi Gesellschaft m.b.H.Inventor: Bernd Binder
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Patent number: 5587467Abstract: Polysaccharide derivative molecules are crosslinked exclusively among themselves on a support such as silica gel with the use of a polyfunctional crosslinking agent to immobilize the polysaccharide derivative on the support. The separating agent for optical isomers produced by the method has a high solvent resistance and, therefore, is most suitable as a separating agent for optical resolution.Type: GrantFiled: January 11, 1995Date of Patent: December 24, 1996Assignee: Daicel Chemical Industries, Ltd.Inventors: Tatsushi Murakami, Akito Ichida
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Patent number: 5585275Abstract: Method and apparatus for simple and rapid preparation of reusable, addressable surface-immobilized arrays of biomolecules (libraries) used for screening for interaction with any biologically significant target. A special plate having on or in its surface a plurality of discreet functionalized substrate areas, typically in arrays of 10.times.10 to 400.times.400, is provided for chemical synthesis or bonding thereon of desired families of biomolecules (e.g. peptides, DNA, RNA, oligosaccharides). In the case of peptides, such as hexapeptides, the resulting permanently hexapeptide-loaded plate is a reusable Addressable Synthetic Peptide Combinatorial Library (ASPCL), in which 1 to 3 (typically two) of the positions in the sequence are uniquely identified by the address location. The preferred plate embodiment employs an HPMP wink of porous polyolefin removably received in holes in the plate. A unique multi-slot block assembly is used to prepare the ASPCLs.Type: GrantFiled: June 18, 1993Date of Patent: December 17, 1996Assignee: Arris Pharmaceutical CorporationInventors: Derek Hudson, Charles R. Johnson, Lutz Giebel
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Patent number: 5583054Abstract: The present invention provides a method for determining the presence of a class of an antibody in a biological sample. In this method, a first reagent including insoluble particles having an antigen to the antibody immobilized on the surface thereof, and a second reagent including insoluble magnetic particles having immobilized on the surface thereof a substance particularly reactive to a specific immunoglobulin class, is reacted with the sample under conditions to promote agglutination of the first and second reagents with the antibody. The unreacted second reagent and the agglutinate are separated from the unreacted first reagent by application of a magnetic field. Then the amount of unreacted first reagent is determined.Type: GrantFiled: September 26, 1994Date of Patent: December 10, 1996Assignee: Mitsubishi Kasei CorporationInventors: Michio Ito, Minoru Ogura, Hideki Kohno
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Patent number: 5576220Abstract: The invention relates to methods and systems of unhindered construction and display of tethered organic ligand molecules, and more particularly to preparation and use of thin film, substantially non-crosslinked hydrophilic polar multi-functionalized polymers (HPMPs) anchored to a variety of functionalized substrates so that the HPMP forms a thin film matrix layer providing a unique highly hydrated, high dielectric environment equivalent to an aqueous solution, for affinity binding of Ligands (L) to Tagged Target Molecules (TTMs). Ligands, and especially MER.sub.n ligand libraries such as peptide libraries, are singly tethered to the HPMP by a "permanent" strong covalent bond so that subsequent displacement of the TTM does not also displace the ligand from the HPMP, thereby making the HPMP tethered Ligand library reusable. The HPMP thin film is on the order of 200-2000 .ANG.Type: GrantFiled: February 19, 1993Date of Patent: November 19, 1996Assignee: Arris Pharmaceutical CorporationInventors: Derek Hudson, Charles R. Johnson, Michael J. Ross, Kevin R. Shoemaker, Robert T. Cass, Lutz B. Giebel
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Patent number: 5571726Abstract: A method and test kit useful in a wide variety of immunoassay systems. A method of producing metal sol reagents containing metal sol particles of a preselected size is provided. A metal containing solution is reduced under optimized pH conditions to produce metal sol particles of a preselected size, the particles are coated with a coupling compound and then bound with at least one selected immunochemically reactive component. Particles having different immunochemical specificities are also mixed to produce reagents having multiple selected immunochemical specificities.Type: GrantFiled: May 19, 1995Date of Patent: November 5, 1996Assignee: Ortho Diagnostic Systems, Inc.Inventors: Houston G. Brooks, Jr., Chi-Deu Chang, Utpal R. Chakraborty, Henry A. Graham, Jr., Lloyd L. Hollenbeck, Jr., Sharon R. Lawler, Jennifer Nasser, Ernest G. Schutt, Albert Venturini
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Patent number: 5569589Abstract: An immunoassay element for quantitatively analyzing a ligand by determining the change in enzymatic activity caused by a reaction between the ligand, a linked product of the ligand and a high molecular weight compound and an enzyme-labelled antibody. The immunoassay element comprises a substrate layer containing a non-diffusible substrate which forms a diffusible material in the presence of the enzyme, and a reagent layer containing a fragmenting enzyme for further fragmenting the non-difussible material. Also provided is a process for quantitatively analyzing a ligand contained in a sample by the use of the immunoassay element.Type: GrantFiled: December 7, 1993Date of Patent: October 29, 1996Assignees: Fuji Photo Film Co., Ltd., Fujirebio Inc.Inventors: Toshikage Hiraoka, Tetsuji Tanimoto, Yoshihiko Makino, Tadashi Ninomiya, Naofumi Hora, Yoshihiro Ashihara, Yukio Sudo, Toshihiro Mori
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Patent number: 5565324Abstract: Encoded combinatorial chemistry is provided, where sequential synthetic schemes are recorded using organic molecules, which define choice of reactant, and stage, as the same or different bit of information. Various products can be produced in the multi-stage synthesis, such as oligomers and synthetic non-repetitive organic molecules. Conveniently, nested families of compounds can be employed as identifiers, where number and/or position of a substituent define the choice. Alternatively, detectable functionalities may be employed, such as radioisotopes, fluorescers, halogens, and the like, where presence and ratios of two different groups can be used to define stage or choice. Particularly, pluralities of identifiers may be used to provide a binary or higher code, so as to define a plurality of choices with only a few detachable tags. The particles may be screened for a characteristic of interest, particularly binding affinity, where the products may be detached from the particle or retained on the particle.Type: GrantFiled: April 13, 1994Date of Patent: October 15, 1996Assignees: The Trustees of Columbia University in the City of New York, Cold Spring Harbor LaboratoryInventors: W. Clark Still, Michael H. Wigler, Michael H. J. Ohlmeyer, Lawrence W. Dillard, John C. Reader
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Patent number: 5565326Abstract: Specific binding ligands can be detected with an assay which utilizes an immobilized receptor for the ligand, a reporter enzyme, an inhibitor antibody and an anti-inhibitor antibody. Both antibodies are specific for the reporter enzyme. The inhibitor antibody effectively shuts down the activity of the reporter enzyme when it is complexed thereto. The anti-inhibitor antibody binds to the reporter enzyme, does not affect the enzymatic activity, but prevents the binding of the inhibitor enzyme. This assay provides a direct correlation of the target specific binding ligand to the signal generated without the use of separation or wash steps.Type: GrantFiled: May 31, 1994Date of Patent: October 15, 1996Assignee: Johnson & Johnson Clinical Diagnostics, Inc.Inventors: John L. Daiss, Kevin M. Gorman, Carolyn R. Hinchman
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Patent number: 5563056Abstract: A chemical specie is immobilized in a three dimensional, crosslinked matrix by bringing together in covalent bonding proximity a desired chemical specie and a polymeric coupling compound such as a photoderivatized polymer having at least two latent photochemical reactive groups per molecule, each latent reactive group being capable when activated of covalently bonding to another coupling compound molecule or to the chemical specie. The chemical specie may be a protein, carbohydrate, nucleic acid or lipid, and desirably is free of latent reactive groups that are activated upon activation of the latent reactive groups of the coupling compound. The latent reactive groups are simultaneously activated to cause formation via covalent bonding of a three-dimensional molecular network in which molecules of the chemical specie are covalently bonded to molecules of the coupling compound, and molecules of the coupling compound are covalently bonded to each other.Type: GrantFiled: February 27, 1995Date of Patent: October 8, 1996Assignee: BSI CorporationInventors: Dale G. Swan, Mark W. Josephson, Melvin J. Swanson
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Patent number: 5561069Abstract: An improved surface plasmon resonance detector, capable of recovering a desired eluted ligate, permits the isolation and characterization of novel ligates and ligands.Type: GrantFiled: November 21, 1994Date of Patent: October 1, 1996Assignee: SmithKline Beecham CorporationInventors: Michael Brigham-Burke, Daniel J. O'Shannessy
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Patent number: 5558839Abstract: An apparatus for performing immunoassays employs a microtiter tray having wells coated with a specific binding partner in conjunction with an array of magnets disposed below the tray. A device for providing relative circular motion of the tray and magnetic array so as to provide a magnet field to the well walls for attracting magnetic particles and subsequent movement of the magnetic field.Type: GrantFiled: March 14, 1994Date of Patent: September 24, 1996Assignee: Pasteur Sanofi DiagnosticInventors: Claude Matte, Anne Muller
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Patent number: 5556743Abstract: A dye is covalently bound to a polymeric film, especially a polyhydric polymer, for assays and other purposes. The dye may be one which, when it comes into contact with hydrogen peroxide, changes color to indicate the presence of hydrogen peroxide. This dyed film may be used in qualitative or quantitative assays. This method chemically immobilizes dyes on support matrices with much higher yields of immobilized dye than has heretofore been possible. The covalently immobilized dye may be immobilized on solid matrix particles and combined with a free-flowing dye component to form a two component dye system. By combining a dyed film-former with a film-opener, the amount of dye available for assay is greatly enhanced. This provides a dye system which can be used to detect and measure quantitatively, accurately and precisely high levels of hydrogen peroxide. These high levels of hydrogen peroxide may result from the enzyme-mediated decomposition of various analytes from undiluted whole blood samples.Type: GrantFiled: May 17, 1994Date of Patent: September 17, 1996Assignee: ActiMed Laboratories, Inc.Inventors: David J. Gibboni, Wai T. Law
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Patent number: 5552288Abstract: A moist unitary non-laminar chromogen agar color reactive test sheet for use in a simplified enzyme-linked immunosorbent assay (ELISA) for the diagnosis of viral, fungal, bacterial and parasitic diseases. The diagnostic test is designed for use in non-laboratory settings where the usual equipment and supplies, including running water, may not be available. The test sheet comprises chromogen agar paper (CAP) impregnated with an enzyme substrate, and electron acceptor, if needed, in agar. It is applied over a conjugate in the form of a species specific enzyme-linked anti-immunoglobulin bound to an antibody-antigen coating of a previously prepared test plate. After incubation to cause a color reaction, the results are read and interpreted in comparison with known standards.Type: GrantFiled: March 10, 1995Date of Patent: September 3, 1996Inventors: Dale A. Christensen, Peter Nash
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Patent number: 5552268Abstract: A non-invasive method to measure total body tissue iron stores comprising recovering iron released from total ferritin contained in a body fluid sample derived from a host, measuring the ferritin-iron in the total ferritin and thereby determining total body tissue iron stores. Such an assay is utilized for diagnosing negative iron balance as well as positive iron balance, wherein the latter promotes cancer, coronary artery disease, atherosclerosis, and hepatic failure among other diseases, as well as the susceptibility to such diseases.Type: GrantFiled: August 8, 1995Date of Patent: September 3, 1996Assignee: Quixote Associates, Inc.Inventors: Victor D. Herbert, Spencer Shaw, Elizabeth Jayatilleke
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Patent number: 5543332Abstract: Water soluble reagents are claimed, comprising a water-soluble polymeric carrier molecule having attached thereto more than one connecting moiety wherein the connecting moiety is derived from divinyl sulfone, and wherein each connecting moiety is attached to a reactive functional group on the polymeric molecule, and wherein the reagents are capable of reaction with a molecular species having a functional group which is reactive towards the terminal vinyl group of the more than one connecting moiety and the molecular species is selected from the group consisting of labelling species, marking species, and targeting species.Type: GrantFiled: November 8, 1991Date of Patent: August 6, 1996Assignee: Immunodex K/SInventors: Allan O. F. Lihme, Thomas Boenisch
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Patent number: 5536644Abstract: A method is disclosed for separating a substance from a liquid medium. The method comprises combining the liquid medium containing the substance with magnetic particles under conditions for non-specific chemical binding of the magnetic particles. Thereafter, the medium is subjected to a magnetic field gradient to separate the particles from the medium. The preferred non-specific binding is achieved as the result of charge interactions between the particles usually by means of a polyionic reagent. The method of the invention has particular application to the separation of cells and microorganisms from aqueous suspensions and also to the determination of an analyte in a sample suspected of containing the analyte. The analyte is a member of a specific binding pair (sbp). The sample is combined in an assay medium with magnetic particles and a sbp member complementary to the analyte.Type: GrantFiled: December 9, 1994Date of Patent: July 16, 1996Assignee: Behringwerke AGInventors: Edwin F. Ullman, Vartan E. Ghazarossian, Nurith Kurn, Litai Weng
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Patent number: 5527681Abstract: A synthetic strategy for the creation of large scale chemical diversity is claimed. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis of an array of polymers that are based on a target polymer. The array includes systematically substituted versions of the target polymer.Type: GrantFiled: November 5, 1992Date of Patent: June 18, 1996Assignee: Affymax Technologies N.V.Inventor: Christopher P. Holmes
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Patent number: 5527713Abstract: The invention describes the use of novel aminodextran compounds containing about 5-20% by weight amine groups to bind a plurality of monoclonal antibodies. The resulting antibody-aminodextran compounds may be used to induce the activation and proliferation of selected mammalian cells. Specific examples are given using an anti-CD3 monoclonal antibody conjugated two aminodextrans containing about 5% and 16%, respectively, by weight amine groups as an agent for inducing the activation and proliferation of T cells.Type: GrantFiled: July 19, 1995Date of Patent: June 18, 1996Assignee: Coulter CorporationInventors: Wade E. Bolton, John A. Maples, Olavi Siiman, Norma S. Kenyon, Cynthia G. Healy
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Patent number: 5501949Abstract: An immunoassay method for the detection or quantitation of an analyte suspected of being in a solution comprising: (a) combining said specimen, a first binding component, insoluble particles, and second binding component labelled with a signal generating material in a solid phase retention and separation apparatus having a sufficient pore size such that said particles are trapped within said filter yet permitting rapid passage of fluid therethrough in such a manner that an immunological reaction occurs if analyte is present in said specimen, resulting in the formation of an immunocomplex of insolublized first binding component:analyte:second labelled binding component on or within said filter means; (b) separating bound from unbound material; and (c) determining the presence and/or amount of signal produced which is correlative with the amount of analyte present in the solution.Type: GrantFiled: August 15, 1994Date of Patent: March 26, 1996Assignee: Murex Diagnostics CorporationInventor: David L. Marshall
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Patent number: 5492840Abstract: Methods for functionalizing sensing surfaces to be used in systems for measuring simultaneously several properties of one biomolecule as well as for simultaneously measuring the concentrations of a plurality of biomolecules in a sample. The invention furthermore also relates to sensor units containing such surfaces, to the use thereof for surface characterization of biomolecules, and to a reagent kit for functionalization of sensing surfaces.Type: GrantFiled: May 10, 1991Date of Patent: February 20, 1996Assignee: Pharmacia Biosensor ABInventors: Magnus Malmqvist, Robert Karlsson, Inger Ronnberg
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Patent number: 5491096Abstract: A method and device for detecting the presence of a suspected antigen in a sample whereby the antigen is trapped using affinity chromatography and the remaining eluant is differentially analyzed against a parallel processed control. The sample is first chromatographically segregated into distinct zones and the resulting eluant is split into two streams. One stream is contacted with a solid phase having immobilized capture ligands specific to the antigen of interest. The other stream is passed through a similar solid phase where the capture ligands have been omitted. The two streams are then differentially analyzed, for example, with ultraviolet light absorption.Type: GrantFiled: December 27, 1993Date of Patent: February 13, 1996Assignee: Eli Lilly and CompanyInventor: J. Richard Sportsman
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Patent number: 5486479Abstract: The invention relates to immunoassay reagents that are both sensitive and specific and which require no sample pretreatment. The invention reagents are particularly useful for assaying digoxin concentrations in patient sera. More particularly, the invention relates to methods and kits comprising (A) an immunoreactant immobilized on a support; and, (B) a buffer agent comprising (i) a buffering agent, (ii) sodium chloride, (iii) choline chloride, (iv) a polysaccharide, (v) fatty-acid-free serum albumin, and (vi) a non-specific reaction suppressor of the formula: ##STR1## wherein X is --NH--(CO)--NH--, --NH--(CS)--NH--, or --N.dbd.C.dbd.N--, R.sub.1 and R.sub.2, which may be the same or different, are C.sub.1 -C.sub.5 linear or branched alkyl groups, or R.sub.1 and R.sub.2, together with nitrogen, is ##STR2## or the metho-p-toluenesulfonate salt thereof, Y, which may be the same or different, is any of H, OH and halogen,R.sub.3 is --NR.sub.1 R.sub.2, --NH.sub.Type: GrantFiled: May 2, 1994Date of Patent: January 23, 1996Assignee: Mitsubishi Chemical CorporationInventors: Michio Ito, Satoshi Sugawa, Atsushi Yanagida
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Patent number: 5470713Abstract: The method of measuring analytes in biological fluids is disclosed wherein a specific binder to a given analyte is covalently immobilized onto a solid support to which a labeled analyte is pre-reacted and stabilized to form a binder-labeled analyte complex. A sample is contacted with said immobilized complex wherein an analyte in the sample, if present, competes with the labeled analyte bound to the immobilized binder for binding sites on said binder thus displacing a given amount of the labeled analyte which is directly proportional to the amount of analyte present in the sample. The affinity of the labeled analyte to the analyte's specific binder is lower than the affinity of the unlabeled analyte to the same binder.Type: GrantFiled: May 28, 1993Date of Patent: November 28, 1995Assignee: Diagnostic Products CorporationInventors: A. Said El Shami, Christopher W. Hand, Susan A. Miller, Robert A. Moore
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Patent number: 5466609Abstract: The invention relates generally to colloidal particle having a core material and a gelatin/aminodextran coating with pendent functional groups attached thereto. Biological substances or molecules, especially monoclonal antibodies, may be attached to said particles. The monoclonal antibody containing particles are useful in a variety of positive and negative biological assays.Type: GrantFiled: October 29, 1992Date of Patent: November 14, 1995Assignee: Coulter CorporationInventors: Olavi Siiman, Alexander Burshteyn, Ravinder K. Gupta
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Patent number: 5462991Abstract: Disclosed are pH dyes containing a suitable compatible substituent which permits binding of the dye to a solid support. Also disclosed are methods for synthesizing such dyes prior to their coupling to the solid supports.Type: GrantFiled: August 22, 1994Date of Patent: October 31, 1995Inventors: Karla M. Robotti, Carl A. Myerholtz
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Patent number: 5460940Abstract: Methods and cards for detecting an antigen or antibody in a fluid sample are disclosed. The fluid sample is added to a microreaction vessel containing a slurry suspension of inert particles and a binding partner to the antigen or antibody to be determined. The fluid sample is added to the micro reaction vessel, with one of the antigen and antibody binding partners being carrier bound. The vessel contents are centrifuged, to cause the binding partners to contact each other to form an optically detectable binding complex. The location of the optically detectable complex is observed to determine the presence of the antibody.Type: GrantFiled: January 4, 1995Date of Patent: October 24, 1995Assignee: Stiftung fur diagnostische ForschungInventors: Lapierre Yves, Dieter Josef, Jean Adam, Susanne Greber-Widmer
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Patent number: 5459041Abstract: Antigenic compositions are disclosed for use in diagnostic kits and the like for detecting the presence of antibodies specific for Campylobacter pylori, bacteria often associated with the occurrence of Type B gastritis and peptic ulcer disease. Samples of bodily fluids, for instance, may be contacted with immobilized antigen which is then washed and tested for the occurrence of significant levels of antigen/antibody complex. Levels exceeding a predetermined positive threshold are indicative of antibodies to Campylobacter pylori in the sample tested. Kits employing the antigenic compositions of the invention preferably include means for detecting the antigen/antibody complex such as materials and reagents for conducting an enzyme-linked immunosorbent assay, Western blot technique, liposome-based assay or other known detection tests.Type: GrantFiled: February 18, 1988Date of Patent: October 17, 1995Assignee: Enteric Research Laboratories, Inc.Inventors: Martin J. Blaser, Guillermo I. Perez-Perez
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Patent number: 5459078Abstract: The present invention includes novel digoxin assays employing a capture reagent, involving a first binding member conjugated to a polymeric anion substance, and a solid phase material containing a reaction site comprising a polymeric cation substance having a nitrogen content of at least about two percent. 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.Type: GrantFiled: June 9, 1993Date of Patent: October 17, 1995Assignee: Abbott LaboratoriesInventors: Steven Kline, Yi-Her Jou, Stephen D. Stroupe, Janina Adamczyk, Daniel S. Berry, Rosario M. Fico, James J. Markese
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Patent number: 5443976Abstract: Antivenoms to snake, spider, scorpion and jelly fish venoms are produced for the treatment of humans and animals, and for analytical use. The antivenom is purified with an antigen matrix containing a single whole venom or a plurality of whole venoms covalently attached to an insoluble support such as aldehyde-activated agarose. Preferably, the whole venoms forming the plurality of whole venoms are selected from the four whole venoms from C. atrox, B. atrox, C. adamanteus and C. durissus terrificus. A combination of immobilized C. atrox and C. durissus terrificus whole venoms can substantially purify antivenom reactive with all four venoms. The antivenom can be horse or avian such as chicken antivenom.Type: GrantFiled: July 14, 1994Date of Patent: August 22, 1995Inventor: Sean B. Carroll
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Patent number: 5439829Abstract: A chelating agent is covalently bonded to a biologically active molecule such as an enzyme or antibody, the biologically active molecule is contacted with a support containing a bound transition metal ion whereby the metal ion is chelated by the chelating agent and the oxidation state of the metal ion is changed by treatment with an oxidizing or a reducing agent to provide a kinetically inert: oxidation state to immobilize the biologically active molecule on the support. The transition metal ion is preferably Co(II), Cr(II) or Ru(III) and the oxidation state of the metal ion is changed to Co(III), Cr(III) or Ru(II), respectively. The chelating agent can be iminodiacetic acid, nitrilotriacetic acid, terpyridine, bipyridine, triethylenetetraamine, biethylenetriamine, 1,4,7-triazacyclonane or a chelating peptide. Certain chelating agents can immobilize more than one biologically active molecule at a metal ion site on the support.Type: GrantFiled: January 24, 1992Date of Patent: August 8, 1995Assignees: Eli Lilly and Company, Hybritech IncorporatedInventors: Leslie D. Anderson, James A. Cook, Gary S. David, Susan M. Hochschwender, Mary S. Kasher, Michele C. Smith, Willem P. C. Stemmer
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Patent number: 5434054Abstract: Subject matter of the invention is a new method of detecting a substance with hydrolase activity in a sample, characterized in that the sample is brought into contact with an indicator enzyme, which is covalently bound to an insoluble carrier material and can be rendered soluble by the hydrolase activity, in that the cleaved off indicator is separated and in that its enzymatic activity is determined and test means for its implementation.Type: GrantFiled: May 27, 1993Date of Patent: July 18, 1995Assignee: Boehringer Mannheim GmbHInventors: Klaus Pollmann, Helmut Freitag, Anselm Rothe
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Patent number: 5376551Abstract: Apparatus for studying the interaction of first and second molecules in a test solution containing fluorescently labeled molecules in addition to the first and second molecules, with the first molecules and the fluorescently labeled molecules being capable of binding with the second molecules. The apparatus comprises a flow channel having opposite, spaced apart walls, with at least one of the walls or a portion thereof being translucent or transparent. A porous matrix is retained in a fixed position between the walls of the flow channel and in direct contact with a translucent or transparent portion of the walls of the flow channel. A test solution flows through the flow channel and around the porous matrix so as to be in contact with the porous matrix.Type: GrantFiled: June 21, 1993Date of Patent: December 27, 1994Assignee: University of Utah Research FoundationInventor: Doju Yoshikami
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Patent number: 5372820Abstract: This granular material consists of a granular porous support bearing negative or positive charges, coated on its surface with a first layer of impregnation with a hydrophilic polymer bearing charges opposite to those of the support, the quantity of said charges present on said polymer being substantially equal to that of the charges present at the surface of the support; and another layer, bound to the first by irreversible chemical coupling, of another hydrophilic polymer which is functional, namely bearing groups endowing said functional hydrophilic polymer with a specific but reversible affinity for at least one biological substance. Among the applications of this material, there are mentioned the separation and purification of antithrombin III and coagulation factors (factors II, VII, VIII, IX, X), and separation of activated coagulation factors (activated factor II, activated factor IX, activated factor X) in solutions containing said non-activated factors.Type: GrantFiled: October 14, 1992Date of Patent: December 13, 1994Assignee: Therapeutiques Subtitutives Groupement D'Interet PublicInventors: Jacqueline Jozefonvicz nee Dorgebray, Xavier-Francois Santarelli, Daniel A. Muller
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Patent number: 5338689Abstract: A method of detecting target antibodies or antigens by reaction with specific binding partners thereto is disclosed. One of the target or the binding partner is bound to a carrier, and the other is unbound. The complex between the target and the binding partner, with one being carrier-bound, forms an optically detectable binding complex. A microreaction vessel having an upper portion, a transition portion and a lower portion is utilized, wherein the upper portion has a greater diameter or width than the lower portion, and the transition portion is situated between the upper portion and the lower portion, and is funnel shaped. The microreaction vessel contains a slurry or suspension of inert particles, and unbound target or binding partner thereto. A solution of the carrier bound target or binding partner thereto is added to the vessel, which is then centrifuged to produce an optical determination of the target.Type: GrantFiled: October 30, 1992Date of Patent: August 16, 1994Assignee: Stiftung fur diagnostische ForschungInventors: Lapierre Yves, Dieter Josef, Jean Adam, Susanne Greber-Widmer
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Patent number: 5326692Abstract: The invention relates to microparticles incorporating a series of two or more fluorescent dyes having overlapping excitation and emission spectra allowing efficient energy transfer from the excitation wavelength of the first dye in the series, transfer through the dyes in the series and re-emitted as an optical signal at the emission wavelength of last dye in the series, resulting in a desired effective Stokes shift which is controlled through selection of appropriate dyes.Type: GrantFiled: May 13, 1992Date of Patent: July 5, 1994Assignee: Molecular Probes, Inc.Inventors: John M. Brinkley, Richard P. Haugland, Victoria L. Singer
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Patent number: 5304498Abstract: A method for determining the amount of free ligand in a test ample where the ligand is also present bound to one or more endogenous receptors, comprising combining the test sample, ligand receptor and unlabelled, differential binding ligand analogue, incubating to permit the free ligand and unlabelled, differential binding ligand analogue to compete for the ligand receptor separating the ligand analogue, determining the amount of ligand receptor bound to the ligand or to the ligand analogue, and correlating the amount of bound ligand receptor to the amount of free ligand present in the test sample.Type: GrantFiled: May 28, 1991Date of Patent: April 19, 1994Inventor: Roger P. Ekins
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Patent number: 5296356Abstract: The invention concerns a method for the detection of an analyte in a sample liquid by an enzyme-immunoassay in which an enzyme-labelled compound is partitioned between a solid and a liquid phase and the amount of enzyme label in the liquid phase outside the solid phase is determined as a measure of the concentration of the analyte. The measurement is carried out in a non-porous molding having the liquid phase contained therein in contact with the solid phase. The method is particularly suitable for carrying out in a cuvette which can be filled via the porous matrix or on a test strip having a space in contact with the solid phase.Type: GrantFiled: December 12, 1990Date of Patent: March 22, 1994Assignee: Boehringer Mannheim GmbHInventors: Dieter Mangold, Ulrich Traeger, Hans Lange
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Patent number: 5294536Abstract: A compound represented by the formula ##STR1## wherein X is a spacer group. The compound is useful for conjugating a compound having an alcohol group or an amine group to a compound having a thiol group. The compound can be used to conjugate a biologically active group such as an antigen to a protein such as an enzyme to provide an enzyme-labeled antigen for use in enzyme-amplified immunoassay methods for analytes or metabolites in sample fluids. The compound can also be used to immobilize a material such as a protein to a solid support.Type: GrantFiled: April 23, 1992Date of Patent: March 15, 1994Assignee: PB Diagnostic Systems, Inc.Inventor: Paul S. Palumbo
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Patent number: 5268306Abstract: A specific binding pair is bound to an insoluble carrier for use in determining an analyte such as in an immunoassay. The carrier is coated with a first polymer containing a protein polymer having a molecular weight of at least about 20,000 and molecules of a first member of a specific binding pair. A second polymer containing a second member of the specific binding pair is bound to the first member on the carrier by binding of the first and second members of the specific binding pair. The first polymer is preferably more hydrophobic than the second polymer. The protein polymer can be prepared by cross-linking hydrophobic protein molecules of 10,000 to 700,000 molecular weight with a bifunctional or polyfunctional compound to obtain a protein polymer of 200,000 to 20,000,000 molecular weight. The second polymer can be the second member of the specific binding pair or the second member cross-linked with a linker or the second member cross-linked to a hydrophobic protein.Type: GrantFiled: December 23, 1991Date of Patent: December 7, 1993Assignee: Boehringer Mannheim GmbHInventors: Michael Berger, Arno Deger, Josef Maier
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Patent number: 5266471Abstract: A modified solid carrier is used to covalently immobilize biomolecules such as proteins. The carrier is based on well-known matrix materials modified to have covalently bound functional groups of formula I ##STR1## that are suitable for covalent immobilization, where A is a spacer group; X is O, S, or NH and n is 0 or 1. The modified solid carrier is prepared by reacting ammonia with glycidyl groups of a carrier to form .alpha.-hydroxy-.beta.-amino groups, reacting these groups with 2,4,6-trichloro-s-triazine to form an N-triazinyl group-containing carrier, reacting this carrier with ammonia and reacting the resultant carrier with 2,4,6-trichloro-s-triazine.Type: GrantFiled: February 25, 1991Date of Patent: November 30, 1993Assignee: ROHMInventor: Stefan Schmitt
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Patent number: 5252496Abstract: Specific binding labels are described which comprise carbon black treated with dextran to which various specific binding reagents are bound by way of fluorescein isothiocyanate.Type: GrantFiled: December 18, 1989Date of Patent: October 12, 1993Assignee: Princeton Biomeditech CorporationInventors: Jemo Kang, Byungwoo Youn, Young H. Oh
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Patent number: 5250443Abstract: A multilayer diagnostic assay element wherein glyoxyl agarose, an aldehyde group - derivatized agarose, is utilized in one or more layers of the element. In a preferred embodiment the glyoxyl agarose is used to immobilize biological species such as a protein in a layer of the element.Type: GrantFiled: February 12, 1992Date of Patent: October 5, 1993Assignee: PB Diagnostic Systems, Inc.Inventors: Edward P. Lindholm, Ernest J. Yamartino, Jr.
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Patent number: 5244663Abstract: Allergens are contained in strictly controlled and reproducible amounts on solid supports to provide a progressive release of the allergen perlingually and sublingually. The compositions are prepared by dissolving an allergen in a polar solvent to obtain a mother solution; preparing dilutions of different predetermined concentrations; fractionating each of the dilutions into sub-dilutions; and impregnating a pharmaceutically acceptable solid support with each sub-dilution, each impregnation step being followed by drying in forced, dried air at a temperature not greater than 30.degree. C.; and applying a protective coating onto the composition.Type: GrantFiled: February 14, 1991Date of Patent: September 14, 1993Assignee: MedibrevexInventors: Georges Bruttmann, Patrick Pedrali, Serge Robert
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Patent number: 5231035Abstract: Methods for determining the presence of a first ligand, preferably a hapten, in a sample suspected to contain the first ligand are provided, along with reagent systems and apparatus suitable for performing the methods. The methods depend upon a color visualization indicating the presence or absence of the first ligand in the sample. Preferred methods comprise contacting the sample with a reagent system which comprises: (1) colored particles which bear on their surface a second ligand which may be the same as or different than the first ligand; and (2) an amount of a receptor which is specific for the first ligand and the second ligand, wherein the amount is sufficient to stabilize the particles. The methods further comprise passing the contacted sample and reagent system through a filter, and then analyzing the color of the filtrate. The presence of ligand in the sample is established where the color of the filtrate is substantially different from the color of the ligand-bearing particles.Type: GrantFiled: January 11, 1991Date of Patent: July 27, 1993Assignee: Akers Research CorporationInventor: Raymond F. Akers, Jr.
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Patent number: 5219926Abstract: A process for covalently bonding biopolymer, such as protein, to an organic polymer surface coated with hydrophilic nonionic polymer having groups reactive with the biopolymer and having a cloud point in the reaction medium that is at least 5.degree. C. above the temperature at which the coated organic polymer surface is to be used, which comprises reacting biopolymer with the surface in an aqueous reaction medium, at a temperature not less than 5.degree. C. below the cloud point; but not above a temperature at which the biopolymer is deleteriously affected, and preferably not above about 100.degree. C., the product comprises a biopolymer immobilized on a hydrophilic solid surface having a nonionic polymer and a hydrophilic layer, coupled thereto via biopolymer-reactive groups of the nonionic polymer, and accordingly has low spontaneous adsorption of proteins and other biopolymers through electrostatic attraction and/or hydrophobic interaction.Type: GrantFiled: September 13, 1991Date of Patent: June 15, 1993Assignee: Berol Nobel ABInventors: Bjorn Lindman, Martin Malmsten, Krister Holmberg, Carina Andren
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Patent number: 5212299Abstract: Aqueous gel compositions and their use in electrophoresis, and anhydrous compositions useful in the preparation of the aqueous gel compositions.The aqueous gel compositions comprise:A. water,B. at least one di- or tri-hydroxy C.sub.2-4 alkyl ether moiety (preferably glyceryl) substituted agarose, andC. from about 20 to about 400 mM of at least one borate compound per liter of aqueous gel composition.The anhydrous compositions comprise the agarose in powder form and the borate in powder or aqueous solution.Type: GrantFiled: May 10, 1991Date of Patent: May 18, 1993Assignee: FMC CorporationInventor: Joshua D. Smith