Patents Examined by Nancy J. Parsons
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Patent number: 5389523Abstract: A method of immunoanalysis combines immobilized immunochemistry with the technique of flow injection analysis, and employs microscopic spherical structures called liposomes, or lipid vesicles, as carriers of detectable reagents. Liposomes are modified on their surface with analytical reagents, and carry in their internal volume a very large number of fluorescent or electroactive molecules. Aspects of this embodiment of the invention include the chemistry for covalent immobilization of antibody fragments in a specified orientation, the use of liposomes in a flow injection analysis system, and the combination of automated sampling and analysis with reusable immunoreactants. Another aspect of the invention involves the non-covalent binding of liposomes to a receptor for use in a homogeneous assay. In another aspect of the invention the intensity of scattered light is quantitated as a measure of liposome aggregation in response to a concentration-dependent immunospecific reaction.Type: GrantFiled: July 23, 1992Date of Patent: February 14, 1995Assignee: The United States of Americas, as represented by the Secretary of CommerceInventors: Anne L. Plant, Laurie Locascio-Brown, Richard A. Durst
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Patent number: 5372948Abstract: Disclosed are a method and device for performing sequential analytical reactions involving a first dry reagent and a second dry reagent comprised of two or more components having different rates of solubilization. The invention enables one to fully solubilize the components of the second reagent before they are brought into contact with each other to thereby avoid interference with the reaction kinetics which result when one or both of the components are not fully dissolved prior to their being brought into contact. The invention is especially useful in conjunction with immunoassay formats involving latex bound antibodies and polymeric agglutinators.Type: GrantFiled: March 17, 1993Date of Patent: December 13, 1994Assignee: Miles Inc.Inventor: Kin F. Yip
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Patent number: 5358849Abstract: The present invention first provides monoclonal antibodies recognizing membrane phospholipase A.sub.2, namely, monoclonal antibodies PL-49, PL-71, PL-76, and PL-78, hybridomas producing them, methods for producing them, and immunoassays of membrane phospholipase A.sub.2 using them.The immunoassay of PLA.sub.2 M is useful for the diagnosis of articular rheumatism, cancers, and a wide variety of inflammatory states.Type: GrantFiled: April 28, 1993Date of Patent: October 25, 1994Assignee: Shionogi & Co., Ltd.Inventors: Nobuo Yoshida, Misao Ide, Masao Kono, Akiko Kanda
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Patent number: 5356781Abstract: Pancreatic disease can be diagnosed by assaying a patient's body fluid such as serum or urine, for pancreatic activation peptides (PAP) released from zymogens by proteolytic activation. Particularly useful are peptides having C-terminal D.sub.4 K sequences. The method uses polyclonal or monoclonal antibodies generated and selected for C-terminal specificity on PAP so that the tests only report free PAP not parent zymogen. Also described are peptides and antibodies labelled with revealing agents and/or immobilised on solid supports and their use in diagnostic assays and kits. In pancreatic disease the tests distinguish necrotising from oedematous acute pancreatitis and permit severity prediction and monitoring as well as diagnosing chronic pancreatitis in exacerbation.Type: GrantFiled: June 26, 1991Date of Patent: October 18, 1994Assignee: Bioscience International, Inc.Inventors: John Hermon-Taylor, Brian M. Austen
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Patent number: 5344758Abstract: A method for determining whether antiphospholipid antibodies are present in a sample is disclosed. The method comprises contacting the sample with a negatively charged phospholipid and with .beta.-2-glycoprotein-I or a homolog or analog thereof and determining whether any antiphospholipid antibodies have bound to the contacted phospholipid and .beta.-2-glycoprotein-I, wherein detection of binding of antiphospholipid antibodies to the phospholipid and .beta.-2-glycoprotein-I, is indicative that antiphospholipid antibodies are present in the sample.Type: GrantFiled: December 6, 1991Date of Patent: September 6, 1994Assignee: Yamasa Shoyu Kabushiki KaishaInventors: Steven A. Krilis, Hugh P. McNeill, Colin N. Chesterman
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Patent number: 5330895Abstract: Dopamine releasing protein (DARP) is a protein which stimulates release of dopamine from dopaminergic neurons, and is effective at extremely low concentrations. DARP is useful for stimulating vertebrate nervous systems, and for treatment of Parkinson's disease. Antibodies to DARP are useful for inhibiting dopamine release, and for quantifying the concentration of DARP in samples.Type: GrantFiled: September 17, 1992Date of Patent: July 19, 1994Inventors: Victor D. Ramirez, Frank Marcus
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Patent number: 5326696Abstract: Disclosed are immunofluorescence staining methods which increase the likelihood that antibodies expressed by a single B cell selected and sorted by fluorescence activated cell sorting are specific for the antigen of interest, and which also allow selection of B cells expressing antibodies of high affinity for the antigen of interest. The selection for B cells expressing antibodies to specific antigens is increased by labeling B cells with at least two antigen probes, where each antigen probe includes the antigen of interest and is labeled with a different fluorochrome. The positive selection is preferably combined with a negative selection step, in which autofluorescent cells and sticky cells are excluded out. The specificity of sorting of the desired B cells can be further enhanced by staining those antigen-specific B cells which produce the immunoglobulin isotype (typically IgG), with targeting molecules reactive with a B cell marker, such as .gamma.Type: GrantFiled: February 17, 1993Date of Patent: July 5, 1994Assignee: Tanox Biosystems, Inc.Inventor: Tse W. Chang
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Patent number: 5322772Abstract: A competitive protein binding assay for rapamycin and biologically-active metabolites, derivatives and analogues thereof in blood and other biological fluids is disclosed, wherein the binding reagent is a specific rapamycin binding protein either substantially purified from the soluble cytoplasm of target cells of rapamycin action, particularly normal or transformed lymphocytes, freshly collected or in established cell lines, or synthesized by recombinant DNA techniques. Solution phase and solid state assay systems are disclosed.Type: GrantFiled: April 9, 1991Date of Patent: June 21, 1994Assignee: Children's Research InstituteInventor: Steven J. Soldin
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Patent number: 5320943Abstract: A method is provided for detecting T-cell dysfunctions. The method includes detecting an alteration in the level of a protein regulating synthesis of the hexasaccharide NeuNAc.alpha.2.fwdarw.3Gal.beta.1.fwdarw.3(NeuNAc.alpha.2.fwdarw.3Gal.beta .1.fwdarw.4GlcNAc.beta.1.fwdarw.6)GalNAc on leukosialin of T-cells from a subject suspected of having a T-cell dysfunction compared to resting T-cells from a normal individual. The protein regulating synthesis of the hexasaccharide can be core 2 GlcNAc transferase and can be detected by either a change in its amount or activity. Also provided is a method of detecting T-cell dysfunctions which includes detecting an alteration in the level of leukosialin having the hexasaccharide NeuNAc.alpha.2.fwdarw.3Gal.beta.1.fwdarw.3(NeuNAc.alpha.2.fwdarw.3Gal.beta .1.fwdarw.4GlcNAc.beta.1.fwdarw.6)GlcNAc on T-cells from a subject suspected of having a T-cell dysfunction compared to resting T-cells from a normal individual. Kits for detecting T-cell dysfunction are provided as well.Type: GrantFiled: March 29, 1991Date of Patent: June 14, 1994Assignee: La Jolla Cancer Research FoundationInventor: Minoru Fukuda
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Patent number: 5312730Abstract: This invention relates to methods that have been found useful in reducing non-specific binding in immunochemical assays, via methods that can be implemented much faster than those used by Ishikawa. The techniques include the use of a lipophilic bridge, such as a liposome, or the elution of the antigen-antibody complex from the solid phase by the use of an anti-idiotypic antibody or an antibody, or the use of a heterologous reversible bridge.Type: GrantFiled: May 27, 1992Date of Patent: May 17, 1994Assignee: Ciba Corning Diagnostics Corp.Inventors: Uri Piran, William J. Riordan, Deborah R. Silbert-Shostek
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Patent number: 5306621Abstract: An enhanced chemiluminescent assay, in which a dihydrophthalazinedione such as luminol, a peroxidase such as HRP and an oxidant such as H.sub.2 O.sub.2 are co-reacted in the presence of an enhancer such as p-iodophenol, is modified. The enhancer is generated by enzyme-catalysed reaction of a pro-enhancer, e.g. p-iodophenol phosphate is cleaved by alkaline phosphatase, enabling this enzyme to be assayed instead of peroxidase. Alternatively, the enhancer is added, an anti-enhancer such as p-nitrophenol is generated by enzymatic reaction of a pro-anti-enhancer such as p-nitrophenol phosphate and the reduction in luminescent emission is measured.Type: GrantFiled: April 1, 1992Date of Patent: April 26, 1994Assignee: British Technology Group LimitedInventor: Larry J. Kricka
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Patent number: 5300423Abstract: This invention uses the evanescent wave detection of particles to distinguish bound from free in an analyte-binding assay. Illumination below the critical angle is employed, and a beveled window is used to eliminate bulk fluorescence from the emitted evanescent wave liquid. The sample is held in a non-rigid film cuvette.Type: GrantFiled: September 3, 1992Date of Patent: April 5, 1994Assignee: E. I. Du Pont de Nemours and CompanyInventors: Steven J. Zoha, James E. Davis, Alan R. Craig, Alan M. Hochberg
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Patent number: 5294535Abstract: The invention concerns a method for detecting an analyte in a blood sample or a derived fraction thereof. In this method one uses the binding affinity between the analyte and its specific binding agent. Moreover, a reaction component containing a peroxidase label is added to the sample and specific binding agent to form a reaction mixture. The incubation of the reaction mixture, containing the analyte and its specific binding agent, with the peroxidase-labeled reaction component has to be carried out in the presence of a quaternary ammonium salt or ionic surfactant.Type: GrantFiled: September 14, 1992Date of Patent: March 15, 1994Assignee: Akzo N.V.Inventors: Thomas C. J. Gribnau, Leonardus P. C. Kuypers, Petrus A. L. Goossens
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Patent number: 5292642Abstract: The present disclosure relates to a new lymphokine molecule, referred to as Monocyte Cytotoxicity Inducing Factor (MCF), and its use as in cancer and other types of therapy. The disclosure also relates to antibodies that immunologically recognize MCF, as well as to the use of such antibodies in detecting the presence of MCF and biologic samples. The disclosure further relates to the development of novel Sezary cell hybridomas which secrete MCF and thereby provide a ready source for MCF isolation and purification.Sezary's Syndrome is a leukemic proliferation of OKT4+ lymphocytes. Sezary cells were isolated by differential centrifugation and fused to CEM.8aza.sup.r.C, an HGPRTase lacking clone of CEM. The hybrid cells were studied for their ability to produce soluble mediators of human monocyte cytotoxicity. The product of a single clone, FtF3, which bore the surface phenotype of Sezary cells, was characterized.Type: GrantFiled: December 7, 1990Date of Patent: March 8, 1994Assignee: Board of Regents, The University of Texas SystemInventor: C. Michael Jones
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Patent number: 5281517Abstract: A method and apparatus are provided for selecting and analyzing a subpopulation of cells or cell objects for a certain parameter such as DNA using image analysis means. The cells are first stained with an alkaline phosphatase technique including a monoclonal antibody specific to a protein in at least one of the cell's cytoplasm or on a cell membrane, thereby marking any cells including the protein as to type. A second staining of the DNA in the nucleus is accomplished by a Feulgen technique that destroys the cell cytoplasm. After the staining and marking, the cells may then be gated using the image analysis means on the visual parameter such as colored DNA or colored antigen into a subpopulation that is to be measured. The selected cells may then be examined by digital image processing and measured for a parameter such as a true actual measurement of DNA in picograms. A quantitation of the measured parameter may be generated and provided.Type: GrantFiled: February 5, 1992Date of Patent: January 25, 1994Assignee: Cell Analysis Systems, Inc.Inventors: James W. Bacus, Robert J. Marder
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Patent number: 5279941Abstract: Methods are provided for detecting receptivity of mammalian endometrium to embryo implantation comprising obtaining a sample of the endometrium, contacting the endometrium with a monoclonal antibody for .beta..sub.3 integrin and detecting .beta..sub.3 integrin in the endometrium. The invention also provides for methods of diagnosing infertility in a mammal and methods of detecting the window of embryo implantation in endometrium. Methods of in vitro fertilization, methods of preventing embryo implantation and a method of monitoring endometrial maturation are also within the scope of the present invention. The present invention is also directed to contraceptives. Diagnostic kits useful in the practice of the methods of the invention are also provided.Type: GrantFiled: June 12, 1992Date of Patent: January 18, 1994Assignee: Trustees of the University of PennsylvaniaInventor: Bruce Lessey
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Patent number: 5279937Abstract: A macroglobulin is used to improve the signal-to-background ratio in an affinity binding assay employing a proteinase (or precursor) as a label. The macroglobulin entraps unbound labeled reagent, thereby reducing its signal generating activity, relative to that of the affinity complex.Type: GrantFiled: April 30, 1992Date of Patent: January 18, 1994Assignee: DeTechnology CanadaInventor: Gerald E. Rowe
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Patent number: 5264344Abstract: There is disclosed a method of culturing cells which produce products and identifying the thereby produced products, characterized in that the cells are cultured on the surface of a quantity of growth medium, which surface has been divided into a plurality of growth areas thereby limiting the amount of growth-medium which is available to the cells so that these reach metabolic stage in which said products are produced, and identifying the thereby produced products by an in situ screening procedure.Type: GrantFiled: November 1, 1991Date of Patent: November 23, 1993Assignee: University of LeicesterInventor: Peter H. A. Sneath
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Patent number: 5256542Abstract: Disclosed are immunofluorescence staining methods which increase the likelihood that antibodies expressed by a single B cell selected and sorted by fluorescence activated cell sorting are specific for the antigen of interest, and which also allow selection of B cells expressing antibodies of high affinity for the antigen of interest. The antigen-specific single B cells are to be used in a procedure which amplifies and selects their V.sub.H and V.sub.L sequences. The selection for B cells expressing antibodies to specific antigens is increased by labeling B cells with at least two antigen probes, where each antigen probe includes the antigen of interest and the difference between the two probes is that each is labeled with a different fluorochrome. The positive selection achieved using antigen probes with two different colors is preferably combined with a negative selection step, in which autofluorescent cells and sticky cells exhibiting fluorescence for the third irrelevant surface marker are excluded out.Type: GrantFiled: June 26, 1992Date of Patent: October 26, 1993Assignee: Tanox Biosystems, Inc.Inventor: Tse W. Chang
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Patent number: 5248590Abstract: A liposome reagent encapsulating a molecule to be targeted to a body site or used as an assay reporter has a ligand and a sulfonate-containing group on the liposome surface. Preferred ligands are antibodies or antibody fragments and preferred encapsulants are enzymes or dyes. In the most preferred reagents, the antibody and sulfonate-containing group are covalently bonded to the liposome surface through a connecting group which includes a succinimidyl group resulting from addition of the ligand or sulfonate-containing group to a maleimidyl group. The invention includes a kit of materials for performing an assay using the reagent of the invention as the tracer.Type: GrantFiled: July 22, 1991Date of Patent: September 28, 1993Assignee: Becton, Dickinson and CompanyInventors: Herman Rutner, Josephine D. Readio, Leslie Oppenheimer