Patents Represented by Attorney, Agent or Law Firm Marilyn L. Amick
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Patent number: 6361955Abstract: The invention concerns an immunological process for the determination of prostate-specific antigen (PSA), particularly for the determination of free PSA, the total concentration of PSA and the concentration of PSA-serpin complexes by incubation of the sample with at least one antibody specifically binding to free PSA but not to complex PSA. The process is characterized in that especially before the determination of the total PSA concentration a nucleophile containing amine is added to the sample. Furthermore, the invention concerns the use of amine-containing nucleophiles for the production of free PSA as well as a procedure for preparing free PSA from complex PSA by incubation of a sample containing complex PSA with a nucleophile containing amine.Type: GrantFiled: April 1, 1999Date of Patent: March 26, 2002Assignee: Roche Diagnostics GmbHInventors: Wolfgang Hösel, Jochen Peter, Carlo Unverzagt
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Patent number: 6333397Abstract: An immunoassay for the determination of myocardial necroses using antibodies to troponin T and a binding partner B for troponin T or for the an antibody, whereby either the antibody or the binding partner B is labelled with a determinable group. The immunological complex formed which contains the determinable group is isolated by separation of the phases and the determinable group is determined in one of the phases. Furthermore, monoclonal and polyclonal antibodies to troponin T are described with a cross-reactivity of less than 5% to skeletal muscle troponin T and less than 2% to troponin I and other myofibrillar proteins.Type: GrantFiled: February 17, 2000Date of Patent: December 25, 2001Assignee: Roche Diagnostics GmbHInventors: Hugo Katus, Anneliese Borgya, Klaus Hallermayer, Siegfried Looser
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Patent number: 6322993Abstract: The invention concerns a method and reagent for the determination of lipase in the presence of a colour substrate and at least one N-substituted carboxylic acid amide derivative or a compound of the general formula (I) or (Ia) in which R1 and R2 independently of one another represent hydrogen or a saturated or unsaturated, substituted or unsubstituted hydrocarbon residue with 2 to 24 carbon atoms, Z denotes a saturated or unsaturated, substituted, cyclic or straight-chained hydrocarbon residue with 1 to 10 carbon atoms, X represents an atom or a group of atoms with positive charge and n is a number from 1 to 3. Tetra-sodium-N-(1,2-dicarboxylethyl)-N-alkylsulfosuccinamide or a mixture containing such a compound has proven to be particularly advantageous for the elimination of unspecific reactions in the determination of lipase in a biological sample.Type: GrantFiled: May 8, 1998Date of Patent: November 27, 2001Assignee: Roche Diagnostics GmbHInventors: Lieselotte Schelong, Ralf Zielenski, Urban Prinzing
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Patent number: 6281021Abstract: The invention concerns methods for the detection of an analyte in a sample by chemiluminescence or electrochemiluminescence using derivatized test reagents. In addition new reagents and reagent kits for chemiluminescence and electrochemiluminescence detection methods are disclosed.Type: GrantFiled: June 18, 1999Date of Patent: August 28, 2001Assignee: Roche Diagnostics GmbHInventors: Martin Egger, Hans-Peter Josel, Gabriele Punzmann
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Patent number: 6246785Abstract: Method for the automated, microscope-aided examination of tissue samples or samples of body fluids with the aid of neural networks. In a first method of examination the sample is firstly classified according to its type and subsequently a digitalized image is divided into connected segments which are examined by one or several neural networks. The sample is classified as pathological if cell types are present which do not belong to the type of sample or if structural cell or tissue changes are present. In a second method of examination the digitalized image is again segmented and the segments are examined for the presence of a cell object. This is followed by an examination whether the cell object is an individual cell or a cell complex. In a third step of the analysis it is determined whether the found cell object is located on one of the image borders. If this is the case then a further image is recorded in which the found cell objects are completely included.Type: GrantFiled: February 19, 1999Date of Patent: June 12, 2001Assignee: Roche Diagnostics GmbHInventors: Bela Molnar, Rainer Schäfer, Winfried Albert
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Patent number: 5939332Abstract: Novel analogs of phencyclidine (PCP) are disclosed. The analogs are capable of reacting with anti-PCT antibodies and are useful in immunoassays.The following analogs are described: ##STR1## wherein wherein X is --OH or a reporter molecule selected from the group consisting of aminofluorescein and aminomethylfluorescein and n is an integer between 1 and 10, inclusive.Type: GrantFiled: February 27, 1998Date of Patent: August 17, 1999Assignee: Roche Diagnostics Corp.Inventors: James C. Lee, Luis Fernando Del Corral, Richard A. Clark, Pedro A. Bonilla
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Patent number: 5830741Abstract: An enzyme composition for dissociating tissues is disclosed. The composition comprises purified collagenase I and collagenase II from Clostridium histolyticum in a mass ratio of about 0.3 to 0.6 and a neutral protease such that the ratio of total FITC casein units of activity to Wunsch units of activity in the composition is about 250:1 to about 600:1. The preferred neutral protease is thermolysin.Type: GrantFiled: December 6, 1996Date of Patent: November 3, 1998Assignee: Boehringer Mannheim CorporationInventors: Francis E. Dwulet, Marilyn E. Smith
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Patent number: 5753485Abstract: A purified enzyme mixture useful for isolating cells or cell clusters from tissue is disclosed. The mixture includes at least two collagenase enzymes, at least two other proteases, and additional non-protease components. The mixture is purified by removing at least some of the non-protease components. The purified mixture may then be used to isolate cells or cell clusters from tissue. Also disclosed are the essential components of the purified enzyme mixture as well as preferred ranges and ratios of these essential components for isolating cells or cell clusters from tissue. Finally, a dissociation system is disclosed that can be used with the purified enzyme mixture to dissociate tissue and recover cells or cell clusters.Type: GrantFiled: January 24, 1996Date of Patent: May 19, 1998Assignee: Boehringer Mannheim CorporationInventors: Francis E. Dwulet, Bernice B. Ellis, John F. Gill, Linda B. Jacobsen, Marilyn E. Smith, David G. Waters
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Patent number: 5709550Abstract: Training apparatus for use with a keyboard comprises a rigid support and a stabilizing bar having optional hand guides. The stabilizing bar is attached to the support, preferably pivotably, such that, when said training apparatus is positioned in front of a keyboard, an operator's hands are positioned between but not touching the support and the stabilizing bar when the operator's fingers are positioned over their home keys on the keyboard. In an alternate embodiment, the support for the stabilizing bar is formed integrally with the keyboard support.Type: GrantFiled: August 28, 1996Date of Patent: January 20, 1998Assignee: Debra E. DevineInventor: Debra E. Devine
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Patent number: 5639631Abstract: The invention is a stable reagent used in assay systems that form a colored ferric ion complex, such as Prussian Blue. Such reagents are useful for the detection or measurement of an analyte from a fluid sample. Surprisingly, it has been found that the inclusion of certain ferric ion chelating agents, such as 3-sulfobenzoic acid, will inhibit formation of the blank reaction in the reagent.Type: GrantFiled: June 22, 1995Date of Patent: June 17, 1997Assignee: Boehringer Mannheim CorporationInventors: Chi-Neng Arthur Han, Kenneth J. Dean, Walter W. Jernigan, William R. Carr
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Patent number: 5589326Abstract: A new group of Os(II) and Os(III) compounds useful as redox mediators in electrochemical biosensors. These compounds have 1) low oxidation potential, 2) fast reaction kinetics between the electroactive center of an enzyme and the compound, 3) slow oxidation of osmium by oxygen, and 4) excellent solubility in aqueous medium. These mediators are particularly useful as a component of a reagent used in an electrochemical biosensor, wherein the biosensor is useful for measuring analytes from a biological fluid, such as blood.Type: GrantFiled: December 30, 1993Date of Patent: December 31, 1996Assignee: Boehringer Mannheim CorporationInventors: Zhi D. Deng, Gerald F. Sigler, Nigel A. Surridge, Christopher D. Wilsey, Robert J. McEnroe, Walter W. Jernigan, Rebecca W. Muddiman
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Patent number: 5525474Abstract: Novel derivatives of procainamide and N-acetylprocainamide (NAPA) are disclosed having the following formula: ##STR1## wherein: X=hydrogen or acetyl;n=1 to p where p=MW of Z/1000;Z=a poly(amino acid) or polysaccharide; andR3=a bond or ##STR2## wherein R2=an alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms. The derivatives include maleimide conjugates of proteins or poly(amino acids), enzymes, enzyme donor polypeptides and labeling substances. Novel activated hapten intermediates useful in the preparation of the conjugates and methods for synthesis of the hapten intermediates and derivatives are also disclosed.Type: GrantFiled: January 31, 1994Date of Patent: June 11, 1996Assignee: Boehringer Mannheim CorporationInventors: Gerald F. Sigler, Charles F. Walter, Todd Glancy, Erasmus Huber, Frank E. Klein
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Patent number: 5508171Abstract: A new electrochemical biosensor and method of its use. The electrochemical biosensor has a pair of electrodes consisting of a working electrode and a counter electrode made of the same electrically conducting materials. The counter electrode may be the same size or smaller than the working electrode. The biosensor includes a sample receiving portion wherein a portion of the electrode surfaces is covered by a reagent that includes a redox mediator and an enzyme. A fluid that contains an analyte is added to the sample receiving portion. A reaction involving the analyte, enzyme and redox mediator occurs. After this reaction is complete, an electrical potential difference is applied between the electrodes. Diffusion limited current is measured and correlated to the concentration of analyte in the fluid.Type: GrantFiled: February 22, 1994Date of Patent: April 16, 1996Assignee: Boehringer Mannheim CorporationInventors: P. Douglas Walling, Joseph E. Bateson, Lance S. Kuhn, M. Luann Ochs, Kent M. Kost, Martin T. Gerber, Klaus H. Pollmann, Chi-Neng A. Han
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Patent number: 5492813Abstract: Muteins of enzyme acceptor polypeptide fragments of .beta.-galactosidase are provided which exhibit substantially increased kinetic complementation activity with no significant loss in stability. A preferred enzyme acceptor fragment has an amino acid other than cysteine located at position 500 of the natural sequence. An especially preferred substitution is serine or valine. Other preferred muteins have an amino acid other than methionine located at position 443, with leucine being especially preferred, or an amino acid other than cysteine at position 76, with leucine being an especially preferred substitution. Also provided are methods for producing the novel muteins, reagent compositions comprising the novel muteins, and immunoassay methods for determining an analyte in which the novel mutein recombines with an enzyme donor polypeptide fragment to form enzymatically active .beta.-galactosidase.Type: GrantFiled: November 1, 1993Date of Patent: February 20, 1996Assignee: Boehringer Mannheim CorporationInventors: Scott J. Eisenbeis, Sophie J. Boguslawski, Mark Krevolin, David J. Ledden
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Patent number: 5464747Abstract: A mutein of an enzyme acceptor polypeptide fragment of .beta.-galactosidase which is resistant to oxidation is provided. The enzyme acceptor fragment has an amino acid other than cysteine located at position 602 of the natural sequence. An especially preferred substitution is serine. Also provided are a method for producing the novel mutein, a reagent composition comprising the novel mutein, and an immunoassay method for determining an analyte in which the novel mutein recombines with an enzyme donor polypeptide fragment to form enzymatically active .beta.-galactosidase.Type: GrantFiled: October 29, 1993Date of Patent: November 7, 1995Assignee: Boehringer Mannheim CorporationInventors: Scott J. Eisenbeis, Mark Krevolin, Christopher P. Bryant, Sophie J. Boguslawski, David J. Ledden, Scott Clark
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Patent number: 5439798Abstract: Novel derivatives of procainamide and N-acetylprocainamide (NAPA) are disclosed having the following formula: ##STR1## wherein: X=hydrogen or acetyl;R.sub.1 =an alkyl group having 1 to 3 carbon atoms;m=an integer from 2 to 10;R.sub.2 =an alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms;Z=a poly(amino acid); andn=1 to p where p=MW of Z/1000.The derivatives include maleimide conjugates of proteins or poly(amino acids), enzymes, enzyme donor polypeptides and labeling substances. Novel activated hapten intermediates useful in the preparation of the conjugates and methods for synthesis of the hapten intermediates and derivatives are also disclosed.Type: GrantFiled: December 17, 1993Date of Patent: August 8, 1995Assignee: Boehringer Mannheim CorporationInventors: Gerald F. Sigler, Charles F. Walter, Charles E. Durant, Todd Glancy, Frank E. Klein, Allan R. Dorn
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Patent number: 5437999Abstract: A method for fabricating high-resolution, biocompatible electrodes is disclosed, allowing production of an electrochemical sensor which is capable of precise analyte concentration determination on a very small sample size. Electrically conducting material is affixed to a first insulating substrate. A second insulating substrate is then affixed to the electrically conducting material and patterned using photolithography to define an electrode area. Alternatively, the electrically conducting material may be screen printed directly onto a standard printed circuit board substrate in the case of a counter or reference electrode. In either case, the substrate may be rigid or flexible. When the electrodes produced in accordance with the present invention are then used in an electrochemical sensor which includes a reagent, the small and highly-defined electrode areas permit highly-accurate electrochemical analyte measurements to be performed on very small sample sizes.Type: GrantFiled: February 22, 1994Date of Patent: August 1, 1995Assignee: Boehringer Mannheim CorporationInventors: Eric R. Diebold, Richard J. Kordal, Nigel A. Surridge, Christopher D. Wilsey
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Patent number: 5427912Abstract: An immunoassay diagnostic kit, method, and apparatus for electrochemically determining the concentration of an analyte in a sample. A mixture is formed which includes the sample, an enzyme-acceptor polypeptide, an enzyme-donor polypeptide linked to an analyte analog (enzyme-donor polypeptide conjugate), a labeled substrate, and an antibody specific for the analyte to be measured. The analyte and the enzyme-donor polypeptide conjugate competitively bind to the antibody. When the enzyme-donor polypeptide conjugate is not bound to antibody, it will spontaneously combine with the enzyme acceptor polypeptide to form an active enzyme complex. The active enzyme hydrolyzes the labeled substrate, resulting in the generation of an electroactive label, which can then be oxidized at the surface of an electrode. A current resulting from the oxidation of the electroactive compound can be measured and correlated to the concentration of the analyte in the sample.Type: GrantFiled: August 27, 1993Date of Patent: June 27, 1995Assignees: Boehringer Mannheim Corporation, Boehringer Mannheim GmbHInventors: Mary E. Brown, Lance S. Kuhn, Robert J. McEnroe, Rebecca W. Muddiman, Mary L. Ochs
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Patent number: 5385846Abstract: A biosensor and method for determining the hematocrit level of a whole blood sample using electrochemistry. The biosensor includes working and counter electrodes. A porous membrane is impregnated with an electroactive compound and is spatially displaced from the surface of the electrodes. When a whole blood sample is applied to the porous substrate, a mixture of the electroactive compound and the blood is formed. The mixture settles on the electrodes and a potential difference is applied sufficient to oxidize or reduce the electroactive compound and generate a current. This current can be measured and correlated to hematocrit level.Type: GrantFiled: June 3, 1993Date of Patent: January 31, 1995Assignee: Boehringer Mannheim CorporationInventors: Lance S. Kuhn, Mary L. Ochs, Gilbert C. Morris
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Patent number: 5288636Abstract: A biosensor that includes working and counter electrodes of substantially the same size and made of the same electrically conducting material. A reagent is contained in a reagent well in the biosensor. The reagent includes a redox mediator, an enzyme, and a buffer, and covers substantially equal surface areas of portions of the working and counter electrodes. When a sample, containing the analyte to be measured, is added to the reagent well, a reaction occurs that oxidizes the analyte and reduces the redox mediator. After this reaction is complete, an electrical potential difference is applied between the electrodes. The amount of oxidized form of the redox mediator at the counter electrode and the applied potential difference must be sufficient to cause diffusion limited electrooxidation of the reduced form of the redox mediator at the surface of the working electrode.Type: GrantFiled: December 14, 1990Date of Patent: February 22, 1994Assignee: Boehringer Mannheim CorporationInventors: Klaus H. Pollmann, Martin T. Gerber