Abstract: The present invention provides a process for the determination of a specifically bindable substance by incubation of the sample solution with at least three receptors R.sub.1, R.sub.2 and R.sub.3, of which R.sub.1 and R.sub.2 are bindable with one another and R.sub.3 is specifically bindable with the substance to be determined and measurement of the agglutination which takes place in the case of the reaction, wherein, as receptor R.sub.1, there is used a conjugate of a partner of a specifically binding pair P and of a substance S which corresponds to the substance to be determined or is a derivative thereof and has at least one epitope of the substance to be determined, as receptor R.sub.2 there is used a receptor which has at least two binding positions for P and as receptor R.sub.3 there is used a receptor which has at least two binding positions, of which at least one binds specifically with an epitope of the substance to be determined or of S.
Abstract: Replication-defective retroviral vector hybrids which are characterized in that they contain a) the U5 region and/or tRNA primer binding site of MESV as the U5 region and/or tRNA primer binding site in the leader region and b) the U3 and R regions from a Friend murine leukaemia virus (F-MuLV) as the U3 and R regions in the 3'-LTR and which are particularly suitable for an effective gene transfer in haematopoietic stem cells.
Type:
Grant
Filed:
March 7, 1997
Date of Patent:
January 12, 1999
Assignee:
Boehringer Mannheim GmbH
Inventors:
Christopher Baum, Carol Stocking-Harbers, Wolfram Ostertag
Abstract: Use of compounds of the formula I ##STR1## in which R.sub.1 signifies an amino, C.sub.1 -C.sub.6 -alkylamino, di-C.sub.1 -C.sub.6 -alkylamino or a hydroxyl group, R.sub.2 and R.sub.3, which are the same or different, each hydrogen, halogen, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkoxy, cyano, carboxyl, halogen-C.sub.1 -C.sub.6 -alkyl, cyano-C.sub.1 -C.sub.6 -alkyl, carboxy-C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 - alkyl, hydroxyl, carboxy-C.sub.1 -C.sub.6 -alkoxy, C.sub.1 -C.sub.6 -alkoxycarbonyl-C.sub.1 -C.sub.6 -alkoxy or aminocarbonyl-C.sub.1 -C.sub.6 -alkoxy, C.sub.1 -C.sub.6 -alkylaminocarbonyl-C.sub.1 -C.sub.6 -alkoxy or di-C.sub.1 -C.sub.6 -alkylaminocarbonyl-C.sub.1 -C.sub.6 -alkoxy and n the number 0 or 1, their tautomers, as well as salts with non-toxic acids or bases, for the preparation of medicaments with PLA.sub.2 -inhibiting action, new compounds and process for their preparation.
Type:
Grant
Filed:
June 26, 1995
Date of Patent:
January 5, 1999
Assignee:
Boehringer Mannheim GmbH
Inventors:
Walter-Gunar Friebe, Werner Scheuer, Ulrich Tibes
Abstract: The present invention relates to an apparatus for transferring a liquid capable of accurately performing detection of a liquid level using a pipetting probe even in a case of a high electric conductivity of a in-flow-passage moving fluid which transmits sucking and discharging operation of a syringe (107) to the pipetting probe (100, 400, 500, 600). The probe has a liquid level sensing electrode (103, 401, 501, 601) and an inner tube (102, 402, 502, 602). The liquid level sensing electrode capable of contacting with a liquid to be pipetted is electrically separated from an inner tube filled with the moving fluid, and the both are insulated by an electric insulating member (104B, 403, 503) between them. A container (111) containing the liquid to be pipetted is held by a container holder (112), and a liquid level can be detected by change in an electrostatic capacitance between the container holder and the liquid level sensing electrode of the probe when the probe is moved downward.
Abstract: Compound of formula (I) are disclosed ##STR1## as well as optically active isomers or pharmacologically acceptable salts thereof. The compounds are useful active ingredients in pharmaceutical compositions, and methods of treating osteoporosis, inflammation or diseases which are due to thromboembolic events. Compounds of formula (II) are also disclosed ##STR2## which are useful as starting compounds for preparing compounds of formula (I).
Abstract: Oxygen-independent cholesterol-converting enzyme obtainable from Actinomycetes or Basidiomycetes which utilizes artificial electron acceptors as well as a method and reagent for the determination of (total) cholesterol using the enzyme.
Type:
Grant
Filed:
October 23, 1995
Date of Patent:
January 5, 1999
Assignee:
Boehringer Mannheim GmbH
Inventors:
Dorothee Ambrosius, Klaus Kaluza, Stephan Gross
Abstract: The present invention relates to a method and a device for metering liquids, wherein the volume of a droplet of a sample liquid is determined by means of optical measuring. The liquid to be metered is brought into contact with a transfer element so that a droplet adheres to the transfer element. The transfer element and the liquid adhering thereto are illuminated from one or several directions and the resulting images are displayed on an optical sensor. The liquid volume is determined on the basis of these images. Metering is accomplished by transferring the liquid volume adhering to the transfer element into an analysis vessel.
Abstract: A vessel for reducing contamination of liquids is formed of a vessel body with an inlet opening and an outlet opening therein. A closing device is attached to the vessel body adjacent the outlet opening. The closing device closes the outlet opening, and includes a normally closed one-way valve which is openable by a predetermined pressure from within the vessel body.
Type:
Grant
Filed:
March 29, 1996
Date of Patent:
January 5, 1999
Assignee:
Boehringer Mannheim GmbH
Inventors:
Gerhard Bienhaus, Michael Fritz, Jurgen Schwab, Edda Geisler, Herbert Harttig, Heinz Macho
Abstract: A process for improving the stability of an antibody or fragment thereof is disclosed. A gene encoding for an amino acid sequence of a variable domain of an antibody or fragment thereof to be modified is provided, and the amino acid sequence of the gene is compared with one of consensus tables 1-6. At least one codon of each pair of codons in the gene, which pair together code for disulfide bridge-forming cysteines, are modified so that all disulfide bridges present in the antibody as produced in a eukaryotic cell are absent from the modified antibody as produced in the method. At least one additional codon in the gene which codes for an amino acid other than a disulfide bridge-forming cysteine is also modified. A prokaryotic microorganism is transformed with the modified gene and additional variable domain DNA, and the modified antibody or fragment thereof is expressed in the prokaryotic microorganism.
Abstract: The use of various thrombolytically active proteins in therapy is disclosed. The proteins are markedly superior to wild type t-PA in their pharmacokinetic, pharmacodynamic, and safety profiles.
Abstract: Process for disintegrating cell tissue and releasing cells or groups of cells contained therein by incubating the cell tissue with a recombinant neutral protease from Clostridium histolyticum which is coded bya) a DNA of nucleotides 1027-1965 from SEQ ID NO:3 or a DNA which is complementary thereto,b) nucleic acids which hybridize with a DNA of nucleotides 1027-1965 from SEQ ID NO:3,c) nucleic acids which, without the degeneracy of the genetic code, would hybridize with one of the nucleic acids mentioned in a) or b)and is the product of a prokaryotic or eukaryotic expression of an exogenous nucleic acid, until the cells or groups of cells have been released to the desired extent and separating the cells or groups of cells from the cell tissue fractions.
Type:
Grant
Filed:
August 26, 1997
Date of Patent:
December 29, 1998
Assignee:
Boehringer Mannheim GmbH
Inventors:
Friederike Hesse, Dorothee Ambrosius, Helmut Burtscher
Abstract: The invention concerns a binding matrix containing a carrier material with an oxidic surface and a solid phase reactant covalently bound thereto via anchor groups which is capable of binding to at least one free reaction partner, which is characterized in that the solid phase reactant forms a diluted and essentially laterally homogeneous binding layer on the surface of the carrier material and that the anchor groups are silane groups and are linked to the solid phase reactant via a spacer molecule.
Abstract: The invention concerns a diagnostic test carrier (1) containing a supporting layer (2) with a detection layer (3) arranged thereon containing reagents required for the determination of an analyte in a liquid sample and an inert layer (4) covering the detection layer (3) wherein the inert layer (4) is arranged at such a distance (5) from the detection layer to enable a capillary active liquid transport between the detection layer and inert layer (3,4), characterized in that the inert layer (4) extends beyond the detection layer and wherein the area (10) that extends beyond the detection layer is attached to the supporting layer (2) in such a way that a continuous capillary active liquid transport between the inert layer and detection layer (4,3) and between the inert layer and supporting layer (4,2) is possible and in addition the inert layer (4) contains several holes (7) in the area of the detection layer (3) through which the sample to be examined and the components contained therein can be applied to the d
Type:
Grant
Filed:
July 21, 1997
Date of Patent:
December 22, 1998
Assignee:
Boehringer Mannheim GmbH
Inventors:
Peter Vetter, Heinz Macho, Peter Vogel, Michael Fritz
Abstract: Isolated nucleic acid molecules encoding polysialyl transferases, and the polysialyl transferases themselves are disclosed. SEQ ID NOS: 1, 2, 7 and 8 present examples of these. The nucleic acid molecules and the proteins can be used diagnostically or therapeutically. Additionally, antisense oligonucleotides and antibodies are described, which can also be used diagnostically or therapeutically.
Type:
Grant
Filed:
December 21, 1995
Date of Patent:
December 15, 1998
Assignees:
Boehringer Mannheim GmbH, La Jolla Cancer Research Foun.
Inventors:
Rita Gerardy-Schahn, Minoru Fukuda, Jun Nakayama, Matthias Eckhardt
Abstract: A conjugate of at least two binding sites that bind specifically to the analyte-specific binding region of the receptor that is used for detection in a test, wherein the binding sites are linked by at least one soluble carrier substance and the conjugate is a product of a synthetic or recombinant production, dissolved in an aqueous solution in an exactly known amount is particularly suitable as a stable calibrator in a test for the detection of an analyte.
Type:
Grant
Filed:
December 12, 1996
Date of Patent:
December 8, 1998
Assignee:
Boehringer Mannheim GmbH
Inventors:
Christoph Seidel, Peter Bialk, Herbert Von der Eltz
Abstract: System for the automatic operation of reactions using several vessels which can be closed by individual closures using a device for automatically opening the closures.
Abstract: The present invention concerns a diagnostic test carrier (1) containing a supporting layer (2) with a detection layer (3) arranged thereon containing the reagents required to determine analyte in a liquid sample and a network (4) covering the detection layer (3) which is larger than the detection layer (3) and which is attached to the supporting layer (2), which is characterized in that the network (4) is hydrophilic but not capillary active on its own and an inert cover (5) made of sample-impermeable material is arranged over the areas (6) of the network that extend beyond the detection layer in such a way that a sample application site (7) remains free on the region of the network (4) covering the detection layer as well as the use of such a test carrier for the determination of analyte in a liquid. In addition the invention concerns a method for the determination of an analyte in a liquid sample with the aid of a test carrier according to the invention.
Abstract: 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:
Grant
Filed:
December 20, 1996
Date of Patent:
December 8, 1998
Assignee:
Boehringer Mannheim Corporation
Inventors:
Zhi David Deng, Gerald F. Sigler, Nigel A. Surridge, Christopher D. Wilsey, Robert J. McEnroe, Walter W. Jernigan, Rebecca W. Muddiman
Abstract: A nucleic acid analog comprising a polymeric strand which includes a sequence of ligands bounds to a backbone made up of linked backbone moieties, which analog is capable of hybridization to a nucleic acid of complementary sequence, further comprising a chelating moiety capable of binding at least one metal ion by chelation.
Type:
Grant
Filed:
May 24, 1996
Date of Patent:
December 1, 1998
Assignee:
Boehringer Mannheim GmbH
Inventors:
Christopher John Stanley, Henrik Orum, Mikkel Jorgensen
Abstract: Novel derivatives of LSD having the formula ##STR1## wherein R.sub.1 is an alkyl, cycloalkyl or aryl group having 1 to 10 carbon atoms, preferably an alkyl group having 1 carbon atom;R.sub.2 is a bond or ##STR2## wherein R.sub.3 is alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms, preferably an alkyl group having 2 or 5 carbon atoms; Z is an immunogenic carrier substance, an enzyme donor polypeptide or a label selected from the group consisting of an enzyme, a substance having fluorescent or luminescent properties and a radioactive substance; and n is 1 to p where p equals MW of Z/1000. The derivatives include maleimide conjugates of an immunogenic poly(amino acid), an enzyme donor polypeptide or a labeling substance such as an enzyme, a fluorescent substance or a radioactive substance. Novel activated hapten intermediates useful in the preparation of the conjugates and methods for synthesis of the hapten intermediates and their conjugate derivatives are also disclosed.
Type:
Grant
Filed:
November 20, 1995
Date of Patent:
December 1, 1998
Assignee:
Boehringer Mannheim Corporation
Inventors:
Gerald F. Sigler, Riaz Rouhani, David Davoudzaheh