Patents Represented by Attorney George M. Gould
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Patent number: 5618703Abstract: Methods are provided for distinguishing between RNA and DNA templates in an amplification reaction. In a preferred embodiment of the invention, the amplification reaction is a PCR and the reaction is catalyzed by a thermostable DNA polymerase or both reverse transcription and amplification of a target RNA. The invention particularly relates to selective amplification of RNA in the presence of homologous DNA, for example, HIV nucleic acids.Type: GrantFiled: February 22, 1994Date of Patent: April 8, 1997Assignee: Hoffmann-La Roche Inc.Inventors: David H. Gelfand, Thomas W. Myers
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Patent number: 5583248Abstract: Compounds of the formula: ##STR1## wherein R.sup.1 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aralkanoyl, heterocyclylcarbonyl or a group of the formula: ##STR2## R.sup.2 is alkyl, cycloalkylalkyl or aralkyl; R.sup.3 is hydrogen and R.sup.4 is hydroxy or R.sup.3 and R.sup.4 together are oxo; R.sup.5 is alkoxycarbonyl or alkylcarbamoyl; R.sup.6 and R.sup.7 together are trimethylene or tetramethylene optionally substituted by alkyl or on adjacent carbon atoms by tetramethylene; R.sup.8 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aroyl, aralkanoyl or heteroeyelylearbonyl; and R.sup.9 is alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, cyanoalkyl, carbamoyl-alkyl, alkylthioalkyl, alkoxyalkyl or alkoxycarbonylalkyl:and pharmaceutically acceptable acid addition salts of those compounds of formula I which are basic, inhibit aspartyl proteases of viral origin and can be used in the form of medicaments for the prophylaxis or treatment of viral infections.Type: GrantFiled: April 5, 1995Date of Patent: December 10, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Joseph A. Martin, Gareth J. Thomas
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Patent number: 5580718Abstract: Oligonucleotides primers can be used to amplify and detect Hepatitis C virus nucleic acids in a process that involves reverse transcription of the viral genomic RNA to create cDNA and the subsequent amplification of the cDNA by the polymerase chain reaction. Oligonucleotide probes can be used to detect the presence of amplified DNA by hybridization. The invention provides improved methods, compositions, and kits for amplifying and detecting U.S., Japan, and HCV-C prototype nucleic acids.Type: GrantFiled: May 24, 1995Date of Patent: December 3, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Robert M. Resnick, Karen K. Y. Young
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Patent number: 5573906Abstract: A process for the detection of a nucleic acid sequence in a homogeneous assay format using an energy transfer system is disclosed. This process utilizes a 5' labeled primer containing a selfcomplementary sequence in an amplification or extension process together with a subsequent detection step using a 3' labeled probe for the amplified or extended region. The labels will be close together in space after hybridizing the probe close to the short piece of double-stranded DNA resulting from backfolding of the selfcomplementary region of the primer which has been incorporated into the amplified or extended product. A new primer for use in this process is also disclosed.Type: GrantFiled: March 22, 1993Date of Patent: November 12, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Wilhelm Bannwarth, Francis Muller
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Patent number: 5571673Abstract: The present invention provides methods of detecting a change in the length of an oligonucleotide labeled with a light-emitting label by measuring the light emission in the presence of a DNA binding compound that interacts with the label to modify the light emission of the label, wherein the degree of interaction depends on the length of the oligonucleotide. The methods are applicable in general to nucleic acid sequence detection assays that utilize a reaction that results in the selective cleavage of hybridized oligonucleotide probes, and, in particular, to amplification/detection assays wherein hybridized probes are cleaved concomitant with primer extension.Type: GrantFiled: November 23, 1994Date of Patent: November 5, 1996Assignee: Hoffmann-La Roche Inc.Inventor: Teresa K. H. Picone
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Patent number: 5560377Abstract: The present disclosure relates to an improved floss implement comprising a composite of a multifilament yarn bonded to an extruded monofilament. Both elements are made of polymer compounds, preferably nylon, to provide desired ease of use of the monofilament as a leader to pass the implement easily between the teeth or under bridges while the multifilament yarn can be provided in looped embodiments, as a bush element or in the form of one or more tails thus providing superior flossing action when passed between the teeth or under bridges.Type: GrantFiled: April 13, 1995Date of Patent: October 1, 1996Inventor: Marion Donovan
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Patent number: 5559232Abstract: The novel carboxamides of the formula ##STR1## wherein A, E, G, L, M, R and Q have the significance given in the description, as well as hydrates or solvates thereof inhibit thrombin-induced platelet aggregation and fibrinogen coagulation in plasma. They can be manufactured starting from the corresponding acid and the corresponding amine H.sub.2 NCH.sub.2 Q.Type: GrantFiled: September 2, 1994Date of Patent: September 24, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Jean Ackermann, David Banner, Klaus Gubernator, Kurt Hilpert, G erard Schmid
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Patent number: 5550039Abstract: The present invention provides primers for the polymerase chain reaction amplification of a nucleic acid sequence encompassing the polymorphic regions of the second, third, and fourth exons of the HLA Class I B gene (HLA-B). The polymorphic regions of the second, third, and fourth exons of the HLA-B gene contain sufficient variability so that each allele is uniquely identified by the nucleic acid sequence within these regions. The primers and amplification methods of the present invention enable genotyping at the HLA-B locus using samples from a variety of sources and for detecting allelic variants not distinguishable by serological methods. The HLA-B DNA genotyping can be used for tissue typing, determining individual identity, and identifying disease susceptible individuals.Type: GrantFiled: March 7, 1995Date of Patent: August 27, 1996Assignee: Hoffmann-La Roche Inc.Inventor: Elizabeth A. Trachtenberg
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Patent number: 5550040Abstract: Methods, reagents and kits are provided for simultaneously amplifying and detecting polynucleotide sequences in bacteria causing Neisseria gonorrhoeae and/or Chlamydia trachomatis using primers and probes specific for each bacterial species.Type: GrantFiled: March 17, 1994Date of Patent: August 27, 1996Assignee: Hoffman-La Roche Inc.Inventors: Ashok P. Purohit, Sheryl B. Silver
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Patent number: 5543323Abstract: Novel antigenic polypeptides having at least one determinant immunologically cross-reactive with determinants on a polypeptide associated with the rhoptry organelles of the merozoite form of the malaria parasite Plasmodium falciparum are described. Also described are immunogenic compositions containing such a polypeptide, DNAs coding for such a polypeptide, recombinant vectors containing such a DNA sequence, host organisms containing a replicable vector, and antibodies which are directed against a polypeptide in accordance with the invention. In addition, processes for the production of the immunogenic compositions, the microorganisms, and the antibodies, as well as the use the polypeptides and the immunogenic compositions for the immunization of mammals against malaria are also described.Type: GrantFiled: November 16, 1994Date of Patent: August 6, 1996Assignee: Hoffman-La Roche Inc.Inventors: Robert G. Ridley, John G. Scaife
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Patent number: 5543559Abstract: The present invention is concerned with a process for the manufacture of optically active compounds of the formula ##STR1## wherein R signifies lower alkyl, lower alkoxy, phenyl, benzyl or --NR.sub.2.sup.1, R.sup.1 signifies lower alkyl, phenyl, benzyl or hydrogen and * signifies an optically active center, by asymmetrically hydrogenating an enol derivative of ketoisophorone of the formula ##STR2## wherein R has the significance given above, in the presence of a rhodium complex of an optically active diphosphine ligand.Type: GrantFiled: June 8, 1995Date of Patent: August 6, 1996Assignee: Hoffman-La Roche Inc.Inventors: Emil A. Broger, Yvo Crameri, Rudolf Schmid, Theodor Siegfried
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Patent number: 5543296Abstract: Methods are provided for detecting carcinoma metastases in selected body tissues and fluids. These methods offer greater than 1,000-fold enhanced sensitivity compared to prior standard diagnostic methods. In one embodiment of the invention, target carcinoma associated nucleic acid sequences are identified for detecting minimal residual disease in lung carcinomas. The methods utilize nucleic acid amplification techniques, preferably, the polymerase chain reaction.Type: GrantFiled: December 16, 1994Date of Patent: August 6, 1996Assignees: Hoffman-La Roche Inc., Regents of the University of CaliforniaInventors: Robert E. Sobol, Mark R. Green, Ernest S. Kawasaki
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Patent number: 5540917Abstract: A pharmaceutical composition comprising at least one water insoluble crude fiber and at least one lipase inhibitor. The lipase inhibitor is present in an amount effective for treating adiposity. The lipase inhibitor is selected from lipstatin in pure form, a biomass comprising a lipase inhibitor, and tetrahydrolipstatin.Type: GrantFiled: May 19, 1995Date of Patent: July 30, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Dorothea Isler, Walter Rehm, Erich Widmer
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Patent number: 5541186Abstract: A compound of the formula ##STR1## wherein R.sup.1 to R, R.sup.a, R.sup.b X, Y, Z, m and n have the significance given in the description, can be used as medicaments, especially for the treatment and prophylaxix of conditions which are associated with endothelin activities.Type: GrantFiled: June 27, 1994Date of Patent: July 30, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Volker Breu, Kaspar Burri, Jean-Marie Cassal, Martine Clozel, Georges Hirth, Bernd-Michael L offler, Marcel M uller, Werner Neidhart, Henri Ramuz
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Patent number: 5541108Abstract: A process for producing 2-keto-L-gulonic acid which comprises converting L-sorbose and/or D-sorbitol into 2-keto-L-gulonic acid with the aid of a microorganism or its cell free extract, said microorganism belonging to the species Gluconobacter oxydans capable of producing 2-keto-L-gulonic acid and having L-sorbose dehydrogenase activity. Also disclosed are specific microorganisms useful in such process.Type: GrantFiled: June 28, 1994Date of Patent: July 30, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Akiko Fujiwara, Teruhide Sugisawa, Masako Shinjoh, Yutaka Setoguchi, Tatsuo Hoshino
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Patent number: 5541065Abstract: A process for determining the genotype of an individual with respect to the alleles at the HLA DP locus involves obtaining a sample of nucleic acid from the individual, and hybridizing the nucleic acids with a panel of probes specific for variant segments of DPalpha and DPbeta genes. Because the variation between DPbeta alleles is highly dispersed throughout the second exon of the DPbeta gene, the discovery of many different DPbeta alleles makes the process far more discriminating and informative than cellular, RFLP, or serological methods. The process can also be carried out on amplified nucleic acid produced by the polymerase chain reaction using primers specific for the second exon of the DPalpha and DPbeta genes. HLA DP DNA typing methods are useful in the prevention of graft rejection and host versus graft disease, in determining susceptibility to autoimmune diseases, in providing evidence concerning the derivation from an individual of forensic samples, and in paternity testing.Type: GrantFiled: February 14, 1994Date of Patent: July 30, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Henry A. Erlich, Glenn T. Horn, Teodorica Bugawan, Ann B. Begovich
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Patent number: 5538725Abstract: Polypeptides which bind to mammalian .alpha.6-integrin and inhibit metastasis.Type: GrantFiled: August 12, 1994Date of Patent: July 23, 1996Assignee: Hoffman-La Roche Inc.Inventor: Beat A. Imhof
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Patent number: 5539074Abstract: The invention is concerned with linear and cyclic polymers or oligomers having a photoreactive ethene group. The polymers are of the formula ##STR1## wherein M.sub.a, M.sub.b, M.sub.c are monomer units for homo- or copolymers;x, y, z are mole fractions of the copolymers, whereby in each case 0<x.ltoreq.1; 0.ltoreq.y.ltoreq.1 and 0.ltoreq.z<1;S.sub.a, S.sub.b are spacer units;Z.sub.a, Z.sub.b are molecule units which can undergo photochemical isomerization/dimerization;n is a magnitude of 4-100 000 andm is 0 or 1,The compounds are used as an orientating layer for liquid crystals.Type: GrantFiled: February 4, 1994Date of Patent: July 23, 1996Assignee: Hoffmann-La Roche Inc.Inventors: Rolf-Peter Herr, Stephen Kelly, Martin Schadt, Klaus Schmitt, Andreas Schuster
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Patent number: 5538871Abstract: Improvements to the in situ polymerase chain reaction (PCR), a process of in vitro enzymatic amplification of specific nucleic acid sequences within the cells where they originate, can be achieved by changing the way that the enzymatic reaction is started. Reaction initiation is delayed until the start of PCR thermal cycling, either by withholding a subset of PCR reagents from the cellular preparation until the preparation has been heated to 50.degree. C. to 80.degree. C., immediately before thermal cycling is begun, or by adding to the PCR reagents a single-stranded DNA binding protein which blocks reaction at temperatures below about 50.degree. C. If the in situ PCR is performed on cellular preparations already attached to a microscope slide, thermal cycling also is facilitated by use of a thermal cycler sample block or compartment designed optimally to hold the microscope slide and any vapor barrier covering the slide.Type: GrantFiled: February 17, 1995Date of Patent: July 23, 1996Assignees: Hoffmann-La Roche Inc., Research Foundation of State of New YorkInventors: Gerard J. Nuovo, Will Bloch
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Patent number: 5539063Abstract: The present invention is a polymer which may be used to produce a physiologically active, substantially non-immunogenic water soluble polyethylene glycol protein conjugate having the same utility as the protein which forms the conjugate, without having the same properties of producing an immunogenic response possessed by the protein which forms this conjugate.Type: GrantFiled: June 1, 1995Date of Patent: July 23, 1996Assignee: Hoffmann-La Roche Inc.Inventors: John Hakimi, Patricia Kilian, Perry Rosen