Patents Issued in January 9, 2001
  • Patent number: 6172190
    Abstract: The present invention relates to the discovery and characterization of two novel forms of Caspase-8. The first Caspase-8 of the invention, Caspase-8h, encodes a 220 amino acid polypeptide which includes two FADD death effector domains. The second caspase of the invention, Caspase-8i, encodes an 81 amino acid polypeptide having one FADD death effector domain. The invention encompasses nucleic acid molecules encoding Caspase-8h and Caspase-8i, vectors containing these nucleic acid molecules, cells harboring recombinant DNA encoding Caspase-8h and/or Caspase-8i, host fusion proteins which include Caspase-8h and/or Caspase-8i, transgenic animals which express Caspase-8h and/or Caspase-8i, therapeutic methods, purified Casapase-8h, purified Casapase-8i, therapeutic compounds and methods employing Caspase-8h and Caspase-8i, and screening methods employing Caspase-8h and Caspase-8i.
    Type: Grant
    Filed: December 31, 1997
    Date of Patent: January 9, 2001
    Assignee: Millennium Pharmaceuticals, Inc.
    Inventors: John J. Hunter, Andrew W. Shyjan, Grace H. W. Wong
  • Patent number: 6172191
    Abstract: The method to isolate a protein, designated as p10, which strongly inhibits the activity of H-Ras bound to GTP in vitro while in the presence of cAMP, which inactivates the biological function of Ras is provided. Protein p10 also inhibits intrinsic GTPase activity of Ras without affecting GTP binding activity in vitro, which keeps Ras in its active form and activates Ras biologically. The invention activates or inhibits Ras in a cAMP dependent manner leading to the stimulation or inhibition of cell proliferation.
    Type: Grant
    Filed: April 24, 1998
    Date of Patent: January 9, 2001
    Inventors: David Tsai, Jenny Yu
  • Patent number: 6172192
    Abstract: The present invention relates to isolated and pure Toxoplasma gondii antigenic fragments, recombinant polypeptides, nucleic acids encoding them, primers and probes derived from the same, as well as the use of these polypeptides, nucleic acids, primers and probes in methods and kits for the diagnosis and prevention of T. gondii infection in mammals (humans and animals).
    Type: Grant
    Filed: June 30, 1998
    Date of Patent: January 9, 2001
    Assignee: Innogenetics N.V.
    Inventors: Dirk Jacobs, Eric Saman, Hugo Van Heuverswyn
  • Patent number: 6172193
    Abstract: The invention provides an isolated mutant hepatitis B surface antigen protein which comprises an amino acid sequence of a surface antigen protein of hepatitis B virus which infects humans, in which the amino acid at position 121 is not cysteine and. at least one of the amino acids at positions 120, 122, 123, 147, or 149 is not a conserved amino acid for its position. The invention also provides a method for detecting in a sample a mutant hepatitis B surface antigen protein or a particle containing the protein.
    Type: Grant
    Filed: November 16, 1998
    Date of Patent: January 9, 2001
    Assignee: DiaSorin International Inc.
    Inventors: Daniele Primi, Gianfranco Fiordalisi, Mario Palla
  • Patent number: 6172194
    Abstract: The INK4A (MTS1, CDKN2) gene encodes a specific inhibitor (InK4a-p16) of the cyclin D-dependent kinases CDK4 and CDK6. InK4a-p16 can block these kinase from phosphorylating the retinoblastoma protein (pRb), preventing exit from the G1 phase of the cell cycle. Deletions and mutations involving the gene encoding InK4a-p16, INK4A, occur frequently in cancer cells, implying that INK4a-p16, like pRb, suppresses tumor formulation. However, a completely unrelated protein (ARF-p19) arises in major part from an alternative reading frame of the mouse INK4A gene. Expression of an ARF-p19 cDNA (SEQ ID NO:1) in rodent fibroblasts induces both G1 and G2 phase arrest.
    Type: Grant
    Filed: February 9, 1999
    Date of Patent: January 9, 2001
    Assignee: St. Jude Children's Research Hospital
    Inventors: Charles J. Sherr, Dawn E. Quelle
  • Patent number: 6172195
    Abstract: The invention provides methods and compositions relating to IKAP proteins which regulate cellular signal transduction and transcriptional activation, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IKAP encoding nucleic acids or purified from human cells. The invention provides isolated IKAP hybridization probes and primers capable of specifically hybridizing with the disclosed IKAP genes, IKAP-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.
    Type: Grant
    Filed: April 6, 1999
    Date of Patent: January 9, 2001
    Assignee: Tularik Inc.
    Inventors: Lucie Cohen, Patrick Baeuerle
  • Patent number: 6172196
    Abstract: The present invention relates to a protein having the amino acid sequence represented by SEQ ID NO: 1, or a protein being capable of complementing the mutation exhibiting low-temperature-sensitive fermentability and having an amino acid sequence wherein one or more amino acid residues are added, deleted or substituted in the amino acid sequence represented by SEQ ID NO: 1; a gene which encodes said protein; and a gene which comprises DNA having the nucleotide sequence represented by SEQ ID NO: 1, or comprises DNA being capable of complementing the mutation exhibiting low-temperature-sensitive fermentability and having a nucleotide sequence wherein one or more DNAs are added, deleted or substituted in the nucleotide sequence represented by SEQ ID NO: 1.
    Type: Grant
    Filed: August 15, 1997
    Date of Patent: January 9, 2001
    Assignee: Kyowa Hakko Kogyo Co., Ltd.
    Inventors: Hideki Kawasaki, Masaya Tokai, Yasuhiro Kikuchi, Kozo Ouchi
  • Patent number: 6172197
    Abstract: A member of a specific binding pair (sbp) is identified by expressing DNA encoding a genetically diverse population of such sbp members in recombinant host cells in which the sbp members are displayed in functional form at the surface of a secreted recombinant genetic display package (rgdp) containing DNA encoding the sbp member or a polypeptide component thereof, by virtue of the sbp member or a polypeptide component thereof being expressed as a fusion with a capsid component of the rgdp. The displayed sbps may be selected by affinity with a complementary sbp member, and the DNA recovered from selected rgdps for expression of the selected sbp members. Antibody sbp members may be thus obtained, with the different chains thereof expressed, one fused to the capsid component and the other in free form for association with the fusion partner polypeptide. A phagemid may be used as an expression vector, with said capsid fusion helping to package the phagemid DNA.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: January 9, 2001
    Assignees: Medical Research Council, Cambridge Antibody Technology Limited
    Inventors: John McCafferty, Anthony Richard Pope, Kevin Stuart Johnson, Henricus Renerus Jacobus Mattheus Hoogenboom, Andrew David Griffiths, Ronald Henry Jackson, Kaspar Philipp Holliger, James David Marks, Timothy Piers Clackson, David John Chiswell, Gregory Paul Winter, Timothy Peter Bonnert
  • Patent number: 6172198
    Abstract: This invention concerns PAPP-A, its immunodetection and the clinical benefits of such immunodetection. Specifically, the invention includes monoclonal antibodies against PAPP-A and the use of these antibodies to detect PAPP-A at a very early stage of pregnancy. The invention also covers the use of the monoclonal antibodies for the detection of specific types of cancer and Down's Syndrome pregnancies.
    Type: Grant
    Filed: October 23, 1997
    Date of Patent: January 9, 2001
    Assignees: Northern Sydney Area Health Service
    Inventor: Michael Joseph Sinosich
  • Patent number: 6172199
    Abstract: The present invention provides a polynucleotide (ubcp) which identifies and encodes a novel ubiquitin-conjugating enzyme (UBCP). The invention provides for genetically engineered expression vectors and host cells comprising the nuclei acid sequence encoding UBCP. The invention also provides for the use of substantially purified UBCP and its agonists, antagonists, or inhibitors in the commercial production of recombinant proteins and in pharmaceutical compositions for the treatment of diseases associated with the expression of UBCP. Additionally, the invention provides for the use of antisense molecules to ubcp in pharmaceutical compositions for treatment of diseases associated with the expression of UBCP. The invention also describes diagnostic assays which utilize diagnostic compositions comprising the polynucleotide, fragments or the complement thereof, which hybridize with the genomic sequence or the transcript of ubcp or anti-UBCP antibodies which specifically bind to UBCP.
    Type: Grant
    Filed: May 25, 1999
    Date of Patent: January 9, 2001
    Assignee: Incyte Pharmaceuticals, Inc.
    Inventors: Janice Au-Young, Surya K. Goli, Jennifer L. Hillman
  • Patent number: 6172200
    Abstract: Invertebrate and vertebrate patched genes are provided, including the mouse and human patched genes, as well as methods for isolation of related genes, where the genes may be of different species or in the same family. The patched genes permit production of patched protein and production of antibodies that bind to patched proteins. Having the ability to regulate the expression of the patched gene, allows for the elucidation of embryonic development, cellular regulation associated with signal transduction by the patched gene, the identification of agonist and antagonist to signal transduction, identification of ligands for binding to patched, isolation of the ligands, and assaying for levels of transcription and expression of the patched gene.
    Type: Grant
    Filed: October 20, 1997
    Date of Patent: January 9, 2001
    Assignee: The Board of Trustees of the Leland S. Stanford University
    Inventors: Matthew P. Scott, Lisa V. Goodrich, Ronald L. Johnson
  • Patent number: 6172201
    Abstract: The present invention is directed to substantially pure human Vpr Interacting Protein (hVIP), and fragments thereof.
    Type: Grant
    Filed: October 13, 1999
    Date of Patent: January 9, 2001
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: David B. Weiner, Velpandi Ayyavoo, Sundarasamy Mahalingam, Mamata Patel
  • Patent number: 6172202
    Abstract: A process for the preparation of a conjugate between a poly (ethylene glycol) and a protein or glycoprotein, the process comprising specifically binding the domain to a specific binder, to shield the domain from the poly (ethylene glycol) in the following conjugating step, thereafter conjugating the poly (ethylene glycol) to the protein or glycoprotein, wherein conjugation of the poly (ethylene glycol) to the domain is avoided and thereafter releasing the specific binder from the domain without releasing the poly (ethylene glycol) from the protein or glycoprotein, wherein the protein or glycoprotein is other than a proteolytic enzyme selected from the group consisting of trypsin, urokinase, tissue plasminogen activator, plasmin, chymotrypsin, elastase and kallikrein.
    Type: Grant
    Filed: July 7, 1997
    Date of Patent: January 9, 2001
    Assignee: Pharmacia S.p.A.
    Inventors: Fabrizio Marcucci, Ruth Gregory
  • Patent number: 6172203
    Abstract: It is obtained a chloroform solution that contains liposubles lipids and proteins extracted by means of a bronchio-alveolar washing of pigs, cows or sheep with slightly hypertonic solution. From the lyophilization of such chloroform solution it is obtained a product resuspensible in physiological solution that constitutes the exogenous pulmonary surfactant utilized in pulmonary therapeutics and also for the clinic research of the pulmonary function when it is associated with radionucleus, in particular with 99 mTc for pulmonary centellography.
    Type: Grant
    Filed: November 1, 1996
    Date of Patent: January 9, 2001
    Inventors: Alfredo Adolfo Hager, Tomas DePaoli
  • Patent number: 6172204
    Abstract: A composition that includes the reaction product of a lignin derivative and a reactant selected from the group consisting of alkylating agents, acylating agents, and combinations thereof, where the reaction product has a measurable cohesive strength, and a plasticizer in an amount sufficient to cause the composition to exhibit plastic deformation in response to an applied tensile stress.
    Type: Grant
    Filed: June 4, 1999
    Date of Patent: January 9, 2001
    Assignee: Regents of the University of Minnesota
    Inventors: Simo Sarkanen, Yan Li
  • Patent number: 6172205
    Abstract: This invention provides a process for the preparation of a Eleutherobin derivative of the formula: wherein R1 is a hydrogen, ester, nitrile or C2H4—R wherein R4 is a carbohydrate, an alcohol an amine, an amide, an alkyne, or, R2 is a linear or branched alkyl moiety, R3 is an ester, an amide, a carbamate, an acetal compound,an ether or a urethane, R4 is a hydrogen or CH2,position C2 and C3 is cis or trans,position C8 is &agr; or &bgr; and a compound is produced having the structures: Additionally, this experiment provides a method for inhibiting growth of cancerous cells comprising contracting an amount of Eleutherobin derivative effective to inhibit the growth of said cells. Further provided is a method for treating cancer in a subject which comprises administering to the subject a therapeutically effective amount of the Eleutherobin derivative.
    Type: Grant
    Filed: December 11, 1998
    Date of Patent: January 9, 2001
    Assignee: The Trustees of Columbia in the City of New York
    Inventors: Samuel J. Danishefsky, Xiao-Tao Chen, Clare E. Gutteridge, Samit K. Bhattacharya, Bishan Zhou
  • Patent number: 6172206
    Abstract: A new crystalline form of morphine-6-glucuronide, referred to as Form A, characterized by its infrared spectrum pattern and/or by its x-ray powder diffraction image, the use thereof and a process for the preparation thereof.
    Type: Grant
    Filed: November 4, 1999
    Date of Patent: January 9, 2001
    Assignee: CeNeS Ltd.
    Inventors: Herwig Schneider, Rudolph Franzmair, Andreas Koch, Franz Rovensky
  • Patent number: 6172207
    Abstract: A process and a device for synthesizing labeled compounds. The process involves preparing a labeling agent, labeling a precursor with the labeling agent, where the precursor is a protected substrate, and deprotecting the labeled precursor to convert the labeled precursor to a labeled compound by passing the labeled precursor through a solid support in a column or a cartridge. The process may be used to convert labeled tetraacetylfluoroglucose (TAFg) to labeled fluoro-deoxy-glucose (FDG) for use in nuclear medical imaging. The process is more rapid than conventional methods and is performed at room temperature rather than high temperature for conventional technology.
    Type: Grant
    Filed: July 29, 1998
    Date of Patent: January 9, 2001
    Assignees: Coincidence S. A., Universite Libre de Bruxelles, Universite de Liege
    Inventors: Philippe E. Damhaut, Michel Monclus, John J. Van Namen, Eric Mulleneers, Jean-Luc E. Morelle, Christian F. Lemaire, Andre Luxen, Benjamin P. Lauricella
  • Patent number: 6172208
    Abstract: An oligonucleotide wherein at least one nucleotide unit of the oligonucleotide is conjugated with a moiety selected from the group consisting of: (a) amino acids; (b) dipeptide mimics; (c) sugars; (d) sugar phosphates; (e) neurotransmitters; (f) poly-hydroxypropylmethacrylamide; (g) dextrans; (h) polymaleic anhydride; (i) cyclodextrins; (j) starches; and (k) polyethyleneimine. The oligonucleotides may be employed for binding to an RNA, and DNA, a protein, or a peptide to inhibit or prevent gene transcription or gene expression, to inhibit or stimulate the activities of target molecules, or the oligonucleotides may be employed as diagnostic probes for determining the presence of specific DNA or RNA sequences or proteins.
    Type: Grant
    Filed: July 6, 1992
    Date of Patent: January 9, 2001
    Assignee: Genzyme Corporation
    Inventor: Alan Frederick Cook
  • Patent number: 6172209
    Abstract: Oligonucleotides and other macromolecules are provided which have increased nuclease resistance, substituent groups (such as 2′-aminooxy groups) for increasing binding affinity to complementary strand, and subsequences of 2′-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H. Such oligonucleotides and macromolecules are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics.
    Type: Grant
    Filed: August 7, 1998
    Date of Patent: January 9, 2001
    Assignee: ISIS Pharmaceuticals Inc.
    Inventors: Muthiah Manoharan, Phillip Dan Cook, Thazha P. Prakash, Andrew M. Kawasaki
  • Patent number: 6172210
    Abstract: An protein preparation that mediates Ca+2 transbilayer movement of phospholipid is disclosed. A recombinantly engineered DNA sequence encoding the protein, an inhibitor of the protein activity, genetically engineered cells with altered protein activity, and therapeutic methods are also disclosed.
    Type: Grant
    Filed: January 29, 1997
    Date of Patent: January 9, 2001
    Assignee: Blood Center Research Foundation
    Inventors: Therese Wiedmer, Peter J. Sims
  • Patent number: 6172211
    Abstract: The present invention is generally directed to the identification of mouse and human genes that inhibit the growth of a tumor and induce apoptosis in cancer cells, and to polypeptides encoded by such genes. In particular, the invention concerns the nucleotide sequence of one such tumor-inhibiting gene, tag7, and the amino acid sequence of a polypeptide encoded by tag7. The invention also provides isolated nucleic acid molecules comprising tag7 polynucleotides, and vectors and host cells comprising these isolated nucleic acid molecules. The invention also provides methods of producing tag7 polypeptides using these nucleic acid molecules, vectors and host cells, tag7 polypeptides made by these methods and antibodies that specifically bind to the tag7 polypeptide. The invention also concerns methods of inhibiting tumor growth and inducing tumor cell apoptosis, and methods of cancer therapy, using the present tag7 nucleic acid molecules and polypeptides.
    Type: Grant
    Filed: July 11, 1997
    Date of Patent: January 9, 2001
    Assignee: Boehringer Ingelheim International GmbH
    Inventors: Georgii P. Georgiev, Sergei L. Kiselev, Egor B. Prokhorchouk, Elinborg Ostermann
  • Patent number: 6172212
    Abstract: The present invention relates generally to the fields of cancer therapy and gene therapy. More particularly, it demonstrates that PEA3 is a tumor suppressor and may be used to treat various forms of cancer, and especially neu-mediated cancer.
    Type: Grant
    Filed: April 30, 1999
    Date of Patent: January 9, 2001
    Assignee: Board of Regents, The University of Texas System
    Inventors: Mien-Chie Hung, Xiangming Xing
  • Patent number: 6172213
    Abstract: The present invention relates to a method for adjusting the affinity of a polypeptide to a target molecule by a combination of steps, including: (1) the identification of aspartyl residues which are prone to isomerization; (2) the substitution of alternative residues and screening the resulting mutants for affinity against the target molecule. In a preferred embodiment, the method of substituting residues is affinity maturation with phage display (AMPD). In a further preferred embodiment the polypeptide is an antibody and the target molecule is an antigen. In a further preferred embodiment, the antibody is anti-IgE and the target molecule is IgE. In another embodiment, the invention relates to an anti-IgE antibody having improved affinity to IgE.
    Type: Grant
    Filed: June 30, 1998
    Date of Patent: January 9, 2001
    Assignee: Genentech, Inc.
    Inventors: Henry B. Lowman, Leonard G. Presta, Paula M. Jardieu, John Lowe
  • Patent number: 6172214
    Abstract: The invention provides a method of tracking, identifying, and/or sorting classes or subpopulations of molecules by the use of oligonucleotide tags. Oligonucleotide tags of the invention comprise oligonucleotides selected from a minimally cross-hybridizing set. Preferably, such oligonucleotides each consist of a plurality of subunits 3 to 9 nucleotides in length. A subunit of a minimally cross-hybridizing set forms a duplex or triplex having two or more mismatches with the complement of any other subunit of the same set. The number of oligonucleotide tags available in a particular embodiment depends on the number of subunits per tag and on the length of the subunit. An important aspect of the invention is the use of the oligonucleotide tags for sorting polynucleotides by specifically hybridizing tags attached to the polynucleotides to their complements on solid phase supports.
    Type: Grant
    Filed: August 7, 1998
    Date of Patent: January 9, 2001
    Assignee: Lynx Therapeutics, Inc.
    Inventor: Sydney Brenner
  • Patent number: 6172215
    Abstract: DNA probes for detecting the presence of Helicobacter pylori are provided. These isolated, purified oligonucleotide probes are useful in assays for the specific detection of Helicobacter pylori because they specifically hybridize to the DNA of H. pylori.
    Type: Grant
    Filed: July 12, 1999
    Date of Patent: January 9, 2001
    Assignee: Fuso Pharmaceutical Industries, Ltd.
    Inventors: Hiroyuki Keshi, Soji Eda, Hirotsugu Uehara, Keigo Nishida, Akio Matsuhisa
  • Patent number: 6172216
    Abstract: Compositions and methods are provided for modulating the expression of bcl-x. Antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding bcl-x are preferred. Methods of using these compounds for modulation of bcl-x expression and for treatment of diseases associated with expression of bcl-x are also provided.
    Type: Grant
    Filed: October 7, 1998
    Date of Patent: January 9, 2001
    Assignee: Isis Pharmaceuticals Inc.
    Inventors: C. Frank Bennett, Nicholas M. Dean, Brett P. Monia, Brian J. Nickoloff, QingQing Zhang
  • Patent number: 6172217
    Abstract: This invention presents novel methods for synthesizing phosphorothioate oligonucleotides, using support-bound phosphoramiditese. Novel intermediates useful in the methods are also provided.
    Type: Grant
    Filed: December 27, 1996
    Date of Patent: January 9, 2001
    Assignee: ISIS Pharmaceuticals Inc.
    Inventors: Douglas L. Cole, Vasulinga Ravikumar
  • Patent number: 6172218
    Abstract: The invention provides a method of tracking, identifying, and/or sorting classes or subpopulations of molecules by the use of oligonucleotide tags. Oligonucleotide tags of the invention comprise oligonucleotides selected from a minimally cross-hybridizing set. Preferably, such oligonucleotides each consist of a plurality of subunits 3 to 9 nucleotides in length. A subunit of a minimally cross-hybridizing set forms a duplex or triplex having two or more mismatches with the complement of any other subunit of the same set. The number of oligonucleotide tags available in a particular embodiment depends on the number of subunits per tag and on the length of the subunit. An important aspect of the invention is the use of the oligonucleotide tags for sorting polynucleotides by specifically hybridizing tags attached to the polynucleotides to their complements on solid phase supports.
    Type: Grant
    Filed: June 5, 1998
    Date of Patent: January 9, 2001
    Assignee: Lynx Therapeutics, Inc.
    Inventor: Sydney Br{umlaut over (e)}nner
  • Patent number: 6172219
    Abstract: The present invention is drawn to inner esters of gellan, wherein the carboxy groups are esterified with hydroxy groups from either the same or different molecules of gellan. The present invention is further drawn to methods of using the present inner esters of gellan in the fields of cosmetics, pharmaceuticals and in sanitary and surgical articles. The present invention is further drawn to products made from inner esters of gellan and to be used in the indicated fields.
    Type: Grant
    Filed: November 25, 1997
    Date of Patent: January 9, 2001
    Assignee: M.U.R.S.T. Italian Ministry for Universities and Scientific and Technological Research
    Inventors: Lanfranco Callegaro, Filippo Biviano, Vittorio Crescenzi
  • Patent number: 6172220
    Abstract: The isolation and purification of lipopolysaccharides from several related strains of eukaryotic algae is disclosed. These lipopolysaccharides have been shown to be structurally and functionally similar to the lipopolysaccharides of gram negative bacteria, or endotoxins, which have been shown to be a cause of sepsis or septic shock. The present invention also relates to the use of these algal lipopolysaccharides to inhibit the release of TNF-a from macrophages, which has been associated with the initiation and escalation of sepsis as a result of bacterial endotoxins.
    Type: Grant
    Filed: January 16, 1998
    Date of Patent: January 9, 2001
    Assignee: Board of Regents of University of Nebraska
    Inventors: Rosevelt L. Pardy, Clare L. Royce
  • Patent number: 6172221
    Abstract: A back extraction process in which beta-lactam antibiotics or clavulanic acid is extracted from an organic solvent phase into an aqeous medium phase, using a mixing region in which the phases are mixed rapidly under high turbulence and shear stress.
    Type: Grant
    Filed: August 27, 1997
    Date of Patent: January 9, 2001
    Assignee: SmithKline Beecham p.l.c.
    Inventor: Simon Ruddick
  • Patent number: 6172222
    Abstract: This invention concerns the treatment of smooth muscle spasticity or excess muscle contraction such as urge urinary incontinence with a compound of the formula wherein: R1 and R2 are independently straight chain alkyl of 1 to 6 carbon atoms, branched alkyl of 3 to 6 carbons atoms, or cycloalkyl of 3 to 6 carbons atoms where R1 and R2 may be substituted by F, Cl, Br, I, OH, NH2, cyano, C1-C6 alkoxy, C1-C6alkylthio, COOH or COOC1-C6 alkyl; R3 is an aryl or heteroaryl as defined herein, optionally substituted with 0 to 4 groups selected independently from C1-C6 alkyl, C1-C6 alkoxy, cyano, F, Cl, Br, C1-C6 alkylthio, CO2R1, CONH2, OH, NH2, and NO2; n is 0 or 1; R4 is a straight chain alkyl group of 1 to 10 carbons atoms, a branched alkyl of 3 to 10 carbons, or a cycloalkyl of 3 to 10 carbons; and all crystalline forms and the pharmaceutically acceptable salts thereof.
    Type: Grant
    Filed: June 7, 1999
    Date of Patent: January 9, 2001
    Assignee: American Home Products Corporation
    Inventors: Adam Matthew Gilbert, Zhen-jia Chen
  • Patent number: 6172224
    Abstract: A process for purifying 2-amino-6-chloro-9-[(1′S,2′R)-1′,2′-bis(hydroxymethyl) cycdopropane-1′-yl]methylpurine represented by the following formula (5) comprises the step of selectively isolating 2-amino-6-chloro-9-[(1′S,2′R)-1′,2′-bis(hydroxymethyl) cyclopropane-1′-yl]methylpurine from a mixture of 2-amino-6-chloro-9-[(1′S,2′R)-1′,2′-bis(hydroxymethyl)cyclopropane-1′-yl]methylpurine and 2-amino-6-chloro-7-[(1′S,2′R)-1′,2′-bis(hydroxymethyl)cyclopropane-1′-yl]methylpurine represented by the following formula (6) by the crystallization. This process has a satisfactory medicinal quality on an industrial scale without necessitating complicated operations such as chromatographic purification.
    Type: Grant
    Filed: March 8, 1999
    Date of Patent: January 9, 2001
    Assignee: Ajinomoto Co., Inc.
    Inventors: Noriyasu Kataoka, Toshihiro Matsuzawa, Masanobu Yatagai
  • Patent number: 6172225
    Abstract: The invention relates to a novel process for producing thereof hydroxyarenes of the general formula (I) in which n represents the numbers 1, 2, 3 or 4, R represents cyano, carboxyl, formyl, nitro, halogen or represents alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylcarbonyl or alkoxycarbonyl, each of which is optionally substituted, and Z represents hydrogen, cyano, nitro, halogen, alkyl, halogenoalkyl, or represents monocyclic or bicyclic, saturated or unsaturated heterocyclyl, heterocyclylamino or heterocyclylimino, each of which is optionally substituted, characterized in that halogenoarenes of the general formula (II) in which n, R and Z are each as defined above and X represents halogen are reacted with 3-hydroxy-propionitrile of the formula (III), HO—CH2CH2—CN  (III), if appropriate in the presence of a reaction auxiliary and if appropriate in the presence of a diluent, at temperatures between 0° C. and 100° C.
    Type: Grant
    Filed: November 12, 1998
    Date of Patent: January 9, 2001
    Assignee: Bayer Aktiengesellschaft
    Inventors: Karl-Heinz Linker, Wilhelm Haas, Otto Schallner, Kurt Findeisen, Roland Andree, Mark Wilhelm Drewes
  • Patent number: 6172226
    Abstract: A method is disclosed for preparing novel PNA synthons having protecting groups capable of removal under mild conditions. The PNA synthons are prepared by coupling novel N-substituted nucleobase intermediates having carbamate protection of the exocyclic amino group of the heterocycle to an amino protected backbone or an amino protected backbone ester of the amino acid N-(2-aminoethyl)-glycine. By the method of this invention, the resultant PNA synthons can have orthogonal protection of the carbamate protected nucleobase and the amino protected backbone. The PNA synthons are useful in the synthesis of peptide nucleic acids (PNAs) and other oligomers such as PNA-DNA chimeras, and may be used in automated synthesizers. Novel compositions of matter are also disclosed. In addition, a guanine PNA synthon having selective carbamate protection of the exocyclic 2-amino group with the C6 carbonyl group unprotected is disclosed.
    Type: Grant
    Filed: July 16, 1998
    Date of Patent: January 9, 2001
    Assignee: PerSeptive Biosystems, Inc.
    Inventors: James M. Coull, Michael Egholm, Richard P. Hodge, Mohamed Ismail, S. B. Rajur
  • Patent number: 6172227
    Abstract: Novel 4,5-diamino pyrimidine derivatives are described by the following general formula I: in which X is a direct bond, C1-4 alkylene, C1-4 alkyleneoxy, C1-4 alkoxyphenyl or phenyl C1-4 alkylene; Y is a direct bond or C1-2 alkyl, R1 is (i) 5-15 membered cyclic or fused heterocompound which includes one or two atoms selected from a group consisting of nitrogen, oxygen and sulfur and which is substituted with one or two substituents selected from a group consisting of hydrogen, halogen, nitro, hydroxy, C1-6 alkyl, C3-6 alkenyl and halogen C1-4 alkoxy, (ii) C4-10 carbocyclic compound or (iii) hydroxy C1-4 alkoxy, R2 is 5-15 membered cyclic or fused heterocompound which includes one or two nitrogen atoms and, optionally, one oxygen or sulfur atom, and which is substituted with one or two substituents selected from a group consisting of hydrogen, hydroxy, halogen, nitro, hydroxy C1-5 alkyl, C1-6 alkyl, C3-6 alkenyl and halogen C1-4 alkoxy; R3 is hydrogen, in which R4 and R5 are
    Type: Grant
    Filed: September 16, 1997
    Date of Patent: January 9, 2001
    Assignee: Cheil Jedang Corporation
    Inventors: Myung Xik Xiang, Byoung Chool Suh, Chung Keun Rhee, Kwang Hyuk Lee, Youn Ha Lee, Young Gi Kim
  • Patent number: 6172228
    Abstract: A process for advantageously preparing a piperazinesulfonamide derivative represented by the general formula (III): wherein R1 is hydrogen atom, a straight or branched chain alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a halogen atom, hydroxyl group, trifluoromethyl group, nitro group or amino group; R2 is a phenyl group which may have as substituents on its phenyl ring 1 to 3 groups selected from the group consisting of an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a halogen atom, hydroxyl group, trifluoromethyl group, nitro group and amino group, 2-pyridyl group, 3-pyridyl group or 4-pyridyl group; each of R3 and R4 is independently hydrogen atom, a straight or branched chain alkyl group having 1 to 6 carbon atoms, a hydroxyalkyl group having 1 to 4 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, or a phenyl group which may be substituted; and Y is an alkylene group having 1 to 12 carbon atoms, and
    Type: Grant
    Filed: December 3, 1999
    Date of Patent: January 9, 2001
    Assignee: Azwell Inc.
    Inventors: Kenichi Kashima, Yasuhiko Sakamoto, Yoichiro Ohta, Kenji Kawanishi, Shigetaka Takemura, Yasuko Takemura
  • Patent number: 6172229
    Abstract: Disclosed are compounds of the formula: or the pharmaceutically acceptable addition salts thereof wherein: R1 is halogen or C1-C4 alkyl; and R2 and R3 are the same or different and represent hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, alkylthio, hydroxy, amino, mono(C1-C4)alkylamino, di(C1-C4)alkylamino, or R2 and R3 together represent a 4 carbon alkenylene moiety that together with the phenyl ring to which they are attached form a naphthyl moiety, which compounds are useful in the treatment of neuropsycological diseases such as schizophrenia, psychotic depression and mania.
    Type: Grant
    Filed: January 11, 1999
    Date of Patent: January 9, 2001
    Assignee: Neurogen Corporation
    Inventors: Andrew Thurkauf, Xi Chen
  • Patent number: 6172230
    Abstract: Described is a process for the preparation of Compound (7) in accordance with the following reaction scheme by reacting Compound (5) with ethylene glycol in a solvent in the presence of a Lewis acid, thereby obtaining Compound (6), and then reacting the resulting compound with a carbonate diester in a solvent in the presence of a metal alkoxide (R1, R6 each represents a C1-6 alkyl group or the like and R5 represents H or C1-5 alkyl group). Compound (7) so obtained is useful as an intermediate for camptothecins useful as antitumor agents.
    Type: Grant
    Filed: October 26, 1998
    Date of Patent: January 9, 2001
    Assignee: Daiichi Pharmaceutical Co., Ltd.
    Inventors: Shinji Kamihara, Kazuaki Kanai, Shigeru Noguchi
  • Patent number: 6172231
    Abstract: The present invention relates to a periodic acid oxidation which converts the penultimate intermediate bearing a primary alcohol to the target endothelin antagonist compound of Formula I having a carboxylic acid.
    Type: Grant
    Filed: April 1, 1999
    Date of Patent: January 9, 2001
    Assignee: Merck & Co., Inc.
    Inventors: Zhiguo Song, Mangzu Zhao, David M. Tschaen
  • Patent number: 6172232
    Abstract: The present invention relates to novel compounds of the formula (I) in which the substituents have the meaning defined in the description. These novel compounds are excellent stabilizers for organic material against the damaging effects of light, heat and oxygen.
    Type: Grant
    Filed: September 3, 1998
    Date of Patent: January 9, 2001
    Assignee: Clariant GmbH
    Inventor: Thomas St{umlaut over (a)}hrfeldt
  • Patent number: 6172233
    Abstract: Compounds of structure (2) are prepared by reaction of an arecoline analogue of structure(4) with an organometallic compound containing an X-substituted phenyl group, such as a compound of structure (3). Suitably the compound of structure (3) is a Grignard reagent, where M is magnesium and Y is a halogen atom, or M may be a Group II metal and Y is a halogen atom or a second X-substituted phenyl group. When structure (3) is a Grignard reagent, the reaction is carried out either in a suitable non-ether solvent, typically a hydrocarbon or a non-reactive chlorinated hydrocarbon, or in a mixture of such a solvent with diethyl ether. Compounds of structure (2) are important intermediates in the preparation of inter alia paroxetine.
    Type: Grant
    Filed: January 15, 1998
    Date of Patent: January 9, 2001
    Assignee: SmithKline Beecham plc
    Inventor: Neal Ward
  • Patent number: 6172234
    Abstract: There are disclosed a process for producing the optically active cyclic amino acid ester derivative of the formula (I): by optical resolution method, a process for producing the same and a process for producing an optically active cyclic amino acid using the compound of the formula (I).
    Type: Grant
    Filed: July 27, 1999
    Date of Patent: January 9, 2001
    Assignee: Sumitomo Chemical Company, Limited
    Inventors: Yukihiro Honda, Miyuki Oikawa, Isao Kurimoto
  • Patent number: 6172235
    Abstract: This invention relates to a key intermediate in the synthesis of an endothelin antagonist and the synthesis of this key intermediate using an asymmetric conjugate addition reaction.
    Type: Grant
    Filed: April 27, 1999
    Date of Patent: January 9, 2001
    Assignee: Merck & Co., Inc.
    Inventors: Ulf H. Dolling, Lisa F. Frey, Richard D. Tillyer, David M. Tschaen
  • Patent number: 6172236
    Abstract: According to a novel process, triazolinethione derivatives of the formula in which R1 and R2 are each as defined in the description can be prepared by reacting triazole derivatives of the formula  with sulphur in the presence of an aprotic polar diluent at temperatures between 140° C. and 160° C., where the amounts of the reaction components are chosen such that between 6 and 15 mol of sulphur are present per mole of triazole derivative of the formula (II), and where air is passed over the reaction mixture during the reaction.
    Type: Grant
    Filed: April 4, 2000
    Date of Patent: January 9, 2001
    Assignee: Bayer Aktiengesellschaft
    Inventors: Manfred Jautelat, David Erdman
  • Patent number: 6172237
    Abstract: This invention relates to a process for preparing eprosartan by reacting 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid or the bisulfite addition compound of 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid with (2-thienylmethyl)propanedioic acid, mono-ethyl ester.
    Type: Grant
    Filed: July 27, 1999
    Date of Patent: January 9, 2001
    Assignee: SmithKline Beecham Corporation
    Inventors: Clifford S. Labaw, Joseph Robert Flisak, Li Liu
  • Patent number: 6172238
    Abstract: A process manufactures of a compound of formula: and unique intermediates.
    Type: Grant
    Filed: December 13, 1999
    Date of Patent: January 9, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Paul Anthony Brown, Hans Hilpert
  • Patent number: 6172239
    Abstract: The invention relates to compounds of the formula The compounds have agreat affinity for the neurotensin receptors.
    Type: Grant
    Filed: August 16, 1999
    Date of Patent: January 9, 2001
    Assignee: Sanofi
    Inventors: Bernard Labeeuw, Danielle Gully, Francis JeanJean, Jean-Charles Molimard, Robert Boigegrain
  • Patent number: 6172240
    Abstract: The present invention relates to pyrrole derivatives, particularly 2-(2-thienyl)-5-(5-tricyanoethenyl-2-thienyl)pyrrole derivatives, which has metallic luster, good stability in air, and a high solubility in an organic solvent, and which is suitable for a film-forming material.
    Type: Grant
    Filed: December 29, 1999
    Date of Patent: January 9, 2001
    Assignee: Chiba University
    Inventor: Katsuyuki Ogura