Patents Represented by Attorney William H. Epstein
  • Patent number: 6331640
    Abstract: A compound of formula 1a which is useful for treating reperfusion injury, and salts, prodrugs, and related compounds.
    Type: Grant
    Filed: September 29, 1999
    Date of Patent: December 18, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Nader Fotouhi, Paul Gillespie, Robert William Guthrie, Sherrie Lynn Pietranico-Cole, Weiya Yun
  • Patent number: 6320054
    Abstract: Compounds of the formula: as well as pharmaceutically usable salts and esters thereof, wherein R1, R2 and R3 have the significance ascribed herein, inhibit binding of adhesive proteins to the surface of different types of cell and accordingly influence cell-cell and cell-matrix interactions. These compounds can be used in the form of pharmaceutical preparations for the control or prevention of neoplasms, tumor metastasing, tumor growth, osteoporosis, Paget's disease, diabetic retinopathy, macular degeneration, restenosis following vascular intervention, psoriasis, arthritis, fibrosis, kidney failure, as well as infection caused by viruses, bacteria or fungi.
    Type: Grant
    Filed: March 15, 2000
    Date of Patent: November 20, 2001
    Assignee: Hoffman-La Roche Inc.
    Inventors: Leo Alig, Albrecht Edenhofer, Kurt Hilpert, Thomas Weller
  • Patent number: 6320050
    Abstract: 2,3-Di-substituted N-heteroaromatic propionamides with said substitution at the 2-position being a substituted phenyl group and at the 3-position being a cycloalkyl ring, said propionamides being glucokinase activators which increase insulin secretion in the treatment of type II diabetes.
    Type: Grant
    Filed: March 15, 2000
    Date of Patent: November 20, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Fred Thomas Bizzarro, Wendy Lea Corbett, Joseph Francis Grippo, Nancy-Ellen Haynes, George William Holland, Robert Francis Kester, Ramakanth Sarabu
  • Patent number: 6316593
    Abstract: This invention relates to a novel process for the synthesis of vasoactive intestinal peptide analog Ac(1-31)-NH2 from four protected peptide fragments.
    Type: Grant
    Filed: December 18, 1998
    Date of Patent: November 13, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: David Robert Bolin, Waleed Danho, Arthur M. Felix
  • Patent number: 6310213
    Abstract: The invention relates to compounds of the general formula wherein R1 signifies hydrogen or hydroxy; R2 signifies hydrogen or methyl; and X signifies —O— or —CH2— and their pharmaceutically acceptable acid addition salts. It has been shown that these compounds have a good affitity to the NMDA receptor and they are therefore useful in the treatment of diseases, wherein the therapeutic indications include acute forms of neurodegeneration caused, e.g., by stroke or brain trauma; chronic forms of neurodegeneration such as Alzheimer's disease, Parkinson's disease, Huntington's disease or ALS (amyotrophic lateral sclerosis); neurodegeneration associated with bacterial or viral infections, and, diseases such as schizophrenia, anxiety, depression and chronic/acute pain.
    Type: Grant
    Filed: June 2, 2000
    Date of Patent: October 30, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Alexander Alanine, Serge Burner, Bernd Büttelmann, Marie-Paule Heitz Neidhart, Georg Jaeschke, Emmanuel Pinard, René Wyler
  • Patent number: 6309861
    Abstract: A process produces a water-soluble, naturally folded eukaryotic polypeptide containing two or several cysteines linked by disulfide bridges. This process involves culturing prokaryotic cells, a) in which the prokaryotic cells contain an expression vector which encodes the polypeptide which contains a prokaryotic signal sequence at the N-terminus, b) under conditions under which the polypeptide is secreted into the periplasm or the medium, c) cleaving the signal sequence and isolating the polypeptide from the periplasm or the medium. In this process, the culturing is carried out in the presence of arginine or a compound of the formula I R2—CO—NR1 (I) in which R and R1 represent hydrogen or a saturated or unsaturated branched or unbranched C1-C4 alkyl chain and R2 represents hydrogen, NHR1 or a saturated or unsaturated branched or unbranched C1-C3 alkyl chain, is suitable for the recombinant production of polypeptides in prokaryotes in a high yield.
    Type: Grant
    Filed: April 20, 2000
    Date of Patent: October 30, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Dorothee Ambrosius, Rainer Rudolph, Joerg Schaeffner, Elisabeth Schwarz
  • Patent number: 6310208
    Abstract: Since the compounds in accordance with the invention can bind to serotonin receptors (5HT2), they are especially suitable for the treatment or prevention of central nervous disorders such as depressions, bipolar disorders, anxiety states, sleep and sexual disorders, psychoses, schizophrenia, migraine and other conditions associated with cephalic pain or pain of a different kind, personality disorders or obsessive-compulsive disorders, social phobias or panic attacks, mental organic disorders, mental disorders in childhood, aggressivity, age-related memory disorders and behavioral disorders, addiction, obesity, bulimia etc., nervous system damage caused by trauma, stroke, neurodegenerative diseases etc.; cardiovascular disorders such as hypertension, thrombosis, stroke etc.; and gastrointestinal disorders such as dysfunction of the gastrointestinal tract motility.
    Type: Grant
    Filed: January 6, 1998
    Date of Patent: October 30, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Michael Bös, Heinz Stadler, Jürgen Wichmann
  • Patent number: 6310262
    Abstract: A new process prepares retiferol derivatives of formula I: wherein A is —C ≡C— or —CH═CH—, and R1 and R2 are independently of each other lower alkyl or lower perfluoroalkyl, one version couples ketones of formula 1I with compounds of formula III A second version couples phosphinoxides of formula IV with aldehydes of formula V. Compounds of formula I are useful in the treatment or prevention of hyperproliferative skin diseases and for reversing the conditions associated with photodamage.
    Type: Grant
    Filed: October 3, 2000
    Date of Patent: October 30, 2001
    Assignee: Basilea Pharmaceutica AG
    Inventor: Hans Hilpert
  • Patent number: 6299906
    Abstract: The present invention relates to a process for manufacturing a pulverous preparation of a submicron-sized biologically active compound comprising the steps of dissolving a biologically active compound under elevated pressure in a compressed gas, liquid or supercritical fluid containing a surface modifier; and rapidly expanding the compressed solution thereby precipitating the dissolved compound. An alternative process comprises dissolving the biologically active compound in compressed dimethylether, which may optionally contain a surface modifier; and spraying the compressed solution into an antisolvent phase, optionally containing a surface modifier, under vacuum, atmospheric pressure or elevated pressure. An optional third step involves converting the antisolvent phase into a pulverous preparation using conventional powder processing.
    Type: Grant
    Filed: April 6, 1999
    Date of Patent: October 9, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Alexander Bausch, Pirmin Hidber
  • Patent number: 6297266
    Abstract: Compounds of formula (I) as well as pharmaceutically usable salts and esters thereof, wherein R1, R2 and R3 have the significance described in the specification, inhibit the binding of adhesive proteins to the surface of different types of cell and accordingly influence cell-cell and cell-matrix interactions. They can be used in the form of pharmaceutical preparations in the control or prevention of neoplasms, tumor metastasizing, tumor growth, osteoporosis, Paget's disease, diabetic retinopathy, macular degeneration, restenosis following vascular intervention, psoriasis, arthritis, fibrosis, kidney failure as well as infections caused by viruses, bacteria or fungi.
    Type: Grant
    Filed: October 19, 1999
    Date of Patent: October 2, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Leo Alig, Kurt Hilpert, Thomas Weller
  • Patent number: 6297375
    Abstract: The compounds of the related invention are related to 4-phenyl-pyridine derivatives connected by a bridge containing oxygen or nitrogen to a phenyl derivative.
    Type: Grant
    Filed: February 22, 2000
    Date of Patent: October 2, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Michael Bös, Quirico Branca, Guido Galley, Thierry Godel, Torsten Hoffmann, Walter Hunkeler, Patrick Schnider, Heinz Stadler
  • Patent number: 6294196
    Abstract: The invention relates to a solid pharmaceutical form of administration containing a diphosphonic acid or a physiologically compatible salt thereof as the active substance, wherein the active substance is present in granulate form, optionally together with pharmaceutical adjuvants in the inner phase, and the outer phase contains a lubricant in the form of less than 5% by weight of stearic acid relative to the total weight of the form of administration.
    Type: Grant
    Filed: October 7, 1999
    Date of Patent: September 25, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Rolf-Dieter Gabel, Walter Preis, Heinrich Woog
  • Patent number: 6294688
    Abstract: A stereospecific method for accomplishing the below reaction: results in the compound of formula 2 having the same stereochemistry at both carbon 1 and carbon 3 as that in the compound of formula 1. Thus, if carbon 3 is in the R-configuration in the compound of formula 1, then carbon 3 will be in the R-configuration in the compound of resulting formula 2. In the above process, R1 is C1-C6 alkyl that can be straight-chain or branched. The process functions using a fluorinated alcohol having a pKa less than about 9, in the presence of a palladium catalyst. The compounds of formula 1, as well as novel intermediates in this process, are useful in manufacturing vitamin D analogs.
    Type: Grant
    Filed: August 7, 2000
    Date of Patent: September 25, 2001
    Assignee: Hoffman-La Roche Inc.
    Inventors: Andrzej Robert Daniewski, Marek Michal Kabat, Masami Okabe, Roumen Nikolaev Radinov
  • Patent number: 6291694
    Abstract: A stereospecific method for accomplishing the below reaction: results in the compound of formula 2 having the same stereochemistry at both carbon 1 and carbon 3 as that in the compound of formula 1. Thus, if carbon 3 is in the R-configuration in the compound of formula 1, then carbon 3 will be in the R-configuration in the compound of resulting formula 2. In the above process, R1 is C1-C6 alkyl that can be straight-chain or branched. The process functions using a fluorinated alcohol having a pKa less than about 9, in the presence of a palladium catalyst. The compounds of formula 1, as well as novel intermediates in this process, are useful in manufacturing vitamin D analogs.
    Type: Grant
    Filed: August 7, 2000
    Date of Patent: September 18, 2001
    Assignee: Hoffman-La Roche Inc.
    Inventors: Andrzej Robert Daniewski, Marek Michal Kabat, Masami Okabe, Roumen Nikolaev Radinov
  • Patent number: 6291465
    Abstract: The invention relates to compounds of the formula wherein R is hydrogen, lower alkyl, lower alkoxy halogen, amino, —N(R6)2 or trifluoromethyl; R1 is hydrogen lower alkoxy or halogen, R and R1 may be together —CH═CH—CH═CH—; R2 is halogen, lower alkyl or trifluoromethyl; R3 is hydrogen or lower alkyl; R4 is hydrogen or a cyclic tertiary amine, optionally substituted by lower alkyl; R5 is hydrogen, nitro, amino or —N(R6)2; R6 is hydrogen or lower alkyl, X is —C(O)N(R6)—, —(CH2)nO—, (CH2)nN(R6)—, —N(R6)C(O)— or —N(R6)(CH2)n—; and n is 1 or 2; and pharmaceutically acceptable acid addition salts thereof. The compounds of formula I may be used for the treatment of diseases related to the NK-1 receptor.
    Type: Grant
    Filed: February 25, 2000
    Date of Patent: September 18, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Michael Bös, Guido Galley, Thierry Godel, Torsten Hoffmann, Walter Hunkeler, Patrick Schnider, Heinz Stadler
  • Patent number: 6291245
    Abstract: A prokaryotic expression vector including an origin of replication, at least one eukaryotic auxotrophy marker gene which encodes an enzyme required for the synthesis of a product necessary for the survival of at auxotrophic prokaryote under the control of a eukaryotic promoter, a foreign gene under the control of a prokaryotic promoter, and one or more transcription terminators.
    Type: Grant
    Filed: June 25, 1999
    Date of Patent: September 18, 2001
    Assignee: Roche Diagnostics GmbH
    Inventors: Erhard Kopetzki, Christian Schantz
  • Patent number: 6291685
    Abstract: The present invention is concerned with a novel process for the preparation of the hydroxybenzothiophene of formula I comprising cyclocarbonylation of a compound of formula II wherein Y is as defined in the specification, followed by saponification. The compound of Formula I is a building block of pharmaceutically active substances, e.g. 5-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-7-benzothiophenylmethyl]-2,4-thiazolidinedione and the corresponding sodium salt which are from agents useful in the treatment of diabetes.
    Type: Grant
    Filed: July 26, 2000
    Date of Patent: September 18, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Bernd Junghans, Michelangelo Scalone, Thomas Albert Zeibig
  • Patent number: 6288280
    Abstract: A process for the racemization of atropisomeric bis(phosphine oxide) compounds of formula I: in their (S) or (R) or non-racemic form, is useful for preparing optical active bisphosphine ligands, that form optical active complexes with transition metals. Racemization is thermal and carried out in high or low boiling solvent, under normal or elevated pressure at 105 to 3.5×107 Pa. Heating is performed in a system that allows heating up to 400° C. (reactor, autoclave, aluminum block, round-bottom flask with heating/stirring mantle and the like) or by microwave irradiation or in the melt at a temperature from 260 to 400° C.
    Type: Grant
    Filed: June 15, 2000
    Date of Patent: September 11, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Frank Kienzle, Michel Lalonde, Rudolf Schmid, Shaoning Wang
  • Patent number: 6288267
    Abstract: It has been discovered that compounds of the formula: and the pharmaceutically acceptable salts and esters thereof wherein X and Y are as defined below, inhibit the binding of VCAM-1 to VLA-4 and are useful in treating inflammation associated with chronic inflammatory diseases such as rheumatoid arthritis (RA), multiple sclerosis, (MS), asthma, and inflammatory bowel disease (I BD).
    Type: Grant
    Filed: February 17, 2000
    Date of Patent: September 11, 2001
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Kenneth Gregory Hull, Achytharao Sidduri, Jefferson Wright Tilley
  • Patent number: 6284785
    Abstract: 1-Arenesulfonyl-2-Aryl-pyrrolidine and pyridine derivatives having activity as ligands of metabotropic glutamate receptors of the formula are disclosed.
    Type: Grant
    Filed: March 24, 2000
    Date of Patent: September 4, 2001
    Assignee: Hoffmann- La Roche Inc.
    Inventors: Vincent Mutel, Eric Vieira, Jürgen Wichmann