Abstract: High-Throughput Screening (HTS) of large compound libraries is the method of drug-lead discovery. It is now well accepted that for a functional assay, quality is more important than quantity. A biochemical NMR method originally proposed by Percival and Withers (Biochemistry, 1992, 31, 498–505) is extended to the screening of Ser/Thr kinases. The method requires the presence of a CF3 (or CF) moiety on the substrate and utilizes 19F NMR spectroscopy for the detection of the starting and enzymatically modified substrates. Experiments can be performed in real time or in an endpoint assay format using protein and substrate concentrations comparable to the ones used by other HTS techniques. Application of this technique to the phosphorylation of a substrate by the protein Ser/Thr kinase AKT1 is presented.
Type:
Grant
Filed:
July 9, 2004
Date of Patent:
August 14, 2007
Assignee:
Pfizer Italia S.r.l.
Inventors:
Claudio Dalvit, Elena Ardini, Maria Magdalena Flocco, Gianpaolo Fogliatto, Nicola Mongelli, Marina Veronesi
Abstract: This invention provides a method for treating or preventing arrhythmias in a human subject comprising the administration of an effective amount of a calcium/calmodulin-dependent protein kinase inhibitor. Also provided are pharmaceutical compositions comprising a calcium/calmodulin-dependent protein kinase inhibitor and a pharmaceutically acceptable carrier and methods for identifying agents useful for the treatment of arrhythmias.
Type:
Grant
Filed:
January 28, 2003
Date of Patent:
July 31, 2007
Assignee:
The Board of Trustees of the Leland Stanford Jr. University
Inventors:
Mark Anderson, Andrew P. Braun, Howard Schulman, Ruey J. Sung
Abstract: Described is a bioprocess for the high-yield production of food flavor-acceptable jasmonic acid and methyl jasmonate, as well as a novel jasmonic acid isomer produced thereby and organoleptic uses thereof. The process yields at least 5% of the “cis” isomer defined according the structure: (wherein R is hydrogen or methyl) or at least 5% of the “cis” isomer defined according to the structure: (wherein R is hydrogen or methyl). Compositions containing at least 98% of the isomer having the structure: with an optical rotation (?D20) of +58° are novel. Compositions containing at least 98% of the isomer having the structure: with an optical rotation (?D20) of +58° are also novel.
Type:
Grant
Filed:
September 3, 2002
Date of Patent:
July 31, 2007
Assignee:
International Flavors & Fragrances Inc.
Inventors:
Mohamad I. Farbood, Robert W. Blocker, Lynda B. McLean, Mark A. Sprecker, Michael P. McLean, Nicolas Kossiakoff, Augustine Yonghwi Kim, Myrna Hagedorn
Abstract: The present invention relates to a method for quickly determining cAMP content or an adenylate cyclase activity in a biological sample containing non-cyclic adenine nucleotides without the use of radioactive agents. Particularly, the present invention provides a method of determining cAMP content or an adenylate cyclase activity in a biological sample containing non-cyclic adenine nucleotides selected from the group consisting of cAMP produced by endogenous adenylate cyclase, and AMP, ATP, ADP and a mixture thereof, which comprises (1) combining a biological sample with effective amounts of apyrase, adenosine deaminase and alkaline phosphatase to enzymatically remove non-cyclic adenine nucleotides other than cAMP, and glucose-6-phosphate in the sample; (2) enzymatically converting cAMP into AMP; (3) determining an amount of AMP without the use of radioactive agents, and a kit to carry out the method.
Abstract: A method for producing an optically active compound comprising: a first step of culturing a microorganism capable of assimilating either the R-isomer or the S-isomer of a compound represented by Formula (1): wherein R is a methyl, ethyl, propyl, chloromethyl, or hydroxyethyl group, in a culture medium whose Ca2+ concentration at the beginning of culturing is controlled and which contains a racemic mixture of the compound as a carbon source; and a second step of recovering the optically active compound remaining in the culture broth.
Abstract: The present invention provides modified platelets having a reduced platelet clearance and methods for reducing platelet clearance. Also provided are compositions for the preservation of platelets. The invention also provides methods for making a pharmaceutical composition containing the modified platelets and for administering the pharmaceutical composition to a mammal to mediate hemostasis.
Type:
Grant
Filed:
November 7, 2003
Date of Patent:
July 10, 2007
Assignees:
The Brigham and Women's Hospital, Inc., Zymequest, Inc.
Inventors:
Thomas P. Stossel, John H. Hartwig, Karin M. Hoffmeister, Henrik Clausen
Abstract: The present invention features methods for transplanting organs, tissues and individual cells. Also featured are methods for maintaining cells in vitro and for enhancing survival and/or function of cells following transplantation. The methods include the administration of carbon monoxide in an amount sufficient to enhance cell survival and/or function.
Type:
Grant
Filed:
June 21, 2002
Date of Patent:
July 3, 2007
Assignees:
Beth Israel Deaconess Medical Center, Inc., Yale University
Inventors:
Fritz H. Bach, Leo E. Otterbein, Miguel P. Soares, Jeanne Gose
Abstract: The invention relates to a method and a medium for microbiological analysis by biochemical means involving chromogenic or fluorogenic substrates that react with enzymes (esterases) specific for the target strains. One object of the invention is to improve the sensitivity, initial translucence, stability and ease of use of such detection/identification media. For this purpose the medium according to the invention is characterized in that it is in a stable, ready-to-use liquid or gel form and in that it contains a solubilizer and stabilizer selected from fatty acid sorbitan esters, bile salts and mixtures thereof, as well as a selective activator selected from alkylsulfate salts, for example the sodium salts. The medium can comprise a solvent, for example dimethyl sulfoxide. The invention further relates to the method of obtaining this medium and to the use of products of the sodium alkylsulfate type as selective activators in such media. Application: microbiological analyses.
Abstract: The present invention provides a method for obtaining optically active 3-chloro-2-methyl-1,2-propanediol, the method comprising: a first step of letting at least one kind of microorganism or processed product thereof having an ability to leave untouched (R)-3-chloro-2-methyl-1,2-propanediol or (S)-3-chloro-2-methyl-1,2-propanediol in the presence of an enantiomeric 3-chloro-2-methyl-1,2-propanediol mixture act on an enantiomeric 3-chloro-2-methyl-1,2-propanediol mixture; and a second step of recovering the untouched optically active 3-chloro-2-methyl-1,2-propanediol.
Abstract: Disclosed herein are compositions and methods used to modulate a NH2-terminal Jun Kinase activity. These compositions and methods can be employed to regulate metabolic disorders associated with, for example, insulin such as diabetes. The reduction in NH2-terminal Jun Kinase activity can lead to the reduction in weight and improve insulin sensitivity.
Type:
Grant
Filed:
April 24, 2002
Date of Patent:
June 19, 2007
Assignee:
Harvard University, President and Fellows of Harvard College
Inventors:
Gokhan S. Hotamisligil, Michael Karin, Lufen Chang
Abstract: Treatment of a lactic acid ester derivative with an enzyme or the like, which has asymmetric ester-hydrolyzing ability, can specifically hydrolyze the ester moiety of an isomer existing as the pair to the racemic derivative.
Abstract: The invention provides a method for converting sesquiterpene. The method includes reacting a sesquiterpene substract with a sesquiterpene converting enzyme. The enzyme is from a species or organism containing sesquiterpenes. The sesquiterpene substrate is not naturally present in the species or organism.
Type:
Grant
Filed:
September 17, 2002
Date of Patent:
May 8, 2007
Assignee:
Plant Research International B.V.
Inventors:
Hendrik Jan Bouwmeester, Jan-Willem de Kraker, Marloes Schurink, Raoul John Bino, Aede de Groot, Maurice Charles R. Franssen
Abstract: Method for the detection of dormant cryptobiotic microbes by detection of electromagnetic radiation emitted from intrinsic alkali earth metal pyridine dicarboxylic acid salts in the 710 nm to 860 nm region when excited with electromagnetic energy in the 610 nm to 680 nm region. Utilizing the novel lower energy emission of intrinsic calcium dipicolinic acid salts makes it possible to quickly detect bacterial spores, fungal spores and oocysts without the need for any added reagents, sample processing, or contact with the sample.
Abstract: The invention concerns contact activators for the endogenous coagulation pathway and their use in exploring coagulation anomalies. The activators of the invention are derivatives of gallic acid, preferably polyethylene glycol gallates.
Abstract: Methods and systems are provided for treating a vascular structure having a defect, for example, a cerebral artery having a weakened wall that has formed an aneurysm. The methods include substantially entrapping a quantity of blood within a vascular defect, and introducing a quantity of a crosslinking agent, for example as a liquid solution, into the entrapped blood. The crosslinking agent is a compound in which each molecule of the compound has at least two nucleophilic-reactive functional groups. The crosslinking agent is allowed to combine with and react with the substantially entrapped blood, and a substantially solid mass made of crosslinked blood is formed within the defect.
Abstract: An isolated enone reductase characterized by a molecular mass of 61300+/?5000 Da; NADPH and NADPH as co-factor; a temperature optimum of 55–60° C. at pH 7.4; a pH optimum of 4.5–8.5 and substrate specificity on ?,?-unsatured ketones; a process for producing it from a microorganism and a process for producing levodione from ketoisophorone using such reductase.
Abstract: Reducing or preventing adhesions which would form in a patient during or after surgery by administering to the wound surface of a patient a fibrinogen solution in an amount of about 0.025 ml fibrinogen/cm2 to about 0.25 ml fibrinogen/cm2 of the surface being at risk for developing adhesions. User of fibrinogen in a preparation comprising fibrinogen at a concentration of 20 to 80 mg/ml for the reduction or prevention of post-surgical adhesion formation.
Type:
Grant
Filed:
October 12, 2001
Date of Patent:
April 3, 2007
Assignees:
Baxter International Inc., Baxter Healthcare S.A.
Abstract: An immunosuppressive peptide of 40 kDa molecular weight, isolated from the submandibular glands (SMG*) of rats, had the capacity to suppress immune reactions upon parenteral administration to rats and mice. The peptide was identified as glandular kallikrein (K1) by partial sequencing and by enzymatic activity.
Type:
Grant
Filed:
June 6, 2002
Date of Patent:
March 27, 2007
Assignee:
The University of Manitoba
Inventors:
Edris Sabbadini, Eva Nagy, Istvan Berczi
Abstract: A membrane for implantation in soft tissue comprising a first domain that supports tissue ingrowth, disrupts contractile forces typically found in a foreign body response, encourages vascularity, and interferes with barrier cell layer formation, and a second domain that is resistant to cellular attachment, is impermeable to cells and cell processes, and allows the passage of analytes. The membrane allows for long-term analyte transport in vivo and is suitable for use as a biointerface for implantable analyte sensors, cell transplantation devices, drug delivery devices, and/or electrical signal delivering or measuring devices. The membrane architecture, including cavity size, depth, and interconnectivity, provide long-term robust functionality of the membrane in vivo.
Type:
Grant
Filed:
August 22, 2003
Date of Patent:
March 20, 2007
Assignee:
DexCom, Inc.
Inventors:
James H. Brauker, Victoria Carr-Brendel, Mark A. Tapsak
Abstract: The present invention relates to the novel isolated 12–30 strain of Pestalotiopsis microspora capable of producing novel antioxidant and antimycotic agents. The present invention also relates to the novel isolated 3,5,7 trisubstituted isobenzofuranone and derivatives thereof, methods of isolating the novel isobenzofuranone from cultures P. microspora 12–30, and to novel uses of the compound as an antioxidant and antimycotic agent. The present invention further relates to a novel 1,5,7 trisubstituted 1,3-dihydroisobenzofuran and derivatives thereof, methods of isolating this novel compound from cultures of Pestalotiopsis microspora 12–30, and to uses thereof.
Type:
Grant
Filed:
January 30, 2003
Date of Patent:
March 20, 2007
Assignee:
Montana State University
Inventors:
Gary Strobel, Eugene Ford, James K. Harper