Abstract: The subject matter of the present invention are recombinant defective adenoviruses comprising a heterologous DNA sequence coding for a mutein having the activity of human Interleukin 6 (hIL-6) antagonists or superantagonist. Moreover, the invention refers to therapeutical uses thereof, in particular for preparing pharmaceutical compositions for treating and/or preventing pathologies caused by hIL-6 overproduction.
Type:
Grant
Filed:
June 30, 1999
Date of Patent:
November 5, 2002
Assignees:
Instituto di Ricerche di Biologgia Molecolare, Centre National de la Recherche Scientifique
Inventors:
Gennaro Ciliberto, Isabella Saggio, Rocco Savino, Michel Perricaudet
Abstract: In accordance with the present invention, there are provided nucleic acids encoding human NMDA receptor protein subunits and the proteins encoded thereby. The NMDA receptor subunits of the invention comprise components of NMDA receptors that have cation-selective channels and bind glutamate and NMDA. In one aspect of the invention, the nucleic acids encode NMDAR1 and NMDAR2 subunits of human NMDA receptors. In a preferred embodiment, the invention nucleic acids encode NMDAR1, NMDAR2A, NMDAR2B, NMDAR2C and NMDAR2D subunits of human NMDA receptors. In addition to being useful for the production of NMDA receptor subunit proteins, these nucleic acids are also useful as probes, thus enabling those skilled in the art, without undue experimentation, to identify and isolate related human receptor subunits.
Abstract: The present invention provides nucleotide sequences encoding the &agr;4 and &dgr; subunits of the human GABAA receptor, preparations of &agr;4 and &dgr; receptor subunit proteins, preparations of receptors including &agr;4 or &dgr; polypeptides, expression vectors including the nucleotide sequences, stably co-transfected eukaryotic cells and methods of their preparation and methods of screening for and designing medicaments which act upon the GABAA receptor.
Type:
Grant
Filed:
June 19, 1997
Date of Patent:
September 24, 2002
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Beatrice Le Bourdelles, Paul John Whiting
Abstract: The present invention relates to a transgenic non-human animal embryo lacking native presenilin 1 and a transgenic non-human animal having only a non-native presenilin 1. The transgenic animals and cells derived therefrom can be used in the study of the expression pattern, activity and modulators of presenilin 1, in the study of the role of presenilin 1 in Alzheimer's Disease and in the study of disorders of the central nervous system.
Type:
Grant
Filed:
May 14, 1998
Date of Patent:
September 17, 2002
Assignees:
Merck & Co., Inc., Johns Hopkins University
Inventors:
Hui Zheng, Ping Jiang, Su Qian, Leonardus H. T. Van Der Ploeg, Philip Chun-Ying Wong, Sangram S. Sisodia
Abstract: A novel prostaglandin receptor has been identified and DNA encoding the receptor has been isolated, purified, sequenced and expressed in host cells. This DNA encoding the novel prostaglandin receptor and host cells expressing the receptor are used to identify modulators of the prostaglandin receptor.
Type:
Grant
Filed:
September 13, 1999
Date of Patent:
August 27, 2002
Assignees:
Merck Frosst Canada, Inc., Vanderbuilt University
Inventors:
Anthony Ford-Hutchinson, Colin Funk, Richard Grygorczyk, Kathleen Metters
Abstract: Bacterial polysaccharides which are used to produced vaccines are isolated then precipitated with a long chain detergent. The precipitated polysaccharides are soluble in organic solvents and can be further derivatized and processed to form the vaccine.
Abstract: The present invention provides novel liquid and lyophilized formulations of vaccines against rotavirus infection and methods of their preparation. The formulations include buffering agents appropriate for oral administration of rotavirus vaccines. The formulations also include compounds to stabilize of the vaccine compositions against loss of potency.
Abstract: A human prostaglandin receptor has been identified and DNA encoding the receptor has been isolated, purified, sequenced and expressed in host cells. This DNA encoding the human prostaglandin receptor and host cells expressing the receptor are used to identify modulators of the prostaglandin receptor.
Type:
Grant
Filed:
June 20, 2000
Date of Patent:
May 28, 2002
Assignee:
Merck Frosst Canada & Co.
Inventors:
Mark Abramovitz, Kathleen Metters, Yves Boie, Nicole Sawyer, Deborah M. Slipetz
Abstract: Adenoviral vectors are used to transfer a promoter/reporter gene construct to mammalian cell cultures. The promoter/reporter gene construct is used to determine if a candidate inducing agent has promoter-inducing activity; or can be used to determine if a candidate promoter has activity in the presence of a known inducer.
Type:
Grant
Filed:
March 7, 2001
Date of Patent:
May 28, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Karen Richards, Thomas H. Rushmore, Manal A. Morsy
Abstract: Isolated DNA encoding each of human calcium channel &agr;1-, &agr;2-, &bgr;- and &ggr;-subunits, including subunits that arise as splice variants of primary transcripts, is provided. Cells and vectors containing the DNA and methods for identifying compounds that modulate the activity of human calcium channels are also provided.
Type:
Grant
Filed:
May 25, 1995
Date of Patent:
May 14, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Michael M. Harpold, Steven B. Ellis, Mark E. Williams, Ann F. McCue
Abstract: The present invention relates to nucleic acid formulations of pharmaceutical products which comprise citrate and/or triethanolamine in concentrations which enhance stability of the nucleic acid. These formulations are suited for situations where prolonged storage occurs during the distribution and/or storage period prior to use.
Type:
Grant
Filed:
December 22, 1998
Date of Patent:
May 14, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Robert K. Evans, David B. Volkin, Mark W. Bruner, Zheng Xu
Abstract: This is a method for reproducing in vitro the RNA-dependent RNA polymerase activity associated with hepatitis C virus. The method is characterized in that sequences contained in NS5B are used in the reaction mixture. The terminal nucleotidyl transferase activity, a further property of the NS5B protein, can also be reproduced using this method. The method takes advantage of the fact that the NS5B protein, either purified to apparent homogeneity or present in extracts of overproducing organisms, can catalyze the addition of ribonucleotides to the 3′-termini of exogenous or endogenous RNA molecules. The invention also relates to a composition of matter that comprises sequences contained in NS5B, and to the use of these compositions for the set up of an enzymatic test capable of selecting, for therapeutic purposes, compounds that inhibit the enzymatic activity associated with NS5B.
Type:
Grant
Filed:
March 23, 1998
Date of Patent:
May 7, 2002
Assignee:
Istituto di Ricerehe di Biologia Molecolare P. Angeletti
S.p.A.
Inventors:
Raffaele De Francesco, Licia Tomei, Sven-Erik Behrens
Abstract: Genes encoding Mycobacterium tuberculosis (M.tb) proteins were cloned into eukaryotic expression vectors to express the encoded proteins in mammalian muscle cells in vivo. Animals were immunized by injection of these DNA constructs, termed polynucleotide vaccines or PNV, into their muscles. Immune antisera was produced against M.tb antigens. Specific T-cell responses were detected in spleen cells of vaccinated mice and the profile of cytokine secretion in response to antigen 85 was indicative of a Th1 type of helper T-cell response (i.e., high IL-2 and IFN-&ggr;). Protective efficacy of an M.tb DNA vaccine was demonstrated in mice after challenge with M.bovis BCG, as measured by a reduction in mycobacterial multiplication in the spleens and lungs of M.tb DNA-vaccinated mice compared to control DNA-vaccinated mice or primary infection in naive mice.
Type:
Grant
Filed:
January 22, 1998
Date of Patent:
May 7, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Jean Content, Kris Huygen, Margaret A. Liu, Donna Montgomery, Jeffrey Ulmer
Abstract: The present invention relates to methods of gene therapy for inhibiting angiogenesis associated with solid tumor growth, tumor metastasis, inflammation, psoriasis, rheumatoid arthritis, hemangiomas, diabetic retinopathy, angiofibromas, and macular degeneration Gene therapy methodology is disclosed for inhibition of primary tumor growth and metastasis by gene transfer of a nucleotide sequence encoding a soluble form of a VEGF tyrosine kinase receptor to a mammalian host. The transferred nucleotide sequence transcribes mRNA and a soluble receptor protein which binds to VEGF in extracellular regions adjacent to the primary tumor and vascular endothelial cells. Formation of a sVEGF-R/VEGF complex will prevent binding of VEGF to the KDR and FLT-1 tyrosine kinase receptors, antagonizing transduction of the normal intracellular signals associated with vascular endothelial cell-induced tumor angiogenesis.
Type:
Grant
Filed:
October 26, 1999
Date of Patent:
April 23, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Kenneth A. Thomas, Jr., Richard L. Kendall, Corey K. Goldman, William R. Huckle, Andrew J. Bett
Abstract: In accordance with the present invention, there are provided nucleic acids encoding human NMDA receptor protein subunits and the proteins encoded thereby. The NMDA receptor subunits of the invention comprise components of NMDA receptors that have cation-selective channels and bind glutamate and NMDA. In one aspect of the invention, the nucleic acids encode NMDAR1 and NMDAR2 subunits of human NMDA receptors. In a preferred embodiment, the invention nucleic acids encode NMDAR1, NMDAR2A, NMDAR2B, NMDAR2C and NMDAR2D subunits of human NMDA receptors. In addition to being useful for the production of NMDA receptor subunit proteins, these nucleic acids are also useful as probes, thus enabling those skilled in the art, without undue experimentation, to identify and isolate related human receptor subunits.
Abstract: A process of purifying target molecules is described that involves the selection of ligands based on identifying, in real time, association and dissociation constants with a given target molecule; using this information to select at least one ligand that exhibit predetermined association and dissociation constants with a given target molecule; anchoring a quantity of ligand to an activated solid support; contacting a quantity of target molecules with the anchored ligand(s); removing low affinity target molecules from anchored ligand and eluting particularly pure target molecules.
Type:
Grant
Filed:
August 21, 1998
Date of Patent:
April 16, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Beth Arnold, Paul M. Keller, Anthony J. Conley, Alan R. Shaw, Jwu-Sheng Tung
Abstract: Automated measurement apparatus and methods for automated drug screening procedures are provided. The apparatus is capable of initiating and measuring rapid or transient events, such as cell receptor and/or ion channel activity. In particular, the apparatus is capable of aligning with predetermined positions, one or more samples contained in a multi-well container, initiating the reaction with reagent addition and measuring a resultant attribute for a period of time. The apparatus can substantially continuously measure and record data corresponding to the measured attribute before, during and after initiation of the reaction so that a time course of the rapid or transient event may be determined. After the reaction(s) are complete in one or more wells of the multi-well container, the apparatus can align one or more different wells to be assayed with the predetermined position and repeat the cycle until a predetermined number of wells are assayed.
Type:
Grant
Filed:
June 6, 1997
Date of Patent:
April 16, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Michael Anthony Akong, Michael Miller Harpold, Gonul Velicelebi, Paul Brust
Abstract: A method is provided for making synthetic capped RNAs. These compounds serve as substrates for the virally encoded endonuclease associated with influenza virus. We are able to assay for this unique and specific viral activity of cleavage of a capped RNA in vitro. Therefore, screening of inhibitors of this activity is possible. In addition, short non-extendible (due to their length or because of the modification of the 3′-end of the oligo, i.e. 3′-dA) RNAs are potent inhibitors of the cleavage of capped RNAs by influenza endonuclease. Finally, these compounds may be used to investigate viral and cellular mechanisms of transcription/translation or mRNA maturation.
Type:
Grant
Filed:
March 30, 1998
Date of Patent:
April 9, 2002
Assignee:
Merck & Co., Inc.
Inventors:
James L. Cole, Lawrence C. Kuo, David B. Olsen, Fritz Benseler
Abstract: A novel prostaglandin receptor has been identified and DNA encoding the receptor has been isolated, purified, sequenced and expressed in host cells. This DNA encoding the novel prostaglandin receptor and host cells expressing the receptor are used to identify modulators of the prostaglandin receptor.
Type:
Grant
Filed:
March 16, 1998
Date of Patent:
April 2, 2002
Assignee:
Merck Frosst Canada & Co.
Inventors:
Mark Abramovitz, Yves Boie, Richard Grygorczyk, Kathleen Metters, Thomas H. Rushmore, Deborah M. Slipetz
Abstract: The invention discloses a cDNA consisting of human cyclooxygenase-2 cDNA attached to 3′ flanking sequence of human cyclooxygenase-1 methods for increasing the expression of human cyclooxygenase-2 in transformed cells and assays for preferentially and independently measuring cyclogenase-2 in samples.