Abstract: Vascular endothelial cell growth factor II is purified from the culture media used to maintain mammalian glioma cells. The protein is a heterodimer, stimulates mitogenesis of mammalian vascular endothelial cells and is useful for the promotion of vascular development and repair. This unique growth factor is also useful in the promotion of tissue repair.
Type:
Grant
Filed:
August 31, 1994
Date of Patent:
March 10, 1998
Assignee:
Merck & Co., Inc.
Inventors:
Marvin L. Bayne, Gregory L. Conn, Kenneth A. Thomas, Jr.
Abstract: An improved process using chiral hydrogenation is described for the synthesis in high yields of a 4-protected-(S)-piperazine-2-tert-butyl-carboxamide, an intermediate for an HIV protease inhibitor.
Type:
Grant
Filed:
June 18, 1996
Date of Patent:
March 3, 1998
Assignee:
Merck & Co., Inc.
Inventors:
Kai Rossen, Steven A. Weissman, Jess Sager, David Askin, Paul J. Reider, Ralph P. Volante
Abstract: A novel method of disrupting cells which do not have a cell wall comprises passing suspended cells through a low pressure impinging jet device. This method disrupts the cells, but does not harm the cell products which are liberated.
Abstract: Methods of obtaining enriched populations of osteoclast precursor cells which can be released from tissue culture dishes and used for biochemical studies are described. Osteoblastic cells and bone marrow cells are co-cultured. Next a .alpha..sub.v .beta..sub.3 receptor ligand, such as echistatin is used for cell detachment. The result is an 75-95% pure enriched population of tartrate resistant acid phosphatase (TRAP.sup.+) cells, in high yields (2-3.times.10.sup.6 cells per experiment). These cells are mostly mononucleated and based on their characteristics are considered to be pre-fusion osteoclasts (pOC cells). The precursor osteoclasts can be reseeded onto osteoblasts to obtain an enriched population of mature, multinucleated osteoclast cells.
Type:
Grant
Filed:
April 10, 1995
Date of Patent:
February 17, 1998
Assignee:
Merck & Co., Inc.
Inventors:
Sevgi B. Rodan, Gregg Wesolowski, Gideon A. Rodan
Abstract: The present invention relates to a stably co-transfected eukaryotic cell line capable of expressing a GABA-A receptor, particularly a human GABA-A receptor, which receptor comprises at least one alpha, one beta and one gamma subunit; to the cloning of novel cDNA sequences encoding the .alpha.-2, .alpha.-3, .alpha.-5, .alpha.-6 and .beta.-2 subunits of the human GABA-A receptor; and to the use of the cell line in designing and developing GABA-A receptor subtype-selective medicaments.
Type:
Grant
Filed:
April 5, 1995
Date of Patent:
February 17, 1998
Assignee:
Merck Sharpe & Dohme Ltd.
Inventors:
Karen Louise Hadingham, Beatrice le Bourdelles, Paul John Whiting, Peter Baxter Wingrove
Abstract: The vascular endothelial cell growth factor (VEGF) inhibitors of the present invention are naturally occurring or recombinantly engineered soluble forms with or without a C-terminal transmembrane region of the receptor for VEGF, a very selective growth factor for endothelial cells. The soluble forms of the receptors will bind the growth factor with high affinity but do not result in signal transduction. These soluble forms of the receptor bind VEGF and inhibit its function.
Type:
Grant
Filed:
April 21, 1994
Date of Patent:
January 27, 1998
Assignee:
Merck & Co., Inc.
Inventors:
Richard L. Kendall, Kenneth A. Thomas, Jr.
Abstract: DNAs encoding bradykinin B.sub.1 receptors from mammalian cells have been cloned and characterized. The recombinant receptor is capable of forming receptors which bind des-Arg.sup.10 kallidin and other B.sub.1 -specific ligands. The DNA has been expressed in recombinant host cells which produce active recombinant protein. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified.
Type:
Grant
Filed:
April 15, 1994
Date of Patent:
January 27, 1998
Assignee:
Merck & Co., Inc.
Inventors:
David L. Linemeyer, John W. Hess, Joseph A. Borkowski, Kathleen K. Bierilo, John G. Menke
Abstract: A process for synthesizing the compounds ##STR1## wherein X is halo, consists of, at a minimum, electrochemical oxidation of the allyl acetonide reactant with halide salt in an aqueous system, the desired compounds being useful as intermediates for the synthesis of inhibitors of renin or HIV protease or other proteases.
Abstract: DNA encoding glutamate and avermectin-sensitive chloride channels have been cloned and characterized. The protein is capable of forming channels selectively opened with either avermectin or glutamate. The cDNA has been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified. Receptor modulators active in the method disclosed herein are useful as ectoparasiticides, antiparasitic, anthelmenthic, acaracidal and insecticide agents.
Type:
Grant
Filed:
May 5, 1995
Date of Patent:
December 2, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Doris F. Cully, Joseph P. Arena, Philip S. Paress, Ken K. Liu
Abstract: DNAs encoding voltage-activated cation channels have been cloned and characterized. The cDNA's have been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells.
Type:
Grant
Filed:
September 30, 1996
Date of Patent:
November 18, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Joseph P. Arena, Guoping Feng, Linda M. Hall, Ken Liu, Leonardus H. T. Van Der Ploeg, Peiyi Wang, Jeffrey W. Warmke
Abstract: An assay for the influenza virus endonuclease has been developed which involves DNA polymerase-catalyzed extension of the viral endonuclease cleavage product using labeled nucleotides and a DNA template containing a 3' region complementary to the product joined to a 5' region consisting of repeated residues. The DNA polymerase coupled assay does not involve gel electrophoretic separation and is amenable to high volume screening of potential inhibitors. Another key feature of the assay is that it is sensitive enough to detect 200 attomoles of product.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
August 26, 1997
Assignee:
Merck & Co., Inc.
Inventors:
James L. Cole, Lawrence C. Kuo, David B. Olsen
Abstract: A novel human protein tyrosine phosphatase (PTP) has been identified and its cDNA has been isolated. This novel PTP, denoted PTP-OB, has a receptor-like three dimensional structure and is present in osteoblasts. PTP-OB is involved in osteoblast differentiation, and modulators of PTP-OB activity in turn modulate osteoblast differentiation, osteoclast differentiation and osteoclast activity.
Type:
Grant
Filed:
December 1, 1994
Date of Patent:
August 19, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Gideon A. Rodan, Su Jane Rutledge, Azriel Schmidt
Abstract: The present invention relates to stably co-transfected eukaryotic cell lines capable of expressing a recombinant GABA.sub.A receptor, particularly a recombinant human GABA.sub.A receptor, which comprises at least one alpha, one beta and one gamma subunit; and to the use of the cell line and/or membrane preparation in selecting compounds and designing medicaments which interact with the respective human recombinant GABA.sub.A receptor.
Abstract: An improved synthesis of a highly potent HIV reverse transcription inhibitor is disclosed, involving an acetylide and a trifluoromethyl ketone which produces a chiral product in the presence of a chiral amino alcohol.
Type:
Grant
Filed:
May 25, 1995
Date of Patent:
May 27, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Andrew S. Thompson, Edward G. Corley, Edward J.J. Grabowski, Nobuyoshi Yasuda
Abstract: The present invention relates to DNA molecules encoding a canine IgE and species-specific regions of the canine IgE constant region. The invention comprises the DNA molecules, proteins encoded by the DNA molecules, antibodies to the proteins, cells transformed by the DNA molecules, assays employing the transformed cells, compounds identified by the assays and kits containing the DNA molecules or derivatives thereof.
Abstract: A novel conjugate vaccine comprising partially hydrolyzed, highly purified, capsular polysaccharide (Ps) from Streptococcus pneumoniae bacteria (pneumococci, Pn) linked to an immunogenic carrier protein, is produced by a new process. The conjugate is useful in the prevention of pneumococcal infections. Vaccines comprising a mixture of from one to ten different pneumococcal polysaccharide-immunogenic protein (Pn-Ps-PRO) conjugates induce broadly protective recipient immune responses against the cognate pathogens from which the polysaccharide components are derived. Young children and infants younger than 2 years old, normally unable to mount a protective immune response to the Pn-Ps alone, exhibit protective immune responses upon vaccination with these Pn-Ps-PRO conjugates.
Type:
Grant
Filed:
May 20, 1994
Date of Patent:
April 22, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Stephen Marburg, Richard L. Tolman, Peter J. Kniskern, William J. Miller, Arpi Hagopian, Charlotte C. Ip, John P. Hennessey, Jr., Dennis J. Kubek, Pamela D. Burke
Abstract: The present invention relates to DNA molecules encoding a canine IgA and species-specific regions of the canine IgA constant region. The invention comprises the DNA molecules, proteins encoded by the DNA molecules, antibodies to the proteins, cells transformed by the DNA molecules, assays employing the transformed cells, compounds identified by the assays and kits containing the DNA molecules or derivatives thereof.
Abstract: A process for making a clinically efficacious HIV protease inhibitor eliminates one step in its synthesis, by an alternative convergent synthesis using 2(S)-4-picolyl-2-piperazine-t-butylcarboxamide as an intermediate.
Type:
Grant
Filed:
March 15, 1995
Date of Patent:
April 8, 1997
Assignee:
Merck & Co., Inc.
Inventors:
David Askin, Kan K. Eng, Paul Reider, Ralph P. Volante
Abstract: Native Herpes Simplex Virus type 1 (HSV type 1) protease has a rather low activity. It has been found however, that the presence of a kosmotropic anion can increase the activity of the protease over 10-fold. This has many advantages, as now assays for protease activity may be run in very small (micromolar and less) amounts of reagents and substrates, and the assays can be run quickly. Activate HSV-1 protease represents a conformational change from native protease.
Type:
Grant
Filed:
April 6, 1995
Date of Patent:
April 8, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Paul L. Darke, Dawn L. Hall, Lawrence C. Kuo
Abstract: In order to produce hepatitis B virus (HBV) surface proteins in the form of particles with substantially reduced entrapped carbohydrate content, DNA encoding the HBV surface proteins was expressed in a recombinant yeast host which is deficient in its ability to glycosylate proteins. These HBV surface proteins display the antigenie sites genetically encoded by the S domain of the HBV virion envelope open reading frame and contains substantially reduced levels of entrapped carbohydrate when compared with HBsAg particles produced in "wild-type" yeast cells. These particles are useful as a vaccine for both the active and passive treatment or prevention of disease and/or infection caused by HBV or other agents serologically related to HBV.