Patents Represented by Attorney Max D. Hensley
  • Patent number: 5641763
    Abstract: This invention relates to new nucleotide analogues and solves the technical problem of their use as biologically active compounds. The subject of this invention are N-(2-phosphonylmethoxyethyl) and N-(3-hydroxy-2-phosphonylmethoxypropyl) derivatives of pyrimidine and purine bases, easily accessible from heterocyclic bases and their N-(2-hydroxyethyl) or N-(2,3-dihydroxypropyl) derivatives. Some of the compounds, according to this invention, exhibit a marked antiviral activity or can be converted into such active compounds by chemical transformations.
    Type: Grant
    Filed: October 11, 1994
    Date of Patent: June 24, 1997
    Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.
    Inventors: Antonin Holy, Ivan Rosenberg, Erik D. A. De Clercq
  • Patent number: 5591852
    Abstract: The present invention relates to a novel and economical process for the synthesis of HPMP-substituted nucleotide antiviral compounds. Also disclosed are novel intermediates produced in the process for the preparation of HPMPC.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: January 7, 1997
    Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.
    Inventors: Purushotham Vemishetti, Paul R. Brodfuehrer, Henry G. Howell, Chester Sapino, Jr.
  • Patent number: 5591851
    Abstract: The internally cyclized congeners of hydroxy-substituted nucleotide analogues have been found to exhibit substantially lower toxicity in vivo than their uncyclized analogues, while retaining essentially the same antiviral activity. This was unexpected because the prior art suggested that the cyclic analogues offered no significant advantages in respect to toxicity. This finding permits the administration of much greater doses of the cyclic congeners than otherwise would have been possible and allows the clinician to omit toxicity ameliorating interventions. Novel compounds are provided for use in the method of this invention. Novel methods for the preparation of these compounds also are provided.
    Type: Grant
    Filed: February 5, 1996
    Date of Patent: January 7, 1997
    Assignee: Gilead Sciences, Inc.
    Inventor: Petr Alexander
  • Patent number: 5514798
    Abstract: An improved method for the preparation of acyclic nucleotide analogues comprises first condensing a cyclic carbonate with a purine or pyrimidine base and then reacting the alkylated base with an activated phosphonate. Novel cyclic carbonates are employed to yield the desired phosphonylmethoxyalkyl nucleotide analogues.
    Type: Grant
    Filed: February 13, 1995
    Date of Patent: May 7, 1996
    Assignee: Gilead Sciences, Inc.
    Inventors: Norbert W. Bischofberger, Kenneth M. Kent
  • Patent number: 5502177
    Abstract: A compound having the structure: ##STR1## wherein R.sup.1 is an oligonucleotide;a is 1 and b is 0;A is C or CH;X is S, O, NH or NCH.sub.2 R.sup.6 ;Z is taken together with A to form an aryl ring structure comprising 6 ring atoms wherein the aryl ring carbon atoms are unsubstituted with other than H or at least 1 nonbridging ring carbon atom is substituted with R.sup.6 or .dbd.O;R.sup.6 is independently H, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, NO.sub.2, N(R.sup.3).sub.2, C.tbd.N or halo, or an R.sup.6 is taken together with an adjacent Z group R.sup.6 to complete a phenyl ring; andR.sup.3 is a protecting group or H; and tautomers, solvates and salts thereof.
    Type: Grant
    Filed: September 17, 1993
    Date of Patent: March 26, 1996
    Assignee: Gilead Sciences, Inc.
    Inventors: Mark D. Matteucci, Robert J. Jones, Kuei-Ying Lin
  • Patent number: 5476938
    Abstract: The present invention relates to a novel and economical process for the synthesis of HPMP-substituted nucleotide antiviral compounds. Also disclosed are novel intermediates produced in the process for the preparation of HPMPC.
    Type: Grant
    Filed: January 21, 1992
    Date of Patent: December 19, 1995
    Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.
    Inventors: Purushortham Vemishetti, Paul R. Brodfuehrer, Henry G. Howell, Chester Sapino, Jr.
  • Patent number: 5352786
    Abstract: The invention relates to new compounds, di(2-propyl) esters of (R)-, (S)- and (RS)-1-fluoro-2-phosphonomethoxy-3-p-toluenesulfonyloxypropane and the method of producing them. The compounds can be used with advantage in the preparation of N-(3-fluoro-2-phosphonomethoxypropyl) derivatives of heterocyclic purine and pyrimidine bases that have antiviral activity.
    Type: Grant
    Filed: January 13, 1993
    Date of Patent: October 4, 1994
    Assignee: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic
    Inventors: Jindrich Jindrich, Antonin Holy
  • Patent number: 5175273
    Abstract: Pyridinone or pyrimidinone nucleoside bases containing fused aromatic polycyclic rings are provided. These polycyclic nucleosides are incorporated into oligonucleotides and hybridized to complementary nucleic acid. Fluorescence spectroscopy and thermal denaturation profiles provided evidence that the polycyclic base is intercalated into the resulting duplex. The fused polycyclic ring systems optionally are substituted with reactive species which inactivate complementary nucleic acids. The oligonucleotides of this invention are useful as improved probes, diagnostic reagents, or for cleaving or derivatizing predetermined domains within nucleic acids.
    Type: Grant
    Filed: July 1, 1988
    Date of Patent: December 29, 1992
    Assignee: Genentech, Inc.
    Inventors: Norbert W. Bischofberger, Mark D. Matteucci
  • Patent number: 5169762
    Abstract: The .beta.-subunit of human nerve growth factor (.beta.NGF) is prepared in essentially pure form in commercially viable quantities using recombinant DNA technology. The nucleotide sequence and vectors encoding human .beta.NGF and host cells transformed with the vectors are also provided.
    Type: Grant
    Filed: September 8, 1988
    Date of Patent: December 8, 1992
    Assignee: Genentech, Inc.
    Inventors: Alane M. Gray, Axel Ullrich
  • Patent number: 5130255
    Abstract: Container systems for stable storage of pharmaceutical compounds are disclosed. The container systems prevent the formation of adducts between pharmaceutical compounds and aldehydes during storage of these compounds in containers sealed with elastomeric stoppers that leach aldehydes. Methods for determining the presence of these adducts are also disclosed.
    Type: Grant
    Filed: December 13, 1990
    Date of Patent: July 14, 1992
    Assignee: Genentech, Inc.
    Inventors: John E. Battersby, William S. Hancock, Virgil B. Lawlis, Jr.
  • Patent number: 5057417
    Abstract: Growth hormone receptor and growth hormone binding protein are purified enabling amino acid sequence and DNA isolates coding for growth hormone receptor and growth hormone binding protein and methods of obtaining such DNA are provided, together with expression systems for recombinant production of growth hormone receptor and growth hormone binding protein. Therapeutically useful forms of the growth hormone receptor and growth hormone binding protein and anti-receptor antibodies are described.
    Type: Grant
    Filed: June 12, 1987
    Date of Patent: October 15, 1991
    Assignee: Genentech, Inc.
    Inventors: R. Glenn Hammonds, David W. Leung, Steven A. Spencer, William I. Wood
  • Patent number: 5049488
    Abstract: Nucleic acid encoding lecithin:cholesterol acyltransferase is ligated into expression vectors and used to transform host cells for the synthesis of lecithin:cholesterol acyltransferase in recombinant cell culture. Lecithin:cholesterol acyltransferase amino acid sequence variants are described for enhancing the properties of lecithin:cholesterol acyltransferase. Lecithin:cholesterol acyltransferase and its variants are employed in the therapy of conditions characterized by hypercholesterolemia and for the mobilization of cholesterol in vivo.
    Type: Grant
    Filed: November 8, 1985
    Date of Patent: September 17, 1991
    Assignee: Genentech, Inc.
    Inventors: Bradford W. Baer, Dennis T. Drayna, Richard M. Lawn, John W. McLean
  • Patent number: 5030576
    Abstract: Hybrid receptors are provided that comprise (a) the ligand binding domain of a predetermined receptor and (b) a heterologous reporter polypeptide. The hybrid receptors are useful for convenient and large scale assay of biologically active ligands or their antagonists or agonists.
    Type: Grant
    Filed: March 13, 1989
    Date of Patent: July 9, 1991
    Assignee: Genentech, Inc.
    Inventors: Thomas J. Dull, Heimo Riedel, Axel Ullrich
  • Patent number: 5024939
    Abstract: A method is described for transient production of a desired heterologous protein comprising: transfecting a eukaryotic host cell with a vector producing a trans-activating protein; transfecting the eukaryotic host cell with an expression vector comprising a stabilizing sequence downstream of a promoter and upstream of a DNA encoding the desired heterologous protein and a polyadenylation sequence downstream of which is a transcription terminatein site; culturing the transfected eukaryotic host cell under conditions favorable for production of said desired heterologous protein; and, recovering the desired protein in useful amounts within about one day to about fourteen days of transfection.
    Type: Grant
    Filed: September 25, 1987
    Date of Patent: June 18, 1991
    Assignee: Genentech, Inc.
    Inventor: Cornelia M. Gorman
  • Patent number: 5017556
    Abstract: A method and therapeutic composition for the treatment of bleeding disorders, for example those characterized by a tendency toward hemorrhage or a hypercoagulative state, by the administration of tissue factor protein or antagonists thereof.
    Type: Grant
    Filed: March 8, 1989
    Date of Patent: May 21, 1991
    Assignee: Genentech, Inc.
    Inventors: Donogh P. O'Brien, Gordon A. Vehar
  • Patent number: 4963354
    Abstract: Tumor necrosis factors, alone or together with cytokines such as IL-1 or INF-.gamma., are capable of serving as non-toxic vaccine adjuvants.
    Type: Grant
    Filed: January 21, 1987
    Date of Patent: October 16, 1990
    Assignee: Genentech, Inc.
    Inventors: H. Michael Shepard, James E. Talmadge
  • Patent number: 4963495
    Abstract: Direct linkage of DNA encoding prokaryotic signals such as E. coli enterotoxin with DNA encoding mature eukaryotic proteins followed by transformation and culture of bacterial hosts characterized by a periplasmic space, yields substantial amounts of periplasmic mature protein.
    Type: Grant
    Filed: October 5, 1984
    Date of Patent: October 16, 1990
    Assignee: Genentech, Inc.
    Inventors: Chung N. Chang, Gregory L. Gray, Herbert L. Heyneker, Michael W. Rey
  • Patent number: 4960700
    Abstract: DNA isolates coding for enkephalinase and methods of obtaining such DNA are provided, together with expression systems for recombinant production of enkephalinase for use in therapeutic or diagnostic compositions. Enkephalinase assays are facilitated by novel enkephalinase substrates.
    Type: Grant
    Filed: January 12, 1987
    Date of Patent: October 2, 1990
    Assignee: Genentech, Inc.
    Inventors: Bernard Malfroy-Camine, Peter R. Schofield
  • Patent number: 4959457
    Abstract: Antibody is provided which is capable of neutralizing the in vitro anti-neoplastic cellular activity of lymphotoxin. This antibody, which preferably is produced of monoclonal fusions, can be used in assays for lymphotoxin or for immunoaffinity purification of lymphotoxin.
    Type: Grant
    Filed: May 31, 1984
    Date of Patent: September 25, 1990
    Assignee: Genentech, Inc.
    Inventor: Timothy S. Bringman
  • Patent number: RE35558
    Abstract: The invention relates to the new compound (2R)-2-[di(2-propyl)phosphonylmethoxy]-3-p-toluenesulfonyloxy-1-trimethyla cetoxypropane and the method of producing it. The compound may be used for producing (S)-N-(3-hydroxy-2-phosphonylmethoxypropyl) derivatives of the heterocyclic purine and pyrimidine bases of antiviral activity.
    Type: Grant
    Filed: July 14, 1994
    Date of Patent: July 8, 1997
    Assignee: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic
    Inventors: Petr Alexander, Antonin Holy, Hana Dvorakova