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1. WO1997026357 - METHODS AND COMPOSITIONS FOR INHIBITING HEXOKINASE

Publication Number WO/1997/026357
Publication Date 24.07.1997
International Application No. PCT/US1997/000787
International Filing Date 17.01.1997
Chapter 2 Demand Filed 19.08.1997
IPC
C07K 14/62 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
435from animals; from humans
575Hormones
62Insulins
C12N 9/10 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
9Enzymes, e.g. ligases (6.); Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating, or purifying enzymes
10Transferases (2.)
C12N 9/12 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
9Enzymes, e.g. ligases (6.); Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating, or purifying enzymes
10Transferases (2.)
12transferring phosphorus containing groups, e.g. kinases (2.7)
C12N 15/11 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09Recombinant DNA-technology
11DNA or RNA fragments; Modified forms thereof
CPC
C07K 14/62
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
435from animals; from humans
575Hormones
62Insulins
C12N 15/1137
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09Recombinant DNA-technology
11DNA or RNA fragments; Modified forms thereof
113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
1137against enzymes
C12N 2310/121
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
2310Structure or type of the nucleic acid
10Type of nucleic acid
12catalytic nucleic acids, e.g. ribozymes
121Hammerhead
C12N 9/1051
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
9Enzymes; Proenzymes; Compositions thereof
10Transferases (2.)
1048Glycosyltransferases (2.4)
1051Hexosyltransferases (2.4.1)
C12N 9/1205
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
9Enzymes; Proenzymes; Compositions thereof
10Transferases (2.)
12transferring phosphorus containing groups, e.g. kinases (2.7)
1205Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
C12Y 207/01001
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
YENZYMES
207Transferases transferring phosphorus-containing groups (2.7)
01Phosphotransferases with an alcohol group as acceptor (2.7.1)
01001Hexokinase (2.7.1.1)
Applicants
  • BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM [US]/[US] (AllExceptUS)
  • BETAGENE, INC. [US]/[US] (AllExceptUS)
  • NEWGARD, Christopher, B. [US]/[US] (UsOnly)
  • HAN, He-Ping [CN]/[US] (UsOnly)
  • THIGPEN, Anice, E. [US]/[US] (UsOnly)
  • NORMINGTON, Karl, D. [US]/[US] (UsOnly)
Inventors
  • NEWGARD, Christopher, B.
  • HAN, He-Ping
  • THIGPEN, Anice, E.
  • NORMINGTON, Karl, D.
Agents
  • FUSSEY, Shelley, P., M.
  • GOWSHALL, Jonathan, V.
Priority Data
08/588,98319.01.1996US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) METHODS AND COMPOSITIONS FOR INHIBITING HEXOKINASE
(FR) COMPOSITIONS ET PROCEDES D'INHIBITION DE L'HEXOKINASE
Abstract
(EN)
Disclosed are compositions and methods for inhibiting hexokinase enzymes in mammalian cells. Specifically provided are proteins that stimulate the production of trehalose-6-phosphate and their respective genes; hexokinase-specific ribozymes and genes encoding such constructs; and agents that competitively reduce hexokinase activity, e.g., by displacing hexokinase from mitochondria, and their respective genes. The latter group of agents includes inactive hexokinases and fragments thereof that retain mitochondrial binding functions and hexokinase-glucokinase chimeras that further substitute glucokinase activity for hexokinase activity. Mammalian cells including such hexokinase inhibitors, methods of making such cells and various $i(in vitro) and $i(in vivo) methods of using cells with reduced hexokinase activity are also described herein.
(FR)
L'invention se rapporte à des compositions et à des procédés d'inhibition des enzymes hexokinase dans des cellules mammaliennes. L'invention se rapporte notamment à des protéines qui stimulent la production de tréhalose-6-phosphate et à leurs gènes respectifs; à des ribozymes spécifiques de l'hexokinase et à des gènes codant ces produits de recombinaison; et à des agents qui réduisent de façon compétitive l'activité de l'hexokinase en délogeant, p.ex., l'hexokinase des mitochondries, et à leurs gènes respectifs. Ce groupe d'agents comprend des hexokinases inactives et des fragments de celles-ci qui conservent les fonctions de liaison mitochondriale et les chimères hexokinase-glucokinase qui substituent également l'activité de la glucokinase à celle de l'hexokinase. L'invention se rapporte aussi à des cellules mammaliennes comprenant ces inhibiteurs d'hexokinase, à des procédés de fabrication de ces cellules et à divers procédés $i(in vitro) et $i(in vivo) d'utilisation des cellules avec une diminution de l'activité de l'hexokinase.
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