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1. WO2004111079 - VIRAL POLYMERASE AND MODULATION THEREOF

Publication Number WO/2004/111079
Publication Date 23.12.2004
International Application No. PCT/AU2004/000781
International Filing Date 11.06.2004
Chapter 2 Demand Filed 23.09.2004
IPC
C07H 19/00 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
19Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro derivatives thereof
C12N 9/12 2006.1
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)
CPC
C07H 19/00
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
19Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides ; Anhydro-derivatives thereof
C07K 2299/00
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2299Coordinates from 3D structures of peptides, e.g. proteins or enzymes
C12N 2730/10122
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
2730Reverse Transcribing DNA Viruses
00011Reverse Transcribing DNA Viruses
10011Hepadnaviridae
10111Orthohepadnavirus, e.g. hepatitis B virus
10122New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
C12N 9/1276
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)
1241Nucleotidyltransferases (2.7.7)
1276RNA-directed DNA polymerase (2.7.7.49), i.e. reverse transcriptase or telomerase
C12Y 207/07049
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
YENZYMES
207Transferases transferring phosphorus-containing groups (2.7)
07Nucleotidyltransferases (2.7.7)
07049RNA-directed DNA polymerase (2.7.7.49), i.e. telomerase or reverse-transcriptase
Applicants
  • MELBOURNE HEALTH [AU]/[AU] (AllExceptUS)
  • BARTHOLOMEUSZ, Angeline, Ingrid [AU]/[AU] (UsOnly)
  • CHALMERS, David [AU]/[AU] (UsOnly)
  • KUIPER, Mike [AU]/[AU] (UsOnly)
  • TEHAN, Ben [AU]/[GB] (UsOnly)
Inventors
  • BARTHOLOMEUSZ, Angeline, Ingrid
  • CHALMERS, David
  • KUIPER, Mike
  • TEHAN, Ben
Agents
  • HUGHES, E., John, L.
Priority Data
200390298313.06.2003AU
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) VIRAL POLYMERASE AND MODULATION THEREOF
(FR) POLYMERASE VIRALE ET SA MODULATION
Abstract
(EN) The present invention provides the tertiary structure of a Hepatitis B Virus (HBV) polymerase reverse transcriptase (rt) domain from which a variant HBV polymerase mutations associated with resistance to or having reduced sensitivity to an anti-viral drug have been mapped. The present invention further provides methods of identifying, designing and/or modifying agents capable of modulating the functional activity of the HBV polymerase based on the atomic co-ordinates provided by the tertiary structure. The present invention still further provides a method of modulating HBV polymerase functional activity and agents useful for same. The agents identified in accordance with the method of the present invention are particularly useful inter alia in the treatment and/or prophylaxis of infection by an HBV resistant to or exhibiting reduced sensitivity to an anti-viral drug. The agents may also have utility as diagnostic agents such as to distinguish between resistance mutations. Furthermore, the present invention enables responses of particular potential anti-viral drugs to be predicted. In addition, new targets within the polymerase have been identified.
(FR) L'invention concerne une structure tertiaire du domaine de la transcriptase inverse de la polymérase du virus de l'hépatite B (HBV), à partir de laquelle des mutations variantes de la polymérase du HBV présentant une résistance à un médicament anti-viral ou présentant une sensibilité réduite à ce médicament ont été reconnues. L'invention concerne, de plus, des procédés pour identifier, concevoir et/ou modifier des agents capables de moduler l'activité fonctionnelle de la polymérase du HBV sur la base de coordonnées atomiques fournies par la structure tertiaire. L'invention concerne, en outre, un procédé pour moduler l'activité fonctionnelle de la polymérase du HBV et des agents utilisés à cet effet. Les agents identifiés selon le procédé de l'invention sont particulièrement utilisés, notamment dans le traitement et/ou la prophylaxie d'infections provoquées par un HBV résistant à un médicament antiviral ou présentant une sensibilité réduite à ce médicament. Les agents peuvent être utilisés en tant qu'agents diagnostiques, de manière à distinguer les mutations de la résistance. De plus, l'invention permet la réponse des médicaments antiviraux potentiels particuliers à prescrire, et l'identification de nouvelles cibles situées à l'intérieur de la polymérase.
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