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WO2000066724A3 - Oligonucleotide derivatives directed against human bcl-xl and human bcl-2 mrna - Google Patents

Oligonucleotide derivatives directed against human bcl-xl and human bcl-2 mrna Download PDF

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Publication number
WO2000066724A3
WO2000066724A3 PCT/EP2000/003708 EP0003708W WO0066724A3 WO 2000066724 A3 WO2000066724 A3 WO 2000066724A3 EP 0003708 W EP0003708 W EP 0003708W WO 0066724 A3 WO0066724 A3 WO 0066724A3
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WO
WIPO (PCT)
Prior art keywords
human bcl
oligonucleotide derivatives
mrna
directed against
bcl
Prior art date
Application number
PCT/EP2000/003708
Other languages
French (fr)
Other versions
WO2000066724A2 (en
Inventor
Uwe Zangemeister-Wittke
Gerd Luedke
Dieter Huesken
Original Assignee
Univ Zuerich
Zangemeister Wittke Uwe
Gerd Luedke
Dieter Huesken
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Zuerich, Zangemeister Wittke Uwe, Gerd Luedke, Dieter Huesken filed Critical Univ Zuerich
Priority to EP00925239A priority Critical patent/EP1181361A2/en
Priority to AU44025/00A priority patent/AU4402500A/en
Publication of WO2000066724A2 publication Critical patent/WO2000066724A2/en
Publication of WO2000066724A3 publication Critical patent/WO2000066724A3/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-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
    • C12N15/1135—Non-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 against oncogenes or tumor suppressor genes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Physics & Mathematics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Plant Pathology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to antisense oligonucleotide derivatives directed against human bcl-xL mRNA and being capable of modulating the biosynthesis of human bcl-xL protein. Furthermore, the present invention relates to antisense oligonucleotide derivatives directed against both human bcl-xL nRNA and human bcl-2 mRNA, and being capable of modulating the biosynthesis of both human bcl-xl protein and human bcl-2 protein. The present invention further relates to a pharmaceutical composition comprising such oligonucleotide derivatives, uses thereof and methods of treatment and diagnosis utilizing such oligonucleotide derivatives.
PCT/EP2000/003708 1999-04-30 2000-04-26 Oligonucleotide derivatives directed against human bcl-xl and human bcl-2 mrna WO2000066724A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP00925239A EP1181361A2 (en) 1999-04-30 2000-04-26 Oligonucleotide derivatives directed against human bcl-xl and human bcl-2 mrna
AU44025/00A AU4402500A (en) 1999-04-30 2000-04-26 Oligonucleotide derivatives directed against human bcl-xl and human bcl-2 mrna

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9910119.8A GB9910119D0 (en) 1999-04-30 1999-04-30 Organic compounds
GB9910119.8 1999-04-30

Publications (2)

Publication Number Publication Date
WO2000066724A2 WO2000066724A2 (en) 2000-11-09
WO2000066724A3 true WO2000066724A3 (en) 2001-02-08

Family

ID=10852654

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/003708 WO2000066724A2 (en) 1999-04-30 2000-04-26 Oligonucleotide derivatives directed against human bcl-xl and human bcl-2 mrna

Country Status (4)

Country Link
EP (1) EP1181361A2 (en)
AU (1) AU4402500A (en)
GB (1) GB9910119D0 (en)
WO (1) WO2000066724A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2832154B1 (en) 2001-11-09 2007-03-16 Centre Nat Rech Scient OLIGONUCLEOTIDES INHIBITORS AND THEIR USE FOR SPECIFICALLY REPRESSING A GENE
DE10258677A1 (en) * 2002-12-13 2004-06-24 Elez, Vera, Dr. Combined use of antisense oligonucleotides for treating cancer, directed against the Polo-like kinase 1 and B cell leukemia/lymphoma 2 genes, having a synergistic effect
FR2852606A1 (en) * 2003-03-18 2004-09-24 Inst Nat Sante Rech Med MEANS FOR SIMULTANEOUSLY INHIBITING THE EXPRESSION OF SEVERAL GENES INVOLVED IN A PATHOLOGY
MX2016009753A (en) 2014-01-28 2017-07-07 Buck Inst For Res On Aging Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders.

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995008350A1 (en) * 1993-09-20 1995-03-30 Reed John C REGULATION OF bcl-2 GENE EXPRESSION
WO1995031470A2 (en) * 1994-05-13 1995-11-23 Merck Frosst Canada Inc. Antisense inhibitors of gene expression
US5470974A (en) * 1985-03-15 1995-11-28 Neu-Gene Development Group Uncharged polynucleotide-binding polymers
WO1998018812A1 (en) * 1996-10-25 1998-05-07 Hisamitsu Pharmaceutical Co., Inc. Oligomers which inhibit the expression of interleukin genes
WO2000001393A2 (en) * 1998-07-02 2000-01-13 The Trustees Of Columbia University In The City Of New York OLIGONUCLEOTIDE INHIBITORS OF bcl-xL
WO2000020432A1 (en) * 1998-10-07 2000-04-13 Isis Pharmaceuticals, Inc. Antisense modulation of bcl-x expression

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5470974A (en) * 1985-03-15 1995-11-28 Neu-Gene Development Group Uncharged polynucleotide-binding polymers
WO1995008350A1 (en) * 1993-09-20 1995-03-30 Reed John C REGULATION OF bcl-2 GENE EXPRESSION
WO1995031470A2 (en) * 1994-05-13 1995-11-23 Merck Frosst Canada Inc. Antisense inhibitors of gene expression
WO1998018812A1 (en) * 1996-10-25 1998-05-07 Hisamitsu Pharmaceutical Co., Inc. Oligomers which inhibit the expression of interleukin genes
WO2000001393A2 (en) * 1998-07-02 2000-01-13 The Trustees Of Columbia University In The City Of New York OLIGONUCLEOTIDE INHIBITORS OF bcl-xL
WO2000020432A1 (en) * 1998-10-07 2000-04-13 Isis Pharmaceuticals, Inc. Antisense modulation of bcl-x expression

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
GAUTSCHI OLIVER ET AL: "Potent anti-tumor activity of a bcl-2/bcl-xL bispecific antisense oligonucleotide against solid tumors of diverse histological origin.", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL, no. 41, March 2000 (2000-03-01), 91st Annual Meeting of the American Association for Cancer Research.;San Francisco, California, USA; April 01-05, 2000, March, 2000, pages 642, XP000926075, ISSN: 0197-016X *
LEUDKE G H ET AL: "Antisense oligodeoxynucleotides designed to downregulates the expression of bcl-xL and of bcl-2 and bcl-xL simultaneously, restore the apoptotic response of lung cancer cell lines.", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL, vol. 39, March 1998 (1998-03-01), 89th Annual Meeting of the American Association for Cancer Research;New Orleans, Louisiana, USA; March 28-April 1, 1998, March, 1998, pages 417, XP000960954, ISSN: 0197-016X *
LUEDTKE G H ET AL: "Antisense oligonucleotides targeting sequences shared by the Bcl-2 and Bcl-xL efficiently downregulate expression of both proteins and induce apoptosis of lung cancer cells", PROCEEDINGS OF THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH,US,PHILADELPHIA, AACR, vol. 38, 1997, pages 170, XP002080870 *
OBIKA S ET AL: "Properties of Novel Oligonucleotide Analogues Containing an Acyclic Nucleoside and a Carbamate Linkage", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,GB,OXFORD, vol. 6, no. 12, 18 June 1996 (1996-06-18), pages 1357 - 1360, XP004134840, ISSN: 0960-894X *
ZANGEMEISTER-WITTKE U ET AL: "Bcl-2 antisense oligodeoxynucleotide 2009 synergizes with chemotherapy on lung cancer cell lines and has antitumor activity against lung cancer xenografts.", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL, vol. 39, March 1998 (1998-03-01), 89th Annual Meeting of the American Association for Cancer Research;New Orleans, Louisiana, USA; March 28-April 1, 1998, March, 1998, pages 417, XP002153619, ISSN: 0197-016X *
ZANGEMEISTER-WITTKE U ET AL: "Novel approaches to the treatment of small-cell lung cancer.", CMLS CELLULAR AND MOLECULAR LIFE SCIENCES, vol. 55, no. 12, September 1999 (1999-09-01), pages 1585 - 1598, XP000960960, ISSN: 1420-682X *
ZANGEMEISTER-WITTKE U ET AL: "Synergistic cytotoxicity of bcl-2 antisense oligodeoxynucleotides and etoposide, doxorubicin and cisplatin on small-cell lung cancer cell lines.", BRITISH JOURNAL OF CANCER, vol. 78, no. 8, October 1998 (1998-10-01), pages 1035 - 1042, XP000965123, ISSN: 0007-0920 *

Also Published As

Publication number Publication date
AU4402500A (en) 2000-11-17
GB9910119D0 (en) 1999-06-30
EP1181361A2 (en) 2002-02-27
WO2000066724A2 (en) 2000-11-09

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