WO2009071681A3 - Rna antagonist compounds for the modulation of bcl-2 - Google Patents

Rna antagonist compounds for the modulation of bcl-2 Download PDF

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Publication number
WO2009071681A3
WO2009071681A3 PCT/EP2008/066921 EP2008066921W WO2009071681A3 WO 2009071681 A3 WO2009071681 A3 WO 2009071681A3 EP 2008066921 W EP2008066921 W EP 2008066921W WO 2009071681 A3 WO2009071681 A3 WO 2009071681A3
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WO
WIPO (PCT)
Prior art keywords
bcl
modulation
antagonist compounds
rna antagonist
rna
Prior art date
Application number
PCT/EP2008/066921
Other languages
French (fr)
Other versions
WO2009071681A2 (en
Inventor
Anja Mølhart HØG
Jens Bo Hansen
Original Assignee
Santaris Pharma A/S
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 Santaris Pharma A/S filed Critical Santaris Pharma A/S
Publication of WO2009071681A2 publication Critical patent/WO2009071681A2/en
Publication of WO2009071681A3 publication Critical patent/WO2009071681A3/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
    • 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
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • 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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
    • 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
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
    • 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 ===---===

Abstract

The present invention relates to oligomer compounds (oligomers), which target BCL-2 mRNA in a cell, leading to reduced expression of Bcl-2. Reduction of BCL-2 expression is beneficial for the treatment of certain medical disorders, such as such as hyperproliferative diseases such as cancer.
PCT/EP2008/066921 2007-12-07 2008-12-05 Rna antagonist compounds for the modulation of bcl-2 WO2009071681A2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US1218507P 2007-12-07 2007-12-07
US61/012,185 2007-12-07
US10626108P 2008-10-17 2008-10-17
US61/106,261 2008-10-17

Publications (2)

Publication Number Publication Date
WO2009071681A2 WO2009071681A2 (en) 2009-06-11
WO2009071681A3 true WO2009071681A3 (en) 2009-12-23

Family

ID=40718259

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/066921 WO2009071681A2 (en) 2007-12-07 2008-12-05 Rna antagonist compounds for the modulation of bcl-2

Country Status (1)

Country Link
WO (1) WO2009071681A2 (en)

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998014172A1 (en) * 1996-10-04 1998-04-09 Board Of Regents, The University Of Texas System Inhibition of bcl-2 protein expression by liposomal antisense oligodeoxynucleotides
US5750390A (en) * 1992-08-26 1998-05-12 Ribozyme Pharmaceuticals, Inc. Method and reagent for treatment of diseases caused by expression of the bcl-2 gene
WO2002017852A2 (en) * 2000-08-25 2002-03-07 Genta Incorporated Methods of treatment of a bcl-2 disorder using bcl-2 antisense oligomers
WO2004046327A2 (en) * 2002-11-14 2004-06-03 Genta Salus Llc Inhibitory oliogonucleotides targeted to bcl-2
CN1587406A (en) * 2004-08-24 2005-03-02 暨南大学 SiRNA double chain for inhibiting bc 1-2 gen expression and use
WO2005061710A1 (en) * 2003-12-23 2005-07-07 Santaris Pharma A/S Oligomeric compounds for the modulation of bcl-2
CN1880331A (en) * 2004-08-24 2006-12-20 暨南大学 siRNA double-chain for suppressing bc1-2 gene expression
CN1880330A (en) * 2004-08-24 2006-12-20 暨南大学 siRNA double-chain for suppressing bc1-2 gene expression
CN1880332A (en) * 2004-08-24 2006-12-20 暨南大学 siRNA double-chain for suppressing bc1-2 gene expression

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5750390A (en) * 1992-08-26 1998-05-12 Ribozyme Pharmaceuticals, Inc. Method and reagent for treatment of diseases caused by expression of the bcl-2 gene
WO1998014172A1 (en) * 1996-10-04 1998-04-09 Board Of Regents, The University Of Texas System Inhibition of bcl-2 protein expression by liposomal antisense oligodeoxynucleotides
WO2002017852A2 (en) * 2000-08-25 2002-03-07 Genta Incorporated Methods of treatment of a bcl-2 disorder using bcl-2 antisense oligomers
WO2004046327A2 (en) * 2002-11-14 2004-06-03 Genta Salus Llc Inhibitory oliogonucleotides targeted to bcl-2
WO2005061710A1 (en) * 2003-12-23 2005-07-07 Santaris Pharma A/S Oligomeric compounds for the modulation of bcl-2
CN1587406A (en) * 2004-08-24 2005-03-02 暨南大学 SiRNA double chain for inhibiting bc 1-2 gen expression and use
CN1880331A (en) * 2004-08-24 2006-12-20 暨南大学 siRNA double-chain for suppressing bc1-2 gene expression
CN1880330A (en) * 2004-08-24 2006-12-20 暨南大学 siRNA double-chain for suppressing bc1-2 gene expression
CN1880332A (en) * 2004-08-24 2006-12-20 暨南大学 siRNA double-chain for suppressing bc1-2 gene expression

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BLOOD, vol. 108, no. 11, Part 1, November 2006 (2006-11-01), 48TH ANNUAL MEETING OF THE AMERICAN-SOCIETY-OF-HEMATOLOGY; ORLANDO, FL, USA; DECEMBER 09 -12, 2006, pages 735A, ISSN: 0006-4971 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; November 2006 (2006-11-01), LIN JIE ET AL: "Induction of apoptosis and anti-tumor effects of a novel pan inhibitor of Bcl-2 and Mcl-1 apogossypolone (ApoG2) in multiple myeloma cells.", XP002539031, Database accession no. PREV200700259351 *
MOLOGNI L ET AL: "In vitro transcriptional and translational block of the bcl-2 gene operated by peptide nucleic acid", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ACADEMIC PRESS INC. ORLANDO, FL, US, vol. 264, no. 2, 22 October 1999 (1999-10-22), pages 537 - 543, XP002323368, ISSN: 0006-291X *

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