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Title:
ANTISENSE OLIGONUCLEOTIDES TO INHIBIT ANGIOGENESIS AND/OR METASTASIS
Document Type and Number:
WIPO Patent Application WO2002000877
Kind Code:
A3
Abstract:
The present invention relates to a novel class of inhibitors of angiogenesis and/or metastasis that targets cell adhesion molecules, and more particularly to antisense phosphorothioate oligonucleotides directed to a subunit of an integrin vitronectin receptor to inhibit angiogenesis and/or metastasis. There is provided an antisense phosphorothioate oligonucleotide directed to one of a alpha v, beta 3 and beta 5 subunit of an integrin vitronectin receptor. The antisense phosphorotihioate oligonucleotide blocks synthesis of the integrin vitronectin receptor on a target cell, thereby inhibiting angiogenesis and/or metastasis. There is provided a method for blocking angiogenesis and/or metastasis in a patient, comprising delivering an efficient amount of such an antisense phosphorothioate oligonucleotide to the target cell of the patient, thereby blocking synthesis of the integrin vitronectin receptor on the target cell and blocking angiogenesis and/or metastasis.

Inventors:
BRODT PNINA (CA)
NIP JOHN (CA)
WONG AMY (US)
Application Number:
PCT/CA2001/000960
Publication Date:
December 27, 2002
Filing Date:
June 28, 2001
Export Citation:
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Assignee:
UNIV MCGILL (CA)
BRODT PNINA (CA)
NIP JOHN (CA)
WONG AMY (US)
International Classes:
A61K48/00; A61P17/00; A61P29/00; A61P35/00; C07H21/04; C12N15/113; A61K38/00; (IPC1-7): C12N15/11; A61K31/70; A61K47/48; C07H21/04
Domestic Patent References:
WO2002031142A22002-04-18
Foreign References:
EP0950709A11999-10-20
Other References:
NIP J ET AL: "Coordinated expression of the vitronectin receptor and the urokinase-type plasminogen activator receptor in metastatic melanoma cells.", JOURNAL OF CLINICAL INVESTIGATION, (1995 MAY) 95 (5) 2096-103., XP002078999
TOWNSEND P A ET AL: "An antisense oligonucleotide targeting the alphaV integrin gene inhibits adhesion and induces apoptosis in breast cancer cells.", EUROPEAN JOURNAL OF CANCER, vol. 36, no. 3, February 2000 (2000-02-01), pages 397 - 409, XP000990241, ISSN: 0959-8049
TREASURYWALA, S. & BERENS, M.: "Migration arrest in glioma cells is dependent on the alphaV integrin subunit", GLIA, vol. 24, October 1998 (1998-10-01), pages 236 - 243, XP002079005
FRIEDLANDER M ET AL: "INVOLVEMENT OF INTEGRINS ALPHAVBETA3 AND ALPHAVBETA5 IN OCULAR NEOVASCULAR DISEASES", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 93, September 1996 (1996-09-01), pages 9764 - 9769, XP000986063, ISSN: 0027-8424
FRIEDLANDER M ET AL: "DEFINITION OF TWO ANGIOGENIC PATHWAYS BY DISTINCT ALPHAV INTEGRINS", SCIENCE, vol. 270, 1 December 1995 (1995-12-01), pages 1500 - 1502, XP000867841, ISSN: 0036-8075
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