Title:
PHOSPHOROTHIOATE-MODIFIED OLIGONUCLEOTIDE AS ANTI-RESTENOSIS AGENT
Document Type and Number:
WIPO Patent Application WO2003035666
Kind Code:
A3
Abstract:
An anti-restenosis agent comprises a phosphorothioate-modified oligonucleotide wherein the oligonucleotide includes at least one hairpin loop and a TG sequence. The hairpin loop preferably has the sequence CAG CGA AGC. Especially preferred oligonucleotides are ones whiich include a sequence selected from TGGGG TGGGG T GGGGT GGGGT CAG CGA AGC and TTGGG TTGGG T GGGTT GGGTT CAG CGA AGC. The anti-restenosis agent may be used as or in a coating on a device for implantation into the body, for instance a stent.
Inventors:
ANDERSEN ERIC (DK)
LE DOAN TRUNG (FR)
LAMIDEY LAURENT (FR)
LE DOAN TRUNG (FR)
LAMIDEY LAURENT (FR)
Application Number:
PCT/EP2002/011964
Publication Date:
December 24, 2003
Filing Date:
October 25, 2002
Export Citation:
Assignee:
CATHNET SCIENCE HOLDING AS (DK)
CT NAT DE RECH SCIENT CNRS (FR)
ANDERSEN ERIC (DK)
LE DOAN TRUNG (FR)
LAMIDEY LAURENT (FR)
CT NAT DE RECH SCIENT CNRS (FR)
ANDERSEN ERIC (DK)
LE DOAN TRUNG (FR)
LAMIDEY LAURENT (FR)
International Classes:
A61F2/82; A61K31/7088; A61L31/16; A61L31/00; A61P9/10; (IPC1-7): A61K31/70; A61L31/10; C07H21/00
Domestic Patent References:
| WO1999003517A1 | 1999-01-28 |
Other References:
LEE, MILLIE ET AL: "Antisense strategies to inhibit restenosis", ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT (1999), 9(5), 487-492, XP009005205
SHI Y ET AL: "DOWNREGULATION OF C-MYC EXPRESSION BY ANTISENSE OLIGONUCLEOTIDES INHIBITS PROLIFERATION OF HUMAN SMOOTH MUSCLE CELLS", CIRCULATION, AMERICAN HEART ASSOCIATION, DALLAS, TX, US, vol. 88, 1993, pages 1190 - 1195, XP000644593, ISSN: 0009-7322
WANG W ET AL: "Sequence-independent Inhibition of In vitro vascular smooth muscle cell proliferation, migration, and In vivo neointimal formation by phosphorothioate oligodeoxynucleotides", JOURNAL OF CLINICAL INVESTIGATION, NEW YORK, NY, US, vol. 98, no. 2, July 1996 (1996-07-01), pages 443 - 450, XP002230445
BURGESS T L ET AL: "THE ANTIPROLIFERATIVE ACTIVITY OF C-MYB AND C-MYE ANTISENSE OLIGONUCLEOTIDES IN SMOOTH MUSCLE CELLS IS CAUSED BY A NONANTISENSE MECHANISM", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 92, no. 9, 25 April 1995 (1995-04-25), pages 4051 - 4055, XP002015216, ISSN: 0027-8424
SUN L-Q ET AL: "SUPPRESSION OF SMOOTH MUSCLE CELL PROLIFERATION BY A C-MYC RNA-CLEAVING DEOXYRIBOZYME", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, US, vol. 274, no. 24, 11 June 1966 (1966-06-11), pages 17236 - 17241, XP001009843, ISSN: 0021-9258
YOSHIZAWA S ET AL: "NUCLEASE RESISTANCE OF AN EXTRAORDINARILY THERMOSTABLE MINI-HAIRPIN DNA FRAGMENT, D(GCGAAGC) AND ITS APPLICATION TO IN VITRO PROTEIN SYNTHESIS", NUCLEIC ACIDS RESEARCH, OXFORD UNIVERSITY PRESS, SURREY, GB, vol. 22, no. 12, 1994, pages 2217 - 2221, XP001084025, ISSN: 0305-1048
KOZIOLKIEWICZ M ET AL: "The mononucleotide-dependent, nonantisense mechanism of action of phosphodiester and phophorothioate oligonucleotides depends upon the activity of an ecto-5'-nucleotidase", BLOOD, vol. 98, no. 4, 15 August 2001 (2001-08-15), pages 995 - 1002, XP002230446
VAERMAN J.L. ET AL: "Antisense Oligodeoxyribonucleotides suppress hematologic cell growth through stepwise release of deoxyribonucleotides", BLOOD, vol. 90, no. 1, 1 July 1997 (1997-07-01), pages 331 - 339, XP002230447
SHI Y ET AL: "DOWNREGULATION OF C-MYC EXPRESSION BY ANTISENSE OLIGONUCLEOTIDES INHIBITS PROLIFERATION OF HUMAN SMOOTH MUSCLE CELLS", CIRCULATION, AMERICAN HEART ASSOCIATION, DALLAS, TX, US, vol. 88, 1993, pages 1190 - 1195, XP000644593, ISSN: 0009-7322
WANG W ET AL: "Sequence-independent Inhibition of In vitro vascular smooth muscle cell proliferation, migration, and In vivo neointimal formation by phosphorothioate oligodeoxynucleotides", JOURNAL OF CLINICAL INVESTIGATION, NEW YORK, NY, US, vol. 98, no. 2, July 1996 (1996-07-01), pages 443 - 450, XP002230445
BURGESS T L ET AL: "THE ANTIPROLIFERATIVE ACTIVITY OF C-MYB AND C-MYE ANTISENSE OLIGONUCLEOTIDES IN SMOOTH MUSCLE CELLS IS CAUSED BY A NONANTISENSE MECHANISM", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 92, no. 9, 25 April 1995 (1995-04-25), pages 4051 - 4055, XP002015216, ISSN: 0027-8424
SUN L-Q ET AL: "SUPPRESSION OF SMOOTH MUSCLE CELL PROLIFERATION BY A C-MYC RNA-CLEAVING DEOXYRIBOZYME", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, US, vol. 274, no. 24, 11 June 1966 (1966-06-11), pages 17236 - 17241, XP001009843, ISSN: 0021-9258
YOSHIZAWA S ET AL: "NUCLEASE RESISTANCE OF AN EXTRAORDINARILY THERMOSTABLE MINI-HAIRPIN DNA FRAGMENT, D(GCGAAGC) AND ITS APPLICATION TO IN VITRO PROTEIN SYNTHESIS", NUCLEIC ACIDS RESEARCH, OXFORD UNIVERSITY PRESS, SURREY, GB, vol. 22, no. 12, 1994, pages 2217 - 2221, XP001084025, ISSN: 0305-1048
KOZIOLKIEWICZ M ET AL: "The mononucleotide-dependent, nonantisense mechanism of action of phosphodiester and phophorothioate oligonucleotides depends upon the activity of an ecto-5'-nucleotidase", BLOOD, vol. 98, no. 4, 15 August 2001 (2001-08-15), pages 995 - 1002, XP002230446
VAERMAN J.L. ET AL: "Antisense Oligodeoxyribonucleotides suppress hematologic cell growth through stepwise release of deoxyribonucleotides", BLOOD, vol. 90, no. 1, 1 July 1997 (1997-07-01), pages 331 - 339, XP002230447
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