WO1998049287A3 - Antisense oligonucleotides specific for thymidylate synthase - Google Patents

Antisense oligonucleotides specific for thymidylate synthase Download PDF

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Publication number
WO1998049287A3
WO1998049287A3 PCT/US1998/008722 US9808722W WO9849287A3 WO 1998049287 A3 WO1998049287 A3 WO 1998049287A3 US 9808722 W US9808722 W US 9808722W WO 9849287 A3 WO9849287 A3 WO 9849287A3
Authority
WO
WIPO (PCT)
Prior art keywords
thymidylate synthase
antisense oligonucleotides
oligonucleotides specific
malignant cell
composition
Prior art date
Application number
PCT/US1998/008722
Other languages
French (fr)
Other versions
WO1998049287A2 (en
Inventor
John C Schmitz
Sudhir Agrawal
Edward Chu
Original Assignee
Hybridon Inc
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 Hybridon Inc filed Critical Hybridon Inc
Priority to AU73649/98A priority Critical patent/AU7364998A/en
Publication of WO1998049287A2 publication Critical patent/WO1998049287A2/en
Publication of WO1998049287A3 publication Critical patent/WO1998049287A3/en

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Classifications

    • 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
    • C12N15/1137—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 enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y201/00—Transferases transferring one-carbon groups (2.1)
    • C12Y201/01—Methyltransferases (2.1.1)
    • C12Y201/01045—Thymidylate synthase (2.1.1.45)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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

Abstract

The present invention discloses synthetic oligonucleotides complementary to thymidylate synthase and methods of downregulating at least a portion of thymidylate synthase mRNA translation or protein expression in a malignant cell and of preventing or overcoming resistance to thymidylate synthase inhibitor compounds in a malignant cell using such oligonucleotides. Also disclosed is a therapeutic composition and a method of treating malignant tumor growth in a mammal utilizing such a composition.
PCT/US1998/008722 1997-04-30 1998-04-30 Antisense oligonucleotides specific for thymidylate synthase WO1998049287A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU73649/98A AU7364998A (en) 1997-04-30 1998-04-30 Antisense oligonucleotides specific for thymidylate synthase

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US4523097P 1997-04-30 1997-04-30
US60/045,230 1997-04-30

Publications (2)

Publication Number Publication Date
WO1998049287A2 WO1998049287A2 (en) 1998-11-05
WO1998049287A3 true WO1998049287A3 (en) 1999-02-04

Family

ID=21936721

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/008722 WO1998049287A2 (en) 1997-04-30 1998-04-30 Antisense oligonucleotides specific for thymidylate synthase

Country Status (2)

Country Link
AU (1) AU7364998A (en)
WO (1) WO1998049287A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003086416A1 (en) * 2002-04-08 2003-10-23 Sarissa Inc. Combinations of antisense oligonucleotides directed against thymidylate synythase mrna and uses thereof
WO1999015648A1 (en) * 1997-09-23 1999-04-01 Zeneca Limited Antisense oligonucleotides against thymidylate synthase
US6087489A (en) * 1998-06-02 2000-07-11 Isis Pharmaceuticals Inc. Antisense oligonucleotide modulation of human thymidylate synthase expression
WO2005093090A1 (en) * 2004-03-26 2005-10-06 Sarissa Inc. Antisense oligonucleotides and uses thereof in improving cancer treatment strategies

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993013740A2 (en) * 1991-12-31 1993-07-22 Worcester Foundation For Experimental Biology Antiparasitic oligonucleotides active against drug resistant malaria
WO1994002498A1 (en) * 1992-07-23 1994-02-03 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993013740A2 (en) * 1991-12-31 1993-07-22 Worcester Foundation For Experimental Biology Antiparasitic oligonucleotides active against drug resistant malaria
WO1994002498A1 (en) * 1992-07-23 1994-02-03 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
89TH ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, NEW ORLEANS, LOUISIANA, USA, MARCH 28-APRIL 1, 1998. *
BLACK A R ET AL: "Expression of rTS correlates with altered growth regulation of thymidylate synthase.", CANCER RESEARCH, (1996 FEB 15) 56 (4) 700-5., XP002081372 *
CHU E ET AL: "Autoregulation of human thymidylate synthase messenger RNA translation by thymidylate synthase.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, (1991 OCT 15) 88 (20) 8977-81., XP002081371 *
CHU E ET AL: "Identification of an RNA binding site for human thymidylate synthase.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, (1993 JAN 15) 90 (2) 517-21., XP002081370 *
CHU E ET AL: "New concepts for the development and use of antifolates.", STEM CELLS, (1996 JAN) 14 (1) 41-6., XP002081366 *
JU, JINGFANG: "INCREASED DRUG SENSITIVITY OF TUMOR CELLS BY MANIPULATION OF CELL CYCLE CONTROL GENES", PH.D. THESIS PRESENTED IN DECEMBER 1996 AT THE FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA, LOS ANGELES, XP002081365 *
KOBAYASHI H ET AL: "Reversal of drug-resistance or inhibition of tumor cell growth by hammerhead ribozymes;", GENE THER.;(1995) 2, PAGE 689; ABSTRACT 065, XP002081367 *
KOROPATNICK J ET AL: "Discrimination of run-on transcription from constitutive genes and antisense expression vectors in the same cells.", BIOTECHNIQUES;(JAN 1997) 22, 1, 64-66, XP002081368 *
LIU Y ET AL: "Levamisole potentiation of 5-fluorouracil and other anti-tumour drugs in cultured cells: Protein tyrosine phosphatase as an alternative to thymidylate synthase as a target.", CELLULAR PHARMACOLOGY 2 (6). 1995. 271-277., XP002081369 *
SCHMITZ J C ET AL: "Specific repression of human TS mRNA translation by antisense oligoribonucleotides.", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL MEETING 39 (0). MARCH 1998. PAGE 645; ABSTRACT 4391, XP002081373 *

Also Published As

Publication number Publication date
AU7364998A (en) 1998-11-24
WO1998049287A2 (en) 1998-11-05

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