WO1999005160A3 - Oligonuclotides having 3' terminal stereospecific phosphorothioates - Google Patents

Oligonuclotides having 3' terminal stereospecific phosphorothioates Download PDF

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Publication number
WO1999005160A3
WO1999005160A3 PCT/US1998/015420 US9815420W WO9905160A3 WO 1999005160 A3 WO1999005160 A3 WO 1999005160A3 US 9815420 W US9815420 W US 9815420W WO 9905160 A3 WO9905160 A3 WO 9905160A3
Authority
WO
WIPO (PCT)
Prior art keywords
antisense oligonucleotides
stereospecific
phosphorothioates
linkages
oligonuclotides
Prior art date
Application number
PCT/US1998/015420
Other languages
French (fr)
Other versions
WO1999005160A2 (en
Inventor
Aharon S Cohen
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 AU85125/98A priority Critical patent/AU8512598A/en
Publication of WO1999005160A2 publication Critical patent/WO1999005160A2/en
Publication of WO1999005160A3 publication Critical patent/WO1999005160A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to antisense oligonucleotides. More particularly, the invention relates to the stabilization of antisense oligonucleotides by modification of internucleoside linkages. The invention provides antisense oligonucleotides which have the benefit of stability provided by phosphorothioate linkages without the side effects. The invention achieves this by providing antisense oligonucleotides having phosphorothiate linkages only at the most 3' positions. This is made possible by incorporating only stereospecific S-enantiomers of phosphorothioate linkages at those positions. Surprisingly, such antisense oligonucleotides retain the stability of antisense oligonucleotides in which all of the internucleoside linkages are phosphorothioates.
PCT/US1998/015420 1997-07-25 1998-07-24 Oligonuclotides having 3' terminal stereospecific phosphorothioates WO1999005160A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU85125/98A AU8512598A (en) 1997-07-25 1998-07-24 Oligonuclotides having 3' terminal stereospecific phosphorothioates

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US5371897P 1997-07-25 1997-07-25
US60/053,718 1997-07-25

Publications (2)

Publication Number Publication Date
WO1999005160A2 WO1999005160A2 (en) 1999-02-04
WO1999005160A3 true WO1999005160A3 (en) 1999-04-08

Family

ID=21986075

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/015420 WO1999005160A2 (en) 1997-07-25 1998-07-24 Oligonuclotides having 3' terminal stereospecific phosphorothioates

Country Status (2)

Country Link
AU (1) AU8512598A (en)
WO (1) WO1999005160A2 (en)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6242589B1 (en) * 1998-07-14 2001-06-05 Isis Pharmaceuticals, Inc. Phosphorothioate oligonucleotides having modified internucleoside linkages
US6867294B1 (en) * 1998-07-14 2005-03-15 Isis Pharmaceuticals, Inc. Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages
KR101881596B1 (en) 2008-12-02 2018-07-24 웨이브 라이프 사이언시스 재팬 인코포레이티드 Method for the synthesis of phosphorous atom modified nucleic acids
CN102596204B (en) 2009-07-06 2016-11-23 波涛生命科学有限公司 New nucleic acid prodrugs and using method thereof
WO2012039448A1 (en) 2010-09-24 2012-03-29 株式会社キラルジェン Asymmetric auxiliary group
ES2626488T3 (en) 2011-07-19 2017-07-25 Wave Life Sciences Pte. Ltd. Procedures for the synthesis of functionalized nucleic acids
SG11201500232UA (en) 2012-07-13 2015-04-29 Wave Life Sciences Pte Ltd Chiral control
EP2873674B1 (en) 2012-07-13 2020-05-06 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant
AU2013288048A1 (en) 2012-07-13 2015-01-22 Wave Life Sciences Ltd. Asymmetric auxiliary group
EP3095459A4 (en) 2014-01-15 2017-08-23 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having antitumor effect and antitumor agent
EP3095461A4 (en) 2014-01-15 2017-08-23 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator
US10322173B2 (en) 2014-01-15 2019-06-18 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent
CN106068325B (en) 2014-01-16 2021-07-09 波涛生命科学有限公司 Chiral design
MA43072A (en) 2015-07-22 2018-05-30 Wave Life Sciences Ltd COMPOSITIONS OF OLIGONUCLEOTIDES AND RELATED PROCESSES

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4521509A (en) * 1982-11-24 1985-06-04 Research Corporation Method for degrading DNA
WO1989003683A1 (en) * 1987-10-22 1989-05-05 Temple University Of The Commonwealth System Of Hi 2',5'-phosphorothioate oligoadenylates and antiviral uses thereof
WO1989005358A1 (en) * 1987-11-30 1989-06-15 University Of Iowa Research Foundation Dna and rna molecules stabilized by modifications of the 3'-terminal phosphodiester linkage and their use as nucleic acid probes and as therapeutic agents to block the expression of specifically targeted genes
WO1993008296A1 (en) * 1991-10-15 1993-04-29 Isis Pharmaceuticals, Inc. Oligonucleotides having chiral phosphorus linkages
WO1996019572A1 (en) * 1994-12-22 1996-06-27 Hybridon, Inc. Synthesis of stereospecific oligonucleotide phosphorothioates
WO1996039154A1 (en) * 1995-06-06 1996-12-12 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4521509A (en) * 1982-11-24 1985-06-04 Research Corporation Method for degrading DNA
WO1989003683A1 (en) * 1987-10-22 1989-05-05 Temple University Of The Commonwealth System Of Hi 2',5'-phosphorothioate oligoadenylates and antiviral uses thereof
WO1989005358A1 (en) * 1987-11-30 1989-06-15 University Of Iowa Research Foundation Dna and rna molecules stabilized by modifications of the 3'-terminal phosphodiester linkage and their use as nucleic acid probes and as therapeutic agents to block the expression of specifically targeted genes
WO1993008296A1 (en) * 1991-10-15 1993-04-29 Isis Pharmaceuticals, Inc. Oligonucleotides having chiral phosphorus linkages
WO1996019572A1 (en) * 1994-12-22 1996-06-27 Hybridon, Inc. Synthesis of stereospecific oligonucleotide phosphorothioates
WO1996039154A1 (en) * 1995-06-06 1996-12-12 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ECKSTEIN F ET AL: "PHOSPHOROTHIOATES IN MOLECULAR BIOLOGY", TIBS TRENDS IN BIOCHEMICAL SCIENCES, vol. 14, 1 March 1989 (1989-03-01), pages 97 - 100, XP000572725 *
ECKSTEIN F: "NUCLEOSIDE PHOSPHOROTHIOATES", ANNUAL REVIEW OF BIOCHEMISTRY, vol. 54, 1985, pages 367 - 402, XP000603155 *
PETERSEN G V ET AL: "Synthesis of Thymidine Dimers Containing Piperazine in the Internucleoside Linkage and their Incorporation into Oligodeoxynucleotides", TETRAHEDRON, vol. 51, no. 7, 13 February 1995 (1995-02-13), pages 2145-2154, XP004104844 *
WANG B H ET AL: "Sequencing of modified oligonucleotides using in-source fragmentation and delayed pulsed ion extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry", INTERNATIONAL JOURNAL OF MASS SPECTROMETRY AND ION PROCESSES, vol. 169-170, December 1997 (1997-12-01), pages 331-350, XP004109255 *

Also Published As

Publication number Publication date
AU8512598A (en) 1999-02-16
WO1999005160A2 (en) 1999-02-04

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