DE69521517D1 - Prodrug-oligonukleotide - Google Patents
Prodrug-oligonukleotideInfo
- Publication number
- DE69521517D1 DE69521517D1 DE69521517T DE69521517T DE69521517D1 DE 69521517 D1 DE69521517 D1 DE 69521517D1 DE 69521517 T DE69521517 T DE 69521517T DE 69521517 T DE69521517 T DE 69521517T DE 69521517 D1 DE69521517 D1 DE 69521517D1
- Authority
- DE
- Germany
- Prior art keywords
- prodrug
- phosphate
- derivatized
- nucleotide
- oligonucleotide
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
Links
- 108091034117 Oligonucleotide Proteins 0.000 title abstract 3
- 229940002612 prodrug Drugs 0.000 title abstract 3
- 239000000651 prodrug Substances 0.000 title abstract 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 title 1
- 239000002773 nucleotide Substances 0.000 abstract 3
- 125000003729 nucleotide group Chemical group 0.000 abstract 3
- 229910019142 PO4 Inorganic materials 0.000 abstract 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 abstract 2
- 239000010452 phosphate Substances 0.000 abstract 2
- 102000004190 Enzymes Human genes 0.000 abstract 1
- 108090000790 Enzymes Proteins 0.000 abstract 1
- 230000001413 cellular effect Effects 0.000 abstract 1
- 125000003636 chemical group Chemical group 0.000 abstract 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 abstract 1
- 230000001172 regenerating effect Effects 0.000 abstract 1
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/555—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
-
- 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
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3515—Lipophilic moiety, e.g. cholesterol
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Oncology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30213294A | 1994-09-07 | 1994-09-07 | |
| PCT/US1995/011477 WO1996007392A2 (en) | 1994-09-07 | 1995-09-07 | Oligonucleotide prodrugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69521517D1 true DE69521517D1 (de) | 2001-08-02 |
| DE69521517T2 DE69521517T2 (de) | 2002-04-18 |
Family
ID=23166398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69521517T Expired - Lifetime DE69521517T2 (de) | 1994-09-07 | 1995-09-07 | Prodrug-oligonukleotide |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0779893B1 (de) |
| JP (1) | JPH10505094A (de) |
| AT (1) | ATE202569T1 (de) |
| AU (1) | AU3675195A (de) |
| CA (1) | CA2199464A1 (de) |
| DE (1) | DE69521517T2 (de) |
| WO (1) | WO1996007392A2 (de) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5849905A (en) * | 1994-11-23 | 1998-12-15 | Centre National De La Recherche Scientifique | Biologically active phosphotriester-type nucleosides and methods for preparing same |
| US9096636B2 (en) | 1996-06-06 | 2015-08-04 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds and their use in gene modulation |
| US7812149B2 (en) | 1996-06-06 | 2010-10-12 | Isis Pharmaceuticals, Inc. | 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations |
| US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
| AU4156197A (en) * | 1996-08-21 | 1998-03-06 | Hybridon, Inc. | Oligonucleotide prodrugs |
| US6117992A (en) * | 1996-08-26 | 2000-09-12 | Hybridon, Inc. | Reagents and process for synthesis of oligonucleotides containing phosphorodithioate internucleoside linkages |
| US6489304B2 (en) * | 1997-05-01 | 2002-12-03 | Hybridon, Inc. | Hyperstructure-forming carriers |
| WO2004044132A2 (en) | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Modified oligonucleotides for use in rna interference |
| WO2005027962A1 (en) | 2003-09-18 | 2005-03-31 | Isis Pharmaceuticals, Inc. | 4’-thionucleosides and oligomeric compounds |
| US8569474B2 (en) | 2004-03-09 | 2013-10-29 | Isis Pharmaceuticals, Inc. | Double stranded constructs comprising one or more short strands hybridized to a longer strand |
| US8394947B2 (en) | 2004-06-03 | 2013-03-12 | Isis Pharmaceuticals, Inc. | Positionally modified siRNA constructs |
| US7884086B2 (en) | 2004-09-08 | 2011-02-08 | Isis Pharmaceuticals, Inc. | Conjugates for use in hepatocyte free uptake assays |
| EP4082551A1 (de) | 2006-08-08 | 2022-11-02 | Rheinische Friedrich-Wilhelms-Universität Bonn | Struktur und verwendung von 5'-phosphat-oligonukleotiden |
| EP1935434A1 (de) * | 2006-12-19 | 2008-06-25 | Novosom AG | Konstruktion und Verwendung von transfektionsverstärkenden Elementen |
| JP5689413B2 (ja) | 2008-05-21 | 2015-03-25 | ライニッシュ フリードリッヒ−ウィルヘルムズ−ユニバーシタット ボン | 平滑末端を有する５’三リン酸オリゴヌクレオチドおよびその使用 |
| CA2744987C (en) | 2008-12-02 | 2018-01-16 | Chiralgen, Ltd. | Method for the synthesis of phosphorus atom modified nucleic acids |
| JP2012513450A (ja) * | 2008-12-23 | 2012-06-14 | ギリンダス・アメリカ・インコーポレイテッド | 硫化剤およびオリゴヌクレオチドを合成するためのその使用 |
| AU2015255202B2 (en) * | 2009-07-06 | 2017-07-27 | Wave Life Sciences Ltd. | Novel nucleic acid prodrugs and methods of use thereof |
| AU2010270714B2 (en) * | 2009-07-06 | 2015-08-13 | Wave Life Sciences Ltd. | Novel nucleic acid prodrugs and methods use thereof |
| EP2620428B1 (de) | 2010-09-24 | 2019-05-22 | Wave Life Sciences Ltd. | Asymmetrische hilfsgruppe |
| EP2508530A1 (de) | 2011-03-28 | 2012-10-10 | Rheinische Friedrich-Wilhelms-Universität Bonn | Reinigung von triphosphorylierten Oligonucleotiden mit Einfang-Tags |
| SG10201700554VA (en) | 2011-07-19 | 2017-03-30 | Wave Life Sciences Pte Ltd | Methods for the synthesis of functionalized nucleic acids |
| WO2014012081A2 (en) | 2012-07-13 | 2014-01-16 | Ontorii, Inc. | Chiral control |
| SG11201500239VA (en) | 2012-07-13 | 2015-03-30 | Wave Life Sciences Japan | Asymmetric auxiliary group |
| BR112015000723A2 (pt) | 2012-07-13 | 2017-06-27 | Shin Nippon Biomedical Laboratories Ltd | adjuvante de ácido nucléico quiral |
| EP2712870A1 (de) | 2012-09-27 | 2014-04-02 | Rheinische Friedrich-Wilhelms-Universität Bonn | Neuartige RIG-I-Liganden und Herstellungsverfahren dafür |
| JP6065263B2 (ja) * | 2012-10-25 | 2017-01-25 | 学校法人神奈川大学 | プロドラッグ化合物、オリゴヌクレオチド型プロドラッグ化合物の合成用試薬、及びオリゴヌクレオチド型プロドラッグ化合物の製造方法 |
| EP3095461A4 (de) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chirales nukleinsäure-adjuvans mit immunitätsinduktionswirkung und immunitätsinduktionsaktivator |
| US10149905B2 (en) | 2014-01-15 | 2018-12-11 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having antitumor effect and antitumor agent |
| JPWO2015108046A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗アレルギー作用を有するキラル核酸アジュバンド及び抗アレルギー剤 |
| MX2016009290A (es) | 2014-01-16 | 2017-02-28 | Wave Life Sciences Ltd | Diseño quiral. |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4547569A (en) * | 1982-11-24 | 1985-10-15 | The United States Of America As Represented By The Department Of Health And Human Services | Intercalating agents specifying nucleotides |
| US4958013A (en) * | 1989-06-06 | 1990-09-18 | Northwestern University | Cholesteryl modified oligonucleotides |
| FR2705099B1 (fr) * | 1993-05-12 | 1995-08-04 | Centre Nat Rech Scient | Oligonucléotides phosphorothioates triesters et procédé de préparation. |
-
1995
- 1995-09-07 DE DE69521517T patent/DE69521517T2/de not_active Expired - Lifetime
- 1995-09-07 AU AU36751/95A patent/AU3675195A/en not_active Abandoned
- 1995-09-07 EP EP95934409A patent/EP0779893B1/de not_active Expired - Lifetime
- 1995-09-07 AT AT95934409T patent/ATE202569T1/de not_active IP Right Cessation
- 1995-09-07 WO PCT/US1995/011477 patent/WO1996007392A2/en active IP Right Grant
- 1995-09-07 CA CA002199464A patent/CA2199464A1/en not_active Abandoned
- 1995-09-07 JP JP8509709A patent/JPH10505094A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP0779893B1 (de) | 2001-06-27 |
| WO1996007392A2 (en) | 1996-03-14 |
| WO1996007392A3 (en) | 1996-05-17 |
| JPH10505094A (ja) | 1998-05-19 |
| DE69521517T2 (de) | 2002-04-18 |
| ATE202569T1 (de) | 2001-07-15 |
| EP0779893A2 (de) | 1997-06-25 |
| CA2199464A1 (en) | 1996-03-14 |
| AU3675195A (en) | 1996-03-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |