DK2363481T3 - Forbindelser og fremgangsmåder til modulering af genekspression - Google Patents
Forbindelser og fremgangsmåder til modulering af genekspression Download PDFInfo
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- DK2363481T3 DK2363481T3 DK11160528.3T DK11160528T DK2363481T3 DK 2363481 T3 DK2363481 T3 DK 2363481T3 DK 11160528 T DK11160528 T DK 11160528T DK 2363481 T3 DK2363481 T3 DK 2363481T3
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- certain embodiments
- short antisense
- certain
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- antisense compound
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- 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
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
- A61P5/46—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of glucocorticosteroids
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- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- 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
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- C12Y203/00—Acyltransferases (2.3)
- C12Y203/01—Acyltransferases (2.3) transferring groups other than amino-acyl groups (2.3.1)
- C12Y203/0102—Diacylglycerol O-acyltransferase (2.3.1.20)
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/11—Antisense
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
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- 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
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/32—Chemical structure of the sugar
- C12N2310/322—2'-R Modification
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/341—Gapmers, i.e. of the type ===---===
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- 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
Claims (14)
1. Kort antisense-forbindelse med en længde på 12 til 14 monomerer, omfattende et 2'-deoxyribonukleotid-gapområde flankeret på hver side af en vinge, hvor hver vinge uafhængigt omfatter 1 til 3 høj-affinitets-modificerede nukleotider der er sukker-modificerede nukleotider der omfatter en bro mellem 4'- og 2'-positionen af sukkeret, og hvor den korte antisense-forbindelse endvidere omfatter en kovalent forbundet konjugeret gruppe.
2. Kort antisense-forbindelse ifølge krav 1 hvor antisense-forbindelsen har en længde på 13 monomerer.
3. Kort antisense-forbindelse ifølge krav 1, hvor hver af broerne, uafhængigt, er 4'-CH2-2', 4^(012)2-2^ 4'-CH2-0-2', 4'-(CH2)2-0-2', 4'-CH2-0-N(Ri)-2' eller 4'-CH2-N(Ri)-0-2', hvor hver Ri uafhængigt er, H, en beskyttelsesgruppe eller Ci-Ci2-alkyl.
4. Kort antisense-forbindelse ifølge krav 1, hvor broen er 4'-CH(CH3)-0-2'.
5. Kort antisense-forbindelse ifølge et hvilket som helst af kravene 1 til 3, hvor den konjugerede gruppe er valgt fra listen bestående af: kolesterol, cholsyre, et thiokolesterol, et Ci6-alkyl, et phospholipid, en polyaminkæde, en polyethylenglycolkæde, adamantan-eddikesyre, en palmityl-del, en octadecylamin-del og en hexylamino-carbonyl-oxykolesterol-del.
6. Kort antisense-forbindelse ifølge et hvilket som helst af kravene 1-4, hvor den konjugerede gruppe er forbundet direkte med moderforbindelsen.
7. Kort antisense-forbindelse ifølge et hvilket som helst af kravene 1-4, hvor den konjugerede gruppe er forbundet med moderforbindelsen via en forbindelsesgruppe.
8. Kort antisense-forbindelse ifølge krav 7 hvor forbindelsesgruppen er en oligomer af gentagelsesenheder, 8-amino-3,6-dioxaoctansyre (ADO), succinimidyl 4-(N-maleimidomethyl) cyclohexan-l-carboxylat (SMCC), 6-aminohexansyre (AHEX eller Al-IA), et substitueret Ci-Cio-alkyl, et substitueret eller ikke-substitueret C2-Cio-alkenyl eller et substitueret eller ikke-substitueret C2-C10-alkynyl.
9. Kort antisense-forbindelse ifølge et hvilket som helst af de foregående krav, hvor nukleobasesekvensen af antisense-forbindelsen er 100% komplementærtil en målnukleinsyre.
10. Kort antisense-forbindelse ifølge et hvilket som helst af de foregående krav, med et motiv valgt fra gruppen bestående af 1-12-1, 2-10-2, 1-10-1, 1-10-2, 3-8-3, 2-8-2, 1-8-1, og 1-9-2 hvor det første tal betegner antallet af monomerer i 5'-vingen, det andet tal betegner antallet af monomerer i gappet, og det tredje tal betegner antallet af monomerer i 3'-vingen.
11. Kort antisense-forbindelse ifølge et hvilket som helst af kravene 1-10, med et 1-1-10-2-motiv, hvor det første tal betegner antallet af monomerer i en første 5'-vinge, det andet tal betegner antallet af monomerer i en anden 5'-vinge, det tredje tal betegner antallet af monomerer i gappet, og det fjerde tal betegner antallet af monomerer i 3'-vingen.
12. Kort antisense-forbindelse ifølge et hvilket som helst af de foregående krav hvor mindst en monomer binding er en modificeret monomer binding, såsom en phosphorthioat-binding.
13. Farmaceutisk sammensætning omfattende en effektiv mængde af en kort antisense forbindelse ifølge et hvilket som helst af de foregående krav og en farmaceutisk acceptabel fortynder, bærer eller excipiens.
14. Kort antisense-forbindelse ifølge et hvilket som helst af kravene 1-12 eller den farmaceutiske sammensætning ifølge krav 13, til anvendelse til behandling af en tilstand eller lidelse hos et pattedyrs-, fortrinsvis menneskeligt, individ.
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
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US74663106P | 2006-05-05 | 2006-05-05 | |
US74705906P | 2006-05-11 | 2006-05-11 | |
US80566006P | 2006-06-23 | 2006-06-23 | |
US86455406P | 2006-11-06 | 2006-11-06 | |
PCT/US2007/061183 WO2007090071A2 (en) | 2006-01-27 | 2007-01-27 | 6-modified bicyclic nucleic acid analogs |
EP07811872A EP2021472B1 (en) | 2006-05-05 | 2007-05-07 | Compounds and methods for modulating gene expression |
Publications (1)
Publication Number | Publication Date |
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DK2363481T3 true DK2363481T3 (da) | 2017-06-26 |
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ID=40134111
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK07811878.3T DK2019692T3 (da) | 2006-05-05 | 2007-05-07 | Forbindelser og fremgangsmåder til modulation af ekspression af gccr |
DK11160528.3T DK2363481T3 (da) | 2006-05-05 | 2007-05-07 | Forbindelser og fremgangsmåder til modulering af genekspression |
DK07811873.4T DK2015758T3 (da) | 2006-05-05 | 2007-05-07 | Forbindelser og fremgangsmåder til modulering af ekspression af apob |
DK11189591.8T DK2458006T3 (da) | 2006-05-05 | 2007-05-07 | Forbindelser og fremgangsmåder til modulering af ApoB ekspression. |
DK07811872.6T DK2021472T3 (da) | 2006-05-05 | 2007-05-07 | Forbindelser og fremgangsmåder til modulering af genekspression |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
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DK07811878.3T DK2019692T3 (da) | 2006-05-05 | 2007-05-07 | Forbindelser og fremgangsmåder til modulation af ekspression af gccr |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK07811873.4T DK2015758T3 (da) | 2006-05-05 | 2007-05-07 | Forbindelser og fremgangsmåder til modulering af ekspression af apob |
DK11189591.8T DK2458006T3 (da) | 2006-05-05 | 2007-05-07 | Forbindelser og fremgangsmåder til modulering af ApoB ekspression. |
DK07811872.6T DK2021472T3 (da) | 2006-05-05 | 2007-05-07 | Forbindelser og fremgangsmåder til modulering af genekspression |
Country Status (16)
Country | Link |
---|---|
US (14) | US20090326041A1 (da) |
EP (10) | EP2023940B1 (da) |
JP (7) | JP5731115B2 (da) |
KR (1) | KR101441700B1 (da) |
CN (1) | CN103554205A (da) |
AT (2) | ATE513912T1 (da) |
AU (4) | AU2007258117B2 (da) |
BR (1) | BRPI0711429A2 (da) |
CA (3) | CA2651309C (da) |
DK (5) | DK2019692T3 (da) |
ES (2) | ES2471978T3 (da) |
HK (1) | HK1128418A1 (da) |
MX (1) | MX2008014100A (da) |
NO (1) | NO20084738L (da) |
PT (1) | PT2015758E (da) |
WO (9) | WO2007134014A2 (da) |
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US20050287558A1 (en) | 2004-05-05 | 2005-12-29 | Crooke Rosanne M | SNPs of apolipoprotein B and modulation of their expression |
BRPI0616158A2 (pt) * | 2005-09-19 | 2011-06-07 | Johnson & Johnson Pharmaceutical Res & Dev L L C | modulação de expressão de receptor de glucagon |
CN103301475B (zh) | 2005-12-28 | 2016-08-03 | 斯克里普斯研究所 | 药物组合物和表达载体以及调节基因表达的方法和核酸分子的应用 |
US7764650B2 (en) | 2006-03-02 | 2010-07-27 | Intel Corporation | Mobile station and method for fast roaming with integrity protection and source authentication using a common protocol |
EP3431602A1 (en) | 2006-04-03 | 2019-01-23 | Roche Innovation Center Copenhagen A/S | Pharmaceutical composition comprising anti-mirna antisense oligonucleotides |
JP5814505B2 (ja) | 2006-04-03 | 2015-11-17 | ロシュ・イノベーション・センター・コペンハーゲン・アクティーゼルスカブRoche Innovation Center Copenhagen A/S | antimiRNAアンチセンスオリゴヌクレオチドを含む医薬組成物 |
WO2007134014A2 (en) * | 2006-05-05 | 2007-11-22 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of gcgr |
EP2052079A2 (en) * | 2006-07-17 | 2009-04-29 | Sirna Therapeutics Inc. | Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina) |
ES2620472T5 (es) * | 2006-10-18 | 2020-07-09 | Ionis Pharmaceuticals Inc | Compuestos antisentido |
EP2102340A2 (en) | 2006-11-27 | 2009-09-23 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
AU2008228243B2 (en) * | 2007-03-22 | 2014-05-15 | Santaris Pharma A/S | RNA antagonist compounds for the inhibition of Apo-B100 expression |
KR20150090284A (ko) * | 2007-03-24 | 2015-08-05 | 젠자임 코포레이션 | 인간 아포리포프로틴 b에 상보적인 안티센스 올리고뉴클레오타이드 투여 |
CA2685444A1 (en) | 2007-05-01 | 2008-11-06 | Jesper Worm | Rna antagonist compounds for the modulation of beta-catenin |
WO2008138904A2 (en) | 2007-05-11 | 2008-11-20 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of her3 |
ES2376507T5 (es) † | 2007-07-05 | 2015-08-31 | Isis Pharmaceuticals, Inc. | Análogos de ácidos nucleicos bicíclicos 6-disustituidos |
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