DK2591105T3 - Fremgangsmåder og sammensætninger til specifik inhibering af beta-catenin ved hjælp af dobbeltstrenget rna - Google Patents
Fremgangsmåder og sammensætninger til specifik inhibering af beta-catenin ved hjælp af dobbeltstrenget rna Download PDFInfo
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- DK2591105T3 DK2591105T3 DK11804230.8T DK11804230T DK2591105T3 DK 2591105 T3 DK2591105 T3 DK 2591105T3 DK 11804230 T DK11804230 T DK 11804230T DK 2591105 T3 DK2591105 T3 DK 2591105T3
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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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
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/32—Chemical structure of the sugar
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
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Claims (12)
1. Isoleret dobbeltstrenget ribonukleinsyre (dsRNA) omfattende første og anden nukleinsyrestreng og en duplex-region på mindst 25 basepar, hvor den første streng er 25-34 nukleotider lang, og den anden streng af dsRNA'en er fuldstændig komplementær til en target-p-catenin-cDNA-sekvens, som er SEQ ID NO: 2348, og dsRNA'en reducerer ekspression af β-catenin-target-genet, når den dobbeltstrengede nukleinsyre indføres i en pattedyrscelle.
2. Isoleret dsRNA ifølge krav 1, hvor a) startende fra det første nukleotid (position 1) ved 3’-terminussen af den første oligonukieotidstreng, position 1,2 og/eller 3 er substitueret med et modificeret nukleotid, eller b) 3’-terminussen af den første streng og 5’-terminussen af den anden streng danner en stump ende, eller c) den første streng er 25 nukleotider lang, eller d) den første streng omfatter en sekvens omfattende SEQ ID NO: 130, eller e) den modificerede nukleotidrest af 3'-terminussen af den første streng er udvalgt fra gruppen bestående af et deoxyribonukleotid, et acycionukieotid og et fluorescerende molekyle, eller f) dsRNA’en er spaltet endogent i cellen af Dicer, eller g) mængden af de isolerede dobbeltstrengede nukleinsyrer, der er tilstrækkelig til at reducere ekspression af target-genet, er udvalgt fra gruppen bestående af 1 nanomol eller mindre, 200 picomol eller mindre, 100 picomoi eller mindre, 50 picomol eller mindre, 20 picomol eller mindre, 10 picomol eller mindre, 5 picomol eller mindre, 2 picomol eller mindre og 1 picomol eller mindre i cellens omgivelser, eller h) den isolerede dsRNA har større styrke end en isoleret 2lmer-siRNA rettet mod SEQ ID NQ: 2348 til at reducere ekspression af target- β-caten i n-genet, analyseret in vitro i en pattedyrscelle ved en virksom koncentration i omgivelserne af en celle på 1 nanomol eller mindre, eller i) den første og anden streng er forbundet af en kemisk linker.
3. In vitro-fremgangsmåde til reduktion af ekspression af et targeh^-catenin-gen i en pattedyrscelle, omfattende at bringe en pattedyrscelle i kontakt med en isoleret dsRNA ifølge krav 1 i en mængde, der er tilstrækkelig til at redu- cere ekspression af et target-p-catenin-gen i cellen, fortrinsvis hvor ekspression af target-p-catenin-genet reduceres med en mængde (udtrykt i %), der er udvalgt fra gruppen bestående af mindst 10 %, mindst 50 % og mindst 80-90 %.
4. Anvendelse af en virksom mængde af en isoleret dsRNA ifølge krav 1 til fremstilling af et medikament til reduktion af ekspression af et target-β-catenin-gen hos et pattedyr.
5. Anvendelse ifølge krav 4, hvor a) den isolerede dsRNA indgives i en dosering udvalgt fra gruppen bestående af 1 mikrogram tii 5 milligram pr. kilogram af pattedyret pr. dag, 100 mikrogram ti! 0,5 milligram pr. kilogram, 0,001 til 0,25 milligram pr. kilogram, 0,01 til 20 mikrogram pr. kilogram, 0,01 til 10 mikrogram pr. kilogram, 0,10 til 5 mikrogram pr. kilogram og 0,1 til 2,5 mikrogram pr. kilogram, eller b) den isolerede dsRNA har større styrke end isoleret 21mer-siRNA'er rettet mod SEQ ID NO: 2348 til at reducere ekspression af target- β-caten i n-genet, analyseret in vitro i en pattedyrscelle ved en virksom koncentration i omgivelserne af en celle på 1 nanomol eller mindre, eller c) indgivelsestrinnet omfatter en måde udvalgt fra gruppen bestående af intravenøs injektion, intramuskulær injektion, intraperitoneal injektion, infusion, subkutan injektion, transdermal, aerosol-, rektal, vaginal, topisk, oral og inhaleret afgivelse.
6. Fremgangsmåde ifølge krav 3 til selektiv inhibering af væksten af en celle, omfattende at bringe en celle i kontakt med en mængde af den isolerede dsRNA ifølge krav 1, der er tilstrækkelig til at inhibere væksten af cellen, fortrinsvis hvor cellen er en tumorcelle af et individ.
7. Sammensætning omfattende den isolerede dsRNA ifølge krav 1, hvor dsRNA'en er til stede i en mængde, der er virksom tii at reducere target-β-catenin-RNA-niveauer, når dsRNA'en indføres i en pattedyrscelle in vitro i en mængde (udtrykt i %) udvalgt fra gruppen bestående af mindst 10 %, mindst 50 % og mindst 80-90 %, og hvor dsRNA'en har større styrke end isoleret 21mer-siRNA'er rettet mod SEQ ID NO: 2348 til at reducere target-B-catenin-RNA-niveauer, analyseret in vitro i en pattedyrscelle ved en virksom koncen tration i omgiveiserne af en ceiie på 1 nanomoi eiler mindre, fortrinsvis hvor den virksomme mængde er udvalgt fra gruppen bestående af 1 nanomoi eller mindre, 200 picomo! eller mindre, 100 picomol eller mindre, 50 picomol eller mindre, 20 picomol eller mindre, 10 picomoi eiler mindre, 5 picomol eller mindre, 2 picomol eller mindre og 1 picomoi elier mindre i cellens omgivelser.
8. Isoleret pattedyrscelie indeholdende den isolerede dsRNA ifølge krav 1.
9. Sammensætning ifølge krav 7, hvor sammensætningen er en farmaceutisk sammensætning omfattende en farmaceutisk acceptabel bærer.
10. Kit omfattende den isolerede dsRNA ifølge krav 1, eller omfattende en sammensætning ifølge krav 7 eller 9, og anvisning til anvendelse deraf.
11. Anvendelse ifølge krav 4, hvor medikamentet er til behandling eiler forebyggelse af en β-catenin-associeret sygdom eller lidelse hos et individ, hvor medikamentet yderligere omfatter en farmaceutisk acceptabel bærer, fortrinsvis hvor den β-catenin-associerede sygdom elier lidelse er kolorektal cancer eller hepatocellulær cancer.
12. Isoleret dsRNA ifølge krav 1, hvor den anden oligonukleotidstreng omfatter 1 -5 enkeltstrengede nukleotider ved dens S'-terminus.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36177610P | 2010-07-06 | 2010-07-06 | |
| PCT/US2011/042820 WO2012006243A2 (en) | 2010-07-06 | 2011-07-01 | Methods and compositions for the specific inhibition of beta-catenin by double-stranded rna |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2591105T3 true DK2591105T3 (da) | 2017-07-31 |
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Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK19171689.3T DK3587579T3 (da) | 2010-07-06 | 2011-07-01 | Fremgangsmåder og sammensætninger til specifik hæmning af beta-catenin ved hjælp af dobbeltstrenget rna |
| DK11804230.8T DK2591105T3 (da) | 2010-07-06 | 2011-07-01 | Fremgangsmåder og sammensætninger til specifik inhibering af beta-catenin ved hjælp af dobbeltstrenget rna |
| DK16155285.6T DK3037538T3 (da) | 2010-07-06 | 2011-07-01 | Fremgangsmåder og sammensætninger til specifik inhibering af beta-catenin ved hjælp af dobbeltstrenget rna |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK19171689.3T DK3587579T3 (da) | 2010-07-06 | 2011-07-01 | Fremgangsmåder og sammensætninger til specifik hæmning af beta-catenin ved hjælp af dobbeltstrenget rna |
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| Application Number | Title | Priority Date | Filing Date |
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| DK16155285.6T DK3037538T3 (da) | 2010-07-06 | 2011-07-01 | Fremgangsmåder og sammensætninger til specifik inhibering af beta-catenin ved hjælp af dobbeltstrenget rna |
Country Status (9)
| Country | Link |
|---|---|
| US (5) | US8815825B2 (da) |
| EP (4) | EP2591105B1 (da) |
| JP (1) | JP5976643B2 (da) |
| AU (1) | AU2011276365B2 (da) |
| CA (2) | CA3146952A1 (da) |
| DK (3) | DK3587579T3 (da) |
| ES (3) | ES2734743T3 (da) |
| PT (1) | PT3587579T (da) |
| WO (1) | WO2012006243A2 (da) |
Families Citing this family (13)
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| US10023862B2 (en) * | 2012-01-09 | 2018-07-17 | Arrowhead Pharmaceuticals, Inc. | Organic compositions to treat beta-catenin-related diseases |
| WO2016141312A1 (en) * | 2015-03-04 | 2016-09-09 | The University Of Chicago | Beta-catenin inhibitors in cancer immunotherapy |
| US10821112B2 (en) | 2016-03-16 | 2020-11-03 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for the treatment of a beta-catenin-associated disease or disorder |
| MA45469A (fr) * | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Acides nucléiques de bêta-caténine et leurs utilisations |
| EP3548005A4 (en) | 2016-11-29 | 2020-06-17 | Puretech Health LLC | Exosomes for delivery of therapeutic agents |
| US10407681B2 (en) * | 2017-03-28 | 2019-09-10 | The United States Of America, As Represented By The Secretary Of Agriculture | Plant-mediated silencing of a fatty acid and retinoid binding protein in Pratylenchus penetrans |
| AU2018244351A1 (en) * | 2017-03-28 | 2019-10-17 | Dicerna Pharmaceuticals, Inc. | Reducing beta-catenin expression to potentiate immunotherapy |
| EP3672980A4 (en) * | 2017-10-18 | 2021-06-16 | Dicerna Pharmaceuticals, Inc. | BETA-CATENIN NUCLEIC ACID INHIBITOR MOLECULE |
| EP3714054A1 (en) * | 2017-11-20 | 2020-09-30 | Alnylam Pharmaceuticals, Inc. | Serum amyloid p component (apcs) irna compositions and methods of use thereof |
| US11813280B2 (en) | 2018-01-05 | 2023-11-14 | Dicerna Pharmaceuticals, Inc. | Reducing beta-catenin and IDO expression to potentiate immunotherapy |
| CN112055597A (zh) * | 2018-03-02 | 2020-12-08 | 迪克纳制药公司 | 用于治疗胆管缺乏相关病况的方法和组合物 |
| US10961534B2 (en) | 2018-07-13 | 2021-03-30 | University of Pittsburgh—of the Commonwealth System of Higher Education | Methods of treating porphyria |
| AU2022316139A1 (en) * | 2021-07-23 | 2024-01-18 | Alnylam Pharmaceuticals, Inc. | Beta-catenin (ctnnb1) irna compositions and methods of use thereof |
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| US5652094A (en) | 1992-01-31 | 1997-07-29 | University Of Montreal | Nucleozymes |
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2011
- 2011-07-01 DK DK19171689.3T patent/DK3587579T3/da active
- 2011-07-01 ES ES16155285T patent/ES2734743T3/es active Active
- 2011-07-01 EP EP11804230.8A patent/EP2591105B1/en active Active
- 2011-07-01 DK DK11804230.8T patent/DK2591105T3/da active
- 2011-07-01 EP EP16155285.6A patent/EP3037538B1/en active Active
- 2011-07-01 EP EP21154097.6A patent/EP3854874A1/en not_active Withdrawn
- 2011-07-01 CA CA3146952A patent/CA3146952A1/en active Pending
- 2011-07-01 ES ES19171689T patent/ES2873893T3/es active Active
- 2011-07-01 PT PT191716893T patent/PT3587579T/pt unknown
- 2011-07-01 DK DK16155285.6T patent/DK3037538T3/da active
- 2011-07-01 AU AU2011276365A patent/AU2011276365B2/en not_active Ceased
- 2011-07-01 WO PCT/US2011/042820 patent/WO2012006243A2/en not_active Ceased
- 2011-07-01 EP EP19171689.3A patent/EP3587579B1/en active Active
- 2011-07-01 ES ES11804230.8T patent/ES2635388T3/es active Active
- 2011-07-01 CA CA2804214A patent/CA2804214C/en active Active
- 2011-07-01 JP JP2013518762A patent/JP5976643B2/ja not_active Expired - Fee Related
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2018
- 2018-07-09 US US16/030,253 patent/US10612023B2/en active Active
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