HRP20221378T1 - Spojevi i postupci za modulaciju smn2 - Google Patents
Spojevi i postupci za modulaciju smn2 Download PDFInfo
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- HRP20221378T1 HRP20221378T1 HRP20221378TT HRP20221378T HRP20221378T1 HR P20221378 T1 HRP20221378 T1 HR P20221378T1 HR P20221378T T HRP20221378T T HR P20221378TT HR P20221378 T HRP20221378 T HR P20221378T HR P20221378 T1 HRP20221378 T1 HR P20221378T1
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- modified oligonucleotide
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- nucleosides
- sugar residue
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- 150000001875 compounds Chemical class 0.000 title claims 19
- 108091034117 Oligonucleotide Proteins 0.000 claims 52
- 239000002777 nucleoside Substances 0.000 claims 29
- 125000003835 nucleoside group Chemical group 0.000 claims 25
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical group CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 19
- 101000617738 Homo sapiens Survival motor neuron protein Proteins 0.000 claims 9
- 102100021947 Survival motor neuron protein Human genes 0.000 claims 9
- 230000000295 complement effect Effects 0.000 claims 9
- 108020004999 messenger RNA Proteins 0.000 claims 9
- 150000004713 phosphodiesters Chemical class 0.000 claims 6
- 150000002632 lipids Chemical class 0.000 claims 5
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims 4
- 239000003085 diluting agent Substances 0.000 claims 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical group P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims 3
- 239000002953 phosphate buffered saline Substances 0.000 claims 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 claims 1
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims 1
- 239000004380 Cholic acid Substances 0.000 claims 1
- 235000012000 cholesterol Nutrition 0.000 claims 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 claims 1
- 229960002471 cholic acid Drugs 0.000 claims 1
- 235000019416 cholic acid Nutrition 0.000 claims 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 150000004671 saturated fatty acids Chemical class 0.000 claims 1
- 229930195734 saturated hydrocarbon Natural products 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- 208000002320 spinal muscular atrophy Diseases 0.000 claims 1
- 229960001295 tocopherol Drugs 0.000 claims 1
- 229930003799 tocopherol Natural products 0.000 claims 1
- 235000010384 tocopherol Nutrition 0.000 claims 1
- 239000011732 tocopherol Substances 0.000 claims 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 claims 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 claims 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims 1
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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
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- 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
- C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
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- C12N2310/321—2'-O-R Modification
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Claims (18)
1. Oligomerni spoj, naznačen time, što sadrži modificirani oligonukleotid koji se sastoji od 14-25 povezanih nukleozida, pri čemu je modificirani oligonukleotid komplementaran s pre-mRNA SMN2; i pri čemu najmanje jedan nukleozid od modificiranog oligonukleotida sadrži ostatak šećera modificiran 2'-O-(N-alkil acetamid) skupinom.
2. Oligomerni spoj prema patentnom zahtjevu 1, naznačen time, što:
a. svaki od 7 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
b. svaki od 8 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
c. svaki od 9 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
d. svaki od 10 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
e. svaki od 11 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
f. svaki od 12 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
g. svaki od 13 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
h. svaki od 14 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
i. svaki od 15 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
j. svaki od 16 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
k. svaki od 17 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
l. svaki od 18 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
m. svaki od 19 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid);
n. svaki od 20 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid).
3. Oligomerni spoj prema patentnom zahtjevu 1 ili zahtjevu 2, naznačen time, što:
a. svaki od ostataka šećera modificiranog skupinom 2'-O-(N-alkil acetamid) jest ostatak šećera modificiran skupinom 2'-O-(N-metil acetamid); ili
b. svaki ostatak šećera od svakog nukleozida od modificiranog oligonukleotida jest ostatak šećera modificiran skupinom 2'-O-(N-alkil acetamid); ili
c. svaki ostatak šećera od svakog nukleozida od modificiranog oligonukleotida jest ostatak šećera modificiran skupinom 2'-O-(N-metil acetamid).
4. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time, što:
a. modificirani oligonukleotid se sastoji od 16-23 povezanih nukleozida; ili
b. modificirani oligonukleotid se sastoji od 18-20 povezanih nukleozida.
5. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 4, naznačen time, što:
a. modificirani oligonukleotid se sastoji od 16 nukleozida;
b. modificirani oligonukleotid se sastoji od 17 nukleozida;
c. modificirani oligonukleotid se sastoji od 18 nukleozida;
d. modificirani oligonukleotid se sastoji od 19 nukleozida; ili
e. modificirani oligonukleotid se sastoji od 20 nukleozida.
6. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 5, naznačen time, što se svaki međunukleozidni veznik od modificiranog oligonukleotida bira između fosforotioatnog međunukleozidnog veznika i fosfodiesterskog međunukleozidnog veznika, pri čemu opcionalno:
a. modificirani oligonukleotid sadrži 5 fosfodiesterskih međunukleozidnih veznika;
b. modificirani oligonukleotid sadrži 6 fosfodiesterskih međunukleozidnih veznika; ili
c. modificirani oligonukleotid sadrži najmanje 6 fosfodiesterskih međunukleozidnih veznika.
7. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 6, naznačen time, što modificirani oligonukleotid sadrži najmanje jednu modificiranu nukleobazu, opcionalno pritom modificirani oligonukleotid sadrži najmanje jedan 5-metil citozin.
8. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 7, naznačen time, što:
a. modificirani oligonukleotid je najmanje 70% komplementaran s pre-mRNA SMN2;
b. modificirani oligonukleotid je najmanje 75% komplementaran s pre-mRNA SMN2;
c. modificirani oligonukleotid je najmanje 80% komplementaran s pre-mRNA SMN2;
d. modificirani oligonukleotid je najmanje 85% komplementaran s pre-mRNA SMN2;
e. modificirani oligonukleotid je najmanje 90% komplementaran s pre-mRNA SMN2;
f. modificirani oligonukleotid je najmanje 95% komplementaran s pre-mRNA SMN2; ili
g. modificirani oligonukleotid je najmanje 100% komplementaran s pre-mRNA SMN2.
9. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 8, naznačen time, što oligomerni spoj sadrži skupinu konjugata, pri čemu opcionalno skupina konjugata sadrži lipidnu ili lipofilnu skupinu, opcionalno pritom:
a. lipidna ili lipofilna skupina se bira između kolesterola, C10-C26 zasićene masne kiseline, C10-C26 nezasićene masne kiseline, C10-C26 alkila, triglicerida, tokoferola, ili holne kiseline;
b. lipidna ili lipofilna skupina je zasićeni ugljikovodični lanac ili nezasićeni ugljikovodični lanac;
c. lipidna ili lipofilna skupina jest C16 alkil; ili
d. lipidna ili lipofilna skupina jest zasićeni C16.
10. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 9, naznačen time, što je modificirani oligonukleotid komplementaran s ISS-N1 od pre-mRNA SMN2.
11. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 10, naznačen time, što nukleobazni slijed od modificiranog oligonukleotida sadrži slijed odabran od SEQ ID NO: 1, 2 ili 3, tako da se pritom nukleobazni slijed od modificiranog oligonukleotida sastoji od SEQ ID NO: 3.
12. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 11, naznačen time, što oligomerni spoj je jednolančani.
13. Modificirani oligonukleotid, naznačen time, što se sastoji od 18 povezanih nukleozida i ima nukleobazni slijed SEQ ID NO: 3, pri čemu svaki nukleozid od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-metil acetamid), i time, što se svaki međunukleozidni veznik od modificiranog oligonukleotida bira između fosforotioatnog međunukleozidnog veznika i fosfodiesterskog međunukleozidnog veznika.
14. Modificirani oligonukleotid, naznačen time, što se sastoji od 18 do 20 povezanih nukleozida koji sadrže nukleobazni slijed SEQ ID NO: 1, pri čemu svaki od 18 nukleozida od modificiranog oligonukleotida sadrži ostatak šećera modificiran skupinom 2'-O-(N-metil acetamid), i time, što se svaki međunukleozidni veznik od modificiranog oligonukleotida bira između fosforotioatnog međunukleozidnog veznika i fosfodiesterskog međunukleozidnog veznika.
15. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 12, ili modificirani oligonukleotid prema patentnom zahtjevu 13 ili zahtjevu 14, naznačen time, što modificirani oligonukleotid je natrijeva sol ili kalijeva sol.
16. Farmaceutski pripravak, naznačen time, što sadrži oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 12 ili 15, ili modificirani oligonukleotid prema bilo kojem od patentnih zahtjeva 13 do 15, te najmanje jedan farmaceutski prihvatljiv nosač ili razrjeđivač.
17. Farmaceutski pripravak prema patentnom zahtjevu 16, naznačen time, što pripravak sadrži farmaceutski prihvatljiv razrjeđivač, i farmaceutski prihvatljiv razrjeđivač je fosfatna puferirana slana otopina (PBS), opcionalno pritom se farmaceutski pripravak sastoji od spoja i PBS.
18. Oligomerni spoj prema bilo kojem od patentnih zahtjeva 1 do 12 ili 15, modificirani oligonukleotid prema bilo kojem od patentnih zahtjeva 13 do 15, ili farmaceutski pripravak prema patentnom zahtjevu 16 ili 17, naznačen time, što je za uporabu u postupku liječenja pacijenta od spinalne muskularne atrofije.
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US201662363195P | 2016-07-15 | 2016-07-15 | |
EP17828625.8A EP3484524B1 (en) | 2016-07-15 | 2017-07-17 | Compounds and methods for modulation of smn2 |
PCT/US2017/042463 WO2018014041A2 (en) | 2016-07-15 | 2017-07-17 | Compounds and methods for modulation of smn2 |
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US (2) | US20190323006A1 (hr) |
EP (2) | EP3484524B1 (hr) |
JP (2) | JP7197463B2 (hr) |
KR (1) | KR102556825B1 (hr) |
CN (1) | CN109844115B (hr) |
AU (1) | AU2017297622A1 (hr) |
BR (1) | BR112019000356A2 (hr) |
CA (1) | CA3030864A1 (hr) |
CL (2) | CL2019000115A1 (hr) |
CO (1) | CO2019001236A2 (hr) |
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ES (1) | ES2935658T3 (hr) |
FI (1) | FI3484524T3 (hr) |
HR (1) | HRP20221378T1 (hr) |
HU (1) | HUE060831T2 (hr) |
IL (2) | IL264216B2 (hr) |
LT (1) | LT3484524T (hr) |
MX (1) | MX2019000619A (hr) |
PE (1) | PE20190513A1 (hr) |
PL (1) | PL3484524T3 (hr) |
PT (1) | PT3484524T (hr) |
RS (1) | RS63928B1 (hr) |
SG (1) | SG11201900238UA (hr) |
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Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014169243A2 (en) * | 2013-04-12 | 2014-10-16 | The Curators Of The University Of Missouri | Smn2 element 1 antisense compositions and methods and uses thereof |
US10053465B2 (en) | 2015-08-26 | 2018-08-21 | Incyte Corporation | Pyrrolopyrimidine derivatives as TAM inhibitors |
CA3019145A1 (en) | 2016-03-28 | 2017-10-05 | Incyte Corporation | Pyrrolotriazine compounds as tam inhibitors |
RS62872B1 (sr) | 2017-09-27 | 2022-02-28 | Incyte Corp | Soli derivata pirrolotriazina korisne kao tam inhibitori |
JP2021529765A (ja) | 2018-06-29 | 2021-11-04 | インサイト・コーポレイションIncyte Corporation | Axl/mer阻害剤の製剤 |
JP2022544538A (ja) * | 2019-08-15 | 2022-10-19 | バイオジェン・エムエイ・インコーポレイテッド | 脊髄性筋萎縮症のための併用療法 |
JPWO2021054370A1 (hr) * | 2019-09-18 | 2021-03-25 | ||
US20220064638A1 (en) | 2020-02-28 | 2022-03-03 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating smn2 |
FR3128873A1 (fr) | 2021-11-10 | 2023-05-12 | Biophytis | Phytoecdysones et/ou dérivés de 20-hydroxyecdysone en combinaison avec un principe actif visant à restaurer l’expression SMN pour leur utilisation dans le traitement de l’amyotrophie spinale |
Family Cites Families (124)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
US4751219A (en) | 1985-02-05 | 1988-06-14 | Nederlandse Centrale Organisatie Voor Toegepast-Natuur-Wetenschappelijk Onderzoek | Synthetic glycolipides, a process for the preparation thereof and several uses for these synthetic glycolipides |
US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
US5506337A (en) | 1985-03-15 | 1996-04-09 | Antivirals Inc. | Morpholino-subunit combinatorial library and method |
US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
JP2828642B2 (ja) | 1987-06-24 | 1998-11-25 | ハワード フローレイ インスティテュト オブ イクスペリメンタル フィジオロジー アンド メディシン | ヌクレオシド誘導体 |
US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
US6005087A (en) | 1995-06-06 | 1999-12-21 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
US5457191A (en) | 1990-01-11 | 1995-10-10 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
US5859221A (en) | 1990-01-11 | 1999-01-12 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
BR9106702A (pt) | 1990-07-27 | 1993-06-08 | Isis Pharmaceuticals Inc | Analogo de oligonucleotideos e processos para modular a producao de uma proteina por um organismo e para tratar um organismo |
US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
US5948903A (en) | 1991-01-11 | 1999-09-07 | Isis Pharmaceuticals, Inc. | Synthesis of 3-deazapurines |
US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
TW393513B (en) | 1991-11-26 | 2000-06-11 | Isis Pharmaceuticals Inc | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
JP3739785B2 (ja) | 1991-11-26 | 2006-01-25 | アイシス ファーマシューティカルズ,インコーポレイティド | 修飾されたピリミジンを含有するオリゴマーを使用する増強された三重らせんおよび二重らせんの成形 |
US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
US6908903B1 (en) | 1994-12-07 | 2005-06-21 | Aletheon Pharmaceuticals, Inc. | Cluster clearing agents |
US6172045B1 (en) | 1994-12-07 | 2001-01-09 | Neorx Corporation | Cluster clearing agents |
US20030119724A1 (en) | 1995-11-22 | 2003-06-26 | Ts`O Paul O.P. | Ligands to enhance cellular uptake of biomolecules |
WO1997020563A1 (en) | 1995-11-22 | 1997-06-12 | The Johns-Hopkins University | Ligands to enhance cellular uptake of biomolecules |
US7875733B2 (en) | 2003-09-18 | 2011-01-25 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising 4′-thionucleosides for use in gene modulation |
US6620916B1 (en) | 1996-09-26 | 2003-09-16 | Ajinomoto Co., Inc. | Modified physiologically active proteins and medicinal compositions containing the same |
JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
US6770748B2 (en) | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
USRE44779E1 (en) | 1997-03-07 | 2014-02-25 | Santaris Pharma A/S | Bicyclonucleoside and oligonucleotide analogues |
IL135000A0 (en) | 1997-09-12 | 2001-05-20 | Exiqon As | Bi- and tri-cyclic nucleoside, nucleotide and oligonucleotide analogues |
US7572582B2 (en) | 1997-09-12 | 2009-08-11 | Exiqon A/S | Oligonucleotide analogues |
US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
US6300319B1 (en) | 1998-06-16 | 2001-10-09 | Isis Pharmaceuticals, Inc. | Targeted oligonucleotide conjugates |
KR100782896B1 (ko) | 1999-05-04 | 2007-12-06 | 엑시콘 에이/에스 | L-리보-lna 유사체 |
US6525191B1 (en) | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
US6383812B1 (en) | 1999-05-28 | 2002-05-07 | Academia Sinica | Anti liver disease drug R-YEEE and method of synthesizing branched galactose-terminal glycoproteins |
US20080281041A1 (en) | 1999-06-07 | 2008-11-13 | Rozema David B | Reversibly Masked Polymers |
US8541548B2 (en) | 1999-06-07 | 2013-09-24 | Arrowhead Madison Inc. | Compounds and methods for reversible modification of biologically active molecules |
US6147200A (en) | 1999-08-19 | 2000-11-14 | Isis Pharmaceuticals, Inc. | 2'-O-acetamido modified monomers and oligomers |
US7491805B2 (en) | 2001-05-18 | 2009-02-17 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
AU2002217980A1 (en) | 2000-12-01 | 2002-06-11 | Cell Works Inc. | Conjugates of glycosylated/galactosylated peptide |
US20030077829A1 (en) | 2001-04-30 | 2003-04-24 | Protiva Biotherapeutics Inc.. | Lipid-based formulations |
US20030175906A1 (en) | 2001-07-03 | 2003-09-18 | Muthiah Manoharan | Nuclease resistant chimeric oligonucleotides |
US20030158403A1 (en) | 2001-07-03 | 2003-08-21 | Isis Pharmaceuticals, Inc. | Nuclease resistant chimeric oligonucleotides |
US20100240730A1 (en) | 2002-02-20 | 2010-09-23 | Merck Sharp And Dohme Corp. | RNA Interference Mediated Inhibition of Gene Expression Using Chemically Modified Short Interfering Nucleic Acid (siNA) |
WO2004024757A2 (en) | 2002-09-11 | 2004-03-25 | Santaris Pharma A/S | Modified pna molecules |
AU2003291753B2 (en) | 2002-11-05 | 2010-07-08 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
WO2004044139A2 (en) | 2002-11-05 | 2004-05-27 | Isis Parmaceuticals, Inc. | Modified oligonucleotides for use in rna interference |
US7723509B2 (en) | 2003-04-17 | 2010-05-25 | Alnylam Pharmaceuticals | IRNA agents with biocleavable tethers |
EP2669377A3 (en) | 2003-04-17 | 2015-10-14 | Alnylam Pharmaceuticals Inc. | Modified iRNA agents |
US7851615B2 (en) | 2003-04-17 | 2010-12-14 | Alnylam Pharmaceuticals, Inc. | Lipophilic conjugated iRNA agents |
JPWO2004101619A1 (ja) | 2003-05-15 | 2006-10-26 | 塩野義製薬株式会社 | 機能的糖ペプチドの合理的設計および合成 |
WO2004106356A1 (en) | 2003-05-27 | 2004-12-09 | Syddansk Universitet | Functionalized nucleotide derivatives |
ES2382807T3 (es) | 2003-08-28 | 2012-06-13 | Takeshi Imanishi | Nuevos ácidos nucleicos artificiales del tipo de enlace N-O con reticulación |
EP1791567B1 (en) | 2004-08-10 | 2015-07-29 | Alnylam Pharmaceuticals Inc. | Chemically modified oligonucleotides |
WO2006031461A2 (en) | 2004-09-09 | 2006-03-23 | Isis Pharmaceuticals, Inc. | Pyrrolidinyl groups for attaching conjugates to oligomeric compounds |
US20060148740A1 (en) | 2005-01-05 | 2006-07-06 | Prosensa B.V. | Mannose-6-phosphate receptor mediated gene transfer into muscle cells |
US20080206869A1 (en) | 2005-01-24 | 2008-08-28 | Avaris Ab | Nucleic Acid Complex |
US7569686B1 (en) | 2006-01-27 | 2009-08-04 | Isis Pharmaceuticals, Inc. | Compounds and methods for synthesis of bicyclic nucleic acid analogs |
KR20130042043A (ko) | 2006-01-27 | 2013-04-25 | 아이시스 파마수티컬즈 인코포레이티드 | 6-변형된 바이시클릭 핵산 유사체 |
DK2066684T3 (da) | 2006-05-11 | 2012-10-22 | Isis Pharmaceuticals Inc | 5´-Modificerede bicycliske nukleinsyreanaloge |
US7666854B2 (en) | 2006-05-11 | 2010-02-23 | Isis Pharmaceuticals, Inc. | Bis-modified bicyclic nucleic acid analogs |
US8658211B2 (en) | 2006-08-18 | 2014-02-25 | Arrowhead Madison Inc. | Polyconjugates for in vivo delivery of polynucleotides |
CN102614528B (zh) | 2006-08-18 | 2014-02-26 | 箭头研究公司 | 用于体内递送多核苷酸的多缀合物 |
WO2008101157A1 (en) | 2007-02-15 | 2008-08-21 | Isis Pharmaceuticals, Inc. | 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom |
EP2606911A1 (en) | 2007-02-16 | 2013-06-26 | KTB Tumorforschungsgesellschaft mbH | Receptor And Antigen Targeted Prodrug |
AU2008242583B2 (en) | 2007-04-23 | 2013-10-10 | Alnylam Pharmaceuticals, Inc. | Glycoconjugates of RNA interference agents |
WO2008150729A2 (en) | 2007-05-30 | 2008-12-11 | Isis Pharmaceuticals, Inc. | N-substituted-aminomethylene bridged bicyclic nucleic acid analogs |
WO2008154401A2 (en) | 2007-06-08 | 2008-12-18 | Isis Pharmaceuticals, Inc. | Carbocyclic bicyclic nucleic acid analogs |
WO2009006478A2 (en) | 2007-07-05 | 2009-01-08 | Isis Pharmaceuticals, Inc. | 6-disubstituted bicyclic nucleic acid analogs |
EP2188298B1 (en) | 2007-08-15 | 2013-09-18 | Isis Pharmaceuticals, Inc. | Tetrahydropyran nucleic acid analogs |
US8546556B2 (en) | 2007-11-21 | 2013-10-01 | Isis Pharmaceuticals, Inc | Carbocyclic alpha-L-bicyclic nucleic acid analogs |
AU2008333811B2 (en) | 2007-12-04 | 2014-05-01 | Alnylam Pharmaceuticals, Inc. | Carbohydrate conjugates as delivery agents for oligonucleotides |
CA2713379A1 (en) | 2008-01-31 | 2009-11-05 | Alnylam Pharmaceuticals, Inc. | Optimized methods for delivery of dsrna targeting the pcsk9 gene |
EP2265627A2 (en) | 2008-02-07 | 2010-12-29 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexitol nucleic acid analogs |
WO2009120878A2 (en) | 2008-03-26 | 2009-10-01 | Alnylam Pharmaceuticals, Inc. | Non-natural ribonucleotides, and methods of use thereof |
EP2274425A2 (en) | 2008-04-11 | 2011-01-19 | Alnylam Pharmaceuticals Inc. | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
AU2009298802A1 (en) | 2008-09-23 | 2010-04-08 | Alnylam Pharmaceuticals, Inc. | Chemical modifications of monomers and oligonucleotides with cycloaddition |
WO2010036698A1 (en) | 2008-09-24 | 2010-04-01 | Isis Pharmaceuticals, Inc. | Substituted alpha-l-bicyclic nucleosides |
HUE037082T2 (hu) | 2008-11-10 | 2018-08-28 | Arbutus Biopharma Corp | Új lipidek és készítmények terápiás hatóanyagok szállítására |
US20120101148A1 (en) | 2009-01-29 | 2012-04-26 | Alnylam Pharmaceuticals, Inc. | lipid formulation |
JP5769701B2 (ja) | 2009-05-05 | 2015-08-26 | テクミラ ファーマシューティカルズ コーポレイションTekmira Pharmaceuticals Corporation | 脂質組成物 |
DK2440183T3 (en) | 2009-06-10 | 2018-10-01 | Arbutus Biopharma Corp | Improved lipid formulation |
EA201270019A1 (ru) | 2009-06-15 | 2012-06-29 | Элнилэм Фармасьютикалз, Инк. | Двуцепочечная рнк, включенная в липидный состав и мишенью которой является ген pcsk9 |
US9012421B2 (en) | 2009-08-06 | 2015-04-21 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexose nucleic acid analogs |
WO2011038356A2 (en) | 2009-09-25 | 2011-03-31 | Johns Hopkins University | Novel liver-targeting agents and their synthesis |
TWI388338B (zh) | 2009-10-26 | 2013-03-11 | Iner Aec Executive Yuan | 對聚合醣鏈進行放射標誌以作為肝受體造影劑之方法 |
TWI391144B (zh) | 2009-10-26 | 2013-04-01 | Iner Aec Executive Yuan | 一種定量肝殘餘功能的檢驗方法與其新穎肝受體造影檢驗藥劑 |
WO2011072290A2 (en) | 2009-12-11 | 2011-06-16 | The Regents Of The University Of Michigan | Targeted dendrimer-drug conjugates |
US9198972B2 (en) | 2010-01-28 | 2015-12-01 | Alnylam Pharmaceuticals, Inc. | Monomers and oligonucleotides comprising cycloaddition adduct(s) |
NZ601737A (en) | 2010-02-24 | 2013-06-28 | Arrowhead Res Corp | Compositions for targeted delivery of sirna |
US20130109817A1 (en) | 2010-03-26 | 2013-05-02 | Mersana Therapeutics, Inc. | Modified Polymers for Delivery of Polynucleotides, Method of Manufacture, and Methods of Use Thereof |
WO2011120053A1 (en) | 2010-03-26 | 2011-09-29 | Mersana Therapeutics, Inc. | Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof |
WO2011123621A2 (en) | 2010-04-01 | 2011-10-06 | Alnylam Pharmaceuticals Inc. | 2' and 5' modified monomers and oligonucleotides |
WO2011133876A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising acyclic and abasic nucleosides and analogs |
US9518259B2 (en) * | 2010-06-15 | 2016-12-13 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating interaction between proteins and target nucleic acids |
WO2011163121A1 (en) | 2010-06-21 | 2011-12-29 | Alnylam Pharmaceuticals, Inc. | Multifunctional copolymers for nucleic acid delivery |
WO2012012467A2 (en) * | 2010-07-19 | 2012-01-26 | Isis Pharmaceuticals, Inc. | Modulation of nuclear-retained rna |
US9290760B2 (en) | 2010-09-15 | 2016-03-22 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
WO2012068187A1 (en) | 2010-11-19 | 2012-05-24 | Merck Sharp & Dohme Corp. | Poly(amide) polymers for the delivery of oligonucleotides |
EP3192800A1 (en) | 2010-12-17 | 2017-07-19 | Arrowhead Pharmaceuticals, Inc. | Galactose cluster-pharmacokinetic modulator targeting moiety for sirna |
US8501930B2 (en) | 2010-12-17 | 2013-08-06 | Arrowhead Madison Inc. | Peptide-based in vivo siRNA delivery system |
CA2976966C (en) | 2010-12-29 | 2021-11-09 | F. Hoffmann-La Roche Ag | Small molecule conjugates for intracellular delivery of nucleic acids |
KR102540778B1 (ko) | 2011-06-21 | 2023-06-07 | 알닐람 파마슈티칼스 인코포레이티드 | 아포리포단백질 c-iii(apoc3) 유전자의 발현 억제를 위한 조성물 및 방법 |
KR20140051357A (ko) | 2011-08-26 | 2014-04-30 | 애로우헤드 리서치 코오포레이션 | In Vivo 핵산 전달용 폴리(비닐 에스테르) 고분자 |
US10023861B2 (en) | 2011-08-29 | 2018-07-17 | Ionis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
KR102263352B1 (ko) | 2011-11-18 | 2021-06-11 | 알닐람 파마슈티칼스 인코포레이티드 | 트랜스티레틴(TTR) 관련 질병을 치료하기 위한 RNAi 제제, 조성 및 그의 사용방법 |
US20150299696A1 (en) | 2012-05-02 | 2015-10-22 | Sirna Therapeutics, Inc. | SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS |
TWI595885B (zh) | 2012-05-02 | 2017-08-21 | 喜納製藥公司 | 包含四galnac之新穎結合物及傳送寡核苷酸之方法 |
US9926559B2 (en) * | 2013-01-09 | 2018-03-27 | Biogen Ma Inc. | Compositions and methods for modulation of SMN2 splicing in a subject |
AU2014259759B2 (en) | 2013-05-01 | 2020-06-18 | Ionis Pharmaceuticals, Inc. | Compositions and methods |
JP2016534035A (ja) * | 2013-10-04 | 2016-11-04 | ラナ セラピューティクス インコーポレイテッド | 筋萎縮性側索硬化症を治療するための組成物及び方法 |
WO2015106128A2 (en) | 2014-01-09 | 2015-07-16 | Alnylam Pharmaceuticals, Inc. | MODIFIED RNAi AGENTS |
EP4162940A1 (en) * | 2014-04-17 | 2023-04-12 | Biogen MA Inc. | Compositions and methods for modulation of smn2 splicing in a subject |
-
2017
- 2017-07-17 LT LTEPPCT/US2017/042463T patent/LT3484524T/lt unknown
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- 2017-07-17 US US16/310,766 patent/US20190323006A1/en not_active Abandoned
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- 2017-07-17 CN CN201780043645.5A patent/CN109844115B/zh active Active
- 2017-07-17 DK DK17828625.8T patent/DK3484524T3/da active
- 2017-07-17 JP JP2019500807A patent/JP7197463B2/ja active Active
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2019
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2020
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2022
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