JP2016523087A5 - - Google Patents
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- JP2016523087A5 JP2016523087A5 JP2016521893A JP2016521893A JP2016523087A5 JP 2016523087 A5 JP2016523087 A5 JP 2016523087A5 JP 2016521893 A JP2016521893 A JP 2016521893A JP 2016521893 A JP2016521893 A JP 2016521893A JP 2016523087 A5 JP2016523087 A5 JP 2016523087A5
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- JP
- Japan
- Prior art keywords
- substituted
- compound according
- alkyl
- compound
- nucleoside
- 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.)
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- 150000001875 compounds Chemical class 0.000 claims description 262
- 239000002777 nucleoside Substances 0.000 claims description 92
- 125000005647 linker group Chemical group 0.000 claims description 89
- 108091034117 Oligonucleotide Proteins 0.000 claims description 77
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 48
- 125000003835 nucleoside group Chemical group 0.000 claims description 35
- 108010056301 Apolipoprotein C-III Proteins 0.000 claims description 31
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 30
- 102000030169 Apolipoprotein C-III Human genes 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 150000002367 halogens Chemical class 0.000 claims description 28
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 25
- 230000000295 complement effect Effects 0.000 claims description 17
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
- 230000004048 modification Effects 0.000 claims description 16
- 238000012986 modification Methods 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- -1 furanosyl nucleoside Chemical class 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 9
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 8
- 108020004707 nucleic acids Proteins 0.000 claims description 8
- 102000039446 nucleic acids Human genes 0.000 claims description 8
- 150000007523 nucleic acids Chemical class 0.000 claims description 8
- 150000004713 phosphodiesters Chemical class 0.000 claims description 7
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical group O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 6
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical group CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 5
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical group NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 4
- 229930024421 Adenine Chemical group 0.000 claims description 4
- 229960000643 adenine Drugs 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 229940104302 cytosine Drugs 0.000 claims description 3
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 3
- 229940113082 thymine Drugs 0.000 claims description 3
- 229940035893 uracil Drugs 0.000 claims description 3
- YIMATHOGWXZHFX-WCTZXXKLSA-N (2r,3r,4r,5r)-5-(hydroxymethyl)-3-(2-methoxyethoxy)oxolane-2,4-diol Chemical compound COCCO[C@H]1[C@H](O)O[C@H](CO)[C@H]1O YIMATHOGWXZHFX-WCTZXXKLSA-N 0.000 claims description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims 5
- 230000000087 stabilizing effect Effects 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 1
- 125000004437 phosphorous atom Chemical group 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 108091081021 Sense strand Proteins 0.000 description 23
- 230000000692 anti-sense effect Effects 0.000 description 22
- 230000008685 targeting Effects 0.000 description 19
- 125000000217 alkyl group Chemical group 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 0 CCC(C(C)C1O)OCC1(NC(C)=O)OCCCCC(NCCCNC(CCOCC(COCCC(NCCCNC(CCCCO[C@](*C(*)[C@](C)C1)C1NC(C)=O)=O)O)(COCCC(NCCCNC(CCCCO[C@@]1O*(C)C(*)C1NC(C)=O)=O)=O)NC(CCCC(NCCCCCCO[C@@]([C@@](*)OC1CONC)[C@@]1O)=O)=O)=O)=O Chemical compound CCC(C(C)C1O)OCC1(NC(C)=O)OCCCCC(NCCCNC(CCOCC(COCCC(NCCCNC(CCCCO[C@](*C(*)[C@](C)C1)C1NC(C)=O)=O)O)(COCCC(NCCCNC(CCCCO[C@@]1O*(C)C(*)C1NC(C)=O)=O)=O)NC(CCCC(NCCCCCCO[C@@]([C@@](*)OC1CONC)[C@@]1O)=O)=O)=O)=O 0.000 description 8
- 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 description 8
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 241000764238 Isis Species 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 238000012739 integrated shape imaging system Methods 0.000 description 6
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical class N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- RUVRGYVESPRHSZ-UHFFFAOYSA-N 2-[2-(2-azaniumylethoxy)ethoxy]acetate Chemical compound NCCOCCOCC(O)=O RUVRGYVESPRHSZ-UHFFFAOYSA-N 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 235000011007 phosphoric acid Nutrition 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 3
- 102100030970 Apolipoprotein C-III Human genes 0.000 description 3
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 description 3
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 125000001033 ether group Chemical group 0.000 description 3
- ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical group CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 2
- 229960002684 aminocaproic acid Drugs 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 102000001493 Cyclophilins Human genes 0.000 description 1
- 108010068682 Cyclophilins Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361838190P | 2013-06-21 | 2013-06-21 | |
| US61/838,190 | 2013-06-21 | ||
| US201361871683P | 2013-08-29 | 2013-08-29 | |
| US61/871,683 | 2013-08-29 | ||
| PCT/US2014/043731 WO2014205451A2 (en) | 2013-06-21 | 2014-06-23 | Compositions and methods for modulation of target nucleic acids |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020029006A Division JP2020099335A (ja) | 2013-06-21 | 2020-02-25 | 標的核酸を調節するための組成物および方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016523087A JP2016523087A (ja) | 2016-08-08 |
| JP2016523087A5 true JP2016523087A5 (enExample) | 2017-08-03 |
| JP6694382B2 JP6694382B2 (ja) | 2020-05-13 |
Family
ID=52105553
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016521893A Active JP6694382B2 (ja) | 2013-06-21 | 2014-06-23 | 標的核酸を調節するための組成物および方法 |
| JP2020029006A Withdrawn JP2020099335A (ja) | 2013-06-21 | 2020-02-25 | 標的核酸を調節するための組成物および方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020029006A Withdrawn JP2020099335A (ja) | 2013-06-21 | 2020-02-25 | 標的核酸を調節するための組成物および方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (3) | US20160122761A1 (enExample) |
| EP (3) | EP3730619A1 (enExample) |
| JP (2) | JP6694382B2 (enExample) |
| AU (2) | AU2014284152B2 (enExample) |
| CA (1) | CA2916252A1 (enExample) |
| WO (1) | WO2014205451A2 (enExample) |
Families Citing this family (73)
| Publication number | Priority date | Publication date | Assignee | Title |
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| SG171914A1 (en) | 2008-12-02 | 2011-07-28 | Chiralgen Ltd | Method for the synthesis of phosphorus atom modified nucleic acids |
| EP2451461A4 (en) | 2009-07-06 | 2013-05-29 | Ontorii Inc | NOVEL NUCLEIC ACID PRODRUGS AND METHOD OF USE THEREOF |
| DK2620428T3 (da) | 2010-09-24 | 2019-07-01 | Wave Life Sciences Ltd | Asymmetrisk hjælpegruppe |
| US9605019B2 (en) | 2011-07-19 | 2017-03-28 | Wave Life Sciences Ltd. | Methods for the synthesis of functionalized nucleic acids |
| DK2872485T3 (da) | 2012-07-13 | 2021-03-08 | Wave Life Sciences Ltd | Asymmetrisk hjælpegruppe |
| CA2921162A1 (en) | 2013-05-01 | 2014-11-06 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| EP4039278A1 (en) * | 2013-07-11 | 2022-08-10 | Alnylam Pharmaceuticals, Inc. | Oligonucleotide-ligand conjugates and process for their preparation |
| KR102423317B1 (ko) | 2014-01-16 | 2022-07-22 | 웨이브 라이프 사이언시스 리미티드 | 키랄 디자인 |
| US10280423B2 (en) * | 2014-05-01 | 2019-05-07 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating complement factor B expression |
| AU2015252841B2 (en) | 2014-05-01 | 2020-03-19 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating growth hormone receptor expression |
| US10570169B2 (en) | 2014-05-22 | 2020-02-25 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| EP3151839A4 (en) * | 2014-06-06 | 2018-02-28 | Ionis Pharmaceuticals, Inc. | Compositions and methods for enhanced intestinal absorption of conjugated oligomeric compounds |
| US20170327524A1 (en) | 2014-10-10 | 2017-11-16 | Hoffmann-La Roche, Inc. | Galnac phosphoramidites, nucleic acid conjugates thereof and their use |
| JP7628764B2 (ja) | 2015-09-29 | 2025-02-12 | アムジエン・インコーポレーテツド | Ａｓｇｒ阻害剤 |
| EP3370708A4 (en) | 2015-11-06 | 2019-06-26 | Ionis Pharmaceuticals, Inc. | MODULATION OF APOLIPOPROTEIN (A) EXPRESSION |
| SI4119569T1 (sl) * | 2015-11-06 | 2024-10-30 | Ionis Pharmaceuticals, Inc. | Konjugirane protismiselne spojine za uporabo v terapiji |
| CN109312342A (zh) | 2016-04-11 | 2019-02-05 | 阿布特斯生物制药公司 | 靶向核酸偶联物组合物 |
| UY37376A (es) | 2016-08-26 | 2018-03-23 | Amgen Inc | Construcciones de arni para inhibir expresión de asgr1 y métodos para su uso |
| KR20190065341A (ko) | 2016-10-06 | 2019-06-11 | 아이오니스 파마수티컬즈, 인코포레이티드 | 올리고머 화합물들의 접합 방법 |
| AU2017368050A1 (en) | 2016-11-29 | 2019-06-20 | Puretech Lyt, Inc. | Exosomes for delivery of therapeutic agents |
| CN108239644B (zh) * | 2016-12-23 | 2021-05-28 | 苏州瑞博生物技术股份有限公司 | 一种小干扰核酸和药物组合物及其用途 |
| WO2018191278A2 (en) | 2017-04-11 | 2018-10-18 | Arbutus Biopharma Corporation | Targeted compositions |
| TN2020000039A1 (en) * | 2017-09-11 | 2021-10-04 | Arrowhead Pharmaceuticals Inc | Rnai agents and compositions for inhibiting expression of apolipoprotein c-iii (apoc3) |
| SG11202002149XA (en) | 2017-09-14 | 2020-04-29 | Janssen Biopharma Inc | Galnac derivatives |
| WO2019105435A1 (zh) | 2017-12-01 | 2019-06-06 | 苏州瑞博生物技术有限公司 | 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途 |
| US11660347B2 (en) | 2017-12-01 | 2023-05-30 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, composition and conjugate containing same, preparation method, and use thereof |
| CN118236391A (zh) | 2017-12-01 | 2024-06-25 | 苏州瑞博生物技术股份有限公司 | 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途 |
| CN110997919B (zh) | 2017-12-01 | 2024-04-02 | 苏州瑞博生物技术股份有限公司 | 双链寡核苷酸、含双链寡核苷酸的组合物与缀合物及制备方法和用途 |
| JP7261494B2 (ja) | 2017-12-01 | 2023-04-20 | スーチョウ リボ ライフ サイエンス カンパニー、リミテッド | 核酸、当該核酸を含む組成物及び複合体ならびに調製方法と使用 |
| UY38003A (es) | 2017-12-12 | 2019-06-28 | Amgen Inc | Construcciones de arni para inhibir la expresión de pnpla3 y métodos de uso de las mismas |
| EP3842534A4 (en) | 2018-08-21 | 2022-07-06 | Suzhou Ribo Life Science Co., Ltd. | NUCLEIC ACID, PHARMACEUTICAL COMPOSITION AND CONJUGATE WITH NUCLEIC ACID AND THEIR USE |
| MX2021002745A (es) | 2018-09-11 | 2021-05-12 | Amgen Inc | Metodos de purificacion de oligonucleotidos ricos en guanina. |
| EP3862024A4 (en) | 2018-09-30 | 2022-08-17 | Suzhou Ribo Life Science Co., Ltd. | SIRNA CONJUGATE, METHOD FOR ITS PRODUCTION AND ITS USE |
| PH12021550801B1 (en) * | 2018-11-13 | 2024-04-26 | Silence Therapeutics Gmbh | Nucleic acids for inhibiting expression of lpa in a cell |
| GB2579253A (en) * | 2018-11-28 | 2020-06-17 | Pedanius Therapeutics Ltd | Antibacterial antisense agents |
| CN119061010A (zh) | 2018-12-10 | 2024-12-03 | 美国安进公司 | 经化学修饰的RNAi构建体及其用途 |
| KR20210102932A (ko) | 2018-12-10 | 2021-08-20 | 암젠 인크 | Pnpla3 발현을 억제하기 위한 rnai 작제물 및 이의 사용 방법 |
| CN112423794A (zh) | 2018-12-28 | 2021-02-26 | 苏州瑞博生物技术股份有限公司 | 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途 |
| AU2020280439B2 (en) | 2019-05-22 | 2025-08-14 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use |
| JP7663951B2 (ja) | 2019-05-22 | 2025-04-17 | スーチョウ リボ ライフ サイエンス カンパニー、リミテッド | 核酸、薬物組成物及び複合体ならびに調製方法と使用 |
| CN113811613B (zh) | 2019-05-22 | 2024-04-05 | 苏州瑞博生物技术股份有限公司 | 核酸、药物组合物与缀合物及制备方法和用途 |
| WO2020238766A1 (zh) | 2019-05-24 | 2020-12-03 | 苏州瑞博生物技术股份有限公司 | 核酸、药物组合物与缀合物及制备方法和用途 |
| AR119061A1 (es) | 2019-05-30 | 2021-11-17 | Amgen Inc | CONSTRUCCIONES DE ARNi PARA INHIBIR LA EXPRESIÓN DE SCAP Y MÉTODOS DE USO DE LAS MISMAS |
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2014
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- 2014-06-23 EP EP20173519.8A patent/EP3730619A1/en not_active Withdrawn
- 2014-06-23 EP EP14813192.3A patent/EP3011028B1/en active Active
- 2014-06-23 EP EP19179457.7A patent/EP3564374A1/en not_active Withdrawn
- 2014-06-23 US US14/898,873 patent/US20160122761A1/en not_active Abandoned
- 2014-06-23 CA CA2916252A patent/CA2916252A1/en not_active Abandoned
- 2014-06-23 AU AU2014284152A patent/AU2014284152B2/en active Active
- 2014-06-23 WO PCT/US2014/043731 patent/WO2014205451A2/en not_active Ceased
-
2018
- 2018-11-05 US US16/181,206 patent/US20190127737A1/en not_active Abandoned
-
2019
- 2019-12-23 AU AU2019284048A patent/AU2019284048A1/en not_active Withdrawn
-
2020
- 2020-02-25 JP JP2020029006A patent/JP2020099335A/ja not_active Withdrawn
- 2020-03-09 US US16/813,241 patent/US20200270609A1/en not_active Abandoned
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