JP2019524151A5 - - Google Patents
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- Publication number
- JP2019524151A5 JP2019524151A5 JP2019511384A JP2019511384A JP2019524151A5 JP 2019524151 A5 JP2019524151 A5 JP 2019524151A5 JP 2019511384 A JP2019511384 A JP 2019511384A JP 2019511384 A JP2019511384 A JP 2019511384A JP 2019524151 A5 JP2019524151 A5 JP 2019524151A5
- Authority
- JP
- Japan
- Prior art keywords
- seq
- rnai construct
- sequence
- composition
- sense strand
- 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.)
- Granted
Links
- 108091030071 RNAI Proteins 0.000 claims description 105
- 230000009368 gene silencing by RNA Effects 0.000 claims description 105
- 230000000692 anti-sense effect Effects 0.000 claims description 51
- 108091081021 Sense strand Proteins 0.000 claims description 46
- 125000003729 nucleotide group Chemical group 0.000 claims description 43
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical group 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 description 30
- 239000002773 nucleotide Substances 0.000 claims description 24
- 101000785944 Homo sapiens Asialoglycoprotein receptor 1 Proteins 0.000 claims description 16
- 102100026292 Asialoglycoprotein receptor 1 Human genes 0.000 claims description 15
- 235000012000 cholesterol Nutrition 0.000 claims description 15
- 239000003446 ligand Substances 0.000 claims description 13
- 208000029078 coronary artery disease Diseases 0.000 claims description 12
- 208000010125 myocardial infarction Diseases 0.000 claims description 12
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 9
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims description 5
- 239000000427 antigen Substances 0.000 claims description 5
- 102000036639 antigens Human genes 0.000 claims description 5
- 108091007433 antigens Proteins 0.000 claims description 5
- 230000000295 complement effect Effects 0.000 claims description 5
- 239000012634 fragment Substances 0.000 claims description 5
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims description 4
- -1 bicyclic nucleic acids Chemical class 0.000 claims description 4
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 4
- 108020004999 messenger RNA Proteins 0.000 claims description 3
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 2
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 claims description 2
- 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 claims description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 2
- 239000003613 bile acid Substances 0.000 claims description 2
- 150000001720 carbohydrates Chemical class 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 125000003929 folic acid group Chemical group 0.000 claims description 2
- 229930182830 galactose Natural products 0.000 claims description 2
- 229930182470 glycoside Natural products 0.000 claims description 2
- 150000002338 glycosides Chemical class 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 108020004707 nucleic acids Proteins 0.000 claims description 2
- 102000039446 nucleic acids Human genes 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 150000003431 steroids Chemical class 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 22
- 230000008878 coupling Effects 0.000 claims 2
- 238000010168 coupling process Methods 0.000 claims 2
- 238000005859 coupling reaction Methods 0.000 claims 2
- 238000000034 method Methods 0.000 description 17
- 239000003814 drug Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 210000003494 hepatocyte Anatomy 0.000 description 4
- 238000008214 LDL Cholesterol Methods 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 102000051237 human ASGR1 Human genes 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022022163A JP7472180B2 (ja) | 2016-08-26 | 2022-02-16 | ＡＳＧＲ１発現を阻害するためのＲＮＡｉコンストラクトおよびその使用方法 |
| JP2024000208A JP2024019733A (ja) | 2016-08-26 | 2024-01-04 | ＡＳＧＲ１発現を阻害するためのＲＮＡｉコンストラクトおよびその使用方法 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662380216P | 2016-08-26 | 2016-08-26 | |
| US62/380,216 | 2016-08-26 | ||
| PCT/US2017/048757 WO2018039647A1 (en) | 2016-08-26 | 2017-08-25 | Rnai constructs for inhibiting asgr1 expression and methods of use thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022022163A Division JP7472180B2 (ja) | 2016-08-26 | 2022-02-16 | ＡＳＧＲ１発現を阻害するためのＲＮＡｉコンストラクトおよびその使用方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019524151A JP2019524151A (ja) | 2019-09-05 |
| JP2019524151A5 true JP2019524151A5 (https=) | 2020-10-01 |
| JP7082610B2 JP7082610B2 (ja) | 2022-06-08 |
Family
ID=59846644
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019511384A Active JP7082610B2 (ja) | 2016-08-26 | 2017-08-25 | ＡＳＧＲ１発現を阻害するためのＲＮＡｉコンストラクトおよびその使用方法 |
| JP2022022163A Active JP7472180B2 (ja) | 2016-08-26 | 2022-02-16 | ＡＳＧＲ１発現を阻害するためのＲＮＡｉコンストラクトおよびその使用方法 |
| JP2024000208A Pending JP2024019733A (ja) | 2016-08-26 | 2024-01-04 | ＡＳＧＲ１発現を阻害するためのＲＮＡｉコンストラクトおよびその使用方法 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022022163A Active JP7472180B2 (ja) | 2016-08-26 | 2022-02-16 | ＡＳＧＲ１発現を阻害するためのＲＮＡｉコンストラクトおよびその使用方法 |
| JP2024000208A Pending JP2024019733A (ja) | 2016-08-26 | 2024-01-04 | ＡＳＧＲ１発現を阻害するためのＲＮＡｉコンストラクトおよびその使用方法 |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US10870856B2 (https=) |
| EP (1) | EP3504333A1 (https=) |
| JP (3) | JP7082610B2 (https=) |
| AR (1) | AR110629A1 (https=) |
| AU (2) | AU2017315952B2 (https=) |
| CA (2) | CA3277899A1 (https=) |
| MX (2) | MX2019002271A (https=) |
| TW (1) | TW201823461A (https=) |
| UY (1) | UY37376A (https=) |
| WO (1) | WO2018039647A1 (https=) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2997444A1 (en) * | 2015-09-29 | 2017-04-06 | Amgen Inc. | Asgr inhibitors for reducing cholesterol levels |
| FI3661562T3 (fi) * | 2017-08-04 | 2024-12-09 | Amgen Inc | Cys-mab:ien konjugointimenetelmä |
| US11492624B2 (en) | 2017-10-17 | 2022-11-08 | Arrowheads Pharmaceuticals, Inc. | RNAi agents and compositions for inhibiting expression of Asialoglycoprotein receptor 1 |
| AU2018360697A1 (en) * | 2017-11-01 | 2020-05-14 | Alnylam Pharmaceuticals, Inc. | Complement component C3 iRNA compositions and methods of use thereof |
| CN112424371B (zh) | 2018-06-07 | 2024-06-28 | 美国安进公司 | 蛋白质-多核苷酸缀合物的检测测定 |
| EP3894554A1 (en) * | 2018-12-10 | 2021-10-20 | Amgen Inc. | Chemically-modified rnai constructs and uses thereof |
| TW202111124A (zh) * | 2019-05-30 | 2021-03-16 | 美商安進公司 | 用於抑制ｓｃａｐ表現之ｒｎａｉ構建體及其使用方法 |
| AU2020301419B2 (en) | 2019-06-25 | 2026-03-19 | Amgen Inc. | Purification methods for carbohydrate-linked oligonucleotides |
| EP4126967A1 (en) | 2020-03-23 | 2023-02-08 | Amgen Inc. | Monoclonal antibodies to chemically-modified nucleic acids and uses thereof |
| CN111705063B (zh) * | 2020-06-02 | 2023-08-08 | 成都中科奥格生物科技有限公司 | Asgr1突变基因及其在制备哺乳动物肝损伤敏感模型中的应用 |
| WO2024046297A1 (zh) * | 2022-09-02 | 2024-03-07 | 北京福元医药股份有限公司 | 抑制去唾液酸糖蛋白受体基因表达的siRNA、其缀合物和药物组合物及用途 |
| WO2025231448A2 (en) * | 2024-05-03 | 2025-11-06 | University Of Massachusetts | Oligonucleotides targeting myostatin (mstn) |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
| US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5981505A (en) | 1993-01-26 | 1999-11-09 | The Trustees Of The University Of Pennsylvania | Compositions and methods for delivery of genetic material |
| US5837533A (en) | 1994-09-28 | 1998-11-17 | American Home Products Corporation | Complexes comprising a nucleic acid bound to a cationic polyamine having an endosome disruption agent |
| US5840710A (en) | 1994-12-09 | 1998-11-24 | Genzyme Corporation | Cationic amphiphiles containing ester or ether-linked lipophilic groups for intracellular delivery of therapeutic molecules |
| US7422902B1 (en) | 1995-06-07 | 2008-09-09 | The University Of British Columbia | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
| US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
| ATE285477T1 (de) | 1995-06-07 | 2005-01-15 | Inex Pharmaceutical Corp | Herstellung von lipid-nukleinsäure partikeln duch ein hydrophobische lipid-nukleinsäuree komplexe zwischenprodukt und zur verwendung in der gentransfer |
| US6217900B1 (en) | 1997-04-30 | 2001-04-17 | American Home Products Corporation | Vesicular complexes and methods of making and using the same |
| DE69834038D1 (de) | 1997-07-01 | 2006-05-18 | Isis Pharmaceutical Inc | Zusammensetzungen und verfahren zur verabreichung von oligonukleotiden über die speiseröhre |
| WO2000003683A2 (en) | 1998-07-20 | 2000-01-27 | Inex Pharmaceuticals Corporation | Liposomal encapsulated nucleic acid-complexes |
| US8137695B2 (en) * | 2006-08-18 | 2012-03-20 | Arrowhead Madison Inc. | Polyconjugates for in vivo delivery of polynucleotides |
| US7833992B2 (en) | 2001-05-18 | 2010-11-16 | Merck Sharpe & Dohme | Conjugates and compositions for cellular delivery |
| US7491805B2 (en) | 2001-05-18 | 2009-02-17 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
| US6693187B1 (en) | 2000-10-17 | 2004-02-17 | Lievre Cornu Llc | Phosphinoamidite carboxlates and analogs thereof in the synthesis of oligonucleotides having reduced internucleotide charge |
| US7109165B2 (en) | 2001-05-18 | 2006-09-19 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
| US20030130186A1 (en) | 2001-07-20 | 2003-07-10 | Chandra Vargeese | Conjugates and compositions for cellular delivery |
| US9181551B2 (en) | 2002-02-20 | 2015-11-10 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| WO2003093449A2 (en) | 2002-05-06 | 2003-11-13 | Nucleonics, Inc. | Methods for delivery of nucleic acids |
| EP2305812A3 (en) * | 2002-11-14 | 2012-06-06 | Dharmacon, Inc. | Fuctional and hyperfunctional sirna |
| DK1620544T3 (en) | 2003-04-17 | 2019-01-14 | Alnylam Pharmaceuticals Inc | MODIFIED iRNA AGENTS |
| US7723509B2 (en) | 2003-04-17 | 2010-05-25 | Alnylam Pharmaceuticals | IRNA agents with biocleavable tethers |
| US7851615B2 (en) | 2003-04-17 | 2010-12-14 | Alnylam Pharmaceuticals, Inc. | Lipophilic conjugated iRNA agents |
| US8017762B2 (en) | 2003-04-17 | 2011-09-13 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
| EP2386316B1 (en) * | 2004-06-10 | 2018-02-28 | Omeros Corporation | Methods for treating conditions associated with MASP-2 dependent complement activation |
| CN1300312C (zh) | 2004-08-23 | 2007-02-14 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | 靶向去唾液酸糖蛋白受体的抗乙型肝炎病毒反义寡核苷酸的结构和用途 |
| KR101270829B1 (ko) * | 2004-09-23 | 2013-06-07 | 제넨테크, 인크. | 시스테인 유전자조작 항체 및 접합체 |
| US8008453B2 (en) | 2005-08-12 | 2011-08-30 | Amgen Inc. | Modified Fc molecules |
| CA2685127C (en) | 2007-04-23 | 2019-01-08 | Alnylam Pharmaceuticals, Inc. | Glycoconjugates of rna interference agents |
| WO2009082607A2 (en) | 2007-12-04 | 2009-07-02 | Alnylam Pharmaceuticals, Inc. | Targeting lipids |
| US20130024961A1 (en) | 2009-12-01 | 2013-01-24 | Christopher Burlak | Methods of Modulating Thrombocytopenia and Modified Transgenic Pigs |
| KR101870915B1 (ko) * | 2011-04-08 | 2018-06-25 | 유니버시티 오브 레스터 | Ｍａｓｐ-2 의존적 보체 활성화와 관련된 질병을 치료하는 방법 |
| WO2012177639A2 (en) * | 2011-06-22 | 2012-12-27 | Alnylam Pharmaceuticals, Inc. | Bioprocessing and bioproduction using avian cell lines |
| AR090905A1 (es) | 2012-05-02 | 2014-12-17 | Merck Sharp & Dohme | Conjugados que contienen tetragalnac y peptidos y procedimientos para la administracion de oligonucleotidos, composicion farmaceutica |
| EP3564374A1 (en) | 2013-06-21 | 2019-11-06 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulation of target nucleic acids |
| EP3286318A2 (en) * | 2015-04-22 | 2018-02-28 | Mina Therapeutics Limited | Sarna compositions and methods of use |
| CA2997444A1 (en) * | 2015-09-29 | 2017-04-06 | Amgen Inc. | Asgr inhibitors for reducing cholesterol levels |
-
2017
- 2017-08-24 UY UY0001037376A patent/UY37376A/es not_active Application Discontinuation
- 2017-08-25 WO PCT/US2017/048757 patent/WO2018039647A1/en not_active Ceased
- 2017-08-25 US US16/328,221 patent/US10870856B2/en active Active
- 2017-08-25 EP EP17764943.1A patent/EP3504333A1/en active Pending
- 2017-08-25 CA CA3277899A patent/CA3277899A1/en active Pending
- 2017-08-25 MX MX2019002271A patent/MX2019002271A/es unknown
- 2017-08-25 AU AU2017315952A patent/AU2017315952B2/en active Active
- 2017-08-25 JP JP2019511384A patent/JP7082610B2/ja active Active
- 2017-08-25 CA CA3034463A patent/CA3034463C/en active Active
- 2017-08-28 AR ARP170102382A patent/AR110629A1/es unknown
- 2017-08-28 TW TW106129226A patent/TW201823461A/zh unknown
-
2019
- 2019-02-25 MX MX2024009873A patent/MX2024009873A/es unknown
-
2020
- 2020-10-26 US US17/080,771 patent/US11732266B2/en active Active
-
2022
- 2022-02-16 JP JP2022022163A patent/JP7472180B2/ja active Active
-
2024
- 2024-01-04 JP JP2024000208A patent/JP2024019733A/ja active Pending
- 2024-02-29 AU AU2024201349A patent/AU2024201349A1/en active Pending
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