PE20181085A1 - Composiciones y metodos para modular la expresion de angiotensinogeno - Google Patents
Composiciones y metodos para modular la expresion de angiotensinogenoInfo
- Publication number
- PE20181085A1 PE20181085A1 PE2018000423A PE2018000423A PE20181085A1 PE 20181085 A1 PE20181085 A1 PE 20181085A1 PE 2018000423 A PE2018000423 A PE 2018000423A PE 2018000423 A PE2018000423 A PE 2018000423A PE 20181085 A1 PE20181085 A1 PE 20181085A1
- Authority
- PE
- Peru
- Prior art keywords
- modulate
- modified oligonucleotide
- modified
- segment consisting
- linked nucleosides
- Prior art date
Links
- 102000004881 Angiotensinogen Human genes 0.000 title abstract 4
- 108090001067 Angiotensinogen Proteins 0.000 title abstract 4
- 239000000203 mixture Substances 0.000 title abstract 2
- 108091034117 Oligonucleotide Proteins 0.000 abstract 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 4
- 239000002777 nucleoside Substances 0.000 abstract 3
- 125000003835 nucleoside group Chemical group 0.000 abstract 3
- 206010020772 Hypertension Diseases 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 201000010099 disease Diseases 0.000 abstract 2
- 230000037361 pathway Effects 0.000 abstract 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 1
- 230000001668 ameliorated effect Effects 0.000 abstract 1
- 230000000692 anti-sense effect Effects 0.000 abstract 1
- 230000000295 complement effect Effects 0.000 abstract 1
- 230000003111 delayed effect Effects 0.000 abstract 1
- 239000003085 diluting agent Substances 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 239000003937 drug carrier Substances 0.000 abstract 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 230000008685 targeting Effects 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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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
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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
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
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- C07—ORGANIC CHEMISTRY
- 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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- C07—ORGANIC CHEMISTRY
- 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
- C07H21/04—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 deoxyribosyl as saccharide radical
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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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- 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
- C12N15/1136—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 growth factors, growth regulators, cytokines, lymphokines or hormones
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- C12N2310/3341—5-Methylcytosine
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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
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- Cardiology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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- Saccharide Compounds (AREA)
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Abstract
La presente invencion esta referida a compuestos que comprenden oligonucleotidos modificados para modular la expresion de angiotensinogeno (AGT) y modular una enfermedad, un trastorno y/o una afeccion relacionado con la via del SRAA en un individuo que lo necesite. Una enfermedad, trastorno y/o afeccion relacionado con la via del SRAA en un individuo tal como hipertension se puede tratar, mejorar, retardar o prevenir con la administracion de compuestos antisentido dirigidos a AGT. Este oligonucleotido modificado consiste en 12 a 30 nucleosidos enlazados que es al menos 80% complementaria a SEQ ID NO: 1. Este oligonucleotido modificado comprende un azucar modificado, que comprende un 2´-O-metoxietilo, un etilo limitado, un 3´-fluoro-HNA o un puente de 4´(CH2)n-O-2´, en donde n es 1 o 2. Tambien refiere que el oligonucleotido modificado comprende: un segmento de hueco que consiste en desoxinucleosidos enlazados; un segmento de ala en 5´que consiste en nucleosidos enlazados; y un segmento de ala 3´que consiste en nucleosidos enlazados. Refiere tambien una composicion que comprende un oligonucleotido modificado o una sal de este y un portador o diluyente farmaceuticamente aceptable. La presente invencion es util para el tratamiento, la prevencion, la mejora o el enlentecimiento de la progresion de la hipertension.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562238831P | 2015-10-08 | 2015-10-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20181085A1 true PE20181085A1 (es) | 2018-07-05 |
Family
ID=58488579
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2018000423A PE20181085A1 (es) | 2015-10-08 | 2016-10-07 | Composiciones y metodos para modular la expresion de angiotensinogeno |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US10912792B2 (es) |
| EP (3) | EP3960183A1 (es) |
| JP (4) | JP2018530325A (es) |
| KR (2) | KR20180055898A (es) |
| CN (2) | CN113817735A (es) |
| AU (3) | AU2016334114B2 (es) |
| BR (2) | BR122020023854B1 (es) |
| CA (1) | CA2998898A1 (es) |
| CL (2) | CL2018000899A1 (es) |
| CO (1) | CO2018002598A2 (es) |
| HK (1) | HK1258275A1 (es) |
| IL (2) | IL295971A (es) |
| MX (2) | MX392014B (es) |
| MY (1) | MY200263A (es) |
| PE (1) | PE20181085A1 (es) |
| SG (1) | SG10202003148VA (es) |
| WO (1) | WO2017062816A2 (es) |
| ZA (1) | ZA201801600B (es) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR122020023687B1 (pt) | 2014-05-22 | 2023-03-07 | Alnylam Pharmaceuticals, Inc | Agente de ácido ribonucleico (rnai) de fita dupla, seus usos e composição farmacêutica |
| TWI851574B (zh) * | 2018-05-14 | 2024-08-11 | 美商阿尼拉製藥公司 | 血管收縮素原(AGT)iRNA組成物及其使用方法 |
| WO2020236755A2 (en) * | 2019-05-17 | 2020-11-26 | Ionis Pharmaceuticals, Inc. | Angiotensin ii type 1 receptor targeted oligonucleotides and uses thereof |
| CN114981431A (zh) * | 2019-11-13 | 2022-08-30 | 阿尔尼拉姆医药品有限公司 | 用于治疗血管紧张素原(agt)相关病症的方法和组合物 |
| US11649458B2 (en) | 2020-05-05 | 2023-05-16 | University Of Kentucky Research Foundation | Inhibiting angiotensinogen to attenuate aortic pathology in Marfan syndrome |
| KR20230108728A (ko) * | 2020-11-18 | 2023-07-18 | 아이오니스 파마수티컬즈, 인코포레이티드 | 앤지오텐시노겐 발현을 조절하기 위한 화합물 및 방법 |
| CN114763547A (zh) * | 2021-01-14 | 2022-07-19 | 施能康生物科技有限公司 | 靶向血管紧张素原的核酸及其用途 |
| WO2022232650A1 (en) * | 2021-04-30 | 2022-11-03 | Ionis Pharmaceuticals, Inc. | Methods for reducing agt expression |
| WO2023056446A1 (en) * | 2021-10-01 | 2023-04-06 | Adarx Pharmaceuticals, Inc. | Angiotensinogen-modulating compositions and methods of use thereof |
| CN113862268B (zh) * | 2021-10-20 | 2025-05-13 | 厦门甘宝利生物医药有限公司 | Agt抑制剂及其用途 |
| MX2024005862A (es) * | 2021-11-16 | 2024-07-10 | Shanghai Argo Biopharmaceutical Co Ltd | Composiciones y metodos para inhibir la expresion de la proteina angiotensinogeno (agt). |
| US20250197853A1 (en) * | 2021-11-19 | 2025-06-19 | Tuojie Biotech (Shanghai) Co., Ltd. | Sirna targeting angiotensinogen and pharmaceutical use of sirna |
| WO2023138650A1 (zh) * | 2022-01-20 | 2023-07-27 | 上海拓界生物医药科技有限公司 | 一种dsRNA、其应用及制备方法 |
| CN117264948B (zh) * | 2022-06-14 | 2024-05-10 | 广州必贝特医药股份有限公司 | 抑制血管紧张素原基因表达的RNAi抑制剂及其应用 |
| WO2024013334A1 (en) * | 2022-07-15 | 2024-01-18 | Silence Therapeutics Gmbh | Nucleic acids for inhibiting expression of agt in a cell |
| WO2024031008A2 (en) * | 2022-08-03 | 2024-02-08 | Sirnaomics, Inc. | Combination sirna and peptide docking vehicle (pdov) compositions and methods of their use for improved regulation and functionality |
| EP4587573A2 (en) * | 2022-09-16 | 2025-07-23 | Sirnaomics, Inc. | Products and compositions |
| CN120981570A (zh) * | 2022-12-20 | 2025-11-18 | 靖因药业有限公司 | 靶向agt的多核酸分子及其用途 |
| CN120752336A (zh) * | 2022-12-22 | 2025-10-03 | 圣诺制药公司 | 产品和组合物 |
| CN119530218A (zh) * | 2023-08-30 | 2025-02-28 | 苏州炫景生物科技有限公司 | 双链寡核苷酸及其在抑制血管紧张素原表达中的应用 |
| WO2024234831A1 (zh) * | 2023-05-15 | 2024-11-21 | 苏州时安生物技术有限公司 | 一种用于调节血管紧张素原基因表达的双链rna、其缀合物、药物组合物及用途 |
| WO2024259134A1 (en) | 2023-06-13 | 2024-12-19 | Arnatar Therapeutics, Inc | Advanced rna targeting (arnatar) for angiotensinogen |
| WO2025097040A1 (en) * | 2023-11-03 | 2025-05-08 | Ionis Pharmaceuticals, Inc. | Methods and compositions for reducing angiotensinogen |
| CN121320348A (zh) * | 2024-09-26 | 2026-01-13 | 杭州天龙药业有限公司 | 靶向抑制AGT基因表达的siRNA及其在治疗高血压中的应用 |
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