RU2017122022A - Композиция для введения нуклеиновой кислоты в клетки - Google Patents
Композиция для введения нуклеиновой кислоты в клетки Download PDFInfo
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- RU2017122022A RU2017122022A RU2017122022A RU2017122022A RU2017122022A RU 2017122022 A RU2017122022 A RU 2017122022A RU 2017122022 A RU2017122022 A RU 2017122022A RU 2017122022 A RU2017122022 A RU 2017122022A RU 2017122022 A RU2017122022 A RU 2017122022A
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- Prior art keywords
- copolymer
- repeating units
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- composition
- nucleic acid
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- 239000000203 mixture Substances 0.000 title claims 9
- 108020004707 nucleic acids Proteins 0.000 title claims 6
- 150000007523 nucleic acids Chemical class 0.000 title claims 6
- 102000039446 nucleic acids Human genes 0.000 title claims 6
- 229920001577 copolymer Polymers 0.000 claims 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 6
- 229920003118 cationic copolymer Polymers 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims 2
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 239000000178 monomer Substances 0.000 claims 2
- 238000006116 polymerization reaction Methods 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229920005684 linear copolymer Polymers 0.000 claims 1
- 108020004999 messenger RNA Proteins 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 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
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
-
- 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
- A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
- A61K48/0025—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid
- A61K48/0041—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid the non-active part being polymeric
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/02—Polyamines
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/02—Polyamines
- C08G73/0206—Polyalkylene(poly)amines
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Claims (26)
1. Статистический полимер, включающий множество повторяющихся звеньев (а), независимо друг от друга выбранных из следующих формул (a1) и (а2):
множество повторяющихся звеньев (b), независимо друг от друга выбранных из следующих формул (b1) - (b4):
где молярное соотношение суммы повторяющихся звеньев (а) и суммы повторяющихся звеньев (b) находится в интервале от 0,7:1,0 до 1,0:0,7, где один или более атомов азота в повторяющихся звеньях (а) и/или (b), содержащихся в сополимере, могут протонироваться с образованием катионного сополимера.
2. Сополимер по п. 1, который является разветвленным или дендритным сополимером, включающим повторяющиеся звенья одного или более типа, выбранных из повторяющихся звеньев (а2), (b2) и (b4).
3. Сополимер по п. 1, который является линейным сополимером, включающим повторяющиеся звенья (a1) и (b1).
4. Сополимер по любому из пп. 1-3, где содержание повторяющихся звеньев (а) и (b) составляет 80 мол. % или более в расчете на все повторяющиеся звенья в сополимере.
5. Сополимер по любому из пп. 1-3, где содержание повторяющихся звеньев (а), выбранных из (a1) и (а2), и повторяющихся звеньев (b), выбранных из (b1) и (b2), составляет 80 мол. % или более в расчете на все повторяющиеся звенья в сополимере.
6. Сополимер по любому из пп. 1-5, где концевые группы сополимера включают группы (с) одного или более типа, независимо выбранные из групп формул (c1)-(c3):
7. Сополимер по любому из пп. 1-6, где молярное соотношение повторяющихся звеньев (а) и повторяющихся звеньев (b) находится в интервале 0,8:1,0 до 1,0:0,8.
8. Сополимер по любому из пп. 1-7, который получают при полимеризации смеси мономеров, включающей азиридин, азетидин и необязательно пирролидин.
9. Композиция, включающая нуклеиновую кислоту и сополимер по любому из пп. 1-8.
10. Композиция по п. 9, где нуклеиновой кислотой является мРНК.
11. Композиция п. 9 или 10, где сополимер представляет собой катионный сополимер и где катионный сополимер образует комплекс с нуклеиновой кислотой.
12. Фармацевтическая композиция, включающая композицию по любому из пп. 9-11 и необязательно дополнительный фармацевтически приемлемый носитель и/или разбавитель.
13. Применение сополимера по любому из пп. 1-8 или композиции или фармацевтической композиции по любому из пп. 9-12 для доставки нуклеиновой кислоты в клетку.
14. Способ доставки нуклеиновой кислоты в клетку-мишень иди ткань-мишень, включающий стадию приведения в контакт композиции или фармацевтической композиции по любому из пп. 9-12 с клеткой-мишенью или тканью-мишенью.
15. Способ получения сополимера по любому из пп. 1-7, включающий стадию полимеризации смеси мономеров, включающей азиридин, азетидин и необязательно пирролидин.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14199439.2 | 2014-12-19 | ||
| EP14199439.2A EP3034539A1 (en) | 2014-12-19 | 2014-12-19 | Compositions for introducing nucleic acid into cells |
| PCT/EP2015/080669 WO2016097377A1 (en) | 2014-12-19 | 2015-12-18 | Compositions for introducing nucleic acid into cells |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2017122022A true RU2017122022A (ru) | 2018-12-24 |
| RU2017122022A3 RU2017122022A3 (ru) | 2019-05-22 |
| RU2715227C2 RU2715227C2 (ru) | 2020-02-26 |
Family
ID=52292658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2017122022A RU2715227C2 (ru) | 2014-12-19 | 2015-12-18 | Композиция для введения нуклеиновой кислоты в клетки |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US11020487B2 (ru) |
| EP (2) | EP3034539A1 (ru) |
| JP (1) | JP6745272B2 (ru) |
| KR (1) | KR102142180B1 (ru) |
| CN (1) | CN107001627B (ru) |
| AU (1) | AU2015366220B2 (ru) |
| BR (1) | BR112017012482B1 (ru) |
| CA (1) | CA2971284C (ru) |
| DK (1) | DK3242903T3 (ru) |
| ES (1) | ES2887404T3 (ru) |
| RU (1) | RU2715227C2 (ru) |
| WO (1) | WO2016097377A1 (ru) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3034539A1 (en) | 2014-12-19 | 2016-06-22 | Ethris GmbH | Compositions for introducing nucleic acid into cells |
| BR122023027721A2 (pt) | 2015-06-30 | 2024-01-30 | ethris GmbH | Composição |
| WO2018010815A1 (en) * | 2016-07-15 | 2018-01-18 | Biontech Rna Pharmaceuticals Gmbh | Formulation for administration of rna |
| JP7668111B2 (ja) * | 2018-01-11 | 2025-04-24 | バイオンテック・エスイー | Ｒｎａの投与のための配合物 |
| KR20210021943A (ko) | 2018-04-25 | 2021-03-02 | 에트리스 게엠베하 | 미립자 제형용 동결 방지제 |
| US20230000990A1 (en) * | 2019-12-17 | 2023-01-05 | Universiteit Gent | Non-viral vectors comprising polypropyleneimine |
| CN111249476B (zh) * | 2020-02-19 | 2023-09-26 | 深圳厚存纳米药业有限公司 | 泊洛沙姆和/或泊洛沙胺与脂质组合中性复合物纳米粒 |
| JP2024507394A (ja) | 2021-02-26 | 2024-02-19 | エスリス ゲーエムベーハー | エアロゾル形成用の製剤および核酸を送達するためのエアロゾル |
| WO2023049814A2 (en) * | 2021-09-22 | 2023-03-30 | Sirnaomics, Inc. | Nanoparticle pharmaceutical compositions with reduced nanoparticle size and improved polydispersity index |
| CN116549626A (zh) * | 2022-01-27 | 2023-08-08 | 深圳瑞吉生物科技有限公司 | 一种载核酸脂质纳米颗粒冻干制剂及其制备方法与应用 |
| EP4327829A1 (en) | 2022-08-26 | 2024-02-28 | Ethris GmbH | Stabilization of lipid or lipidoid nanoparticle suspensions |
| JP2025529925A (ja) | 2022-08-26 | 2025-09-09 | エスリス ゲーエムベーハー | 安定な脂質またはリピドイドナノ粒子懸濁液 |
| WO2024240962A1 (en) | 2023-05-25 | 2024-11-28 | Ethris Gmbh | Gm-csf-encoding nucleic acids, pharmaceutical compositions, methods and uses thereof |
| CN116478410B (zh) * | 2023-06-20 | 2023-09-12 | 觅投克(北京)生物医学技术有限公司 | 一种菊糖修饰的聚乙烯亚胺衍生物及其制备方法和应用 |
| WO2025045767A1 (en) | 2023-08-25 | 2025-03-06 | Ethris Gmbh | Stabilized lipid and lipidoid nanoparticle formulations with specific surfactant properties for enhanced pharmaceutical applications |
| WO2025064850A1 (en) | 2023-09-22 | 2025-03-27 | BioNTech SE | Rna constructs with n-terminal degrons to enhance an immune response |
| FR3155424A1 (fr) | 2023-11-15 | 2025-05-23 | BioNTech SE | Compositions immunogènes contre le sars-cov-2 |
| WO2025106754A1 (en) | 2023-11-15 | 2025-05-22 | BioNTech SE | Coronavirus vaccine |
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| JPS5821590A (ja) | 1981-07-31 | 1983-02-08 | 株式会社東芝 | 制御棒駆動水圧装置 |
| JPS58215490A (ja) * | 1982-06-08 | 1983-12-14 | Nippon Shokubai Kagaku Kogyo Co Ltd | 石炭−水スラリ−用分散剤 |
| CA1223831A (en) | 1982-06-23 | 1987-07-07 | Dean Engelhardt | Modified nucleotides, methods of preparing and utilizing and compositions containing the same |
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| 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 |
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2014
- 2014-12-19 EP EP14199439.2A patent/EP3034539A1/en not_active Withdrawn
-
2015
- 2015-12-18 RU RU2017122022A patent/RU2715227C2/ru active
- 2015-12-18 KR KR1020177019543A patent/KR102142180B1/ko active Active
- 2015-12-18 EP EP15823330.4A patent/EP3242903B1/en active Active
- 2015-12-18 JP JP2017533008A patent/JP6745272B2/ja active Active
- 2015-12-18 US US15/537,096 patent/US11020487B2/en active Active
- 2015-12-18 BR BR112017012482-3A patent/BR112017012482B1/pt active IP Right Grant
- 2015-12-18 ES ES15823330T patent/ES2887404T3/es active Active
- 2015-12-18 AU AU2015366220A patent/AU2015366220B2/en active Active
- 2015-12-18 CN CN201580068845.7A patent/CN107001627B/zh active Active
- 2015-12-18 DK DK15823330.4T patent/DK3242903T3/da active
- 2015-12-18 WO PCT/EP2015/080669 patent/WO2016097377A1/en not_active Ceased
- 2015-12-18 CA CA2971284A patent/CA2971284C/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| KR20170097124A (ko) | 2017-08-25 |
| DK3242903T3 (da) | 2021-09-27 |
| WO2016097377A1 (en) | 2016-06-23 |
| EP3034539A1 (en) | 2016-06-22 |
| AU2015366220A1 (en) | 2017-06-01 |
| RU2715227C2 (ru) | 2020-02-26 |
| US20180236090A1 (en) | 2018-08-23 |
| JP2018502956A (ja) | 2018-02-01 |
| RU2017122022A3 (ru) | 2019-05-22 |
| AU2015366220B2 (en) | 2019-09-19 |
| CA2971284A1 (en) | 2016-06-23 |
| US11020487B2 (en) | 2021-06-01 |
| KR102142180B1 (ko) | 2020-08-07 |
| ES2887404T3 (es) | 2021-12-22 |
| BR112017012482A2 (pt) | 2018-02-27 |
| JP6745272B2 (ja) | 2020-08-26 |
| EP3242903B1 (en) | 2021-07-28 |
| CN107001627B (zh) | 2020-01-14 |
| EP3242903A1 (en) | 2017-11-15 |
| CN107001627A (zh) | 2017-08-01 |
| BR112017012482B1 (pt) | 2021-10-19 |
| CA2971284C (en) | 2023-01-10 |
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