RU2013117285A - СИСТЕМА ДОСТАВКИ миРНК IN VIVO НА ОСНОВЕ ПЕПТИДОВ - Google Patents
СИСТЕМА ДОСТАВКИ миРНК IN VIVO НА ОСНОВЕ ПЕПТИДОВ Download PDFInfo
- Publication number
- RU2013117285A RU2013117285A RU2013117285/10A RU2013117285A RU2013117285A RU 2013117285 A RU2013117285 A RU 2013117285A RU 2013117285/10 A RU2013117285/10 A RU 2013117285/10A RU 2013117285 A RU2013117285 A RU 2013117285A RU 2013117285 A RU2013117285 A RU 2013117285A
- Authority
- RU
- Russia
- Prior art keywords
- melitin
- composition according
- seq
- composition
- peptide
- Prior art date
Links
Classifications
-
- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
-
- 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
- A61K47/54—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 compound
- A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3515—Lipophilic moiety, e.g. cholesterol
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Toxicology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Inorganic Chemistry (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
Abstract
1. Композиция системы доставки на основе конъюгата для доставки полинуклеотида интерферирующей РНК в клетку печени in vivo, содержащая:РНКи-А+Мелитин-(L-Gal)где Мелитин представляет собой пептид мелитина,L представляет собой физиологически лабильную связь,Gal представляет собой лиганд рецептора асиалогликопротеина (ASGPr),x представляет собой целое число, имеющее значение выше чем 80% первичных аминов Мелитина,РНКи представляет собой полинуклеотид интерферирующей РНК, и А представляет собой гидрофобную группу, содержащую по меньшей мере 20 атомов углерода, или галактозный кластер.2. Композиция по п.1, отличающаяся тем, что полинуклеотид интерферирующей РНК выбран из группы, состоящей из: ДНК, РНК, днРНК, миРНК и микроРНК.3. Композиция по п.1, отличающаяся тем, что клетка печени представляет собой гепатоцит.4. Композиция по п.1, отличающаяся тем, что лиганды ASGPr обратимо связаны по меньшей мере с 90% аминов множества пептидов мелитина.5. Композиция по п.1, отличающаяся тем, что пептид мелитина выбран из перечня последовательностей, состоящего из: Seq. ID 1, Seq. ID 7, Seq. ID 11, Seq. ID 51, Seq. ID 57, Seq. ID 58, Seq. ID 92 и Seq. ID 96.6. Композиция по п.1, отличающаяся тем, что пептид мелитина состоит из аминокислот в D-форме.7. Композиция по п.1, отличающаяся тем, что L представляет собой дизамещенный малеамат.8. Композиция по п.1, отличающаяся тем, что L представляет собой амидобензилкарбамат.9. Композиция по п.7, дополнительно содержащая полиэтиленгликоль (PEG), ковалентно связанный с амино-концом пептида мелитина.10. Композиция по п.7, дополнительно содержащая конъюгат лиганд ASGPr-PEG, ковалентно связанный с амино-концом пептида мелитина.11. Композиция по п.8, дополнительно содержа
Claims (20)
1. Композиция системы доставки на основе конъюгата для доставки полинуклеотида интерферирующей РНК в клетку печени in vivo, содержащая:
РНКи-А+Мелитин-(L-Gal)x,
где Мелитин представляет собой пептид мелитина,
L представляет собой физиологически лабильную связь,
Gal представляет собой лиганд рецептора асиалогликопротеина (ASGPr),
x представляет собой целое число, имеющее значение выше чем 80% первичных аминов Мелитина,
РНКи представляет собой полинуклеотид интерферирующей РНК, и А представляет собой гидрофобную группу, содержащую по меньшей мере 20 атомов углерода, или галактозный кластер.
2. Композиция по п.1, отличающаяся тем, что полинуклеотид интерферирующей РНК выбран из группы, состоящей из: ДНК, РНК, днРНК, миРНК и микроРНК.
3. Композиция по п.1, отличающаяся тем, что клетка печени представляет собой гепатоцит.
4. Композиция по п.1, отличающаяся тем, что лиганды ASGPr обратимо связаны по меньшей мере с 90% аминов множества пептидов мелитина.
5. Композиция по п.1, отличающаяся тем, что пептид мелитина выбран из перечня последовательностей, состоящего из: Seq. ID 1, Seq. ID 7, Seq. ID 11, Seq. ID 51, Seq. ID 57, Seq. ID 58, Seq. ID 92 и Seq. ID 96.
6. Композиция по п.1, отличающаяся тем, что пептид мелитина состоит из аминокислот в D-форме.
7. Композиция по п.1, отличающаяся тем, что L представляет собой дизамещенный малеамат.
8. Композиция по п.1, отличающаяся тем, что L представляет собой амидобензилкарбамат.
9. Композиция по п.7, дополнительно содержащая полиэтиленгликоль (PEG), ковалентно связанный с амино-концом пептида мелитина.
10. Композиция по п.7, дополнительно содержащая конъюгат лиганд ASGPr-PEG, ковалентно связанный с амино-концом пептида мелитина.
11. Композиция по п.8, дополнительно содержащая полиэтиленгликоль (PEG), ковалентно связанный с амино-концом пептида мелитина.
12. Композиция по п.8, дополнительно содержащая конъюгат лиганд ASGPr-PEG, ковалентно связанный с амино-концом пептида мелитина.
13. Композиция по п.1, отличающаяся тем, что лиганд ASGPr выбран из группы, состоящей из лактозы, галактозы, N-ацетилгалактозамина (GalNAc), галактозамина, N-формилгалактозамина, N-ацетилгалактозамина, N-пропионилгалактозамина, N-н-бутаноилгалактозамина и N-изо-бутаноилгалактозамина.
14. Композиция по п.1, отличающаяся тем, что РНКи связана с А через физиологически лабильную связь L2.
15. Композиция по п.14, отличающаяся тем, что L2 является ортогональной по отношению к L.
16. Композиция по п.1, отличающаяся тем, что галактозный кластер состоит из тримера N-ацетилгалактозамина.
17. Композиция по п.1, отличающаяся тем, что гидрофобная группа состоит из холестерина.
18. Композиция по п.1, отличающаяся тем, что указанная композиция представлена в фармацевтически приемлемом носителе или разбавителе.
19. Способ подавления экспрессии гена, который экспрессируется в клетке печени млекопитающего, включающий:
а) получение полинуклеотида РНКи, имеющего последовательность, идентичную или почти идентичную части последовательности указанного гена; и,
а) инъекцию в сосуд указанного млекопитающего композиции по п.1.
20. Способ получения композиции для доставки полинуклеотида интерферирующей РНК, включающий:
a) получение пептида мелитина;
b) получение множества незаряженных маскирующих агентов, каждый из которых содержит лиганд ASGPr, ковалентно связанный с дизамещенным малеиновым ангидридом или дипептид-амидобензильным амино-реактивным карбонатом;
c) модифицирование более 80% первичных аминов популяции пептидов мелитина маскирующими агентами этапа b,
d) связывание полинуклеотида интерферирующей РНК с гидрофобной группой, содержащей по меньшей мере 20 атомов углерода или галактозный тример;
f) обеспечение полинуклеотида интерферирующей РНК и модифицированного пептида мелитина в растворе, подходящем для введения in vivo.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201061424191P | 2010-12-17 | 2010-12-17 | |
US61/424,191 | 2010-12-17 | ||
US13/326,433 | 2011-12-15 | ||
US13/326,433 US8501930B2 (en) | 2010-12-17 | 2011-12-15 | Peptide-based in vivo siRNA delivery system |
PCT/US2011/065525 WO2012083185A2 (en) | 2010-12-17 | 2011-12-16 | Peptide-based in vivo sirna delivery system |
Publications (3)
Publication Number | Publication Date |
---|---|
RU2013117285A true RU2013117285A (ru) | 2015-01-27 |
RU2623160C2 RU2623160C2 (ru) | 2017-06-22 |
RU2623160C9 RU2623160C9 (ru) | 2018-02-26 |
Family
ID=46245391
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU2013117285A RU2623160C9 (ru) | 2010-12-17 | 2011-12-16 | Композиция системы доставки на основе конъюгата для доставки полинуклеотида РНК-интерференции в клетку печени и способ ее получения |
Country Status (15)
Country | Link |
---|---|
US (3) | US8501930B2 (ru) |
EP (1) | EP2651420B1 (ru) |
JP (2) | JP5926739B2 (ru) |
KR (1) | KR20140012624A (ru) |
CN (1) | CN103547272B (ru) |
AU (2) | AU2011343532B2 (ru) |
BR (1) | BR112013011702A2 (ru) |
CA (1) | CA2816042C (ru) |
MX (1) | MX346145B (ru) |
NZ (1) | NZ611662A (ru) |
PE (1) | PE20140180A1 (ru) |
RU (1) | RU2623160C9 (ru) |
SG (1) | SG189945A1 (ru) |
WO (1) | WO2012083185A2 (ru) |
ZA (1) | ZA201302900B (ru) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2795400C2 (ru) * | 2017-12-29 | 2023-05-03 | Сучжоу Рибо Лайф Сайенс Ко., Лтд | Конъюгаты и их получение и применение |
Families Citing this family (157)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080281041A1 (en) * | 1999-06-07 | 2008-11-13 | Rozema David B | Reversibly Masked Polymers |
US8877917B2 (en) * | 2007-04-23 | 2014-11-04 | Alnylam Pharmaceuticals, Inc. | Glycoconjugates of RNA interference agents |
EP3578205A1 (en) | 2010-08-06 | 2019-12-11 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
CN108129554A (zh) | 2010-08-10 | 2018-06-08 | 洛桑聚合联合学院 | 红细胞结合性治疗剂 |
US9850296B2 (en) | 2010-08-10 | 2017-12-26 | Ecole Polytechnique Federale De Lausanne (Epfl) | Erythrocyte-binding therapeutics |
US9517257B2 (en) | 2010-08-10 | 2016-12-13 | Ecole Polytechnique Federale De Lausanne (Epfl) | Erythrocyte-binding therapeutics |
HUE058896T2 (hu) | 2010-10-01 | 2022-09-28 | Modernatx Inc | N1-metil-pszeudo-uracilt tartalmazó ribonukleinsavak és azok felhasználásai |
AU2011352204B2 (en) * | 2010-12-29 | 2015-05-21 | Arrowhead Pharmaceuticals, Inc. | In vivo polynucleotide delivery conjugates having enzyme sensitive linkages |
JP2014511687A (ja) | 2011-03-31 | 2014-05-19 | モデルナ セラピューティクス インコーポレイテッド | 工学操作された核酸の送達および製剤 |
WO2012139137A2 (en) | 2011-04-08 | 2012-10-11 | Tufts Medical Center, Inc. | Pepducin design and use |
TWI695066B (zh) | 2011-06-30 | 2020-06-01 | 美商艾羅海德製藥公司 | 用於抑制b型肝炎病毒基因表現之組合物及方法 |
EP3640332A1 (en) | 2011-08-29 | 2020-04-22 | Ionis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
RU2648950C2 (ru) | 2011-10-03 | 2018-04-02 | Модерна Терапьютикс, Инк. | Модифицированные нуклеозиды, нуклеотиды и нуклеиновые кислоты и их применение |
EP2791160B1 (en) | 2011-12-16 | 2022-03-02 | ModernaTX, Inc. | Modified mrna compositions |
AU2013243951A1 (en) | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of secreted proteins |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
US9254311B2 (en) | 2012-04-02 | 2016-02-09 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins |
EP2922554B1 (en) | 2012-11-26 | 2022-02-23 | ModernaTX, Inc. | Terminally modified rna |
WO2014089146A1 (en) * | 2012-12-04 | 2014-06-12 | Isis Pharmaceuticals, Inc. | Compositions and methods for in vivo delivery of antisense compounds |
AU2014204012B2 (en) | 2013-01-03 | 2018-03-29 | Washington University | Compositions and methods for polynucleotide transfection |
EP2961843A2 (en) | 2013-02-28 | 2016-01-06 | Arrowhead Research Corporation | Organic compositions to treat epas1-related diseases |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
NZ631552A (en) | 2013-05-01 | 2017-02-24 | Ionis Pharmaceuticals Inc | Compositions and methods for modulating hbv expression |
IL293657A (en) * | 2013-05-22 | 2022-08-01 | Alnylam Pharmaceuticals Inc | Preparations of tmprss6 irna and methods of using them |
EP4039278A1 (en) * | 2013-07-11 | 2022-08-10 | Alnylam Pharmaceuticals, Inc. | Oligonucleotide-ligand conjugates and process for their preparation |
EP3030244B1 (en) * | 2013-08-07 | 2021-04-21 | Arrowhead Pharmaceuticals, Inc. | Polyconjugates for delivery of rnai triggers to tumor cells in vivo |
WO2015048744A2 (en) | 2013-09-30 | 2015-04-02 | Moderna Therapeutics, Inc. | Polynucleotides encoding immune modulating polypeptides |
EA201690675A1 (ru) | 2013-10-03 | 2016-08-31 | Модерна Терапьютикс, Инк. | Полинуклеотиды, кодирующие рецептор липопротеинов низкой плотности |
EP3065758B1 (en) | 2013-11-06 | 2019-09-25 | Merck Sharp & Dohme Corp. | Peptide containing conjugates for dual molecular delivery of oligonucleotides |
WO2015069586A2 (en) | 2013-11-06 | 2015-05-14 | Merck Sharp & Dohme Corp. | Dual molecular delivery of oligonucleotides and peptide containing conjugates |
US10953101B2 (en) | 2014-02-21 | 2021-03-23 | École Polytechnique Fédérale De Lausanne (Epfl) | Glycotargeting therapeutics |
US10046056B2 (en) | 2014-02-21 | 2018-08-14 | École Polytechnique Fédérale De Lausanne (Epfl) | Glycotargeting therapeutics |
US10946079B2 (en) | 2014-02-21 | 2021-03-16 | Ecole Polytechnique Federale De Lausanne | Glycotargeting therapeutics |
WO2015140648A2 (en) * | 2014-02-21 | 2015-09-24 | Ecole Polytecnique Federale De Lausanne (Epfl) Epfl-Tto | Glycotargeting therapeutics |
WO2015168172A1 (en) | 2014-04-28 | 2015-11-05 | Isis Pharmaceuticals, Inc. | Linkage modified oligomeric compounds |
CA2946003A1 (en) | 2014-05-01 | 2015-11-05 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating angiopoietin-like 3 expression |
CN106232804B (zh) | 2014-05-01 | 2019-10-25 | Ionis制药公司 | 用于调节补体因子b表达的组合物和方法 |
EP3757215A3 (en) | 2014-05-01 | 2021-03-17 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating growth hormone receptor expression |
AU2015252917B2 (en) | 2014-05-01 | 2019-09-26 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating PKK expression |
WO2015179693A1 (en) | 2014-05-22 | 2015-11-26 | Isis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
TW201620526A (zh) | 2014-06-17 | 2016-06-16 | 愛羅海德研究公司 | 用於抑制α-1抗胰蛋白酶基因表現之組合物及方法 |
US10436802B2 (en) | 2014-09-12 | 2019-10-08 | Biogen Ma Inc. | Methods for treating spinal muscular atrophy |
US10517898B2 (en) | 2014-11-20 | 2019-12-31 | The Regents Of The University Of California | Compositions and methods related to hematologic recovery |
WO2016085852A1 (en) | 2014-11-24 | 2016-06-02 | Alnylam Pharmaceuticals, Inc. | Tmprss6 irna compositions and methods of use thereof |
JP2018509913A (ja) | 2015-03-17 | 2018-04-12 | アローヘッド ファーマシューティカルズ インコーポレイテッド | 第xii因子の遺伝子発現を阻害するための組成物と方法 |
US9976141B2 (en) | 2015-05-29 | 2018-05-22 | Arrowhead Pharmaceuticals, Inc. | Compositions and methods for inhibiting gene expression of Hif2alpha |
WO2017004512A1 (en) * | 2015-07-02 | 2017-01-05 | Washington University | Peptide-polynucleotide complex for polynucleotide transfection |
KR102640776B1 (ko) | 2015-07-10 | 2024-02-23 | 아이오니스 파마수티컬즈, 인코포레이티드 | 디아실글리세롤 아실전이효소 2(dgat2) 조절제 |
KR101935095B1 (ko) * | 2015-07-31 | 2019-01-04 | 이화여자대학교 산학협력단 | 신규한 세포투과성 펩타이드 |
MX369556B (es) | 2015-08-06 | 2019-11-12 | Hoffmann La Roche | Procesos para la preparacion de derivados acidos de n-acetilgalactosamina (galnac). |
EP3332007A4 (en) * | 2015-08-07 | 2019-07-17 | Arrowhead Pharmaceuticals, Inc. | RNA INTERFERENCE THERAPY FOR HEPATITIS B VIRUS INFECTION |
JO3769B1 (ar) * | 2015-08-07 | 2021-01-31 | Arrowhead Pharmaceuticals Inc | علاج RNAi لعدوى فيروس التهاب الكبد B |
MX2018003411A (es) * | 2015-09-19 | 2018-09-06 | Ecole Polytechnique Fed Lausanne Epfl | Terapia glucodirigida. |
US20180273577A1 (en) | 2015-09-24 | 2018-09-27 | Ionis Pharmaceuticals, Inc. | Modulators of kras expression |
JOP20210043A1 (ar) | 2015-10-01 | 2017-06-16 | Arrowhead Pharmaceuticals Inc | تراكيب وأساليب لتثبيط تعبير جيني للـ lpa |
EP3371201A4 (en) | 2015-11-06 | 2019-09-18 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds for use in therapy |
BR122023026882A2 (pt) | 2015-11-06 | 2024-01-23 | Ionis Pharmaceuticals, Inc | Uso de um composto oligomérico |
CA3005029A1 (en) | 2015-11-13 | 2017-05-18 | Oasis Pharmaceuticals, LLC | Protease-activated receptor-2 modulators |
BR112018003910B1 (pt) | 2015-11-16 | 2022-03-22 | F. Hoffmann-La Roche Ag | Derivado de fosforamidita galnac, processo para a preparação de um derivado de fosforamidita galnac de fórmula i e uso dos derivados de fosforamidita galnac de fórmula i |
WO2017134525A1 (en) | 2016-02-02 | 2017-08-10 | Olix Pharmaceuticals, Inc. | TREATMENT OF ATOPIC DERMATITIS AND ASTHMA USING RNA COMPLEXES THAT TARGET lL4Rα, TRPA1, OR F2RL1 |
TWI783434B (zh) * | 2016-03-07 | 2022-11-11 | 美商愛羅海德製藥公司 | 治療性化合物之標靶性配體 |
MA45328A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Compositions acide nucléique-polypeptide et utilisations de celles-ci |
AU2017279512B2 (en) | 2016-06-06 | 2021-08-19 | Arrowhead Pharmaceuticals, Inc. | 5'-cyclo-phosphonate modified nucleotides |
EP3484524B1 (en) | 2016-07-15 | 2022-11-09 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulation of smn2 |
WO2018017814A1 (en) | 2016-07-20 | 2018-01-25 | President And Fellows Of Harvard College | Peptidoglycan glycosyltransferase inhibitors of sed proteins for treating bacterial infections |
JOP20170161A1 (ar) | 2016-08-04 | 2019-01-30 | Arrowhead Pharmaceuticals Inc | عوامل RNAi للعدوى بفيروس التهاب الكبد ب |
US11981703B2 (en) | 2016-08-17 | 2024-05-14 | Sirius Therapeutics, Inc. | Polynucleotide constructs |
JOP20170056B1 (ar) * | 2016-09-02 | 2021-08-17 | Arrowhead Pharmaceuticals Inc | مركبات ترابطية مستهدفة |
WO2018053142A2 (en) | 2016-09-14 | 2018-03-22 | President And Fellows Of Harvard College | Methods and compositions for modulating erythropoiesis |
CN109661233A (zh) | 2016-10-06 | 2019-04-19 | Ionis 制药公司 | 缀合低聚化合物的方法 |
CN110177544A (zh) | 2016-11-29 | 2019-08-27 | 普尔泰克健康有限公司 | 用于递送治疗剂的外泌体 |
WO2018112033A1 (en) | 2016-12-13 | 2018-06-21 | President And Fellows Of Harvard College | Methods and compositions for targeting tumor-infiltrating tregs |
WO2018112360A1 (en) | 2016-12-16 | 2018-06-21 | Evelo Biosciences, Inc. | Combination therapies for treating cancer |
WO2018112365A2 (en) | 2016-12-16 | 2018-06-21 | Evelo Biosciences, Inc. | Methods of treating colorectal cancer and melanoma using parabacteroides goldsteinii |
WO2018112364A1 (en) | 2016-12-16 | 2018-06-21 | Evelo Biosciences, Inc. | Combination therapies for treating melanoma |
WO2018112363A1 (en) | 2016-12-16 | 2018-06-21 | Evelo Biosciences, Inc. | Methods of treating cancer using parabacteroides |
SG10202107429WA (en) | 2017-01-06 | 2021-08-30 | Avidity Biosciences Inc | Nucleic acid-polypeptide compositions and methods of inducing exon skipping |
EP3568482A4 (en) * | 2017-01-10 | 2020-12-16 | Arrowhead Pharmaceuticals, Inc. | ALPHA-1 ANTITRYPSIN (AAT) RNA INTERFERENCE (RNA) AGENTS, COMPOSITIONS CONTAINING THEM, AND PROCEDURES FOR USE THEREOF |
WO2018136598A1 (en) | 2017-01-18 | 2018-07-26 | Evelo Biosciences, Inc. | Methods of treating cancer |
EP3570856A2 (en) | 2017-01-18 | 2019-11-27 | Evelo Biosciences, Inc. | Methods of treating cancer |
JOP20190215A1 (ar) | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
WO2018197926A1 (en) * | 2017-04-26 | 2018-11-01 | Robert Penchovsky | Methods for creating novel antibacterial agents using chimeric antisense oligonucleotides |
WO2018215049A1 (en) | 2017-05-23 | 2018-11-29 | F. Hoffmann-La Roche Ag | Process for galnac oligonucleotide conjugates |
US11253579B2 (en) | 2017-06-16 | 2022-02-22 | The University Of Chicago | Compositions and methods for inducing immune tolerance |
US11597744B2 (en) | 2017-06-30 | 2023-03-07 | Sirius Therapeutics, Inc. | Chiral phosphoramidite auxiliaries and methods of their use |
US10590416B2 (en) | 2017-07-06 | 2020-03-17 | Arrowhead Pharmaceuticals, Inc. | RNAi agents for inhibiting expression of alpha-ENaC and methods of use |
GB201711809D0 (en) * | 2017-07-21 | 2017-09-06 | Governors Of The Univ Of Alberta | Antisense oligonucleotide |
WO2019046401A1 (en) | 2017-08-29 | 2019-03-07 | Evelo Biosciences, Inc. | TREATMENT OF CANCER USING BLAUTIA STRAIN |
KR20200044013A (ko) | 2017-09-11 | 2020-04-28 | 애로우헤드 파마슈티컬스 인코포레이티드 | 아포지단백질 C-III (APOC3)의 발현을 억제하기 위한 RNAi 작용제 및 조성물 |
TN2020000038A1 (en) | 2017-09-14 | 2021-10-04 | Arrowhead Pharmaceuticals Inc | Rnai agents and compositions for inhibiting expression of angiopoietin-like 3 (angptl3), and methods of use |
MX2020003596A (es) | 2017-10-04 | 2020-07-22 | Avidity Biosciences Inc | Composiciones de acido nucleico-polipeptido y usos de las mismos. |
CA3079413A1 (en) | 2017-10-17 | 2019-04-25 | Arrowhead Pharmaceuticals, Inc. | Rnai agents and compositions for inhibiting expression of asialoglycoprotein receptor 1 |
WO2019105414A1 (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 |
US11492620B2 (en) | 2017-12-01 | 2022-11-08 | Suzhou Ribo Life Science Co., Ltd. | Double-stranded oligonucleotide, composition and conjugate comprising double-stranded oligonucleotide, preparation method thereof and use thereof |
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 |
EP3719127A4 (en) | 2017-12-01 | 2021-10-20 | Suzhou Ribo Life Science Co., Ltd. | NUCLEIC ACID, COMPOSITION AND CONJUGATE WITH IT, MANUFACTURING METHOD AND USE |
CA3083526A1 (en) | 2017-12-06 | 2019-06-13 | Andrew John Geall | Compositions and methods of treating muscle atrophy and myotonic dystrophy |
TW201936201A (zh) | 2017-12-14 | 2019-09-16 | 美商堅固生物科技公司 | 基因之非病毒生產及遞送 |
US11021692B2 (en) | 2017-12-19 | 2021-06-01 | Janssen Sciences Ireland Unlimited Company | Hepatitis B virus (HBV) vaccines and uses thereof |
KR102617947B1 (ko) | 2017-12-29 | 2023-12-27 | 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 | 접합체와 제조 및 그 용도 |
RU2020127049A (ru) | 2018-01-15 | 2022-02-17 | Айонис Фармасьютикалс, Инк. | Модуляторы экспрессии dnm2 |
AU2019218987A1 (en) | 2018-02-12 | 2020-07-23 | Ionis Pharmaceuticals, Inc. | Modified compounds and uses thereof |
WO2019169143A1 (en) | 2018-02-28 | 2019-09-06 | Evelo Biosciences, Inc. | Compositions and methods for treating cancer using turicibacter sanguinis |
WO2019169138A1 (en) | 2018-02-28 | 2019-09-06 | Evelo Biosciences, Inc. | Compositions and methods for treating cancer using paraclostridium benzoelyticum |
WO2019169168A1 (en) | 2018-02-28 | 2019-09-06 | Evelo Biosciences, Inc. | Compositions and methods for treating cancer using agathobaculum |
WO2019169160A1 (en) | 2018-02-28 | 2019-09-06 | Evelo Biosciences, Inc. | Compositions and methods for treating cancer using ruminococcus gnavus |
WO2019178057A1 (en) | 2018-03-12 | 2019-09-19 | Evelo Biosciences, Inc. | Methods of treating cancer using burkholderia |
CU20200082A7 (es) | 2018-05-09 | 2021-06-08 | Ionis Pharmaceuticals Inc | Compuestos y métodos para la reducción de la expresión de fxi |
EP3833397A4 (en) | 2018-08-08 | 2023-06-14 | Arcturus Therapeutics, Inc. | COMPOSITIONS AND AGENTS AGAINST NON-ALCOHOLIC STEATOHEPATITIS |
JP2021533800A (ja) | 2018-08-21 | 2021-12-09 | 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Suzhou Ribo Life Science Co., Ltd. | 核酸、当該核酸を含む薬物組成物及び複合体ならびにその使用 |
WO2020047229A1 (en) | 2018-08-29 | 2020-03-05 | University Of Massachusetts | Inhibition of protein kinases to treat friedreich ataxia |
US11273137B2 (en) | 2018-09-04 | 2022-03-15 | Board Of Trustees Of Michigan State University | Methods and compositions to prevent and treat disorders associated with mutations in the ODC1 gene |
TW202023573A (zh) | 2018-09-19 | 2020-07-01 | 美商Ionis製藥公司 | Pnpla3表現之調節劑 |
CN111655297A (zh) | 2018-09-30 | 2020-09-11 | 苏州瑞博生物技术有限公司 | 一种siRNA缀合物及其制备方法和用途 |
SG11202106593UA (en) | 2018-12-21 | 2021-07-29 | Avidity Biosciences Inc | Anti-transferrin receptor antibodies and uses thereof |
CN113507920A (zh) | 2019-02-07 | 2021-10-15 | 箭头药业股份有限公司 | 用于乙型肝炎病毒感染的RNAi剂 |
CN114949201A (zh) | 2019-03-12 | 2022-08-30 | 哈佛大学校长及研究员协会 | 治疗癌症的方法和组合物 |
CA3132170A1 (en) | 2019-04-18 | 2020-10-22 | Michael BIERMER | Combination therapy for treating hepatitis b virus infection |
TW202106294A (zh) | 2019-04-18 | 2021-02-16 | 美商健生醫藥公司 | 用於治療b型肝炎病毒感染的組合療法(一) |
AU2020287880A1 (en) | 2019-06-06 | 2022-01-20 | Avidity Biosciences, Inc. | UNA amidites and uses thereof |
EP3980436A4 (en) | 2019-06-06 | 2023-12-20 | Avidity Biosciences, Inc. | NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF |
WO2020252257A1 (en) | 2019-06-12 | 2020-12-17 | President And Fellows Of Harvard College | Methods and compositions for modulation of an interspecies gut bacterial pathway for levodopa metabolism |
JP2022536945A (ja) | 2019-06-18 | 2022-08-22 | ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー | B型肝炎ウイルス(HBV)ワクチンおよびHBVを標的化するRNAiの組合せ |
EP3986456A1 (en) | 2019-06-18 | 2022-04-27 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and hbv-targeting rnai |
WO2021022110A1 (en) | 2019-08-01 | 2021-02-04 | Evelo Biosciences, Inc. | Inducing immune effects using bacteria of the genus bifidobacterium |
WO2021074772A1 (en) | 2019-10-14 | 2021-04-22 | Astrazeneca Ab | Modulators of pnpla3 expression |
CN111041025B (zh) * | 2019-12-17 | 2021-06-18 | 深圳市瑞吉生物科技有限公司 | 基于结合N-乙酰半乳糖胺多肽的mRNA靶向分子及其制备方法 |
WO2021141368A2 (ko) | 2020-01-06 | 2021-07-15 | 주식회사 시선테라퓨틱스 | 세포 투과성 핵산 복합체를 유효성분으로 함유하는 황반변성의 예방 또는 치료용 조성물 |
CN115279379A (zh) | 2020-02-28 | 2022-11-01 | Ionis 制药公司 | 用于调节smn2的化合物和方法 |
WO2021178556A1 (en) | 2020-03-04 | 2021-09-10 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for sensitization of tumor cells to immune therapy |
TW202146011A (zh) | 2020-03-05 | 2021-12-16 | 美商詹森藥物公司 | 治療b型肝炎病毒感染之組合療法 |
JP2023537798A (ja) | 2020-03-19 | 2023-09-06 | アビディティー バイオサイエンシーズ,インク. | 顔面肩甲上腕型筋ジストロフィーを処置するための組成物および方法 |
MX2022011907A (es) | 2020-03-26 | 2023-01-05 | Arrowhead Pharmaceuticals Inc | Agentes de arni para inhibir la expresión de pnpla3, composiciones farmacéuticas de estos, y métodos de uso. |
EP4157264A4 (en) | 2020-05-27 | 2024-06-19 | Univ California | COMPOSITIONS AND METHODS FOR TRANSDIFFERENTIATION OF CELLS |
CA3185614A1 (en) | 2020-06-22 | 2021-12-30 | Janssen Pharmaceuticals, Inc. | Compositions and methods for treatment of hepatitis d virus infection |
CN111744019B (zh) | 2020-07-01 | 2023-08-04 | 深圳瑞吉生物科技有限公司 | 基于甘露糖的mRNA靶向递送系统及其应用 |
EP4211243A2 (en) | 2020-09-11 | 2023-07-19 | Arrowhead Pharmaceuticals, Inc. | Rnai agents for inhibiting expression of dux4, compositions thereof, and methods of use |
AU2021340710A1 (en) | 2020-09-11 | 2023-04-06 | Arrowhead Pharmaceuticals, Inc. | Skeletal muscle delivery platforms and methods of use |
EP4210759A1 (en) | 2020-09-11 | 2023-07-19 | Arrowhead Pharmaceuticals, Inc. | Lipid conjugates for the delivery of therapeutic agents |
WO2022056454A2 (en) | 2020-09-14 | 2022-03-17 | President And Fellows Of Harvard College | Methods and compositions for treating hpv-positive cancers |
US20230340124A1 (en) | 2020-09-16 | 2023-10-26 | President And Fellows Of Harvard College | Methods of treating an individual that has failed an anti-pd-1/anti-pd-l1 therapy |
JP2023545401A (ja) * | 2020-10-02 | 2023-10-30 | エムユーエスシー ファウンデーション フォー リサーチ ディベロップメント | 高度な細胞透過性ペプチド担体 |
IL302817A (en) | 2020-11-18 | 2023-07-01 | Ionis Pharmaceuticals Inc | Compounds and methods for modulating angiotensinogen expression |
US20240009269A1 (en) * | 2020-11-20 | 2024-01-11 | The Johns Hopkins University | Membrane-active peptides and methods for reversible blood- brain barrier opening |
WO2022133230A1 (en) | 2020-12-18 | 2022-06-23 | Janssen Pharmaceuticals, Inc. | Combination therapy for treating hepatitis b virus infection |
WO2022152869A1 (en) | 2021-01-15 | 2022-07-21 | Janssen Sciences Ireland Unlimited Company | Use of oligonucleotides for individuals with hepatic impairment |
CN117529490A (zh) * | 2021-04-23 | 2024-02-06 | 中天(上海)生物科技有限公司 | 用于将药物递送至肝细胞的环状肽-N-乙酰半乳糖胺(GalNAc)缀合物 |
EP4330392A1 (en) | 2021-04-26 | 2024-03-06 | Alnylam Pharmaceuticals, Inc. | Transmembrane protease, serine 6 (tmprss6) irna compositions and methods of use thereof |
WO2022234346A1 (en) * | 2021-05-07 | 2022-11-10 | Twinpig Biolab, Inc. | Peptides targeting macrophages, and conjugates, compositions, and uses thereof |
US11549112B1 (en) | 2021-06-21 | 2023-01-10 | Arrowhead Pharmaceuticals, Inc. | RNAi agents for inhibiting expression of xanthine dehydrogenase (XDH), pharmaceutical compositions thereof, and methods of use |
WO2023281434A1 (en) | 2021-07-09 | 2023-01-12 | Janssen Pharmaceuticals, Inc. | Use of oligonucleotides for individuals with renal impairment |
WO2023150181A1 (en) | 2022-02-01 | 2023-08-10 | President And Fellows Of Harvard College | Methods and compositions for treating cancer |
WO2023233290A1 (en) | 2022-05-31 | 2023-12-07 | Janssen Sciences Ireland Unlimited Company | Rnai agents targeting pd-l1 |
US11912997B2 (en) | 2022-06-15 | 2024-02-27 | Arrowhead Pharmaceuticals, Inc. | RNAi agents for inhibiting expression of Superoxide Dismutase 1 (SOD1), compositions thereof, and methods of use |
WO2024010867A1 (en) * | 2022-07-06 | 2024-01-11 | Board Of Regents, The University Of Texas System | Reversible, covalent polynucleotide condensation approach for enhanced gene delivery |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL9201440A (nl) | 1992-08-11 | 1994-03-01 | Univ Leiden | Triantennaire clusterglycosiden, hun bereiding en toepassing. |
DE19618797C2 (de) * | 1996-05-10 | 2000-03-23 | Bertling Wolf | Vehikel zum Transport molekularer Substanz |
WO2000075164A1 (en) | 1999-06-07 | 2000-12-14 | Mirus Corporation | COMPOSITIONS AND METHODS FOR DRUG DELIVERY USING pH SENSITIVE MOLECULES |
US7019113B2 (en) | 1999-06-07 | 2006-03-28 | Mirus Bio Corporation | Reversible modification of membrane interaction |
US7091186B2 (en) * | 2001-09-24 | 2006-08-15 | Seattle Genetics, Inc. | p-Amidobenzylethers in drug delivery agents |
EP1506218B1 (en) * | 2002-05-24 | 2017-04-12 | Arrowhead Pharmaceuticals, Inc. | Reversible modification of membrane interaction |
US7816337B2 (en) | 2003-02-18 | 2010-10-19 | Roche Madison Inc. | Reversible attachment of a membrane active polymer to a polynucleotide |
US20040162235A1 (en) * | 2003-02-18 | 2004-08-19 | Trubetskoy Vladimir S. | Delivery of siRNA to cells using polyampholytes |
JP2008537551A (ja) * | 2005-03-31 | 2008-09-18 | カランド ファーマシューティカルズ, インコーポレイテッド | リボヌクレオチドレダクターゼサブユニット2の阻害剤およびその使用 |
WO2008022309A2 (en) | 2006-08-18 | 2008-02-21 | F. Hoffmann-La Roche Ag | Polyconjugates for in vivo delivery of polynucleotides |
TWI412367B (zh) * | 2006-12-28 | 2013-10-21 | Medarex Llc | 化學鏈接劑與可裂解基質以及其之綴合物 |
CA2702028A1 (en) * | 2007-10-02 | 2009-04-09 | Rxi Pharmaceuticals Corp. | Tripartite rnai constructs |
JP5788312B2 (ja) | 2008-04-11 | 2015-09-30 | アルニラム ファーマスーティカルズ インコーポレイテッドAlnylam Pharmaceuticals, Inc. | 標的リガンドをエンドソーム分解性成分と組み合わせることによる核酸の部位特異的送達 |
JP2012525146A (ja) * | 2009-04-28 | 2012-10-22 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | 細胞透過のための過剰に荷電されたタンパク質 |
CA2761106C (en) * | 2009-05-05 | 2019-01-15 | Miragen Therapeutics | Lipophilic polynucleotide conjugates |
JP6137834B2 (ja) | 2010-02-24 | 2017-05-31 | アローヘッド ファーマシューティカルズ インコーポレイテッド | siRNAの標的化送達のための組成物 |
BR112013016761B1 (pt) | 2010-12-29 | 2021-04-06 | F. Hoffmann-La Roche Ag | Uso de um composto, composto e composição farmacêutica |
-
2011
- 2011-12-15 US US13/326,433 patent/US8501930B2/en active Active
- 2011-12-16 AU AU2011343532A patent/AU2011343532B2/en not_active Ceased
- 2011-12-16 NZ NZ61166211A patent/NZ611662A/en not_active IP Right Cessation
- 2011-12-16 EP EP11849449.1A patent/EP2651420B1/en active Active
- 2011-12-16 MX MX2013006747A patent/MX346145B/es active IP Right Grant
- 2011-12-16 BR BR112013011702A patent/BR112013011702A2/pt not_active IP Right Cessation
- 2011-12-16 JP JP2013544831A patent/JP5926739B2/ja active Active
- 2011-12-16 KR KR20137015679A patent/KR20140012624A/ko not_active Application Discontinuation
- 2011-12-16 WO PCT/US2011/065525 patent/WO2012083185A2/en active Application Filing
- 2011-12-16 SG SG2013029921A patent/SG189945A1/en unknown
- 2011-12-16 CA CA2816042A patent/CA2816042C/en active Active
- 2011-12-16 RU RU2013117285A patent/RU2623160C9/ru not_active IP Right Cessation
- 2011-12-16 PE PE2013001434A patent/PE20140180A1/es not_active Application Discontinuation
- 2011-12-16 CN CN201180059394.2A patent/CN103547272B/zh active Active
-
2013
- 2013-04-22 ZA ZA2013/02900A patent/ZA201302900B/en unknown
- 2013-06-25 US US13/926,380 patent/US9107957B2/en active Active
-
2015
- 2015-07-01 US US14/789,142 patent/US9526796B2/en active Active
- 2015-08-06 AU AU2015210397A patent/AU2015210397B2/en active Active
-
2016
- 2016-04-22 JP JP2016085719A patent/JP2016188207A/ja active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2795400C2 (ru) * | 2017-12-29 | 2023-05-03 | Сучжоу Рибо Лайф Сайенс Ко., Лтд | Конъюгаты и их получение и применение |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2013117285A (ru) | СИСТЕМА ДОСТАВКИ миРНК IN VIVO НА ОСНОВЕ ПЕПТИДОВ | |
JP2014507392A5 (ru) | ||
US20170073679A1 (en) | Compositions and Methods for Selective Delivery of Oligonucleotide Molecules to Cell Types | |
US11492619B2 (en) | Dynamic pharmacokinetic-modifying anchors | |
US10179837B2 (en) | Dendronized polymers for nucleic acid delivery | |
US6572881B1 (en) | Lipid-conjugated polyamide compounds and related compositions and methods thereof | |
CN108601795A (zh) | 用于治疗serpinc1相关病症的方法和组合物 | |
CN1271992C (zh) | 作为遗传物质转移系统的阳离子病毒体 | |
JP7021076B2 (ja) | Hif2αの遺伝子発現を阻害する組成物及び方法 | |
CN102892420A (zh) | 用于递送寡核苷酸的新型单一化学实体和方法 | |
CN108472385A (zh) | 与钉合或拼接肽缀合的生物活性化合物 | |
WO2011154331A1 (en) | Polymers for delivery of nucleic acids | |
WO2013060261A1 (zh) | 嵌段共聚物与液体组合物和核酸制剂及其制备方法和应用 | |
CN115698291A (zh) | 用于SARS-CoV-2调节的寡核苷酸 | |
Zhang et al. | Charged group surface accessibility determines micelleplexes formation and cellular interaction | |
US20230061751A1 (en) | Universal dynamic pharmacokinetic-modifying anchors | |
US9057067B2 (en) | Method for transfecting nucleic acid to cell and nucleic acid complex | |
RU2008153051A (ru) | Способ направленной доставки днк в опухолевые и стволовые клетки | |
US20210214726A1 (en) | Peptide Docking Vehicle for Targeted Nucleic Acid Delivery | |
CN111655758B (zh) | 核酸投递用聚合物 | |
Yu et al. | Sequential conjugation of 6-aminohexanoic acids and L-arginines to poly (amidoamine) dendrimer to modify hydrophobicity and flexibility of the polymeric gene carrier | |
CN114632161B (zh) | 肿瘤坏死因子-α作为一种核酸基因药物体内递送载体的应用 | |
WO2023134609A1 (zh) | 一种抑制PCSK9基因表达的RNAi剂及其应用 | |
CN115975182A (zh) | 一种氨基酸共聚物及其应用 | |
KR20240035940A (ko) | 면역원성이 감소된 바이러스 벡터 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
HZ9A | Changing address for correspondence with an applicant | ||
TC4A | Change in inventorship |
Effective date: 20180116 |
|
TK4A | Correction to the publication in the bulletin (patent) | ||
TH4A | Reissue of patent specification | ||
MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20191217 |