RU2019120040A - Модуляторы тау и способы и композиции для их доставки - Google Patents
Модуляторы тау и способы и композиции для их доставки Download PDFInfo
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- RU2019120040A RU2019120040A RU2019120040A RU2019120040A RU2019120040A RU 2019120040 A RU2019120040 A RU 2019120040A RU 2019120040 A RU2019120040 A RU 2019120040A RU 2019120040 A RU2019120040 A RU 2019120040A RU 2019120040 A RU2019120040 A RU 2019120040A
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- Prior art keywords
- genetic
- mapt
- domain
- pharmaceutical composition
- gene delivery
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- 239000000203 mixture Substances 0.000 title 1
- 230000002068 genetic effect Effects 0.000 claims 10
- 238000001476 gene delivery Methods 0.000 claims 7
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 108091033319 polynucleotide Proteins 0.000 claims 6
- 239000002157 polynucleotide Substances 0.000 claims 6
- 102000040430 polynucleotide Human genes 0.000 claims 6
- 101150070547 MAPT gene Proteins 0.000 claims 3
- 230000004568 DNA-binding Effects 0.000 claims 2
- 101710163270 Nuclease Proteins 0.000 claims 2
- 101710185494 Zinc finger protein Proteins 0.000 claims 2
- 102100023597 Zinc finger protein 816 Human genes 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 230000001105 regulatory effect Effects 0.000 claims 2
- 230000002103 transcriptional effect Effects 0.000 claims 2
- 239000013607 AAV vector Substances 0.000 claims 1
- 108020005004 Guide RNA Proteins 0.000 claims 1
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 238000000185 intracerebroventricular administration Methods 0.000 claims 1
- 238000007917 intracranial administration Methods 0.000 claims 1
- 238000007913 intrathecal administration Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 230000001629 suppression Effects 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
-
- 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
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
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- 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
- C12N15/113—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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- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
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- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
- C12N15/864—Parvoviral vectors, e.g. parvovirus, densovirus
- C12N15/8645—Adeno-associated virus
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
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- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- Neurosurgery (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Virology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Marine Sciences & Fisheries (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (18)
1. Генетический модулятор гена, ассоциированного с микротрубочками белка тау (MAPT), где модулятор включает
ДНК-связывающий домен, который связывается с сайтом-мишенью из по крайней мере 12 нуклеотидов в гене MAPT; и
регулирующий транскрипцию домен или нуклеазный домен.
2. Генетический модулятор по п. 1, где ДНК-связывающий домен включает белок с цинковыми пальцами (ZFP), белок с TAL-эффекторным доменом (TALE) или химерную руководящую РНК.
3. Генетический модулятор по п. 1 или 2, где регулирующий транскрипцию домен включает подавляющий домен или активирующий домен.
4. Полинуклеотид, кодирующий генетический модулятор по любому из пп. 1-3.
5. Средство доставки генов, включающее полинуклеотид по п.4.
6. Средство доставки генов по п. 5, где средство доставки гена включает AAV вектор.
7. Фармацевтическая композиция, содержащая один или более генетических модуляторов по любому из пп. 1-3, один или более полинуклеотидов по п. 4 и/или одно или более средств доставки генов по п. 5 или 6.
8. Фармацевтическая композиция по п. 7, где генетический модулятор включает нуклеазный домен, и генетический модулятор расщепляет ген MAPT.
9. Фармацевтическая композиция по п. 8, дополнительно содержащая донорную молекулу, которая интегрируется в расщепленный ген MAPT.
10. Выделенная клетка, содержащая один или более генетических модуляторов по любому из пп. 1-3, один или более полинуклеотидов по п. 4, одно или более средств доставки генов по п. 5 или 6 и/или фармацевтическую композицию по любому из пп. 7-9.
11. Применение одного или более генетических модуляторов по любому из пп. 1-3, одного или более полинуклеотидов по п. 4, одного или более средств доставки генов по п. 5 или 6 и/или фармацевтической композиции по любому из пп. 7-9 для модуляции экспрессии MAPT у субъекта.
12. Применение по п. 11, где экспрессия MAPT подавляется.
13. Применение по п. 11 или 12, где введение субъекту является интрацеребровентрикулярным, интратекальным, интракраниальным, внутривенным, ретроорбитальным или интрацистернальным.
14. Применение по любому из пп. 11-13, где подавление экспрессии MAPT у субъекта лечит и/или предотвращает таупатию.
15. Применение по любому из пп. 11-14, где количество тау у субъекта снижается.
16. Набор, включающий один или более генетических модуляторов по любому из пп. 1-3, один или более полинуклеотидов по п. 4, одно или более средств доставки генов по п. 5 или 6, фармацевтическую композицию по любому из пп. 7-9, и/или инструкции по применению.
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662428871P | 2016-12-01 | 2016-12-01 | |
| US62/428,871 | 2016-12-01 | ||
| US201762450895P | 2017-01-26 | 2017-01-26 | |
| US62/450,895 | 2017-01-26 | ||
| US201762466198P | 2017-03-02 | 2017-03-02 | |
| US62/466,198 | 2017-03-02 | ||
| US201762500807P | 2017-05-03 | 2017-05-03 | |
| US62/500,807 | 2017-05-03 | ||
| US201762584342P | 2017-11-10 | 2017-11-10 | |
| US62/584,342 | 2017-11-10 | ||
| PCT/US2017/064181 WO2018102665A1 (en) | 2016-12-01 | 2017-12-01 | Tau modulators and methods and compositions for delivery thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2019120040A true RU2019120040A (ru) | 2021-01-11 |
| RU2019120040A3 RU2019120040A3 (ru) | 2021-04-09 |
| RU2789459C2 RU2789459C2 (ru) | 2023-02-03 |
Family
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Also Published As
| Publication number | Publication date |
|---|---|
| IL266862B1 (en) | 2023-09-01 |
| AU2017367722A8 (en) | 2019-06-13 |
| CN110214184B (zh) | 2024-07-02 |
| JP2020500526A (ja) | 2020-01-16 |
| JP7292204B2 (ja) | 2023-06-16 |
| RU2019120040A3 (ru) | 2021-04-09 |
| US20230270774A1 (en) | 2023-08-31 |
| IL266862B2 (en) | 2024-01-01 |
| US20180153921A1 (en) | 2018-06-07 |
| WO2018102665A1 (en) | 2018-06-07 |
| MX2019006426A (es) | 2019-08-14 |
| CA3043635A1 (en) | 2018-06-07 |
| AU2017367722A1 (en) | 2019-05-30 |
| IL266862A (en) | 2019-07-31 |
| CN110214184A (zh) | 2019-09-06 |
| EP3548616A4 (en) | 2020-05-13 |
| KR20190085529A (ko) | 2019-07-18 |
| BR112019010014A2 (pt) | 2019-08-20 |
| AU2017367722B2 (en) | 2024-02-01 |
| KR102674612B1 (ko) | 2024-06-14 |
| EP3548616A1 (en) | 2019-10-09 |
| JP2023078446A (ja) | 2023-06-06 |
| US11504389B2 (en) | 2022-11-22 |
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