MX2019014379A - Casetes de expresion optimizados del gen del factor de coagulacion ix humano y su uso. - Google Patents
Casetes de expresion optimizados del gen del factor de coagulacion ix humano y su uso.Info
- Publication number
- MX2019014379A MX2019014379A MX2019014379A MX2019014379A MX2019014379A MX 2019014379 A MX2019014379 A MX 2019014379A MX 2019014379 A MX2019014379 A MX 2019014379A MX 2019014379 A MX2019014379 A MX 2019014379A MX 2019014379 A MX2019014379 A MX 2019014379A
- Authority
- MX
- Mexico
- Prior art keywords
- gene expression
- expression cassettes
- clotting factor
- optimized human
- human clotting
- Prior art date
Links
- 230000014509 gene expression Effects 0.000 title abstract 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 title 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 title 1
- 101150108210 IX gene Proteins 0.000 title 1
- 239000003114 blood coagulation factor Substances 0.000 title 1
- 229960004222 factor ix Drugs 0.000 title 1
- 210000004185 liver Anatomy 0.000 abstract 2
- 102100022641 Coagulation factor IX Human genes 0.000 abstract 1
- 108010076282 Factor IX Proteins 0.000 abstract 1
- 208000031169 hemorrhagic disease Diseases 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 102000039446 nucleic acids Human genes 0.000 abstract 1
- 108020004707 nucleic acids Proteins 0.000 abstract 1
- 150000007523 nucleic acids Chemical class 0.000 abstract 1
- 102000040430 polynucleotide Human genes 0.000 abstract 1
- 108091033319 polynucleotide Proteins 0.000 abstract 1
- 239000002157 polynucleotide Substances 0.000 abstract 1
- 229920001184 polypeptide Polymers 0.000 abstract 1
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 1
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 1
Classifications
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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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/644—Coagulation factor IXa (3.4.21.22)
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- 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)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
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- 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
- A61K48/005—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 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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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
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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
- C07K14/81—Protease inhibitors
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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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- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/067—Hepatocytes
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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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0693—Tumour cells; Cancer cells
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21022—Coagulation factor IXa (3.4.21.22)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C12N2510/00—Genetically modified cells
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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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- 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
- C12N2800/00—Nucleic acids vectors
- C12N2800/10—Plasmid DNA
- C12N2800/106—Plasmid DNA for vertebrates
- C12N2800/107—Plasmid DNA for vertebrates for mammalian
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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
- C12N2800/00—Nucleic acids vectors
- C12N2800/22—Vectors comprising a coding region that has been codon optimised for expression in a respective host
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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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Virology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Oncology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
La invencion se refiere a promotores sinteticos especificos de higado y construcciones de expresion para producir polipeptidos y acidos nucleicos funcionales en el higado de un sujeto; la invencion ademas esta relacionada con secuencias de polinucleotido optimizadas que codifican proteinas del Factor IX, vectores que comprenden los mismos, y metodos para utilizar estas composiciones para tratar un trastorno hemorragico.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762512833P | 2017-05-31 | 2017-05-31 | |
PCT/US2018/035267 WO2018222792A1 (en) | 2017-05-31 | 2018-05-31 | Optimized human clotting factor ix gene expression cassettes and their use |
Publications (1)
Publication Number | Publication Date |
---|---|
MX2019014379A true MX2019014379A (es) | 2020-01-23 |
Family
ID=64456331
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
MX2019014379A MX2019014379A (es) | 2017-05-31 | 2018-05-31 | Casetes de expresion optimizados del gen del factor de coagulacion ix humano y su uso. |
Country Status (9)
Country | Link |
---|---|
US (2) | US11530402B2 (es) |
EP (1) | EP3630978A4 (es) |
JP (2) | JP7119009B2 (es) |
KR (2) | KR102625470B1 (es) |
CN (2) | CN114875051A (es) |
AU (1) | AU2018275549A1 (es) |
CA (1) | CA3064450A1 (es) |
MX (1) | MX2019014379A (es) |
WO (1) | WO2018222792A1 (es) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB201420139D0 (en) | 2014-11-12 | 2014-12-24 | Ucl Business Plc | Factor IX gene therapy |
US10842885B2 (en) | 2018-08-20 | 2020-11-24 | Ucl Business Ltd | Factor IX encoding nucleotides |
CN115279896A (zh) * | 2019-09-30 | 2022-11-01 | 比奥维拉迪维治疗股份有限公司 | 慢病毒载体配制品 |
EP4051324A4 (en) * | 2019-10-28 | 2023-11-29 | University Of Florida Research Foundation, Incorporated | GENE THERAPY VECTORS |
IL296986A (en) * | 2020-04-06 | 2022-12-01 | Homology Medicines Inc | Adeno-associated virus preparations for ids gene transfer and methods of use thereof |
CN113817759B (zh) * | 2020-07-10 | 2023-06-02 | 南京吉迈生物技术有限公司 | 修饰的因子ix、组合物、方法及其在基因治疗中的应用 |
CN117693593A (zh) * | 2021-06-23 | 2024-03-12 | 英斯培瑞有限公司 | 用于治疗b型血友病的组合物和方法 |
CN114277057B (zh) * | 2021-07-09 | 2023-10-13 | 上海天泽云泰生物医药有限公司 | 用于治疗或预防b型血友病的重组腺相关病毒载体和方法 |
TW202334194A (zh) * | 2021-10-27 | 2023-09-01 | 美商雷傑納榮製藥公司 | 用於表現因子ix以便治療b型血友病的組成物及方法 |
CN117247973B (zh) * | 2022-04-19 | 2024-05-10 | 康霖生物科技(杭州)有限公司 | 一种用于遗传性凝血因子缺乏病治疗的核酸构建体及其用途 |
CN115029360A (zh) * | 2022-05-30 | 2022-09-09 | 上海勉亦生物科技有限公司 | 用于治疗粘多糖贮积症iiia型的转基因表达盒 |
CN115948408A (zh) * | 2022-09-23 | 2023-04-11 | 上海信致医药科技有限公司 | 改进的人凝血因子viii基因表达盒及其应用 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2650838A1 (fr) * | 1989-08-09 | 1991-02-15 | Transgene Sa | Vecteurs d'expression du facteur ix dans une cellule eucaryote superieure, procede de preparation de facteur ix par des animaux transgeniques et facteur ix obtenu |
CA2162497A1 (en) * | 1993-06-10 | 1994-12-22 | Sheila Connelly | Adenoviral vectors for treatment of hemophilia |
ES2436741T3 (es) | 2004-09-22 | 2014-01-07 | St. Jude Children's Research Hospital | Expresión mejorada de Factor IX en vectores de terapia génica |
US7943374B2 (en) * | 2005-08-21 | 2011-05-17 | Markus Hildinger | Super-size adeno-associated viral vector harboring a recombinant genome larger than 5.7 kb |
EP2021499A4 (en) * | 2005-12-16 | 2010-02-17 | Univ Leland Stanford Junior | FUNCTIONAL ARRAYS FOR THE IDENTIFICATION OF ELEMENTS FOR GENE PRESSION REGULATION WITH HIGH THROUGHPUT |
EP2037892B1 (en) * | 2006-06-19 | 2015-03-18 | Asklepios Biopharmaceutical, Inc. | Modified factor viii and factor ix genes and vectors for gene therapy |
CN102628041B (zh) * | 2008-02-14 | 2013-09-11 | 财团法人牧岩生命工学研究所 | 适于表达用于基因治疗的编码序列的表达载体 |
EP2282764B1 (en) * | 2008-04-22 | 2019-07-24 | Vib Vzw | Liver-specific nucleic acid regulatory elements and methods and use thereof |
RU2585532C2 (ru) | 2014-01-31 | 2016-05-27 | Федеральное государственное учреждение "Федеральный исследовательский центр "Фундаментальные основы биотехнологии" Российской академии наук"(ФИЦ Биотехнологии РАН) | Плазмида для экспрессии рекомбинантного фактора свёртываемости крови ix человека, клетка сно - продуцент рекомбинантного фактора свёртываемости крови ix человека и способ получения указанного фактора |
CA2939950C (en) * | 2014-03-09 | 2023-08-22 | The Trustees Of The University Of Pennsylvania | Compositions useful in treatment of ornithine transcarbamylase (otc) deficiency |
GB201420139D0 (en) * | 2014-11-12 | 2014-12-24 | Ucl Business Plc | Factor IX gene therapy |
JP6800863B2 (ja) * | 2015-02-06 | 2020-12-16 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | 最適化されたヒト凝固第viii因子遺伝子発現カセットおよびその使用 |
CN108138159A (zh) * | 2015-06-23 | 2018-06-08 | 费城儿童医院 | 经修饰的因子ix、以及用于基因转移到细胞、器官和组织的组合物、方法和用途 |
US10086089B2 (en) * | 2015-09-18 | 2018-10-02 | DNARx | Systems and methods for nucleic acid expression in vivo |
EP3442597A1 (en) * | 2016-04-15 | 2019-02-20 | The Trustees Of The University Of Pennsylvania | Gene therapy for treating hemophilia b |
JP2020511521A (ja) * | 2017-03-23 | 2020-04-16 | ディーエヌエーアールエックス | in vivoでの核酸発現のためのシステム及び方法 |
-
2018
- 2018-05-31 AU AU2018275549A patent/AU2018275549A1/en active Pending
- 2018-05-31 MX MX2019014379A patent/MX2019014379A/es unknown
- 2018-05-31 EP EP18809332.2A patent/EP3630978A4/en active Pending
- 2018-05-31 WO PCT/US2018/035267 patent/WO2018222792A1/en active Application Filing
- 2018-05-31 CN CN202210750672.9A patent/CN114875051A/zh active Pending
- 2018-05-31 KR KR1020197036397A patent/KR102625470B1/ko active IP Right Grant
- 2018-05-31 JP JP2019566601A patent/JP7119009B2/ja active Active
- 2018-05-31 US US16/616,784 patent/US11530402B2/en active Active
- 2018-05-31 CN CN201810547030.2A patent/CN108977452B/zh active Active
- 2018-05-31 CA CA3064450A patent/CA3064450A1/en active Pending
- 2018-05-31 KR KR1020247001130A patent/KR20240010098A/ko active Application Filing
-
2022
- 2022-08-03 JP JP2022123665A patent/JP2022159358A/ja active Pending
- 2022-11-17 US US18/056,424 patent/US20230091502A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
CN108977452B (zh) | 2022-07-19 |
AU2018275549A1 (en) | 2019-11-21 |
JP7119009B2 (ja) | 2022-08-16 |
JP2022159358A (ja) | 2022-10-17 |
KR20200014318A (ko) | 2020-02-10 |
JP2020522259A (ja) | 2020-07-30 |
KR102625470B1 (ko) | 2024-01-16 |
KR20240010098A (ko) | 2024-01-23 |
EP3630978A4 (en) | 2021-03-24 |
US20200087646A1 (en) | 2020-03-19 |
US20230091502A1 (en) | 2023-03-23 |
EP3630978A1 (en) | 2020-04-08 |
CN108977452A (zh) | 2018-12-11 |
CA3064450A1 (en) | 2018-12-06 |
WO2018222792A1 (en) | 2018-12-06 |
US11530402B2 (en) | 2022-12-20 |
CN114875051A (zh) | 2022-08-09 |
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