JP7159048B2 - 遺伝子修正自己ケラチノサイトを使用する劣性栄養障害型表皮水疱症のための遺伝子療法 - Google Patents
遺伝子修正自己ケラチノサイトを使用する劣性栄養障害型表皮水疱症のための遺伝子療法 Download PDFInfo
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- JP7159048B2 JP7159048B2 JP2018534551A JP2018534551A JP7159048B2 JP 7159048 B2 JP7159048 B2 JP 7159048B2 JP 2018534551 A JP2018534551 A JP 2018534551A JP 2018534551 A JP2018534551 A JP 2018534551A JP 7159048 B2 JP7159048 B2 JP 7159048B2
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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
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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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
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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
- 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
- A61K48/0075—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 delivery route, e.g. oral, subcutaneous
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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
- A61K48/0091—Purification or manufacturing processes for gene therapy compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3695—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the function or physical properties of the final product, where no specific conditions are defined to achieve this
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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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
- C12N5/0625—Epidermal cells, skin cells; Cells of the oral mucosa
- C12N5/0629—Keratinocytes; Whole skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea
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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
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16041—Use of virus, viral particle or viral elements as a vector
- C12N2760/16043—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)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Botany (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Manufacturing & Machinery (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022164008A JP7555380B2 (ja) | 2016-01-04 | 2022-10-12 | 遺伝子修正自己ケラチノサイトを使用する劣性栄養障害型表皮水疱症のための遺伝子療法 |
| JP2024156801A JP2024167419A (ja) | 2016-01-04 | 2024-09-10 | 遺伝子修正自己ケラチノサイトを使用する劣性栄養障害型表皮水疱症のための遺伝子療法 |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662274700P | 2016-01-04 | 2016-01-04 | |
| US62/274,700 | 2016-01-04 | ||
| US201662414533P | 2016-10-28 | 2016-10-28 | |
| US62/414,533 | 2016-10-28 | ||
| PCT/US2017/012061 WO2017120147A1 (en) | 2016-01-04 | 2017-01-03 | Gene therapy for recessive dystrophic epidermolysis bullosa using genetically corrected autologous keratinocytes |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022164008A Division JP7555380B2 (ja) | 2016-01-04 | 2022-10-12 | 遺伝子修正自己ケラチノサイトを使用する劣性栄養障害型表皮水疱症のための遺伝子療法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019506925A JP2019506925A (ja) | 2019-03-14 |
| JP2019506925A5 JP2019506925A5 (enExample) | 2020-02-13 |
| JP7159048B2 true JP7159048B2 (ja) | 2022-10-24 |
Family
ID=58010360
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018534551A Active JP7159048B2 (ja) | 2016-01-04 | 2017-01-03 | 遺伝子修正自己ケラチノサイトを使用する劣性栄養障害型表皮水疱症のための遺伝子療法 |
| JP2022164008A Active JP7555380B2 (ja) | 2016-01-04 | 2022-10-12 | 遺伝子修正自己ケラチノサイトを使用する劣性栄養障害型表皮水疱症のための遺伝子療法 |
| JP2024156801A Pending JP2024167419A (ja) | 2016-01-04 | 2024-09-10 | 遺伝子修正自己ケラチノサイトを使用する劣性栄養障害型表皮水疱症のための遺伝子療法 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022164008A Active JP7555380B2 (ja) | 2016-01-04 | 2022-10-12 | 遺伝子修正自己ケラチノサイトを使用する劣性栄養障害型表皮水疱症のための遺伝子療法 |
| JP2024156801A Pending JP2024167419A (ja) | 2016-01-04 | 2024-09-10 | 遺伝子修正自己ケラチノサイトを使用する劣性栄養障害型表皮水疱症のための遺伝子療法 |
Country Status (17)
| Country | Link |
|---|---|
| US (4) | US12173314B2 (enExample) |
| EP (2) | EP3842520A1 (enExample) |
| JP (3) | JP7159048B2 (enExample) |
| KR (1) | KR20180093967A (enExample) |
| CN (2) | CN114699558B (enExample) |
| AU (2) | AU2017205925B2 (enExample) |
| BR (1) | BR112018013576A2 (enExample) |
| CA (1) | CA3008676A1 (enExample) |
| DK (1) | DK3400287T3 (enExample) |
| ES (1) | ES2861453T3 (enExample) |
| IL (2) | IL260038B (enExample) |
| MX (1) | MX2018007986A (enExample) |
| NZ (1) | NZ743682A (enExample) |
| PT (1) | PT3400287T (enExample) |
| RU (2) | RU2021121824A (enExample) |
| WO (1) | WO2017120147A1 (enExample) |
| ZA (1) | ZA201803962B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3842520A1 (en) * | 2016-01-04 | 2021-06-30 | The Board of Trustees of the Leland Stanford Junior University | Gene therapy for recessive dystrophic epidermolysis bullosa using genetically corrected autologous keratinocytes |
| IT201700094210A1 (it) * | 2017-08-17 | 2019-02-17 | Holostem Terapie Avanzate S R L | Metodo per produrre lembi cellulari |
| IT201700104587A1 (it) * | 2017-09-19 | 2019-03-19 | Holostem Terapie Avanzate S R L | Usi terapeutici di lembi di cellule geneticamente modificate |
| SG11202005934WA (en) * | 2017-12-29 | 2020-07-29 | Genemedicine Co Ltd | Cell sheet for gene delivery |
| RU2730661C2 (ru) * | 2018-12-27 | 2020-08-24 | Селл энд Джин Терапи Лтд | Генотерапевтический ДНК-вектор на основе генотерапевтического ДНК-вектора VTvaf17, несущий целевой ген, выбранный из группы генов COL1A1, COL1A2, P4HA1, P4HA2, COL7A1, CLCA2, ELN, PLOD1 для повышения уровня экспрессии этих целевых генов, способ его получения и применения, штамм Escherichia coli SCS110-AF/VTvaf17-COL1A1, или Escherichia coli SCS110-AF/VTvaf17-COL1A2, или Escherichia coli SCS110-AF/VTvaf17-P4HA1, или Escherichia coli SCS110-AF/VTvaf17-P4HA2, или Escherichia coli SCS110-AF/VTvaf17-COL7A1, или Escherichia coli SCS110-AF/VTvaf17-CLCA2, или Escherichia coli SCS110-AF/VTvaf17-ELN, или Escherichia coli SCS110-AF/VTvaf17- PLOD1, несущий генотерапевтический ДНК-вектор, способ его получения, способ производства в промышленных масштабах генотерапевтического ДНК-вектора |
| KR20210116531A (ko) | 2019-01-18 | 2021-09-27 | 고꾸리쯔 다이가꾸 호우징 오사까 다이가꾸 | 영양 장애형 표피 수포증 치료약 |
| CN116529361B (zh) * | 2019-10-18 | 2024-01-26 | 北赛泓升(北京)生物科技有限公司 | 使用多顺反子sox2、klf4和任选的c-myc产生诱导多能干细胞 |
| KR20230043906A (ko) | 2020-07-22 | 2023-03-31 | 고꾸리쯔 다이가꾸 호우징 오사까 다이가꾸 | 영양 장애형 표피 수포증의 치료약 |
| MX2024004434A (es) | 2021-10-12 | 2024-07-09 | Phoenix Tissue Repair Inc | Terapia de reemplazo de proteínas con colágeno 7. |
| JP2025094280A (ja) | 2022-01-21 | 2025-06-25 | 国立大学法人大阪大学 | 細胞シート |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5830725A (en) * | 1995-04-28 | 1998-11-03 | The Board Of Trustees For The Leland Stanford Junior University | Rapid, stable high-titre production of recombing retrovirus |
| US20020090725A1 (en) | 2000-11-17 | 2002-07-11 | Simpson David G. | Electroprocessed collagen |
| MXPA02000152A (es) * | 1999-07-02 | 2002-07-30 | Human Genome Sciences Inc | Factor 2 de crecimiento de queratinocitos. |
| FR2857671B1 (fr) * | 2003-07-18 | 2007-10-05 | Centre Nat Rech Scient | Nouveau procede de culture de keratinocytes et ses applications |
| CN1916166B (zh) * | 2006-09-08 | 2010-08-11 | 北京赛尔泰和生物医药科技有限公司 | 自体角膜上皮的制备方法 |
| US8865199B2 (en) * | 2008-11-17 | 2014-10-21 | Ingeneron, Inc. | Biomatrix composition and methods of biomatrix seeding |
| GB201202561D0 (en) * | 2012-02-15 | 2012-03-28 | Univ Dundee | Treatment of skin disorders |
| JP6334550B2 (ja) * | 2012-11-06 | 2018-05-30 | インベッド バイオサイエンシズ,インコーポレイテッド | 創傷治癒の方法と組成物 |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| CN105087565A (zh) * | 2015-08-21 | 2015-11-25 | 内蒙古自治区人民医院 | 一种营养不良型大疱性表皮松解症核苷酸及其应用 |
| EP3842520A1 (en) * | 2016-01-04 | 2021-06-30 | The Board of Trustees of the Leland Stanford Junior University | Gene therapy for recessive dystrophic epidermolysis bullosa using genetically corrected autologous keratinocytes |
| US20190192636A1 (en) * | 2016-03-18 | 2019-06-27 | Intrexon Corporation | Compositions and methods for treatment of type viii collagen deficiencies |
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2017
- 2017-01-03 EP EP20210538.3A patent/EP3842520A1/en active Pending
- 2017-01-03 JP JP2018534551A patent/JP7159048B2/ja active Active
- 2017-01-03 IL IL260038A patent/IL260038B/en unknown
- 2017-01-03 BR BR112018013576A patent/BR112018013576A2/pt not_active Application Discontinuation
- 2017-01-03 US US16/066,253 patent/US12173314B2/en active Active
- 2017-01-03 CN CN202210368934.5A patent/CN114699558B/zh not_active Expired - Fee Related
- 2017-01-03 WO PCT/US2017/012061 patent/WO2017120147A1/en not_active Ceased
- 2017-01-03 PT PT177043270T patent/PT3400287T/pt unknown
- 2017-01-03 MX MX2018007986A patent/MX2018007986A/es unknown
- 2017-01-03 ES ES17704327T patent/ES2861453T3/es active Active
- 2017-01-03 RU RU2021121824A patent/RU2021121824A/ru unknown
- 2017-01-03 KR KR1020187018813A patent/KR20180093967A/ko not_active Ceased
- 2017-01-03 NZ NZ743682A patent/NZ743682A/en not_active IP Right Cessation
- 2017-01-03 CA CA3008676A patent/CA3008676A1/en active Pending
- 2017-01-03 AU AU2017205925A patent/AU2017205925B2/en not_active Ceased
- 2017-01-03 EP EP17704327.0A patent/EP3400287B1/en active Active
- 2017-01-03 CN CN201780005233.2A patent/CN108473952B/zh not_active Expired - Fee Related
- 2017-01-03 RU RU2018127524A patent/RU2753248C2/ru active
- 2017-01-03 DK DK17704327.0T patent/DK3400287T3/da active
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2018
- 2018-06-13 ZA ZA2018/03962A patent/ZA201803962B/en unknown
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2020
- 2020-09-25 AU AU2020239779A patent/AU2020239779A1/en not_active Abandoned
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2022
- 2022-05-31 IL IL293465A patent/IL293465B2/en unknown
- 2022-10-12 JP JP2022164008A patent/JP7555380B2/ja active Active
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2023
- 2023-11-03 US US18/501,837 patent/US12110504B2/en active Active
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2024
- 2024-09-10 JP JP2024156801A patent/JP2024167419A/ja active Pending
- 2024-10-31 US US18/933,687 patent/US12385010B2/en active Active
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2025
- 2025-04-29 US US19/192,918 patent/US20250257319A1/en active Pending
Non-Patent Citations (6)
| Title |
|---|
| EXPERIMENTAL DERMATOLOGY,2013年12月30日,VOL. 23, NO. 1,PAGES. 1 - 6,https://www.ncbi.nlm.nih.gov/pubmed/24107073 |
| HUMAN GENE THERAPY,2010年10月,VOL:21, NR:10,PAGE(S):1299 - 1310,http://dx.doi.org/10.1089/hum.2010.023 |
| INVESTIGATIVE OPTHALMOLOGY & VISUAL SCIENCE,2014年04月11日,VOL. 55, NO. 4,PAGES. 2337-2343,https://www.ncbi.nlm.nih.gov/pubmed/24651553 |
| JOURNAL OF INVESTIGATIVE DERMATOLOGY,2014年,VOL. 134, NO. SUPPL 1,PAGES. S75,https://www.researchgate.net/publication/285484247_Phase_I_clinical_trial_of_genetically_corrected_autologous_epidermal_keratinocytes_for_recessive_dystrophic_epidermolysis_bullosa |
| Mol.Ther.,2014年,Vol.22, Suppl.1,S218 No.562 |
| SCIENCE TRANSLATIONAL MEDICINE,2014年11月26日,VOL. 6, NO. 264,PAGES. 264RA163-1/23,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428910/ |
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