HUE051953T2 - Idõskori makula degeneráció kezelése AAV2 variáns és aflibercept alkalmazásával - Google Patents
Idõskori makula degeneráció kezelése AAV2 variáns és aflibercept alkalmazásávalInfo
- Publication number
- HUE051953T2 HUE051953T2 HUE17814223A HUE17814223A HUE051953T2 HU E051953 T2 HUE051953 T2 HU E051953T2 HU E17814223 A HUE17814223 A HU E17814223A HU E17814223 A HUE17814223 A HU E17814223A HU E051953 T2 HUE051953 T2 HU E051953T2
- Authority
- HU
- Hungary
- Prior art keywords
- aflibercept
- treatment
- macular degeneration
- aav2 variant
- elderly macular
- Prior art date
Links
- 241000702423 Adeno-associated virus - 2 Species 0.000 title 1
- 229960002833 aflibercept Drugs 0.000 title 1
- 108010081667 aflibercept Proteins 0.000 title 1
- 208000002780 macular degeneration Diseases 0.000 title 1
Classifications
-
- 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
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/179—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
- A61K35/761—Adenovirus
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- 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
-
- 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
- C12N2750/14122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Ophthalmology & Optometry (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Plant Pathology (AREA)
- Mycology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Dispersion Chemistry (AREA)
- Hematology (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662351234P | 2016-06-16 | 2016-06-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HUE051953T2 true HUE051953T2 (hu) | 2021-04-28 |
Family
ID=60663653
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HUE17814223A HUE051953T2 (hu) | 2016-06-16 | 2017-06-16 | Idõskori makula degeneráció kezelése AAV2 variáns és aflibercept alkalmazásával |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US20190151409A1 (enExample) |
| EP (2) | EP3795181B1 (enExample) |
| JP (4) | JP6814822B2 (enExample) |
| KR (2) | KR20210021113A (enExample) |
| CN (2) | CN109641065A (enExample) |
| AU (3) | AU2017286673B2 (enExample) |
| BR (1) | BR112018076124A2 (enExample) |
| CA (1) | CA3027737A1 (enExample) |
| CY (1) | CY1123697T1 (enExample) |
| DK (2) | DK3795181T3 (enExample) |
| ES (1) | ES2840059T3 (enExample) |
| FI (1) | FI3795181T3 (enExample) |
| HR (1) | HRP20201842T1 (enExample) |
| HU (1) | HUE051953T2 (enExample) |
| IL (3) | IL279919B2 (enExample) |
| LT (1) | LT3471780T (enExample) |
| MX (2) | MX391779B (enExample) |
| PT (2) | PT3795181T (enExample) |
| RS (2) | RS67328B1 (enExample) |
| SG (1) | SG11201811232XA (enExample) |
| SI (2) | SI3795181T1 (enExample) |
| SM (2) | SMT202100010T1 (enExample) |
| WO (1) | WO2017218974A2 (enExample) |
| ZA (1) | ZA201808538B (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102288849B1 (ko) | 2014-03-17 | 2021-08-12 | 애드베룸 바이오테크놀로지스, 인코포레이티드 | 원추세포에서 증강된 유전자 발현을 위한 조성물 및 방법 |
| KR20170137730A (ko) | 2015-03-02 | 2017-12-13 | 애드베룸 바이오테크놀로지스, 인코포레이티드 | 망막 추상체에 폴리뉴클레오타이드의 유리체 내 전달을 위한 조성물 및 방법 |
| HUE051953T2 (hu) * | 2016-06-16 | 2021-04-28 | Adverum Biotechnologies Inc | Idõskori makula degeneráció kezelése AAV2 variáns és aflibercept alkalmazásával |
| US11192925B2 (en) | 2016-10-19 | 2021-12-07 | Adverum Biotechnologies, Inc. | Modified AAV capsids and uses thereof |
| EP4653536A2 (en) | 2017-03-17 | 2025-11-26 | Adverum Biotechnologies, Inc. | Compositions and methods for enhanced gene expression |
| CN107661492A (zh) * | 2017-08-31 | 2018-02-06 | 中山大学中山眼科中心 | Vegf‑b的新用途 |
| CN107537026A (zh) * | 2017-08-31 | 2018-01-05 | 中山大学中山眼科中心 | Vegf‑b的应用 |
| AU2018350990A1 (en) * | 2017-10-18 | 2020-05-21 | Regenxbio Inc. | Treatment of ocular diseases and metastatic colon cancer with human post-translationally modified VEGF-Trap |
| AU2018372235B9 (en) * | 2017-11-27 | 2022-03-10 | 4D Molecular Therapeutics Inc. | Adeno-associated virus variant capsids and use for inhibiting angiogenesis |
| JP2021506861A (ja) | 2017-12-19 | 2021-02-22 | アコーオス インコーポレイテッド | 内耳への治療用抗体のａａｖ媒介送達 |
| WO2019198084A1 (en) * | 2018-04-12 | 2019-10-17 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Anti-aging compositions and methods of use |
| NZ770284A (en) | 2018-05-10 | 2025-11-28 | Regeneron Pharma | High concentration vegf receptor fusion protein containing formulations |
| US20200297869A1 (en) * | 2019-03-04 | 2020-09-24 | Adverum Biotechnologies, Inc. | Sequential intravitreal administration of aav gene therapy to contralateral eyes |
| BR112021021156A2 (pt) * | 2019-04-24 | 2022-02-08 | Regenxbio Inc | Terapêuticos anticorpos totalmente humanos pós-tradução modificados |
| WO2021050649A1 (en) * | 2019-09-11 | 2021-03-18 | Adverum Biotechnologies, Inc. | Methods of treating ocular neovascular diseases using aav2 variants encoding aflibercept |
| MX2022002960A (es) * | 2019-09-11 | 2022-04-06 | Adverum Biotechnologies Inc | Metodos para tratar enfermedades neovasculares oculares usando variantes de aav2 que codifican para aflibercept. |
| TWI819268B (zh) * | 2020-01-16 | 2023-10-21 | 詹姆斯 Ｗ 希爾 | 藉由基因轉導改變眼睛顏色 |
| FR3111913A1 (fr) * | 2020-06-30 | 2021-12-31 | Eyevensys | Construction d’adn pour le traitement de pathologies oculaires |
| CN113952473A (zh) * | 2020-07-21 | 2022-01-21 | 英斯培瑞有限公司 | 用于治疗眼部疾病的组合物和方法 |
| CN113952474A (zh) * | 2020-07-21 | 2022-01-21 | 英斯培瑞有限公司 | 用于治疗眼部疾病的组合物和方法 |
| AU2021313839A1 (en) * | 2020-07-21 | 2023-03-23 | FTGEN Corp | Composition and method for treating eye diseases |
| CN113817775B (zh) * | 2020-08-25 | 2023-02-17 | 南京吉迈生物技术有限公司 | 修饰的阿柏西普、组合物、方法及其在基因治疗中的应用 |
| MX2023002695A (es) * | 2020-09-03 | 2023-05-19 | Univ Massachusetts | Virus adeno-asociado para la administración de kh902 (conbercept) y usos del mismo. |
| IL303317A (en) | 2020-12-01 | 2023-07-01 | Akouos Inc | ANTI-NATURAL ANTIBODY STRUCTURES AND RELATED METHODS FOR THE TREATMENT OF SYMPTOMS ASSOCIATED WITH VESTIBULAR SWANNOMA |
| JP2021049374A (ja) * | 2020-12-09 | 2021-04-01 | 株式会社三洋物産 | 遊技機 |
| CA3215855A1 (en) * | 2021-04-27 | 2022-11-03 | Julie Clark | Methods of treating ocular diseases using aav2 variants encoding aflibercept |
| WO2023155918A1 (zh) | 2022-02-21 | 2023-08-24 | 上海瑞宏迪医药有限公司 | Vegf结合分子及其医药用途 |
| WO2025072688A2 (en) * | 2023-09-27 | 2025-04-03 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Adeno-associated virus vectors for nucleic acid delivery to retinal cells, for nucleic acid delivery across retinal regions, or for nucleic acid delivery to retinal ganglion cells and/or retinal pigment epithelium cells |
| WO2025073297A1 (zh) * | 2023-10-06 | 2025-04-10 | 甘李药业股份有限公司 | 表达抗vegf融合蛋白的aav病毒载体及其用途 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RS66184B1 (sr) * | 2011-04-22 | 2024-12-31 | Univ California | Adeno-povezani virioni virusa sa varijantama kapsida i postupci za njihovu primenu |
| US10568934B2 (en) * | 2012-05-07 | 2020-02-25 | Allergan, Inc. | Method of treating AMD in patients refractory to anti-VEGF therapy |
| TWI775096B (zh) * | 2012-05-15 | 2022-08-21 | 澳大利亞商艾佛蘭屈澳洲私營有限公司 | 使用腺相關病毒(aav)sflt-1治療老年性黃斑部退化(amd) |
| WO2013188316A1 (en) * | 2012-06-11 | 2013-12-19 | Avalanche Biotechnologies, Inc. | Optical regulation of gene expression in the retina |
| MX2016000364A (es) * | 2013-07-12 | 2016-05-09 | Ophthotech Corp | Metodos para tratar o prevenir afecciones oftalmologicas. |
| JP6607850B2 (ja) | 2013-10-18 | 2019-11-20 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | Ｖｅｇｆアンタゴニスト及び抗ｃｔｌａ−４抗体の組み合わせを含む方法及び組成物 |
| KR20170137730A (ko) * | 2015-03-02 | 2017-12-13 | 애드베룸 바이오테크놀로지스, 인코포레이티드 | 망막 추상체에 폴리뉴클레오타이드의 유리체 내 전달을 위한 조성물 및 방법 |
| HUE051953T2 (hu) * | 2016-06-16 | 2021-04-28 | Adverum Biotechnologies Inc | Idõskori makula degeneráció kezelése AAV2 variáns és aflibercept alkalmazásával |
-
2017
- 2017-06-16 HU HUE17814223A patent/HUE051953T2/hu unknown
- 2017-06-16 CN CN201780050283.2A patent/CN109641065A/zh active Pending
- 2017-06-16 RS RS20251055A patent/RS67328B1/sr unknown
- 2017-06-16 CN CN202311530329.4A patent/CN117531025A/zh active Pending
- 2017-06-16 SG SG11201811232XA patent/SG11201811232XA/en unknown
- 2017-06-16 PT PT201966579T patent/PT3795181T/pt unknown
- 2017-06-16 BR BR112018076124A patent/BR112018076124A2/pt unknown
- 2017-06-16 SM SM20210010T patent/SMT202100010T1/it unknown
- 2017-06-16 FI FIEP20196657.9T patent/FI3795181T3/fi active
- 2017-06-16 WO PCT/US2017/038003 patent/WO2017218974A2/en not_active Ceased
- 2017-06-16 KR KR1020217004488A patent/KR20210021113A/ko not_active Ceased
- 2017-06-16 JP JP2018565845A patent/JP6814822B2/ja active Active
- 2017-06-16 DK DK20196657.9T patent/DK3795181T3/da active
- 2017-06-16 ES ES17814223T patent/ES2840059T3/es active Active
- 2017-06-16 HR HRP20201842TT patent/HRP20201842T1/hr unknown
- 2017-06-16 IL IL279919A patent/IL279919B2/en unknown
- 2017-06-16 AU AU2017286673A patent/AU2017286673B2/en active Active
- 2017-06-16 SM SM20250400T patent/SMT202500400T1/it unknown
- 2017-06-16 SI SI201731629T patent/SI3795181T1/sl unknown
- 2017-06-16 MX MX2018015512A patent/MX391779B/es unknown
- 2017-06-16 IL IL314568A patent/IL314568B2/en unknown
- 2017-06-16 RS RS20201517A patent/RS61311B1/sr unknown
- 2017-06-16 SI SI201730553T patent/SI3471780T1/sl unknown
- 2017-06-16 LT LTEP17814223.8T patent/LT3471780T/lt unknown
- 2017-06-16 DK DK17814223.8T patent/DK3471780T3/da active
- 2017-06-16 EP EP20196657.9A patent/EP3795181B1/en active Active
- 2017-06-16 CA CA3027737A patent/CA3027737A1/en active Pending
- 2017-06-16 PT PT178142238T patent/PT3471780T/pt unknown
- 2017-06-16 KR KR1020197001023A patent/KR102218265B1/ko active Active
- 2017-06-16 EP EP17814223.8A patent/EP3471780B1/en active Active
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2018
- 2018-12-12 US US16/218,353 patent/US20190151409A1/en not_active Abandoned
- 2018-12-13 IL IL263686A patent/IL263686B/en active IP Right Grant
- 2018-12-13 MX MX2022004786A patent/MX2022004786A/es unknown
- 2018-12-18 ZA ZA2018/08538A patent/ZA201808538B/en unknown
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2020
- 2020-09-16 JP JP2020155475A patent/JP2020203941A/ja not_active Withdrawn
- 2020-11-30 CY CY20201101133T patent/CY1123697T1/el unknown
-
2021
- 2021-09-01 AU AU2021225178A patent/AU2021225178B2/en active Active
- 2021-09-20 US US17/479,968 patent/US20220265740A1/en active Pending
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2022
- 2022-07-15 JP JP2022113865A patent/JP2022137244A/ja active Pending
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2024
- 2024-06-12 JP JP2024095160A patent/JP2024113193A/ja active Pending
-
2025
- 2025-04-28 AU AU2025202930A patent/AU2025202930A1/en active Pending
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