IL252848B2 - Intravenous Genaxolone Formulations and Their Use in the Treatment of Epileptic Seizures and Other Seizure Disorders - Google Patents
Intravenous Genaxolone Formulations and Their Use in the Treatment of Epileptic Seizures and Other Seizure DisordersInfo
- Publication number
- IL252848B2 IL252848B2 IL252848A IL25284817A IL252848B2 IL 252848 B2 IL252848 B2 IL 252848B2 IL 252848 A IL252848 A IL 252848A IL 25284817 A IL25284817 A IL 25284817A IL 252848 B2 IL252848 B2 IL 252848B2
- Authority
- IL
- Israel
- Prior art keywords
- ganaxolone
- cyclodextrin
- formulation
- captisol
- sulfobutyl ether
- Prior art date
Links
Classifications
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
-
- 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
- A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- 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
- A61K9/08—Solutions
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562112943P | 2015-02-06 | 2015-02-06 | |
| PCT/US2016/016977 WO2016127170A1 (en) | 2015-02-06 | 2016-02-08 | Intravenous ganaxolone formulations and their use in treating status epilepticus and other seizure disorders |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| IL252848A0 IL252848A0 (en) | 2017-08-31 |
| IL252848B1 IL252848B1 (en) | 2024-03-01 |
| IL252848B2 true IL252848B2 (en) | 2024-07-01 |
Family
ID=56564813
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL252848A IL252848B2 (en) | 2015-02-06 | 2016-02-08 | Intravenous Genaxolone Formulations and Their Use in the Treatment of Epileptic Seizures and Other Seizure Disorders |
| IL302203A IL302203A (en) | 2015-02-06 | 2016-02-08 | Intravenous Genaxolone formulations and their use in the treatment of epileptic seizures and other convulsive disorders |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL302203A IL302203A (en) | 2015-02-06 | 2016-02-08 | Intravenous Genaxolone formulations and their use in the treatment of epileptic seizures and other convulsive disorders |
Country Status (8)
| Country | Link |
|---|---|
| US (4) | US20160228454A1 (enExample) |
| EP (2) | EP4059522A1 (enExample) |
| JP (4) | JP2018504420A (enExample) |
| CN (3) | CN115487313A (enExample) |
| AU (1) | AU2016214996B2 (enExample) |
| CA (2) | CA3254865A1 (enExample) |
| IL (2) | IL252848B2 (enExample) |
| WO (1) | WO2016127170A1 (enExample) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2862076C (en) | 2012-01-23 | 2020-04-21 | Sage Therapeutics, Inc. | Neuroactive steroid formulations and methods of treating cns disorders |
| PL2887944T3 (pl) | 2012-08-21 | 2022-02-21 | Sage Therapeutics, Inc. | Allopregnanolon do leczenia lekoopornego stanu padaczkowego |
| US9549909B2 (en) | 2013-05-03 | 2017-01-24 | The Katholieke Universiteit Leuven | Method for the treatment of dravet syndrome |
| JOP20200195A1 (ar) | 2014-09-08 | 2017-06-16 | Sage Therapeutics Inc | سترويدات وتركيبات نشطة عصبياً، واستخداماتها |
| CN115487313A (zh) * | 2015-02-06 | 2022-12-20 | 马瑞纳斯制药公司 | 静脉内加奈索酮制剂及其用途 |
| MA45276A (fr) * | 2015-06-18 | 2018-04-25 | Sage Therapeutics Inc | Solutions de stéroïdes neuroactifs et leurs méthodes d'utilisation |
| CA3001722A1 (en) | 2015-10-16 | 2017-04-20 | Marinus Pharmaceuticals, Inc. | Injectable neurosteroid formulations containing nanoparticles |
| JP2019507111A (ja) | 2015-12-22 | 2019-03-14 | ゾゲニクス インターナショナル リミテッド | 代謝抵抗性フェンフルラミン類縁体およびその使用法 |
| KR102688278B1 (ko) | 2015-12-22 | 2024-07-26 | 조게닉스 인터내셔널 리미티드 | 펜플루라민 조성물 및 그 제조 방법 |
| CN113616661A (zh) | 2016-03-08 | 2021-11-09 | 萨奇治疗股份有限公司 | 神经活性类固醇、其组合物及用途 |
| US20180042903A1 (en) | 2016-08-11 | 2018-02-15 | Ovid Therapeutics Inc. | Methods and compositions for treatment of epileptic disorders |
| CA3032996C (en) | 2016-08-24 | 2025-05-06 | Zogenix International Ltd | Formulation for inhibiting formation of 5-ht 2b agonists and methods of using same |
| US10391105B2 (en) | 2016-09-09 | 2019-08-27 | Marinus Pharmaceuticals Inc. | Methods of treating certain depressive disorders and delirium tremens |
| EP3525797A4 (en) * | 2016-10-14 | 2020-06-24 | Marinus Pharmaceuticals, Inc. | Method of administering a neurosteroid to effect electroencephalographic (eeg) burst suppression |
| CN110225754A (zh) * | 2016-11-22 | 2019-09-10 | 奥维德医疗公司 | 用氟吡汀治疗发育障碍和/或癫痫发作紊乱的方法 |
| US10682317B2 (en) | 2017-09-26 | 2020-06-16 | Zogenix International Limited | Ketogenic diet compatible fenfluramine formulation |
| WO2019094724A1 (en) * | 2017-11-10 | 2019-05-16 | Marinus Pharmaceuticals, Inc. | Ganaxolone for use in treating genetic epileptic disoders |
| CN108535398B (zh) * | 2018-04-04 | 2020-03-27 | 福州海王福药制药有限公司 | 一种采用反相高效液相色谱法分离盐酸噻加宾手性对映体的方法 |
| CA3097335A1 (en) | 2018-05-11 | 2019-11-14 | Zogenix International Limited | Compositions and methods for treating seizure-induced sudden death |
| WO2019241005A1 (en) | 2018-06-14 | 2019-12-19 | Zogenix International Limited | Compositions and methods for treating respiratory depression with fenfluramine |
| WO2020097045A1 (en) * | 2018-11-05 | 2020-05-14 | Ovid Therapeutics Inc. | Use of gaboxadol, ganaxolone and allopregnanolone to treat movement disorders |
| AU2019384963B2 (en) | 2018-11-19 | 2022-05-26 | Zogenix International Limited | Methods of treating Rett syndrome using fenfluramine |
| WO2020118142A1 (en) | 2018-12-07 | 2020-06-11 | Marinus Pharmaceuticals, Inc. | Ganaxolone for use in prophylaxis and treatment of pospartum depression |
| MX2021006317A (es) * | 2018-12-14 | 2021-08-11 | Eisai R&D Man Co Ltd | Formulaciones farmaceuticas de base acuosa de compuestos de 1,2-dihidropiridina. |
| WO2020157257A1 (en) * | 2019-02-01 | 2020-08-06 | H. Lundbeck A/S | Injectable carbamazepine composition essentially free of 10-br-carbamazepine |
| MX2021009777A (es) * | 2019-02-15 | 2021-12-15 | Saol Int Development Ltd | Formulaciones inyectables de fenol y metodos de su uso. |
| EP3930841A4 (en) * | 2019-02-25 | 2022-11-30 | Zogenix International Limited | A formulation for improving seizure control |
| US20200338090A1 (en) * | 2019-04-29 | 2020-10-29 | Marsh and Wang Medical Systems, LLC | Seizure control compositions and methods of using same |
| US20210260074A1 (en) * | 2019-04-29 | 2021-08-26 | Marsh and Wang Medical Systems, LLC | Seizure control compositions and methods of using same |
| SG11202112111WA (en) | 2019-05-10 | 2021-11-29 | Brii Biosciences Inc | Pharmaceutical composition containing brexanolone, ganaxolone, or zuranolone, and use thereof |
| CA3145923A1 (en) * | 2019-08-05 | 2021-02-11 | David Czekai | Ganaxolone for use in treatment of status epilepticus |
| IL293525A (en) | 2019-12-06 | 2022-08-01 | Marinus Pharmaceuticals Inc | Ganaxolone for use in the treatment of multiple sclerosis complex |
| US11612574B2 (en) | 2020-07-17 | 2023-03-28 | Zogenix International Limited | Method of treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) |
| WO2022109440A1 (en) * | 2020-11-23 | 2022-05-27 | Marinus Pharmaceuticals, Inc. | Ganaxolone for use in treatment of super refractory status epilepticus |
| EP4255438A4 (en) * | 2020-12-07 | 2024-10-16 | Marinus Pharmaceuticals, Inc. | USE OF GANAXOLONE IN THE TREATMENT OF AN EPILEPTIC DISORDER |
| WO2023060020A1 (en) * | 2021-10-04 | 2023-04-13 | Marinus Pharmaceuticals, Inc. | Ganaxolone for use in treatment of established status epilepticus |
| CN114272216B (zh) * | 2021-10-11 | 2023-07-04 | 浙江歌文达生物医药科技有限公司 | 一种2-氧代-1-吡咯烷衍生物的冻干制剂及其制备 |
| CN116769070B (zh) * | 2023-06-07 | 2025-07-01 | 浙江工业大学 | 一种功能化磁性纳米颗粒及作为手性萃取剂在液-液萃取拆分手性化合物中的应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011088503A1 (en) * | 2010-01-21 | 2011-07-28 | Goodchild Investments Pty Ltd | Anaesthetic formulation |
| US8022054B2 (en) * | 2005-11-28 | 2011-09-20 | Marinus Pharmaceuticals | Liquid ganaxolone formulations and methods for the making and use thereof |
| WO2014085668A1 (en) * | 2012-11-30 | 2014-06-05 | The Regents Of The University Of California | Anticonvulsant activity of steroids |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
| US5376645A (en) | 1990-01-23 | 1994-12-27 | University Of Kansas | Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof |
| PL2887944T3 (pl) * | 2012-08-21 | 2022-02-21 | Sage Therapeutics, Inc. | Allopregnanolon do leczenia lekoopornego stanu padaczkowego |
| JOP20200195A1 (ar) * | 2014-09-08 | 2017-06-16 | Sage Therapeutics Inc | سترويدات وتركيبات نشطة عصبياً، واستخداماتها |
| CN115487313A (zh) * | 2015-02-06 | 2022-12-20 | 马瑞纳斯制药公司 | 静脉内加奈索酮制剂及其用途 |
| US10391105B2 (en) * | 2016-09-09 | 2019-08-27 | Marinus Pharmaceuticals Inc. | Methods of treating certain depressive disorders and delirium tremens |
-
2016
- 2016-02-08 CN CN202211152228.3A patent/CN115487313A/zh active Pending
- 2016-02-08 EP EP22152108.1A patent/EP4059522A1/en active Pending
- 2016-02-08 AU AU2016214996A patent/AU2016214996B2/en active Active
- 2016-02-08 CA CA3254865A patent/CA3254865A1/en active Pending
- 2016-02-08 EP EP16706109.2A patent/EP3253418A1/en not_active Withdrawn
- 2016-02-08 CN CN202211150855.3A patent/CN115381772A/zh active Pending
- 2016-02-08 JP JP2017540743A patent/JP2018504420A/ja active Pending
- 2016-02-08 WO PCT/US2016/016977 patent/WO2016127170A1/en not_active Ceased
- 2016-02-08 US US15/018,258 patent/US20160228454A1/en not_active Abandoned
- 2016-02-08 CN CN201680008938.5A patent/CN107427458A/zh active Pending
- 2016-02-08 IL IL252848A patent/IL252848B2/en unknown
- 2016-02-08 CA CA2973140A patent/CA2973140C/en active Active
- 2016-02-08 IL IL302203A patent/IL302203A/en unknown
-
2021
- 2021-07-02 JP JP2021110619A patent/JP7273897B2/ja active Active
-
2023
- 2023-03-17 JP JP2023042531A patent/JP7566961B2/ja active Active
- 2023-03-28 US US18/191,445 patent/US20230293549A1/en not_active Abandoned
- 2023-09-21 US US18/472,048 patent/US20240016817A1/en not_active Abandoned
-
2024
- 2024-10-02 JP JP2024173821A patent/JP2024178469A/ja not_active Withdrawn
- 2024-12-20 US US18/989,280 patent/US20250325562A1/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8022054B2 (en) * | 2005-11-28 | 2011-09-20 | Marinus Pharmaceuticals | Liquid ganaxolone formulations and methods for the making and use thereof |
| WO2011088503A1 (en) * | 2010-01-21 | 2011-07-28 | Goodchild Investments Pty Ltd | Anaesthetic formulation |
| WO2014085668A1 (en) * | 2012-11-30 | 2014-06-05 | The Regents Of The University Of California | Anticonvulsant activity of steroids |
Also Published As
| Publication number | Publication date |
|---|---|
| JP7566961B2 (ja) | 2024-10-15 |
| IL252848A0 (en) | 2017-08-31 |
| CN115381772A (zh) | 2022-11-25 |
| CA2973140C (en) | 2025-09-16 |
| CN107427458A (zh) | 2017-12-01 |
| AU2016214996A1 (en) | 2017-06-29 |
| IL252848B1 (en) | 2024-03-01 |
| US20240016817A1 (en) | 2024-01-18 |
| EP4059522A1 (en) | 2022-09-21 |
| CA2973140A1 (en) | 2016-08-11 |
| EP3253418A1 (en) | 2017-12-13 |
| AU2016214996B2 (en) | 2021-03-04 |
| CN115487313A (zh) | 2022-12-20 |
| JP2024178469A (ja) | 2024-12-24 |
| JP2018504420A (ja) | 2018-02-15 |
| JP2021155457A (ja) | 2021-10-07 |
| WO2016127170A1 (en) | 2016-08-11 |
| JP2023078301A (ja) | 2023-06-06 |
| IL302203A (en) | 2023-06-01 |
| US20160228454A1 (en) | 2016-08-11 |
| JP7273897B2 (ja) | 2023-05-15 |
| US20230293549A1 (en) | 2023-09-21 |
| CA3254865A1 (en) | 2025-05-28 |
| US20250325562A1 (en) | 2025-10-23 |
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