TWI837478B - 用於治療ｂｒａｆ相關的疾病和病症之化合物 - Google Patents
用於治療ｂｒａｆ相關的疾病和病症之化合物 Download PDFInfo
- Publication number
- TWI837478B TWI837478B TW110120375A TW110120375A TWI837478B TW I837478 B TWI837478 B TW I837478B TW 110120375 A TW110120375 A TW 110120375A TW 110120375 A TW110120375 A TW 110120375A TW I837478 B TWI837478 B TW I837478B
- Authority
- TW
- Taiwan
- Prior art keywords
- formula
- braf
- cancer
- subject
- pharmaceutically acceptable
- Prior art date
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Endocrinology (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063036522P | 2020-06-09 | 2020-06-09 | |
| US63/036,522 | 2020-06-09 | ||
| US202063116204P | 2020-11-20 | 2020-11-20 | |
| US63/116,204 | 2020-11-20 | ||
| US202163175655P | 2021-04-16 | 2021-04-16 | |
| US63/175,655 | 2021-04-16 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW202214577A TW202214577A (zh) | 2022-04-16 |
| TWI837478B true TWI837478B (zh) | 2024-04-01 |
Family
ID=76355554
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW110120375A TWI837478B (zh) | 2020-06-09 | 2021-06-04 | 用於治療ｂｒａｆ相關的疾病和病症之化合物 |
| TW112143784A TW202426436A (zh) | 2020-06-09 | 2021-06-04 | 用於治療ｂｒａｆ相關的疾病和病症之化合物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW112143784A TW202426436A (zh) | 2020-06-09 | 2021-06-04 | 用於治療ｂｒａｆ相關的疾病和病症之化合物 |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US12303509B2 (https=) |
| EP (1) | EP4161907A1 (https=) |
| JP (2) | JP7312335B2 (https=) |
| KR (1) | KR102904179B1 (https=) |
| CN (1) | CN116096710B (https=) |
| AU (1) | AU2021289163B2 (https=) |
| CL (1) | CL2022003326A1 (https=) |
| CO (1) | CO2022017876A2 (https=) |
| CR (1) | CR20220626A (https=) |
| DO (1) | DOP2022000282A (https=) |
| EC (1) | ECSP22093029A (https=) |
| IL (1) | IL298300B1 (https=) |
| MX (1) | MX2022015703A (https=) |
| PE (1) | PE20231651A1 (https=) |
| PY (1) | PY2146661A (https=) |
| TW (2) | TWI837478B (https=) |
| UA (1) | UA130198C2 (https=) |
| UY (1) | UY39261A (https=) |
| WO (1) | WO2021250521A1 (https=) |
| ZA (1) | ZA202212876B (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7667097B2 (ja) | 2019-06-14 | 2025-04-22 | ヤンセン ファーマシューティカ エヌ．ベー． | 置換ピラゾロ－ピリジンアミド及びｇｌｕｎ２ｂ受容体調節因子としてのその使用 |
| KR20220024403A (ko) | 2019-06-14 | 2022-03-03 | 얀센 파마슈티카 엔.브이. | 치환된 피라졸로-피라진 및 이들의 glun2b 수용체 조절제로서의 용도 |
| PL4073065T3 (pl) | 2019-12-10 | 2025-05-19 | F. Hoffmann-La Roche Ag | Nowe pochodne metylochinazolinonu |
| PH12022551118A1 (en) * | 2019-12-10 | 2023-09-18 | Hoffmann La Roche | New braf inhibitors as paradox breakers |
| WO2021250521A1 (en) * | 2020-06-09 | 2021-12-16 | Array Biopharma Inc. | 4-oxo-3,4-dihydroquinazolinon compounds for the treatment of braf-associated diseases and disorders |
| JP7834721B2 (ja) | 2020-08-28 | 2026-03-24 | アルビナス・オペレーションズ・インコーポレイテッド | 急速進行性線維肉腫タンパク質分解化合物及び関連する使用方法 |
| WO2022129259A1 (en) | 2020-12-18 | 2022-06-23 | F. Hoffmann-La Roche Ag | New quinazolinone derivatives |
| TWI825637B (zh) | 2021-03-31 | 2023-12-11 | 美商輝瑞股份有限公司 | 啶－１，６（２ｈ，７ｈ）－二酮 |
| WO2022261250A1 (en) | 2021-06-08 | 2022-12-15 | C4 Therapeutics, Inc. | Therapeutics for the degradation of mutant braf |
| EP4444710A1 (en) * | 2021-12-08 | 2024-10-16 | Array BioPharma Inc. | Crystalline form of n-(2-chloro-3-((5-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino)-4-fluorophenyl)-3-fluoroazetidine-1-sulfonamide |
| CA3255688A1 (en) * | 2022-03-17 | 2023-09-21 | St. Jude Children's Research Hospital | TREATMENT OF A LOW-QUALITY GILOMA WITH MIRDAMETIN B |
| WO2023183470A1 (en) * | 2022-03-24 | 2023-09-28 | Vibliome Therapeutics, Llc | Modulators of protein kinases |
| WO2023230554A1 (en) | 2022-05-25 | 2023-11-30 | Pfizer Inc. | Combination of a braf inhibitor, an egfr inhibitor, and a pd-1 antagonist for the treatment of braf v600e-mutant, msi-h/dmmr colorectal cancer |
| CN117304205A (zh) * | 2022-06-20 | 2023-12-29 | 中国科学院广州生物医药与健康研究院 | 一种苯并咪唑类三元并环化合物、其药学上可接受的盐及其应用 |
| EP4584258A1 (en) | 2022-09-07 | 2025-07-16 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use |
| CN120359214A (zh) * | 2022-12-15 | 2025-07-22 | 豪夫迈·罗氏有限公司 | 用于癌症治疗的组合疗法 |
| WO2024218632A1 (en) | 2023-04-17 | 2024-10-24 | Array Biopharma Inc. | Erk protein kinase inhibitors |
| WO2025014933A1 (en) * | 2023-07-10 | 2025-01-16 | Northwestern University | Targeting tim-3 in mapk-driven glioma |
| WO2025108405A1 (zh) * | 2023-11-22 | 2025-05-30 | 西藏海思科制药有限公司 | 作为激酶抑制剂的喹唑啉酮衍生物的制备及其用途 |
| WO2025176139A1 (zh) * | 2024-02-20 | 2025-08-28 | 海思科医药集团股份有限公司 | 一种喹唑啉酮衍生物的晶型及其制备方法和应用 |
| WO2026037755A1 (en) * | 2024-08-13 | 2026-02-19 | F. Hoffmann-La Roche Ag | New methylquinazolinone derivatives |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG2013013339A (en) | 2002-03-13 | 2014-12-30 | Array Biopharma Inc | N3 alkylated benzimidazole derivatives as mek inhibitors |
| US7144907B2 (en) | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| US7517994B2 (en) | 2003-11-19 | 2009-04-14 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| CA2546353A1 (en) | 2003-11-19 | 2005-06-09 | Array Biopharma Inc. | Bicyclic inhibitors of mek and methods of use thereof |
| US7732616B2 (en) | 2003-11-19 | 2010-06-08 | Array Biopharma Inc. | Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof |
| BRPI0514691A (pt) | 2004-08-31 | 2008-06-17 | Astrazeneca Ab | composto ou um sal farmaceuticamente aceitável do mesmo, processo para preparar o mesmo, composição farmacêutica, e, uso de um composto ou um sal farmaceuticamente aceitável do mesmo |
| SG177981A1 (en) | 2005-05-18 | 2012-02-28 | Array Biopharma Inc | 4-(phenylamino)-6-oxo-1, 6-dihydropyridazine-3-carboxamide derivatives as mek inhibitors for the treatment of hyperproliferative diseases |
| WO2007113557A1 (en) | 2006-04-05 | 2007-10-11 | Astrazeneca Ab | Substituted quinazolines with anti-cancer activity |
| CN101415688A (zh) | 2006-04-05 | 2009-04-22 | 阿斯利康(瑞典)有限公司 | 具有b-raf抑制活性的喹唑啉酮衍生物 |
| CN101421253A (zh) | 2006-04-18 | 2009-04-29 | 阿斯利康(瑞典)有限公司 | 喹唑啉-4-酮衍生物、其制备方法及含有它们的药用组合物 |
| PE20081581A1 (es) | 2006-12-21 | 2008-11-12 | Plexxikon Inc | COMPUESTOS PIRROLO[2,3-b]PIRIDINAS COMO MODULADORES DE QUINASA |
| JP2010533729A (ja) | 2007-07-17 | 2010-10-28 | プレキシコン，インコーポレーテッド | キナーゼ調節のための化合物と方法、及びそのための適応 |
| SI2324008T1 (sl) | 2008-07-24 | 2012-08-31 | Nerviano Medical Sciences Srl | 3,4-diarilpirazoli kot protein-kinazni inhibitorji |
| JO3002B1 (ar) | 2009-08-28 | 2016-09-05 | Irm Llc | مركبات و تركيبات كمثبطات كيناز بروتين |
| WO2012118492A1 (en) * | 2011-03-01 | 2012-09-07 | Array Biopharma Inc. | Heterocyclic sulfonamides as raf inhibitors |
| CN108542906A (zh) | 2011-11-11 | 2018-09-18 | 诺华股份有限公司 | 治疗增生性疾病的方法 |
| CA3008312A1 (en) | 2016-01-06 | 2017-07-13 | Trillium Therapeutics Inc. | Novel fluorinated quinazoline derivatives as egfr inhibitors |
| JP7219218B2 (ja) | 2016-12-22 | 2023-02-07 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規のベンジルアミノ置換キナゾリンおよびｓｏｓ１阻害剤としての誘導体 |
| EP3684772B1 (en) | 2017-09-20 | 2023-12-06 | ABM Therapeutics Corporation | Cyclic iminopyrimidine derivatives as kinase inhibitors |
| WO2019071351A1 (en) | 2017-10-12 | 2019-04-18 | Trillium Therapeutics Inc. | NOVEL 4-ARYLOXYQUINAZOLINE FLUORIN DERIVATIVES AS EGFR INHIBITORS USEFUL FOR THE TREATMENT OF CANCERS |
| RU2678455C1 (ru) | 2018-06-01 | 2019-01-29 | Сергей Викторович Леонов | Кристаллическая форма n-(3-(5-(4-хлорофенил)-1н-пиразоло[3,4-в]пиридин-3-карбонил)-2,4-дифторофенил) пропан-1-сульфонамида, активный компонент, фармацевтическая композиция и лекарственное средство |
| WO2020055992A1 (en) | 2018-09-11 | 2020-03-19 | NetraDyne, Inc. | Inward/outward vehicle monitoring for remote reporting and in-cab warning enhancements |
| TWI817018B (zh) | 2019-06-28 | 2023-10-01 | 美商艾瑞生藥股份有限公司 | 用於治療ｂｒａｆ相關的疾病和失調症之化合物 |
| PH12022551118A1 (en) * | 2019-12-10 | 2023-09-18 | Hoffmann La Roche | New braf inhibitors as paradox breakers |
| PL4073065T3 (pl) | 2019-12-10 | 2025-05-19 | F. Hoffmann-La Roche Ag | Nowe pochodne metylochinazolinonu |
| WO2021250521A1 (en) * | 2020-06-09 | 2021-12-16 | Array Biopharma Inc. | 4-oxo-3,4-dihydroquinazolinon compounds for the treatment of braf-associated diseases and disorders |
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2021
- 2021-06-04 WO PCT/IB2021/054919 patent/WO2021250521A1/en not_active Ceased
- 2021-06-04 JP JP2022575381A patent/JP7312335B2/ja active Active
- 2021-06-04 CR CR20220626A patent/CR20220626A/es unknown
- 2021-06-04 IL IL298300A patent/IL298300B1/en unknown
- 2021-06-04 TW TW110120375A patent/TWI837478B/zh active
- 2021-06-04 PE PE2022002894A patent/PE20231651A1/es unknown
- 2021-06-04 CN CN202180056068.XA patent/CN116096710B/zh active Active
- 2021-06-04 UA UAA202204519A patent/UA130198C2/uk unknown
- 2021-06-04 MX MX2022015703A patent/MX2022015703A/es unknown
- 2021-06-04 US US17/338,767 patent/US12303509B2/en active Active
- 2021-06-04 EP EP21731307.1A patent/EP4161907A1/en active Pending
- 2021-06-04 KR KR1020237000172A patent/KR102904179B1/ko active Active
- 2021-06-04 AU AU2021289163A patent/AU2021289163B2/en active Active
- 2021-06-04 TW TW112143784A patent/TW202426436A/zh unknown
- 2021-06-08 UY UY0001039261A patent/UY39261A/es unknown
- 2021-06-09 PY PY202102146661A patent/PY2146661A/es unknown
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2022
- 2022-11-25 CL CL2022003326A patent/CL2022003326A1/es unknown
- 2022-11-25 ZA ZA2022/12876A patent/ZA202212876B/en unknown
- 2022-12-07 EC ECSENADI202293029A patent/ECSP22093029A/es unknown
- 2022-12-08 DO DO2022000282A patent/DOP2022000282A/es unknown
- 2022-12-09 CO CONC2022/0017876A patent/CO2022017876A2/es unknown
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2023
- 2023-07-07 JP JP2023112365A patent/JP2023123854A/ja active Pending
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2025
- 2025-04-16 US US19/180,762 patent/US20250241915A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CL2022003326A1 (es) | 2023-02-24 |
| TW202214577A (zh) | 2022-04-16 |
| DOP2022000282A (es) | 2023-03-31 |
| IL298300B1 (en) | 2026-02-01 |
| US20220288074A1 (en) | 2022-09-15 |
| JP2023123854A (ja) | 2023-09-05 |
| PE20231651A1 (es) | 2023-10-17 |
| AU2021289163B2 (en) | 2024-05-02 |
| JP7312335B2 (ja) | 2023-07-20 |
| JP2023524910A (ja) | 2023-06-13 |
| NZ795045A (en) | 2025-05-30 |
| ECSP22093029A (es) | 2023-02-28 |
| PY2146661A (es) | 2022-10-20 |
| US12303509B2 (en) | 2025-05-20 |
| CN116096710A (zh) | 2023-05-09 |
| IL298300A (en) | 2023-01-01 |
| EP4161907A1 (en) | 2023-04-12 |
| MX2022015703A (es) | 2023-01-24 |
| CA3186343A1 (en) | 2021-12-16 |
| WO2021250521A1 (en) | 2021-12-16 |
| US20250241915A1 (en) | 2025-07-31 |
| ZA202212876B (en) | 2024-10-30 |
| CR20220626A (es) | 2023-01-23 |
| UY39261A (es) | 2022-01-31 |
| TW202426436A (zh) | 2024-07-01 |
| CN116096710B (zh) | 2025-07-25 |
| CO2022017876A2 (es) | 2022-12-20 |
| KR102904179B1 (ko) | 2025-12-26 |
| KR20230019944A (ko) | 2023-02-09 |
| BR112022024597A2 (pt) | 2022-12-27 |
| UA130198C2 (uk) | 2025-12-17 |
| AU2021289163A1 (en) | 2022-12-22 |
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