CA3022250A1 - Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride - Google Patents
Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochlorideInfo
- Publication number
- CA3022250A1 CA3022250A1 CA3022250A CA3022250A CA3022250A1 CA 3022250 A1 CA3022250 A1 CA 3022250A1 CA 3022250 A CA3022250 A CA 3022250A CA 3022250 A CA3022250 A CA 3022250A CA 3022250 A1 CA3022250 A1 CA 3022250A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- crystalline form
- imidazo
- methylpiperazin
- trifluoromethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
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- ZQBFAOFFOQMSGJ-UHFFFAOYSA-N hexafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1F ZQBFAOFFOQMSGJ-UHFFFAOYSA-N 0.000 description 10
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- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229960001346 nilotinib Drugs 0.000 description 1
- 150000002829 nitrogen Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000238 one-dimensional nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000011170 pharmaceutical development Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000006069 physical mixture Substances 0.000 description 1
- PJGSXYOJTGTZAV-UHFFFAOYSA-N pinacolone Chemical compound CC(=O)C(C)(C)C PJGSXYOJTGTZAV-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000011027 product recovery Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 150000003334 secondary amides Chemical class 0.000 description 1
- AQRYNYUOKMNDDV-UHFFFAOYSA-M silver behenate Chemical compound [Ag+].CCCCCCCCCCCCCCCCCCCCCC([O-])=O AQRYNYUOKMNDDV-UHFFFAOYSA-M 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 229940068117 sprycel Drugs 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000012496 stress study Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 229940069905 tasigna Drugs 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 238000001107 thermogravimetry coupled to mass spectrometry Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- 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
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA3167093A CA3167093A1 (en) | 2012-12-12 | 2013-05-09 | Crystalline form c of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261736543P | 2012-12-12 | 2012-12-12 | |
| US61/736,543 | 2012-12-12 | ||
| US201261737007P | 2012-12-13 | 2012-12-13 | |
| US61/737,007 | 2012-12-13 | ||
| US201361788208P | 2013-03-15 | 2013-03-15 | |
| US61/788,208 | 2013-03-15 | ||
| CA2815506A CA2815506C (en) | 2012-12-12 | 2013-05-09 | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2815506A Division CA2815506C (en) | 2012-12-12 | 2013-05-09 | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3167093A Division CA3167093A1 (en) | 2012-12-12 | 2013-05-09 | Crystalline form c of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3022250A1 true CA3022250A1 (en) | 2014-06-12 |
Family
ID=50929140
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3022250A Abandoned CA3022250A1 (en) | 2012-12-12 | 2013-05-09 | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
| CA3167093A Pending CA3167093A1 (en) | 2012-12-12 | 2013-05-09 | Crystalline form c of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
| CA2815506A Active CA2815506C (en) | 2012-12-12 | 2013-05-09 | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3167093A Pending CA3167093A1 (en) | 2012-12-12 | 2013-05-09 | Crystalline form c of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
| CA2815506A Active CA2815506C (en) | 2012-12-12 | 2013-05-09 | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
Country Status (9)
| Country | Link |
|---|---|
| US (9) | US9493470B2 (Direct) |
| JP (4) | JP6447508B2 (Direct) |
| CN (2) | CN115043843A (Direct) |
| CA (3) | CA3022250A1 (Direct) |
| CL (1) | CL2015001643A1 (Direct) |
| HK (1) | HK1218878A1 (Direct) |
| MX (11) | MX359147B (Direct) |
| NZ (1) | NZ709648A (Direct) |
| WO (2) | WO2014093579A2 (Direct) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
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| DK2495016T3 (da) | 2005-12-23 | 2019-12-16 | Ariad Pharma Inc | Bicykliske heteroarylforbindelser |
| TWI568722B (zh) | 2012-06-15 | 2017-02-01 | 葛蘭馬克製藥公司 | 作爲ｍＰＧＥＳ－１抑制劑之三唑酮化合物 |
| CA3022250A1 (en) | 2012-12-12 | 2014-06-12 | Ariad Pharmaceuticals, Inc. | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
| US9725454B2 (en) | 2013-07-04 | 2017-08-08 | Sandoz Ag | Crystalline forms of ponatinib hydrochloride |
| CN104496994B (zh) * | 2014-01-06 | 2016-12-07 | 广东东阳光药业有限公司 | 一种炔类杂芳基化合物的新晶型 |
| EA201991197A1 (ru) * | 2016-12-15 | 2020-01-13 | Ариад Фармасьютикалз, Инк. | БЕНЗИМИДАЗОЛЬНЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ c-Kit |
| US10221184B2 (en) | 2017-01-20 | 2019-03-05 | Apicore Us Llc | Polymorphs of ponatinib hydrochloride |
| CA3067271A1 (en) * | 2017-06-20 | 2018-12-27 | Apotex Inc. | Crystalline forms of ponatinib hydrochloride |
| CA3095869C (en) * | 2018-04-02 | 2025-10-21 | Stealth Biotherapeutics Inc. | CRYSTALLINE DIPEPTIDES USEFUL IN THE SYNTHESIS OF ELAMIPRETIDE |
| EP3781568A1 (en) | 2018-06-22 | 2021-02-24 | Johnson Matthey Public Limited Company | Form of ponatinib |
| IL282737B2 (en) | 2018-11-01 | 2025-05-01 | Syros Pharmaceuticals Inc | Cyclin-dependent kinase 7 (CDK7) inhibitors |
| WO2020223235A1 (en) | 2019-04-29 | 2020-11-05 | Incyte Corporation | Mini-tablet dosage forms of ponatinib |
| CN111004240B (zh) * | 2019-12-13 | 2020-12-01 | 山东铂源药业有限公司 | 一种泊那替尼中间体3-乙炔基咪唑并[1,2-b]哒嗪的合成方法 |
Family Cites Families (30)
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| US5099067A (en) | 1988-08-05 | 1992-03-24 | Northwestern University | Use of ammonium formate as a hydrogen transfer reagent for reduction of chiral nitro compounds with retention of configuration |
| JP4903963B2 (ja) * | 1999-11-08 | 2012-03-28 | シェーリング コーポレイション | Ｎ−（４−ヒドロキシ−フェニル）−ｎ’−（４’−アミノフェニル）−ピペラジンを調製するためのプロセス |
| HN2001000008A (es) | 2000-01-21 | 2003-12-11 | Inc Agouron Pharmaceuticals | Compuesto de amida y composiciones farmaceuticas para inhibir proteinquinasas, y su modo de empleo |
| DE10021246A1 (de) | 2000-04-25 | 2001-10-31 | Schering Ag | Substituierte Benzoesäureamide und deren Verwendung als Arzneimittel |
| IL159811A0 (en) | 2001-07-13 | 2004-06-20 | Neurogen Corp | Heteroaryl substituted fused bicyclic heteroaryl compounds as gabaa receptor ligands |
| AR041992A1 (es) | 2002-11-06 | 2005-06-08 | Smithkline Beecham Corp | Compuesto de piridinil benzoheterociclico, composicion farmaceutica que lo comprende y su uso para prepararla |
| GB0230089D0 (en) | 2002-12-24 | 2003-01-29 | Astrazeneca Ab | Therapeutic agents |
| KR20060110307A (ko) | 2003-11-28 | 2006-10-24 | 노파르티스 아게 | 단백질 키나아제 의존성 질환의 치료에서의 디아릴 우레아유도체 |
| AU2004296242A1 (en) * | 2003-12-05 | 2005-06-23 | Biovitrum Ab | Improved synthesis of 2-substituted adenosines |
| DE602004018193D1 (de) | 2003-12-24 | 2009-01-15 | Astrazeneca Ab | Pyrimidine mit tie2 (tek) aktivität |
| WO2005060969A1 (en) | 2003-12-24 | 2005-07-07 | Astrazeneca Ab | Pyrimidines with tie2 (tek) activity |
| BRPI0508790A (pt) | 2004-04-07 | 2007-09-04 | Applied Research Systems | ácido carboxìlicos, uso de um ácido carboxìlico, composto farmacêutico, método de preparação de ácido carboxìlico e composto intermediário |
| CA2573185A1 (en) | 2004-07-14 | 2006-02-23 | Ptc Therapeutics, Inc. | Methods for treating hepatitis c |
| US7776869B2 (en) | 2004-10-18 | 2010-08-17 | Amgen Inc. | Heteroaryl-substituted alkyne compounds and method of use |
| GB0502418D0 (en) | 2005-02-05 | 2005-03-16 | Astrazeneca Ab | Compounds |
| US20080194552A1 (en) | 2005-03-31 | 2008-08-14 | Astrazeneca Ab | Aminopyrimidine Derivatives With Tie2 Inhibiting Activity |
| JP2009502734A (ja) | 2005-07-29 | 2009-01-29 | アステラス製薬株式会社 | Ｌｃｋ阻害剤としての縮合複素環 |
| EP1940843A4 (en) | 2005-08-11 | 2010-09-15 | Ariad Pharma Inc | UNSATURATED HETEROCYCLIC DERIVATIVES |
| DK2495016T3 (da) | 2005-12-23 | 2019-12-16 | Ariad Pharma Inc | Bicykliske heteroarylforbindelser |
| CN101389338B (zh) * | 2005-12-23 | 2013-06-26 | 阿里亚德医药股份有限公司 | 双环杂芳基化合物 |
| US8278307B2 (en) | 2006-05-08 | 2012-10-02 | Ariad Pharmaceuticals, Inc. | Monocyclic Heteroaryl compounds |
| EA200870514A1 (ru) | 2006-05-08 | 2009-04-28 | Ариад Фармасьютикалз, Инк. | Ацетиленовые гетероарильные соединения |
| EP2107054A1 (en) | 2008-04-01 | 2009-10-07 | Università Degli Studi Di Milano - Bicocca | Antiproliferative compounds and therapeutic uses thereof |
| WO2010124047A1 (en) | 2009-04-23 | 2010-10-28 | Wyeth Llc | Bisaryl alkynylamides as negative allosteric modulators of metabotropic glutamate receptor 5 (mglur5) |
| US8329724B2 (en) * | 2009-08-03 | 2012-12-11 | Hoffmann-La Roche Inc. | Process for the manufacture of pharmaceutically active compounds |
| EP2762142A1 (en) * | 2009-10-30 | 2014-08-06 | ARIAD Pharmaceuticals, Inc. | Compositions for treating cancer |
| CN103582478A (zh) * | 2011-04-07 | 2014-02-12 | 阿里亚德医药股份有限公司 | 治疗神经退行性疾病的方法和组合物 |
| JP2014513078A (ja) | 2011-04-07 | 2014-05-29 | アリアド・ファーマシューティカルズ・インコーポレイテッド | パーキンソン病の治療方法及び治療用組成物 |
| JP2015514802A (ja) | 2012-04-25 | 2015-05-21 | アリアド・ファーマシューティカルズ・インコーポレイテッド | Ｒａｆキナーゼ媒介疾患用の方法及び組成物 |
| CA3022250A1 (en) | 2012-12-12 | 2014-06-12 | Ariad Pharmaceuticals, Inc. | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
-
2013
- 2013-05-09 CA CA3022250A patent/CA3022250A1/en not_active Abandoned
- 2013-05-09 CA CA3167093A patent/CA3167093A1/en active Pending
- 2013-05-09 CA CA2815506A patent/CA2815506C/en active Active
- 2013-12-12 NZ NZ709648A patent/NZ709648A/en unknown
- 2013-12-12 WO PCT/US2013/074571 patent/WO2014093579A2/en not_active Ceased
- 2013-12-12 HK HK16106954.3A patent/HK1218878A1/zh unknown
- 2013-12-12 CN CN202210369530.8A patent/CN115043843A/zh active Pending
- 2013-12-12 MX MX2015007578A patent/MX359147B/es active IP Right Grant
- 2013-12-12 WO PCT/US2013/074585 patent/WO2014093583A2/en not_active Ceased
- 2013-12-12 JP JP2015547524A patent/JP6447508B2/ja active Active
- 2013-12-12 US US14/651,577 patent/US9493470B2/en active Active
- 2013-12-12 MX MX2018010998A patent/MX391445B/es unknown
- 2013-12-12 CN CN201380072027.5A patent/CN105188701A/zh active Pending
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2015
- 2015-06-12 MX MX2021002264A patent/MX2021002264A/es unknown
- 2015-06-12 MX MX2021002256A patent/MX2021002256A/es unknown
- 2015-06-12 MX MX2021002255A patent/MX2021002255A/es unknown
- 2015-06-12 MX MX2021002254A patent/MX2021002254A/es unknown
- 2015-06-12 MX MX2021002257A patent/MX2021002257A/es unknown
- 2015-06-12 MX MX2021002261A patent/MX2021002261A/es unknown
- 2015-06-12 MX MX2021002253A patent/MX2021002253A/es unknown
- 2015-06-12 MX MX2021002259A patent/MX2021002259A/es unknown
- 2015-06-12 CL CL2015001643A patent/CL2015001643A1/es unknown
- 2015-06-12 MX MX2021002258A patent/MX2021002258A/es unknown
-
2016
- 2016-11-02 US US15/341,898 patent/US10125136B2/en active Active
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2018
- 2018-07-09 JP JP2018129624A patent/JP7042175B2/ja active Active
- 2018-09-28 US US16/146,143 patent/US10662197B2/en active Active
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2020
- 2020-05-22 US US16/881,790 patent/US11279705B2/en active Active
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2021
- 2021-05-12 US US17/318,876 patent/US11384086B2/en active Active
- 2021-05-12 US US17/318,677 patent/US11192895B2/en active Active
- 2021-05-12 US US17/318,772 patent/US11192896B2/en active Active
- 2021-05-12 US US17/318,832 patent/US11192897B2/en active Active
- 2021-12-15 JP JP2021203538A patent/JP7352841B2/ja active Active
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2023
- 2023-02-27 US US18/175,272 patent/US20240083902A1/en not_active Abandoned
- 2023-09-19 JP JP2023150905A patent/JP2023179498A/ja active Pending
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