JP2014097929A5 - - Google Patents
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- Publication number
- JP2014097929A5 JP2014097929A5 JP2012217359A JP2012217359A JP2014097929A5 JP 2014097929 A5 JP2014097929 A5 JP 2014097929A5 JP 2012217359 A JP2012217359 A JP 2012217359A JP 2012217359 A JP2012217359 A JP 2012217359A JP 2014097929 A5 JP2014097929 A5 JP 2014097929A5
- Authority
- JP
- Japan
- Prior art keywords
- cancer
- flt3
- administered
- patient
- crenolanib
- 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.)
- Granted
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 26
- 230000002062 proliferating effect Effects 0.000 claims 25
- 201000010099 disease Diseases 0.000 claims 22
- DYNHJHQFHQTFTP-UHFFFAOYSA-N crenolanib Chemical compound C=1C=C2N(C=3N=C4C(N5CCC(N)CC5)=CC=CC4=CC=3)C=NC2=CC=1OCC1(C)COC1 DYNHJHQFHQTFTP-UHFFFAOYSA-N 0.000 claims 17
- 229950009240 crenolanib Drugs 0.000 claims 17
- 150000001875 compounds Chemical class 0.000 claims 14
- 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 claims 12
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 claims 11
- 150000003839 salts Chemical class 0.000 claims 10
- 239000003795 chemical substances by application Substances 0.000 claims 7
- 230000002074 deregulated effect Effects 0.000 claims 7
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 claims 6
- 208000032839 leukemia Diseases 0.000 claims 6
- 108091008598 receptor tyrosine kinases Proteins 0.000 claims 5
- 102000027426 receptor tyrosine kinases Human genes 0.000 claims 5
- 206010048643 Hypereosinophilic syndrome Diseases 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 230000000694 effects Effects 0.000 claims 4
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims 4
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 claims 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 3
- 206010005003 Bladder cancer Diseases 0.000 claims 3
- 206010006187 Breast cancer Diseases 0.000 claims 3
- 208000026310 Breast neoplasm Diseases 0.000 claims 3
- 206010008342 Cervix carcinoma Diseases 0.000 claims 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 3
- 206010009944 Colon cancer Diseases 0.000 claims 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 3
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 3
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims 3
- 208000014767 Myeloproliferative disease Diseases 0.000 claims 3
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 claims 3
- 206010061306 Nasopharyngeal cancer Diseases 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 3
- 206010033128 Ovarian cancer Diseases 0.000 claims 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 3
- 206010060862 Prostate cancer Diseases 0.000 claims 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 3
- 206010038389 Renal cancer Diseases 0.000 claims 3
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 claims 3
- 206010061934 Salivary gland cancer Diseases 0.000 claims 3
- 208000000453 Skin Neoplasms Diseases 0.000 claims 3
- 206010041067 Small cell lung cancer Diseases 0.000 claims 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 3
- 208000024313 Testicular Neoplasms Diseases 0.000 claims 3
- 206010057644 Testis cancer Diseases 0.000 claims 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 3
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 3
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims 3
- 201000007455 central nervous system cancer Diseases 0.000 claims 3
- 201000010881 cervical cancer Diseases 0.000 claims 3
- 238000002512 chemotherapy Methods 0.000 claims 3
- 208000029742 colonic neoplasm Diseases 0.000 claims 3
- 230000003831 deregulation Effects 0.000 claims 3
- 201000004101 esophageal cancer Diseases 0.000 claims 3
- 206010017758 gastric cancer Diseases 0.000 claims 3
- 201000010536 head and neck cancer Diseases 0.000 claims 3
- 208000014829 head and neck neoplasm Diseases 0.000 claims 3
- 201000010982 kidney cancer Diseases 0.000 claims 3
- 201000007270 liver cancer Diseases 0.000 claims 3
- 208000014018 liver neoplasm Diseases 0.000 claims 3
- 201000005202 lung cancer Diseases 0.000 claims 3
- 208000020816 lung neoplasm Diseases 0.000 claims 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 3
- 201000000050 myeloid neoplasm Diseases 0.000 claims 3
- 201000002120 neuroendocrine carcinoma Diseases 0.000 claims 3
- 201000002528 pancreatic cancer Diseases 0.000 claims 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 3
- 239000013610 patient sample Substances 0.000 claims 3
- 238000001959 radiotherapy Methods 0.000 claims 3
- 102220198339 rs1057520026 Human genes 0.000 claims 3
- 102200039430 rs121913488 Human genes 0.000 claims 3
- 102200039431 rs121913488 Human genes 0.000 claims 3
- 239000000523 sample Substances 0.000 claims 3
- 201000000849 skin cancer Diseases 0.000 claims 3
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 3
- 201000011549 stomach cancer Diseases 0.000 claims 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 3
- 238000001356 surgical procedure Methods 0.000 claims 3
- 201000003120 testicular cancer Diseases 0.000 claims 3
- 230000001225 therapeutic effect Effects 0.000 claims 3
- 201000002510 thyroid cancer Diseases 0.000 claims 3
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims 3
- 206010046766 uterine cancer Diseases 0.000 claims 3
- WRFPVMFCRNYQNR-UHFFFAOYSA-N 2-hydroxyphenylalanine Chemical compound OC(=O)C(N)CC1=CC=CC=C1O WRFPVMFCRNYQNR-UHFFFAOYSA-N 0.000 claims 2
- 206010014950 Eosinophilia Diseases 0.000 claims 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims 2
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 claims 2
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 238000009093 first-line therapy Methods 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- 230000009885 systemic effect Effects 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 238000001647 drug administration Methods 0.000 claims 1
- 201000005787 hematologic cancer Diseases 0.000 claims 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims 1
- 208000024364 idiopathic hypereosinophilic syndrome Diseases 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 239000008177 pharmaceutical agent Substances 0.000 claims 1
- 230000001766 physiological effect Effects 0.000 claims 1
- 230000000069 prophylactic effect Effects 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261704053P | 2012-09-21 | 2012-09-21 | |
| US61/704,053 | 2012-09-21 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017031277A Division JP6542277B2 (ja) | 2012-09-21 | 2017-02-22 | 恒常的に活性であるリン酸化型ｆｌｔ３キナーゼの阻害方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014097929A JP2014097929A (ja) | 2014-05-29 |
| JP2014097929A5 true JP2014097929A5 (enExample) | 2015-11-12 |
| JP6407504B2 JP6407504B2 (ja) | 2018-10-17 |
Family
ID=50295126
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012217359A Active JP6407504B2 (ja) | 2012-09-21 | 2012-09-28 | 恒常的に活性であるリン酸化型ｆｌｔ３キナーゼの阻害方法 |
| JP2017031277A Active JP6542277B2 (ja) | 2012-09-21 | 2017-02-22 | 恒常的に活性であるリン酸化型ｆｌｔ３キナーゼの阻害方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017031277A Active JP6542277B2 (ja) | 2012-09-21 | 2017-02-22 | 恒常的に活性であるリン酸化型ｆｌｔ３キナーゼの阻害方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (5) | US9023880B2 (enExample) |
| JP (2) | JP6407504B2 (enExample) |
| KR (2) | KR101738063B1 (enExample) |
| CN (1) | CN103655564B (enExample) |
| AU (1) | AU2013204935B2 (enExample) |
| CA (1) | CA2812245C (enExample) |
| MX (1) | MX365094B (enExample) |
| TW (1) | TWI569799B (enExample) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2861066C (en) | 2012-01-12 | 2024-01-02 | Yale University | Compounds and methods for the enhanced degradation of targeted proteins and other polypeptides by an e3 ubiquitin ligase |
| TWI569799B (zh) * | 2012-09-21 | 2017-02-11 | 安羅格製藥股份有限公司 | 抑制組成型活性磷酸化ｆｌｔ３激酶的方法 |
| US10835525B2 (en) | 2012-09-26 | 2020-11-17 | Arog Pharmaceuticals, Inc. | Method of inhibiting mutant C-KIT |
| US11642340B2 (en) | 2012-09-26 | 2023-05-09 | Arog Pharmaceuticals, Inc. | Method of inhibiting mutant C-KIT |
| JP6042157B2 (ja) | 2012-09-26 | 2016-12-14 | アログ・ファーマシューティカルズ・リミテッド・ライアビリティ・カンパニーＡｒｏｇ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，ＬＬＣ | 変異型ｃ−ｋｉｔの阻害方法 |
| BR112015016282A2 (en) | 2013-01-07 | 2017-07-11 | Arog Pharmaceuticals, Inc. | crenolanib for treatment of mutated flt3 proliferative disorders |
| GB201311888D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| HK1249058A1 (zh) | 2015-03-18 | 2018-10-26 | Arvinas, Inc. | 用於增强靶向蛋白质降解的化合物和方法 |
| US12534764B2 (en) | 2016-11-02 | 2026-01-27 | Arog Pharmaceuticals, Inc. | Crenolanib for treating FLT3 mutated proliferative disorders associated mutations |
| AU2017382436C1 (en) | 2016-12-23 | 2021-05-27 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of Rapidly Accelerated Fibrosarcoma polypeptides |
| US10806737B2 (en) | 2016-12-23 | 2020-10-20 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of fetal liver kinase polypeptides |
| US11173211B2 (en) | 2016-12-23 | 2021-11-16 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides |
| US10994015B2 (en) | 2016-12-23 | 2021-05-04 | Arvinas Operations, Inc. | EGFR proteolysis targeting chimeric molecules and associated methods of use |
| KR102747905B1 (ko) | 2017-01-31 | 2024-12-31 | 아비나스 오퍼레이션스, 인코포레이티드 | 세레블론 리간드 및 이를 포함하는 이작용성 화합물 |
| EP3743066A4 (en) | 2018-01-26 | 2021-09-08 | Yale University | IMIDE-BASED PROTEOLYSIS MODULATORS AND RELATED METHODS OF USE |
| CN110840893A (zh) * | 2018-12-13 | 2020-02-28 | 安罗格制药有限责任公司 | 含克莱拉尼的药物组合物及其用途 |
| CN115175901B (zh) | 2019-12-19 | 2024-03-22 | 阿尔维纳斯运营股份有限公司 | 用于雄激素受体的靶向降解的化合物和方法 |
| EP4181923A4 (en) * | 2020-07-20 | 2024-08-07 | Arog Pharmaceuticals, Inc. | Crystal forms of crenolanib and methods of use thereof |
| WO2022019998A1 (en) | 2020-07-20 | 2022-01-27 | Arog Pharmaceuticals, Inc. | Crystal forms of crenolanib and methods of use thereof |
| JP2023539663A (ja) | 2020-08-28 | 2023-09-15 | 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 |
| US20220079934A1 (en) * | 2020-09-17 | 2022-03-17 | Arog Pharmaceuticals, Inc. | Crenolanib for treating pain |
| WO2022090547A1 (en) | 2020-10-30 | 2022-05-05 | Dsm Ip Assets B.V. | Production of carotenoids by fermentation |
| US11969420B2 (en) | 2020-10-30 | 2024-04-30 | Arog Pharmaceuticals, Inc. | Combination therapy of crenolanib and apoptosis pathway agents for the treatment of proliferative disorders |
| CN113683594B (zh) * | 2021-09-07 | 2022-12-27 | 曲靖师范学院 | 一种喹啉-苯并咪唑盐类化合物及其合成方法和应用 |
| US11957759B1 (en) | 2022-09-07 | 2024-04-16 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5990146A (en) | 1997-08-20 | 1999-11-23 | Warner-Lambert Company | Benzimidazoles for inhibiting protein tyrosine kinase mediated cellular proliferation |
| WO1999016755A1 (en) | 1997-09-26 | 1999-04-08 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| UA75055C2 (uk) | 1999-11-30 | 2006-03-15 | Пфайзер Продактс Інк. | Похідні бензоімідазолу, що використовуються як антипроліферативний засіб, фармацевтична композиція на їх основі |
| CA2424689A1 (en) | 2000-10-17 | 2002-04-25 | Merck & Co., Inc. | Orally active salts with tyrosine kinase activity |
| AR035885A1 (es) | 2001-05-14 | 2004-07-21 | Novartis Ag | Derivados de 4-amino-5-fenil-7-ciclobutilpirrolo (2,3-d)pirimidina, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos derivados para la preparacion de una composicion farmaceutica |
| WO2003024931A1 (en) | 2001-09-14 | 2003-03-27 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US7101884B2 (en) | 2001-09-14 | 2006-09-05 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| TWI259081B (en) | 2001-10-26 | 2006-08-01 | Sugen Inc | Treatment of acute myeloid leukemia with indolinone compounds |
| ES2269793T3 (es) | 2001-10-30 | 2007-04-01 | Novartis Ag | Derivados de estaurospina como inhibidores de la actividad de tirosina quinasa receptora flt3. |
| RU2316554C2 (ru) | 2001-12-27 | 2008-02-10 | Тереванс, Инк. | Производные индолина, используемые как ингибиторы протеинкиназы |
| TW200406374A (en) | 2002-05-29 | 2004-05-01 | Novartis Ag | Diaryl urea derivatives useful for the treatment of protein kinase dependent diseases |
| MY141867A (en) | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
| GB0215676D0 (en) | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| US7304071B2 (en) | 2002-08-14 | 2007-12-04 | Vertex Pharmaceuticals Incorporated | Protein kinase inhibitors and uses thereof |
| WO2004018419A2 (en) | 2002-08-23 | 2004-03-04 | Chiron Corporation | Benzimidazole quinolinones and uses thereof |
| PA8580301A1 (es) | 2002-08-28 | 2005-05-24 | Pfizer Prod Inc | Nuevos derivados de benzoimidazol utiles como agentes antiproliferativos |
| AU2003280599A1 (en) | 2002-10-29 | 2004-05-25 | Kirin Beer Kabushiki Kaisha | QUINOLINE DERIVATIVES AND QUINAZOLINE DERIVATIVES INHIBITING AUTOPHOSPHORYLATION OF Flt3 AND MEDICINAL COMPOSITIONS CONTAINING THE SAME |
| WO2004043389A2 (en) | 2002-11-13 | 2004-05-27 | Chiron Corporation | Methods of treating cancer and related methods |
| TWI335913B (en) | 2002-11-15 | 2011-01-11 | Vertex Pharma | Diaminotriazoles useful as inhibitors of protein kinases |
| AU2003297160A1 (en) | 2002-12-18 | 2004-07-22 | Vertex Pharmaceuticals Incorporated | Benzisoxazole derivatives useful as inhibitors of protein kinases |
| JP2007516168A (ja) | 2003-06-24 | 2007-06-21 | ファイザー・プロダクツ・インク | １−［２−（ベンゾイミダゾル−１−イル）キノリン−８−イル］−ピペリジン−４−イルアミン誘導体の製造方法 |
| BRPI0516453A (pt) * | 2004-10-07 | 2008-09-02 | Pfizer Prod Inc | derivados de benzoimidazol úteis como agentes antiproliferativos |
| JP2013505230A (ja) * | 2009-09-17 | 2013-02-14 | ラモット・アット・テル・アビブ・ユニバーシテイ・リミテッド | 酸化ストレス関連障害を処置するためのペプチド |
| WO2012052757A1 (en) * | 2010-10-20 | 2012-04-26 | Astrazeneca Ab | Tumour phenotype patient selection method |
| US9133162B2 (en) | 2011-02-28 | 2015-09-15 | Sunshine Lake Pharma Co., Ltd. | Substituted quinoline compounds and methods of use |
| TWI569799B (zh) | 2012-09-21 | 2017-02-11 | 安羅格製藥股份有限公司 | 抑制組成型活性磷酸化ｆｌｔ３激酶的方法 |
| JP6042157B2 (ja) | 2012-09-26 | 2016-12-14 | アログ・ファーマシューティカルズ・リミテッド・ライアビリティ・カンパニーＡｒｏｇ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，ＬＬＣ | 変異型ｃ−ｋｉｔの阻害方法 |
| BR112015016282A2 (en) | 2013-01-07 | 2017-07-11 | Arog Pharmaceuticals, Inc. | crenolanib for treatment of mutated flt3 proliferative disorders |
| US11969420B2 (en) * | 2020-10-30 | 2024-04-30 | Arog Pharmaceuticals, Inc. | Combination therapy of crenolanib and apoptosis pathway agents for the treatment of proliferative disorders |
-
2012
- 2012-09-28 TW TW101135890A patent/TWI569799B/zh active
- 2012-09-28 JP JP2012217359A patent/JP6407504B2/ja active Active
- 2012-09-28 KR KR1020120109033A patent/KR101738063B1/ko active Active
- 2012-09-29 CN CN201210378283.4A patent/CN103655564B/zh active Active
-
2013
- 2013-04-10 CA CA2812245A patent/CA2812245C/en active Active
- 2013-04-12 AU AU2013204935A patent/AU2013204935B2/en active Active
- 2013-09-13 US US14/026,778 patent/US9023880B2/en active Active
- 2013-09-20 MX MX2013010839A patent/MX365094B/es active IP Right Grant
-
2015
- 2015-03-27 US US14/671,613 patent/US9801869B2/en active Active
-
2017
- 2017-02-22 JP JP2017031277A patent/JP6542277B2/ja active Active
- 2017-05-15 KR KR1020170059888A patent/KR20170056495A/ko not_active Ceased
- 2017-09-26 US US15/715,219 patent/US10780086B2/en active Active
-
2020
- 2020-08-19 US US16/997,000 patent/US11738017B2/en active Active
-
2023
- 2023-06-27 US US18/342,157 patent/US20230338360A1/en not_active Abandoned
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