JP2019525948A5 - - Google Patents
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- Publication number
- JP2019525948A5 JP2019525948A5 JP2019515782A JP2019515782A JP2019525948A5 JP 2019525948 A5 JP2019525948 A5 JP 2019525948A5 JP 2019515782 A JP2019515782 A JP 2019515782A JP 2019515782 A JP2019515782 A JP 2019515782A JP 2019525948 A5 JP2019525948 A5 JP 2019525948A5
- Authority
- JP
- Japan
- Prior art keywords
- compound
- therapeutically effective
- fluoro
- composition
- methyl
- 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
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- ACWZRVQXLIRSDF-UHFFFAOYSA-N binimetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1F ACWZRVQXLIRSDF-UHFFFAOYSA-N 0.000 claims description 73
- 150000001875 compounds Chemical class 0.000 claims description 57
- 229940126062 Compound A Drugs 0.000 claims description 44
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 44
- 206010009944 Colon cancer Diseases 0.000 claims description 30
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 30
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 27
- 229960005395 cetuximab Drugs 0.000 claims description 26
- 238000009101 premedication Methods 0.000 claims description 18
- 230000009885 systemic effect Effects 0.000 claims description 18
- 230000035772 mutation Effects 0.000 claims description 16
- 238000001990 intravenous administration Methods 0.000 claims description 14
- 238000001802 infusion Methods 0.000 claims description 13
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 12
- 229940127089 cytotoxic agent Drugs 0.000 claims description 12
- 239000002254 cytotoxic agent Substances 0.000 claims description 12
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 12
- 102200055464 rs113488022 Human genes 0.000 claims description 10
- CMJCXYNUCSMDBY-ZDUSSCGKSA-N lgx818 Chemical compound COC(=O)N[C@@H](C)CNC1=NC=CC(C=2C(=NN(C=2)C(C)C)C=2C(=C(NS(C)(=O)=O)C=C(Cl)C=2)F)=N1 CMJCXYNUCSMDBY-ZDUSSCGKSA-N 0.000 claims description 9
- 206010052358 Colorectal cancer metastatic Diseases 0.000 claims description 7
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 claims description 6
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 6
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 6
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 6
- MPJKWIXIYCLVCU-UHFFFAOYSA-N Folinic acid Natural products NC1=NC2=C(N(C=O)C(CNc3ccc(cc3)C(=O)NC(CCC(=O)O)CC(=O)O)CN2)C(=O)N1 MPJKWIXIYCLVCU-UHFFFAOYSA-N 0.000 claims description 6
- 238000011394 anticancer treatment Methods 0.000 claims description 6
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 229960004117 capecitabine Drugs 0.000 claims description 6
- 239000003246 corticosteroid Substances 0.000 claims description 6
- 229960002949 fluorouracil Drugs 0.000 claims description 6
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 claims description 6
- 235000008191 folinic acid Nutrition 0.000 claims description 6
- 239000011672 folinic acid Substances 0.000 claims description 6
- 229960004768 irinotecan Drugs 0.000 claims description 6
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 6
- 229960001691 leucovorin Drugs 0.000 claims description 6
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 6
- 229960001756 oxaliplatin Drugs 0.000 claims description 6
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 229960001334 corticosteroids Drugs 0.000 claims 1
- 239000000938 histamine H1 antagonist Substances 0.000 claims 1
- 238000000034 method Methods 0.000 description 178
- 206010028980 Neoplasm Diseases 0.000 description 66
- 238000000634 powder X-ray diffraction Methods 0.000 description 48
- 201000011510 cancer Diseases 0.000 description 46
- 238000002648 combination therapy Methods 0.000 description 43
- 229940124647 MEK inhibitor Drugs 0.000 description 21
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 21
- 230000004614 tumor growth Effects 0.000 description 16
- 229940125431 BRAF inhibitor Drugs 0.000 description 15
- 230000005764 inhibitory process Effects 0.000 description 15
- 208000011581 secondary neoplasm Diseases 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 230000004083 survival effect Effects 0.000 description 12
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 description 11
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 description 11
- 230000003111 delayed effect Effects 0.000 description 10
- 229950003054 binimetinib Drugs 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 7
- 230000002062 proliferating effect Effects 0.000 description 7
- 206010061818 Disease progression Diseases 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 230000005750 disease progression Effects 0.000 description 5
- 229950001969 encorafenib Drugs 0.000 description 5
- 230000009291 secondary effect Effects 0.000 description 5
- 230000003248 secreting effect Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 206010014733 Endometrial cancer Diseases 0.000 description 4
- 206010014759 Endometrial neoplasm Diseases 0.000 description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 4
- 208000009905 Neurofibromatoses Diseases 0.000 description 4
- 206010033701 Papillary thyroid cancer Diseases 0.000 description 4
- 206010038389 Renal cancer Diseases 0.000 description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 description 4
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 4
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 4
- 201000010982 kidney cancer Diseases 0.000 description 4
- 201000007270 liver cancer Diseases 0.000 description 4
- 208000014018 liver neoplasm Diseases 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 201000001441 melanoma Diseases 0.000 description 4
- 201000004931 neurofibromatosis Diseases 0.000 description 4
- 210000000496 pancreas Anatomy 0.000 description 4
- 201000002510 thyroid cancer Diseases 0.000 description 4
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 4
- KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 3
- 101100381978 Mus musculus Braf gene Proteins 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- 108010091528 Proto-Oncogene Proteins B-raf Proteins 0.000 description 2
- 102000018471 Proto-Oncogene Proteins B-raf Human genes 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 240000006063 Averrhoa carambola Species 0.000 description 1
- 235000010082 Averrhoa carambola Nutrition 0.000 description 1
- 244000183685 Citrus aurantium Species 0.000 description 1
- 235000007716 Citrus aurantium Nutrition 0.000 description 1
- 235000005976 Citrus sinensis Nutrition 0.000 description 1
- 240000000560 Citrus x paradisi Species 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 244000294611 Punica granatum Species 0.000 description 1
- 235000014360 Punica granatum Nutrition 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000007481 next generation sequencing Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662345389P | 2016-06-03 | 2016-06-03 | |
| US62/345,389 | 2016-06-03 | ||
| PCT/US2017/035653 WO2017210538A1 (en) | 2016-06-03 | 2017-06-02 | Pharmaceutical combinations |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020201152A Division JP2021054832A (ja) | 2016-06-03 | 2020-12-03 | 薬学的組み合わせ |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019525948A JP2019525948A (ja) | 2019-09-12 |
| JP2019525948A5 true JP2019525948A5 (enExample) | 2020-05-28 |
| JP6805336B2 JP6805336B2 (ja) | 2020-12-23 |
Family
ID=60477982
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019515782A Active JP6805336B2 (ja) | 2016-06-03 | 2017-06-02 | 薬学的組み合わせ |
| JP2020201152A Pending JP2021054832A (ja) | 2016-06-03 | 2020-12-03 | 薬学的組み合わせ |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020201152A Pending JP2021054832A (ja) | 2016-06-03 | 2020-12-03 | 薬学的組み合わせ |
Country Status (26)
| Country | Link |
|---|---|
| US (3) | US10485788B2 (enExample) |
| EP (1) | EP3463345B1 (enExample) |
| JP (2) | JP6805336B2 (enExample) |
| KR (1) | KR102439911B1 (enExample) |
| CN (1) | CN109890386B (enExample) |
| AU (1) | AU2017275650B2 (enExample) |
| BR (1) | BR112018074941A2 (enExample) |
| CA (1) | CA3026361A1 (enExample) |
| CL (1) | CL2018003421A1 (enExample) |
| CO (1) | CO2019000010A2 (enExample) |
| CR (1) | CR20190002A (enExample) |
| DK (1) | DK3463345T3 (enExample) |
| FI (1) | FI3463345T3 (enExample) |
| HU (1) | HUE060653T2 (enExample) |
| IL (1) | IL263431A (enExample) |
| MA (1) | MA45187A (enExample) |
| MX (1) | MX387795B (enExample) |
| PH (1) | PH12018502549A1 (enExample) |
| PL (1) | PL3463345T3 (enExample) |
| PT (1) | PT3463345T (enExample) |
| RU (1) | RU2759669C2 (enExample) |
| SG (1) | SG11201810793XA (enExample) |
| SI (1) | SI3463345T1 (enExample) |
| UA (1) | UA125436C2 (enExample) |
| WO (1) | WO2017210538A1 (enExample) |
| ZA (1) | ZA201900019B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112018074941A2 (pt) | 2016-06-03 | 2019-03-12 | Caponigro Giordano | combinações farmacêuticas |
| CN109715163B (zh) | 2016-09-19 | 2022-11-22 | 诺华股份有限公司 | 包含raf抑制剂和erk抑制剂的治疗组合 |
| WO2018203219A1 (en) | 2017-05-02 | 2018-11-08 | Novartis Ag | Combination therapy |
| EP4563150A3 (en) | 2019-05-13 | 2025-07-23 | Novartis AG | New crystalline forms of n-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methvlphenyl)-2(trifluoromethyl) isonicotinamide as raf inhibitors for the treatment of cancer |
| JP7676371B2 (ja) | 2019-10-11 | 2025-05-14 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | 薬剤用量決定デバイスおよび方法 |
| EP4103286A4 (en) * | 2020-02-10 | 2024-03-20 | Cedars-Sinai Medical Center | METHOD OF TREATMENT OF PANCREATIC CANCER |
| JP7288220B2 (ja) | 2021-03-29 | 2023-06-07 | ダイキン工業株式会社 | モータ、送風装置、および冷凍装置 |
| 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 |
| JP2025541200A (ja) * | 2022-12-15 | 2025-12-18 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | がん処置のための併用療法 |
| WO2025003956A1 (en) | 2023-06-30 | 2025-01-02 | Pfizer Inc. | High drug loading formulations of encorafenib |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU4128089A (en) | 1988-09-15 | 1990-03-22 | Rorer International (Overseas) Inc. | Monoclonal antibodies specific to human epidermal growth factor receptor and therapeutic methods employing same |
| CA2222231A1 (en) | 1995-06-07 | 1996-12-19 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth of tumors |
| SG2013013339A (en) | 2002-03-13 | 2014-12-30 | Array Biopharma Inc | N3 alkylated benzimidazole derivatives as mek inhibitors |
| US7235537B2 (en) * | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
| WO2008120004A1 (en) | 2007-04-02 | 2008-10-09 | Astrazeneca Ab | Combination of a mek- inhibitor and a b-raf inhibitor for the treatment of cancer |
| EP2324008B1 (en) | 2008-07-24 | 2012-05-09 | Nerviano Medical Sciences S.R.L. | 3,4-diarylpyrazoles as protein kinase inhibitors |
| JP5527878B2 (ja) * | 2009-07-30 | 2014-06-25 | トムソン ライセンシング | 表示装置及び音声出力装置 |
| JO3002B1 (ar) | 2009-08-28 | 2016-09-05 | Irm Llc | مركبات و تركيبات كمثبطات كيناز بروتين |
| AU2012267888A1 (en) * | 2011-06-07 | 2014-01-30 | Caris Mpi, Inc. | Molecular profiling for cancer |
| JP6150813B2 (ja) | 2011-11-11 | 2017-06-21 | ノバルティス アーゲー | 増殖性疾患の治療方法 |
| CA2856406C (en) | 2011-11-23 | 2020-06-23 | Novartis Ag | Pharmaceutical formulations |
| AR091876A1 (es) * | 2012-07-26 | 2015-03-04 | Novartis Ag | Combinaciones farmaceuticas para el tratamiento de enfermedades proliferativas |
| IN2015DN00450A (enExample) * | 2012-08-07 | 2015-06-26 | Novartis Ag | |
| CA3079071C (en) * | 2012-10-19 | 2022-06-07 | Array Biopharma Inc. | Preparation of crystallized benzimidazole derivative as mek inhibitor and formulation comprising same |
| JP2016503399A (ja) * | 2012-10-25 | 2016-02-04 | ノバルティス アーゲー | 組合せ |
| US9913844B2 (en) | 2013-03-21 | 2018-03-13 | Novartis Ag | Combination therapy |
| WO2015008729A1 (ja) | 2013-07-18 | 2015-01-22 | 株式会社ダイセル | 酸化物の製造方法 |
| US20150087279A1 (en) * | 2013-09-20 | 2015-03-26 | Better Mousetrap, LLC | Mobile accident processing system and method |
| BR112016011222A2 (pt) * | 2013-12-12 | 2017-09-19 | Novartis Ag | Combinações de trametinib, panitumumab e dabrafenib para o tratamento de câncer |
| CN105566225A (zh) * | 2015-02-16 | 2016-05-11 | 苏州晶云药物科技有限公司 | 一种口服丝裂原活化蛋白激酶抑制剂的晶型及其制备方法 |
| US10323035B2 (en) * | 2015-04-01 | 2019-06-18 | Crystal Pharmatech Co., Ltd. | Co-crystal of a CDK inhibitor and an MEK inhibitor and process of preparation thereof |
| WO2017019279A1 (en) | 2015-07-27 | 2017-02-02 | Southern Research Institute | Methods and compositions to treat cancers involving egfr |
| BR112018074941A2 (pt) | 2016-06-03 | 2019-03-12 | Caponigro Giordano | combinações farmacêuticas |
-
2017
- 2017-06-02 BR BR112018074941-9A patent/BR112018074941A2/pt not_active Application Discontinuation
- 2017-06-02 HU HUE17807555A patent/HUE060653T2/hu unknown
- 2017-06-02 KR KR1020187037798A patent/KR102439911B1/ko active Active
- 2017-06-02 MX MX2018014973A patent/MX387795B/es unknown
- 2017-06-02 MA MA045187A patent/MA45187A/fr unknown
- 2017-06-02 UA UAA201813074A patent/UA125436C2/uk unknown
- 2017-06-02 SI SI201731293T patent/SI3463345T1/sl unknown
- 2017-06-02 CR CR20190002A patent/CR20190002A/es unknown
- 2017-06-02 EP EP17807555.2A patent/EP3463345B1/en not_active Revoked
- 2017-06-02 PL PL17807555.2T patent/PL3463345T3/pl unknown
- 2017-06-02 CA CA3026361A patent/CA3026361A1/en active Pending
- 2017-06-02 WO PCT/US2017/035653 patent/WO2017210538A1/en not_active Ceased
- 2017-06-02 CN CN201780048857.2A patent/CN109890386B/zh not_active Expired - Fee Related
- 2017-06-02 DK DK17807555.2T patent/DK3463345T3/da active
- 2017-06-02 RU RU2018146812A patent/RU2759669C2/ru active
- 2017-06-02 PT PT178075552T patent/PT3463345T/pt unknown
- 2017-06-02 AU AU2017275650A patent/AU2017275650B2/en not_active Ceased
- 2017-06-02 FI FIEP17807555.2T patent/FI3463345T3/fi active
- 2017-06-02 JP JP2019515782A patent/JP6805336B2/ja active Active
- 2017-06-02 SG SG11201810793XA patent/SG11201810793XA/en unknown
-
2018
- 2018-11-30 CL CL2018003421A patent/CL2018003421A1/es unknown
- 2018-12-03 IL IL263431A patent/IL263431A/en unknown
- 2018-12-03 US US16/208,172 patent/US10485788B2/en active Active
- 2018-12-03 PH PH12018502549A patent/PH12018502549A1/en unknown
-
2019
- 2019-01-02 ZA ZA2019/00019A patent/ZA201900019B/en unknown
- 2019-01-02 CO CONC2019/0000010A patent/CO2019000010A2/es unknown
- 2019-09-24 US US16/580,505 patent/US11376239B2/en not_active Expired - Fee Related
-
2020
- 2020-12-03 JP JP2020201152A patent/JP2021054832A/ja active Pending
-
2022
- 2022-05-16 US US17/745,136 patent/US20230044943A1/en not_active Abandoned
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