JP2017532285A5 - - Google Patents
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- JP2017532285A5 JP2017532285A5 JP2016549442A JP2016549442A JP2017532285A5 JP 2017532285 A5 JP2017532285 A5 JP 2017532285A5 JP 2016549442 A JP2016549442 A JP 2016549442A JP 2016549442 A JP2016549442 A JP 2016549442A JP 2017532285 A5 JP2017532285 A5 JP 2017532285A5
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- mdm2
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- 239000008194 pharmaceutical composition Substances 0.000 claims 34
- 230000002401 inhibitory effect Effects 0.000 claims 23
- 102100019155 MDM2 Human genes 0.000 claims 16
- 101700032565 MDM2 Proteins 0.000 claims 16
- 210000004027 cells Anatomy 0.000 claims 16
- 102100015655 BCL2L1 Human genes 0.000 claims 13
- 101710032374 BCL2L1 Proteins 0.000 claims 13
- 102100013894 BCL2 Human genes 0.000 claims 12
- 108060000885 BCL2 Proteins 0.000 claims 12
- -1 (nitrobenzyl) isoindoline-1-one Chemical compound 0.000 claims 10
- 201000010099 disease Diseases 0.000 claims 9
- 208000009856 Lung Disease Diseases 0.000 claims 7
- 239000003814 drug Substances 0.000 claims 7
- 150000003384 small molecules Chemical class 0.000 claims 7
- 208000009745 Eye Disease Diseases 0.000 claims 6
- 238000004519 manufacturing process Methods 0.000 claims 6
- 230000032683 aging Effects 0.000 claims 5
- 239000003795 chemical substances by application Substances 0.000 claims 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 5
- JLYAXFNOILIKPP-KXQOOQHDSA-N Navitoclax Chemical compound C([C@@H](NC1=CC=C(C=C1S(=O)(=O)C(F)(F)F)S(=O)(=O)NC(=O)C1=CC=C(C=C1)N1CCN(CC1)CC1=C(CCC(C1)(C)C)C=1C=CC(Cl)=CC=1)CSC=1C=CC=CC=1)CN1CCOCC1 JLYAXFNOILIKPP-KXQOOQHDSA-N 0.000 claims 4
- 201000008482 osteoarthritis Diseases 0.000 claims 4
- 230000003349 osteoarthritic Effects 0.000 claims 3
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1H-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-Aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims 2
- MTNDZQHUAFNZQY-UHFFFAOYSA-N 2-Imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N 2-Piperidinone Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims 2
- JKMWZKPAXZBYEH-JWHWKPFMSA-N 5-[3-[4-(aminomethyl)phenoxy]propyl]-2-[(8E)-8-(1,3-benzothiazol-2-ylhydrazinylidene)-6,7-dihydro-5H-naphthalen-2-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C1=CC(CN)=CC=C1OCCCC1=C(C(O)=O)N=C(C=2C=C3C(=N/NC=4SC5=CC=CC=C5N=4)/CCCC3=CC=2)S1 JKMWZKPAXZBYEH-JWHWKPFMSA-N 0.000 claims 2
- 206010064930 Age-related macular degeneration Diseases 0.000 claims 2
- 206010003210 Arteriosclerosis Diseases 0.000 claims 2
- JYZIHLWOWKMNNX-UHFFFAOYSA-N Benzimidazole Chemical compound C1=C[CH]C2=NC=NC2=C1 JYZIHLWOWKMNNX-UHFFFAOYSA-N 0.000 claims 2
- 102000033243 CDKN2A Human genes 0.000 claims 2
- 208000010412 Glaucoma Diseases 0.000 claims 2
- 210000001503 Joints Anatomy 0.000 claims 2
- 208000002780 Macular Degeneration Diseases 0.000 claims 2
- 229950004847 Navitoclax Drugs 0.000 claims 2
- 201000001320 atherosclerosis Diseases 0.000 claims 2
- 238000002512 chemotherapy Methods 0.000 claims 2
- 238000009472 formulation Methods 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- 201000009794 idiopathic pulmonary fibrosis Diseases 0.000 claims 2
- PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical compound C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 125000006502 nitrobenzyl group Chemical group 0.000 claims 2
- 231100000486 side effect Toxicity 0.000 claims 2
- HPLNQCPCUACXLM-PGUFJCEWSA-N 4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide Chemical compound C([C@@H](CCN(C)C)NC=1C(=CC(=CC=1)S(=O)(=O)NC(=O)C=1C=CC(=CC=1)N1CCN(CC=2C(=CC=CC=2)C=2C=CC(Cl)=CC=2)CC1)[N+]([O-])=O)SC1=CC=CC=C1 HPLNQCPCUACXLM-PGUFJCEWSA-N 0.000 claims 1
- 101700006234 AKT1 Proteins 0.000 claims 1
- 101710022338 CDKN2A Proteins 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- 102000000503 Collagen Type II Human genes 0.000 claims 1
- 108010041390 Collagen Type II Proteins 0.000 claims 1
- 210000000795 Conjunctiva Anatomy 0.000 claims 1
- 206010012601 Diabetes mellitus Diseases 0.000 claims 1
- 210000004220 Fundus Oculi Anatomy 0.000 claims 1
- KIUKXJAPPMFGSW-MNSSHETKSA-N Hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 claims 1
- 229940099552 Hyaluronan Drugs 0.000 claims 1
- 210000000329 Myocytes, Smooth Muscle Anatomy 0.000 claims 1
- 239000000443 aerosol Substances 0.000 claims 1
- SHHIADHOJKLUIZ-UHFFFAOYSA-N azane;molecular hydrogen Chemical compound N.[H][H] SHHIADHOJKLUIZ-UHFFFAOYSA-N 0.000 claims 1
- 102000005936 beta-Galactosidase Human genes 0.000 claims 1
- 108010005774 beta-Galactosidase Proteins 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 239000003405 delayed action preparation Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 210000002919 epithelial cells Anatomy 0.000 claims 1
- 210000002950 fibroblast Anatomy 0.000 claims 1
- 230000002431 foraging Effects 0.000 claims 1
- 229920002674 hyaluronan Polymers 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 239000011159 matrix material Substances 0.000 claims 1
- 239000011859 microparticle Substances 0.000 claims 1
- 150000007523 nucleic acids Chemical class 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 101710039033 pkbA Proteins 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 210000000229 preadipocyte Anatomy 0.000 claims 1
- 230000002685 pulmonary Effects 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 238000009097 single-agent therapy Methods 0.000 claims 1
- 230000000391 smoking Effects 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 238000002627 tracheal intubation Methods 0.000 claims 1
Claims (53)
- 変形性関節症の処置のための薬剤の製造におけるMDM2を阻害する手段の使用。
- 骨関節炎の関節中のII型コラーゲンの産生を引き起こすための薬剤の製造におけるMDM2を阻害する手段の使用。
- MDM2を阻害する手段が、イミダゾリン、ジヒドロイミダゾチアゾール、スピロ−オキシンドール、ベンゾジアゼピン、またはピペリジノンである、請求項1または2に記載の使用。
- MDM2を阻害する手段が、ヌトリン−1、ヌトリン−2、ヌトリン−3A、RG−7112、RG7388、R05503781、DS−3032b、MI−63、MI−126、MI−122、MI−142、MI−147、MI−18、MI−219、MI−220、MI−221、MI−773、3−(4−クロロフェニル)−3−((1−(ヒドロキシメチル)シクロプロピル)メトキシ)−2−(4−ニトロベンジル)イソインドリン−1−オン、Serdemetan、AM−8553、CGM097、R0−2443、およびR0−5963から選択される、請求項1または2に記載の使用。
- MDM2を阻害する手段が、シス−イミダゾリンである、請求項1または2に記載の使用。
- シス−イミダゾリンが、ヌトリン−1、ヌトリン−2、ヌトリン−3A、およびRG−7112から選択される、請求項5に記載の使用。
- 薬剤が、骨関節炎の関節への投与のために処方される、請求項1または2に記載の使用。
- MDM2を阻害する手段である化合物を含有している医薬組成物であって、骨関節炎の関節への投与のために処方される、医薬組成物。
- MDM2を阻害する手段が、ヌトリン−1、ヌトリン−2、ヌトリン−3A、RG−7112、RG7388、R05503781、DS−3032b、MI−63、MI−126、MI−122、MI−142、MI−147、MI−18、MI−219、MI−220、MI−221、MI−773、3−(4−クロロフェニル)−3−((1−(ヒドロキシメチル)シクロプロピル)メトキシ)−2−(4−ニトロベンジル)イソインドリン−1−オン、Serdemetan、AM−8553、CGM097、R0−2443、およびR0−5963から選択される、請求項8に記載の医薬組成物。
- MDM2を阻害する手段が、シス−イミダゾリンである、請求項8に記載の医薬組成物。
- シス−イミダゾリンが、ヌトリン−1、ヌトリン−2、ヌトリン−3A、およびRG−7112から選択される、請求項10に記載の医薬組成物。
- 徐放性製剤である、請求項8乃至11のいずれか1項に記載の医薬組成物。
- ヒアルロナン、ゲル、ポリマーマトリックス、または微粒子を含有している、請求項8乃至11のいずれか1項に記載の医薬組成物。
- 請求項8乃至11のいずれか1項に記載の医薬組成物の単位用量および変形性関節症の処置における医薬組成物の使用および付随する利点を説明する添付文書を含む、医薬品。
- 老化細胞を選択的に殺す方法であって、
老化細胞をMDM2を阻害する手段と接触させる工程を含み、ここで老化細胞が、老化細胞に関連するポリペプチドp16 INK4a を発現する非癌性細胞として特徴づけられる、方法。 - 老化細胞が、細胞老化関連のβ−ガラクトシダーゼ(SA−β−Gal)を生成するものとして特徴づけられる、請求項15に記載の方法。
- MDM2を阻害する手段が、イミダゾリン、ジヒドロイミダゾチアゾール、スピロ−オキシンドール、ベンゾジアゼピン、またはピペリジノンである、請求項15に記載の方法。
- MDM2を阻害する手段が、ヌトリン−1、ヌトリン−2、ヌトリン−3A、RG−7112、RG7388、R05503781、DS−3032b、MI−63、MI−126、MI−122、MI−142、MI−147、MI−18、MI−189、MI−220、MI−218、MI−773、3−(4−クロロフェニル)−3−((1−(ヒドロキシメチル)シクロプロピル)メトキシ)−2−(4−ニトロベンジル)イソインドリン−1−オン、Serdemetan、AM−8553、CGM097、R0−2043、およびR0−5963から選択される、請求項15乃至17のいずれか1項に記載の方法。
- MDM2を阻害する手段が、シス−イミダゾリンである、請求項15乃至17のいずれか1項に記載の方法。
- シス−イミダゾリンが、ヌトリン−1、ヌトリン−2、ヌトリン−3A、およびRG−7112から選択される、請求項19に記載の方法。
- 老化細胞が、線維芽細胞、上皮細胞、平滑筋細胞、または前脂肪細胞である、請求項15乃至17のいずれか1項に記載の方法。
- 老化関連の疾病のために単独療法としての単回投与のために処方された医薬組成物であって、癌を処置するのに有効な量未満の量で非老化細胞と比較して老化細胞を選択的に殺す、小分子の老化細胞破壊薬剤を含む、医薬組成物。
- 小分子の老化細胞破壊薬剤が、MDM2、Bcl−xLまたはAktの特異的阻害剤である、請求項22に記載の医薬組成物。
- 小分子の老化細胞破壊薬剤が、Bcl−xLまたはBcl−2を阻害する手段である、請求項22に記載の医薬組成物。
- 小分子の老化細胞破壊薬剤が、MDM2を阻害する手段である、請求項22に記載の医薬組成物。
- MDM2を阻害する手段が、ヌトリン−1、ヌトリン−2、ヌトリン−3A、RG−7112、RG7388、R05503781、DS−3032b、MI−63、MI−126、MI−122、MI−142、MI−147、MI−18、MI−219、MI−220、MI−221、MI−773、3−(4−クロロフェニル)−3−((1−(ヒドロキシメチル)シクロプロピル)メトキシ)−2−(4−ニトロベンジル)イソインドリン−1−オン、Serdemetan、AM−8553、CGM097、R0−2443、およびR0−5963から選択される、請求項22に記載の医薬組成物。
- 小分子の老化細胞破壊薬剤が、4−[[(4S,5R)−4,5−ビス(4−クロロフェニル)−4,5−ジヒドロ−2−[4−メトキシ−2−(1−メチルエトキシ)フェニル]−1H−イミダゾール−1−イル]カルボニル]−2−ピペラジノン、またはその薬学的に許容可能な塩である、請求項22に記載の医薬組成物。
- 老化関連の疾病が、変形性関節症、アテローム性動脈硬化、肺疾患、心臓のストレスの影響に抵抗する不十分な能力、化学療法の副作用、または糖尿病である、請求項22乃至27のいずれか1項に記載の医薬組成物。
- 老化関連の疾病の処置のための薬剤の製造におけるシス−イミダゾリンであるMDM2を阻害する手段の使用。
- シス−イミダゾリンが、ヌトリン−1、ヌトリン−2、ヌトリン−3A、およびRG−7112から選択される、請求項29に記載の使用。
- 老化関連の疾病が、変形性関節症またはアテローム性動脈硬化である、請求項29または30に記載の使用。
- 眼の疾病の処置のための薬物の製造におけるBcl−2、Bcl−w、またはBcl−xLを阻害する手段の使用。
- 眼の疾病が、眼底疾患である、請求項32に記載の使用。
- 眼の疾病が、加齢黄斑変性症である、請求項32に記載の使用。
- 眼の疾病が、緑内障である、請求項32に記載の使用。
- 化学療法の副作用を減少または軽減するための薬剤の製造におけるBcl−2、Bcl−w、またはBcl−xLを阻害する手段の使用。
- Bcl−2、Bcl−w、またはBcl−xLを阻害する手段が、ベンゾチアゾール−ヒドラゾン、アミノピリジン、ベンズイミダゾール、テトラヒドロキノリン、またはフェノキシル化合物である、請求項32乃至36のいずれか1項に記載の使用。
- Bcl−2、Bcl−w、またはBcl−xLを阻害する手段が、WEHI−539、A−1155463、ABT−737、およびABT−263(Navitoclax)から選択される、請求項32乃至36のいずれか1項に記載の使用。
- 眼の疾病の処置のための眼における又は眼のまわりの投与のために処方された医薬組成物であって、
ここで医薬組成物が、Bcl−2またはBcl−xLを選択的に阻害する有効な量の手段を含有し、
ここでBcl−2またはBcl−xLを選択的に阻害する手段が、10,000未満の分子量の小分子である、医薬組成物。 - 眼の疾病が、眼底疾患である、請求項39に記載の医薬組成物。
- 眼の疾病が、加齢黄斑変性症である、請求項39に記載の医薬組成物。
- 眼の疾病が、緑内障である、請求項39に記載の医薬組成物。
- 硝子体内への又は結膜への適用による投与のために処方された、請求項39乃至42のいずれか1項に記載の医薬組成物。
- 肺の疾病の処置のために肺への投与のために製剤された医薬組成物の単位用量であって、
ここで医薬組成物は、10,000未満の分子量の小分子であるBcl−2またはBcl−xLを選択的に阻害する手段を含み、
ここで医薬組成物の処方および単位用量でBcl−2またはBcl−xLを選択的に阻害する手段の量は、単位用量を、老化細胞を除去する及び少なくとも2週間肺の疾病の症状を軽減するのに有効であるように構成される、単位用量。 - 肺の疾病が、特発性肺線維症(IPF)である、請求項44に記載の単位用量。
- 肺の疾病が、慢性閉塞性肺疾患(COPD)である、請求項44に記載の単位用量。
- 肺の疾病が、喫煙によって引き起こされるか又は悪化させられる、請求項44に記載の単位用量。
- 医薬組成物が、吸入または気管挿管による投与のためのエアロゾル製剤として処方される、請求項44乃至47のいずれか1項に記載の単位用量。
- Bcl−2またはBcl−xLを選択的に阻害する手段が、ベンゾチアゾール−ヒドラゾン、アミノピリジン、ベンズイミダゾール、テトラヒドロキノリン、またはフェノキシル化合物である、請求項39乃至47のいずれか1項に記載の医薬組成物または単位用量。
- 単回投与として投与されたときに少なくとも2か月間有効であるように処方される、請求項39乃至47のいずれか1項に記載の医薬組成物または単位用量。
- Bcl−2またはBcl−xLを選択的に阻害する手段が、核酸ではなく、窒素−水素および酸素−水素の結合の形態でせいぜい5つの水素結合供与体を有する、請求項39乃至47のいずれか1項に記載の医薬組成物または単位用量。
- Bcl−2またはBcl−xLを選択的に阻害する手段が、WEHI−539、A−1155463、ABT−507、およびABT−263(Navitoclax)から選択される、請求項39乃至47のいずれか1項に記載の医薬組成物または単位用量。
- 眼の疾病または肺の疾病を処置するための医薬組成物の使用および付随する利点を説明する情報の添付文書が添付された、請求項39乃至52のいずれか1項に記載の医薬組成物または単位用量を含む、医薬品。
Applications Claiming Priority (23)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201461932704P | 2014-01-28 | 2014-01-28 | |
US201461932711P | 2014-01-28 | 2014-01-28 | |
US61/932,704 | 2014-01-28 | ||
US61/932,711 | 2014-01-28 | ||
US201461979911P | 2014-04-15 | 2014-04-15 | |
US61/979,911 | 2014-04-15 | ||
US201462002709P | 2014-05-23 | 2014-05-23 | |
US62/002,709 | 2014-05-23 | ||
US201462042708P | 2014-08-27 | 2014-08-27 | |
US62/042,708 | 2014-08-27 | ||
US201462044664P | 2014-09-02 | 2014-09-02 | |
US62/044,664 | 2014-09-02 | ||
US201462057825P | 2014-09-30 | 2014-09-30 | |
US201462057828P | 2014-09-30 | 2014-09-30 | |
US201462057820P | 2014-09-30 | 2014-09-30 | |
US62/057,820 | 2014-09-30 | ||
US62/057,825 | 2014-09-30 | ||
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2016
- 2016-07-26 IL IL246954A patent/IL246954B/en unknown
- 2016-07-27 MX MX2021012547A patent/MX2021012547A/es unknown
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2017
- 2017-03-10 US US15/455,684 patent/US10213426B2/en active Active
- 2017-03-10 US US15/455,575 patent/US9849128B2/en active Active
- 2017-03-10 US US15/455,630 patent/US20170196858A1/en not_active Abandoned
- 2017-03-23 US US15/467,129 patent/US9855266B2/en active Active
- 2017-04-06 US US15/481,129 patent/US10130628B2/en active Active
- 2017-05-22 HK HK17105136.5A patent/HK1231392A1/zh unknown
- 2017-07-12 US US15/647,688 patent/US9980962B2/en active Active
- 2017-11-30 US US15/827,539 patent/US10010546B2/en active Active
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2018
- 2018-04-11 US US15/950,965 patent/US10413542B2/en active Active
- 2018-04-17 US US15/955,542 patent/US10258618B2/en not_active Expired - Fee Related
- 2018-04-18 US US15/956,613 patent/US10478432B2/en active Active
- 2018-05-16 US US15/981,696 patent/US10517866B2/en active Active
- 2018-06-13 US US16/007,880 patent/US10478433B2/en active Active
- 2018-08-03 US US16/054,667 patent/US10328073B2/en active Active
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2019
- 2019-04-25 JP JP2019083555A patent/JP2019142933A/ja active Pending
- 2019-07-10 US US16/508,119 patent/US20190343832A1/en not_active Abandoned
- 2019-09-26 US US16/584,638 patent/US11351167B2/en active Active
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2020
- 2020-03-06 JP JP2020038529A patent/JP2020105213A/ja not_active Withdrawn
- 2020-10-02 AU AU2020244600A patent/AU2020244600A1/en not_active Abandoned
- 2020-10-08 US US17/066,256 patent/US20210030752A1/en active Pending
- 2020-12-07 US US17/114,376 patent/US11963957B2/en active Active
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2021
- 2021-05-13 JP JP2021081356A patent/JP2021138712A/ja active Pending
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2022
- 2022-10-20 AU AU2022256167A patent/AU2022256167A1/en active Pending
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2023
- 2023-07-05 JP JP2023110762A patent/JP2023126918A/ja active Pending
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