ES2703627T3 - Análogos de folato/antifolato marcados con 18F - Google Patents
Análogos de folato/antifolato marcados con 18F Download PDFInfo
- Publication number
- ES2703627T3 ES2703627T3 ES13721738T ES13721738T ES2703627T3 ES 2703627 T3 ES2703627 T3 ES 2703627T3 ES 13721738 T ES13721738 T ES 13721738T ES 13721738 T ES13721738 T ES 13721738T ES 2703627 T3 ES2703627 T3 ES 2703627T3
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- Prior art keywords
- independently
- compound according
- substituted
- alkyl
- acid
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- 239000011724 folic acid Substances 0.000 title description 61
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 title description 60
- 235000019152 folic acid Nutrition 0.000 title description 50
- 229940014144 folate Drugs 0.000 title description 47
- 230000003432 anti-folate effect Effects 0.000 title description 16
- 229940127074 antifolate Drugs 0.000 title description 16
- 239000004052 folic acid antagonist Substances 0.000 title description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 51
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 24
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 8
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims abstract description 5
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract 2
- 206010028980 Neoplasm Diseases 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 36
- 102000006815 folate receptor Human genes 0.000 claims description 33
- 108020005243 folate receptor Proteins 0.000 claims description 33
- 238000011282 treatment Methods 0.000 claims description 24
- -1 C1 -C12 Chemical group 0.000 claims description 23
- 201000011510 cancer Diseases 0.000 claims description 18
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- 238000001727 in vivo Methods 0.000 claims description 9
- 238000002059 diagnostic imaging Methods 0.000 claims description 7
- KRHYYFGTRYWZRS-BJUDXGSMSA-M fluorine-18(1-) Chemical compound [18F-] KRHYYFGTRYWZRS-BJUDXGSMSA-M 0.000 claims description 7
- 238000001514 detection method Methods 0.000 claims description 6
- 238000012544 monitoring process Methods 0.000 claims description 5
- 238000000163 radioactive labelling Methods 0.000 claims description 5
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 4
- 238000000376 autoradiography Methods 0.000 claims description 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 abstract 1
- GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 abstract 1
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- 239000000523 sample Substances 0.000 description 22
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 18
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- KBPLFHHGFOOTCA-UHFFFAOYSA-N caprylic alcohol Natural products CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 15
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- 239000000700 radioactive tracer Substances 0.000 description 15
- LCZVKKUAUWQDPX-UHFFFAOYSA-N tert-butyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl]amino]acetate Chemical compound CC(=O)OC1=CC=CC=C1CN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1=CC=CC=C1OC(C)=O LCZVKKUAUWQDPX-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 229960000304 folic acid Drugs 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 239000000872 buffer Substances 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000002347 injection Methods 0.000 description 11
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 9
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
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- 239000003981 vehicle Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 125000001589 carboacyl group Chemical group 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
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- 229910052757 nitrogen Inorganic materials 0.000 description 7
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- 239000012071 phase Substances 0.000 description 7
- 210000002381 plasma Anatomy 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 102000056797 Proton-Coupled Folate Transporter Human genes 0.000 description 6
- 108091007566 SLC46A1 Proteins 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 229960002989 glutamic acid Drugs 0.000 description 6
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 6
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- FWGIJWOFKSZSIS-VIFPVBQESA-N (2s)-2-[[6-[(2-amino-4-oxo-1h-pteridin-6-yl)methylamino]-2-fluoropyridine-3-carbonyl]amino]pentanedioic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C(F)=N1 FWGIJWOFKSZSIS-VIFPVBQESA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
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- 229910000162 sodium phosphate Inorganic materials 0.000 description 5
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 4
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0459—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
- C07D475/04—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/06—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4
- C07D475/08—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/60—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances involving radioactive labelled substances
-
- 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
- C07B2200/05—Isotopically modified compounds, e.g. labelled
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
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- Urology & Nephrology (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
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- Biotechnology (AREA)
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- Cell Biology (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12167126 | 2012-05-08 | ||
| PCT/EP2013/059584 WO2013167653A1 (en) | 2012-05-08 | 2013-05-08 | 18f-labelled folate/antifolate analogues |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2703627T3 true ES2703627T3 (es) | 2019-03-11 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13721738T Active ES2703627T3 (es) | 2012-05-08 | 2013-05-08 | Análogos de folato/antifolato marcados con 18F |
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|---|---|
| US (1) | US10357576B2 (enExample) |
| EP (1) | EP2864329B1 (enExample) |
| JP (1) | JP6198814B2 (enExample) |
| KR (1) | KR102116000B1 (enExample) |
| CN (1) | CN104379585B (enExample) |
| AU (1) | AU2013258027B2 (enExample) |
| CA (1) | CA2870124C (enExample) |
| DK (1) | DK2864329T3 (enExample) |
| EA (1) | EA201401225A1 (enExample) |
| ES (1) | ES2703627T3 (enExample) |
| IL (1) | IL235476B (enExample) |
| PL (1) | PL2864329T3 (enExample) |
| PT (1) | PT2864329T (enExample) |
| SG (1) | SG11201406481TA (enExample) |
| TR (1) | TR201819802T4 (enExample) |
| WO (1) | WO2013167653A1 (enExample) |
| ZA (1) | ZA201407266B (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR101646577B1 (ko) * | 2014-08-14 | 2016-08-09 | 원광대학교산학협력단 | 엽산수용체 표적용 화합물 또는 이의 약학적으로 허용가능한 염과, 이를 유효성분으로 포함하는 암 예방, 진단 또는 치료용 조성물 |
| CA3057042A1 (en) | 2017-03-20 | 2018-09-27 | Merck Patent Gmbh | Isomerically pure 18f-labelled tetrahydrofolates |
| EP3671511B1 (en) | 2018-12-19 | 2022-07-06 | Rohde & Schwarz GmbH & Co. KG | Communication system and method |
| DE102019110904B4 (de) * | 2019-04-26 | 2022-01-20 | Helmholtz-Zentrum Dresden - Rossendorf E. V. | N-(4-methoxy-7-morpholinobenzo[d]thiazol-2-yl)-acetamid-Derivate und deren Verwendung |
| WO2021257863A1 (en) | 2020-06-19 | 2021-12-23 | Incyte Corporation | Pyrrolotriazine compounds as jak2 v617f inhibitors |
| WO2021257857A1 (en) | 2020-06-19 | 2021-12-23 | Incyte Corporation | Naphthyridinone compounds as jak2 v617f inhibitors |
| US11767323B2 (en) | 2020-07-02 | 2023-09-26 | Incyte Corporation | Tricyclic pyridone compounds as JAK2 V617F inhibitors |
| WO2022006457A1 (en) | 2020-07-02 | 2022-01-06 | Incyte Corporation | Tricyclic urea compounds as jak2 v617f inhibitors |
| WO2022046989A1 (en) | 2020-08-27 | 2022-03-03 | Incyte Corporation | Tricyclic urea compounds as jak2 v617f inhibitors |
| US11919908B2 (en) | 2020-12-21 | 2024-03-05 | Incyte Corporation | Substituted pyrrolo[2,3-d]pyrimidine compounds as JAK2 V617F inhibitors |
| WO2022182839A1 (en) | 2021-02-25 | 2022-09-01 | Incyte Corporation | Spirocyclic lactams as jak2 v617f inhibitors |
| JP2025509672A (ja) | 2022-03-17 | 2025-04-11 | インサイト・コーポレイション | Ｊａｋ２ ｖ６１７ｆ阻害剤としての三環式尿素化合物 |
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| RU2007128036A (ru) | 2004-12-23 | 2009-01-27 | Пердью Рисерч Фаундейшн (Us) | Способ получения изображения позитронно-эмиссионной томографией |
| JP4503039B2 (ja) | 2006-04-27 | 2010-07-14 | 三洋電機株式会社 | 回路装置 |
| EP2109466B1 (en) | 2007-02-07 | 2014-11-12 | Purdue Research Foundation | Positron emission tomography imaging method |
| CN101646639A (zh) | 2007-04-11 | 2010-02-10 | 默克阿泼洛发股份公司 | 18f-标记的叶酸 |
| AU2008237935B2 (en) | 2007-04-11 | 2014-03-27 | Merck & Cie | Folate-conjugates and corresponding metal-chelate complexes for use in diagnostic imaging and radiotherapy |
| CN104447750A (zh) | 2007-04-11 | 2015-03-25 | 默克和西伊公司 | 18f-标记的叶酸酯 |
| AU2008237932C1 (en) | 2007-04-11 | 2014-04-24 | Merck & Cie | 18 F-labelled folates |
| PT2346870E (pt) | 2008-10-10 | 2015-10-21 | Merck & Cie | Folatos marcados com 18f como marcadores radioactivos de pet |
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2013
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Also Published As
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| PL2864329T3 (pl) | 2019-03-29 |
| JP6198814B2 (ja) | 2017-09-20 |
| TR201819802T4 (tr) | 2019-01-21 |
| CN104379585A (zh) | 2015-02-25 |
| IL235476A0 (en) | 2014-12-31 |
| AU2013258027A1 (en) | 2014-11-13 |
| CA2870124C (en) | 2021-02-16 |
| CN104379585B (zh) | 2018-07-06 |
| SG11201406481TA (en) | 2014-11-27 |
| KR20150010970A (ko) | 2015-01-29 |
| AU2013258027B2 (en) | 2017-11-30 |
| EP2864329B1 (en) | 2018-09-26 |
| PT2864329T (pt) | 2019-01-10 |
| WO2013167653A1 (en) | 2013-11-14 |
| EP2864329A1 (en) | 2015-04-29 |
| DK2864329T3 (en) | 2019-01-21 |
| CA2870124A1 (en) | 2013-11-14 |
| EA201401225A1 (ru) | 2015-04-30 |
| IL235476B (en) | 2019-09-26 |
| HK1202548A1 (en) | 2015-10-02 |
| US10357576B2 (en) | 2019-07-23 |
| ZA201407266B (en) | 2016-09-28 |
| KR102116000B1 (ko) | 2020-05-29 |
| JP2015516405A (ja) | 2015-06-11 |
| US20150125390A1 (en) | 2015-05-07 |
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