MY172739A - Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators - Google Patents

Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators

Info

Publication number
MY172739A
MY172739A MYPI2014003289A MYPI2014003289A MY172739A MY 172739 A MY172739 A MY 172739A MY PI2014003289 A MYPI2014003289 A MY PI2014003289A MY PI2014003289 A MYPI2014003289 A MY PI2014003289A MY 172739 A MY172739 A MY 172739A
Authority
MY
Malaysia
Prior art keywords
receptor modulators
heteroaryl
glucocorticoid receptor
fused azadecalin
ketone fused
Prior art date
Application number
MYPI2014003289A
Other languages
English (en)
Inventor
Hazel Hunt
Tony Johnson
Nicholas Ray
Iain Walters
Original Assignee
Corcept Therapeutics Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Corcept Therapeutics Inc filed Critical Corcept Therapeutics Inc
Publication of MY172739A publication Critical patent/MY172739A/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/472Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965Non-condensed pyrazines
    • A61K31/497Non-condensed pyrazines containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53831,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/38Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/46Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of glucocorticosteroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04Ortho-condensed systems

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Obesity (AREA)
  • Endocrinology (AREA)
  • Psychiatry (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Electroluminescent Light Sources (AREA)
  • Plural Heterocyclic Compounds (AREA)
MYPI2014003289A 2012-05-25 2013-05-24 Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators MY172739A (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201261651669P 2012-05-25 2012-05-25
US201261691083P 2012-08-20 2012-08-20
US201261715907P 2012-10-19 2012-10-19
US201361759520P 2013-02-01 2013-02-01
US201361781629P 2013-03-14 2013-03-14
PCT/US2013/042732 WO2013177559A2 (en) 2012-05-25 2013-05-24 Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators

Publications (1)

Publication Number Publication Date
MY172739A true MY172739A (en) 2019-12-11

Family

ID=49624542

Family Applications (1)

Application Number Title Priority Date Filing Date
MYPI2014003289A MY172739A (en) 2012-05-25 2013-05-24 Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators

Country Status (24)

Country Link
EP (6) EP3590517B1 (https=)
JP (1) JP6172871B2 (https=)
KR (1) KR102062640B1 (https=)
CN (1) CN104619328B (https=)
AU (1) AU2013266110C1 (https=)
BR (1) BR112014028857B1 (https=)
CA (1) CA2872260C (https=)
CL (1) CL2014003173A1 (https=)
DK (5) DK4119561T3 (https=)
ES (5) ES2753816T3 (https=)
FI (1) FI4119561T3 (https=)
HK (1) HK1250014B (https=)
IL (1) IL235868A (https=)
MX (1) MX365423B (https=)
MY (1) MY172739A (https=)
NZ (1) NZ701469A (https=)
PE (1) PE20150352A1 (https=)
PH (1) PH12014502584B1 (https=)
PL (5) PL3851107T3 (https=)
PT (5) PT3590517T (https=)
RU (1) RU2639867C2 (https=)
SG (1) SG11201407682TA (https=)
WO (1) WO2013177559A2 (https=)
ZA (1) ZA201408182B (https=)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11648245B2 (en) 2012-05-25 2023-05-16 Corcept Therapeutics, Inc. Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators
US11925626B2 (en) 2018-12-19 2024-03-12 Corcept Therapeutics Incorporated Pharmaceutical formulations containing relacorilant, a heteroaryl-ketone fused azadecalin compound
US12226412B2 (en) 2012-05-25 2025-02-18 Corcept Therapeutics, Inc. Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators
US12589094B2 (en) 2020-05-27 2026-03-31 Corcept Therapeutics Incorporated Concomitant administration of glucocorticoid receptor modulator relacorilant and paclitaxel, a dual substrate of CYP2C8 and CYP3A4

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL3848027T3 (pl) 2013-11-25 2023-07-24 Corcept Therapeutics Incorporated Skondensowane oktahydrozwiązki azadekaliny jako modulatory receptora glukokortykoidowego
AU2016226451B2 (en) * 2015-03-02 2019-12-19 Corcept Therapeutics, Inc. Use of glucocorticoid receptor antagonist and somatostatin analogues to treat ACTH-secreting tumors
US10610534B2 (en) * 2015-03-30 2020-04-07 Corcept Therapeutics, Inc. Use of glucocorticoid receptor antagonists in combination with glucocorticoids to treat adrenal insufficiency
KR20180008627A (ko) * 2015-05-18 2018-01-24 코어셉트 쎄라퓨틱스, 잉크. 쿠싱 증후군을 진단하고 이에 대한 치료를 평가하는 방법
KR20180052120A (ko) * 2015-08-13 2018-05-17 코어셉트 쎄라퓨틱스, 잉크. Acth-의존성 쿠싱 증후군을 감별 진단하는 방법
WO2017151613A1 (en) * 2016-03-01 2017-09-08 Corcept Therapeutics, Inc. The use of glucocorticoid receptor modulators to potentiate checkpoint inhibitors
US9943505B2 (en) 2016-09-09 2018-04-17 Corcept Therapeutics, Inc. Glucocorticoid receptor modulators to treat pancreatic cancer
MX2019011543A (es) * 2017-03-31 2019-12-16 Corcept Therapeutics Inc Moduladores del receptor de glucocorticoides para el tratamiento de cancer cervical.
WO2018236749A2 (en) 2017-06-20 2018-12-27 Corcept Therapeutics, Inc. Methods of treating neuroepithelial tumors using selective glucocorticoid receptor modulators
ES3038908T3 (en) * 2018-04-23 2025-10-15 Corcept Therapeutics Inc Methods of preparing regioselective n-alkyl triazoles
US10946005B2 (en) * 2018-11-09 2021-03-16 Corcept Therapeutics Incorporated Methods for shrinking pituitary tumors
US11234971B2 (en) 2018-12-19 2022-02-01 Corcept Therapeutics Incorporated Methods of treating cancer comprising administration of a glucocorticoid receptor modulator and a cancer chemotherapy agent
US11389432B2 (en) 2018-12-19 2022-07-19 Corcept Therapeutics Incorporated Methods of treating cancer comprising administration of a glucocorticoid receptor modulator and a cancer chemotherapy agent
SG11202105746TA (en) * 2018-12-20 2021-07-29 Corcept Therapeutics Inc Methods for imaging and treatment of somatostatin-receptor positive tumors
JP7789561B2 (ja) 2019-02-22 2025-12-22 コーセプト セラピューティクス, インコーポレイテッド レラコリラント、ヘテロアリール-ケトン縮合アザデカリングルココルチコイド受容体調節物質の治療用途
AU2020367769B2 (en) * 2019-10-16 2023-10-12 Corcept Therapeutics Incorporated Method of normalizing the neutrophil to lymphocyte ratio in cancer patients with a selective glucocorticoid receptor antagonist
JP7569492B2 (ja) 2019-12-11 2024-10-18 コーセプト セラピューティクス, インコーポレイテッド 抗精神病薬誘発性体重増加のミリコリラントによる治療方法
ES3060361T3 (en) * 2019-12-21 2026-03-26 Corcept Therapeutics Inc Treatment of, and differential diagnosis between, acth-dependent cushing's syndrome and acth-independent cushing's syndrome
AU2021220763B2 (en) * 2020-02-10 2024-01-18 Corcept Therapeutics Incorporated Methods of stimulating an anti-tumor response using a selective glucocorticoid receptor modulator
WO2022134033A1 (en) * 2020-12-25 2022-06-30 Corcept Therapeutics Incorporated Methods of preparing heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators
WO2022166810A1 (zh) * 2021-02-03 2022-08-11 江苏恒瑞医药股份有限公司 稠合的氮杂三环类衍生物、其制备方法及其在医药上的应用
CN114907340A (zh) * 2021-02-09 2022-08-16 江苏恒瑞医药股份有限公司 稠合的氮杂三环类衍生物、其制备方法及其在医药上的应用
CN114907349A (zh) * 2021-02-10 2022-08-16 江苏恒瑞医药股份有限公司 稠合的氮杂三环类衍生物、其制备方法及其在医药上的应用
CN117510490A (zh) * 2022-08-03 2024-02-06 江苏恒瑞医药股份有限公司 一种稠合氮杂萘烷类衍生物的晶型及其制备方法
KR20250073629A (ko) 2022-10-06 2025-05-27 코어셉트 쎄라퓨틱스 인코포레이티드 글루코코르티코이드 수용체 조절제의 제형
US12433882B2 (en) 2022-10-28 2025-10-07 Corcept Therapeutics Incorporated Treatments for amyotrophic lateral sclerosis using dazucorilant
CN120752040A (zh) * 2023-02-17 2025-10-03 科赛普特治疗学股份有限公司 用于治疗亨廷顿舞蹈症及其症状的方法和组合物

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US4391904A (en) 1979-12-26 1983-07-05 Syva Company Test strip kits in immunoassays and compositions therein
GB8828669D0 (en) * 1988-12-08 1989-01-11 Lilly Industries Ltd Organic compounds
CA2558899C (en) * 2004-03-09 2013-02-05 Corcept Therapeutics, Inc. Fused ring azadecalin glucocorticoid receptor modulators
US7640389B2 (en) * 2006-02-28 2009-12-29 Freescale Semiconductor, Inc. Non-volatile memory having a multiple block erase mode and method therefor
EP1932843A1 (en) * 2006-12-14 2008-06-18 sanofi-aventis Sulfonyl-phenyl-2H-(1,2,4) oxadiazole-5-one derivatives, processes for their preparation and their use as pharmaceuticals
CN103080108A (zh) * 2010-08-27 2013-05-01 科赛普特治疗公司 吡啶基-胺稠合的氮杂萘烷调节剂

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11648245B2 (en) 2012-05-25 2023-05-16 Corcept Therapeutics, Inc. Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators
US12226412B2 (en) 2012-05-25 2025-02-18 Corcept Therapeutics, Inc. Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators
US11925626B2 (en) 2018-12-19 2024-03-12 Corcept Therapeutics Incorporated Pharmaceutical formulations containing relacorilant, a heteroaryl-ketone fused azadecalin compound
US12514849B2 (en) 2018-12-19 2026-01-06 Corcept Therapeutics Incorporated Pharmaceutical formulations containing relacorilant, a heteroaryl-ketone fused azadecalin compound
US12589094B2 (en) 2020-05-27 2026-03-31 Corcept Therapeutics Incorporated Concomitant administration of glucocorticoid receptor modulator relacorilant and paclitaxel, a dual substrate of CYP2C8 and CYP3A4

Also Published As

Publication number Publication date
KR20150021955A (ko) 2015-03-03
MX365423B (es) 2019-06-03
EP3851107A1 (en) 2021-07-21
EP3338781A1 (en) 2018-06-27
AU2013266110C1 (en) 2018-07-12
EP4119561A1 (en) 2023-01-18
EP4434584A3 (en) 2024-11-20
DK3338781T3 (da) 2019-12-09
HK1250014B (en) 2020-06-12
WO2013177559A2 (en) 2013-11-28
DK2854814T3 (en) 2018-03-12
EP3590517A1 (en) 2020-01-08
DK4119561T3 (da) 2024-09-30
ES2995026T3 (en) 2025-02-05
CA2872260C (en) 2020-12-22
PH12014502584A1 (en) 2015-01-21
RU2639867C2 (ru) 2017-12-25
PL3338781T3 (pl) 2020-03-31
EP3338781B1 (en) 2019-09-11
PH12014502584B1 (en) 2015-01-21
BR112014028857B1 (pt) 2021-09-28
IL235868A (en) 2017-12-31
ES2665338T3 (es) 2018-04-25
WO2013177559A3 (en) 2014-01-16
ES2753816T3 (es) 2020-04-14
PT3851107T (pt) 2022-10-28
DK3851107T3 (da) 2022-11-21
EP2854814A4 (en) 2016-01-27
CL2014003173A1 (es) 2015-02-27
PL3851107T3 (pl) 2023-03-06
PE20150352A1 (es) 2015-03-16
DK3590517T3 (da) 2021-05-03
BR112014028857A2 (pt) 2017-08-15
RU2014152625A (ru) 2016-07-20
JP2015517580A (ja) 2015-06-22
PL3590517T3 (pl) 2021-09-20
PT3338781T (pt) 2019-11-29
PL2854814T3 (pl) 2018-07-31
AU2013266110B2 (en) 2017-04-20
EP4119561B1 (en) 2024-09-11
PT3590517T (pt) 2021-04-07
CA2872260A1 (en) 2013-11-28
ZA201408182B (en) 2017-09-27
EP3590517B1 (en) 2021-03-17
HK1208818A1 (en) 2016-03-18
CN104619328B (zh) 2018-10-02
EP4434584A2 (en) 2024-09-25
PT4119561T (pt) 2024-09-30
PL4119561T3 (pl) 2024-11-25
IL235868A0 (en) 2015-01-29
AU2013266110A1 (en) 2014-11-20
NZ701469A (en) 2017-06-30
PT2854814T (pt) 2018-03-15
EP2854814B1 (en) 2018-01-31
ES2873949T3 (es) 2021-11-04
EP2854814A2 (en) 2015-04-08
KR102062640B1 (ko) 2020-01-06
MX2014014239A (es) 2015-08-05
ES2930298T3 (es) 2022-12-09
FI4119561T3 (fi) 2024-11-01
CN104619328A (zh) 2015-05-13
JP6172871B2 (ja) 2017-08-02
SG11201407682TA (en) 2014-12-30
EP3851107B1 (en) 2022-10-19

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