ES2759347T3 - Composiciones de inhibidores de quinasas y su uso para el tratamiento del cáncer y otras enfermedades relacionadas con las quinasas - Google Patents

Composiciones de inhibidores de quinasas y su uso para el tratamiento del cáncer y otras enfermedades relacionadas con las quinasas Download PDF

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Publication number
ES2759347T3
ES2759347T3 ES16156340T ES16156340T ES2759347T3 ES 2759347 T3 ES2759347 T3 ES 2759347T3 ES 16156340 T ES16156340 T ES 16156340T ES 16156340 T ES16156340 T ES 16156340T ES 2759347 T3 ES2759347 T3 ES 2759347T3
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substituted
heterocycle
aryl
alkyl
compound
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English (en)
Spanish (es)
Inventor
Chiang Li
Ji-Feng Liu
Youzhi Li
Wei Li
Henry Rogoff
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Sumitomo Pharma Oncology Inc
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Boston Biomedical Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • 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
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Oncology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Obesity (AREA)
  • Endocrinology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Transplantation (AREA)
  • Vascular Medicine (AREA)
  • Dermatology (AREA)
  • Hospice & Palliative Care (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Emergency Medicine (AREA)
ES16156340T 2007-09-06 2008-09-05 Composiciones de inhibidores de quinasas y su uso para el tratamiento del cáncer y otras enfermedades relacionadas con las quinasas Active ES2759347T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US97041007P 2007-09-06 2007-09-06
US1338907P 2007-12-13 2007-12-13
US7429508P 2008-06-20 2008-06-20

Publications (1)

Publication Number Publication Date
ES2759347T3 true ES2759347T3 (es) 2020-05-08

Family

ID=40429714

Family Applications (2)

Application Number Title Priority Date Filing Date
ES16156340T Active ES2759347T3 (es) 2007-09-06 2008-09-05 Composiciones de inhibidores de quinasas y su uso para el tratamiento del cáncer y otras enfermedades relacionadas con las quinasas
ES08829600.9T Active ES2591028T3 (es) 2007-09-06 2008-09-05 Composiciones de inhibidores de quinasa y su uso para el tratamiento del cáncer y otras enfermedades relacionadas con quinasas

Family Applications After (1)

Application Number Title Priority Date Filing Date
ES08829600.9T Active ES2591028T3 (es) 2007-09-06 2008-09-05 Composiciones de inhibidores de quinasa y su uso para el tratamiento del cáncer y otras enfermedades relacionadas con quinasas

Country Status (15)

Country Link
US (5) US8299106B2 (enExample)
EP (2) EP2197878B1 (enExample)
JP (5) JP5452490B2 (enExample)
CN (1) CN101848908B (enExample)
CA (1) CA2736177A1 (enExample)
CY (1) CY1118012T1 (enExample)
DK (1) DK2197878T3 (enExample)
ES (2) ES2759347T3 (enExample)
HR (1) HRP20161114T1 (enExample)
HU (1) HUE030774T2 (enExample)
LT (1) LT2197878T (enExample)
PL (1) PL2197878T3 (enExample)
PT (1) PT2197878T (enExample)
SI (1) SI2197878T1 (enExample)
WO (1) WO2009033033A2 (enExample)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
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CA2736177A1 (en) * 2007-09-06 2009-03-12 Boston Biomedical, Inc. Compositions of kinase inhibitors and their use for treatment of cancer and other diseases related to kinases
KR101300916B1 (ko) * 2007-12-10 2013-08-27 인터디지탈 패튼 홀딩스, 인크 무선 링크 제어 패킷 폐기 및 무선 링크 제어 재확립을 트리거하는 방법 및 장치
AU2012222812A1 (en) 2011-02-28 2013-05-02 Mcmaster University Treatment of cancer with dopamine receptor antagonists
WO2014030001A1 (en) * 2012-08-23 2014-02-27 The Institute Of Cancer Research: Royal Cancer Hospital Fused heterocyclic compounds and their use
JP6378308B2 (ja) * 2013-03-13 2018-08-22 ボストン バイオメディカル, インコーポレイテッド がんの処置のための、がん幹細胞経路キナーゼの阻害剤としての3−(アリールまたはヘテロアリール)メチレンインドリン−2−オン誘導体
US9227962B2 (en) 2013-03-13 2016-01-05 Boston Biomedical, Inc. Heterocyclic substituted-3-heteroarylidenyl-2-indolinone derivative
US9187454B2 (en) 2013-03-13 2015-11-17 Boston Biomedical, Inc. Inhibitors of kinases and cancer stem cells, and methods of preparation and use thereof
EP3010903A1 (en) * 2013-06-20 2016-04-27 Boehringer Ingelheim International GmbH Olefin substituted oxindoles having ampk activity
MX2016009655A (es) * 2014-01-27 2016-11-09 Boston Biomedical Inc Metodos novedosos para el tratamiento del cancer.
WO2016057931A1 (en) 2014-10-10 2016-04-14 The Research Foundation For The State University Of New York Trifluoromethoxylation of arenes via intramolecular trifluoromethoxy group migration
KR20170141716A (ko) * 2015-04-27 2017-12-26 보스톤 바이오메디칼, 인크. Stat3 경로 저해제 및 카이나제 저해제를 사용하여 암을 치료하는 방법
JPWO2017026119A1 (ja) * 2015-08-10 2018-05-24 大日本住友製薬株式会社 5−(チアゾール−4−イル)インドリン−2−オン誘導体の精製方法
WO2017160978A1 (en) 2016-03-15 2017-09-21 Boston Biomedical, Inc. Cell cultures and use thereof
WO2018005444A2 (en) 2016-06-28 2018-01-04 Boston Biomedical, Inc. Methods for treating cancer
WO2018098352A2 (en) 2016-11-22 2018-05-31 Jun Oishi Targeting kras induced immune checkpoint expression
CA3045306A1 (en) 2016-11-29 2018-06-07 Boston Biomedical, Inc. Naphthofuran derivatives, preparation, and methods of use thereof
KR102964218B1 (ko) * 2018-09-18 2026-05-13 1글로브 바이오메디칼 씨오., 엘티디. 비만의 치료
BR112021005086A2 (pt) * 2018-09-18 2021-06-08 1Globe Biomedical Co., Ltd. tratamento para doença hepática gordurosa não alcoólica
US20250129067A1 (en) 2021-11-08 2025-04-24 Progentos Therapeutics, Inc. Platelet-derived growth factor receptor (pdgfr) alpha inhibitors and uses thereof

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DK0513387T3 (da) * 1990-11-30 2000-06-05 Otsuka Pharma Co Ltd Thiazolderivater som inhibitorer af aktivt oxygen
EP0929520B1 (en) * 1996-08-23 2005-11-02 Sugen, Inc. Indolinone combinatorial libraries and related products and methods for the treatment of disease
GB9716557D0 (en) * 1997-08-06 1997-10-08 Glaxo Group Ltd Benzylidene-1,3-dihydro-indol-2-one derivatives having anti-cancer activity
JP2001517666A (ja) * 1997-09-23 2001-10-09 藤沢薬品工業株式会社 チアゾール誘導体
HRP20020751B1 (hr) * 2000-02-15 2011-01-31 Sugen Pirolom supstituirani 2-indolinoni kao inhibitori protein kinaze
WO2001064681A2 (en) 2000-02-28 2001-09-07 Sugen, Inc. 3-(pyrolyllactone)-2-indolinone compounds as kinase inhibitors
JP2003535847A (ja) * 2000-06-02 2003-12-02 スージェン・インコーポレーテッド 蛋白質キナーゼ/ホスファターゼ阻害剤としてのインドリノン誘導体
ATE497603T1 (de) * 2001-03-02 2011-02-15 Gpc Biotech Ag Drei-hybrid-assaysystem
US6797725B2 (en) 2001-04-09 2004-09-28 Sugen, Inc. Prodrugs of a 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
US20030119839A1 (en) * 2001-12-13 2003-06-26 Nan-Horng Lin Protein kinase inhibitors
SE0200979D0 (sv) * 2002-03-28 2002-03-28 Astrazeneca Ab New compounds
US20050032871A1 (en) * 2002-09-03 2005-02-10 Sugen, Inc. Sulfonylated pyrrole-2-indolinone derivatives as kinase inhibitors
MXPA06004438A (es) * 2003-10-24 2006-06-20 Schering Ag Derivados de indolinona y su uso en el tratamiento de enfermedades como el cancer.
PL1973910T3 (pl) * 2006-01-27 2013-11-29 Shanghai hengrui pharmaceutical co ltd Pirolo[3,2-c]pirydyn-4-onowo-2-indolinonowe inhibitory kinazy białkowej
AU2008257693B2 (en) * 2007-06-01 2011-01-27 F. Hoffmann-La Roche Ag Piperidine-amide derivatives
CA2736177A1 (en) * 2007-09-06 2009-03-12 Boston Biomedical, Inc. Compositions of kinase inhibitors and their use for treatment of cancer and other diseases related to kinases
US9187454B2 (en) * 2013-03-13 2015-11-17 Boston Biomedical, Inc. Inhibitors of kinases and cancer stem cells, and methods of preparation and use thereof

Also Published As

Publication number Publication date
US8299106B2 (en) 2012-10-30
HUE030774T2 (hu) 2017-05-29
HK1148529A1 (en) 2011-09-09
US9725444B2 (en) 2017-08-08
WO2009033033A2 (en) 2009-03-12
US20100285006A1 (en) 2010-11-11
CY1118012T1 (el) 2017-05-17
EP2197878B1 (en) 2016-08-17
JP5452490B2 (ja) 2014-03-26
ES2591028T3 (es) 2016-11-24
EP3037419A1 (en) 2016-06-29
JP2010538091A (ja) 2010-12-09
US20180022743A1 (en) 2018-01-25
JP5701372B2 (ja) 2015-04-15
HRP20161114T1 (hr) 2016-11-04
LT2197878T (lt) 2016-09-26
SI2197878T1 (sl) 2016-10-28
WO2009033033A3 (en) 2009-04-30
CN101848908B (zh) 2014-07-02
US20190248781A1 (en) 2019-08-15
JP2019070051A (ja) 2019-05-09
EP2197878A2 (en) 2010-06-23
EP2197878A4 (en) 2012-02-08
EP3037419B1 (en) 2019-09-04
PL2197878T3 (pl) 2017-01-31
JP6495868B2 (ja) 2019-04-03
JP5974124B2 (ja) 2016-08-23
HK1226071A1 (en) 2017-09-22
US20120321622A1 (en) 2012-12-20
JP2014058573A (ja) 2014-04-03
CA2736177A1 (en) 2009-03-12
JP2016180013A (ja) 2016-10-13
PT2197878T (pt) 2016-11-04
JP2015129152A (ja) 2015-07-16
CN101848908A (zh) 2010-09-29
DK2197878T3 (en) 2016-11-14
US20150197517A1 (en) 2015-07-16

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