DK2034839T3 - TREATMENT OF NEURODEGENERATIVE DISEASES BY INHIBITION OF HSP90 - Google Patents
TREATMENT OF NEURODEGENERATIVE DISEASES BY INHIBITION OF HSP90 Download PDFInfo
- Publication number
- DK2034839T3 DK2034839T3 DK07812557.2T DK07812557T DK2034839T3 DK 2034839 T3 DK2034839 T3 DK 2034839T3 DK 07812557 T DK07812557 T DK 07812557T DK 2034839 T3 DK2034839 T3 DK 2034839T3
- Authority
- DK
- Denmark
- Prior art keywords
- tau
- hsp90
- compound
- disease
- brain
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Toxicology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80642706P | 2006-06-30 | 2006-06-30 | |
| PCT/US2007/072671 WO2008005937A2 (en) | 2006-06-30 | 2007-07-02 | Treatment of neurodegenerative diseases through inhibiton of hsp90 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2034839T3 true DK2034839T3 (en) | 2017-12-04 |
Family
ID=38895418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK07812557.2T DK2034839T3 (en) | 2006-06-30 | 2007-07-02 | TREATMENT OF NEURODEGENERATIVE DISEASES BY INHIBITION OF HSP90 |
Country Status (8)
| Country | Link |
|---|---|
| US (5) | US10336757B2 (OSRAM) |
| EP (2) | EP2034839B1 (OSRAM) |
| JP (5) | JP5599610B2 (OSRAM) |
| AU (1) | AU2007269144B2 (OSRAM) |
| CA (1) | CA2656202C (OSRAM) |
| DK (1) | DK2034839T3 (OSRAM) |
| ES (1) | ES2645095T3 (OSRAM) |
| WO (1) | WO2008005937A2 (OSRAM) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9403828B2 (en) | 2005-02-01 | 2016-08-02 | Sloan-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| US7834181B2 (en) * | 2005-02-01 | 2010-11-16 | Slaon-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| CA2652263A1 (en) * | 2006-05-12 | 2007-11-22 | Myriad Genetics, Inc. | Therapeutic compounds and their use in cancer |
| WO2008005937A2 (en) * | 2006-06-30 | 2008-01-10 | Sloan-Kettering Institute For Cancer Research | Treatment of neurodegenerative diseases through inhibiton of hsp90 |
| EP2069324B1 (en) | 2007-03-20 | 2013-07-31 | Curis, Inc. | Fused amino pyridine as hsp90 inhibitors |
| AU2008322503A1 (en) * | 2007-11-14 | 2009-05-22 | Myrexis, Inc. | Therapeutic compounds and their use in treating diseases and disorders |
| US20090258869A1 (en) * | 2008-02-08 | 2009-10-15 | The Regents Of The University Of California | Methods and compounds for treatment or prevention of substance-related disorders |
| ES2385735T3 (es) | 2008-06-26 | 2012-07-31 | Orphazyme Aps | Uso de Hsp70 como regulador de la actividad enzimática |
| ES2444777T3 (es) | 2009-06-12 | 2014-02-26 | Bristol-Myers Squibb Company | Compuestos de nicotinamida útiles como moduladores de quinasas |
| AU2013204109B2 (en) * | 2009-10-07 | 2016-05-05 | Sloan-Kettering Institute For Cancer Research | Purine derivatives useful as hsp90 inhibitors |
| NZ599138A (en) | 2009-10-07 | 2014-06-27 | Sloan Kettering Inst Cancer | Purine derivatives useful as hsp90 inhibitors |
| RU2013125923A (ru) | 2010-11-30 | 2015-01-10 | Орфазиме Апс | СПОСОБЫ УВЕЛИЧЕНИЯ ВНУТРИКЛЕТОЧНОЙ АКТИВНОСТИ Hsp70 |
| CA2832530C (en) * | 2011-04-05 | 2021-02-16 | Sloan-Kettering Institute For Cancer Research | Hsp90 inhibitors |
| CN103596955B (zh) | 2011-04-05 | 2016-11-16 | 索隆-基特林癌症研究协会 | Hsp90抑制剂 |
| CN104081203B (zh) * | 2011-07-08 | 2018-07-31 | 索隆-基特林癌症研究协会 | 标记的hsp90抑制剂的用途 |
| US20140079636A1 (en) | 2012-04-16 | 2014-03-20 | Dinesh U. Chimmanamada | Targeted therapeutics |
| EP2879675B1 (en) | 2012-08-06 | 2019-11-13 | Duke University | Compounds and methods for targeting hsp90 |
| EP2948447B1 (en) | 2013-01-23 | 2016-09-21 | Astrazeneca AB | Chemical compounds |
| CA2905509A1 (en) | 2013-03-15 | 2014-09-18 | Memorial Sloan-Kettering Cancer Center | Hsp90-targeted cardiac imaging and therapy |
| EP3033338A4 (en) | 2013-08-16 | 2017-06-14 | Memorial Sloan-Kettering Cancer Center | Selective grp94 inhibitors and uses thereof |
| WO2015038649A1 (en) | 2013-09-10 | 2015-03-19 | Synta Pharmaceuticals Corp. | Targeted therapeutics |
| WO2015066053A2 (en) | 2013-10-28 | 2015-05-07 | Synta Pharmaceuticals Corp. | Targeted therapeutics |
| RU2016128528A (ru) | 2013-12-23 | 2018-01-30 | Мемориал Слоун-Кеттеринг Кэнсэ Сентр | Способы и реактивы для введения радиоактивной метки |
| JP2017505777A (ja) | 2014-01-29 | 2017-02-23 | シンタ ファーマスーティカルズ コーポレーション | 標的化治療薬 |
| JP6576942B6 (ja) | 2014-03-03 | 2019-11-27 | マドリガル ファーマシューティカルズ インコーポレイテッド | 標的治療薬 |
| EP3131586A4 (en) | 2014-03-18 | 2017-10-25 | Madrigal Pharmaceuticals, Inc. | Targeted therapeutics |
| DK3193840T3 (da) | 2014-09-15 | 2021-08-16 | Orphazyme As | Arimoclomol-formulering |
| AU2015317632B2 (en) * | 2014-09-17 | 2022-01-13 | Memorial Sloan Kettering Cancer Center | Hsp90-targeted inflammation and infection imaging and therapy |
| EA201890623A1 (ru) | 2015-10-05 | 2018-09-28 | Мемориал Слоун Кеттеринг Кэнсер Сентр | Рациональная комбинированная терапия для лечения рака |
| US10898476B2 (en) | 2016-04-13 | 2021-01-26 | Orphazyme A/S | Heat shock proteins and cholesterol homeostasis |
| WO2017184956A1 (en) | 2016-04-22 | 2017-10-26 | Duke University | Compounds and methods for targeting hsp90 |
| DK3782624T3 (da) | 2016-04-29 | 2025-12-15 | Zevra Denmark As | Arimoclomol til behandling af glucocerebrosidase-associerede lidelser |
| US11014927B2 (en) | 2017-03-20 | 2021-05-25 | Forma Therapeutics, Inc. | Pyrrolopyrrole compositions as pyruvate kinase (PKR) activators |
| SG10201913562VA (en) * | 2017-04-24 | 2020-03-30 | Samus Therapeutics Inc | Hsp90 inhibitor oral formulations and related methods |
| US11491145B2 (en) | 2017-06-20 | 2022-11-08 | Madrigal Pharmaceuticals, Inc. | Combination therapies comprising targeted therapeutics |
| CA3067572A1 (en) | 2017-06-20 | 2018-12-27 | Madrigal Pharmaceuticals, Inc. | Targeted therapeutics |
| KR20200019220A (ko) * | 2017-06-23 | 2020-02-21 | 사무스 테라퓨틱스, 인코포레이티드 | 외상성 뇌 손상 및 이의 후유증에 대한 에피샤페롬 저해제 치료법 |
| CN112074505B (zh) | 2018-03-08 | 2024-04-05 | 因赛特公司 | 作为PI3K-γ抑制剂的氨基吡嗪二醇化合物 |
| US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
| ES2989438T3 (es) | 2018-09-19 | 2024-11-26 | Novo Nordisk Healthcare Ag | Activación de la piruvato cinasa R |
| US12053458B2 (en) | 2018-09-19 | 2024-08-06 | Novo Nordisk Health Care Ag | Treating sickle cell disease with a pyruvate kinase R activating compound |
| EP4031132A4 (en) | 2019-09-19 | 2023-09-13 | Forma Therapeutics, Inc. | Activating pyruvate kinase r |
| EP4247792A1 (en) | 2020-11-19 | 2023-09-27 | Zevra Denmark A/S | Processes for preparing arimoclomol citrate and intermediates thereof |
| US12128035B2 (en) | 2021-03-19 | 2024-10-29 | Novo Nordisk Health Care Ag | Activating pyruvate kinase R |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69841549D1 (de) | 1997-05-14 | 2010-04-22 | Sloan Kettering Inst Cancer | Verfahren und zubereitungen zur zerstörung bestimmter proteine |
| WO2000061578A1 (en) | 1999-04-09 | 2000-10-19 | Sloan-Kettering Institute For Cancer Research | Methods and compositions for degradation and/or inhibition of her-family tyrosine kinases |
| EP1335920B1 (en) * | 2000-11-02 | 2013-04-03 | Sloan-Kettering Institute For Cancer Research | Compositions containing purine derivatives for binding to hsp90 |
| WO2002094259A1 (en) * | 2001-05-03 | 2002-11-28 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Compounds that inhibit hsp90 and stimulate hsp70 and hsp40, useful in the prevention or treatment of diseases associated with protein aggregation and amyloid formation |
| CA2464031A1 (en) | 2001-10-30 | 2003-05-08 | Conforma Therapeutics Corporation | Purine analogs having hsp90-inhibiting activity |
| WO2003041643A2 (en) | 2001-11-09 | 2003-05-22 | Conforma Therapeutics Corporation | Hsp90-inhibiting zearalanol compounds and methods of producing and using same |
| JP2005524661A (ja) | 2002-02-28 | 2005-08-18 | アストラゼネカ アクチボラグ | 3−シクリル−5−(窒素含有5員環)メチル−オキサゾリジノン誘導体と抗菌剤としてのその使用 |
| US7138402B2 (en) | 2003-09-18 | 2006-11-21 | Conforma Therapeutics Corporation | Pyrrolopyrimidines and related analogs as HSP90-inhibitors |
| CA2522700A1 (en) | 2003-04-18 | 2004-11-04 | Cytovia, Inc. | Methods of treating diseases responsive to induction of apoptosis and screening assays |
| GB0315111D0 (en) | 2003-06-27 | 2003-07-30 | Cancer Rec Tech Ltd | Substituted 5-membered ring compounds and their use |
| US20070178537A1 (en) | 2003-06-30 | 2007-08-02 | Sloan-Kettering Institute For Cancer Research | Assays for detection of bioactive compounds that interact with heat shock protein 90 |
| US9403828B2 (en) | 2005-02-01 | 2016-08-02 | Sloan-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| US7834181B2 (en) * | 2005-02-01 | 2010-11-16 | Slaon-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| KR101617774B1 (ko) | 2005-02-25 | 2016-05-04 | 에사넥스, 인코포레이티드 | 테트라히드로인돌론 및 테트라히드로인다졸론 유도체 |
| WO2006130469A1 (en) * | 2005-05-27 | 2006-12-07 | Oregon Health & Science University | Stimulation of neurite outgrowth by small molecules |
| US20110263693A1 (en) | 2006-03-31 | 2011-10-27 | Dana-Farber Cancer Institute, Inc. | Celastrol, gedunin, and derivatives thereof as hsp90 inhibitors |
| CA2652263A1 (en) | 2006-05-12 | 2007-11-22 | Myriad Genetics, Inc. | Therapeutic compounds and their use in cancer |
| WO2008005937A2 (en) | 2006-06-30 | 2008-01-10 | Sloan-Kettering Institute For Cancer Research | Treatment of neurodegenerative diseases through inhibiton of hsp90 |
| WO2008013985A2 (en) | 2006-07-27 | 2008-01-31 | University Of Florida | Use of heat shock activators for tissue regeneration |
| WO2008033747A2 (en) | 2006-09-11 | 2008-03-20 | Curis, Inc. | Multi-functional small molecules as anti-proliferative agents |
| CL2007002994A1 (es) | 2006-10-19 | 2008-02-08 | Wyeth Corp | Compuestos derivados heterociclicos que contienen sulfamoilo, inhibidores de hsp90; composicion farmaceutica; y uso para el tratamiento del cancer, tal como cancer de mama, de colon y prostata, entre otros. |
| GB0622084D0 (en) | 2006-11-06 | 2006-12-13 | Chroma Therapeutics Ltd | Inhibitors of HSP90 |
| WO2008070472A2 (en) | 2006-11-27 | 2008-06-12 | University Of Maryland, Baltimore | Use of plasma hsp90 related to malignancy |
| EP2069324B1 (en) | 2007-03-20 | 2013-07-31 | Curis, Inc. | Fused amino pyridine as hsp90 inhibitors |
| US20080234297A1 (en) | 2007-03-20 | 2008-09-25 | Changgeng Qian | HSP90 Inhibitors Containing a Zinc Binding Moiety |
| WO2009007399A1 (en) | 2007-07-12 | 2009-01-15 | Crystax Pharmaceuticals, S.L. | New compounds as hsp90 inhibitors |
| WO2009042646A1 (en) | 2007-09-24 | 2009-04-02 | Curis, Inc. | Anti-proliferative agents |
| AU2008322503A1 (en) | 2007-11-14 | 2009-05-22 | Myrexis, Inc. | Therapeutic compounds and their use in treating diseases and disorders |
| NZ599138A (en) | 2009-10-07 | 2014-06-27 | Sloan Kettering Inst Cancer | Purine derivatives useful as hsp90 inhibitors |
| CN103596955B (zh) | 2011-04-05 | 2016-11-16 | 索隆-基特林癌症研究协会 | Hsp90抑制剂 |
| CA2832530C (en) | 2011-04-05 | 2021-02-16 | Sloan-Kettering Institute For Cancer Research | Hsp90 inhibitors |
| EP3033338A4 (en) | 2013-08-16 | 2017-06-14 | Memorial Sloan-Kettering Cancer Center | Selective grp94 inhibitors and uses thereof |
-
2007
- 2007-07-02 WO PCT/US2007/072671 patent/WO2008005937A2/en not_active Ceased
- 2007-07-02 EP EP07812557.2A patent/EP2034839B1/en active Active
- 2007-07-02 CA CA2656202A patent/CA2656202C/en active Active
- 2007-07-02 US US12/307,063 patent/US10336757B2/en active Active
- 2007-07-02 JP JP2009518602A patent/JP5599610B2/ja not_active Expired - Fee Related
- 2007-07-02 EP EP17177927.5A patent/EP3305297A1/en not_active Withdrawn
- 2007-07-02 AU AU2007269144A patent/AU2007269144B2/en not_active Ceased
- 2007-07-02 DK DK07812557.2T patent/DK2034839T3/en active
- 2007-07-02 ES ES07812557.2T patent/ES2645095T3/es active Active
-
2013
- 2013-03-21 JP JP2013058040A patent/JP5824698B2/ja not_active Expired - Fee Related
-
2014
- 2014-09-10 US US14/482,628 patent/US20140378452A1/en not_active Abandoned
-
2015
- 2015-09-04 JP JP2015174609A patent/JP2016028063A/ja active Pending
-
2017
- 2017-06-05 JP JP2017110721A patent/JP6427227B2/ja not_active Expired - Fee Related
-
2018
- 2018-10-26 JP JP2018202024A patent/JP6585266B2/ja not_active Expired - Fee Related
-
2019
- 2019-04-30 US US16/398,650 patent/US20190389864A1/en not_active Abandoned
-
2021
- 2021-10-15 US US17/502,563 patent/US20230060990A1/en not_active Abandoned
-
2023
- 2023-05-26 US US18/202,704 patent/US12473288B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| ES2645095T3 (es) | 2017-12-04 |
| US20240158397A1 (en) | 2024-05-16 |
| AU2007269144A1 (en) | 2008-01-10 |
| JP2016028063A (ja) | 2016-02-25 |
| US20230060990A1 (en) | 2023-03-02 |
| CA2656202A1 (en) | 2008-01-10 |
| JP5599610B2 (ja) | 2014-10-01 |
| WO2008005937A2 (en) | 2008-01-10 |
| JP6427227B2 (ja) | 2018-11-21 |
| EP3305297A1 (en) | 2018-04-11 |
| CA2656202C (en) | 2018-01-16 |
| WO2008005937A3 (en) | 2008-12-11 |
| JP6585266B2 (ja) | 2019-10-02 |
| AU2007269144B2 (en) | 2013-05-16 |
| US12473288B2 (en) | 2025-11-18 |
| US10336757B2 (en) | 2019-07-02 |
| US20090298857A1 (en) | 2009-12-03 |
| EP2034839B1 (en) | 2017-08-23 |
| JP2013177389A (ja) | 2013-09-09 |
| JP5824698B2 (ja) | 2015-11-25 |
| JP2019038829A (ja) | 2019-03-14 |
| US20190389864A1 (en) | 2019-12-26 |
| JP2009542716A (ja) | 2009-12-03 |
| US20140378452A1 (en) | 2014-12-25 |
| JP2017214379A (ja) | 2017-12-07 |
| EP2034839A2 (en) | 2009-03-18 |
| EP2034839A4 (en) | 2012-08-29 |
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