DK2160380T3 - Cyano-guanidin derivater som glutaminyl cyclase inhibitorer - Google Patents

Cyano-guanidin derivater som glutaminyl cyclase inhibitorer

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Publication number
DK2160380T3
DK2160380T3 DK08736361.0T DK08736361T DK2160380T3 DK 2160380 T3 DK2160380 T3 DK 2160380T3 DK 08736361 T DK08736361 T DK 08736361T DK 2160380 T3 DK2160380 T3 DK 2160380T3
Authority
DK
Denmark
Prior art keywords
cyano
guanidine derivatives
glutaminyl cyclase
cyclase inhibitors
inhibitors
Prior art date
Application number
DK08736361.0T
Other languages
Danish (da)
English (en)
Inventor
Mirko Buchholz
Ulrich Heiser
Torsten Hoffmann
Livia Böhme
Original Assignee
Probiodrug Ag
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 Probiodrug Ag filed Critical Probiodrug Ag
Application granted granted Critical
Publication of DK2160380T3 publication Critical patent/DK2160380T3/da

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C07D233/61—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
    • 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
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • 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
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/24—Antidepressants
    • 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
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • 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
    • A61P35/04—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
    • 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
    • A61P5/00—Drugs for disorders of the endocrine 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
    • 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
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D417/12—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 linked by a chain containing hetero atoms as chain links

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Psychiatry (AREA)
  • Diabetes (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Reproductive Health (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Endocrinology (AREA)
  • Psychology (AREA)
  • Pain & Pain Management (AREA)
  • Vascular Medicine (AREA)
  • Gynecology & Obstetrics (AREA)
  • Hospice & Palliative Care (AREA)
  • Communicable Diseases (AREA)
  • Anesthesiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pregnancy & Childbirth (AREA)
DK08736361.0T 2007-04-18 2008-04-18 Cyano-guanidin derivater som glutaminyl cyclase inhibitorer DK2160380T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US91252807P 2007-04-18 2007-04-18
PCT/EP2008/054712 WO2008128983A1 (en) 2007-04-18 2008-04-18 Cyano-guanidine derivatives as glutaminyl cyclase inhibitors

Publications (1)

Publication Number Publication Date
DK2160380T3 true DK2160380T3 (da) 2014-06-30

Family

ID=39639502

Family Applications (1)

Application Number Title Priority Date Filing Date
DK08736361.0T DK2160380T3 (da) 2007-04-18 2008-04-18 Cyano-guanidin derivater som glutaminyl cyclase inhibitorer

Country Status (6)

Country Link
US (1) US8227498B2 (enExample)
EP (1) EP2160380B1 (enExample)
JP (1) JP5675342B2 (enExample)
DK (1) DK2160380T3 (enExample)
ES (1) ES2474693T3 (enExample)
WO (1) WO2008128983A1 (enExample)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7732162B2 (en) * 2003-05-05 2010-06-08 Probiodrug Ag Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases
US8188094B2 (en) * 2007-04-20 2012-05-29 Probiodrug Ag Inhibitors of glutaminyl cyclase
EP2195336B1 (en) * 2007-09-12 2015-01-21 Probiodrug AG Transgenic mice
WO2009090190A1 (en) * 2008-01-14 2009-07-23 Probiodrug Ag Mouse models carrying a knock-out mutation of the glutaminyl cyclase gene
US8058405B2 (en) 2008-07-21 2011-11-15 Probiodrug (AG) Antibodies specific for N-terminal truncated and pyroglutamate modified amyloid-beta peptides
PL2475428T3 (pl) 2009-09-11 2015-12-31 Probiodrug Ag Pochodne heterocykliczne jako inhibitory cyklazy glutaminowej
US20110152341A1 (en) 2009-12-22 2011-06-23 Probiodrug Ag Cleavage of b-amyloid precursor protein
SG182615A1 (en) 2010-02-18 2012-08-30 Probiodrug Ag Methods of diagnosing inflammatory diseases by determining pyroglutamate-modified mcp-1 and screening methods for inhibitors of glutaminyl cyclase
BR112013023211B1 (pt) 2011-03-16 2022-11-08 Vivoryon Therapeutics N.V. Anticorpo monoclonal, seu uso, composição, linhagem celular, método diagnóstico in vitro e kit
EP2742062A2 (en) * 2011-08-12 2014-06-18 Probiodrug AG In vivo screening models for treatment of qc-related disorders
CA2879454A1 (en) 2012-07-19 2014-01-23 Drexel University Novel sigma receptor ligands and methods of modulating cellular protein homeostasis using same
WO2016097305A1 (en) 2014-12-19 2016-06-23 Probiodrug Ag Novel method for the detection of pglu-abeta peptides
WO2019022600A1 (en) 2017-07-24 2019-01-31 Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis TREATMENT OF PATHOLOGICAL CONDITIONS BY DIRECT AND INDIRECT TARGETING OF SIRPA INTERACTION - CD47
ES2812698T3 (es) 2017-09-29 2021-03-18 Probiodrug Ag Inhibidores de glutaminil ciclasa
WO2019089902A1 (en) 2017-11-01 2019-05-09 Drexel University Compounds, compositions, and methods for treating diseases
EP3521308B1 (en) 2018-01-31 2024-03-13 Vivoryon Therapeutics N.V. Humanized and de-immunized antibodies
CN116745281A (zh) * 2021-03-30 2023-09-12 纳美仕有限公司 固化催化剂、树脂组合物、密封材料、粘接剂和固化物

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3044566A1 (de) * 1980-11-26 1982-07-15 Basf Ag, 6700 Ludwigshafen N-substituierte imidazol-derivate, ihre herstellung, diese enthaltende arzneimittel und ihre verwendung
BR9809234A (pt) * 1997-05-07 2000-06-27 Novo Nordisk As Composto, composição farmacêutica, uso de um composto, processos para tratar ou prevenir doenças do sistema endocrinológico, para fabricar um medicamento, para preparar um composto e um conjunto, conjunto, e, uso do mesmo.
US6948038B2 (en) * 2001-07-24 2005-09-20 Microsoft Corporation System and method for backing up and restoring data
DE602004026289D1 (de) * 2003-05-05 2010-05-12 Probiodrug Ag Glutaminylcyclase-hemmer
KR20100038477A (ko) * 2003-05-05 2010-04-14 프로비오드룩 아게 글루타미닐 및 글루타메이트 사이클라제의 이펙터의 용도
US7732162B2 (en) * 2003-05-05 2010-06-08 Probiodrug Ag Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases
US8338120B2 (en) * 2003-05-05 2012-12-25 Probiodrug Ag Method of treating inflammation with glutaminyl cyclase inhibitors
EP1675578B9 (en) * 2003-10-15 2014-06-25 Probiodrug AG Inhibitors of glutaminyl and glutamate cyclases for the treatment of the neurodegenerative diseases fbd and fdd
US20050171112A1 (en) * 2003-11-03 2005-08-04 Probiodrug Ag Combinations useful for the treatment of neuronal disorders
EP2338490A3 (en) * 2003-11-03 2012-06-06 Probiodrug AG Combinations useful for the treatment of neuronal disorders
US7667044B2 (en) * 2003-11-03 2010-02-23 Probiodrug Ag Compounds for the treatment of neurological disorders
EP1713780B1 (en) * 2004-02-05 2012-01-18 Probiodrug AG Novel inhibitors of glutaminyl cyclase
WO2008034891A2 (en) * 2006-09-21 2008-03-27 Probiodrug Ag Novel genes related to glutaminyl cyclase
US8420684B2 (en) * 2006-11-09 2013-04-16 Probiodrug Ag Inhibitors of glutaminyl cyclase
US7741354B2 (en) * 2006-11-09 2010-06-22 Probiodrug Ag Inhibitors of glutaminyl cyclase
EP2091948B1 (en) * 2006-11-30 2012-04-18 Probiodrug AG Novel inhibitors of glutaminyl cyclase
JP2010516235A (ja) * 2007-01-19 2010-05-20 プロビオドルグ エージー アルツハイマー病及び他のｑｐｃｔ関連障害の治療のためのインビボスクリーニングモデル
WO2008110523A1 (en) * 2007-03-09 2008-09-18 Probiodrug Ag Imidazo [1,5-a] pyridine derivatives as inhibitors of glutaminyl cyclase

Also Published As

Publication number Publication date
JP2010524895A (ja) 2010-07-22
ES2474693T3 (es) 2014-07-09
WO2008128983A1 (en) 2008-10-30
EP2160380B1 (en) 2014-04-02
US20080267912A1 (en) 2008-10-30
EP2160380A1 (en) 2010-03-10
JP5675342B2 (ja) 2015-02-25
US8227498B2 (en) 2012-07-24

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