GB0324159D0 - Novel compounds - Google Patents

Novel compounds

Info

Publication number
GB0324159D0
GB0324159D0 GBGB0324159.3A GB0324159A GB0324159D0 GB 0324159 D0 GB0324159 D0 GB 0324159D0 GB 0324159 A GB0324159 A GB 0324159A GB 0324159 D0 GB0324159 D0 GB 0324159D0
Authority
GB
United Kingdom
Prior art keywords
novel compounds
novel
compounds
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
GBGB0324159.3A
Other languages
English (en)
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Glaxo Group Ltd
Original Assignee
Glaxo Group Ltd
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 Glaxo Group Ltd filed Critical Glaxo Group Ltd
Priority to GBGB0324159.3A priority Critical patent/GB0324159D0/en
Publication of GB0324159D0 publication Critical patent/GB0324159D0/en
Priority to EP04765973A priority patent/EP1675838A1/en
Priority to JP2006534702A priority patent/JP4824567B2/ja
Priority to PCT/EP2004/011619 priority patent/WO2005040144A1/en
Priority to US10/576,492 priority patent/US7846922B2/en
Priority to US12/912,026 priority patent/US8492375B2/en
Ceased legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/06Antimigraine agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/20Hypnotics; Sedatives
    • 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
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D243/00Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/08Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/02Heterocyclic 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
    • C07D417/10Heterocyclic 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 carbon chain containing aromatic rings

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Child & Adolescent Psychology (AREA)
  • Psychology (AREA)
  • Addiction (AREA)
  • Hospice & Palliative Care (AREA)
  • Anesthesiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
GBGB0324159.3A 2003-10-15 2003-10-15 Novel compounds Ceased GB0324159D0 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
GBGB0324159.3A GB0324159D0 (en) 2003-10-15 2003-10-15 Novel compounds
EP04765973A EP1675838A1 (en) 2003-10-15 2004-10-14 1-benzoyl substituted diazepine derivatives as selective histamine h3 receptor agonists
JP2006534702A JP4824567B2 (ja) 2003-10-15 2004-10-14 新規化合物
PCT/EP2004/011619 WO2005040144A1 (en) 2003-10-15 2004-10-14 Novel compounds
US10/576,492 US7846922B2 (en) 2003-10-15 2004-10-14 1-benzoyl substituted diazepine derivatives as selective histamine H3 receptor agonists
US12/912,026 US8492375B2 (en) 2003-10-15 2010-10-26 1-benzoyl substituted diazepine derivatives as selective histamine H3 receptor agonists

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GBGB0324159.3A GB0324159D0 (en) 2003-10-15 2003-10-15 Novel compounds

Publications (1)

Publication Number Publication Date
GB0324159D0 true GB0324159D0 (en) 2003-11-19

Family

ID=29559346

Family Applications (1)

Application Number Title Priority Date Filing Date
GBGB0324159.3A Ceased GB0324159D0 (en) 2003-10-15 2003-10-15 Novel compounds

Country Status (5)

Country Link
US (2) US7846922B2 (enExample)
EP (1) EP1675838A1 (enExample)
JP (1) JP4824567B2 (enExample)
GB (1) GB0324159D0 (enExample)
WO (1) WO2005040144A1 (enExample)

Families Citing this family (32)

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CN100558718C (zh) 2002-10-23 2009-11-11 詹森药业有限公司 哌嗪基和二氮杂环庚基苯甲酰胺和硫代苯甲酰胺
GB0324159D0 (en) 2003-10-15 2003-11-19 Glaxo Group Ltd Novel compounds
CN1972914A (zh) 2004-03-31 2007-05-30 詹森药业有限公司 作为组胺h3受体配合体的非咪唑杂环化合物
WO2007044085A2 (en) * 2005-05-19 2007-04-19 Xenon Pharmaceuticals Inc. Heteroaryl compounds and their uses as therapeutic agents
PT1948607E (pt) 2005-09-16 2010-06-02 Janssen Pharmaceutica Nv Ciclopropilaminas como moduladores do receptor h3 de histamina
CN101282936B (zh) * 2005-10-07 2012-05-16 橘生药品工业株式会社 氮化杂环化合物及包含其的药物组合物
EA015555B1 (ru) * 2006-05-30 2011-08-30 Янссен Фармацевтика Н.В. Замещенные пиридиламидные соединения в качестве модуляторов гистаминового h-рецептора
EP2049466A1 (en) 2006-06-29 2009-04-22 Janssen Pharmaceutica N.V. Butyl and butynyl benzyl amine compounds
JP2009544579A (ja) 2006-06-29 2009-12-17 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 置換ベンジルアミン化合物
EP2038269A1 (en) * 2006-06-29 2009-03-25 Janssen Pharmaceutica N.V. Substituted benzamide modulators of the histamine h3 receptor
GB0617575D0 (en) * 2006-09-06 2006-10-18 Syngenta Ltd Herbicidal compounds and compositions
US7893257B2 (en) * 2006-12-14 2011-02-22 Janssen Pharmaceutica Nv Process for the preparation of piperazinyl and diazepanyl benzamide derivatives
MX2009010491A (es) 2007-04-11 2009-11-09 Kissei Pharmaceutical Derivado heterociclico de 5 miembros y su uso para propositos medicos.
WO2008151184A1 (en) * 2007-06-03 2008-12-11 Vanderbilt University Benzamide mglur5 positive allosteric modulators and methods of making and using same
US8853392B2 (en) 2007-06-03 2014-10-07 Vanderbilt University Benzamide mGluR5 positive allosteric modulators and methods of making and using same
TWI577285B (zh) 2007-08-13 2017-04-11 孟山都科技有限責任公司 控制植物寄生性線蟲的化合物及方法以及被覆有該化合物之種子
JP5718053B2 (ja) 2007-08-27 2015-05-13 ヘリコン・セラピューティクス・インコーポレーテッド 治療用イソオキサゾール化合物
CL2008002622A1 (es) * 2007-09-06 2009-11-27 Glaxo Group Ltd 1-(1-metiletil)-4-{[4-(tetrahidro-2h-piran-4-iloxi)fenil]carbonil}piperazina y su sal hidrocloruro; formas cristalinas de la sal; proceso de preparacion; composicion farmaceutica; y uso para el tratamiento o profilaxis de deterioro cognitivo, fatiga o trastorno del sueno.
US8883776B2 (en) * 2007-11-20 2014-11-11 Janssen Pharmaceutica N.V. Cycloalkyloxy- and heterocycloalkyloxypyridine compounds as modulators of the histamine H3 receptor
US20090131417A1 (en) * 2007-11-20 2009-05-21 Letavic Michael A Substituted pyridyl amide compounds as modulators of the histamine h3 receptor
EP2257536A4 (en) 2008-02-14 2011-03-23 Amira Pharmaceuticals Inc CYCLIC DIARYL ETHERS AS ANTAGONISTS OF PROSTAGLANDIN D2 RECEPTORS
EP2268611A2 (en) 2008-04-02 2011-01-05 Amira Pharmaceuticals, Inc. Aminoalkylphenyl antagonists of prostaglandin d2 receptors
EP2276761B1 (en) 2008-04-23 2015-07-29 Rigel Pharmaceuticals, Inc. Carboxamide compounds for the treatment of metabolic disorders
WO2009143153A1 (en) * 2008-05-23 2009-11-26 Janssen Pharmaceutica Nv Substituted pyrrolidine amides as modulators of the histamine h3 receptor
EP2326642A2 (en) * 2008-08-15 2011-06-01 Glaxo Group Limited Salt of, and processes for the preparation of, 1-isopropyl-4-{[4-(tetrahydro-2h-pyran- 4-yloxy)phenyl]carbonyl}hexahydro-1h-1,4-diazepine
US20110189280A1 (en) * 2008-08-29 2011-08-04 Allan James Clarke Dosage form comprising 1-isopropyl-4-hexahydro-1h-1,4-diazepine or a salt thereof
WO2010057118A2 (en) 2008-11-17 2010-05-20 Amira Pharmaceuticals, Inc. Heterocyclic antagonists of prostaglandin d2 receptors
KR20110132564A (ko) * 2009-02-11 2011-12-08 선오비온 파마슈티컬스 인코포레이티드 히스타민 h3 역 작용제 및 길항제, 및 이의 사용 방법
JP5722883B2 (ja) * 2009-05-25 2015-05-27 中南大学Central South University 1−(置換ベンジル)−5−トリフルオロメチル−2−(1h)ピリドン化合物及びその塩、並びにその製造方法及びその用途
WO2013151982A1 (en) 2012-04-03 2013-10-10 Arena Pharmaceuticals, Inc. Methods and compounds useful in treating pruritus, and methods for identifying such compounds
EP2647377A1 (en) 2012-04-06 2013-10-09 Sanofi Use of an h3 receptor antagonist for the treatment of alzheimer's disease
JO3407B1 (ar) 2012-05-31 2019-10-20 Eisai R&D Man Co Ltd مركبات رباعي هيدرو بيرازولو بيريميدين

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EP0968200A1 (en) 1997-02-24 2000-01-05 ZymoGenetics, Inc. Calcitonin mimetics
US6268367B1 (en) 1998-02-23 2001-07-31 Zymogenetics, Inc. Piperazine derivatives for treating bone deficit conditions
KR20030024799A (ko) 2000-07-20 2003-03-26 뉴로젠 코포레이션 캡사이신 수용체 리간드
HUP0302893A3 (en) * 2000-08-08 2006-04-28 Ortho Mcneil Pharm Inc Non-imidazole aryloxypiperidines and pharmaceutical compositions containing them and their use
ATE449090T1 (de) 2001-07-02 2009-12-15 High Point Pharmaceuticals Llc Substituierte piperazin- und diazepanderivate zur verwendung als histamin h3 rezeptormodulatoren
DE10144226A1 (de) * 2001-09-07 2003-03-27 Henkel Kgaa Neue verbrückte p-Phenylendiamine
AU2002337142B2 (en) * 2001-09-19 2007-10-11 Aventis Pharma S.A. Indolizines as kinase protein inhibitors
AU2003203148A1 (en) * 2002-02-05 2003-09-02 High Point Pharmaceuticals, Llc Novel aryl- and heteroarylpiperazines
GB0224084D0 (en) * 2002-10-16 2002-11-27 Glaxo Group Ltd Novel compounds
EP1554260A1 (en) 2002-10-22 2005-07-20 Glaxo Group Limited Aryloxyalkylamine derivatives as h3 receptor ligands
CN100558718C (zh) 2002-10-23 2009-11-11 詹森药业有限公司 哌嗪基和二氮杂环庚基苯甲酰胺和硫代苯甲酰胺
US7449464B2 (en) * 2003-03-12 2008-11-11 Kudos Pharmaceuticals Limited Phthalazinone derivatives
KR101146806B1 (ko) 2003-03-12 2012-05-22 메이브릿지 리미티드 프탈라지논 유도체
SI1615909T1 (sl) 2003-04-23 2008-12-31 Glaxo Group Ltd Derivati piperazina in njihova uporaba za zdravljenje nevroloĺ kih in psihiatriäśnih bolezni
GB0324159D0 (en) 2003-10-15 2003-11-19 Glaxo Group Ltd Novel compounds
HRP20080227T3 (hr) 2004-10-15 2008-06-30 Glaxo Group Limited Pirolidinski derivati kao ligandi histaminskih receptora
CA2628210A1 (en) 2005-10-31 2007-05-10 Janssen Pharmaceutica N.V. Novel processes for the preparation of piperazinyl and diazapanyl benzamide derivatives
NZ592864A (en) 2005-10-31 2012-09-28 Janssen Pharmaceutica Nv Processes for the preparation of cyclopropyl-amide derivatives
US7893257B2 (en) 2006-12-14 2011-02-22 Janssen Pharmaceutica Nv Process for the preparation of piperazinyl and diazepanyl benzamide derivatives
TW201446748A (zh) 2007-08-22 2014-12-16 Astrazeneca Ab 環丙基醯胺衍生物
CL2008002622A1 (es) 2007-09-06 2009-11-27 Glaxo Group Ltd 1-(1-metiletil)-4-{[4-(tetrahidro-2h-piran-4-iloxi)fenil]carbonil}piperazina y su sal hidrocloruro; formas cristalinas de la sal; proceso de preparacion; composicion farmaceutica; y uso para el tratamiento o profilaxis de deterioro cognitivo, fatiga o trastorno del sueno.
US8883776B2 (en) 2007-11-20 2014-11-11 Janssen Pharmaceutica N.V. Cycloalkyloxy- and heterocycloalkyloxypyridine compounds as modulators of the histamine H3 receptor

Also Published As

Publication number Publication date
US8492375B2 (en) 2013-07-23
US20080045505A1 (en) 2008-02-21
JP2007508346A (ja) 2007-04-05
US7846922B2 (en) 2010-12-07
JP4824567B2 (ja) 2011-11-30
WO2005040144A1 (en) 2005-05-06
EP1675838A1 (en) 2006-07-05
US20110039833A1 (en) 2011-02-17

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AT Applications terminated before publication under section 16(1)