ATE450522T1 - Neue thiophensulfoximine zur behandlung von komplementvermittelten krankheiten und leiden - Google Patents

Neue thiophensulfoximine zur behandlung von komplementvermittelten krankheiten und leiden

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Publication number
ATE450522T1
ATE450522T1 AT06738277T AT06738277T ATE450522T1 AT E450522 T1 ATE450522 T1 AT E450522T1 AT 06738277 T AT06738277 T AT 06738277T AT 06738277 T AT06738277 T AT 06738277T AT E450522 T1 ATE450522 T1 AT E450522T1
Authority
AT
Austria
Prior art keywords
complement
thiophensulfoximines
treatment
new
conditions
Prior art date
Application number
AT06738277T
Other languages
English (en)
Inventor
Nalin Subasinghe
Shelley Ballentine
Jeremy Travins
Ehab Khalil
Farah Ali
Kristi Leonard
Joan Gushue
Michael Winters
Heather Hufnagel
Maxwell CUMMINGS
Original Assignee
Janssen Pharmaceutica Nv
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 Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv
Application granted granted Critical
Publication of ATE450522T1 publication Critical patent/ATE450522T1/de

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/12—Heterocyclic 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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
    • 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
    • A61P1/04—Drugs 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
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • 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
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • 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
    • 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
    • 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
    • A61P3/08—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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • 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
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Dermatology (AREA)
  • Hematology (AREA)
  • Pulmonology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Obesity (AREA)
  • Transplantation (AREA)
  • Pain & Pain Management (AREA)
  • Vascular Medicine (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Emergency Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
AT06738277T 2005-03-16 2006-03-14 Neue thiophensulfoximine zur behandlung von komplementvermittelten krankheiten und leiden ATE450522T1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US66251805P 2005-03-16 2005-03-16
PCT/US2006/009196 WO2006101860A1 (en) 2005-03-16 2006-03-14 Novel thiophene sulfoximines for treating complement-mediated diseases and conditions

Publications (1)

Publication Number Publication Date
ATE450522T1 true ATE450522T1 (de) 2009-12-15

Family

ID=36645595

Family Applications (1)

Application Number Title Priority Date Filing Date
AT06738277T ATE450522T1 (de) 2005-03-16 2006-03-14 Neue thiophensulfoximine zur behandlung von komplementvermittelten krankheiten und leiden

Country Status (10)

Country Link
US (2) US7385066B2 (de)
EP (1) EP1863785B1 (de)
JP (1) JP5081807B2 (de)
KR (1) KR20080002832A (de)
AT (1) ATE450522T1 (de)
AU (1) AU2006227778A1 (de)
CA (1) CA2601523A1 (de)
DE (1) DE602006010834D1 (de)
MX (1) MX2007011293A (de)
WO (1) WO2006101860A1 (de)

Families Citing this family (22)

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Publication number Priority date Publication date Assignee Title
EP2099757B1 (de) * 2006-11-16 2014-06-25 Allergan, Inc. Sulfoximine als kinaseinhibitoren
US8558002B2 (en) 2006-11-16 2013-10-15 Allergan, Inc. Sulfoximines as kinase inhibitors
WO2009151634A1 (en) * 2008-06-12 2009-12-17 The Board Of Trustees Of The Leland Stanford Junior University Complement inhibitory agents as therapeutics in posttraumatic and degenerative arthritis
JP5793188B2 (ja) 2011-05-13 2015-10-14 国立大学法人 東京大学 自己免疫疾患治療及び予防薬としてのctrp6
WO2014066744A2 (en) 2012-10-25 2014-05-01 True North Therapeutics, Inc. Anti-complement c1s antibodies and uses thereof
ES2912396T3 (es) 2012-11-02 2022-05-25 Bioverativ Usa Inc Anticuerpos anti-C1s del complemento y uso de los mismos
UY36547A (es) 2015-02-05 2016-06-01 Bayer Cropscience Ag Derivados heterocíclicos condensados bicíclicos sustituidos por 2-(het)arilo como pesticidas
EP4212175A1 (de) 2015-04-06 2023-07-19 Bioverativ USA Inc. Humanisierte anti-c1s-antikörper und verfahren zur verwendung davon
AR105607A1 (es) 2015-08-07 2017-10-18 Bayer Cropscience Ag Derivados heterocíclicos condensados sustituidos por 2-(het)arilo como pesticidas
IL326479A (en) 2016-10-12 2026-04-01 Bioverativ Usa Inc Anti-c1s antibodies and methods of use thereof
CN106518734B (zh) * 2016-10-21 2018-06-26 丽水学院 一种用硫酚或硫醇制备亚磺酸酯的方法
CN108191792B (zh) * 2017-12-28 2020-03-27 上海博志研新药物技术有限公司 一种氢溴酸沃替西汀及其中间体的制备方法
WO2019231935A1 (en) 2018-05-29 2019-12-05 Omeros Corporation Masp-2 inhibitors and methods of use
US12240855B2 (en) 2019-03-06 2025-03-04 Daiichi Sankyo Company, Limited Pyrrolopyrazole derivative
MX2021011507A (es) 2019-03-22 2021-12-15 Achillion Pharmaceuticals Inc Compuestos farmaceuticos para el tratamiento de trastornos mediados por complemento.
AU2020395306B2 (en) * 2019-12-04 2025-04-24 Omeros Corporation MASP-2 inhibitors and methods of use
JP7699389B2 (ja) * 2019-12-04 2025-06-27 オメロス コーポレーション Masp-2阻害剤および使用方法
BR112022010895A2 (pt) 2019-12-04 2022-09-06 Omeros Corp Composto, composição farmacêutica, e, método para tratar uma doença ou distúrbio associado à serina protease-2 associada à lectina de ligação ao manan
CN115052862A (zh) 2019-12-04 2022-09-13 奥默罗斯公司 Masp-2抑制剂和使用方法
CA3193488A1 (en) * 2020-09-23 2022-03-31 Jason Allan Wiles Pharmaceutical compounds for the treatment of complement mediated disorders
CN116789570B (zh) * 2022-03-14 2026-01-27 长沙理工大学 磺酰胺脱氨制备磺酸衍生物的方法
MA71249A (fr) 2022-06-24 2025-04-30 Bioverativ Usa Inc. Méthodes de traitement de maladies médiées par complément

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4025506A (en) * 1973-12-14 1977-05-24 Pfizer Inc. Broad spectrum antibiotics
EP1169315A2 (de) * 1999-04-09 2002-01-09 Basf Aktiengesellschaft Verfahren zur herstellung von thiophenyl-amidinen
CA2369378A1 (en) 1999-04-09 2000-10-19 Basf Aktiengesellschaft Low-molecular inhibitors of complement proteases
EP1349874A2 (de) * 2000-06-21 2003-10-08 ZymoGenetics, Inc. Peptid- und polypeptid-inhibitoren des c1s-komplements

Also Published As

Publication number Publication date
US7868023B2 (en) 2011-01-11
MX2007011293A (es) 2008-03-18
CA2601523A1 (en) 2006-09-28
US7385066B2 (en) 2008-06-10
WO2006101860A1 (en) 2006-09-28
JP2008533156A (ja) 2008-08-21
KR20080002832A (ko) 2008-01-04
US20070066667A1 (en) 2007-03-22
DE602006010834D1 (de) 2010-01-14
AU2006227778A1 (en) 2006-09-28
EP1863785A1 (de) 2007-12-12
EP1863785B1 (de) 2009-12-02
US20080255108A1 (en) 2008-10-16
JP5081807B2 (ja) 2012-11-28

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