HK1102020A1 - Imidazole compounds - Google Patents

Imidazole compounds

Info

Publication number
HK1102020A1
HK1102020A1 HK07106767.1A HK07106767A HK1102020A1 HK 1102020 A1 HK1102020 A1 HK 1102020A1 HK 07106767 A HK07106767 A HK 07106767A HK 1102020 A1 HK1102020 A1 HK 1102020A1
Authority
HK
Hong Kong
Prior art keywords
imidazole compounds
imidazole
compounds
Prior art date
Application number
HK07106767.1A
Other languages
English (en)
Inventor
Daniel J Buzard
James P Edwards
David E Kindrachuk
Jennifer D Venable
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
Publication of HK1102020A1 publication Critical patent/HK1102020A1/xx

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • A61P3/04—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
    • 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
    • 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
    • A61P37/04—Immunostimulants
    • 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
    • A61P37/08—Antiallergic agents
    • 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
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B55/00—Racemisation; Complete or partial inversion
    • 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
    • C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/04—Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/12—Heterocyclic 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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/14—Heterocyclic 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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/12—Heterocyclic 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
    • 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
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal 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)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Hematology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Cardiology (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Obesity (AREA)
  • Pain & Pain Management (AREA)
  • Diabetes (AREA)
  • Communicable Diseases (AREA)
  • Child & Adolescent Psychology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Dermatology (AREA)
  • Neurology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
HK07106767.1A 2004-03-25 2007-06-25 Imidazole compounds HK1102020A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US55635604P 2004-03-25 2004-03-25
PCT/US2005/009715 WO2005092066A2 (en) 2004-03-25 2005-03-24 Imidazole compounds

Publications (1)

Publication Number Publication Date
HK1102020A1 true HK1102020A1 (en) 2007-11-02

Family

ID=35056771

Family Applications (1)

Application Number Title Priority Date Filing Date
HK07106767.1A HK1102020A1 (en) 2004-03-25 2007-06-25 Imidazole compounds

Country Status (19)

Country Link
US (9) US7253200B2 (ko)
EP (1) EP1737297B1 (ko)
JP (1) JP5162236B2 (ko)
KR (1) KR101217103B1 (ko)
CN (1) CN101022728B (ko)
AU (1) AU2005226729B2 (ko)
BR (1) BRPI0509164A (ko)
CA (1) CA2560896C (ko)
CR (1) CR8704A (ko)
EA (1) EA011242B1 (ko)
EC (1) ECSP066882A (ko)
HK (1) HK1102020A1 (ko)
IL (2) IL178287A (ko)
MX (1) MXPA06011021A (ko)
NO (1) NO20064848L (ko)
NZ (1) NZ550087A (ko)
UA (1) UA89226C2 (ko)
WO (1) WO2005092066A2 (ko)
ZA (1) ZA200608836B (ko)

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JP5162236B2 (ja) * 2004-03-25 2013-03-13 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 イミダゾール化合物
GB0525068D0 (en) 2005-12-08 2006-01-18 Novartis Ag Organic compounds
SI2007752T1 (sl) * 2006-03-31 2010-12-31 Janssen Pharmaceutica Nv Benzoimidazol-2-il pirimidini in pirazini kot modulatorji histamin H4 receptorja
US7589087B2 (en) * 2006-03-31 2009-09-15 Janssen Pharmaceutica, N.V. Benzoimidazol-2-yl pyridines as modulators of the histamine H4receptor
US20090069343A1 (en) * 2006-04-10 2009-03-12 Dunford Paul J Combination Histamine H1R and H4R Antagonist Therapy for Treating Pruritus
CN101511190A (zh) * 2006-07-11 2009-08-19 詹森药业有限公司 组胺h4受体的苯并呋喃并-和苯并噻吩并嘧啶调节剂
US7985745B2 (en) 2006-10-02 2011-07-26 Abbott Laboratories Method for pain treatment
TW200904437A (en) * 2007-02-14 2009-02-01 Janssen Pharmaceutica Nv 2-aminopyrimidine modulators of the histamine H4 receptor
BRPI0816922A2 (pt) 2007-09-14 2015-03-17 Janssen Pharmaceutica Nv Moduladores tieno e furo-pirimidina do receptor de histamina h4
US8084466B2 (en) * 2007-12-18 2011-12-27 Janssen Pharmaceutica Nv Bicyclic heteroaryl-substituted imidazoles as modulators of the histamine H4 receptor
PE20110052A1 (es) * 2008-06-12 2011-01-31 Janssen Pharmaceutica Nv Uso de un antagonista h4 de histamina para el tratamiento de adherencias postoperatorias
US9371311B2 (en) 2008-06-30 2016-06-21 Janssen Pharmaceutica Nv Benzoimidazol-2-yl pyrimidine derivatives
JP2011526911A (ja) 2008-06-30 2011-10-20 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 ベンゾイミダゾール−２−イルピリミジン誘導体を製造する方法
PT3279195T (pt) * 2008-12-01 2020-09-29 Oyster Point Pharma Inc Síntese e novas formas de sal de (r)-5-((e)-2-pirrolidin- 3-ilvinil)pirimidina
US9145396B2 (en) 2008-12-01 2015-09-29 Targacept, Inc. Synthesis and novel salt forms of (R)-5-((E)-2-pyrrolidin-3ylvinyl)pyrimidine
EP2201982A1 (en) 2008-12-24 2010-06-30 INSERM (Institut National de la Santé et de la Recherche Médicale) Histamine H4 receptor antagonists for the treatment of vestibular disorders
US8349852B2 (en) 2009-01-13 2013-01-08 Novartis Ag Quinazolinone derivatives useful as vanilloid antagonists
CZ30474U1 (cs) * 2009-08-20 2017-03-14 Yeda Research And Development Co., Ltd. Glatiramer acetát a terapeutická kompozice s jeho obsahem pro použití k léčení s nízkou frekvencí ošetření
USRE49251E1 (en) 2010-01-04 2022-10-18 Mapi Pharma Ltd. Depot systems comprising glatiramer or pharmacologically acceptable salt thereof
AR080056A1 (es) 2010-02-01 2012-03-07 Novartis Ag Derivados de ciclohexil-amida como antagonistas de los receptores de crf
AR080055A1 (es) 2010-02-01 2012-03-07 Novartis Ag Derivados de pirazolo-[5,1-b]-oxazol como antagonistas de los receptores de crf -1
EP2531490B1 (en) 2010-02-02 2014-10-15 Novartis AG Cyclohexyl amide derivatives as crf receptor antagonists
US8546416B2 (en) 2011-05-27 2013-10-01 Novartis Ag 3-spirocyclic piperidine derivatives as ghrelin receptor agonists
EP2852591A1 (en) 2012-05-03 2015-04-01 Novartis AG L-malate salt of 2, 7 - diaza - spiro [4.5]dec- 7 - yle derivatives and crystalline forms thereof as ghrelin receptor agonists
US9688989B2 (en) 2012-06-08 2017-06-27 Sensorion H4 receptor inhibitors for treating tinnitus
JP6471103B2 (ja) 2013-03-06 2019-02-13 ヤンセン ファーマシューティカ エヌ．ベー． ヒスタミンｈ４受容体のベンゾイミダゾール−２−イルピリミジンモジュレータ
US10414766B2 (en) * 2015-12-15 2019-09-17 Alembic Pharmaceuticals Limited Polymorph of Riociguat and its process for the preparation
EP3600553A4 (en) 2017-03-26 2020-09-02 Mapi Pharma Ltd. GLATIRAMER DEPOT SYSTEMS FOR TREATMENT OF PROGRESSIVE FORMS OF MULTIPLE SCLEROSIS

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SE0202462D0 (sv) * 2002-08-14 2002-08-14 Astrazeneca Ab Novel use
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AU2004286933B2 (en) * 2003-09-30 2010-11-18 Janssen Pharmaceutica N.V. Benzoimidazole compounds
JP5162236B2 (ja) * 2004-03-25 2013-03-13 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 イミダゾール化合物

Also Published As

Publication number Publication date
IL178287A (en) 2012-12-31
US7928131B2 (en) 2011-04-19
US20050261309A1 (en) 2005-11-24
US20070149541A1 (en) 2007-06-28
CA2560896A1 (en) 2005-10-06
CN101022728A (zh) 2007-08-22
US20070265250A1 (en) 2007-11-15
ECSP066882A (es) 2006-11-24
US8017639B2 (en) 2011-09-13
US7956066B2 (en) 2011-06-07
US20100261899A1 (en) 2010-10-14
US7956057B2 (en) 2011-06-07
EA011242B1 (ru) 2009-02-27
US8017600B2 (en) 2011-09-13
NO20064848L (no) 2006-10-25
IL178287A0 (en) 2006-12-31
US20100261898A1 (en) 2010-10-14
EP1737297A4 (en) 2009-07-15
JP2007530570A (ja) 2007-11-01
UA89226C2 (en) 2010-01-11
KR20070021186A (ko) 2007-02-22
US8039498B2 (en) 2011-10-18
EP1737297A2 (en) 2007-01-03
AU2005226729B2 (en) 2010-01-28
ZA200608836B (en) 2008-05-28
CR8704A (es) 2008-11-24
US20070173512A1 (en) 2007-07-26
EP1737297B1 (en) 2012-12-19
EA200601766A1 (ru) 2007-04-27
MXPA06011021A (es) 2007-04-13
WO2005092066A8 (en) 2007-03-29
US20070173513A1 (en) 2007-07-26
IL205159A0 (en) 2010-11-30
JP5162236B2 (ja) 2013-03-13
US20070173510A1 (en) 2007-07-26
CA2560896C (en) 2013-06-18
US7253200B2 (en) 2007-08-07
WO2005092066A2 (en) 2005-10-06
US20070173509A1 (en) 2007-07-26
WO2005092066A3 (en) 2006-01-12
AU2005226729A1 (en) 2005-10-06
CN101022728B (zh) 2012-08-08
BRPI0509164A (pt) 2007-09-11
US7951808B2 (en) 2011-05-31
NZ550087A (en) 2009-06-26
US7956071B2 (en) 2011-06-07
KR101217103B1 (ko) 2012-12-31

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PC Patent ceased (i.e. patent has lapsed due to the failure to pay the renewal fee)

Effective date: 20210326