ATE493415T1 - Neue diazabizyklische arylderivate und medizinische verwendung dafür - Google Patents
Neue diazabizyklische arylderivate und medizinische verwendung dafürInfo
- Publication number
- ATE493415T1 ATE493415T1 AT05801524T AT05801524T ATE493415T1 AT E493415 T1 ATE493415 T1 AT E493415T1 AT 05801524 T AT05801524 T AT 05801524T AT 05801524 T AT05801524 T AT 05801524T AT E493415 T1 ATE493415 T1 AT E493415T1
- Authority
- AT
- Austria
- Prior art keywords
- diseases
- disorders
- aryl derivatives
- new
- diazabicyclic aryl
- Prior art date
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 8
- 201000010099 disease Diseases 0.000 abstract 4
- 208000035475 disorder Diseases 0.000 abstract 4
- 210000003169 central nervous system Anatomy 0.000 abstract 2
- 230000001713 cholinergic effect Effects 0.000 abstract 2
- 210000001428 peripheral nervous system Anatomy 0.000 abstract 2
- 108010078791 Carrier Proteins Proteins 0.000 abstract 1
- 208000017701 Endocrine disease Diseases 0.000 abstract 1
- 206010061218 Inflammation Diseases 0.000 abstract 1
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 abstract 1
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 abstract 1
- 208000002193 Pain Diseases 0.000 abstract 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 208000030172 endocrine system disease Diseases 0.000 abstract 1
- 230000004054 inflammatory process Effects 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 230000004770 neurodegeneration Effects 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- 102000005962 receptors Human genes 0.000 abstract 1
- 108020003175 receptors Proteins 0.000 abstract 1
- 230000016160 smooth muscle contraction Effects 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- 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
- A61P1/10—Laxatives
-
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
- 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
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
- A61P25/32—Alcohol-abuse
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- 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
- A61P25/34—Tobacco-abuse
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- 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
- 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
- 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
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Psychology (AREA)
- Pulmonology (AREA)
- Reproductive Health (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Gynecology & Obstetrics (AREA)
- Child & Adolescent Psychology (AREA)
- Dermatology (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200401603 | 2004-10-20 | ||
| US62032704P | 2004-10-21 | 2004-10-21 | |
| PCT/EP2005/055333 WO2006045716A1 (en) | 2004-10-20 | 2005-10-18 | Novel diazabicyclic aryl derivatives and their medical use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ATE493415T1 true ATE493415T1 (de) | 2011-01-15 |
Family
ID=38731691
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT05801524T ATE493415T1 (de) | 2004-10-20 | 2005-10-18 | Neue diazabizyklische arylderivate und medizinische verwendung dafür |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20080153806A1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP1805183B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2008517032A (cg-RX-API-DMAC7.html) |
| CN (1) | CN101035792B (cg-RX-API-DMAC7.html) |
| AT (1) | ATE493415T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU2005298693A1 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2584838A1 (cg-RX-API-DMAC7.html) |
| DE (1) | DE602005025667D1 (cg-RX-API-DMAC7.html) |
| MX (1) | MX2007004269A (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ553622A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2006045716A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101389335A (zh) | 2004-10-18 | 2009-03-18 | 安姆根有限公司 | 噻二唑化合物和使用方法 |
| US7662812B2 (en) | 2005-02-16 | 2010-02-16 | Neurosearch A/S | Diazabicyclic aryl derivatives and their use as chinolinergic ligands at nicotinic acetylcholine receptors |
| AU2006323986A1 (en) | 2005-12-06 | 2007-06-14 | Neurosearch A/S | Novel diazabicyclic aryl derivatives and their medical use |
| WO2007090888A1 (en) | 2006-02-10 | 2007-08-16 | Neurosearch A/S | 3-heteroaryl- 3,9-diazabicyclo[3.3.1]nonane derivatives as nicotinic acetylcholine receptor agonists |
| WO2007090886A1 (en) | 2006-02-10 | 2007-08-16 | Neurosearch A/S | 3,9-diazabicyclo[3.3.1]nonane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| WO2007090887A1 (en) | 2006-02-10 | 2007-08-16 | Neurosearch A/S | 3, 9-diazabicyclo [3.3. 1]nonane derivatives and their use as monoamine?neurotransmitter re-uptake inhibitors |
| EP1987032A1 (en) | 2006-02-14 | 2008-11-05 | NeuroSearch A/S | 3, 9-diazabicyclo(3.3.1)non-3-yl-aryl methanone derivatives as nicotinic acetylcholine receptor agonists |
| EP2029607A1 (en) | 2006-05-23 | 2009-03-04 | NeuroSearch A/S | Novel 8,10-diaza-bicycloý4.3.1¨decane derivatives and their medical use |
| US8314119B2 (en) * | 2006-11-06 | 2012-11-20 | Abbvie Inc. | Azaadamantane derivatives and methods of use |
| US7897619B2 (en) | 2007-07-17 | 2011-03-01 | Amgen Inc. | Heterocyclic modulators of PKB |
| US7919504B2 (en) | 2007-07-17 | 2011-04-05 | Amgen Inc. | Thiadiazole modulators of PKB |
| SA08290475B1 (ar) * | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
| FR2937641A1 (fr) | 2008-10-28 | 2010-04-30 | Sanofi Aventis | Derives d'urees de tropane, leur preparation et leur application en therapeutique |
| CA2809675A1 (en) | 2010-09-23 | 2012-03-29 | Shuang Chen | Monohydrate of an azaadamantane derivative |
| FR2974365B1 (fr) * | 2011-04-20 | 2017-08-25 | Centre Nat De La Rech Scient (C N R S) | 1,2,3-triazoles 1,4-disubstituees, leurs procedes de preparation et leurs utilisations diagnostiques et therapeutiques |
| TW201311698A (zh) * | 2011-08-22 | 2013-03-16 | Targacept Inc | 作為神經元菸鹼乙醯膽鹼受體配位體之１，４－二氮雜雙環［３．２．２］壬烷 |
| US8729263B2 (en) * | 2012-08-13 | 2014-05-20 | Novartis Ag | 1,4-disubstituted pyridazine analogs there of and methods for treating SMN-deficiency-related conditions |
| KR20200142039A (ko) | 2018-04-10 | 2020-12-21 | 스카이호크 테라퓨틱스, 인코포레이티드 | 암 치료용 화합물 |
| JP7190612B2 (ja) | 2020-07-17 | 2022-12-15 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 置換ピペリジン化合物及びその用途 |
| JP7591592B2 (ja) * | 2022-01-14 | 2024-11-28 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 置換ピペリジン化合物を含有する医薬 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7265115B2 (en) * | 1999-01-29 | 2007-09-04 | Abbott Laboratories | Diazabicyclic CNS active agents |
| AU774867B2 (en) * | 1999-05-04 | 2004-07-08 | Neurosearch A/S | Heteroaryl diazabicycloalkanes, their preparation and use |
| US20050065178A1 (en) * | 2003-09-19 | 2005-03-24 | Anwer Basha | Substituted diazabicycloakane derivatives |
| US7399765B2 (en) * | 2003-09-19 | 2008-07-15 | Abbott Laboratories | Substituted diazabicycloalkane derivatives |
-
2005
- 2005-10-18 MX MX2007004269A patent/MX2007004269A/es active IP Right Grant
- 2005-10-18 NZ NZ553622A patent/NZ553622A/en unknown
- 2005-10-18 EP EP05801524A patent/EP1805183B1/en not_active Expired - Lifetime
- 2005-10-18 WO PCT/EP2005/055333 patent/WO2006045716A1/en not_active Ceased
- 2005-10-18 AU AU2005298693A patent/AU2005298693A1/en not_active Abandoned
- 2005-10-18 DE DE602005025667T patent/DE602005025667D1/de not_active Expired - Lifetime
- 2005-10-18 US US11/665,387 patent/US20080153806A1/en not_active Abandoned
- 2005-10-18 CA CA002584838A patent/CA2584838A1/en not_active Abandoned
- 2005-10-18 AT AT05801524T patent/ATE493415T1/de not_active IP Right Cessation
- 2005-10-18 CN CN2005800337300A patent/CN101035792B/zh not_active Expired - Fee Related
- 2005-10-18 JP JP2007537263A patent/JP2008517032A/ja not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2005298693A1 (en) | 2006-05-04 |
| DE602005025667D1 (de) | 2011-02-10 |
| CN101035792B (zh) | 2010-09-15 |
| NZ553622A (en) | 2010-08-27 |
| US20080153806A1 (en) | 2008-06-26 |
| JP2008517032A (ja) | 2008-05-22 |
| MX2007004269A (es) | 2007-06-15 |
| EP1805183B1 (en) | 2010-12-29 |
| CN101035792A (zh) | 2007-09-12 |
| EP1805183A1 (en) | 2007-07-11 |
| WO2006045716A1 (en) | 2006-05-04 |
| CA2584838A1 (en) | 2006-05-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RER | Ceased as to paragraph 5 lit. 3 law introducing patent treaties |