TWI314053B - Use of compounds that are effective as selective opiate receptor modulators - Google Patents
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- TWI314053B TWI314053B TW092112843A TW92112843A TWI314053B TW I314053 B TWI314053 B TW I314053B TW 092112843 A TW092112843 A TW 092112843A TW 92112843 A TW92112843 A TW 92112843A TW I314053 B TWI314053 B TW I314053B
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- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 235000014393 valine Nutrition 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 108020001588 κ-opioid receptors Proteins 0.000 description 1
Classifications
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/45—Non condensed piperidines, e.g. piperocaine having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic 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
-
- 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
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- 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
- A61P35/00—Antineoplastic 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
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02011047 | 2002-05-17 |
Publications (2)
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| TW200307541A TW200307541A (en) | 2003-12-16 |
| TWI314053B true TWI314053B (en) | 2009-09-01 |
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| TW092112843A TWI314053B (en) | 2002-05-17 | 2003-05-12 | Use of compounds that are effective as selective opiate receptor modulators |
Country Status (20)
| Country | Link |
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| US (1) | US20050176746A1 (https=) |
| EP (2) | EP1505974B1 (https=) |
| JP (1) | JP2005531557A (https=) |
| KR (1) | KR101108014B1 (https=) |
| CN (2) | CN101310723A (https=) |
| AR (1) | AR040028A1 (https=) |
| AT (1) | ATE429226T1 (https=) |
| AU (1) | AU2003242527B2 (https=) |
| BR (1) | BR0309969A (https=) |
| CA (1) | CA2486000A1 (https=) |
| DE (1) | DE60327315D1 (https=) |
| DK (1) | DK1505974T3 (https=) |
| ES (1) | ES2325782T3 (https=) |
| MX (1) | MXPA04011333A (https=) |
| PE (1) | PE20040455A1 (https=) |
| PL (1) | PL371596A1 (https=) |
| RU (1) | RU2336871C2 (https=) |
| TW (1) | TWI314053B (https=) |
| WO (1) | WO2003097051A2 (https=) |
| ZA (1) | ZA200410160B (https=) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
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| DE10259245A1 (de) * | 2002-12-17 | 2004-07-01 | Merck Patent Gmbh | Derivate des Asimadolins mit kovalent gebundenen Säuren |
| SG168407A1 (en) | 2003-01-28 | 2011-02-28 | Ironwood Pharmaceuticals Inc | Methods and compositions for the treatment of gastrointestinal disorders |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| EP1870096A3 (en) * | 2003-04-29 | 2011-04-20 | Orexigen Therapeutics, Inc. | Compositions for affecting weight loss |
| EP1617832B1 (en) | 2003-04-29 | 2008-03-12 | Orexigen Therapeutics, Inc. | Compositions for affecting weight loss |
| US20080090859A1 (en) * | 2003-10-30 | 2008-04-17 | Tioga Pharmaceuticals, Inc. | Use of Selective Opiate Receptor Modulators In the Treatment Of Neuropathy |
| CN101370488B (zh) | 2005-11-22 | 2012-07-18 | 奥雷西根治疗公司 | 增加胰岛素敏感性的组合物 |
| US8916195B2 (en) | 2006-06-05 | 2014-12-23 | Orexigen Therapeutics, Inc. | Sustained release formulation of naltrexone |
| KR20170077291A (ko) | 2006-11-09 | 2017-07-05 | 오렉시젠 세러퓨틱스 인크. | 단위 용량 팩키지 |
| CN101677997B (zh) * | 2007-03-30 | 2012-05-09 | 泰奥加制药公司 | 用于治疗腹泻型和交替型肠易激综合征的κ-阿片剂激动剂 |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| EP2527360B1 (en) | 2007-06-04 | 2015-10-28 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| WO2009158114A1 (en) | 2008-05-30 | 2009-12-30 | Orexigen Therapeutics, Inc. | Methods for treating visceral fat conditions |
| EP2810951B1 (en) | 2008-06-04 | 2017-03-15 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EP3241839B1 (en) | 2008-07-16 | 2019-09-04 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| CA2994066A1 (en) | 2008-12-03 | 2010-06-10 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase c agonists and methods of use |
| WO2018129556A1 (en) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| SI2384318T1 (en) | 2008-12-31 | 2018-03-30 | Ardelyx, Inc. | MEASURES AND PROCEDURES FOR THE INHIBITION OF ANTIPORT INHIBITED BY NHE IN THE TREATMENT OF DISEASES RELATED TO STRENGTH OF FLAMMABILITY OR TRADEMARITY WITH SOLO, AND THE EMISSION OF GASTROINTESTINAL TREATMENT |
| RU2413512C1 (ru) * | 2009-07-29 | 2011-03-10 | Федеральное государственное автономное образовательное учреждение высшего профессионального образования "ЮЖНЫЙ ФЕДЕРАЛЬНЫЙ УНИВЕРСИТЕТ" | Средство, обладающее каппа-опиоидной агонистической активностью |
| MX344303B (es) | 2010-01-11 | 2016-12-13 | Orexigen Therapeutics Inc | Metodos para proveer terapia de perdida de peso en pacientes con depresion mayor. |
| WO2012012410A2 (en) * | 2010-07-19 | 2012-01-26 | Dr. Reddy's Laboratories Ltd. | Kappa opioid receptor agonists |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| ES2664873T3 (es) | 2011-03-01 | 2018-04-23 | Synergy Pharmaceuticals Inc. | Proceso de preparación de agonistas de guanilato ciclasa C |
| CN110893181A (zh) | 2012-06-06 | 2020-03-20 | 纳丙药业有限责任公司 | 治疗超重和肥胖症的方法 |
| US10376481B2 (en) | 2012-08-21 | 2019-08-13 | Ardelyx, Inc. | Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| MX366293B (es) | 2012-08-21 | 2019-07-04 | Ardelyx Inc | Compuestos y metodos para inhibir al antipuerto mediado por nhe en el tratamiento de trastornos asociados con la retencion de fluidos o la sobrecarga de sal y trastornos del tracto gastrointestinal. |
| US9675587B2 (en) | 2013-03-14 | 2017-06-13 | Allergan Holdings Unlimited Company | Opioid receptor modulator dosage formulations |
| CA2905435A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| CA2905438A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| LT2983667T (lt) | 2013-04-12 | 2019-07-10 | Ardelyx, Inc. | Nhe3 rišantys junginiai ir fosfato pernešimo slopinimo būdai |
| SI3004138T1 (sl) | 2013-06-05 | 2024-07-31 | Bausch Health Ireland Limited | Ultra čisti agonisti gvanilat ciklaze C, postopek za njihovo pripravo in uporabo |
| EA023231B1 (ru) * | 2013-07-18 | 2016-05-31 | Федеральное государственное бюджетное учреждение "Научно-исследовательский институт нормальной физиологии имени П.К. Анохина" Российской академии медицинских наук (ФГБУ "НИИНФ им. П.К. Анохина" РАМН) | Применение агониста каппа опиоидных рецепторов периферического действия ici 204,448 для приготовления средств для лечения синдрома отмены никотина |
| US20160250277A1 (en) * | 2013-10-28 | 2016-09-01 | Cara Therapeutics, Inc. | Peripheral kappa opioid receptor agonists for preventing, inhibiting or treating nausea and vomiting |
| US8969371B1 (en) | 2013-12-06 | 2015-03-03 | Orexigen Therapeutics, Inc. | Compositions and methods for weight loss in at risk patient populations |
| EA201991676A1 (ru) | 2017-01-09 | 2020-01-30 | Арделикс, Инк. | Ингибиторы nhe-опосредованного антипорта |
| CA3049678A1 (en) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Compounds useful for treating gastrointestinal tract disorders |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4889860A (en) * | 1985-09-23 | 1989-12-26 | Nova Pharmaceutical Corporation | Oximes of oxymorphone, naltrexone and naloxone as potent, selective opioid receptor agonists and antagonists |
| DE3935371A1 (de) | 1988-12-23 | 1990-07-05 | Merck Patent Gmbh | Stickstoffhaltige ringverbindungen |
| DE4034785A1 (de) | 1990-11-02 | 1992-05-07 | Merck Patent Gmbh | 1-(2-arylethyl)-pyrrolidine |
| US5389686A (en) * | 1989-02-20 | 1995-02-14 | Jouveinal Sa | Analgesic properties of fedotozine |
| DE4215213A1 (de) | 1992-05-09 | 1993-11-11 | Merck Patent Gmbh | Arylacetamide |
| DE4215231C1 (en) | 1992-05-09 | 1993-05-13 | Dornier Luftfahrt Gmbh, 8031 Wessling, De | Arrangement for mfg. fibre reinforced thermoplastic components - including unit for accommodating component, pressurising unit for assembled component and heating unit |
| DE19523502A1 (de) * | 1995-06-28 | 1997-01-02 | Merck Patent Gmbh | Kappa-Opiatagonisten für entzündliche Darmerkrankungen |
| DE19531464A1 (de) * | 1995-08-26 | 1997-02-27 | Merck Patent Gmbh | N-Methyl-N-[(1S-)-1-phenyl-2-((3S)-3-hydroxypyrrolidin 1-yl-)-ethyl]-2,2-diphenyl-acetamid |
| IL135258A0 (en) * | 1997-09-26 | 2001-05-20 | Noven Pharma | Bioadhesive compositions and methods for topical administration of active agents |
| US20010051181A1 (en) * | 1997-12-22 | 2001-12-13 | Van Osdol William W. | Novel formulations for the transdermal administration of asimadoline |
| JPH11343244A (ja) * | 1998-03-30 | 1999-12-14 | Taisho Pharmaceut Co Ltd | 経口用組成物 |
| JP2000080047A (ja) * | 1998-06-30 | 2000-03-21 | Takeda Chem Ind Ltd | 医 薬 |
| WO2000004050A2 (en) * | 1998-07-14 | 2000-01-27 | Janssen Pharmaceutica N.V. | Neurotrophic growth factor |
| ATE289586T1 (de) * | 1999-03-01 | 2005-03-15 | Pfizer Prod Inc | Oxamsäuren mit einer cyanogruppe als liganden für den thyroidrezeptor |
| WO2001097753A2 (en) * | 2000-06-19 | 2001-12-27 | Eisai Co. Ltd. | Novel methods using pyridine derivatives |
| GB0015562D0 (en) * | 2000-06-23 | 2000-08-16 | Pfizer Ltd | Heterocycles |
| DE10030893A1 (de) * | 2000-06-23 | 2002-01-03 | Henkel Kgaa | Paraaminophenol-Derivate und deren Verwendung |
| US6262062B1 (en) * | 2000-08-15 | 2001-07-17 | Cpd, Llc | Method of treating the syndrome of coronary heart disease risk factors in humans |
| US6569449B1 (en) * | 2000-11-13 | 2003-05-27 | University Of Kentucky Research Foundation | Transdermal delivery of opioid antagonist prodrugs |
| US6780891B2 (en) * | 2001-11-30 | 2004-08-24 | Sepracor Inc. | Tramadol analogs and uses thereof |
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2003
- 2003-04-28 US US10/514,887 patent/US20050176746A1/en not_active Abandoned
- 2003-04-28 MX MXPA04011333A patent/MXPA04011333A/es active IP Right Grant
- 2003-04-28 KR KR1020047018468A patent/KR101108014B1/ko not_active Expired - Fee Related
- 2003-04-28 BR BR0309969-5A patent/BR0309969A/pt not_active Application Discontinuation
- 2003-04-28 AU AU2003242527A patent/AU2003242527B2/en not_active Ceased
- 2003-04-28 EP EP03752716A patent/EP1505974B1/en not_active Expired - Lifetime
- 2003-04-28 EP EP09158047A patent/EP2074997A1/en not_active Withdrawn
- 2003-04-28 DK DK03752716T patent/DK1505974T3/da active
- 2003-04-28 PL PL03371596A patent/PL371596A1/xx not_active Application Discontinuation
- 2003-04-28 AT AT03752716T patent/ATE429226T1/de not_active IP Right Cessation
- 2003-04-28 CN CNA2008101295692A patent/CN101310723A/zh active Pending
- 2003-04-28 WO PCT/EP2003/004428 patent/WO2003097051A2/en not_active Ceased
- 2003-04-28 JP JP2004505050A patent/JP2005531557A/ja active Pending
- 2003-04-28 CN CNB038111373A patent/CN100411618C/zh not_active Expired - Fee Related
- 2003-04-28 ES ES03752716T patent/ES2325782T3/es not_active Expired - Lifetime
- 2003-04-28 RU RU2004137091/15A patent/RU2336871C2/ru not_active IP Right Cessation
- 2003-04-28 DE DE60327315T patent/DE60327315D1/de not_active Expired - Lifetime
- 2003-04-28 CA CA002486000A patent/CA2486000A1/en not_active Abandoned
- 2003-05-12 TW TW092112843A patent/TWI314053B/zh not_active IP Right Cessation
- 2003-05-13 PE PE2003000457A patent/PE20040455A1/es not_active Application Discontinuation
- 2003-05-16 AR ARP030101709A patent/AR040028A1/es unknown
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2004
- 2004-12-15 ZA ZA2004/10160A patent/ZA200410160B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE60327315D1 (de) | 2009-06-04 |
| DK1505974T3 (da) | 2009-08-17 |
| KR20050010807A (ko) | 2005-01-28 |
| AR040028A1 (es) | 2005-03-09 |
| RU2336871C2 (ru) | 2008-10-27 |
| ES2325782T3 (es) | 2009-09-17 |
| ZA200410160B (en) | 2005-12-28 |
| US20050176746A1 (en) | 2005-08-11 |
| AU2003242527A1 (en) | 2003-12-02 |
| EP1505974A2 (en) | 2005-02-16 |
| HK1079451A1 (zh) | 2006-04-07 |
| CN100411618C (zh) | 2008-08-20 |
| KR101108014B1 (ko) | 2012-01-25 |
| BR0309969A (pt) | 2005-04-26 |
| TW200307541A (en) | 2003-12-16 |
| WO2003097051A3 (en) | 2004-12-09 |
| ATE429226T1 (de) | 2009-05-15 |
| PL371596A1 (en) | 2005-06-27 |
| MXPA04011333A (es) | 2005-02-14 |
| AU2003242527B2 (en) | 2008-10-23 |
| RU2004137091A (ru) | 2005-09-10 |
| WO2003097051A2 (en) | 2003-11-27 |
| CA2486000A1 (en) | 2003-11-27 |
| CN1655784A (zh) | 2005-08-17 |
| PE20040455A1 (es) | 2004-08-07 |
| CN101310723A (zh) | 2008-11-26 |
| EP2074997A1 (en) | 2009-07-01 |
| JP2005531557A (ja) | 2005-10-20 |
| EP1505974B1 (en) | 2009-04-22 |
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| MM4A | Annulment or lapse of patent due to non-payment of fees |