UA75957C2 - Alkynarylnaphthyridine-4(1h) as an phosphodiesterase iv inhibitor - Google Patents
Alkynarylnaphthyridine-4(1h) as an phosphodiesterase iv inhibitor Download PDFInfo
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- UA75957C2 UA75957C2 UA2004032266A UA2004032266A UA75957C2 UA 75957 C2 UA75957 C2 UA 75957C2 UA 2004032266 A UA2004032266 A UA 2004032266A UA 2004032266 A UA2004032266 A UA 2004032266A UA 75957 C2 UA75957 C2 UA 75957C2
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- Prior art keywords
- alkyl
- dihydro
- phenyl
- carboxamide
- isopropyl
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
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- 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
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- 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
-
- 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
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- 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
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- Life Sciences & Earth Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
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- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
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- Oncology (AREA)
- Communicable Diseases (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Psychology (AREA)
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- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
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- Heart & Thoracic Surgery (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US31609301P | 2001-08-29 | 2001-08-29 | |
PCT/CA2002/001324 WO2003018579A1 (en) | 2001-08-29 | 2002-08-27 | Alkyne-aryl phosphodiesterase-4 inhibitors |
Publications (1)
Publication Number | Publication Date |
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UA75957C2 true UA75957C2 (en) | 2006-06-15 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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UA2004032266A UA75957C2 (en) | 2001-08-29 | 2002-08-27 | Alkynarylnaphthyridine-4(1h) as an phosphodiesterase iv inhibitor |
Country Status (28)
Country | Link |
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US (2) | US6743802B2 (ko) |
EP (2) | EP2305677A1 (ko) |
JP (1) | JP4157035B2 (ko) |
KR (1) | KR100928849B1 (ko) |
CN (1) | CN100338061C (ko) |
AR (1) | AR036365A1 (ko) |
AU (1) | AU2002322940B2 (ko) |
BR (1) | BR0212042A (ko) |
CA (1) | CA2456817C (ko) |
DO (1) | DOP2002000456A (ko) |
EA (1) | EA006800B1 (ko) |
EC (1) | ECSP044992A (ko) |
GE (1) | GEP20063805B (ko) |
HK (1) | HK1080073B (ko) |
HR (1) | HRP20040151A2 (ko) |
HU (1) | HUP0401729A3 (ko) |
IL (1) | IL160213A0 (ko) |
IS (1) | IS7138A (ko) |
JO (1) | JO2311B1 (ko) |
MX (1) | MXPA04001889A (ko) |
NO (1) | NO330521B1 (ko) |
NZ (1) | NZ530931A (ko) |
PE (1) | PE20030416A1 (ko) |
PL (1) | PL367716A1 (ko) |
RS (1) | RS17004A (ko) |
UA (1) | UA75957C2 (ko) |
WO (1) | WO2003018579A1 (ko) |
ZA (1) | ZA200400952B (ko) |
Families Citing this family (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JO2311B1 (en) * | 2001-08-29 | 2005-09-12 | ميرك فروست كندا ليمتد | Alkyl inhibitors Ariel phosphodiesterase-4 |
US7351719B2 (en) | 2002-10-31 | 2008-04-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Amide compounds having MCH-antagonistic activity and medicaments comprising these compounds |
DE10250708A1 (de) * | 2002-10-31 | 2004-05-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Alkin-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
US7452911B2 (en) | 2002-10-31 | 2008-11-18 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Alkyne compounds with MCH antagonistic activity and medicaments comprising these compounds |
US20060069115A1 (en) * | 2002-11-15 | 2006-03-30 | Scolnick Edward M | Use of pde4 inhibitors as adjunct therapy for psychiatric disorders |
WO2004047836A1 (en) * | 2002-11-22 | 2004-06-10 | Merck Frosst Canada & Co. | Use of phosphodiesterase-4 inhibitors as enhancers of cognition |
AR042194A1 (es) * | 2002-11-22 | 2005-06-15 | Merck & Co Inc | Metodo para preparar inhibidores de fosfodiesterasa - 4 |
GB0307863D0 (en) * | 2003-04-04 | 2003-05-14 | Merck Sharp & Dohme | Therapeutic treatment |
GB0322722D0 (en) * | 2003-09-27 | 2003-10-29 | Glaxo Group Ltd | Compounds |
GB0322726D0 (en) * | 2003-09-27 | 2003-10-29 | Glaxo Group Ltd | Compounds |
US7592373B2 (en) | 2003-12-23 | 2009-09-22 | Boehringer Ingelheim International Gmbh | Amide compounds with MCH antagonistic activity and medicaments comprising these compounds |
US7524862B2 (en) | 2004-04-14 | 2009-04-28 | Boehringer Ingelheim International Gmbh | Alkyne compounds with MCH antagonistic activity and medicaments comprising these compounds |
DE102004017934A1 (de) | 2004-04-14 | 2005-11-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Alkin-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
DE102004017930A1 (de) * | 2004-04-14 | 2005-11-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Alkin-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
EP1742628A4 (en) * | 2004-04-26 | 2009-06-03 | Merck Frosst Canada Ltd | ALTERNATIVE FORMS OF PHOSPHODIESTERASE-4-HEMMER N-CYCLOPROPYL-1- (3-1 / 4 (1-OXIDOPYRIDIN-3-YL) ETHYNYL-PHENYL) -4-OXO-1,4-DIYHDRO-1,8-NAPHTHYRIDINE- 3-carboxyamide |
JP4264388B2 (ja) * | 2004-07-01 | 2009-05-13 | 富士通株式会社 | 半導体チップの接合方法および接合装置 |
WO2006004191A1 (en) * | 2004-07-05 | 2006-01-12 | Astellas Pharma Inc. | Pyrrolopyridazine derivatives which inhibit pde iv and tnf alfa |
US7687490B2 (en) * | 2005-04-12 | 2010-03-30 | Meiji Seika Kaisha, Ltd. | 2-thioethenyl substituted carbapenem derivatives |
JP2006016407A (ja) * | 2005-06-15 | 2006-01-19 | Yamaha Motor Co Ltd | ホスホジエステラーゼ阻害剤 |
EP2258358A3 (en) | 2005-08-26 | 2011-09-07 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
CA2620333A1 (en) | 2005-08-26 | 2007-03-01 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
EP1931338A4 (en) * | 2005-09-28 | 2009-05-27 | Merck Frosst Canada Inc | AEROSOL POWDER FORMULATION COMPRISING A TAMISED LACTOSE |
EP1940389A2 (en) | 2005-10-21 | 2008-07-09 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
WO2007053596A1 (en) | 2005-10-31 | 2007-05-10 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
WO2007070319A2 (en) * | 2005-12-13 | 2007-06-21 | Wyeth | Dibenzonaphthyridine derivatives and methods of use thereof |
US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
EP2026813A2 (en) | 2006-05-09 | 2009-02-25 | Braincells, Inc. | 5 ht receptor mediated neurogenesis |
CA2651813A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
EP2068872A1 (en) | 2006-09-08 | 2009-06-17 | Braincells, Inc. | Combinations containing a 4-acylaminopyridine derivative |
US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
US20100204230A1 (en) | 2007-02-12 | 2010-08-12 | Peter Blurton | Piperazine derivatives for treatment of ad and related conditions |
US20090182035A1 (en) * | 2007-04-11 | 2009-07-16 | Alcon Research, Ltd. | Use of a combination of olopatadine and cilomilast to treat non-infectious rhinitis and allergic conjunctivitis |
WO2008127975A2 (en) * | 2007-04-11 | 2008-10-23 | Alcon Research, Ltd. | Use of an inhibitor of tnfa plus an antihistamine to treat allergic rhinitis and allergic conjunctivitis |
WO2008156721A1 (en) | 2007-06-20 | 2008-12-24 | Merck & Co., Inc. | Diphenyl substituted alkanes |
RU2470639C2 (ru) * | 2007-10-25 | 2012-12-27 | Мерк Фросст Кэнада Лтд. | Композиции для ингаляции, содержащие кислоту монтелукаст и ингибитор pde-4 или ингаляционный кортикостероид |
EP2291181B9 (en) | 2008-04-18 | 2013-09-11 | University College Dublin National University Of Ireland, Dublin | Captodiamine for the treatment of depression symptoms |
US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
EP2482798A1 (en) * | 2009-10-01 | 2012-08-08 | Alcon Research, Ltd. | Olopatadine compositions and uses thereof |
FR2952934B1 (fr) * | 2009-11-23 | 2012-06-22 | Sanofi Aventis | Derives de pyridino-pyridinones, leur preparation et leur application en therapeutique |
MX343165B (es) | 2010-02-12 | 2016-10-26 | Raqualia Pharma Inc | Agonistas del receptor 5-ht4 para el tratamiento de demencia. |
WO2012116410A1 (en) * | 2011-03-02 | 2012-09-07 | Bionomics Limited | Methods of treating a disease or condition of the central nervous system |
CN103183675A (zh) * | 2011-12-27 | 2013-07-03 | 山东轩竹医药科技有限公司 | 磷酸二酯酶-4抑制剂 |
CN102643268B (zh) * | 2011-12-30 | 2014-05-21 | 沈阳药科大学 | 喹啉类及噌啉类化合物及其应用 |
WO2013106547A1 (en) | 2012-01-10 | 2013-07-18 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
CN103214478B (zh) * | 2012-01-19 | 2015-07-15 | 山东轩竹医药科技有限公司 | 吡啶并氧代哒嗪衍生物 |
CN105121439A (zh) | 2013-02-19 | 2015-12-02 | 辉瑞公司 | 作为pde4亚型抑制剂用于治疗cns和其他病症的氮杂苯并咪唑化合物 |
WO2016012896A1 (en) | 2014-07-24 | 2016-01-28 | Pfizer Inc. | Pyrazolopyrimidine compounds |
HUE044040T2 (hu) | 2014-08-06 | 2019-09-30 | Pfizer | Imidazopiridazin vegyületek |
CN113423435A (zh) | 2018-12-28 | 2021-09-21 | 雷杰纳荣制药公司 | 使用花生四烯酸15-脂氧合酶(alox15)抑制剂治疗呼吸系统病症 |
Family Cites Families (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9212673D0 (en) | 1992-06-15 | 1992-07-29 | Celltech Ltd | Chemical compounds |
GB9212693D0 (en) | 1992-06-15 | 1992-07-29 | Celltech Ltd | Chemical compounds |
DE59304166D1 (de) | 1992-07-01 | 1996-11-21 | Hoechst Ag | 3,4,5-Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
GB9222253D0 (en) | 1992-10-23 | 1992-12-09 | Celltech Ltd | Chemical compounds |
US5622977A (en) | 1992-12-23 | 1997-04-22 | Celltech Therapeutics Limited | Tri-substituted (aryl or heteroaryl) derivatives and pharmaceutical compositions containing the same |
GB9226830D0 (en) | 1992-12-23 | 1993-02-17 | Celltech Ltd | Chemical compounds |
DE4306152A1 (de) | 1993-02-27 | 1994-09-01 | Hoechst Ag | Positiv arbeitendes strahlungsempfindliches Gemisch und damit hergestelltes Aufzeichnungsmaterial |
GB9304919D0 (en) | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
GB9304920D0 (en) | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
US5455252A (en) | 1993-03-31 | 1995-10-03 | Syntex (U.S.A.) Inc. | Optionally substituted 6,8-quinolines |
DE4318756A1 (de) | 1993-06-05 | 1994-12-08 | Hoechst Ag | Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
JP3806144B2 (ja) | 1993-12-22 | 2006-08-09 | セルテック セラピューティックス リミテッド | 三置換フェニル誘導体、その調製方法とホスホジエステラーゼ(iv型)阻害剤としてのその使用 |
GB9326600D0 (en) | 1993-12-22 | 1994-03-02 | Celltech Ltd | Chemical compounds |
GB9326173D0 (en) | 1993-12-22 | 1994-02-23 | Celltech Ltd | Chemical compounds and process |
US5786354A (en) | 1994-06-21 | 1998-07-28 | Celltech Therapeutics, Limited | Tri-substituted phenyl derivatives and processes for their preparation |
US6245774B1 (en) | 1994-06-21 | 2001-06-12 | Celltech Therapeutics Limited | Tri-substituted phenyl or pyridine derivatives |
GB9412573D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
GB9412571D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
GB9412672D0 (en) | 1994-06-23 | 1994-08-10 | Celltech Ltd | Chemical compounds |
EP0765867A1 (de) | 1995-09-27 | 1997-04-02 | Hoechst Aktiengesellschaft | Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Antiarrhytmika oder Diagnostikum sowie sie enthaltendes Medikament |
GB9526243D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
GB9526245D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
GB9526246D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
DE19622370A1 (de) | 1996-06-04 | 1997-12-11 | Hoechst Ag | Ortho-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
GB9625184D0 (en) | 1996-12-04 | 1997-01-22 | Celltech Therapeutics Ltd | Chemical compounds |
CN1245486A (zh) | 1996-12-11 | 2000-02-23 | Basf公司 | 用作钙蛋白酶抑制剂的酮苯甲酰胺 |
EP0958297A1 (en) | 1997-08-06 | 1999-11-24 | Suntory Limited | 1-aryl-1,8-naphthylidin-4-one derivative as type iv phosphodiesterase inhibitor |
AU8780898A (en) | 1997-08-20 | 1999-03-08 | First Data Corporation | Interactive tax payment system |
CN1156476C (zh) * | 1998-01-29 | 2004-07-07 | 第一三得利制药株式会社 | 作为ⅳ型磷酸二酯酶抑制剂的1-环烷基-1,8-二氮杂萘-4-酮衍生物 |
ID27843A (id) * | 1998-08-11 | 2001-04-26 | Pfizer Prod Inc | Substitusi 1, 8-naftiridin-4(ih)-on sebagai penghambat fosfodiesterase 4 |
JO2311B1 (en) * | 2001-08-29 | 2005-09-12 | ميرك فروست كندا ليمتد | Alkyl inhibitors Ariel phosphodiesterase-4 |
IS7839A (is) * | 2002-11-22 | 2004-05-23 | Merck Frosst Canada Ltd. | 4-oxó-1-(3-setið fenýl-1,4-díhýdró-1,8-naftýridín-3-karboxamíð fosfódíesterasa-4 hindrar |
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2002
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- 2002-08-23 US US10/226,980 patent/US6743802B2/en not_active Expired - Lifetime
- 2002-08-26 PE PE2002000819A patent/PE20030416A1/es not_active Application Discontinuation
- 2002-08-27 KR KR1020047002912A patent/KR100928849B1/ko not_active IP Right Cessation
- 2002-08-27 US US10/487,047 patent/US20050070569A1/en not_active Abandoned
- 2002-08-27 MX MXPA04001889A patent/MXPA04001889A/es active IP Right Grant
- 2002-08-27 EA EA200400361A patent/EA006800B1/ru not_active IP Right Cessation
- 2002-08-27 IL IL16021302A patent/IL160213A0/xx unknown
- 2002-08-27 AR ARP020103210A patent/AR036365A1/es not_active Application Discontinuation
- 2002-08-27 UA UA2004032266A patent/UA75957C2/uk unknown
- 2002-08-27 HU HU0401729A patent/HUP0401729A3/hu unknown
- 2002-08-27 AU AU2002322940A patent/AU2002322940B2/en not_active Ceased
- 2002-08-27 NZ NZ530931A patent/NZ530931A/en not_active IP Right Cessation
- 2002-08-27 GE GE5495A patent/GEP20063805B/en unknown
- 2002-08-27 CN CNB028213270A patent/CN100338061C/zh not_active Expired - Fee Related
- 2002-08-27 EP EP10191086A patent/EP2305677A1/en not_active Withdrawn
- 2002-08-27 BR BR0212042-9A patent/BR0212042A/pt not_active Application Discontinuation
- 2002-08-27 WO PCT/CA2002/001324 patent/WO2003018579A1/en active IP Right Grant
- 2002-08-27 RS YUP-170/04A patent/RS17004A/sr unknown
- 2002-08-27 PL PL02367716A patent/PL367716A1/xx not_active Application Discontinuation
- 2002-08-27 EP EP02754079.8A patent/EP1436290B8/en not_active Expired - Lifetime
- 2002-08-27 JP JP2003523241A patent/JP4157035B2/ja not_active Expired - Fee Related
- 2002-08-27 CA CA2456817A patent/CA2456817C/en not_active Expired - Fee Related
- 2002-08-29 DO DO2002000456A patent/DOP2002000456A/es unknown
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2004
- 2004-01-30 IS IS7138A patent/IS7138A/is unknown
- 2004-02-05 ZA ZA200400952A patent/ZA200400952B/en unknown
- 2004-02-16 HR HR20040151A patent/HRP20040151A2/hr not_active Application Discontinuation
- 2004-02-27 EC EC2004004992A patent/ECSP044992A/es unknown
- 2004-03-26 NO NO20041293A patent/NO330521B1/no not_active IP Right Cessation
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