CA2425497C - (n)-((s)-2-hydroxy-3-methyl-butyryl-1-(l-alaninyl)-(s)-1-amino-3-methyl-2,3,4,5-tetrahydro-1h-3-benzazepin-2-one dihydrate and its use in the treatment of alzheimer's disease - Google Patents
(n)-((s)-2-hydroxy-3-methyl-butyryl-1-(l-alaninyl)-(s)-1-amino-3-methyl-2,3,4,5-tetrahydro-1h-3-benzazepin-2-one dihydrate and its use in the treatment of alzheimer's disease Download PDFInfo
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- CA2425497C CA2425497C CA2425497A CA2425497A CA2425497C CA 2425497 C CA2425497 C CA 2425497C CA 2425497 A CA2425497 A CA 2425497A CA 2425497 A CA2425497 A CA 2425497A CA 2425497 C CA2425497 C CA 2425497C
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- acid
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- 208000024827 Alzheimer disease Diseases 0.000 title claims description 23
- 238000000034 method Methods 0.000 claims abstract description 88
- 230000008569 process Effects 0.000 claims abstract description 52
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- 125000003118 aryl group Chemical group 0.000 claims description 56
- 238000006243 chemical reaction Methods 0.000 claims description 54
- 239000002253 acid Substances 0.000 claims description 49
- -1 amino-protected amino Chemical group 0.000 claims description 47
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 125000001072 heteroaryl group Chemical group 0.000 claims description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 33
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 32
- 239000007787 solid Substances 0.000 claims description 29
- 238000005859 coupling reaction Methods 0.000 claims description 27
- 230000015572 biosynthetic process Effects 0.000 claims description 26
- 238000003786 synthesis reaction Methods 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
- 238000002425 crystallisation Methods 0.000 claims description 21
- 230000008025 crystallization Effects 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- 125000000304 alkynyl group Chemical group 0.000 claims description 19
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 19
- 230000008878 coupling Effects 0.000 claims description 18
- 238000010168 coupling process Methods 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 16
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 15
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- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 14
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- 125000001246 bromo group Chemical group Br* 0.000 claims description 14
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
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- AVNSYQHGYITKAM-UHFFFAOYSA-N 5-amino-3-methyl-2,5,8,9-tetrahydro-1h-3-benzazepin-4-one Chemical compound NC1C(=O)N(C)CCC2=C1C=CCC2 AVNSYQHGYITKAM-UHFFFAOYSA-N 0.000 claims description 12
- 125000004104 aryloxy group Chemical group 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 12
- MIOPJNTWMNEORI-XVKPBYJWSA-N (R)-camphorsulfonic acid Chemical compound C1C[C@]2(CS(O)(=O)=O)C(=O)C[C@H]1C2(C)C MIOPJNTWMNEORI-XVKPBYJWSA-N 0.000 claims description 11
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- NSFIAKFOCAEBER-ROUUACIJSA-N (2r,3r)-2,3-dihydroxy-2,3-bis(4-methylphenyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1[C@](O)(C(O)=O)[C@@](O)(C(O)=O)C1=CC=C(C)C=C1 NSFIAKFOCAEBER-ROUUACIJSA-N 0.000 claims description 10
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- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 5
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- NWPLRPGCKFLFGL-XWMUTSTRSA-N (5s)-2-amino-5-[(2s)-2-aminopropanoyl]-3-methyl-2,5,8,9-tetrahydro-1h-3-benzazepin-4-one Chemical compound C1C(N)N(C)C(=O)[C@H](C(=O)[C@@H](N)C)C2=C1CCC=C2 NWPLRPGCKFLFGL-XWMUTSTRSA-N 0.000 claims description 3
- NGEWQZIDQIYUNV-BYPYZUCNSA-N (S)-2-hydroxy-3-methylbutyric acid Chemical compound CC(C)[C@H](O)C(O)=O NGEWQZIDQIYUNV-BYPYZUCNSA-N 0.000 claims description 3
- IHFRMUGEILMHNU-UHFFFAOYSA-N 2-hydroxy-5-nitrobenzaldehyde Chemical compound OC1=CC=C([N+]([O-])=O)C=C1C=O IHFRMUGEILMHNU-UHFFFAOYSA-N 0.000 claims description 3
- FABVMBDCVAJXMB-UHFFFAOYSA-N 3,5-dichloro-2-hydroxybenzaldehyde Chemical compound OC1=C(Cl)C=C(Cl)C=C1C=O FABVMBDCVAJXMB-UHFFFAOYSA-N 0.000 claims description 3
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- 239000000243 solution Substances 0.000 description 55
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
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- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
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- 239000000346 nonvolatile oil Substances 0.000 description 1
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- 239000004033 plastic Substances 0.000 description 1
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
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- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- 239000004208 shellac Substances 0.000 description 1
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- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
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- 239000012312 sodium hydride Substances 0.000 description 1
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- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
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- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Cephalosporin Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24965600P | 2000-11-17 | 2000-11-17 | |
| US60/249,656 | 2000-11-17 | ||
| PCT/US2001/027795 WO2002040451A2 (en) | 2000-11-17 | 2001-11-02 | Lactam compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2425497A1 CA2425497A1 (en) | 2002-05-23 |
| CA2425497C true CA2425497C (en) | 2010-08-17 |
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ID=22944436
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2425497A Expired - Fee Related CA2425497C (en) | 2000-11-17 | 2001-11-02 | (n)-((s)-2-hydroxy-3-methyl-butyryl-1-(l-alaninyl)-(s)-1-amino-3-methyl-2,3,4,5-tetrahydro-1h-3-benzazepin-2-one dihydrate and its use in the treatment of alzheimer's disease |
Country Status (33)
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA74849C2 (en) * | 2000-11-17 | 2006-02-15 | Lilly Co Eli | Lactam |
| EP2186516B1 (en) | 2002-12-20 | 2013-01-16 | Glaxo Group Limited | Novel benzazepine derivative |
| NZ540612A (en) | 2003-01-14 | 2008-02-29 | Arena Pharm Inc | 1,2,3-Trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia |
| AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| JP5039543B2 (ja) | 2005-04-08 | 2012-10-03 | 第一三共株式会社 | ピリジルメチルスルホン誘導体 |
| WO2007088878A1 (ja) | 2006-01-31 | 2007-08-09 | Api Corporation | ベンゾアゼピノン類の製造方法 |
| TW200920362A (en) | 2007-09-11 | 2009-05-16 | Daiichi Sankyo Co Ltd | Alkylsulfone derivatives |
| FR2932800B1 (fr) * | 2008-06-20 | 2015-02-20 | Servier Lab | Nouveau procede de synthese de la 7,8-dimethoxy-1,3-dihydro- 2h-3-benzazepin-2-one, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| CN103221410B (zh) | 2010-09-22 | 2017-09-15 | 艾尼纳制药公司 | Gpr119受体调节剂和对与其相关的障碍的治疗 |
| KR101899014B1 (ko) | 2012-01-06 | 2018-09-17 | 삼성전자주식회사 | 비엘디씨 모터의 제어 장치 및 그 방법 |
| CN102690231B (zh) * | 2012-04-11 | 2014-07-09 | 南京友杰医药科技有限公司 | 治疗阿尔茨海默病潜在药物司马西特的合成方法 |
| US20160067306A1 (en) | 2013-04-19 | 2016-03-10 | National University Corporation Hokkaido University | Treatment agent for cognitive impairment induced by amyloid beta-protein, therapeutic agent for alzheimer's disease, and treatment method and pathological analysis method related to these |
| EP4445956A3 (en) | 2015-01-06 | 2024-12-04 | Arena Pharmaceuticals, Inc. | Compound for use in treating conditions related to the s1p1 receptor |
| PL3310760T3 (pl) | 2015-06-22 | 2023-03-06 | Arena Pharmaceuticals, Inc. | Krystaliczna sól L-argininy kwasu (R)-2-(7-(4-cyklopentylo-3-(trifluorometylo)benzyloksy)- 1,2,3,4-tetrahydrocyklo-penta[b]indol-3-ilo)octowego do zastosowania w zaburzeniach związanych z receptorem S1P1 |
| MA47504A (fr) | 2017-02-16 | 2019-12-25 | Arena Pharm Inc | Composés et méthodes de traitement de l'angiocholite biliaire primitive |
| ES2987794T3 (es) | 2018-06-06 | 2024-11-18 | Arena Pharm Inc | Procedimientos de tratamiento de afecciones relacionadas con el receptor S1P1 |
| AU2021244215A1 (en) | 2020-03-26 | 2022-10-13 | Seagen Inc. | Methods of treating multiple myeloma |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT951466E (pt) * | 1996-12-23 | 2009-04-09 | Lilly Co Eli | Compostos cicloalquilo, lactama, lactona e relacionados, composições farmacêuticas compreendendo os mesmos, e métodos para a inibição da libertação do péptido β-amilóide e/ou da sua síntese pela utilização de tais compostos |
| AU4707999A (en) * | 1998-06-22 | 2000-01-10 | Elan Pharmaceuticals, Inc. | Compounds for inhibiting beta-amyloid peptide release and/or its synthesis |
| CA2390376A1 (en) * | 1999-11-09 | 2001-05-17 | William Leonard Scott | .beta.-aminoacid compounds useful for inhibiting .beta.-amyloid peptide release and/or its synthesis |
-
2001
- 2001-02-11 UA UA2003054406A patent/UA77165C2/uk unknown
- 2001-11-02 WO PCT/US2001/027795 patent/WO2002040451A2/en not_active Ceased
- 2001-11-02 DK DK01996530T patent/DK1353910T3/da active
- 2001-11-02 HR HR20030385A patent/HRP20030385A2/hr not_active Application Discontinuation
- 2001-11-02 AU AU2002224321A patent/AU2002224321B2/en not_active Ceased
- 2001-11-02 CZ CZ20031340A patent/CZ20031340A3/cs unknown
- 2001-11-02 IL IL15527501A patent/IL155275A0/xx unknown
- 2001-11-02 MX MXPA03004250A patent/MXPA03004250A/es active IP Right Grant
- 2001-11-02 DZ DZ013454A patent/DZ3454A1/fr active
- 2001-11-02 CN CN200910203885A patent/CN101624372A/zh active Pending
- 2001-11-02 ES ES01996530T patent/ES2286162T3/es not_active Expired - Lifetime
- 2001-11-02 CN CNB018189962A patent/CN100516047C/zh not_active Expired - Fee Related
- 2001-11-02 BR BR0115424-9A patent/BR0115424A/pt not_active Application Discontinuation
- 2001-11-02 US US10/415,548 patent/US20040248878A1/en not_active Abandoned
- 2001-11-02 EA EA200300579A patent/EA006919B1/ru unknown
- 2001-11-02 SK SK543-2003A patent/SK287794B6/sk not_active IP Right Cessation
- 2001-11-02 AT AT01996530T patent/ATE362919T1/de active
- 2001-11-02 AU AU2432102A patent/AU2432102A/xx active Pending
- 2001-11-02 CA CA2425497A patent/CA2425497C/en not_active Expired - Fee Related
- 2001-11-02 DE DE60128587T patent/DE60128587T2/de not_active Expired - Lifetime
- 2001-11-02 JP JP2002542779A patent/JP4116431B2/ja not_active Expired - Fee Related
- 2001-11-02 KR KR10-2003-7006660A patent/KR20030045194A/ko not_active Ceased
- 2001-11-02 PL PL360991A patent/PL211018B1/pl unknown
- 2001-11-02 EP EP01996530A patent/EP1353910B1/en not_active Expired - Lifetime
- 2001-11-02 HU HU0301862A patent/HUP0301862A3/hu unknown
- 2001-11-02 PT PT01996530T patent/PT1353910E/pt unknown
- 2001-11-15 AR ARP010105339A patent/AR031356A1/es not_active Application Discontinuation
- 2001-11-15 MY MYPI20015251A patent/MY141607A/en unknown
- 2001-11-15 TW TW090128351A patent/TWI235151B/zh not_active IP Right Cessation
- 2001-11-16 PE PE2001001143A patent/PE20020798A1/es not_active Application Discontinuation
- 2001-11-16 SV SV2001000741A patent/SV2003000741A/es unknown
-
2003
- 2003-05-02 ZA ZA200303411A patent/ZA200303411B/en unknown
- 2003-05-13 EC EC2003004598A patent/ECSP034598A/es unknown
- 2003-05-15 NO NO20032215A patent/NO325217B1/no unknown
-
2007
- 2007-06-28 CY CY20071100848T patent/CY1106682T1/el unknown
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20151102 |