CA2442878C - Nouveau procede de synthese industriel du ranelate de strontium et de ses hydrates - Google Patents
Nouveau procede de synthese industriel du ranelate de strontium et de ses hydrates Download PDFInfo
- Publication number
- CA2442878C CA2442878C CA002442878A CA2442878A CA2442878C CA 2442878 C CA2442878 C CA 2442878C CA 002442878 A CA002442878 A CA 002442878A CA 2442878 A CA2442878 A CA 2442878A CA 2442878 C CA2442878 C CA 2442878C
- Authority
- CA
- Canada
- Prior art keywords
- formula
- compound
- process according
- synthesis process
- iii
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
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- 238000000034 method Methods 0.000 title claims abstract description 40
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 37
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 36
- ZHEZAQJNZMLYBA-UHFFFAOYSA-J distrontium;5-[bis(carboxylatomethyl)amino]-3-(carboxylatomethyl)-4-cyanothiophene-2-carboxylate;octahydrate Chemical compound O.O.O.O.O.O.O.O.[Sr+2].[Sr+2].[O-]C(=O)CN(CC([O-])=O)C=1SC(C([O-])=O)=C(CC([O-])=O)C=1C#N ZHEZAQJNZMLYBA-UHFFFAOYSA-J 0.000 title claims abstract description 22
- 229940079488 strontium ranelate Drugs 0.000 title claims abstract description 22
- 150000004677 hydrates Chemical class 0.000 title claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 92
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 238000010992 reflux Methods 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 239000011541 reaction mixture Substances 0.000 claims description 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 239000011593 sulfur Substances 0.000 claims description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 9
- 238000001556 precipitation Methods 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 claims description 8
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 8
- UUCCCPNEFXQJEL-UHFFFAOYSA-L strontium dihydroxide Chemical compound [OH-].[OH-].[Sr+2] UUCCCPNEFXQJEL-UHFFFAOYSA-L 0.000 claims description 8
- 229910001866 strontium hydroxide Inorganic materials 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
- 239000002244 precipitate Substances 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 5
- 239000006184 cosolvent Substances 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 238000004821 distillation Methods 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 238000002955 isolation Methods 0.000 claims description 4
- 230000003197 catalytic effect Effects 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims 1
- -1 ethyl diester Chemical class 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- 229910052712 strontium Inorganic materials 0.000 description 7
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 5
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- RNJOKCPFLQMDEC-UHFFFAOYSA-N 4(R),8-dimethyl-trans-2-nonenoyl-CoA Chemical compound COC(=O)CC(=O)CC(=O)OC RNJOKCPFLQMDEC-UHFFFAOYSA-N 0.000 description 2
- KNPBNTMMZCNVIE-UHFFFAOYSA-N 5-amino-3-(carboxymethyl)-4-cyanothiophene-2-carboxylic acid Chemical compound NC=1SC(C(O)=O)=C(CC(O)=O)C=1C#N KNPBNTMMZCNVIE-UHFFFAOYSA-N 0.000 description 2
- YXGHUSALBGWCAV-UHFFFAOYSA-N 5-amino-4-cyano-3-(2-methoxy-2-oxoethyl)thiophene-2-carboxylic acid Chemical compound COC(=O)CC1=C(C(O)=O)SC(N)=C1C#N YXGHUSALBGWCAV-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
- 150000004689 octahydrates Chemical class 0.000 description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- DJSXNILVACEBLP-UHFFFAOYSA-N ranelic acid Chemical compound OC(=O)CN(CC(O)=O)C=1SC(C(O)=O)=C(CC(O)=O)C=1C#N DJSXNILVACEBLP-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- AHKYFPXBUQSQAK-UHFFFAOYSA-N 3-cyanothiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC=CC=1C#N AHKYFPXBUQSQAK-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101150030723 RIR2 gene Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003262 anti-osteoporosis Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- ZSANYRMTSBBUCA-UHFFFAOYSA-N diethyl 3-oxopentanedioate Chemical compound CCOC(=O)CC(=O)CC(=O)OCC ZSANYRMTSBBUCA-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000000267 glycino group Chemical group [H]N([*])C([H])([H])C(=O)O[H] 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- BLYLWUDQKYBGJD-UHFFFAOYSA-N methyl 5-amino-4-cyano-3-(2-methoxy-2-oxoethyl)thiophene-2-carboxylate Chemical compound COC(=O)CC1=C(C(=O)OC)SC(N)=C1C#N BLYLWUDQKYBGJD-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012958 reprocessing Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- WCLHZVGJULAEJH-UHFFFAOYSA-N tridecan-2-amine Chemical compound CCCCCCCCCCCC(C)N WCLHZVGJULAEJH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Inorganic Insulating Materials (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0211763A FR2844795B1 (fr) | 2002-09-24 | 2002-09-24 | Nouveau procede de synthese industriel du ranelate de strontium et de ses hydrates |
| FR02/11763 | 2002-09-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2442878A1 CA2442878A1 (fr) | 2004-03-24 |
| CA2442878C true CA2442878C (fr) | 2009-03-03 |
Family
ID=29415189
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002442878A Expired - Fee Related CA2442878C (fr) | 2002-09-24 | 2003-09-23 | Nouveau procede de synthese industriel du ranelate de strontium et de ses hydrates |
Country Status (37)
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004098618A2 (en) * | 2003-05-07 | 2004-11-18 | Osteologix A/S | Strontium combinations for prophylaxis/treatment of cartilage and/or bone conditions |
| ES2275218T3 (es) * | 2003-05-07 | 2007-06-01 | Osteologix A/S | Sales de estroncio hidrosolubles para el tratamiento de afecciones de cartilagos y/o huesos. |
| PL1732575T3 (pl) | 2004-02-26 | 2011-05-31 | Osteologix As | Związki zawierające stron do stosowania w zapobieganiu lub leczeniu stanów nekrotycznych kości |
| JP4954867B2 (ja) * | 2004-05-06 | 2012-06-20 | オステオロジックス エイ／エス | 有機金属塩類を製造するための高収率で迅速な合成法 |
| CA2571449C (en) | 2004-06-25 | 2015-12-08 | John Nikolaj Hvarre Christensen | Compositions comprising strontium and vitamin d and uses thereof |
| FR2875807B1 (fr) * | 2004-09-30 | 2006-11-17 | Servier Lab | Forme cristalline alpha du ranelate de strontium, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| CN100538672C (zh) * | 2005-04-18 | 2009-09-09 | 索尼株式会社 | 控制设备和方法 |
| CN100391955C (zh) * | 2005-04-30 | 2008-06-04 | 河北医科大学 | 一种雷尼酸锶中间体的合成方法 |
| CA2619720A1 (en) * | 2005-08-19 | 2007-02-22 | Glenmark Pharmaceuticals Limited | Process for the preparation of strontium ranelate |
| US20070292535A1 (en) * | 2006-06-19 | 2007-12-20 | Tabbiner Philip S | Strontium compositions and methods of treating arthritic and or osteoporitic conditions |
| US20070292529A1 (en) * | 2006-06-19 | 2007-12-20 | Tabbiner Philip S | Strontium compositions and methods of treating osteoporotic conditions |
| FR2921367B1 (fr) * | 2007-09-26 | 2009-10-30 | Servier Lab | Nouveau procede de synthese du ranelate de strontium et de ses hydrates |
| US20120123131A1 (en) * | 2008-08-22 | 2012-05-17 | Koilpillai Joseph Prabahar | Process for the preparation of strontium ranelate |
| HU228820B1 (en) | 2010-01-14 | 2013-05-28 | Richter Gedeon Nyrt | Process for the preparation of distrontium ranelate |
| WO2011110597A1 (de) | 2010-03-11 | 2011-09-15 | Azad Pharmaceutical Ingredients Ag | Verfahren zur herstellung von strontiumranelat |
| WO2011124992A1 (en) * | 2010-03-24 | 2011-10-13 | Actavis Group Ptc Ehf | Substantially pure strontium ranelate |
| US9301945B2 (en) | 2011-07-21 | 2016-04-05 | Emory University | Methods for treating inflammatory conditions and states, and cancers by antagonizing NF-κB activation |
| CN102321068B (zh) * | 2011-08-01 | 2013-01-23 | 山东铂源药业有限公司 | 一种雷奈酸锶的制备方法 |
| WO2013175270A1 (en) * | 2012-05-25 | 2013-11-28 | Fleming Laboratories Limited | Improved process for the preparation of strontium ranelate hydrates and new polymorphic form of monohydrate |
| ES2505716T3 (es) | 2013-01-21 | 2015-09-04 | Galenicum Health S.L. | Composiciones farmacéuticas que comprenden una sal de ácido |
| CN103319454B (zh) * | 2013-06-14 | 2014-06-18 | 广东众生药业股份有限公司 | 一种高纯度雷尼酸四乙酯及其中间体的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2651497B1 (fr) * | 1989-09-01 | 1991-10-25 | Adir | Nouveaux sels de metaux bivalents de l'acide n, n-di (carboxymethyl)amino-2 cyano-3 carboxymethyl-4 carboxy-5 thiophene, leur procede de preparation et les compositions pharmaceutiques les renfermant. |
| FR2749759B1 (fr) * | 1996-06-17 | 1999-11-26 | Adir | Utilisation de sels de strontium pour l'obtention de compositions pharmaceutiques destinees au traitement de l'arthrose |
| FR2844797B1 (fr) * | 2002-09-24 | 2004-10-22 | Servier Lab | Nouveau procede de synthese industriel des tetraesters de l'acide 5-[bis (carboxymethyl)]-3-carboxymethyl-4-cyano-2- thiophenecarboxylique, et application a la synthese des sels bivalents de l'acide ranelique et de leurs hydrates |
| FR2844796A1 (fr) * | 2002-09-24 | 2004-03-26 | Servier Lab | Nouveau procede de synthese industrielle du diester methylique de l'acide 5-amino-3-carboxymethyl-4-cyano-2- thiophenecarboxylique, et application a la synthese des sels bivalents de l'acide ranelique et de leurs hydrates |
-
2002
- 2002-09-24 FR FR0211763A patent/FR2844795B1/fr not_active Expired - Fee Related
-
2003
- 2003-09-17 MY MYPI20033542A patent/MY134921A/en unknown
- 2003-09-22 AP AP2005003256A patent/AP1910A/xx active
- 2003-09-22 ME MEP-2008-689A patent/ME00455B/me unknown
- 2003-09-22 WO PCT/FR2003/002777 patent/WO2004029036A1/fr not_active Ceased
- 2003-09-22 HR HRP20050359AA patent/HRP20050359B1/hr not_active IP Right Cessation
- 2003-09-22 AU AU2003282179A patent/AU2003282179A1/en not_active Abandoned
- 2003-09-22 AU AU2003248281A patent/AU2003248281B2/en not_active Ceased
- 2003-09-22 EP EP03292319.5A patent/EP1403266B1/fr not_active Expired - Lifetime
- 2003-09-22 UA UAA200503858A patent/UA79156C2/uk unknown
- 2003-09-22 GE GEAP20048761A patent/GEP20074215B/en unknown
- 2003-09-22 OA OA1200500083A patent/OA12934A/en unknown
- 2003-09-22 DK DK03292319.5T patent/DK1403266T3/da active
- 2003-09-22 RS RSP20050240 patent/RS53509B1/sr unknown
- 2003-09-22 RS YUP-2005/0240A patent/RS20050240A/sr unknown
- 2003-09-22 ES ES03292319.5T patent/ES2478620T3/es not_active Expired - Lifetime
- 2003-09-22 PT PT3292319T patent/PT1403266E/pt unknown
- 2003-09-22 JP JP2003330440A patent/JP4136867B2/ja not_active Expired - Fee Related
- 2003-09-22 SI SI200332352T patent/SI1403266T1/sl unknown
- 2003-09-23 EA EA200300925A patent/EA007489B1/ru not_active IP Right Cessation
- 2003-09-23 BR BR0304213-8A patent/BR0304213A/pt not_active Application Discontinuation
- 2003-09-23 NO NO20034235A patent/NO328638B1/no not_active IP Right Cessation
- 2003-09-23 NZ NZ528402A patent/NZ528402A/en not_active IP Right Cessation
- 2003-09-23 KR KR1020030065783A patent/KR100551501B1/ko not_active Expired - Fee Related
- 2003-09-23 MX MXPA03008643A patent/MXPA03008643A/es active IP Right Grant
- 2003-09-23 CA CA002442878A patent/CA2442878C/fr not_active Expired - Fee Related
- 2003-09-23 PL PL362365A patent/PL214400B1/pl unknown
- 2003-09-23 ZA ZA200307409A patent/ZA200307409B/xx unknown
- 2003-09-23 AR ARP030103453A patent/AR041355A1/es not_active Application Discontinuation
- 2003-09-24 MA MA27321A patent/MA26102A1/fr unknown
- 2003-09-24 US US10/669,301 patent/US7214805B2/en not_active Expired - Fee Related
- 2003-09-24 CN CNB031348130A patent/CN1212321C/zh not_active Expired - Fee Related
- 2003-09-24 SG SG200305555A patent/SG110071A1/en unknown
-
2005
- 2005-03-08 IL IL167316A patent/IL167316A/en not_active IP Right Cessation
- 2005-03-18 CR CR7764A patent/CR7764A/es unknown
- 2005-03-23 TN TNP2005000087A patent/TNSN05087A1/fr unknown
- 2005-04-19 IS IS7807A patent/IS7807A/is unknown
- 2005-04-22 EC EC2005005741A patent/ECSP055741A/es unknown
-
2014
- 2014-06-05 CY CY20141100397T patent/CY1115162T1/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20180924 |