ZA200505656B - A process for preparing duloxetine and intermediates for use therein - Google Patents
A process for preparing duloxetine and intermediates for use therein Download PDFInfo
- Publication number
- ZA200505656B ZA200505656B ZA200505656A ZA200505656A ZA200505656B ZA 200505656 B ZA200505656 B ZA 200505656B ZA 200505656 A ZA200505656 A ZA 200505656A ZA 200505656 A ZA200505656 A ZA 200505656A ZA 200505656 B ZA200505656 B ZA 200505656B
- Authority
- ZA
- South Africa
- Prior art keywords
- duloxetine
- acid
- addition salt
- acid addition
- process according
- Prior art date
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- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 title claims description 17
- 229960002866 duloxetine Drugs 0.000 title claims description 17
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 239000000543 intermediate Substances 0.000 title description 27
- ZEUITGRIYCTCEM-UHFFFAOYSA-N duloxetine Chemical compound C=1C=CC2=CC=CC=C2C=1OC(CCNC)C1=CC=CS1 ZEUITGRIYCTCEM-UHFFFAOYSA-N 0.000 claims abstract description 95
- 239000002253 acid Substances 0.000 claims abstract description 68
- 150000003839 salts Chemical class 0.000 claims abstract description 68
- 238000000034 method Methods 0.000 claims abstract description 60
- 150000001875 compounds Chemical class 0.000 claims abstract description 33
- ZEUITGRIYCTCEM-QGZVFWFLSA-N (R)-duloxetine Chemical compound C1([C@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-QGZVFWFLSA-N 0.000 claims abstract description 22
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 10
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 22
- 239000002585 base Substances 0.000 claims description 15
- HZBOQOXQPRQKTF-UHFFFAOYSA-N bis(4-methylphenyl) 2,3-dihydroxybutanedioate Chemical compound C1=CC(C)=CC=C1OC(=O)C(O)C(O)C(=O)OC1=CC=C(C)C=C1 HZBOQOXQPRQKTF-UHFFFAOYSA-N 0.000 claims description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- NSFIAKFOCAEBER-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methylphenyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1C(O)(C(O)=O)C(O)(C(O)=O)C1=CC=C(C)C=C1 NSFIAKFOCAEBER-UHFFFAOYSA-N 0.000 claims description 9
- 239000012458 free base Substances 0.000 claims description 9
- 230000001335 demethylating effect Effects 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 6
- 229960002496 duloxetine hydrochloride Drugs 0.000 claims description 6
- 235000006408 oxalic acid Nutrition 0.000 claims description 6
- 239000012452 mother liquor Substances 0.000 claims description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 229940095064 tartrate Drugs 0.000 claims description 4
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims description 2
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims description 2
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 claims description 2
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- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 claims description 2
- 150000003983 crown ethers Chemical class 0.000 claims description 2
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- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims 1
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- 239000002184 metal Substances 0.000 claims 1
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- 125000006308 propyl amino group Chemical group 0.000 description 3
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- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 229940071104 xylenesulfonate Drugs 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
- C07D333/06—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- 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
- A61P25/24—Antidepressants
-
- 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
- C07D333/06—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0229583.0A GB0229583D0 (en) | 2002-12-19 | 2002-12-19 | A process for preparing duloxetine and intermediates for use therein |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200505656B true ZA200505656B (en) | 2006-04-26 |
Family
ID=9949985
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200505656A ZA200505656B (en) | 2002-12-19 | 2005-07-14 | A process for preparing duloxetine and intermediates for use therein |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US7645890B2 (ja) |
| EP (2) | EP1587801B1 (ja) |
| JP (1) | JP5259048B2 (ja) |
| KR (1) | KR100926723B1 (ja) |
| CN (2) | CN100579975C (ja) |
| AT (1) | ATE353081T1 (ja) |
| AU (2) | AU2003292396B2 (ja) |
| BR (1) | BR0316902A (ja) |
| CA (1) | CA2510750A1 (ja) |
| DE (1) | DE60311599T2 (ja) |
| ES (1) | ES2279971T3 (ja) |
| GB (1) | GB0229583D0 (ja) |
| HR (1) | HRP20050657A2 (ja) |
| IL (1) | IL169232A (ja) |
| IS (1) | IS7915A (ja) |
| MA (1) | MA27706A1 (ja) |
| MX (1) | MXPA05006659A (ja) |
| NZ (2) | NZ569874A (ja) |
| PL (1) | PL377380A1 (ja) |
| PT (1) | PT1587801E (ja) |
| RU (1) | RU2351594C2 (ja) |
| TN (1) | TNSN05167A1 (ja) |
| WO (1) | WO2004056795A1 (ja) |
| ZA (1) | ZA200505656B (ja) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006027798A2 (en) * | 2004-08-05 | 2006-03-16 | Sun Pharmaceutical Industries Limited | A process for preparation of an antidepressant compound |
| CZ297560B6 (cs) * | 2004-10-26 | 2007-02-07 | Zentiva, A. S. | Zpusob výroby hydrochloridu (S)-N-methyl-3-(1-naftyloxy)-3-(2-thienyl)propylaminu (duloxetinu) |
| EP1730132A2 (en) * | 2004-12-23 | 2006-12-13 | Teva Pharmaceutical Industries Ltd | Process for preparing pharmaceutically acceptable salts of duloxetine and intermediates thereof |
| WO2006081515A2 (en) * | 2005-01-27 | 2006-08-03 | Teva Pharmaceutical Industries Ltd. | Duloxetine hydrochloride polymorphs |
| WO2006096809A1 (en) * | 2005-03-08 | 2006-09-14 | Teva Pharmaceutical Industries Ltd. | Crystal forms of (s)-(+)-n,n-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl) propanamine oxalate and the preparation thereof |
| TW200639162A (en) * | 2005-03-14 | 2006-11-16 | Teva Pharma | Pure duloxetine hydrochloride |
| US8093408B2 (en) * | 2005-06-21 | 2012-01-10 | The Company Wockhardt | Antidepressant oral pharmaceutical compositions |
| US8153824B2 (en) * | 2005-06-22 | 2012-04-10 | The Wockhardt Company | Antidepressant oral liquid compositions |
| US7842717B2 (en) | 2005-09-22 | 2010-11-30 | Teva Pharmaceutical Industries Ltd. | DNT-maleate and methods of preparation thereof |
| US7759500B2 (en) * | 2005-12-05 | 2010-07-20 | Teva Pharmaceutical Industries Ltd. | 2-(N-methyl-propanamine)-3-(2-naphthol)thiophene, an impurity of duloxetine hydrochloride |
| EP1971591A2 (en) * | 2005-12-12 | 2008-09-24 | Medichem, S.A. | Improved synthesis and preparations of duloxetine salts |
| CZ299270B6 (cs) | 2006-01-04 | 2008-06-04 | Zentiva, A. S. | Zpusob výroby hydrochloridu (S)-N-methyl-3-(1-naftyloxy)-3-(2-thienyl)propylaminu |
| WO2007077580A2 (en) * | 2006-01-06 | 2007-07-12 | Msn Laboratories Limited | Improved process for pure duloxetine hydrochloride |
| US7538232B2 (en) | 2006-01-19 | 2009-05-26 | Eli Lilly And Company | Process for the asymmetric synthesis of duloxetine |
| BRPI0707724A2 (pt) * | 2006-02-13 | 2011-05-10 | Teva Pharma | um novo processo para preparaÇço de (s)-(+)-n, n-dimetil-3-(1-naftaleniloxi)-3-(2-tienil)propanamina), um intermediÁrio de duloxetina |
| HU228458B1 (en) * | 2006-03-13 | 2013-03-28 | Egis Gyogyszergyar Nyrt | Duloxetine salts for producing pharmaceutical compositions |
| SI1857451T1 (sl) | 2006-05-05 | 2010-11-30 | Fidia Farmaceutici | Postopek priprave intermediata ki je uporaben zaasimetrično sintezo duloksetina |
| US20080027128A1 (en) * | 2006-05-23 | 2008-01-31 | Santiago Ini | Duloxetine HCL polymorphs |
| EP2044049A2 (en) | 2006-07-03 | 2009-04-08 | Ranbaxy Laboratories Limited | Process for the preparation of enantiomerically pure salts of n-methyl- 3 -( 1-naph-thaleneoxy)- 3 - (-2-thienyl) propanamine |
| CZ300116B6 (cs) * | 2006-12-05 | 2009-02-11 | Zentiva, A. S. | Zpusob cištení hydrochloridu (S)-N-methyl-3-(1-naftyloxy)-3-(2-thienyl)propylaminu |
| ATE552250T1 (de) | 2006-12-22 | 2012-04-15 | Synthon Bv | Verfahren zur herstellung von duloxetin und verwandten verbindungen |
| HU227730B1 (en) | 2006-12-22 | 2012-01-30 | Richter Gedeon Nyrt | Process for the preparation of duloxetine and for their the intermediates |
| EP2132192B1 (en) | 2007-03-05 | 2013-04-24 | Lupin Limited | Novel process for preparation of duloxetine hydrochloride |
| WO2009019719A2 (en) * | 2007-08-09 | 2009-02-12 | Ind-Swift Laboratories Limited | Process for the preparation of 3-aryloxy-3-arylpropanamines |
| WO2009130708A2 (en) * | 2008-04-22 | 2009-10-29 | Shodhana Laboratories Limited | Preparation of duloxetine and its salts |
| WO2010025287A2 (en) | 2008-08-27 | 2010-03-04 | Codexis, Inc. | Ketoreductase polypeptides for the production of 3-aryl-3-hydroxypropanamine from a 3-aryl-3-ketopropanamine |
| SI2329013T1 (sl) | 2008-08-27 | 2016-03-31 | Codexis, Inc. | Polipeptidi ketoreduktaze za proizvodnjo 3-aril-3-hidroksipropanamina iz 3-aril-3-ketopropanamina |
| WO2011033366A2 (en) | 2009-09-16 | 2011-03-24 | Jubilant Life Sciences Limited | Process for the preparation of duloxetine hydrochloride and its precursors |
| CN103360365A (zh) * | 2012-04-06 | 2013-10-23 | 李晓红 | 一种抗抑郁症药物原料药盐酸度洛西汀的制备新工艺 |
| CN104230882B (zh) * | 2014-08-29 | 2017-03-08 | 宁波美诺华药业股份有限公司 | 一种度洛西汀盐酸盐杂质的制备方法 |
| CN104829587B (zh) * | 2015-05-08 | 2017-07-21 | 上海万巷制药有限公司 | 盐酸度洛西汀的制备 |
| CN107382958B (zh) * | 2017-07-05 | 2021-11-09 | 浙江华海药业股份有限公司 | 一种度洛西汀中间体的结晶方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH578532A5 (ja) * | 1971-08-03 | 1976-08-13 | Cassella Farbwerke Mainkur Ag | |
| GR75395B (ja) | 1980-11-14 | 1984-07-13 | Lilly Co Eli | |
| US4777291A (en) * | 1985-02-27 | 1988-10-11 | Eli Lilly And Company | Racemization process |
| JPS62286959A (ja) * | 1986-06-05 | 1987-12-12 | Seitetsu Kagaku Co Ltd | 光学活性シアノカルニチン塩の製造方法 |
| US4956388A (en) * | 1986-12-22 | 1990-09-11 | Eli Lilly And Company | 3-aryloxy-3-substituted propanamines |
| KR880007433A (ko) * | 1986-12-22 | 1988-08-27 | 메리 앤 터커 | 3-아릴옥시-3-치환된 프로판아민 |
| CA2042346A1 (en) | 1990-05-17 | 1991-11-18 | Michael Alexander Staszak | Chiral synthesis of 1-aryl-3-aminopropan-1-ols |
| JPH09176157A (ja) * | 1992-12-09 | 1997-07-08 | Takeda Chem Ind Ltd | 光学活性アミノクマラン誘導体 |
| US5362886A (en) * | 1993-10-12 | 1994-11-08 | Eli Lilly And Company | Asymmetric synthesis |
| US6162949A (en) | 1994-12-16 | 2000-12-19 | Uop Llc | Process for preparation of the pharmaceutically desired (S)-oxetine enantiomers |
| US6458955B1 (en) | 1994-12-16 | 2002-10-01 | Uop Llc | Process for preparation of pharmaceutically desired enantiomers |
| ES2194536T3 (es) | 1998-11-13 | 2003-11-16 | Lilly Co Eli | Combinacion de duloxetina con farmacos antiinflamatorios no esteroideos. |
| ATE309196T1 (de) * | 1999-04-09 | 2005-11-15 | Lilly Co Eli | Verfahren zur herstellung von 3-aryloxy-3- arylpropylamine und deren zwischenprodukte |
| AU1724201A (en) * | 1999-12-17 | 2001-06-25 | Ranbaxy Laboratories Limited | Process for the preparation of fluoxetine hydrochloride |
| EP1478641A1 (en) * | 2002-01-24 | 2004-11-24 | Eli Lilly And Company | Process for preparing an intermediate useful for the asymmetric synthesis of duloxetine |
-
2002
- 2002-12-19 GB GBGB0229583.0A patent/GB0229583D0/en not_active Ceased
-
2003
- 2003-12-10 JP JP2004561607A patent/JP5259048B2/ja not_active Expired - Fee Related
- 2003-12-10 CN CN200380109793A patent/CN100579975C/zh not_active Expired - Fee Related
- 2003-12-10 NZ NZ569874A patent/NZ569874A/en not_active IP Right Cessation
- 2003-12-10 AT AT03767973T patent/ATE353081T1/de not_active IP Right Cessation
- 2003-12-10 PL PL377380A patent/PL377380A1/pl unknown
- 2003-12-10 EP EP03767973A patent/EP1587801B1/en not_active Revoked
- 2003-12-10 AU AU2003292396A patent/AU2003292396B2/en not_active Ceased
- 2003-12-10 ES ES03767973T patent/ES2279971T3/es not_active Expired - Lifetime
- 2003-12-10 PT PT03767973T patent/PT1587801E/pt unknown
- 2003-12-10 BR BR0316902-2A patent/BR0316902A/pt not_active IP Right Cessation
- 2003-12-10 CA CA002510750A patent/CA2510750A1/en not_active Abandoned
- 2003-12-10 MX MXPA05006659A patent/MXPA05006659A/es active IP Right Grant
- 2003-12-10 CN CN2007101531328A patent/CN101125848B/zh not_active Expired - Fee Related
- 2003-12-10 RU RU2005122662/04A patent/RU2351594C2/ru not_active IP Right Cessation
- 2003-12-10 EP EP06075798A patent/EP1690861B1/en not_active Expired - Lifetime
- 2003-12-10 US US10/539,415 patent/US7645890B2/en not_active Expired - Fee Related
- 2003-12-10 DE DE60311599T patent/DE60311599T2/de not_active Revoked
- 2003-12-10 KR KR1020057011506A patent/KR100926723B1/ko not_active IP Right Cessation
- 2003-12-10 WO PCT/GB2003/005357 patent/WO2004056795A1/en active IP Right Grant
- 2003-12-10 NZ NZ540881A patent/NZ540881A/en not_active IP Right Cessation
-
2005
- 2005-06-16 IL IL169232A patent/IL169232A/en not_active IP Right Cessation
- 2005-06-17 TN TNP2005000167A patent/TNSN05167A1/en unknown
- 2005-06-24 IS IS7915A patent/IS7915A/is unknown
- 2005-07-14 ZA ZA200505656A patent/ZA200505656B/en unknown
- 2005-07-18 MA MA28400A patent/MA27706A1/fr unknown
- 2005-07-19 HR HR20050657A patent/HRP20050657A2/hr not_active Application Discontinuation
-
2010
- 2010-01-14 AU AU2010200142A patent/AU2010200142B2/en not_active Ceased
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