CA2419842C - New aporphine esters and their use in therapy - Google Patents
New aporphine esters and their use in therapy Download PDFInfo
- Publication number
- CA2419842C CA2419842C CA2419842A CA2419842A CA2419842C CA 2419842 C CA2419842 C CA 2419842C CA 2419842 A CA2419842 A CA 2419842A CA 2419842 A CA2419842 A CA 2419842A CA 2419842 C CA2419842 C CA 2419842C
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- aporphine
- alkanoyl
- formula
- group
- 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
Links
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
- A61P5/12—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH for decreasing, blocking or antagonising the activity of the posterior pituitary hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Reproductive Health (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Psychology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0002934-8 | 2000-08-17 | ||
| SE0002934A SE0002934D0 (sv) | 2000-08-17 | 2000-08-17 | New aporphine esters and in their use in therapy |
| PCT/SE2001/001658 WO2002014279A1 (en) | 2000-08-17 | 2001-07-20 | New aporphine esters and their use in therapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2419842A1 CA2419842A1 (en) | 2002-02-21 |
| CA2419842C true CA2419842C (en) | 2011-10-18 |
Family
ID=20280719
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2419842A Expired - Fee Related CA2419842C (en) | 2000-08-17 | 2001-07-20 | New aporphine esters and their use in therapy |
Country Status (19)
| Country | Link |
|---|---|
| US (3) | US7238705B2 (https=) |
| EP (1) | EP1309553A1 (https=) |
| JP (1) | JP2004506041A (https=) |
| KR (1) | KR100865503B1 (https=) |
| CN (1) | CN1242991C (https=) |
| AU (2) | AU2001271228B2 (https=) |
| BR (1) | BR0113291A (https=) |
| CA (1) | CA2419842C (https=) |
| CZ (1) | CZ2003454A3 (https=) |
| EA (1) | EA006388B1 (https=) |
| HU (1) | HUP0301685A3 (https=) |
| IL (2) | IL154096A0 (https=) |
| MX (1) | MXPA03001465A (https=) |
| NO (1) | NO324409B1 (https=) |
| NZ (1) | NZ523893A (https=) |
| PL (1) | PL360089A1 (https=) |
| SE (1) | SE0002934D0 (https=) |
| WO (1) | WO2002014279A1 (https=) |
| ZA (1) | ZA200300828B (https=) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0002934D0 (sv) * | 2000-08-17 | 2000-08-17 | Axon Biochemicals Bv | New aporphine esters and in their use in therapy |
| SE0102036D0 (sv) * | 2001-06-08 | 2001-06-08 | Axon Biochemicals Bv | Pharmaceutical formulation for the efficient administration of apomorphine, 6aR- (-) -N- Propyl- norapomorphine and their derivatives and pro-drugs thereof |
| BR0318360A (pt) * | 2003-06-19 | 2006-07-25 | Lotus Pharmaceutical Co Ltd | aporfina e oxoaporfina e o uso médico das mesmas |
| US20070065463A1 (en) | 2003-06-20 | 2007-03-22 | Ronald Aung-Din | Topical therapy for the treatment of migranes, muscle sprains, muscle spasms, spasticity and related conditions |
| AU2005232748A1 (en) | 2004-04-13 | 2005-10-27 | The Mclean Hospital Corporation | R(-)-11-hydroxyaporphine derivatives and uses thereof |
| GB2437488A (en) * | 2006-04-25 | 2007-10-31 | Optinose As | Pharmaceutical oily formulation for nasal or buccal administration |
| US20110111014A1 (en) * | 2007-06-26 | 2011-05-12 | Parkinson's Institute | Methods and compositions for treatment of neurological disorders |
| WO2009009083A1 (en) * | 2007-07-12 | 2009-01-15 | The Mclean Hospital Corporation | R(-)-2-methoxy-11-hydroxyaporphine and derivatives thereof |
| US8129530B2 (en) | 2007-08-31 | 2012-03-06 | H. Lundbeck A/S | Catecholamine derivatives and prodrugs thereof |
| TWI404702B (zh) * | 2007-08-31 | 2013-08-11 | Lundbeck & Co As H | 兒茶酚胺衍生物和其前藥 |
| ES2315203B1 (es) * | 2007-09-11 | 2010-01-13 | Universidade De Santiago De Compostela | Uso de oxoisoaporfinas y sus derivados como inhibidores selectivos de la monoamino oxidasa a. |
| GB0721394D0 (en) * | 2007-10-31 | 2007-12-12 | Vectura Group Plc | Compositions for trating parkinson's disease |
| US8592424B2 (en) | 2008-06-30 | 2013-11-26 | Afgin Pharma Llc | Topical regional neuro-affective therapy |
| EP2419508A4 (en) * | 2009-04-17 | 2012-11-14 | Somalabs Inc | METHOD OF INDUCING REWARD RESPONSE BY MODULATION OF DOPAMINERGIC SYSTEMS IN THE CENTRAL NERVOUS SYSTEM |
| PT2952191T (pt) | 2009-06-12 | 2018-11-30 | Sunovion Pharmaceuticals Inc | Apomorfina sublingual |
| NZ612686A (en) | 2010-12-16 | 2015-11-27 | Cynapsus Therapeutics Inc | Sublingual films |
| ES2673672T3 (es) * | 2011-02-11 | 2018-06-25 | The Regents Of The University Of Michigan | Composiciones tripeptídicas y su uso para el tratamiento de la diabetes |
| JP7211706B2 (ja) | 2015-04-21 | 2023-01-24 | サノヴィオン ファーマシュティカルズ インコーポレーテッド | 口腔粘膜へのアポモルフィンの投与によるパーキンソン病の治療方法 |
| US10989704B2 (en) | 2015-06-24 | 2021-04-27 | Koninklijke Philips N.V. | Sweat monitoring apparatus and monitoring method |
| JP7320507B2 (ja) | 2017-11-24 | 2023-08-03 | ハー・ルンドベック・アクチエゼルスカベット | パーキンソン病の治療に使用するための新規なカテコールアミンプロドラッグ |
| HUE070062T2 (hu) * | 2018-01-18 | 2025-05-28 | Leukos Biotech S L | Apomorfin-palmitinsav kokristály szilárd részecske kristályos forma |
| JP2021522196A (ja) * | 2018-04-20 | 2021-08-30 | ザ ジェネラル ホスピタル コーポレイション | 血液脳関門を越えて送達するためのアセチル化プロドラッグ |
| US11130775B2 (en) | 2019-05-20 | 2021-09-28 | H. Lundbeck A/S | Solid forms of (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4A,5,10,10A-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid |
| US11111263B2 (en) | 2019-05-20 | 2021-09-07 | H. Lundbeck A/S | Process for the manufacture of (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid |
| US11168056B2 (en) | 2019-05-20 | 2021-11-09 | H. Lundbeck A/S | Process for the manufacturing of (6aR,10aR)-7-propyl-6,6a,7,8,9,10,10a,11-octahydro-[1,3]dioxolo[4′,5′:5,6]benzo[1,2-G]quinoline and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[G]quinoline-6,7-diol |
| WO2020234274A1 (en) | 2019-05-21 | 2020-11-26 | H. Lundbeck A/S | New catecholamine prodrugs for use in the treatment of parkinson's disease |
| JP7562562B2 (ja) | 2019-05-21 | 2024-10-07 | ハー・ルンドベック・アクチエゼルスカベット | パーキンソン病の治療に使用するための新規なカテコールアミンプロドラッグ |
| EP3972971A1 (en) | 2019-05-21 | 2022-03-30 | H. Lundbeck A/S | New catecholamine prodrugs for use in the treatment of parkinson's diseases |
| CN113727712B (zh) | 2019-05-21 | 2024-11-15 | H.隆德贝克有限公司 | 用于治疗帕金森病的儿茶酚胺氨基甲酸酯前药 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4080456A (en) * | 1971-10-26 | 1978-03-21 | Schering Aktiengesellschaft | Diacylapomorphines |
| AU3140577A (en) * | 1976-12-13 | 1979-06-14 | Sterling Drug Inc | N-propylnorapormorphine diesters |
| DE2717001C2 (de) | 1977-04-18 | 1984-06-20 | Karl O. Helm Ag, 2000 Hamburg | Arzneimittel mit antithrombotischer Wirkung |
| DE3171561D1 (en) | 1980-05-08 | 1985-09-05 | Univ Northeastern | N-substituted aporphines, a method of inducing emesis and a method of controlling psychosis utilising the same |
| US4353912A (en) * | 1980-05-08 | 1982-10-12 | Northeastern University | N-Haloalkyl nor apomorphines and method of inactivating dopamine receptor sites and enhancing dopaminergic activity therewith |
| WO1990012574A1 (en) * | 1989-04-25 | 1990-11-01 | Northeastern University | Dopamine agonist compounds |
| GB9517062D0 (en) | 1995-08-18 | 1995-10-25 | Scherer Ltd R P | Pharmaceutical compositions |
| GB9700878D0 (en) | 1997-01-17 | 1997-03-05 | Scherer Ltd R P | Dosage forms and method for ameliorating male erectile dysfunction |
| US6403605B1 (en) | 1998-05-29 | 2002-06-11 | Queen's University At Kingston | Methods for the normalization of sexual response and amelioration of long term genital tissue degradation |
| IT1299566B1 (it) | 1998-07-17 | 2000-03-16 | Ifi Istituto Farmacoterapico I | Cerotto transdermico e composizioni farmaceutiche comprendenti r (-)- norapropilapomorfina cloridrato e/o s (+) - norapropilapomorfina |
| WO2000069416A1 (en) | 1999-05-13 | 2000-11-23 | Unihart Corporation | Pharmaceutical compositions comprising apocodeine and/or its derivatives |
| BR0109515A (pt) * | 2000-04-07 | 2004-08-10 | Tap Pharmaceutical Prod Inc | Derivados da apomorfina e métodos para seu uso |
| SE0102036D0 (sv) * | 2001-06-08 | 2001-06-08 | Axon Biochemicals Bv | Pharmaceutical formulation for the efficient administration of apomorphine, 6aR- (-) -N- Propyl- norapomorphine and their derivatives and pro-drugs thereof |
| SE0002934D0 (sv) | 2000-08-17 | 2000-08-17 | Axon Biochemicals Bv | New aporphine esters and in their use in therapy |
| EP1950203A1 (en) | 2007-01-24 | 2008-07-30 | Laboratorios del Dr. Esteve S.A. | Substituted pyrazoline compounds with ACAT, their preparation and use as medicaments |
-
2000
- 2000-08-17 SE SE0002934A patent/SE0002934D0/xx unknown
-
2001
- 2001-07-20 JP JP2002519422A patent/JP2004506041A/ja active Pending
- 2001-07-20 BR BR0113291-1A patent/BR0113291A/pt not_active Application Discontinuation
- 2001-07-20 WO PCT/SE2001/001658 patent/WO2002014279A1/en not_active Ceased
- 2001-07-20 CA CA2419842A patent/CA2419842C/en not_active Expired - Fee Related
- 2001-07-20 NZ NZ523893A patent/NZ523893A/en not_active IP Right Cessation
- 2001-07-20 PL PL36008901A patent/PL360089A1/xx not_active Application Discontinuation
- 2001-07-20 CZ CZ2003454A patent/CZ2003454A3/cs unknown
- 2001-07-20 AU AU2001271228A patent/AU2001271228B2/en not_active Ceased
- 2001-07-20 IL IL15409601A patent/IL154096A0/xx unknown
- 2001-07-20 MX MXPA03001465A patent/MXPA03001465A/es active IP Right Grant
- 2001-07-20 CN CNB018142222A patent/CN1242991C/zh not_active Expired - Fee Related
- 2001-07-20 EP EP01950203A patent/EP1309553A1/en not_active Withdrawn
- 2001-07-20 EA EA200300266A patent/EA006388B1/ru not_active IP Right Cessation
- 2001-07-20 US US10/344,420 patent/US7238705B2/en not_active Expired - Lifetime
- 2001-07-20 AU AU7122801A patent/AU7122801A/xx active Pending
- 2001-07-20 KR KR1020037002274A patent/KR100865503B1/ko not_active Expired - Fee Related
- 2001-07-20 HU HU0301685A patent/HUP0301685A3/hu unknown
-
2003
- 2003-01-23 IL IL154096A patent/IL154096A/en active IP Right Grant
- 2003-01-30 ZA ZA200300828A patent/ZA200300828B/en unknown
- 2003-02-11 NO NO20030677A patent/NO324409B1/no not_active IP Right Cessation
-
2005
- 2005-02-22 US US11/061,881 patent/US7332503B2/en not_active Expired - Lifetime
-
2008
- 2008-01-29 US US12/021,560 patent/US20080119504A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0301685A2 (hu) | 2003-08-28 |
| US20080119504A1 (en) | 2008-05-22 |
| CA2419842A1 (en) | 2002-02-21 |
| WO2002014279A1 (en) | 2002-02-21 |
| MXPA03001465A (es) | 2004-12-13 |
| EA200300266A1 (ru) | 2003-08-28 |
| PL360089A1 (en) | 2004-09-06 |
| NZ523893A (en) | 2003-10-31 |
| IL154096A (en) | 2009-11-18 |
| BR0113291A (pt) | 2004-01-06 |
| EA006388B1 (ru) | 2005-12-29 |
| US20050143408A1 (en) | 2005-06-30 |
| CN1447792A (zh) | 2003-10-08 |
| HUP0301685A3 (en) | 2010-03-29 |
| SE0002934D0 (sv) | 2000-08-17 |
| US20040018956A1 (en) | 2004-01-29 |
| IL154096A0 (en) | 2003-07-31 |
| US7238705B2 (en) | 2007-07-03 |
| NO20030677D0 (no) | 2003-02-11 |
| AU2001271228B2 (en) | 2006-02-02 |
| ZA200300828B (en) | 2004-05-17 |
| CZ2003454A3 (cs) | 2003-06-18 |
| CN1242991C (zh) | 2006-02-22 |
| KR100865503B1 (ko) | 2008-10-28 |
| JP2004506041A (ja) | 2004-02-26 |
| US7332503B2 (en) | 2008-02-19 |
| KR20030036703A (ko) | 2003-05-09 |
| EP1309553A1 (en) | 2003-05-14 |
| NO324409B1 (no) | 2007-10-08 |
| NO20030677L (no) | 2003-03-05 |
| AU7122801A (en) | 2002-02-25 |
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