CA2444876A1 - Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists - Google Patents
Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists Download PDFInfo
- Publication number
- CA2444876A1 CA2444876A1 CA002444876A CA2444876A CA2444876A1 CA 2444876 A1 CA2444876 A1 CA 2444876A1 CA 002444876 A CA002444876 A CA 002444876A CA 2444876 A CA2444876 A CA 2444876A CA 2444876 A1 CA2444876 A1 CA 2444876A1
- Authority
- CA
- Canada
- Prior art keywords
- use according
- lhrh antagonist
- methyl
- treatment
- monthly
- 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.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/10—Peptides having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/09—Luteinising hormone-releasing hormone [LHRH], i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
-
- 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
- A61P25/28—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
Abstract
The present invention relates to the treatment of dementia and neurodegenerative diseases like Alzheimer's disease with intermediate doses of LHRH antagonists which do not cause a castration. A preferred LHRH antagonist is cetrorelix.
Description
Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists The present invention relates to the treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists which do not cause a castration.
FURUYA, Shuichi et al. in WO 01/78780 teach preventives and remedies for Alzheimer's disesase containing a compound having GnRH antagonism have effects of preventing and treating Alzheimer's disease with little toxicity.
It has been shown in a study by Bowen R.L et al. that serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were significantly higher in individuals suffering of dementia , e.g. Alzheimer's disease. Bowen R.L.
et al. propose in their patent application CA 2,309,395 (US priority June 4, 1999, 09/326,180) to lower FSH and LH to minimal levels by the use of castrating doses of analogues of the LH-releasing hormone (LHRH), either super-agonists or antagonists.
This treatment would be accompanied by highly undesirable side effects as lowering sex hormone levels to castration levels would result in loss or reduction of libido, sexual desire and sexual potency. In men and pre-menopausal women this treatment would also result in the typical symptoms of drop of sex hormones (ike hot flushes, etc. Women would additionally suffer from loss of bone minerals that would limit the treatment.
These side effects could be reduced by hormone replacement therapy.
It has been found now that the treatment with intermediate doses of LHRH
antagonists results in a sub-maximal lowering of FSH and LH to normal levels that leaves sex hormone levels above the castration treshold.
This treatment is highly advantageous as it gives the desired results of normalising FSH and LH levels without the undesirable side-effects of sex hormone blockade. Thus the additional treatment of sex hormone replacement becomes superfluous.
The present invention relates to the treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists, wherein the antagonist is preferably cetrorelix, teverelix, antide or abarelix. The antagonist can also be the LHRH antagonist D-63 153 (Ac-D-Nal-D-pCl-Phe-D-Pal-Ser-N-Me-Tyr-D-Hci-Nle-Arg-Pro-D-Ala-NH2) as described in the PCT application WO 00155190 A1.
The mentioned LHRH antagonists can also exhibit a heterocyclic skeletal structure. Such peptidomimetics can be for example - 1-[7-Chloro-3-(3,5-dimethyl-phenyl)-2-oxo-4-(2-piperidin-2-yl-ethoxy)-1,2-dihydro-quinolin-6-yl]-3-pyridin-2-yl-urea (described in WO 97/44339), - 3-[Benzyl-methyl-amino)-methyl]-2-tert-butyl-8-(2-fluoro-benzyl)-6-(3-methoxy-phenyl)-7-methyl-8H imidazo[1,2-a]pyrimidin-5-one (described in WO
01 /29044), - 2-(2,5-Dimethyl-furan-3-yl)-8-(2-fluoro-benzyl)-3-([methyl-(2-pyridin-2-yl-ethyl)-amino]-methyl)-5-oxo-5,8-dihydro-imidazo[1,2-a]pyrimidine-6-carboxylic acid 1-ethyl-propylester (described in WO 00/69859), - 3-((2-[2-(3,5-Difluoro-phenyl)-1-(2-methoxy-benzoyl)-2-oxo-ethylidene]-2,3-dihydro-1 H benzoimidazol-5-yl-amino)-methyl)-benzonitrile (described in WO
02/02533).
The LHRH antagonist is given in a monthly dose of 10 to 100 mg per month and the treatment is repeated monthly, two-monthly or lasting several months.
In a preferred embodiment the LHRH antagonist is given in a monthly dose of 30 to 60 mg per month and the treatment is repeated monthly, two-monthly or lasting several months.
Pharmaceutical formulations of the LHRH antagonist suitable for the therapeutic management of dementia and neurodegenerative diseases may be for example a) acetate salt formulations of the active compounds in the concentration of 1 mg/1 ml or lower where the lyophilisate powder may be dissolved in water for injection or in gluconic acid;
b) acetate salt formulations of the active compounds in the concentration of 1.5 mg/1 ml to 5.0 mg/1 ml, preferably 2.5 mg/1 ml where the lyophilisate powder may be dissolved in water for injection or in gluconic acid;
c) pamoate salt formulations of the active compounds in the concentration of mg/1 ml to 30 mg/1 ml, preferably 15 mg/1 ml where the lyophilisate powder may be dissolved in giuconic acid or in wafer for injection.
Suitable excipients and dosage forms are for example described by K.H. Bauer, K.-H. Fromming and C. Fuhrer, Lehrbuch der Pharmazeutischen Technologie, 6'"
edition, Stuttgart 1999, pages 163-186 (excipients) and pages 227-386 (dosage forms), including the references as cited therein.
The LHRH antagonist can be administered for example subcutaneous, oral, intramuscular or inhalative.
The disease as mentioned, for example can be treated in accordance with the following scheme.
Example In one embodiment of the invention a single dose of 30-60 mg of cetrorelix is administered by injection per month. The treatment is continued monthly.
In another embodiment the treatment is continued two-mothly or lasting several months after the administration of the single dose.
FURUYA, Shuichi et al. in WO 01/78780 teach preventives and remedies for Alzheimer's disesase containing a compound having GnRH antagonism have effects of preventing and treating Alzheimer's disease with little toxicity.
It has been shown in a study by Bowen R.L et al. that serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were significantly higher in individuals suffering of dementia , e.g. Alzheimer's disease. Bowen R.L.
et al. propose in their patent application CA 2,309,395 (US priority June 4, 1999, 09/326,180) to lower FSH and LH to minimal levels by the use of castrating doses of analogues of the LH-releasing hormone (LHRH), either super-agonists or antagonists.
This treatment would be accompanied by highly undesirable side effects as lowering sex hormone levels to castration levels would result in loss or reduction of libido, sexual desire and sexual potency. In men and pre-menopausal women this treatment would also result in the typical symptoms of drop of sex hormones (ike hot flushes, etc. Women would additionally suffer from loss of bone minerals that would limit the treatment.
These side effects could be reduced by hormone replacement therapy.
It has been found now that the treatment with intermediate doses of LHRH
antagonists results in a sub-maximal lowering of FSH and LH to normal levels that leaves sex hormone levels above the castration treshold.
This treatment is highly advantageous as it gives the desired results of normalising FSH and LH levels without the undesirable side-effects of sex hormone blockade. Thus the additional treatment of sex hormone replacement becomes superfluous.
The present invention relates to the treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists, wherein the antagonist is preferably cetrorelix, teverelix, antide or abarelix. The antagonist can also be the LHRH antagonist D-63 153 (Ac-D-Nal-D-pCl-Phe-D-Pal-Ser-N-Me-Tyr-D-Hci-Nle-Arg-Pro-D-Ala-NH2) as described in the PCT application WO 00155190 A1.
The mentioned LHRH antagonists can also exhibit a heterocyclic skeletal structure. Such peptidomimetics can be for example - 1-[7-Chloro-3-(3,5-dimethyl-phenyl)-2-oxo-4-(2-piperidin-2-yl-ethoxy)-1,2-dihydro-quinolin-6-yl]-3-pyridin-2-yl-urea (described in WO 97/44339), - 3-[Benzyl-methyl-amino)-methyl]-2-tert-butyl-8-(2-fluoro-benzyl)-6-(3-methoxy-phenyl)-7-methyl-8H imidazo[1,2-a]pyrimidin-5-one (described in WO
01 /29044), - 2-(2,5-Dimethyl-furan-3-yl)-8-(2-fluoro-benzyl)-3-([methyl-(2-pyridin-2-yl-ethyl)-amino]-methyl)-5-oxo-5,8-dihydro-imidazo[1,2-a]pyrimidine-6-carboxylic acid 1-ethyl-propylester (described in WO 00/69859), - 3-((2-[2-(3,5-Difluoro-phenyl)-1-(2-methoxy-benzoyl)-2-oxo-ethylidene]-2,3-dihydro-1 H benzoimidazol-5-yl-amino)-methyl)-benzonitrile (described in WO
02/02533).
The LHRH antagonist is given in a monthly dose of 10 to 100 mg per month and the treatment is repeated monthly, two-monthly or lasting several months.
In a preferred embodiment the LHRH antagonist is given in a monthly dose of 30 to 60 mg per month and the treatment is repeated monthly, two-monthly or lasting several months.
Pharmaceutical formulations of the LHRH antagonist suitable for the therapeutic management of dementia and neurodegenerative diseases may be for example a) acetate salt formulations of the active compounds in the concentration of 1 mg/1 ml or lower where the lyophilisate powder may be dissolved in water for injection or in gluconic acid;
b) acetate salt formulations of the active compounds in the concentration of 1.5 mg/1 ml to 5.0 mg/1 ml, preferably 2.5 mg/1 ml where the lyophilisate powder may be dissolved in water for injection or in gluconic acid;
c) pamoate salt formulations of the active compounds in the concentration of mg/1 ml to 30 mg/1 ml, preferably 15 mg/1 ml where the lyophilisate powder may be dissolved in giuconic acid or in wafer for injection.
Suitable excipients and dosage forms are for example described by K.H. Bauer, K.-H. Fromming and C. Fuhrer, Lehrbuch der Pharmazeutischen Technologie, 6'"
edition, Stuttgart 1999, pages 163-186 (excipients) and pages 227-386 (dosage forms), including the references as cited therein.
The LHRH antagonist can be administered for example subcutaneous, oral, intramuscular or inhalative.
The disease as mentioned, for example can be treated in accordance with the following scheme.
Example In one embodiment of the invention a single dose of 30-60 mg of cetrorelix is administered by injection per month. The treatment is continued monthly.
In another embodiment the treatment is continued two-mothly or lasting several months after the administration of the single dose.
Claims (12)
1. Use of a LHRH antagonist for the preparation of a medicament for the treatment of dementia and neurodegenerative diseases in humans by administration of intermediate doses, which do not cause a castration.
2. Use according to claim 1, characterized in that the monthly single dose is in the range of 10 -100 mg LHRH antagonist.
3. Use according to claims 1 and 2, characterized in that the monthly single dose is about 30 to about 60 mg LHRH antagonist.
4. Use according to one of claims 1 to 3, characterized in that the administration is continued on a monthly or two-monthly or lasting several months base.
5. Use according to one of claims 1 to 4, characterized in that the treated disease is Alzheimer's disease.
6. Use according to one of claims 1 to 5, characterized in that the LHRH
antagonist is cetrorelix.
antagonist is cetrorelix.
7. Use according to one of claims 1 to 5, characterized in that the LHRH
antagonist is teverelix.
antagonist is teverelix.
8. Use according to one of claims 1 to 5, characterized in that the LHRH
antagonist is antide.
antagonist is antide.
9. Use according to one of claims 1 to 5, characterized in that the LHRH
antagonist is abarelix.
antagonist is abarelix.
10. Use according to one of claims 1 to 5, characterized in that the LHRH
antagonist is D-63 153 (Ac-D-Nal-D-pCl-Phe-D-Pal-Ser-N-Me-Tyr-D-Hcl-Nle-Arg-Pro-D-Ala-NH2).
antagonist is D-63 153 (Ac-D-Nal-D-pCl-Phe-D-Pal-Ser-N-Me-Tyr-D-Hcl-Nle-Arg-Pro-D-Ala-NH2).
11. Use according to one of claims 1 to 5, characterized in that the LHRH
antagonist is a peptidomimetic.
antagonist is a peptidomimetic.
12. Use according to claim 11 in which the peptidomimetic is a compound - 1-[7-Chloro-3-(3,5-dimethyl-phenyl)-2-oxo-4-(2-piperidin-2-yl-ethoxy)-1,2-dihydro-quinolin-6-yl]-3-pyridin-2-yl-urea - 3-[Benzyl-methyl-amino)-methyl]-2-tert-butyl-8-(2-fluoro-benzyl)-6-(3-methoxy-phenyl)-7-methyl-8H-imidazo[1,2-a]pyrimidin-5-one - 2-(2,5-Dimethyl-furan-3-yl)-8-(2-fluoro-benzyl)-3-([methyl-(2-pyridin-2-yl-ethyl)-amino]-methyl)-5-oxo-5,8-dihydro-imidazo[1,2-a]pyrimidine-6-carboxylic acid 1-ethyl-propylester or - 3-((2-[2-(3,5-Difluoro-phenyl)-1-(2-methoxy-benzoyl)-2-oxo-ethylidene]-2,3-dihydro-1H-benzoimidazol-5-yl-amino)-methyl)-benzonitrile.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28743401P | 2001-04-30 | 2001-04-30 | |
| US60/287,434 | 2001-04-30 | ||
| PCT/EP2002/004677 WO2002102401A1 (en) | 2001-04-30 | 2002-04-27 | Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2444876A1 true CA2444876A1 (en) | 2002-12-27 |
Family
ID=23102886
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002444876A Abandoned CA2444876A1 (en) | 2001-04-30 | 2002-04-27 | Treatment of dementia and neurodegenerative diseases with intermediate doses of lhrh antagonists |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US7288517B2 (en) |
| EP (1) | EP1392348B1 (en) |
| JP (1) | JP2004529207A (en) |
| KR (1) | KR20040000446A (en) |
| CN (1) | CN1317030C (en) |
| AT (1) | ATE400287T1 (en) |
| AU (1) | AU2002310788B2 (en) |
| BG (1) | BG108339A (en) |
| BR (1) | BR0209290A (en) |
| CA (1) | CA2444876A1 (en) |
| CZ (1) | CZ20033167A3 (en) |
| DE (1) | DE60227507D1 (en) |
| DK (1) | DK1392348T3 (en) |
| ES (1) | ES2307760T3 (en) |
| HK (1) | HK1072000A1 (en) |
| HU (1) | HUP0400067A2 (en) |
| IL (1) | IL156777A0 (en) |
| MX (1) | MXPA03008666A (en) |
| NO (1) | NO20034322D0 (en) |
| NZ (1) | NZ544417A (en) |
| PL (1) | PL362319A1 (en) |
| PT (1) | PT1392348E (en) |
| RU (1) | RU2319501C2 (en) |
| SI (1) | SI1392348T1 (en) |
| SK (1) | SK14512003A3 (en) |
| UA (1) | UA80679C2 (en) |
| WO (1) | WO2002102401A1 (en) |
| ZA (1) | ZA200305326B (en) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6828415B2 (en) * | 1993-02-19 | 2004-12-07 | Zentaris Gmbh | Oligopeptide lyophilisate, their preparation and use |
| US20020077327A1 (en) * | 1999-09-23 | 2002-06-20 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| AU2001271022B2 (en) * | 2000-07-05 | 2006-08-17 | Astellas Pharma Inc. | Propane-1,3-dione derivatives |
| DE10137174A1 (en) * | 2001-07-31 | 2003-02-13 | Zentaris Ag | Method of modifying T-cell populations, e.g. for treatment of HIV infection or cancer, comprises administrating luteinizing hormone releasing hormone antagonist at controlled dose insufficient to cause chemical castration |
| CA2568590C (en) | 2004-06-04 | 2011-01-18 | Astellas Pharma Inc. | Propane-1,3-dione derivative or salt thereof useful as gnrh receptor antagonist |
| US20080171736A1 (en) * | 2004-12-23 | 2008-07-17 | Gregory Christopher W | Treatment of Alzheimer's Disease and Mild Cognitive impairment using GnRH-I analogs and one or more of acetylcholinesterase inhibitors and NMDA receptor antagonists |
| JP2008525439A (en) * | 2004-12-23 | 2008-07-17 | ボイジャー・ファーマシューティカル・コーポレーション | Leuprolide acetate and acetylcholinesterase inhibitors or NMDA receptor agonists for the treatment of Alzheimer's disease |
| AU2006232469B2 (en) * | 2005-03-31 | 2011-03-31 | Astellas Pharma Inc. | Propane-1,3-dion derivative or salt thereof |
| JP5406030B2 (en) * | 2006-10-21 | 2014-02-05 | アボット ゲーエムベーハー ウント カンパニー カーゲー | Heterocyclic compounds and their use as glycogen synthase kinase 3 inhibitors |
| RU2010113981A (en) * | 2007-09-11 | 2011-10-20 | Мондобайотек Лабораториз Аг (Li) | APPLICATION OF A HEXAPEPTIDE ANTAGONIST RECEPTOR OF THROMBOCITARY FIBRINOGEN AND ALPHA-ENDORPHINE AS A THERAPEUTIC |
| EP2187943A2 (en) * | 2007-09-11 | 2010-05-26 | Mondobiotech Laboratories AG | Gamma 1 msh alone or in combination with pentagastrin as a therapeutic agent |
| EP2095818A1 (en) | 2008-02-29 | 2009-09-02 | AEterna Zentaris GmbH | Use of LHRH antagonists at non-castrating doses |
| CA2726247C (en) * | 2008-05-29 | 2018-06-26 | Isr Immune System Regulation Ab | Method and means for treating viral disease, in particular hiv/aids |
| EP2621914B1 (en) | 2010-09-27 | 2016-12-28 | Abbott GmbH & Co. KG | Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors |
| US9090592B2 (en) | 2010-12-30 | 2015-07-28 | AbbVie Deutschland GmbH & Co. KG | Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors |
| EP3560555A1 (en) * | 2018-04-26 | 2019-10-30 | LifeArc | A composition for treating one or more estrogen related diseases |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3135743A (en) * | 1960-06-29 | 1964-06-02 | Sterling Drug Inc | Steroido[2. 3-d]isoxazoles and preparation thereof |
| EP0901489A1 (en) | 1996-05-20 | 1999-03-17 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| DE19911771B4 (en) | 1999-03-17 | 2006-03-30 | Zentaris Gmbh | LHRH antagonist, process for its preparation and its use |
| EP1185530A1 (en) | 1999-05-14 | 2002-03-13 | Neurocrine Biosciences, Inc. | Imidazo- and pyrrolo[1,2-a]pyrimid-4-ones as gonadotropin-releasing hormone receptor antagonists |
| CA2309395A1 (en) | 1999-06-04 | 2000-12-04 | Richard Lloyd Bowen | Methods for preventing and treating alzheimer's disease |
| WO2001029044A1 (en) * | 1999-10-15 | 2001-04-26 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| EP1393747A1 (en) | 2000-04-13 | 2004-03-03 | Takeda Chemical Industries, Ltd. | Preventives/remedies for alzheimer's disease |
| AU2001271022B2 (en) | 2000-07-05 | 2006-08-17 | Astellas Pharma Inc. | Propane-1,3-dione derivatives |
-
2002
- 2002-04-27 MX MXPA03008666A patent/MXPA03008666A/en active IP Right Grant
- 2002-04-27 DK DK02735312T patent/DK1392348T3/en active
- 2002-04-27 RU RU2003134949/14A patent/RU2319501C2/en not_active IP Right Cessation
- 2002-04-27 EP EP02735312A patent/EP1392348B1/en not_active Expired - Lifetime
- 2002-04-27 CZ CZ20033167A patent/CZ20033167A3/en unknown
- 2002-04-27 AT AT02735312T patent/ATE400287T1/en not_active IP Right Cessation
- 2002-04-27 AU AU2002310788A patent/AU2002310788B2/en not_active Ceased
- 2002-04-27 PT PT02735312T patent/PT1392348E/en unknown
- 2002-04-27 SK SK1451-2003A patent/SK14512003A3/en unknown
- 2002-04-27 CN CNB028042964A patent/CN1317030C/en not_active Expired - Fee Related
- 2002-04-27 US US10/133,967 patent/US7288517B2/en not_active Expired - Fee Related
- 2002-04-27 KR KR10-2003-7014128A patent/KR20040000446A/en not_active Application Discontinuation
- 2002-04-27 IL IL15677702A patent/IL156777A0/en unknown
- 2002-04-27 NZ NZ544417A patent/NZ544417A/en unknown
- 2002-04-27 UA UA2003109180A patent/UA80679C2/en unknown
- 2002-04-27 BR BR0209290-5A patent/BR0209290A/en not_active IP Right Cessation
- 2002-04-27 WO PCT/EP2002/004677 patent/WO2002102401A1/en active IP Right Grant
- 2002-04-27 CA CA002444876A patent/CA2444876A1/en not_active Abandoned
- 2002-04-27 ES ES02735312T patent/ES2307760T3/en not_active Expired - Lifetime
- 2002-04-27 HU HU0400067A patent/HUP0400067A2/en unknown
- 2002-04-27 SI SI200230730T patent/SI1392348T1/en unknown
- 2002-04-27 DE DE60227507T patent/DE60227507D1/en not_active Expired - Fee Related
- 2002-04-27 PL PL36231902A patent/PL362319A1/en not_active Application Discontinuation
- 2002-04-27 JP JP2003504987A patent/JP2004529207A/en not_active Withdrawn
-
2003
- 2003-07-10 ZA ZA200305326A patent/ZA200305326B/en unknown
- 2003-09-26 NO NO20034322A patent/NO20034322D0/en not_active Application Discontinuation
- 2003-11-10 BG BG108339A patent/BG108339A/en unknown
-
2005
- 2005-06-08 HK HK05104803A patent/HK1072000A1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1392348A1 (en) | 2004-03-03 |
| KR20040000446A (en) | 2004-01-03 |
| NO20034322L (en) | 2003-09-26 |
| US7288517B2 (en) | 2007-10-30 |
| IL156777A0 (en) | 2004-02-08 |
| HUP0400067A2 (en) | 2004-04-28 |
| DK1392348T3 (en) | 2008-09-29 |
| RU2319501C2 (en) | 2008-03-20 |
| ZA200305326B (en) | 2003-07-30 |
| CZ20033167A3 (en) | 2004-08-18 |
| SI1392348T1 (en) | 2008-12-31 |
| MXPA03008666A (en) | 2004-10-15 |
| ATE400287T1 (en) | 2008-07-15 |
| BR0209290A (en) | 2004-07-13 |
| PL362319A1 (en) | 2004-10-18 |
| NZ544417A (en) | 2008-03-28 |
| JP2004529207A (en) | 2004-09-24 |
| PT1392348E (en) | 2008-09-09 |
| RU2003134949A (en) | 2005-02-10 |
| HK1072000A1 (en) | 2005-08-12 |
| UA80679C2 (en) | 2007-10-25 |
| EP1392348B1 (en) | 2008-07-09 |
| CN1317030C (en) | 2007-05-23 |
| AU2002310788B2 (en) | 2007-04-05 |
| DE60227507D1 (en) | 2008-08-21 |
| NO20034322D0 (en) | 2003-09-26 |
| SK14512003A3 (en) | 2004-08-03 |
| BG108339A (en) | 2004-11-30 |
| CN1575185A (en) | 2005-02-02 |
| WO2002102401A1 (en) | 2002-12-27 |
| US20020177556A1 (en) | 2002-11-28 |
| ES2307760T3 (en) | 2008-12-01 |
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