ES2296342T3 - Tratamiento de la obesidad. - Google Patents
Tratamiento de la obesidad. Download PDFInfo
- Publication number
- ES2296342T3 ES2296342T3 ES98941152T ES98941152T ES2296342T3 ES 2296342 T3 ES2296342 T3 ES 2296342T3 ES 98941152 T ES98941152 T ES 98941152T ES 98941152 T ES98941152 T ES 98941152T ES 2296342 T3 ES2296342 T3 ES 2296342T3
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- Prior art keywords
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- peptide
- hgh
- cys
- resin
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- 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 - Lifetime
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- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
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- 229960005070 ascorbic acid Drugs 0.000 description 1
- QLRGSUBBRSJVLL-UHFFFAOYSA-N benzene;chloroform;methanol Chemical compound OC.ClC(Cl)Cl.C1=CC=CC=C1 QLRGSUBBRSJVLL-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
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- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
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- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
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- 238000012866 crystallographic experiment Methods 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 102000034238 globular proteins Human genes 0.000 description 1
- 108091005896 globular proteins Proteins 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N glycerol 1-phosphate Chemical class OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000003688 hormone derivative Substances 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000002608 insulinlike Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 108010078274 isoleucylvaline Proteins 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 235000019626 lipase activity Nutrition 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000013227 male C57BL/6J mice Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 238000007479 molecular analysis Methods 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000007030 peptide scission Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000009596 postnatal growth Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 231100000272 reduced body weight Toxicity 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 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
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-N sodium;5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,6-trione Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)NC1=O QGMRQYFBGABWDR-UHFFFAOYSA-N 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 108010048412 somatotropin (177-191) Proteins 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-N sorbic acid group Chemical group C(\C=C\C=C\C)(=O)O WSWCOQWTEOXDQX-MQQKCMAXSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 229960001005 tuberculin Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/61—Growth hormone [GH], i.e. somatotropin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
-
- 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
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Materials For Photolithography (AREA)
- Reverberation, Karaoke And Other Acoustics (AREA)
- Percussion Or Vibration Massage (AREA)
- Mechanical Treatment Of Semiconductor (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPO9001A AUPO900197A0 (en) | 1997-09-08 | 1997-09-08 | Treatment of obesity |
| AUPO9001 | 1997-09-08 | ||
| AUPP0398A AUPP039897A0 (en) | 1997-11-13 | 1997-11-13 | Treatment of obesity |
| AUPP0398 | 1997-11-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2296342T3 true ES2296342T3 (es) | 2008-04-16 |
Family
ID=25645599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES98941152T Expired - Lifetime ES2296342T3 (es) | 1997-09-08 | 1998-09-04 | Tratamiento de la obesidad. |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US6737407B1 (https=) |
| EP (1) | EP1012189B1 (https=) |
| JP (1) | JP4334761B2 (https=) |
| CN (1) | CN1195776C (https=) |
| AT (1) | ATE377026T1 (https=) |
| BR (1) | BR9811755A (https=) |
| CA (1) | CA2303395C (https=) |
| DE (1) | DE69838647T2 (https=) |
| ES (1) | ES2296342T3 (https=) |
| NZ (1) | NZ502993A (https=) |
| RU (1) | RU2223970C2 (https=) |
| WO (1) | WO1999012969A1 (https=) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPQ387599A0 (en) | 1999-11-05 | 1999-12-02 | Metabolic Pharmaceuticals Limited | Product and method for control of obesity |
| GB0121709D0 (en) * | 2001-09-07 | 2001-10-31 | Imp College Innovations Ltd | Food inhibition agent |
| DE60332358D1 (de) * | 2002-09-09 | 2010-06-10 | Hanall Pharmaceutical Co Ltd | Protease-resistente modifizierte interferon alpha polypeptide |
| US7476653B2 (en) | 2003-06-18 | 2009-01-13 | Tranzyme Pharma, Inc. | Macrocyclic modulators of the ghrelin receptor |
| GB0315182D0 (en) * | 2003-06-28 | 2003-08-06 | Asterion Ltd | Cytokine variant polypeptides |
| WO2005007859A2 (en) * | 2003-07-11 | 2005-01-27 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF ACETYL-COA CARBOXYLASE GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| US8008433B2 (en) * | 2004-05-04 | 2011-08-30 | Metabolic Pharmaceutical Limited | Methods for preventing or treating bone disorders |
| US7998930B2 (en) | 2004-11-04 | 2011-08-16 | Hanall Biopharma Co., Ltd. | Modified growth hormones |
| ES2258923B1 (es) * | 2005-02-23 | 2007-11-01 | Universitat De Les Illes Balears | Uso de la leptina para la prevencion del exceso de peso corporal y composicion que contiene leptina. |
| EP1919506A1 (en) * | 2005-08-02 | 2008-05-14 | Metabolic Pharmaceuticals Ltd. | Peptide conjugate for oral delivery of hydrophilic peptide analgesics |
| WO2007068039A1 (en) * | 2005-12-12 | 2007-06-21 | Metabolic Pharmaceuticals Limited | Treatment of weight gain in estrogen deficient mammals |
| CN101657436A (zh) | 2007-02-09 | 2010-02-24 | 特兰齐姆制药公司 | 大环生长素释放肽受体调节剂及其使用方法 |
| WO2008098280A1 (en) * | 2007-02-16 | 2008-08-21 | Polychip Pharmaceuticals Pty Ltd | Methods for the synthesis of dicarba bridges in growth hormone peptides |
| US20110237524A1 (en) * | 2008-09-19 | 2011-09-29 | Nektar Therapeutics | Polymer conjugates of aod-like peptides |
| WO2010033240A2 (en) | 2008-09-19 | 2010-03-25 | Nektar Therapeutics | Carbohydrate-based drug delivery polymers and conjugates thereof |
| CA2857686C (en) * | 2011-12-09 | 2023-01-17 | Metabolic Pharmaceuticals Pty Ltd | Use of growth hormone fragments |
| CN102827290A (zh) * | 2012-09-07 | 2012-12-19 | 浙江大学 | 人血清白蛋白与人生长激素脂肪分解结构域的融合蛋白 |
| GB2507341A (en) * | 2012-10-29 | 2014-04-30 | Peter Kenny | Fat loss composition comprising a prostaglandin F2 alpha analogue and a fragment of amino acids 176-191 of human growth hormone |
| CN112218650A (zh) * | 2018-01-15 | 2021-01-12 | 单侧Ip私人有限公司 | 肽及其用途 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BG49718A3 (bg) | 1983-07-15 | 1992-01-15 | Bio- Technology General Corp | Метод за получаване на полипептид със супероксиддисмутазна активност |
| US4863901A (en) | 1986-01-09 | 1989-09-05 | Brigham & Women's Hospital | Use of growth hormone for nitrogen retention under hypocaloric conditions |
| US5534617A (en) * | 1988-10-28 | 1996-07-09 | Genentech, Inc. | Human growth hormone variants having greater affinity for human growth hormone receptor at site 1 |
| US5126324A (en) | 1990-06-07 | 1992-06-30 | Genentech, Inc. | Method of enhancing growth in patients using combination therapy |
| AU693478B2 (en) * | 1994-11-10 | 1998-07-02 | Metabolic Pharmaceuticals Limited | Treatment of obesity |
-
1998
- 1998-09-04 BR BR9811755-6A patent/BR9811755A/pt not_active Application Discontinuation
- 1998-09-04 RU RU2000109265/04A patent/RU2223970C2/ru active
- 1998-09-04 JP JP2000510774A patent/JP4334761B2/ja not_active Expired - Fee Related
- 1998-09-04 EP EP98941152A patent/EP1012189B1/en not_active Expired - Lifetime
- 1998-09-04 DE DE69838647T patent/DE69838647T2/de not_active Expired - Lifetime
- 1998-09-04 WO PCT/AU1998/000724 patent/WO1999012969A1/en not_active Ceased
- 1998-09-04 US US09/508,054 patent/US6737407B1/en not_active Expired - Lifetime
- 1998-09-04 CN CNB988100894A patent/CN1195776C/zh not_active Expired - Lifetime
- 1998-09-04 CA CA002303395A patent/CA2303395C/en not_active Expired - Lifetime
- 1998-09-04 AT AT98941152T patent/ATE377026T1/de not_active IP Right Cessation
- 1998-09-04 ES ES98941152T patent/ES2296342T3/es not_active Expired - Lifetime
- 1998-09-04 NZ NZ502993A patent/NZ502993A/xx not_active IP Right Cessation
-
2004
- 2004-05-11 US US10/842,485 patent/US20040192608A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1012189A1 (en) | 2000-06-28 |
| CA2303395C (en) | 2008-12-02 |
| US6737407B1 (en) | 2004-05-18 |
| NZ502993A (en) | 2002-12-20 |
| CA2303395A1 (en) | 1999-03-18 |
| DE69838647T2 (de) | 2008-08-28 |
| US20040192608A1 (en) | 2004-09-30 |
| DE69838647D1 (de) | 2007-12-13 |
| CN1195776C (zh) | 2005-04-06 |
| JP4334761B2 (ja) | 2009-09-30 |
| CN1275132A (zh) | 2000-11-29 |
| WO1999012969A1 (en) | 1999-03-18 |
| ATE377026T1 (de) | 2007-11-15 |
| EP1012189B1 (en) | 2007-10-31 |
| RU2223970C2 (ru) | 2004-02-20 |
| BR9811755A (pt) | 2000-08-29 |
| JP2002501004A (ja) | 2002-01-15 |
| EP1012189A4 (en) | 2004-10-20 |
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