EA200400565A1 - Конъюгаты химически модифицированного гормона роста человека - Google Patents
Конъюгаты химически модифицированного гормона роста человекаInfo
- Publication number
- EA200400565A1 EA200400565A1 EA200400565A EA200400565A EA200400565A1 EA 200400565 A1 EA200400565 A1 EA 200400565A1 EA 200400565 A EA200400565 A EA 200400565A EA 200400565 A EA200400565 A EA 200400565A EA 200400565 A1 EA200400565 A1 EA 200400565A1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- chemically modified
- growth hormone
- human growth
- modified human
- conjugates
- Prior art date
Links
- 102000002265 Human Growth Hormone Human genes 0.000 title abstract 5
- 108010000521 Human Growth Hormone Proteins 0.000 title abstract 5
- 239000000854 Human Growth Hormone Substances 0.000 title abstract 5
- 230000000694 effects Effects 0.000 abstract 2
- 230000002349 favourable effect Effects 0.000 abstract 1
- 102000035118 modified proteins Human genes 0.000 abstract 1
- 108091005573 modified proteins Proteins 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 229920003169 water-soluble polymer Polymers 0.000 abstract 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH], i.e. somatotropin
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Endocrinology (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Reproductive Health (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Abstract
Согласно настоящему изобретению предложен химически модифицированный гормон роста человека (hGH), полученный путем связывания водорастворимого полимера с белком. Химически модифицированный белок по настоящему изобретению может иметь намного более продолжительную активность hGH, чем активность немодифицированного hGH, что дает возможность снизить дозу и создать благоприятные условия режима введения.Отчет о международном поиске был опубликован 2003.08.21.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US33190701P | 2001-11-20 | 2001-11-20 | |
PCT/US2002/037270 WO2003044056A2 (en) | 2001-11-20 | 2002-11-20 | Chemically-modified human growth hormone conjugates |
Publications (2)
Publication Number | Publication Date |
---|---|
EA200400565A1 true EA200400565A1 (ru) | 2005-06-30 |
EA008505B1 EA008505B1 (ru) | 2007-06-29 |
Family
ID=23295870
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EA200700431A EA200700431A1 (ru) | 2001-11-20 | 2002-11-20 | Конъюгаты химически модифицированного гормона роста человека |
EA200400565A EA008505B1 (ru) | 2001-11-20 | 2002-11-20 | Конъюгаты химически модифицированного гормона роста человека |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EA200700431A EA200700431A1 (ru) | 2001-11-20 | 2002-11-20 | Конъюгаты химически модифицированного гормона роста человека |
Country Status (25)
Country | Link |
---|---|
EP (1) | EP1453859A2 (ru) |
JP (2) | JP2005525302A (ru) |
KR (2) | KR20050044858A (ru) |
CN (1) | CN1608079A (ru) |
AP (1) | AP2004003050A0 (ru) |
AU (1) | AU2002356990A1 (ru) |
BR (1) | BR0214451A (ru) |
CA (1) | CA2467731A1 (ru) |
CO (1) | CO5580794A2 (ru) |
EA (2) | EA200700431A1 (ru) |
EC (1) | ECSP045114A (ru) |
GE (1) | GEP20063860B (ru) |
HR (1) | HRP20040448A2 (ru) |
HU (1) | HUP0500997A2 (ru) |
IL (1) | IL162031A0 (ru) |
IS (1) | IS7268A (ru) |
MA (1) | MA27544A1 (ru) |
MX (1) | MXPA04004809A (ru) |
NO (1) | NO20042182L (ru) |
OA (1) | OA13063A (ru) |
PL (1) | PL374354A1 (ru) |
RS (1) | RS53104A (ru) |
TN (1) | TNSN04090A1 (ru) |
WO (1) | WO2003044056A2 (ru) |
ZA (1) | ZA200403907B (ru) |
Families Citing this family (46)
Publication number | Priority date | Publication date | Assignee | Title |
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US20030171285A1 (en) * | 2001-11-20 | 2003-09-11 | Finn Rory F. | Chemically-modified human growth hormone conjugates |
AU2002357806A1 (en) * | 2001-12-11 | 2003-06-23 | Sun Bio, Inc. | Novel monofunctional polyethylene glycol aldehydes |
US7041855B2 (en) | 2001-12-11 | 2006-05-09 | Sun Bio, Inc. | Monofunctional polyethylene glycol aldehydes |
US6956135B2 (en) | 2001-12-11 | 2005-10-18 | Sun Bio, Inc. | Monofunctional polyethylene glycol aldehydes |
US6916962B2 (en) | 2001-12-11 | 2005-07-12 | Sun Bio, Inc. | Monofunctional polyethylene glycol aldehydes |
ME00239B (me) * | 2002-01-18 | 2011-05-10 | Biogen Ma Inc | Polimerna jedinjenja polialkilena i njihova upotreba |
EP1591467A1 (en) * | 2002-09-09 | 2005-11-02 | Nektar Therapeutics Al, Corporation | Conjugate between a polyethylene glycol having a terminal alkanal group and a human growth hormone |
ES2897470T3 (es) | 2002-09-09 | 2022-03-01 | Nektar Therapeutics | Alcanales poliméricos solubles en agua |
US20040142870A1 (en) * | 2002-11-20 | 2004-07-22 | Finn Rory F. | N-terminally monopegylated human growth hormone conjugates, process for their preparation, and methods of use thereof |
US20050281778A1 (en) * | 2003-03-28 | 2005-12-22 | Myung-Ok Park | Human growth hormone conjugated with biocompatible polymer |
CN100580087C (zh) * | 2003-10-10 | 2010-01-13 | 诺和诺德医疗保健公司 | 肽的缀合 |
US7524813B2 (en) | 2003-10-10 | 2009-04-28 | Novo Nordisk Health Care Ag | Selectively conjugated peptides and methods of making the same |
EP2368579A1 (en) * | 2004-01-21 | 2011-09-28 | Novo Nordisk Health Care AG | Transglutaminase mediated conjugation of peptides |
AU2005278903A1 (en) * | 2004-08-31 | 2006-03-09 | Pharmacia & Upjohn Company Llc | Glycerol branched polyethylene glycol human growth hormone conjugates, process for their preparation, and methods of use thereof |
CN103290084A (zh) * | 2004-12-22 | 2013-09-11 | Ambrx公司 | 表达和纯化重组人类生长激素的方法 |
US7638491B2 (en) | 2004-12-22 | 2009-12-29 | Ambrx, Inc. | Therapies using non-natural amino acids and polypeptides |
CN103690936A (zh) * | 2004-12-22 | 2014-04-02 | Ambrx公司 | 经修饰的人类生长激素 |
US20090105134A1 (en) | 2005-02-10 | 2009-04-23 | Novo Nordisk A/S | C-Terminally Pegylated Growth Hormones |
EP1877439B1 (en) | 2005-04-18 | 2011-02-09 | Novo Nordisk A/S | Il-21 variants |
US8293708B2 (en) | 2005-08-30 | 2012-10-23 | Novo Nordisk Health Care A/G | Liquid formulations N-terminal serine of pegylated growth hormone |
AU2006311568B2 (en) | 2005-11-08 | 2010-11-11 | Ambrx, Inc. | Accelerants for the modification of non-natural amino acids and non-natural amino acid polypeptides |
US20080317670A1 (en) | 2005-12-14 | 2008-12-25 | Ambrx, Inc. | Compositions Containing, Methods Involving, and Uses of Non-Natural Amino Acids and Polypeptides |
KR20100014215A (ko) | 2006-07-07 | 2010-02-10 | 노보 노르디스크 헬스 케어 악티엔게젤샤프트 | 신규 단백질 접합체 및 그것의 제조 방법 |
CN101108895B (zh) * | 2006-07-19 | 2011-10-26 | 北京键凯科技有限公司 | 聚乙二醇乙醛衍生物及其与药物的结合物 |
JP2010507382A (ja) | 2006-10-26 | 2010-03-11 | ノヴォ ノルディスク アクティーゼルスカブ | Il−21変異体 |
CL2008002399A1 (es) * | 2007-08-16 | 2009-01-02 | Pharmaessentia Corp | Conjugado sustancialmente puro que posee una porcion polimerica, una porcion proteica (interferon alfa 2b) y un ligante alifatico de 1 a 10 atomos de carbono, util en el tratamiento de las hepatitis b o c. |
CA2720306C (en) | 2008-04-03 | 2016-03-15 | Biosteed Gene Expression Tech. Co., Ltd. | Double-stranded polyethylene glycol modified growth hormone, preparation method and application thereof |
KR101104574B1 (ko) * | 2008-05-14 | 2012-01-11 | 성균관대학교산학협력단 | 폴리에틸렌글리콜로 화학적으로 수식된 인간 성장 호르몬, 이의 제조방법 및 용도 |
KR101533757B1 (ko) * | 2008-07-31 | 2015-07-03 | 파마이센시아 코퍼레이션 | 펩티드-중합체 접합체 |
WO2010015668A1 (en) | 2008-08-06 | 2010-02-11 | Novo Nordisk A/S | Conjugated proteins with prolonged in vivo efficacy |
RU2409669C9 (ru) * | 2008-08-18 | 2012-05-27 | ООО "Саентифик Фьючер Менеджмент" ("Scientific Future Management", "SFM") | Способ иммобилизации биологически активного вещества (бав) на носитель (варианты) и конъюгат бав-носитель, полученный данными способами |
JP5766118B2 (ja) * | 2008-09-11 | 2015-08-19 | ウェルズ ファーゴ バンク ナショナル アソシエイション | ポリマー性アルファ−ヒドロキシアルデヒドおよびケトン反応剤ならびに抱合方法 |
EP2389389B1 (en) | 2009-01-22 | 2015-04-15 | Novo Nordisk Health Care AG | Stable growth hormone compounds |
CN105963710A (zh) | 2009-08-06 | 2016-09-28 | 诺沃—诺迪斯克保健股份有限公司 | 具有延长的体内功效的生长激素 |
CN102711733A (zh) | 2009-12-15 | 2012-10-03 | 阿森迪斯药物股份有限公司 | 瞬时连接于聚合物载体的干生长激素组合物 |
US9211342B2 (en) | 2010-01-22 | 2015-12-15 | Novo Nordisk Healthcare Ag | Stable growth hormone compounds resistant to proteolytic degradation |
KR101813595B1 (ko) | 2010-01-22 | 2017-12-29 | 노보 노르디스크 헬스 케어 악티엔게젤샤프트 | 장기적 생체 내 효능을 갖는 성장 호르몬 |
NZ603399A (en) * | 2010-05-17 | 2014-09-26 | Cebix Inc | Pegylated c-peptide |
EP2446898A1 (en) | 2010-09-30 | 2012-05-02 | Laboratorios Del. Dr. Esteve, S.A. | Use of growth hormone to enhance the immune response in immunosuppressed patients |
EA019967B1 (ru) * | 2011-12-21 | 2014-07-30 | Общество С Ограниченной Ответственностью "Форт" (Ооо "Форт") | Ковалентный конъюгат полиэтиленгликоля с гормоном роста человека |
EP2981282B1 (en) | 2013-04-05 | 2020-11-04 | Novo Nordisk Health Care AG | Growth hormone compound formulation |
WO2016073825A1 (en) | 2014-11-06 | 2016-05-12 | Pharmaessentia Corporation | Dosage regimen for pegylated interferon |
ES2896971T3 (es) | 2014-11-21 | 2022-02-28 | Ascendis Pharma Endocrinology Div A/S | Formas de administración de hormona del crecimiento de acción prolongada |
US20190290733A1 (en) * | 2015-03-11 | 2019-09-26 | Nektar Therapeutics | Conjugates of an il-7 moiety and a polymer |
RU2738416C2 (ru) * | 2015-09-18 | 2020-12-14 | Юниверсити Оф Миязаки | Длительно действующее производное адреномедуллина |
CN114539384A (zh) * | 2020-11-19 | 2022-05-27 | 江苏众红生物工程创药研究院有限公司 | 聚乙二醇化长效生长激素及其制备方法和医药应用 |
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US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
US4904584A (en) * | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
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JPH06506217A (ja) * | 1991-03-18 | 1994-07-14 | エンゾン,インコーポレーテッド | ポリペプチドまたはグリコポリペプチドとポリマーとのヒドラジン含有結合体 |
AU2147192A (en) * | 1991-06-28 | 1993-01-25 | Genentech Inc. | Method of stimulating immune response using growth hormone |
NZ250375A (en) * | 1992-12-09 | 1995-07-26 | Ortho Pharma Corp | Peg hydrazone and peg oxime linkage forming reagents and protein derivatives |
US5824784A (en) * | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
DE69638117D1 (de) * | 1995-09-21 | 2010-03-04 | Genentech Inc | Varianten des menschlichen Wachstumshormons |
WO1999003887A1 (en) * | 1997-07-14 | 1999-01-28 | Bolder Biotechnology, Inc. | Derivatives of growth hormone and related proteins |
IL144259A0 (en) * | 1999-01-14 | 2002-05-23 | Bolder Biotechnology Inc | Methods for making proteins containing free cysteine residues |
ATE246202T1 (de) * | 1999-01-29 | 2003-08-15 | Hoffmann La Roche | Gcsf konjugate |
AU2001289307A1 (en) * | 2000-04-06 | 2001-10-23 | Pharmacia Corporation | Chemically-modified myelopoietin conjugates |
JP2004524020A (ja) * | 2001-01-11 | 2004-08-12 | マキシゲン・エイピーエス | 改良された成長ホルモン分子 |
-
2002
- 2002-11-20 MX MXPA04004809A patent/MXPA04004809A/es not_active Application Discontinuation
- 2002-11-20 EA EA200700431A patent/EA200700431A1/ru unknown
- 2002-11-20 OA OA1200400143A patent/OA13063A/en unknown
- 2002-11-20 CA CA002467731A patent/CA2467731A1/en not_active Abandoned
- 2002-11-20 WO PCT/US2002/037270 patent/WO2003044056A2/en not_active Application Discontinuation
- 2002-11-20 EP EP02803695A patent/EP1453859A2/en not_active Withdrawn
- 2002-11-20 AP APAP/P/2004/003050A patent/AP2004003050A0/en unknown
- 2002-11-20 AU AU2002356990A patent/AU2002356990A1/en not_active Abandoned
- 2002-11-20 JP JP2003545691A patent/JP2005525302A/ja active Pending
- 2002-11-20 BR BRPI0214451-4A patent/BR0214451A/pt not_active IP Right Cessation
- 2002-11-20 RS YU53104A patent/RS53104A/sr unknown
- 2002-11-20 CN CNA028259289A patent/CN1608079A/zh active Pending
- 2002-11-20 KR KR1020047007708A patent/KR20050044858A/ko active IP Right Grant
- 2002-11-20 GE GE5599A patent/GEP20063860B/en unknown
- 2002-11-20 PL PL02374354A patent/PL374354A1/xx unknown
- 2002-11-20 EA EA200400565A patent/EA008505B1/ru unknown
- 2002-11-20 KR KR1020077011730A patent/KR20070072924A/ko not_active Application Discontinuation
- 2002-11-20 IL IL16203102A patent/IL162031A0/xx unknown
- 2002-11-20 HU HU0500997A patent/HUP0500997A2/hu unknown
-
2004
- 2004-05-17 IS IS7268A patent/IS7268A/is unknown
- 2004-05-19 MA MA27686A patent/MA27544A1/fr unknown
- 2004-05-20 HR HR20040448A patent/HRP20040448A2/hr not_active Application Discontinuation
- 2004-05-20 CO CO04046633A patent/CO5580794A2/es not_active Application Discontinuation
- 2004-05-20 ZA ZA200403907A patent/ZA200403907B/en unknown
- 2004-05-20 EC EC2004005114A patent/ECSP045114A/es unknown
- 2004-05-20 TN TNP2004000090A patent/TNSN04090A1/fr unknown
- 2004-05-26 NO NO20042182A patent/NO20042182L/no not_active Application Discontinuation
-
2006
- 2006-07-14 JP JP2006193577A patent/JP2006321808A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
EA200700431A1 (ru) | 2008-02-28 |
HRP20040448A2 (en) | 2006-02-28 |
PL374354A1 (en) | 2005-10-17 |
KR20070072924A (ko) | 2007-07-06 |
CA2467731A1 (en) | 2003-05-30 |
EA008505B1 (ru) | 2007-06-29 |
BR0214451A (pt) | 2006-05-30 |
TNSN04090A1 (fr) | 2006-06-01 |
MXPA04004809A (es) | 2004-08-11 |
MA27544A1 (fr) | 2005-10-03 |
ZA200403907B (en) | 2007-12-27 |
WO2003044056A2 (en) | 2003-05-30 |
CN1608079A (zh) | 2005-04-20 |
NO20042182L (no) | 2004-08-11 |
JP2005525302A (ja) | 2005-08-25 |
ECSP045114A (es) | 2004-07-23 |
WO2003044056A3 (en) | 2003-08-21 |
OA13063A (en) | 2006-11-10 |
GEP20063860B (en) | 2006-06-26 |
KR20050044858A (ko) | 2005-05-13 |
HUP0500997A2 (en) | 2007-11-28 |
CO5580794A2 (es) | 2005-11-30 |
AP2004003050A0 (en) | 2004-06-30 |
EP1453859A2 (en) | 2004-09-08 |
JP2006321808A (ja) | 2006-11-30 |
AU2002356990A1 (en) | 2003-06-10 |
IL162031A0 (en) | 2005-11-20 |
IS7268A (is) | 2004-05-17 |
RS53104A (en) | 2006-10-27 |
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