RS50730B - Polisaharidi sa antitrombičkom aktivnošću koji sadrže najmanje jednu kovalentnu vezu sa biotinom ili derivatom biotina - Google Patents

Polisaharidi sa antitrombičkom aktivnošću koji sadrže najmanje jednu kovalentnu vezu sa biotinom ili derivatom biotina

Info

Publication number
RS50730B
RS50730B YUP-197/03A YUP19703A RS50730B RS 50730 B RS50730 B RS 50730B YU P19703 A YUP19703 A YU P19703A RS 50730 B RS50730 B RS 50730B
Authority
RS
Serbia
Prior art keywords
biotin
covalent bond
polysaccharides
antithrombotic activity
derivative
Prior art date
Application number
YUP-197/03A
Other languages
English (en)
Inventor
Philippe Duchaussoy
Pierre Savi
Jean-Marc Herbert
Maurice Petitou
Original Assignee
Sanofi-Aventis
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Sanofi-Aventis filed Critical Sanofi-Aventis
Priority to MEP-236/08A priority Critical patent/MEP23608A/xx
Publication of YU19703A publication Critical patent/YU19703A/sh
Publication of RS50730B publication Critical patent/RS50730B/sr

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08BPOLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/006Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08BPOLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/006Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0063Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/08Vasodilators for multiple indications
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08BPOLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Polymers & Plastics (AREA)
  • Materials Engineering (AREA)
  • Biochemistry (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Epidemiology (AREA)
  • Neurology (AREA)
  • Communicable Diseases (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Obesity (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Pulmonology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

Sintetički polisaharidi sa antitrombičnim dejstvom i njihove farmaceutski prihvatljive soli karakteristične po tome što imaju najmanje jednu kovalentnu vezu sa biotinom ili derivatom biotina Prijava sadrži još 6 nezavisnih i 9 zavisnih patentnih zahteva.
YUP-197/03A 2000-09-22 2001-09-20 Polisaharidi sa antitrombičkom aktivnošću koji sadrže najmanje jednu kovalentnu vezu sa biotinom ili derivatom biotina RS50730B (sr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
MEP-236/08A MEP23608A (en) 2000-09-22 2001-09-20 Polysaccharides with antithrombotic activity comprising at least a covalent bond with biotin or a biotin derivative

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR0012094A FR2814463B1 (fr) 2000-09-22 2000-09-22 Nouveaux polysaccharides a activite antithrombotique comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine

Publications (2)

Publication Number Publication Date
YU19703A YU19703A (sh) 2006-05-25
RS50730B true RS50730B (sr) 2010-08-31

Family

ID=8854579

Family Applications (1)

Application Number Title Priority Date Filing Date
YUP-197/03A RS50730B (sr) 2000-09-22 2001-09-20 Polisaharidi sa antitrombičkom aktivnošću koji sadrže najmanje jednu kovalentnu vezu sa biotinom ili derivatom biotina

Country Status (40)

Country Link
US (3) US6844329B2 (sr)
EP (1) EP1322673B1 (sr)
JP (2) JP5016778B2 (sr)
KR (2) KR100891388B1 (sr)
CN (1) CN1235914C (sr)
AR (1) AR030774A1 (sr)
AT (1) ATE374215T1 (sr)
AU (2) AU2001291960C1 (sr)
BG (1) BG66191B1 (sr)
BR (1) BR0114007A (sr)
CA (1) CA2418815C (sr)
CY (1) CY1108076T1 (sr)
CZ (1) CZ300856B6 (sr)
DE (1) DE60130669T2 (sr)
DK (1) DK1322673T3 (sr)
EA (1) EA005133B1 (sr)
EC (1) ECSP034514A (sr)
EE (1) EE05202B1 (sr)
ES (1) ES2292625T3 (sr)
FR (1) FR2814463B1 (sr)
GE (1) GEP20053616B (sr)
HK (1) HK1053316A1 (sr)
HR (1) HRP20030219B1 (sr)
HU (2) HUP0303551A3 (sr)
IL (2) IL154848A0 (sr)
IS (1) IS2550B (sr)
ME (2) ME00080B (sr)
MX (1) MXPA03002483A (sr)
NO (2) NO332905B1 (sr)
NZ (1) NZ524472A (sr)
PE (1) PE20020471A1 (sr)
PL (1) PL206727B1 (sr)
PT (1) PT1322673E (sr)
RS (1) RS50730B (sr)
SI (1) SI1322673T1 (sr)
SK (2) SK287218B6 (sr)
TW (1) TWI308153B (sr)
UA (1) UA79736C2 (sr)
WO (1) WO2002024754A1 (sr)
ZA (1) ZA200301692B (sr)

Families Citing this family (33)

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Publication number Priority date Publication date Assignee Title
FR2814463B1 (fr) * 2000-09-22 2002-11-15 Sanofi Synthelabo Nouveaux polysaccharides a activite antithrombotique comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine
FR2874924B1 (fr) * 2004-09-09 2006-12-01 Sanofi Aventis Sa Hexadecasaccharides biotinyles, leur preparation et leur utilisation therapeutique
TWI403334B (zh) * 2004-12-23 2013-08-01 Merck Sharp & Dohme 包含生物素殘基之抗血栓雙重抑制劑
TWI376234B (en) * 2005-02-01 2012-11-11 Msd Oss Bv Conjugates of a polypeptide and an oligosaccharide
US8183228B2 (en) * 2005-10-10 2012-05-22 MSD OSS B.V. Netherlands Anticoagulant antithrombotic dual inhibitors comprising a biotin label
BRPI0617215A2 (pt) * 2005-10-10 2011-07-19 Organon Nv composto anti-trombótico, composição farmacêutica, e, uso do composto
CN1317035C (zh) * 2005-10-24 2007-05-23 天津大学 基于酰肼基的微粒表面多重生物功能因子组装方法
EP1886696A1 (en) * 2006-08-03 2008-02-13 Endotis Pharma Conjugates of antithrombin binding oligosaccharide derivatives and therapeutic proteins
FR2912409B1 (fr) * 2007-02-14 2012-08-24 Sanofi Aventis Heparines de bas poids moleculaire comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine leur procede de preparation,leur utilisation
EP2233143A1 (en) 2009-03-24 2010-09-29 Sanofi-Aventis Use of idrabiotaparinux for decreasing the incidence of bleedings during an antithrombotic treatment
TW201006479A (en) * 2008-07-18 2010-02-16 Sanofi Aventis Use of idrabiotaparinux for decreasing the incidence of bleedings during an antithrombotic treatment
EP2145624A1 (en) 2008-07-18 2010-01-20 Sanofi-Aventis Use of idrabiotaparinux for decreasing the incidence of bleedings during an antithrombotic treatment
FR2935386B1 (fr) * 2008-08-26 2010-09-10 Sanofi Aventis Nouveaux polysaccharides a activite antithrombotique comprenant une liaion covalente avec une chaine amine
WO2010029552A1 (en) * 2008-09-10 2010-03-18 Transpharma Medical Ltd. Transdermal delivery of oligosaccharides
AU2009335709A1 (en) 2008-12-19 2011-07-14 Supernus Pharmaceuticals, Inc. Method of treatment of aggression
FR2952935B1 (fr) 2009-11-20 2011-12-02 Sanofi Aventis Procede de preparation du n-biotinyl-6-aminocaproate de n succinimidyle
CN102892411B (zh) 2009-12-18 2015-01-21 恩多提斯药业公司 含有合成的低聚糖的药物口服剂型
CZ302669B6 (cs) * 2010-03-29 2011-08-24 Univerzita Palackého v Olomouci Efektivní zpusob biotinylace aminosloucenin pomocí syntézy na pevné fázi pro potreby afinitní chromatografie
CZ302510B6 (cs) * 2010-03-29 2011-06-22 Univerzita Palackého v Olomouci Efektivní zpusob biotinylace sloucenin s karboxylovou skupinou pomocí syntézy na pevné fázi pro potreby afinitní chromatografie
EP2552423B1 (en) 2010-03-31 2017-07-12 Supernus Pharmaceuticals, Inc. Stabilized formulations of cns compounds
FR2964660B1 (fr) * 2010-09-10 2012-09-28 Sanofi Aventis Nouveaux polysaccharides biotinyles a activite antithrombotique et presentant une stabilite metabolique amelioree
WO2012042123A1 (fr) 2010-09-10 2012-04-05 Sanofi Polysaccharides biotinyles a activite antithrombotique et presentant une stabilite metabolique amelioree
EP2484366A1 (en) 2011-02-07 2012-08-08 Sanofi Idrabiotaparinux for the treatment of pulmonary embolism and for the secondary prevention of venous thromboembolic events
CA2839139A1 (en) * 2011-06-17 2012-12-20 Carbomimetics Synthetic pentasaccharides having short half-life and high activity
WO2014078394A1 (en) * 2012-11-13 2014-05-22 Supernus Pharmaceuticals, Inc. Method of treatment of aggression
WO2015195404A1 (en) 2014-06-20 2015-12-23 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Methods for detection of an analyte by movement of tethered microparticles
WO2016205239A1 (en) 2015-06-15 2016-12-22 The United States Of America, As Represented By The Secretary Department Of Health And Human Services Non-hormonal mammalian sperm decoy contraception based on the n-terminus of the zp2 protein
CN110234600B (zh) 2016-10-21 2023-03-21 美国政府(由卫生和人类服务部的部长所代表) 分子纳米标签
CN108976318B (zh) * 2017-06-01 2021-03-30 首都医科大学 单-6-(生物素酰胺基)-6-脱氧-β-环糊精及其制备方法和应用
WO2019133727A1 (en) 2017-12-29 2019-07-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Universal influenza virus probe set for enrichment of any influenza virus nucleic acid
AU2020310172A1 (en) 2019-07-09 2022-03-03 Optimvia Llc Methods for synthesizing anticoagulant polysaccharides
CN114556685B (zh) * 2019-10-17 2024-04-02 株式会社自动网络技术研究所 布线模块
WO2022056078A1 (en) 2020-09-11 2022-03-17 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Rnase h-assisted detection assay for rna (radar)

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US3960884A (en) * 1974-04-24 1976-06-01 Sergei Ivanovich Zavyalov Method of preparing racemic biotin
AU563351C (en) * 1982-01-15 2003-06-19 Glaxo Group Limited Synthesis of oligosaccharides
IL102758A (en) * 1991-08-23 1997-03-18 Akzo Nv Glycosaminoglycanoid derivatives, their preparation and pharmaceutical compositions comprising them
US20010023288A1 (en) * 1999-07-07 2001-09-20 Wilbur D. Scott Trifunctional reagent for conjugation to a biomolecule
FR2751334B1 (fr) * 1996-07-19 1998-10-16 Sanofi Sa Polysaccharides synthetiques, procede pour leur preparation et compositions pharmaceutiques les contenant
FR2773801B1 (fr) * 1998-01-19 2000-05-12 Sanofi Sa Nouveaux pentasaccharides, procedes pour leurs preparations et compositions pharmaceutiques les contenant
FR2773804B1 (fr) * 1998-01-19 2000-02-18 Sanofi Sa Polysaccharides de synthese, procede pour leur preparation et compositions pharmaceutiques le contenant
GB2335490B (en) * 1998-03-20 2003-05-14 Ortho Clinical Diagnostics An assay surface that permits an analyte releasiing step
AU8366398A (en) * 1998-07-07 2000-01-24 Department Of Radiation Oncology University Of Washington Trifunctional reagent for conjugation to a biomolecule
CN1286699A (zh) 1998-07-31 2001-03-07 生化学工业株式会社 新的糖胺聚糖和使用同样物质作为活性成分的药用组合物
FR2814463B1 (fr) * 2000-09-22 2002-11-15 Sanofi Synthelabo Nouveaux polysaccharides a activite antithrombotique comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine

Also Published As

Publication number Publication date
AU9196001A (en) 2002-04-02
EA200300237A1 (ru) 2003-08-28
FR2814463B1 (fr) 2002-11-15
GEP20053616B (en) 2005-09-26
US20040024197A1 (en) 2004-02-05
JP2004509902A (ja) 2004-04-02
JP2012131809A (ja) 2012-07-12
US6844329B2 (en) 2005-01-18
EE200300114A (et) 2005-02-15
PT1322673E (pt) 2007-12-03
SK287054B6 (sk) 2009-10-07
BG66191B1 (bg) 2011-12-30
SI1322673T1 (sl) 2008-02-29
PL206727B1 (pl) 2010-09-30
YU19703A (sh) 2006-05-25
ME00080B (me) 2010-10-10
EP1322673B1 (fr) 2007-09-26
NO332905B1 (no) 2013-01-28
ATE374215T1 (de) 2007-10-15
SK3562003A3 (en) 2003-11-04
TWI308153B (en) 2009-04-01
FR2814463A1 (fr) 2002-03-29
DE60130669D1 (de) 2007-11-08
ZA200301692B (en) 2004-03-01
EE05202B1 (et) 2009-08-17
US7943595B2 (en) 2011-05-17
BR0114007A (pt) 2003-08-12
NO20031295D0 (no) 2003-03-20
KR100891388B1 (ko) 2009-04-02
CZ2003814A3 (cs) 2003-06-18
ECSP034514A (es) 2003-04-25
IS2550B (is) 2009-10-15
EP1322673A1 (fr) 2003-07-02
NO20031295L (no) 2003-05-22
US20110144042A1 (en) 2011-06-16
CN1235914C (zh) 2006-01-11
HUP0303551A2 (hu) 2004-03-01
NO20110401L (no) 2003-05-22
MEP23608A (en) 2010-06-10
KR20030055269A (ko) 2003-07-02
UA79736C2 (uk) 2007-07-25
AU2001291960B2 (en) 2007-03-01
PE20020471A1 (es) 2002-06-01
HK1053316A1 (en) 2003-10-17
HU1400034D0 (hu) 2004-03-01
CZ300856B6 (cs) 2009-08-26
KR20080049139A (ko) 2008-06-03
CA2418815C (en) 2011-05-10
WO2002024754A1 (fr) 2002-03-28
EA005133B1 (ru) 2004-12-30
AR030774A1 (es) 2003-09-03
CA2418815A1 (en) 2002-03-28
HRP20030219B1 (en) 2011-10-31
US8318696B2 (en) 2012-11-27
WO2002024754A8 (fr) 2003-07-03
US20060160768A1 (en) 2006-07-20
BG107650A (bg) 2003-11-28
ES2292625T3 (es) 2008-03-16
CY1108076T1 (el) 2014-02-12
MXPA03002483A (es) 2004-05-24
DK1322673T3 (da) 2008-01-14
IL154848A0 (en) 2003-10-31
NZ524472A (en) 2004-10-29
IS6733A (is) 2003-02-28
JP5016778B2 (ja) 2012-09-05
CN1466594A (zh) 2004-01-07
AU2001291960C1 (en) 2009-10-08
PL363368A1 (en) 2004-11-15
HRP20030219A2 (en) 2003-06-30
IL154848A (en) 2010-11-30
DE60130669T2 (de) 2008-07-17
HUP0303551A3 (en) 2004-03-29
SK287218B6 (sk) 2010-03-08

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