ES2175434T3 - Sistema de suministros de terapia de genes para dirigir al endotelio. - Google Patents

Sistema de suministros de terapia de genes para dirigir al endotelio.

Info

Publication number
ES2175434T3
ES2175434T3 ES97930670T ES97930670T ES2175434T3 ES 2175434 T3 ES2175434 T3 ES 2175434T3 ES 97930670 T ES97930670 T ES 97930670T ES 97930670 T ES97930670 T ES 97930670T ES 2175434 T3 ES2175434 T3 ES 2175434T3
Authority
ES
Spain
Prior art keywords
endothelium
direct
supply system
dna
positively charged
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 - Lifetime
Application number
ES97930670T
Other languages
English (en)
Inventor
Lisbeth Illum
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kyowa Kirin Services Ltd
Original Assignee
West Pharmaceutical Services Drug Delivery and Clinical Research Center Ltd
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
Priority claimed from GBGB9614471.2A external-priority patent/GB9614471D0/en
Priority claimed from GBGB9614441.5A external-priority patent/GB9614441D0/en
Application filed by West Pharmaceutical Services Drug Delivery and Clinical Research Center Ltd filed Critical West Pharmaceutical Services Drug Delivery and Clinical Research Center Ltd
Application granted granted Critical
Publication of ES2175434T3 publication Critical patent/ES2175434T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
    • 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
    • A61K47/61—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 the organic macromolecular compound being a polysaccharide or a derivative thereof
    • 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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6927—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
    • 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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6927—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
    • A61K47/6929—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
    • A61K47/6931—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
    • A61K47/6939—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/88—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using amphiphile liposome vesicle

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Nanotechnology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Biophysics (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Zoology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Plant Pathology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Biochemistry (AREA)
  • Medical Informatics (AREA)
  • Immunology (AREA)
  • Optics & Photonics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Electrotherapy Devices (AREA)
  • Prostheses (AREA)

Abstract

La presente invención se refiere a una composición que contiene microesferas biodegradables que hacen las veces de vehículos para el aporte de ADN a las células endoteliales de una red vascular, en la que las microesferas llevan una carga negativa neta, siendo unas partículas con carga positiva de menor tamaño absorbidas sobre dichas microesferas, y comprendiendo dichas partículas un conjugado de ADN y de un agente de compresión catiónica.
ES97930670T 1996-07-10 1997-07-10 Sistema de suministros de terapia de genes para dirigir al endotelio. Expired - Lifetime ES2175434T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9614471.2A GB9614471D0 (en) 1996-07-10 1996-07-10 Gene delivery to epithelial cells
GBGB9614441.5A GB9614441D0 (en) 1996-07-10 1996-07-10 Gene therapy delivery system for targeting to the lung endothelia

Publications (1)

Publication Number Publication Date
ES2175434T3 true ES2175434T3 (es) 2002-11-16

Family

ID=26309674

Family Applications (2)

Application Number Title Priority Date Filing Date
ES97930669T Expired - Lifetime ES2175433T3 (es) 1996-07-10 1997-07-10 Composiciones indicadas para la administracion de genes en celulas epiteliales.
ES97930670T Expired - Lifetime ES2175434T3 (es) 1996-07-10 1997-07-10 Sistema de suministros de terapia de genes para dirigir al endotelio.

Family Applications Before (1)

Application Number Title Priority Date Filing Date
ES97930669T Expired - Lifetime ES2175433T3 (es) 1996-07-10 1997-07-10 Composiciones indicadas para la administracion de genes en celulas epiteliales.

Country Status (13)

Country Link
EP (2) EP0994726B1 (es)
JP (2) JP2000514086A (es)
KR (2) KR20000067855A (es)
AT (2) ATE216265T1 (es)
AU (2) AU726518C (es)
CA (2) CA2257408A1 (es)
DE (2) DE69712108T2 (es)
DK (1) DK0986404T3 (es)
ES (2) ES2175433T3 (es)
GB (2) GB2330532A (es)
NO (2) NO990002L (es)
PT (2) PT986404E (es)
WO (2) WO1998001160A2 (es)

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US20060165606A1 (en) 1997-09-29 2006-07-27 Nektar Therapeutics Pulmonary delivery particles comprising water insoluble or crystalline active agents
JPH11246392A (ja) * 1998-03-03 1999-09-14 Makoto Otsuka 経口用固形製剤
WO1999058656A2 (en) * 1998-05-13 1999-11-18 The Regents Of The University Of Michigan Sustained dna delivery from structural matrices
ATE251466T1 (de) 1999-04-08 2003-10-15 Genentech Inc Zusammensetzung auf basis gegensätzlich geladener polypeptide
DE19940795A1 (de) * 1999-08-27 2001-03-01 Lohmann Therapie Syst Lts Schnellzerfallende Pellets auf der Basis von Chitosan
SE9904121D0 (sv) * 1999-11-15 1999-11-15 Gustaf Jederstroem Hydrophobe biomolecular structure
ES2230784T3 (es) * 1999-11-18 2005-05-01 Cognis Iberia, S.L. Microcapsulas.
FR2801811B1 (fr) * 1999-12-06 2002-05-03 Gerard Habar Procede de fabrication de microcapsules portant des charges cationiques
US7871598B1 (en) 2000-05-10 2011-01-18 Novartis Ag Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use
AUPR011700A0 (en) 2000-09-14 2000-10-05 Austin Research Institute, The Composition comprising immunogenic virus sized particles (VSP)
AU2001287375B2 (en) * 2000-09-14 2005-12-15 Px Biosolutions Pty Ltd Composition comprising immunogenic microparticles
ES2295391T3 (es) 2001-08-16 2008-04-16 Cmp Therapeutics Limited Microparticulas de quitina y sus usos medicos.
WO2003028657A2 (en) * 2001-10-03 2003-04-10 The Johns Hopkins University Compositions for oral gene therapy and methods of using same
EP1458360B1 (en) 2001-12-19 2011-05-11 Novartis AG Pulmonary delivery of aminoglycosides
NO317653B1 (no) 2002-05-03 2004-11-29 Stiftelsen Biopolymer Formulering som omfatter komplekser av kitosanoligomerer og nukleinsyre, fremgangsmate for a fremstille formuleringen samt anvendelser derav.
AU2003253508A1 (en) * 2002-07-15 2004-02-02 Feyecon Development And Implementation B.V. Method for particle precipitation using near-critical and supercritical antisolvents
US20040014698A1 (en) * 2002-07-18 2004-01-22 Gonzalo Hortelano Oral administration of therapeutic agent coupled to transporting agent
US20040048260A1 (en) * 2002-09-10 2004-03-11 Fu-Hsiung Chang Transfection of nucleic acid
CA2549994A1 (en) 2002-12-18 2004-08-12 Hough Ear Institute Otologic nanotechnology
US7723311B2 (en) 2003-06-18 2010-05-25 Nanobiomagnetics, Inc. Delivery of bioactive substances to target cells
US7344491B1 (en) 2003-11-26 2008-03-18 Nanobiomagnetics, Inc. Method and apparatus for improving hearing
US8651113B2 (en) 2003-06-18 2014-02-18 Swr&D Inc. Magnetically responsive nanoparticle therapeutic constructs and methods of making and using
DE10329087B4 (de) 2003-06-27 2014-02-13 Biomedical International R + D Gmbh Antigenhaltige Mikrosphären zur Allergietherapie
GB0315632D0 (en) 2003-07-04 2003-08-13 West Pharm Serv Drug Res Ltd Pharmaceutical formulations
JP4674288B2 (ja) * 2004-03-31 2011-04-20 恵雄 岡畑 歯科用材料。
US7282194B2 (en) * 2004-10-05 2007-10-16 Gp Medical, Inc. Nanoparticles for protein drug delivery
US8846102B2 (en) 2006-03-30 2014-09-30 Engene, Inc. Non-viral compositions and methods for transfecting gut cells in vivo
US8257685B2 (en) * 2006-04-04 2012-09-04 Stc.Unm Swellable particles for drug delivery
ATE523592T1 (de) * 2007-07-06 2011-09-15 Univ Aarhus Dehydratisierte chitosan-nanopartikel
NO2195035T3 (es) * 2007-09-28 2018-05-05
CA2729764A1 (en) * 2008-07-01 2010-01-07 Nitto Denko Corporation Pharmaceutical composition containing surface-coated microparticles
CN101869704A (zh) * 2010-06-08 2010-10-27 中国药科大学 单剂免疫破伤风类毒素阳离子葡聚糖微球及其制备方法
US8802076B2 (en) 2010-10-04 2014-08-12 Duke University Compositions and methods for modulating an immune response
CA3168875A1 (en) * 2020-01-22 2021-07-29 Engene, Inc. Localized expression of therapeutic nucleic acids in lung epithelial cells

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US4046750A (en) * 1974-09-30 1977-09-06 California Institute Of Technology Ionene modified small polymeric beads
JPH03198782A (ja) * 1989-12-27 1991-08-29 Bitamin Kenkyusho:Kk 遺伝子導入用キャリアー、該キャリアーと遺伝子との複合体及び細胞への遺伝子導入法
US5972600A (en) * 1992-04-03 1999-10-26 The Regents Of The University Of California Separation of active complexes
AU2946295A (en) * 1994-06-27 1996-01-19 Johns Hopkins University, The Targeted gene delivery system
GB9416884D0 (en) * 1994-08-20 1994-10-12 Danbiosyst Uk Drug delivery compositions
FR2724935B1 (fr) * 1994-09-27 1996-12-20 Centre Nat Rech Scient Compositions nanoparticulaires contenant des derives nucleotidiques, leur preparation et leur emploi en therapeutique
KR960016882A (ko) * 1994-11-01 1996-06-17 강재헌 치주염치료를 위한 서방출형 생분해성 제제
JPH10511957A (ja) * 1995-01-05 1998-11-17 ザ ボード オブ リージェンツ オブ ザ ユニヴァーシティ オブ ミシガン 表面改質ナノ微粒子並びにその製造及び使用方法

Also Published As

Publication number Publication date
KR20000067855A (ko) 2000-11-25
AU720989B2 (en) 2000-06-22
EP0994726A2 (en) 2000-04-26
WO1998001161A2 (en) 1998-01-15
JP2000514086A (ja) 2000-10-24
CA2257408A1 (en) 1998-01-15
EP0994726B1 (en) 2002-04-17
WO1998001160A2 (en) 1998-01-15
PT986404E (pt) 2002-09-30
PT994726E (pt) 2002-09-30
GB2330534B (en) 2000-09-06
GB9900048D0 (en) 1999-02-24
AU726518B2 (en) 2000-11-09
EP0986404A2 (en) 2000-03-22
DE69712110D1 (de) 2002-05-23
DK0986404T3 (da) 2002-05-13
KR20000023716A (ko) 2000-04-25
DE69712108D1 (de) 2002-05-23
NO990002D0 (no) 1999-01-04
AU3454697A (en) 1998-02-02
NO990003L (no) 1999-01-04
DE69712108T2 (de) 2002-12-12
ATE216265T1 (de) 2002-05-15
ATE216264T1 (de) 2002-05-15
AU3454597A (en) 1998-02-02
AU726518C (en) 2002-01-03
CA2257300A1 (en) 1998-01-15
GB2330534A (en) 1999-04-28
GB9900054D0 (en) 1999-02-24
WO1998001161A3 (en) 1998-03-12
ES2175433T3 (es) 2002-11-16
DE69712110T2 (de) 2002-12-12
GB2330532A (en) 1999-04-28
JP2001500109A (ja) 2001-01-09
NO990002L (no) 1999-01-04
NO990003D0 (no) 1999-01-04
WO1998001160A3 (en) 1998-03-05
EP0986404B1 (en) 2002-04-17

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