DE69728149D1 - Modifizierte liganden für den tie-2-rezeptor - Google Patents

Modifizierte liganden für den tie-2-rezeptor

Info

Publication number
DE69728149D1
DE69728149D1 DE69728149T DE69728149T DE69728149D1 DE 69728149 D1 DE69728149 D1 DE 69728149D1 DE 69728149 T DE69728149 T DE 69728149T DE 69728149 T DE69728149 T DE 69728149T DE 69728149 D1 DE69728149 D1 DE 69728149D1
Authority
DE
Germany
Prior art keywords
tie
receptor
modified ligands
modified
ligands
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
DE69728149T
Other languages
English (en)
Other versions
DE69728149T2 (de
Inventor
Samuel Davis
D Yancopoulos
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.)
Regeneron Pharmaceuticals Inc
Original Assignee
Regeneron Pharmaceuticals Inc
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 Regeneron Pharmaceuticals Inc filed Critical Regeneron Pharmaceuticals Inc
Application granted granted Critical
Publication of DE69728149D1 publication Critical patent/DE69728149D1/de
Publication of DE69728149T2 publication Critical patent/DE69728149T2/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • 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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • 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
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/515—Angiogenesic factors; Angiogenin
    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/30—Bird
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/01—Animal expressing industrially exogenous proteins
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/0331—Animal model for proliferative diseases
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0375—Animal model for cardiovascular diseases
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0381—Animal model for diseases of the hematopoietic system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Zoology (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Vascular Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Hematology (AREA)
  • Cell Biology (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
DE69728149T 1996-08-02 1997-08-01 Modifizierte liganden für den tie-2-rezeptor Expired - Lifetime DE69728149T2 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US2299996P 1996-08-02 1996-08-02
US22999P 1996-08-02
US740223 1996-10-25
US08/740,223 US6265564B1 (en) 1996-08-02 1996-10-25 Expressed ligand-vascular intercellular signalling molecule
PCT/US1997/013557 WO1998005779A1 (en) 1996-08-02 1997-08-01 Modified tie-2-receptor ligands

Publications (2)

Publication Number Publication Date
DE69728149D1 true DE69728149D1 (de) 2004-04-22
DE69728149T2 DE69728149T2 (de) 2004-10-28

Family

ID=26696604

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69728149T Expired - Lifetime DE69728149T2 (de) 1996-08-02 1997-08-01 Modifizierte liganden für den tie-2-rezeptor

Country Status (21)

Country Link
US (5) US6265564B1 (de)
EP (1) EP0915974B1 (de)
JP (1) JP3977434B2 (de)
KR (1) KR100481560B1 (de)
CN (1) CN1171997C (de)
AT (1) ATE262037T1 (de)
AU (1) AU724032C (de)
CA (1) CA2262409C (de)
CZ (1) CZ295371B6 (de)
DE (1) DE69728149T2 (de)
DK (1) DK0915974T3 (de)
ES (1) ES2216163T3 (de)
HK (1) HK1017379A1 (de)
HU (1) HU227995B1 (de)
IL (1) IL128311A (de)
NO (1) NO990470L (de)
NZ (2) NZ333994A (de)
PL (1) PL189639B1 (de)
PT (1) PT915974E (de)
RU (1) RU2233880C2 (de)
WO (1) WO1998005779A1 (de)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6265564B1 (en) * 1996-08-02 2001-07-24 Regeneron Pharmaceuticals, Inc. Expressed ligand-vascular intercellular signalling molecule
US6348350B1 (en) 1997-09-19 2002-02-19 Genentech, Inc. Ligand homologues
US6030831A (en) 1997-09-19 2000-02-29 Genetech, Inc. Tie ligand homologues
AU4643699A (en) * 1998-06-24 2000-01-10 Compugen Ltd. Angiopoietin-like growth factor sequences
CA2354846A1 (en) * 1998-12-23 2000-06-29 Regeneron Pharmaceuticals, Inc. Method of enhancing the biological activity of ligands
US6455035B1 (en) 1999-03-26 2002-09-24 Regeneron Pharmaceuticals, Inc. Angiopoietins and methods of use thereof
CA2397833A1 (en) * 2000-01-20 2001-07-26 Hadasit Medical Research Services & Development Company Ltd. Novel haptotactic peptides
MXPA03001535A (es) 2000-08-21 2004-12-13 Pacific Corp Derivados de tiourea novedosos y las composiciones farmaceuticas que contienen los mismos.
AU2001291019A1 (en) 2000-09-15 2002-03-26 Genvec, Inc. Method of modulating neovascularization
US7138370B2 (en) 2001-10-11 2006-11-21 Amgen Inc. Specific binding agents of human angiopoietin-2
US7205275B2 (en) 2001-10-11 2007-04-17 Amgen Inc. Methods of treatment using specific binding agents of human angiopoietin-2
US7658924B2 (en) 2001-10-11 2010-02-09 Amgen Inc. Angiopoietin-2 specific binding agents
US7521053B2 (en) 2001-10-11 2009-04-21 Amgen Inc. Angiopoietin-2 specific binding agents
WO2003034990A2 (en) 2001-10-25 2003-05-01 Regeneron Pharmaceuticals, Inc. Angiopoietins and methods of use thereof
WO2003048185A2 (en) * 2001-11-30 2003-06-12 Genvec, Inc. Angiopioetin related factors
US7081443B2 (en) 2002-05-21 2006-07-25 Korea Advanced Institutes Of Science And Technology (Kaist) Chimeric comp-ang1 molecule
US7569543B2 (en) * 2003-02-27 2009-08-04 The Trustees Of The University Of Pennsylvania Compositions of Angiopoietin, fragments, mutants and analogs thereof and uses of the same
WO2005013890A2 (en) * 2003-05-29 2005-02-17 The Trustees Of The University Of Pennsylvania Function and regulation of angiopoietin-3/angiopoietin-4
US7871610B2 (en) * 2003-08-12 2011-01-18 Dyax Corp. Antibodies to Tie1 ectodomain
CA2535171A1 (en) * 2003-08-12 2005-03-03 Dyax Corp. Tie1-binding ligands
US7485297B2 (en) * 2003-08-12 2009-02-03 Dyax Corp. Method of inhibition of vascular development using an antibody
CN1323723C (zh) * 2003-12-26 2007-07-04 上海新世界基因技术开发有限公司 Tie2受体介导的靶向性肿瘤基因治疗的基因转移系统
US8298532B2 (en) * 2004-01-16 2012-10-30 Regeneron Pharmaceuticals, Inc. Fusion polypeptides capable of activating receptors
RU2394839C2 (ru) 2004-12-21 2010-07-20 Астразенека Аб Антитела против ангиопоэтина-2 и их применение
US20080213253A1 (en) * 2007-01-12 2008-09-04 Dyax Corp. Combination therapy for the treatment of cancer
JO2913B1 (en) 2008-02-20 2015-09-15 امجين إنك, Antibodies directed towards angiopoietin-1 and angiopoietin-2 proteins and their uses
EP2307456B1 (de) 2008-06-27 2014-10-15 Amgen Inc. Die inhibierung von ang-2 zur behandlung multipler sklerose
BRPI1013771A2 (pt) * 2009-04-13 2016-04-05 Apceth Gmbh & Co Kg "células-tronco mesenquimais projetadas e método de uso das mesmas para tratar tumores."
WO2012162561A2 (en) 2011-05-24 2012-11-29 Zyngenia, Inc. Multivalent and monovalent multispecific complexes and their uses
KR101967345B1 (ko) * 2012-10-18 2019-04-09 삼성전자주식회사 안지오포이에틴-2와 인테그린 간의 결합을 저해하는 펩타이드 및 그 용도
US10150800B2 (en) 2013-03-15 2018-12-11 Zyngenia, Inc. EGFR-binding modular recognition domains
RU2538701C1 (ru) * 2013-07-11 2015-01-10 Федеральное государственное бюджетное учреждение науки "Тюменский научный центр Сибирского отделения РАН" (ТюмНЦ СО РАН) Способ извлечения куриного эмбриона из яйца для дальнейшего получения клеточных трансплантатов из фетальных тканей
BR112017005730B1 (pt) 2014-09-26 2023-12-12 Somalogic Operating Co., Inc Método para triagem de um indivíduo quanto ao risco de um evento cardiovascular ou para predizer a probabilidade que um indivíduo tenha tal evento
ES2867249T3 (es) 2015-11-06 2021-10-20 Regeneron Pharma Angiopoyetinas para usar en la promoción de la coagulación sanguínea y en el tratamiento de trastornos de la coagulación sanguínea

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5070192A (en) * 1988-03-23 1991-12-03 The Johns Hopkins University Cloned human topoisomerase i: cdna expression, and use for autoantibody detection
US5814464A (en) * 1994-10-07 1998-09-29 Regeneron Pharma Nucleic acids encoding TIE-2 ligand-2
ATE273384T1 (de) * 1995-04-06 2004-08-15 Regeneron Pharma Tie-2 liganden, herstellungsverfahren und verwendung
US6265564B1 (en) * 1996-08-02 2001-07-24 Regeneron Pharmaceuticals, Inc. Expressed ligand-vascular intercellular signalling molecule

Also Published As

Publication number Publication date
JP2000516807A (ja) 2000-12-19
HK1017379A1 (en) 1999-11-19
EP0915974A1 (de) 1999-05-19
CA2262409A1 (en) 1998-02-12
JP3977434B2 (ja) 2007-09-19
US20030092891A1 (en) 2003-05-15
CN1171997C (zh) 2004-10-20
HU227995B1 (en) 2012-08-28
RU2233880C2 (ru) 2004-08-10
IL128311A0 (en) 2000-01-31
KR100481560B1 (ko) 2005-04-08
CZ295371B6 (cs) 2005-07-13
PL331405A1 (en) 1999-07-19
EP0915974B1 (de) 2004-03-17
NZ333994A (en) 2000-09-29
CN1232501A (zh) 1999-10-20
NZ505684A (en) 2001-12-21
HUP0400256A3 (en) 2006-01-30
US20050106099A1 (en) 2005-05-19
US7045302B2 (en) 2006-05-16
CA2262409C (en) 2007-11-20
DE69728149T2 (de) 2004-10-28
PL189639B1 (pl) 2005-09-30
US20050186665A1 (en) 2005-08-25
NO990470D0 (no) 1999-02-01
NO990470L (no) 1999-04-06
ATE262037T1 (de) 2004-04-15
US6441137B1 (en) 2002-08-27
AU3968797A (en) 1998-02-25
KR20000029778A (ko) 2000-05-25
AU724032C (en) 2001-08-16
HUP0400256A2 (hu) 2004-04-28
ES2216163T3 (es) 2004-10-16
AU724032B2 (en) 2000-09-07
PT915974E (pt) 2004-05-31
US6265564B1 (en) 2001-07-24
CZ31099A3 (cs) 2000-03-15
US6825008B2 (en) 2004-11-30
IL128311A (en) 2007-08-19
WO1998005779A1 (en) 1998-02-12
DK0915974T3 (da) 2004-07-12

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