ES2168273T3 - Ligando para el receptor c-kit y metodos de uso del mismo. - Google Patents

Ligando para el receptor c-kit y metodos de uso del mismo.

Info

Publication number
ES2168273T3
ES2168273T3 ES93910645T ES93910645T ES2168273T3 ES 2168273 T3 ES2168273 T3 ES 2168273T3 ES 93910645 T ES93910645 T ES 93910645T ES 93910645 T ES93910645 T ES 93910645T ES 2168273 T3 ES2168273 T3 ES 2168273T3
Authority
ES
Spain
Prior art keywords
methods
kit
binding
presented
same
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
ES93910645T
Other languages
English (en)
Inventor
Peter Besmer
Jochen Buck
Malcolm A S Moore
Karl Nocka
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.)
Memorial Sloan Kettering Cancer Center
Original Assignee
Memorial Sloan Kettering Cancer Center
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 Memorial Sloan Kettering Cancer Center filed Critical Memorial Sloan Kettering Cancer Center
Application granted granted Critical
Publication of ES2168273T3 publication Critical patent/ES2168273T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/715Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14Blood; Artificial blood
    • A61K35/16Blood plasma; Blood serum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/02Peptides of undefined number of amino acids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/191Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/193Colony stimulating factors [CSF]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/2006IL-1
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/202IL-3
    • 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
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/14Decongestants or antiallergics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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
    • A61P7/06Antianaemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/71Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Pulmonology (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Ophthalmology & Optometry (AREA)
  • Virology (AREA)
  • Oncology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Communicable Diseases (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Neurosurgery (AREA)

Abstract

SE PRESENTA UNA COMPOSICION FARMACEUTICA QUE CONTIENE EL LIGANDO C-KIT (KL) PURIFICADO MEDIANTE LOS METODOS DE LOS SOLICITANTES DE LA PATENTE Y PRODUCIDO SEGUN LOS METODOS RECOMBINANTES LLEVADOS A CABO POR LOS SOLICITANTES DE LA PATENTE JUNTO CON TOROS FACTORES HEMATOPOYETICOS Y UN SOPORTE FARMACEUTICAMENTE ACEPTABLE ASI COMO LOS METODOS DE TRATAMIENTO DE PACIENTES QUE CONSISTEN EN ADMINISTRAR AL PACIENTE LA COMPOSICION FARMACEUTICA DE ESTA INVENCION. EN ESTA INVENCION SE PRESENTAN TERAPIAS COMBINADAS UTILIZANDO EL LIGADO C-KIT (KL) Y UN POLIPEPTIDO DEL LIGANDO C-KIT PURIFICADO (KL), O UN FRAGMENTO SOLUBLE DEL MISMO Y OTROS FACTORES HEMATOPOYETICOS. TAMBIEN SE PRESENTAN LOS METODOS Y COMPOSICIONES PARA EL USO EX-VIVO DEL KL POR SI SOLO O EN UNA TERAPIA COMBINADA. TAMBIEN SE DESCRIBE UN ANTAGONISTA DEL KL MUTADO. TAL ANTAGONISTA PUEDE SER TAMBIEN UNA MOLECULA PEQUEÑA. TAMBIEN SE DESCRIBEN ACIDOS NUCLEICOS ANTISENTIDO AL KL COMO AGENTES TERAPEUTICOS. POR ULTIMO SE DESCRIBEN LAS COMPOSICIONESY LOS METODOS QUE SE BENEFICIAN DEL PAPEL DEL KL EN LOS GAMETOS, CELULAS MASTICAS Y MELANOCITOS.
ES93910645T 1992-04-23 1993-04-16 Ligando para el receptor c-kit y metodos de uso del mismo. Expired - Lifetime ES2168273T3 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US87396292A 1992-04-23 1992-04-23

Publications (1)

Publication Number Publication Date
ES2168273T3 true ES2168273T3 (es) 2002-06-16

Family

ID=25362700

Family Applications (1)

Application Number Title Priority Date Filing Date
ES93910645T Expired - Lifetime ES2168273T3 (es) 1992-04-23 1993-04-16 Ligando para el receptor c-kit y metodos de uso del mismo.

Country Status (15)

Country Link
US (1) US6159461A (es)
EP (2) EP0639979B1 (es)
JP (1) JP3750819B2 (es)
KR (1) KR100313064B1 (es)
AT (1) ATE206309T1 (es)
AU (1) AU675429B2 (es)
CA (1) CA2133982C (es)
DE (1) DE69330878T2 (es)
DK (1) DK0639979T3 (es)
ES (1) ES2168273T3 (es)
HK (1) HK1041205A1 (es)
HU (1) HU219540B (es)
PT (1) PT639979E (es)
RU (1) RU2180850C2 (es)
WO (1) WO1993021936A1 (es)

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US7144731B2 (en) 1989-10-16 2006-12-05 Amgen Inc. SCF antibody compositions and methods of using the same
US6852313B1 (en) 1989-10-16 2005-02-08 Amgen Inc. Method of stimulating growth of melanocyte cells by administering stem cell factor
US20050276784A1 (en) * 1990-08-27 2005-12-15 Solan-Kettering Institute For Cancer Research Ligand for the c-kit receptor and methods of use thereof
US5525708A (en) * 1994-03-28 1996-06-11 Cytomed, Inc. Covalent dimer of kit ligand
DE4412794A1 (de) * 1994-04-14 1995-12-14 Univ Ludwigs Albert Verfahren zur Herstellung von dendritischen Zellen, so erhaltene Zellen und Behälter zur Durchführung dieses Verfahrens
CN1170926C (zh) * 1994-11-16 2004-10-13 安姆根有限公司 干细胞因子和可溶性白介素-6受体在血细胞生成多能性细胞体外扩增中的应用
US6248326B1 (en) * 1997-09-10 2001-06-19 Harry C. Blair Regulation of osteoclast formation by inhibition of osteoblastic stem cell factor
US6599710B1 (en) 1999-03-10 2003-07-29 The General Hospital Corporation Treatment of autoimmune disease
US7572631B2 (en) 2000-02-24 2009-08-11 Invitrogen Corporation Activation and expansion of T cells
US7541184B2 (en) 2000-02-24 2009-06-02 Invitrogen Corporation Activation and expansion of cells
WO2002066069A1 (en) * 2001-02-20 2002-08-29 Kansai Technology Licensing Organization Co., Ltd. Remedies for inflammatory/tumor diseases
CA2448599A1 (en) * 2001-04-27 2002-11-07 Invitrogen Corporation Maturation of antigen-presenting cells using activated t cells
US7628988B2 (en) 2002-06-27 2009-12-08 The General Hospital Corporation Methods and compositions for treating type 1 diabetes
US7582313B2 (en) * 2002-06-27 2009-09-01 The General Hospital Corporation Methods of organ regeneration using Hox 11-expressing pluripotent cells
WO2004072264A2 (en) * 2003-02-12 2004-08-26 Johns Hopkins University School Of Medicine Fate determination by hes 1 in hematopoietic stem-progenitor cells and uses thereof
US20080102054A1 (en) * 2005-01-18 2008-05-01 Faustman Denise L Compositions Containing Agm Cells And Methods Of Use Thereof
EP1722275B1 (en) 2005-05-10 2010-10-27 Agfa Graphics N.V. Method for processing lithographic printing plates
PL2953634T3 (pl) 2013-02-07 2021-11-22 The General Hospital Corporation Sposoby namnażania lub zubożania limfocytów t-regulatorowych
CN111879948A (zh) 2013-10-17 2020-11-03 综合医院公司 鉴定响应于用于自身免疫性疾病的治疗的受试者的方法以及用于治疗该疾病的组合物
RU2563235C1 (ru) * 2014-07-29 2015-09-20 Федеральное государственное бюджетное учреждение "Научный центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова" Министерства здравоохранения Российской Федерации Способ увеличения пула стволовых клеток в организме
EP3294773A1 (en) 2015-05-15 2018-03-21 The General Hospital Corporation Antagonistic anti-tumor necrosis factor receptor superfamily antibodies
WO2017040312A1 (en) 2015-08-28 2017-03-09 The General Hospital Corporation Agonistic anti-tumor necrosis factor receptor 2 antibodies
US11266730B2 (en) 2015-09-29 2022-03-08 The General Hospital Corporation Methods of treating and diagnosing disease using biomarkers for BCG therapy
CA3023930C (en) 2016-05-13 2025-09-23 The General Hospital Corporation TUMOR-ANTAGONISTIC ANTIBODIES OF THE NECROSIS FACTOR RECEPTOR SUPERFAMILY
CN113302205B (zh) 2018-11-15 2024-12-06 综合医院公司 激动性肿瘤坏死因子受体超家族多肽

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991014757A1 (en) * 1990-03-28 1991-10-03 Nisshin Steel Co., Ltd. Hot rolling lubricant for stainless steel
US5399493A (en) * 1989-06-15 1995-03-21 The Regents Of The University Of Michigan Methods and compositions for the optimization of human hematopoietic progenitor cell cultures
SG59931A1 (en) * 1989-10-16 1999-02-22 Amgen Inc Stem cell factor
AU8196891A (en) * 1990-06-25 1992-01-23 Immunex Corporation Mast cell growth factor
DE4026026A1 (de) * 1990-08-17 1992-02-20 Hoechst Ag Acylaminomethyl-phosphinsaeuren und verfahren zur herstellung von acylaminomethanphosphonsaeuren und acylaminomethyl-phosphinsaeuren
US5767074A (en) * 1990-08-27 1998-06-16 Sloan-Kettering Institute For Cancer Research Compositions of soluble C-kit ligand and hematopoietic factors
US20030125519A1 (en) * 1990-08-27 2003-07-03 Peter Besmer Ligand for the c-kit receptor and methods of use thereof
WO1992006220A1 (en) * 1990-10-05 1992-04-16 President And Fellows Of Harvard College Detection and isolation of ligands
US5409825A (en) * 1991-04-09 1995-04-25 Indiana University Foundation Expansion of human hematopoietic progenitor cells in a liquid medium
US5199942A (en) * 1991-06-07 1993-04-06 Immunex Corporation Method for improving autologous transplantation
US6001803A (en) * 1992-04-23 1999-12-14 Sloan-Kettering Institute For Cancer Research Composition of c-kit ligand, GM-CSF, and TNF-α and method of use

Also Published As

Publication number Publication date
AU675429B2 (en) 1997-02-06
EP0639979B1 (en) 2001-10-04
EP1127577A2 (en) 2001-08-29
DE69330878T2 (de) 2002-05-29
EP1127577A3 (en) 2002-11-27
AU4106593A (en) 1993-11-29
KR100313064B1 (ko) 2002-04-06
DK0639979T3 (da) 2002-12-02
JPH07508721A (ja) 1995-09-28
RU94046426A (ru) 1997-01-10
HK1041205A1 (en) 2002-07-05
HU219540B (hu) 2001-05-28
DE69330878D1 (de) 2001-11-08
WO1993021936A1 (en) 1993-11-11
CA2133982A1 (en) 1993-11-11
EP0639979A1 (en) 1995-03-01
HUT70696A (en) 1995-10-30
EP0639979A4 (en) 1996-10-23
US6159461A (en) 2000-12-12
CA2133982C (en) 2008-02-12
ATE206309T1 (de) 2001-10-15
HU9403054D0 (en) 1995-02-28
RU2180850C2 (ru) 2002-03-27
PT639979E (pt) 2002-03-28
JP3750819B2 (ja) 2006-03-01
KR950701226A (ko) 1995-03-23

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