ES2192585T3 - Superagonistas y antagonistas de la h il-6 y metodo de modelado tridimensional para su seleccion. - Google Patents
Superagonistas y antagonistas de la h il-6 y metodo de modelado tridimensional para su seleccion.Info
- Publication number
- ES2192585T3 ES2192585T3 ES95940409T ES95940409T ES2192585T3 ES 2192585 T3 ES2192585 T3 ES 2192585T3 ES 95940409 T ES95940409 T ES 95940409T ES 95940409 T ES95940409 T ES 95940409T ES 2192585 T3 ES2192585 T3 ES 2192585T3
- Authority
- ES
- Spain
- Prior art keywords
- interleucine
- superagonists
- antagonists
- superantagonists
- location
- 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
Links
- 239000005557 antagonist Substances 0.000 title abstract 4
- 238000000034 method Methods 0.000 title abstract 3
- 108090001005 Interleukin-6 Proteins 0.000 title 1
- 229940088597 hormone Drugs 0.000 abstract 2
- 239000005556 hormone Substances 0.000 abstract 2
- 230000003993 interaction Effects 0.000 abstract 2
- 241000283690 Bos taurus Species 0.000 abstract 1
- 108010025020 Nerve Growth Factor Proteins 0.000 abstract 1
- 102000007072 Nerve Growth Factors Human genes 0.000 abstract 1
- 150000001413 amino acids Chemical group 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 238000009413 insulation Methods 0.000 abstract 1
- 208000032839 leukemia Diseases 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 239000012528 membrane Substances 0.000 abstract 1
- 239000003900 neurotrophic factor Substances 0.000 abstract 1
- 239000002699 waste material Substances 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5412—IL-6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
-
- 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
- A61P7/06—Antianaemics
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
- G01N33/6869—Interleukin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/14—Lymphokine; related peptides
- Y10S930/141—Interleukin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Toxicology (AREA)
- Analytical Chemistry (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Pathology (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Obesity (AREA)
Abstract
SE SABE QUE LOS LIGANDOS DEL GRUPO DE CITOQUINAS SIMILAR A LA INTERLEUCINA 6(IL-6), QUE ES ONCOSTATINA-M(OSM), EL FACTOR INHIBITORIO DE LA LEUCEMIA (LIF), EL FACTOR NEUROTROFICO CILIAR (CNTF) E LA INTERLEUCINA II (IL-II), INDUCEN LA FORMACION DE UN COMPLEJO RECEPTOR DEL CUAL FORMA PARTE LA MOLECULA DE MEMBRANA GP 130. LA PRESENTE INVENCION SE REFIERE A UNA METODOLOGIA PARA LA SELECCION DE SUPERAGONISTAS, ANTAGONISTAS Y SUPERANTAGONISTAS DE LA INTERLEUCINA-6 HUMANA QUE COMPRENDE LAS SIGUIENTES OPERACIONES: COMPARAR LA SECUENCIA DE AMINOACIDO DE LA COLONIA DE GRANULOCITOS BOVINOS QUE ESTIMULAN EL FACTOR (BG-CSF) CON LA SECUENCIA DE DICHA HORMONA, Y EN BASE A LA COMPARACION ANTERIORMENTE MENCIONADA, FORMULAR UN MODELO TRIDIMENSIONAL DE DICHA HORMONA, EL CUAL PERMITE LA IDENTIFICACION DE LOS RESIDUOS QUE FORMAN EL EMPLAZAMIENTO DE LA INTERACCION CON EL RECEPTOR ESPECIFICO (EMPLAZAMIENTO 1) Y ESOS QUE CONSTITUYEN EL EMPLAZAMIENTO DE LA INTERACCION CON EL GP 130 (EMPLAZAMIENTO 2) RESPECTIVAMENTE.LA INVENCION PERMITE LA IDENTIFICACION DE ESTOS EMPLAZAMIENTOS EN INTERLEUCINA-6 HUMANA Y EL AISLAMIENTO DE LAS VARIANTES QUE TIENEN, CON RESPECTO A LA HORMONA DE TIPO SALVAJE, UNA MAYOR AFINIDAD PARA EL RECEPTOR ESPECIFICO (SUPERAGONISTAS Y SUPERANTAGONISTAS) O AFINIDAD PARA EL GP 130 REDUCIDO O ABOLIDO (ANTAGONISTAS Y ANTAGONISTAS). LA FIGURA DEMUESTRA UN ESQUEMA QUE ILUSTRA LA METODOLOGIA APLICADA PARA IDENTIFICAR EL EMPLAZAMIENTO 1 Y EL EMPLAZAMIENTO 2 EN EL CASO DE LA INTERLEUCINA-6 HUMANA. LA INVENCION TAMBIEN DESCRIBE LA OBTENCION DE SUPERAGONISTAS Y SUPERANTAGONISTAS ESPECIFICAS DE LA INTERLEUCINA-6 Y EL USO DE SUPERANTAGONISTAS COMO INHIBIDORES DE DOSIS BAJA DEL CRECIMIENTO DE CELULAS DE MIELOMAS HUMANOS DEPENDIENTES DE LA INTERLEUCINA-6 DE TIPO SALAVAJE.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITRM940805A IT1274782B (it) | 1994-12-14 | 1994-12-14 | Metodo per selezionare superagonisti, antagonisti e superantagonisti di ormoni del cui complesso recettoriale fa parte gp 130 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2192585T3 true ES2192585T3 (es) | 2003-10-16 |
Family
ID=11402859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES95940409T Expired - Lifetime ES2192585T3 (es) | 1994-12-14 | 1995-12-13 | Superagonistas y antagonistas de la h il-6 y metodo de modelado tridimensional para su seleccion. |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US5849283A (es) |
| EP (1) | EP0745094B1 (es) |
| JP (2) | JP3206919B2 (es) |
| CN (1) | CN1070866C (es) |
| AT (1) | ATE234864T1 (es) |
| AU (1) | AU702783B2 (es) |
| CA (1) | CA2177838A1 (es) |
| DE (1) | DE69529973T2 (es) |
| DK (1) | DK0745094T3 (es) |
| ES (1) | ES2192585T3 (es) |
| HK (1) | HK1011032A1 (es) |
| IT (1) | IT1274782B (es) |
| PT (1) | PT745094E (es) |
| WO (1) | WO1996018648A1 (es) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0871472A4 (en) * | 1995-10-27 | 2001-05-30 | Amrad Operations Pty Ltd | CYTOKINES AND THEIR USE IN THE TREATMENT AND / OR PROPHYLAXIS OF BREAST CANCER |
| AU723057B2 (en) * | 1995-11-07 | 2000-08-17 | Kaneka Corporation | Autoantigen |
| IT1285790B1 (it) * | 1996-09-24 | 1998-06-24 | Angeletti P Ist Richerche Bio | Adenovirus difettivi ricombinanti che codificano per mutanti di interleuchina 6 umana (hil-6) con attivita' antagonista o |
| AUPO439396A0 (en) | 1996-12-24 | 1997-01-23 | Walter And Eliza Hall Institute Of Medical Research, The | A method of treatment and prophylaxis |
| GB9702944D0 (en) * | 1997-02-13 | 1997-04-02 | Univ Manchester | Reducing fibrosis |
| ES2382488T3 (es) | 1997-03-21 | 2012-06-08 | Chugai Seiyaku Kabushiki Kaisha | Un agente preventivo o terapéutico para enfermedades mediadas por células t sensibilizadas que comprende un antagonista de il-6 como ingrediente activo |
| CA2237915A1 (en) * | 1998-05-19 | 1999-11-19 | Stephen Shaughnessy | Osteoporosis treatment |
| JP2002519387A (ja) | 1998-07-06 | 2002-07-02 | ザ ガバメント オブ ザ ユナイテッド ステイツ オブ アメリカ， アズ レプレゼンテッド バイ ザ セクレタリー， デパートメント オブ ヘルス アンド ヒューマン サービシーズ | 体外受精のための組成物および方法 |
| US8440196B1 (en) | 1998-08-24 | 2013-05-14 | Chugai Seiyaku Kabushiki Kaisha | Treatment for pancreatitis using IL-6 receptor antagonist antibodies |
| JP4799516B2 (ja) * | 1998-08-24 | 2011-10-26 | 中外製薬株式会社 | Ｉｌ−６アンタゴニストを有効成分として含有する膵炎の予防又は治療剤 |
| US6541244B1 (en) * | 1999-06-07 | 2003-04-01 | Cedars-Sinai Medical Center | Suppressor of cytokine signaling (SOCS)-3 promoter and methods for its use in genetic therapy in humans |
| WO2001016166A2 (en) | 1999-08-27 | 2001-03-08 | The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Polypeptides, comprising il-6 ligand-binding receptor domains, and related nucleic acids, antibodies, compositions, and methods of use |
| UA80091C2 (en) | 2001-04-02 | 2007-08-27 | Chugai Pharmaceutical Co Ltd | Remedies for infant chronic arthritis-relating diseases and still's disease which contain an interleukin-6 (il-6) antagonist |
| US7247618B2 (en) * | 2001-04-30 | 2007-07-24 | Tripathi Rajavashisth | Methods for inhibiting macrophage colony stimulating factor and c-FMS-dependent cell signaling |
| PT2308888T (pt) * | 2001-11-14 | 2017-05-03 | Janssen Biotech Inc | Anticorpos anti-il-6, composições, métodos e utilizações |
| EP1542719A4 (en) | 2001-12-05 | 2006-06-21 | Baylor College Medicine | METHODS AND COMPOSITIONS FOR REGULATING OS FORMATION BY MODULATING THE SYMPATHETIC TONUS |
| AU2004212843B2 (en) | 2003-02-24 | 2009-06-25 | Chugai Seiyaku Kabushiki Kaisha | Remedy for spinal injury containing interleukin-6 antagonist |
| GB2401040A (en) | 2003-04-28 | 2004-11-03 | Chugai Pharmaceutical Co Ltd | Method for treating interleukin-6 related diseases |
| ES2392824T3 (es) | 2003-10-17 | 2012-12-14 | Chugai Seiyaku Kabushiki Kaisha | Agente terapéutico contra el mesotelioma |
| US20050100550A1 (en) * | 2003-11-10 | 2005-05-12 | Mohit Trikha | Anti-angiogenic uses of IL-6 antagonists |
| AR048210A1 (es) | 2003-12-19 | 2006-04-12 | Chugai Pharmaceutical Co Ltd | Un agente preventivo para la vasculitis. |
| JO3058B1 (ar) | 2005-04-29 | 2017-03-15 | Applied Molecular Evolution Inc | الاجسام المضادة لمضادات -اي ال-6,تركيباتها طرقها واستعمالاتها |
| JP5014143B2 (ja) | 2005-10-14 | 2012-08-29 | 学校法人福岡大学 | 膵島移植における移植膵島障害抑制剤 |
| BRPI0617664B8 (pt) | 2005-10-21 | 2021-05-25 | Chugai Pharmaceutical Co Ltd | uso de um anticorpo que reconhece a il-6 para a produção de uma composição farmacêutica para tratar o enfarte do miocárdio ou suprimir a remodelagem ventricular esquerda depois do enfarte do miocárdio |
| AR057582A1 (es) | 2005-11-15 | 2007-12-05 | Nat Hospital Organization | Agentes para suprimir la induccion de linfocitos t citotoxicos |
| WO2007061029A1 (ja) | 2005-11-25 | 2007-05-31 | Keio University | 前立腺癌治療剤 |
| ES2685915T3 (es) | 2006-01-27 | 2018-10-15 | Keio University | Agentes terapéuticos para enfermedades que implican neovascularización coroidea |
| EP2025346B1 (en) | 2006-04-07 | 2016-08-10 | Osaka University | Muscle regeneration promoter |
| WO2008090901A1 (ja) | 2007-01-23 | 2008-07-31 | Shinshu University | 慢性拒絶反応抑制剤 |
| EP2305306B1 (en) | 2008-06-05 | 2016-02-10 | National Cancer Center | Neuroinvasion inhibitor |
| US8188235B2 (en) * | 2008-06-18 | 2012-05-29 | Pfizer Inc. | Antibodies to IL-6 and their uses |
| EP2578233B1 (en) | 2010-05-28 | 2017-04-26 | National Cancer Center | Therapeutic agent for pancreatic cancer |
| JP6051049B2 (ja) | 2010-05-28 | 2016-12-21 | 中外製薬株式会社 | 抗腫瘍ｔ細胞応答増強剤 |
| CN104998254A (zh) | 2010-11-08 | 2015-10-28 | 基因技术公司 | 皮下施用的抗-il-6受体抗体 |
| WO2014200018A1 (ja) | 2013-06-11 | 2014-12-18 | 独立行政法人 国立精神・神経医療研究センター | 再発寛解型多発性硬化症（ｒｒｍｓ）患者の治療予後予測方法、及び新規治療適応判断方法 |
| EP2898896A1 (en) | 2014-01-22 | 2015-07-29 | Université Pierre et Marie Curie (Paris 6) | Agents for use in the treatment of retinal inflammation |
| BR112017014067B1 (pt) | 2015-02-27 | 2021-01-12 | Chugai Seiyaku Kabushiki Kaisha | usos de um anticorpo receptor de il-6 para no tratamento de doenças relacionadas a il-6 |
| WO2017151409A1 (en) | 2016-02-29 | 2017-09-08 | University Of Florida Research Foundation, Incorporated | Chemotherapeutic methods |
| WO2018203545A1 (ja) | 2017-05-02 | 2018-11-08 | 国立研究開発法人国立精神・神経医療研究センター | Ｉｌ－６及び好中球の関連する疾患の治療効果の予測及び判定方法 |
| TWI822728B (zh) | 2018-01-31 | 2023-11-21 | 加藤元一 | 含有il-6抑制劑的哮喘治療劑 |
| KR20220019670A (ko) | 2019-04-17 | 2022-02-17 | 고쿠리츠다이가쿠호진 히로시마다이가쿠 | Il-6 저해제 및 ccr2 저해제를 조합하여 투여하는 것을 특징으로 하는 비뇨기암의 치료제 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0672144A1 (en) * | 1992-10-20 | 1995-09-20 | Chiron Corporation | Interleukin-6 receptor antagonists |
| IT1263022B (it) * | 1992-11-06 | 1996-07-23 | Angeletti P Ist Richerche Bio | Interleuchina-6 mutante con attivita' biologica migliorata rispetto all'interleuchina-6 selvatica. |
-
1994
- 1994-12-14 IT ITRM940805A patent/IT1274782B/it active IP Right Grant
-
1995
- 1995-12-13 AT AT95940409T patent/ATE234864T1/de not_active IP Right Cessation
- 1995-12-13 JP JP51856296A patent/JP3206919B2/ja not_active Expired - Fee Related
- 1995-12-13 PT PT95940409T patent/PT745094E/pt unknown
- 1995-12-13 US US08/693,182 patent/US5849283A/en not_active Expired - Fee Related
- 1995-12-13 DK DK95940409T patent/DK0745094T3/da active
- 1995-12-13 EP EP95940409A patent/EP0745094B1/en not_active Expired - Lifetime
- 1995-12-13 DE DE69529973T patent/DE69529973T2/de not_active Expired - Fee Related
- 1995-12-13 CA CA002177838A patent/CA2177838A1/en not_active Abandoned
- 1995-12-13 AU AU41871/96A patent/AU702783B2/en not_active Ceased
- 1995-12-13 ES ES95940409T patent/ES2192585T3/es not_active Expired - Lifetime
- 1995-12-13 CN CN95191575A patent/CN1070866C/zh not_active Expired - Fee Related
- 1995-12-13 WO PCT/IT1995/000216 patent/WO1996018648A1/en active IP Right Grant
-
1998
- 1998-01-16 US US09/008,482 patent/US5914106A/en not_active Expired - Fee Related
- 1998-11-13 HK HK98111981A patent/HK1011032A1/xx not_active IP Right Cessation
-
2001
- 2001-04-24 JP JP2001125516A patent/JP3286310B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| PT745094E (pt) | 2003-07-31 |
| ITRM940805A0 (it) | 1994-12-14 |
| JP2001354698A (ja) | 2001-12-25 |
| US5849283A (en) | 1998-12-15 |
| HK1011032A1 (en) | 1999-07-02 |
| JP3286310B2 (ja) | 2002-05-27 |
| DE69529973D1 (de) | 2003-04-24 |
| US5914106A (en) | 1999-06-22 |
| ATE234864T1 (de) | 2003-04-15 |
| DK0745094T3 (da) | 2003-06-10 |
| JP3206919B2 (ja) | 2001-09-10 |
| CA2177838A1 (en) | 1996-06-15 |
| AU702783B2 (en) | 1999-03-04 |
| ITRM940805A1 (it) | 1996-06-14 |
| IT1274782B (it) | 1997-07-24 |
| AU4187196A (en) | 1996-07-03 |
| EP0745094B1 (en) | 2003-03-19 |
| CN1070866C (zh) | 2001-09-12 |
| EP0745094A1 (en) | 1996-12-04 |
| CN1140456A (zh) | 1997-01-15 |
| DE69529973T2 (de) | 2003-12-04 |
| WO1996018648A1 (en) | 1996-06-20 |
| JPH09502460A (ja) | 1997-03-11 |
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