ES2136596T3 - Hil-6 modificada. - Google Patents
Hil-6 modificada.Info
- Publication number
- ES2136596T3 ES2136596T3 ES91301166T ES91301166T ES2136596T3 ES 2136596 T3 ES2136596 T3 ES 2136596T3 ES 91301166 T ES91301166 T ES 91301166T ES 91301166 T ES91301166 T ES 91301166T ES 2136596 T3 ES2136596 T3 ES 2136596T3
- Authority
- ES
- Spain
- Prior art keywords
- modified
- well
- hil
- difficiencies
- unglycosylated
- 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
- 101100338243 Caenorhabditis elegans hil-6 gene Proteins 0.000 title 1
- 102000004889 Interleukin-6 Human genes 0.000 abstract 3
- 108090001005 Interleukin-6 Proteins 0.000 abstract 3
- 230000001154 acute effect Effects 0.000 abstract 1
- 230000004071 biological effect Effects 0.000 abstract 1
- 208000018706 hematopoietic system disease Diseases 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 229940100601 interleukin-6 Drugs 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 229920001184 polypeptide Polymers 0.000 abstract 1
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 1
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 1
- 206010043554 thrombocytopenia Diseases 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Abstract
SE SUMINISTRAN DERIVADOS DE "INTERLEUKINA-6" PEGILATADOS (PEG-IL-6) QUE PRESENTAN UNA VIDA MEDIA DE PLASMA MAS LARGA, ASI COMO UNA ACTIVIDAD BIOLOGICA Y IL-6 "IN VIVO" MEJORADA. TAMBIEN SE PRESENTAN METODOS PARA PRODUCIR LOS POLIPEPTIDOS CON LAS PROTEINAS IL-6 GLICOSILATADAS Y NO GLICOSILATADAS, MODIFICADAS, ASI COMO, METODOS PARA SU USO EN EL TRATAMIENTO DE ENFERMEDADES HEMATOPOIETICAS PARTICULARMENTE LA TROMBOCITOPENIA AGUDA.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3227390 | 1990-02-13 | ||
| JP22235390 | 1990-08-22 | ||
| JP2250460A JPH04218000A (ja) | 1990-02-13 | 1990-09-21 | 修飾ポリペプチド |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2136596T3 true ES2136596T3 (es) | 1999-12-01 |
Family
ID=27287645
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES91301166T Expired - Lifetime ES2136596T3 (es) | 1990-02-13 | 1991-02-13 | Hil-6 modificada. |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5264209A (es) |
| EP (1) | EP0442724B1 (es) |
| JP (1) | JPH04218000A (es) |
| AT (1) | ATE185602T1 (es) |
| AU (1) | AU634343B2 (es) |
| CA (1) | CA2036197C (es) |
| DE (1) | DE69131699T2 (es) |
| DK (1) | DK0442724T3 (es) |
| ES (1) | ES2136596T3 (es) |
Families Citing this family (79)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU639428B2 (en) * | 1988-12-01 | 1993-07-29 | Imclone Systems, Inc. | Synthetic interleukin-6 |
| US5552391A (en) * | 1990-01-16 | 1996-09-03 | La Jolla Pharmaceutical Company | Chemically-defined non-polymeric valency platform molecules and conjugates thereof |
| US20060084797A1 (en) * | 1990-06-11 | 2006-04-20 | Gilead Sciences, Inc. | High affinity TGFbeta nucleic acid ligands and inhibitors |
| US6465188B1 (en) * | 1990-06-11 | 2002-10-15 | Gilead Sciences, Inc. | Nucleic acid ligand complexes |
| US5766897A (en) * | 1990-06-21 | 1998-06-16 | Incyte Pharmaceuticals, Inc. | Cysteine-pegylated proteins |
| MX9304075A (es) * | 1992-07-08 | 1994-04-29 | Applied Research Systems | Composicion farmaceutica para el tratamiento o profilaxis de los desordenes trombohemorragicos consuntivos. |
| AU5098193A (en) * | 1992-09-01 | 1994-03-29 | Berlex Laboratories, Inc. | Glycolation of glycosylated macromolecules |
| KR100361933B1 (ko) | 1993-09-08 | 2003-02-14 | 라 졸라 파마슈티칼 컴파니 | 화학적으로정의된비중합성결합가플랫폼분자및그것의콘주게이트 |
| DK0642798T3 (da) * | 1993-09-08 | 2007-09-10 | Jolla Pharma | Kemisk definerede, ikke polymere valensplatformmolekyler og konjugater deraf |
| US5795569A (en) * | 1994-03-31 | 1998-08-18 | Amgen Inc. | Mono-pegylated proteins that stimulate megakaryocyte growth and differentiation |
| US5766581A (en) * | 1994-03-31 | 1998-06-16 | Amgen Inc. | Method for treating mammals with monopegylated proteins that stimulates megakaryocyte growth and differentiation |
| RU2158603C2 (ru) * | 1994-05-31 | 2000-11-10 | Амген Инк. | Способы и препараты для стимулирования роста и дифференцировки мегакариоцитов |
| US20030053982A1 (en) | 1994-09-26 | 2003-03-20 | Kinstler Olaf B. | N-terminally chemically modified protein compositions and methods |
| US6010871A (en) * | 1994-09-29 | 2000-01-04 | Ajinomoto Co., Inc. | Modification of peptide and protein |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| US5770577A (en) * | 1994-11-14 | 1998-06-23 | Amgen Inc. | BDNF and NT-3 polypeptides selectively linked to polyethylene glycol |
| US8071737B2 (en) * | 1995-05-04 | 2011-12-06 | Glead Sciences, Inc. | Nucleic acid ligand complexes |
| US5874409A (en) | 1995-06-07 | 1999-02-23 | La Jolla Pharmaceutical Company | APL immunoreactive peptides, conjugates thereof and methods of treatment for APL antibody-mediated pathologies |
| US5861500A (en) * | 1996-07-25 | 1999-01-19 | The Trustees Of Columbia University In The City Of New York | Kaposi's sarcoma-associated herpesvirus (KSHV) interleukin 6 (IL-6) and uses thereof |
| US5854398A (en) * | 1996-07-25 | 1998-12-29 | The Trustees Of Columbia University In The City Of New York | Kaposi's sarcoma-associated herpesvirus (KSHV) interleukin 6 (IL-6) and uses thereof |
| CA2277757C (en) * | 1997-01-15 | 2008-09-16 | Phoenix Pharmacologics, Inc. | Modified tumor necrosis factor |
| US6183738B1 (en) | 1997-05-12 | 2001-02-06 | Phoenix Pharamacologics, Inc. | Modified arginine deiminase |
| ATE279430T1 (de) | 1998-03-05 | 2004-10-15 | Chiron Corp | Verfahren zur verbesserung der serum halbwertszeit von biologisch aktiven molekülen |
| US6887674B1 (en) | 1998-04-13 | 2005-05-03 | California Institute Of Technology | Artery- and vein-specific proteins and uses therefor |
| AU4208799A (en) * | 1998-05-29 | 1999-12-13 | Human Genome Sciences, Inc. | Interleukins-21 and 22 |
| US6858210B1 (en) | 1998-06-09 | 2005-02-22 | La Jolla Pharmaceutical Co. | Therapeutic and diagnostic domain 1 β2GPI polypeptides and methods of using same |
| EE05111B1 (et) | 1998-10-16 | 2008-12-15 | Biogen, Incorporated | Interferoon-beetaga sulandatud valgud ja nende kasutamine |
| HU229888B1 (en) | 1998-10-16 | 2014-11-28 | Biogen Idec Ma Inc Cambridge | Polymer conjugates of interferon betha-1a and uses |
| DK2319928T3 (da) | 1998-10-23 | 2013-06-24 | Kirin Amgen Inc | Dimere trombopoietiske peptidomimetika, der binder til MPL-receptor og har trombopoietisk aktivitet |
| US6458953B1 (en) | 1998-12-09 | 2002-10-01 | La Jolla Pharmaceutical Company | Valency platform molecules comprising carbamate linkages |
| US6399578B1 (en) | 1998-12-09 | 2002-06-04 | La Jolla Pharmaceutical Company | Conjugates comprising galactose α1,3 galactosyl epitopes and methods of using same |
| CN1762990A (zh) * | 1999-06-08 | 2006-04-26 | 拉卓拉药物公司 | 包含氨基氧基的化合价平台分子 |
| US7135461B1 (en) * | 2000-06-16 | 2006-11-14 | Myelos Corporation | Retro-inverso peptides derived from interleukin-6 |
| AU2223401A (en) * | 1999-12-24 | 2001-07-09 | Kyowa Hakko Kogyo Co. Ltd. | Branched polyalkylene glycols |
| IT1317835B1 (it) * | 2000-02-15 | 2003-07-15 | San Raffaele Centro Fond | Citochine modificate per uso nella terapia del cancro. |
| CN1434726A (zh) | 2000-06-08 | 2003-08-06 | 拉卓拉药物公司 | 包含高分子量聚环氧乙烷的多价平台分子 |
| AU2001273385B2 (en) * | 2000-09-08 | 2005-04-07 | Gryphon Therapeutics, Inc. | Polymer-modified synthetic proteins |
| US7118737B2 (en) | 2000-09-08 | 2006-10-10 | Amylin Pharmaceuticals, Inc. | Polymer-modified synthetic proteins |
| DE10059336A1 (de) * | 2000-11-29 | 2002-06-13 | Scil Proteins Gmbh | Herstellung von rekombinantem BMP-2 |
| IL142875A (en) | 2001-04-30 | 2009-08-03 | Avigdor Shafferman | PEG-linked cholinesterases for the detoxification of circulating organophosphorus |
| ITMI20011986A1 (it) * | 2001-09-25 | 2003-03-25 | San Raffaele Centro Fond | Metodo e composizione per l'attivazione di cellule presentanti l'antigene |
| GB0209893D0 (en) * | 2002-04-30 | 2002-06-05 | Molmed Spa | Conjugate |
| GB0209896D0 (en) * | 2002-04-30 | 2002-06-05 | Molmed Spa | Conjugate |
| CA2490747A1 (en) * | 2002-06-21 | 2003-12-31 | Centocor, Inc. | Method for generating monoclonal antibodies |
| PL396711A1 (pl) * | 2002-12-26 | 2011-12-19 | Mountain View Pharmaceuticals, Inc. | Koniugaty polimerów z cytokinami, chemokinami, czynnikami wzrostu, hormonami polipeptydowymi i ich antagonistami, kompozycja farmaceutyczna i sposób zapobiegania, diagnozowania lub leczenia |
| US7655618B2 (en) | 2002-12-27 | 2010-02-02 | Diobex, Inc. | Compositions and methods for the prevention and control of insulin-induced hypoglycemia |
| WO2004060387A1 (en) | 2002-12-27 | 2004-07-22 | Diobex, Inc. | Compositions and methods for the prevention and control of insulin-induced hypoglycemia |
| US20050130892A1 (en) * | 2003-03-07 | 2005-06-16 | Xencor, Inc. | BAFF variants and methods thereof |
| US7553930B2 (en) * | 2003-01-06 | 2009-06-30 | Xencor, Inc. | BAFF variants and methods thereof |
| US20050221443A1 (en) * | 2003-01-06 | 2005-10-06 | Xencor, Inc. | Tumor necrosis factor super family agonists |
| US20060014248A1 (en) * | 2003-01-06 | 2006-01-19 | Xencor, Inc. | TNF super family members with altered immunogenicity |
| JP2006521111A (ja) | 2003-03-12 | 2006-09-21 | バスジーン セラピューティクス, インコーポレイテッド | 血管形成及び腫瘍増殖阻害用ポリペプチド化合物及びその応用 |
| US7381410B2 (en) * | 2003-03-12 | 2008-06-03 | Vasgene Therapeutics, Inc. | Polypeptide compounds for inhibiting angiogenesis and tumor growth |
| EP1491554A1 (en) * | 2003-06-23 | 2004-12-29 | CONARIS research institute AG | PEGylated soluble gp130-dimers useful as a medicament |
| IL159558A0 (en) * | 2003-12-24 | 2004-06-01 | Applied Research Systems | Use of il-6 in liver injury |
| WO2005085283A1 (ja) * | 2004-03-03 | 2005-09-15 | Yamanouchi Pharmaceutical Co., Ltd. | 修飾インターロイキン−11及びそれを含有する医薬組成物 |
| CN102718867A (zh) | 2004-03-12 | 2012-10-10 | 瓦斯基因治疗公司 | 结合ephb4、抑制血管发生和肿瘤生长的抗体 |
| US7977463B2 (en) | 2004-03-12 | 2011-07-12 | Vasgene Therapeutics, Inc. | Polypeptide compounds for inhibiting angiogenesis and tumor growth |
| JP2007530569A (ja) * | 2004-03-23 | 2007-11-01 | アムジエン・インコーポレーテツド | 化学修飾タンパク質組成物及び方法 |
| RU2298560C2 (ru) * | 2004-04-30 | 2007-05-10 | Открытое Акционерное Общество "Верофарм" | Конъюгаты белка и производного полиэтиленгликоля, фармацевтическая композиция, способ борьбы с вирусной инфекцией |
| CA2572765C (en) | 2004-07-08 | 2013-05-21 | Amgen Inc. | Compound having improved bioefficiency when administered in a multidose regimen |
| US20060204512A1 (en) * | 2004-09-23 | 2006-09-14 | Vasgene Therapeutics, Inc. | Polypeptide compounds for inhibiting angiogenesis and tumor growth |
| EP2364995A1 (en) | 2004-12-23 | 2011-09-14 | Molmed SpA | Conjugation product |
| JPWO2006080171A1 (ja) | 2005-01-31 | 2008-06-19 | 株式会社 エフェクター細胞研究所 | 免疫増強剤 |
| WO2006116948A1 (en) * | 2005-04-30 | 2006-11-09 | Chengdu Institute Of Biological Products | Interleukin-6 polyethylene glycol conjugate and its preparing method and use |
| AU2006295340B2 (en) | 2005-08-05 | 2010-11-11 | Amgen Inc. | Stable aqueous protein or antibody pharmaceutical formulations and their preparation |
| JP2009513680A (ja) * | 2005-10-28 | 2009-04-02 | セントカー・インコーポレーテツド | 抗体の生成におけるb細胞増殖剤の使用 |
| JO3324B1 (ar) | 2006-04-21 | 2019-03-13 | Amgen Inc | مركبات علاجية مجففة بالتبريد تتعلق بالعصارة الهضمية |
| ATE480568T1 (de) | 2006-06-30 | 2010-09-15 | Conaris Res Inst Ag | Verbesserte sgp 130fc dimere |
| TW200817438A (en) | 2006-08-17 | 2008-04-16 | Hoffmann La Roche | A conjugate of an antibody against CCR5 and an antifusogenic peptide |
| AR067537A1 (es) * | 2007-07-17 | 2009-10-14 | Hoffmann La Roche | Purificacion de polipeptidos pegilados |
| AR067536A1 (es) * | 2007-07-17 | 2009-10-14 | Hoffmann La Roche | Metodo para obtener una eritropoyetina mono-pegilada en una forma sustancialmente homogenea |
| AR067584A1 (es) | 2007-07-20 | 2009-10-14 | Hoffmann La Roche | Un conjugado de un anticuerpo contra la cd4 y peptidos antifusogenicos |
| JP5735650B2 (ja) | 2010-09-14 | 2015-06-17 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | Peg化エリスロポエチンを精製するための方法 |
| US20140349866A1 (en) * | 2011-06-27 | 2014-11-27 | Galderma Research & Development | New th-17 differentiation markers for rosacea and uses thereof |
| MX2017007067A (es) | 2014-12-01 | 2018-04-30 | Ferring Bv | Administracion de un inhibidor selectivo de la trans-señalizacion de il-6. |
| MD3227325T2 (ro) | 2014-12-01 | 2024-09-30 | Ferring Bv | Compoziții de inhibitor selectiv trans-semnalizare de IL-6 |
| WO2018011381A1 (en) | 2016-07-15 | 2018-01-18 | F. Hoffmann-La Roche Ag | Method for purifying pegylated erythropoietin |
| TW202330584A (zh) * | 2022-01-20 | 2023-08-01 | 丹麥商諾佛 儂迪克股份有限公司 | 前藥及其用途 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4732863A (en) * | 1984-12-31 | 1988-03-22 | University Of New Mexico | PEG-modified antibody with reduced affinity for cell surface Fc receptors |
| DE3676670D1 (de) * | 1985-06-26 | 1991-02-07 | Cetus Corp | Solubilisierung von proteinen fuer pharmazeutische zusammensetzungen mittels polymerkonjugierung. |
| US4766106A (en) * | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| ES8800982A1 (es) * | 1985-07-05 | 1987-12-01 | Takeda Chemical Industries Ltd | Un metodo para producir la enzima superoxido-dismutasa modificada con derivados de polietilenglicol y triazina. |
| US4810643A (en) * | 1985-08-23 | 1989-03-07 | Kirin- Amgen Inc. | Production of pluripotent granulocyte colony-stimulating factor |
| JP2514950B2 (ja) * | 1986-03-10 | 1996-07-10 | エフ・ホフマン―ラ ロシユ アーゲー | 化学修飾蛋白質,その製造法および中間体 |
| CA1283046C (en) * | 1986-05-29 | 1991-04-16 | Nandini Katre | Tumor necrosis factor formulation |
| US4791192A (en) * | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| IE67035B1 (en) * | 1986-07-08 | 1996-02-21 | Genetics Inst | Production and use of non-glycosylated IL-6 |
| EP0585957A1 (en) * | 1986-08-06 | 1994-03-09 | Ajinomoto Co., Inc. | Recombinant B-cell differentiation factor |
| JPS6360938A (ja) * | 1986-09-02 | 1988-03-17 | Meiji Milk Prod Co Ltd | 修飾組織型プラスミノ−ゲン活性化因子およびその製造方法 |
| US4904584A (en) * | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
| US4847325A (en) * | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
| CA1340810C (en) * | 1988-03-31 | 1999-11-02 | Motoo Yamasaki | Polypeptide derivatives of human granulocyte colony stimulating factor |
| JPH0372429A (ja) * | 1988-10-07 | 1991-03-27 | Chugai Pharmaceut Co Ltd | 血小板減少症の治療剤 |
| AU639428B2 (en) * | 1988-12-01 | 1993-07-29 | Imclone Systems, Inc. | Synthetic interleukin-6 |
-
1990
- 1990-09-21 JP JP2250460A patent/JPH04218000A/ja active Pending
- 1990-12-21 US US07/632,070 patent/US5264209A/en not_active Expired - Lifetime
-
1991
- 1991-02-07 AU AU70878/91A patent/AU634343B2/en not_active Ceased
- 1991-02-12 CA CA002036197A patent/CA2036197C/en not_active Expired - Lifetime
- 1991-02-13 EP EP91301166A patent/EP0442724B1/en not_active Expired - Lifetime
- 1991-02-13 DE DE69131699T patent/DE69131699T2/de not_active Expired - Fee Related
- 1991-02-13 DK DK91301166T patent/DK0442724T3/da active
- 1991-02-13 AT AT91301166T patent/ATE185602T1/de not_active IP Right Cessation
- 1991-02-13 ES ES91301166T patent/ES2136596T3/es not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE69131699D1 (de) | 1999-11-18 |
| EP0442724B1 (en) | 1999-10-13 |
| EP0442724A2 (en) | 1991-08-21 |
| EP0442724A3 (en) | 1992-02-26 |
| DE69131699T2 (de) | 2000-02-24 |
| DK0442724T3 (da) | 2000-04-10 |
| ATE185602T1 (de) | 1999-10-15 |
| AU7087891A (en) | 1991-08-15 |
| CA2036197C (en) | 2001-09-18 |
| CA2036197A1 (en) | 1991-08-14 |
| AU634343B2 (en) | 1993-02-18 |
| US5264209A (en) | 1993-11-23 |
| JPH04218000A (ja) | 1992-08-07 |
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