ES2010299A6 - Un procedimiento para la preparacion de analogos de insulina humana que presentan actividad biologica. - Google Patents
Un procedimiento para la preparacion de analogos de insulina humana que presentan actividad biologica.Info
- Publication number
- ES2010299A6 ES2010299A6 ES888802408A ES8802408A ES2010299A6 ES 2010299 A6 ES2010299 A6 ES 2010299A6 ES 888802408 A ES888802408 A ES 888802408A ES 8802408 A ES8802408 A ES 8802408A ES 2010299 A6 ES2010299 A6 ES 2010299A6
- Authority
- ES
- Spain
- Prior art keywords
- dna
- circular
- sequence
- insulin
- isolate
- 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
Links
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical class C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 title abstract 2
- 238000002360 preparation method Methods 0.000 title abstract 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 abstract 6
- 102000004877 Insulin Human genes 0.000 abstract 3
- 108090001061 Insulin Proteins 0.000 abstract 3
- 229940125396 insulin Drugs 0.000 abstract 3
- 108020004638 Circular DNA Proteins 0.000 abstract 2
- 239000002243 precursor Substances 0.000 abstract 2
- 108020004635 Complementary DNA Proteins 0.000 abstract 1
- 108020004414 DNA Proteins 0.000 abstract 1
- 230000004071 biological effect Effects 0.000 abstract 1
- 238000010804 cDNA synthesis Methods 0.000 abstract 1
- 239000002299 complementary DNA Substances 0.000 abstract 1
- 206010012601 diabetes mellitus Diseases 0.000 abstract 1
- 239000013604 expression vector Substances 0.000 abstract 1
- 239000012634 fragment Substances 0.000 abstract 1
- 238000000338 in vitro Methods 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 239000013598 vector 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
-
- 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
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
- C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
-
- 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
- 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)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Endocrinology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Mycology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Obesity (AREA)
- Plant Pathology (AREA)
- General Chemical & Material Sciences (AREA)
- Emergency Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
UN PROCEDIMIENTO PARA LA PREPARACION DE ANALOGOS DE INSULINA HUMANA QUE PRESENTAN ACTIVIDAD BIOLOGICA. COMPRENDE: INSERTAR LA SECUENCIA DEL PRECURSOR DE INSULINA AISLADA DEL PLASMIDO DE EXPRESION EN UN VECTOR DEL BACTERIOFAGO M13 CIRCULAR MONOFILAMENTAR; FUSIONAR AL GENOMA MONOFILAMENTAR UNA HEBRA DE ADN COMPLEMENTARIA CICLADA QUE CONTIENE LA SECUENCIA DESEADA RODEADA DE SECUENCIAS COMPLETAMENTE HOMOLOGAS A LAS SECUENCIAS DE INSULINA EN EL ADN CIRCULAR; PROLONGAR IN VITRO EL CEBADOR SOBRE LA LONGITUD COMPLETA DEL GENOMA CIRCULAR BIOQUIMICAMENTE UTILIZANDO POLIMERASA KLENOW, OBTENIENDOSE FAGOS MONOFILAMENTARES QUE AL CRECER EN E.COLI PERMITEN AISLAR ADN DE DOBLE HEBRA CON LA SECUENCIA DESEADA; AISLAR UN FRAGMENTO DE RESTRICCION DE ESTE ADN Y REINSERTARLO EN EL VECTOR DE EXPRESION; TRANSFORMARLO EN UN HUESPED, CULTIVAR Y AISLAR EL PRECURSOR DE INSULINA DEL MEDIO DE CULTIVO. ESTOS PRODUCTOS TIENEN UTILIDAD EN EL TRATAMIENTO DE LA DIABETES MELLITUS.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/DK1988/000124 WO1990001038A1 (en) | 1988-07-20 | 1988-07-20 | Human insulin analogs and preparations containing them |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2010299A6 true ES2010299A6 (es) | 1989-11-01 |
Family
ID=8153493
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES888802408A Expired ES2010299A6 (es) | 1988-07-20 | 1988-08-01 | Un procedimiento para la preparacion de analogos de insulina humana que presentan actividad biologica. |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US5149777A (es) |
| EP (1) | EP0425482B1 (es) |
| JP (1) | JPH03506023A (es) |
| KR (1) | KR900701842A (es) |
| AT (1) | ATE93238T1 (es) |
| AU (1) | AU616205B2 (es) |
| ES (1) | ES2010299A6 (es) |
| FI (1) | FI910286A0 (es) |
| NO (1) | NO905472L (es) |
| WO (1) | WO1990001038A1 (es) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK336188D0 (da) * | 1988-06-20 | 1988-06-20 | Nordisk Gentofte | Propeptider |
| IL94718A (en) * | 1989-07-05 | 1994-10-21 | Schering Ag | Carboxamide non-ionic contrast media and method for the preparation thereof |
| DK10191D0 (da) * | 1991-01-22 | 1991-01-22 | Novo Nordisk As | Hidtil ukendte peptider |
| DK33591D0 (es) * | 1991-02-27 | 1991-02-27 | Novo Nordisk As | |
| WO1994003624A1 (en) * | 1992-08-04 | 1994-02-17 | Auerbach Jeffrey I | Methods for the isothermal amplification of nucleic acid molecules |
| US6261808B1 (en) * | 1992-08-04 | 2001-07-17 | Replicon, Inc. | Amplification of nucleic acid molecules via circular replicons |
| DK72793D0 (da) * | 1993-06-21 | 1993-06-21 | Novo Nordisk As | Nyt produkt |
| WO1995016708A1 (en) * | 1993-12-17 | 1995-06-22 | Novo Nordisk A/S | Proinsulin-like compounds |
| US6001604A (en) * | 1993-12-29 | 1999-12-14 | Bio-Technology General Corp. | Refolding of proinsulins without addition of reducing agents |
| US5461031A (en) * | 1994-06-16 | 1995-10-24 | Eli Lilly And Company | Monomeric insulin analog formulations |
| US5504188A (en) * | 1994-06-16 | 1996-04-02 | Eli Lilly And Company | Preparation of stable zinc insulin analog crystals |
| US5474978A (en) * | 1994-06-16 | 1995-12-12 | Eli Lilly And Company | Insulin analog formulations |
| US5547929A (en) * | 1994-09-12 | 1996-08-20 | Eli Lilly And Company | Insulin analog formulations |
| US5597893A (en) * | 1994-10-31 | 1997-01-28 | Eli Lilly And Company | Preparation of stable insulin analog crystals |
| US5948751A (en) * | 1996-06-20 | 1999-09-07 | Novo Nordisk A/S | X14-mannitol |
| JP2001521006A (ja) | 1997-10-24 | 2001-11-06 | イーライ・リリー・アンド・カンパニー | 不溶性インシュリン組成物 |
| US6531448B1 (en) | 1997-12-23 | 2003-03-11 | Eli Lilly And Company | Insoluble compositions for controlling blood glucose |
| AUPP609198A0 (en) * | 1998-09-22 | 1998-10-15 | Curtin University Of Technology | Use of non-peptidyl compounds for the treatment of insulin related ailments |
| US6933272B1 (en) | 1998-09-22 | 2005-08-23 | Erik Helmerhorst | Use of non-peptidyl compounds for the treatment of insulin related ailments |
| WO2001000223A2 (en) * | 1999-06-25 | 2001-01-04 | Minimed Inc. | Multiple agent diabetes therapy |
| WO2002067969A2 (en) * | 2001-02-21 | 2002-09-06 | Medtronic Minimed, Inc. | Stabilized insulin formulations |
| US6737401B2 (en) | 2001-06-28 | 2004-05-18 | Metronic Minimed, Inc. | Methods of evaluating protein formulation stability and surfactant-stabilized insulin formulations derived therefrom |
| ES2642214T3 (es) | 2004-01-21 | 2017-11-15 | Novo Nordisk Health Care Ag | Conjugación de péptidos mediante transglutaminasa |
| US7833513B2 (en) | 2004-12-03 | 2010-11-16 | Rhode Island Hospital | Treatment of Alzheimer's Disease |
| CN102660614A (zh) | 2005-08-16 | 2012-09-12 | 诺沃-诺迪斯克有限公司 | 制备成熟胰岛素多肽的方法 |
| WO2007081824A2 (en) * | 2006-01-06 | 2007-07-19 | Case Western Reserve University | Fibrillation resistant proteins |
| CN101573133B (zh) | 2006-07-31 | 2014-08-27 | 诺沃-诺迪斯克有限公司 | Peg化延长的胰岛素 |
| RU2524150C2 (ru) | 2006-09-22 | 2014-07-27 | Ново Нордиск А/С | Аналоги инсулина, устойчивые к протеазам |
| EP2069502B1 (en) | 2006-09-27 | 2014-02-26 | Novo Nordisk A/S | Method for making maturated insulin polypeptides |
| WO2008043033A2 (en) | 2006-10-04 | 2008-04-10 | Case Western Reserve University | Fibrillation-resistant insulin and insulin analogues |
| JP5496082B2 (ja) | 2007-04-30 | 2014-05-21 | ノボ・ノルデイスク・エー/エス | タンパク質組成物を乾燥させる方法、乾燥タンパク質組成物、及び乾燥タンパク質を含有する薬学的組成物 |
| EP2017288A1 (en) * | 2007-07-16 | 2009-01-21 | Novo Nordisk A/S | Protease stabilized, pegylated insulin analogues |
| JP5688969B2 (ja) * | 2007-07-16 | 2015-03-25 | ノボ・ノルデイスク・エー/エス | プロテアーゼに対して安定しているペグ化インスリンアナログ |
| WO2009112583A2 (en) * | 2008-03-14 | 2009-09-17 | Novo Nordisk A/S | Protease-stabilized insulin analogues |
| HUE032284T2 (en) | 2008-03-18 | 2017-09-28 | Novo Nordisk As | Protease-stabilized, acylated insulin analogues |
| US8993516B2 (en) * | 2008-04-14 | 2015-03-31 | Case Western Reserve University | Meal-time insulin analogues of enhanced stability |
| EP2296692A4 (en) * | 2008-04-22 | 2012-06-06 | Univ Case Western Reserve | ISOFORM-SPECIFIC INSULIN ANALOG |
| US9200053B2 (en) | 2008-07-31 | 2015-12-01 | Case Western Reserve University | Insulin analogues containing penta-fluoro-Phenylalanine at position B24 |
| MX2011001181A (es) | 2008-07-31 | 2011-04-05 | Univ Case Western Reserve | Insulina estabilizada con halogeno. |
| KR20120129875A (ko) * | 2008-07-31 | 2012-11-28 | 케이스 웨스턴 리저브 유니버시티 | 염소화 아미노산을 갖는 인슐린 유사체 |
| JP2012511506A (ja) * | 2008-12-09 | 2012-05-24 | ノヴォ・ノルディスク・アー/エス | 新規インスリンアナログ |
| MA33248B1 (fr) | 2009-04-01 | 2012-05-02 | Genentech Inc | Traitement de troubles résistant à l'insuline |
| US8399407B2 (en) * | 2009-09-17 | 2013-03-19 | Case Western Reserve University | Non-standard insulin analogues |
| AU2010327949A1 (en) | 2009-12-11 | 2012-06-28 | Case Western Reserve University | Insulin analogues with chlorinated amino acids |
| JP2014509603A (ja) * | 2011-03-15 | 2014-04-21 | ノヴォ ノルディスク アー/エス | システイン置換を含むヒトインスリン類似体およびヒトインスリン誘導体 |
| KR20150021011A (ko) | 2011-10-27 | 2015-02-27 | 케이스 웨스턴 리저브 유니버시티 | 초고도 농축된, 속효성 인슐린 유사체 제형 |
| KR20140104994A (ko) | 2011-12-15 | 2014-08-29 | 샹하이 헨그루이 파마수티컬 컴퍼니 리미티드 | 인간 인슐린 유사체 및 이의 아실화 유도체 |
| CN104364260B (zh) | 2012-04-11 | 2017-02-22 | 诺和诺德股份有限公司 | 胰岛素制剂 |
| EP2877200B1 (en) | 2012-07-17 | 2019-05-08 | Case Western Reserve University | O-linked carbohydrate-modified insulin analogues |
| JP6499184B2 (ja) | 2013-10-07 | 2019-04-10 | ノヴォ ノルディスク アー/エス | インスリン類似体の新規な誘導体 |
| BR112017004544A2 (pt) | 2014-10-06 | 2018-01-23 | Univ Case Western Reserve | insulina de cadeia simples, composição farmacêutica e método para tratar diabetes mellitus |
| EP3260548A1 (en) | 2016-06-21 | 2017-12-27 | Enzypep B.V. | Enzymatic coupling of (oligo)peptides to the b-chain of an insulin receptor ligand |
| PE20210857A1 (es) | 2016-12-16 | 2021-05-18 | Novo Nordisk As | Composiciones farmaceuticas que contienen insulina |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK113585D0 (da) * | 1985-03-12 | 1985-03-12 | Novo Industri As | Nye peptider |
| DK347086D0 (da) * | 1986-07-21 | 1986-07-21 | Novo Industri As | Novel peptides |
| DK119785D0 (da) * | 1985-03-15 | 1985-03-15 | Nordisk Gentofte | Insulinpraeparat |
| PH25772A (en) * | 1985-08-30 | 1991-10-18 | Novo Industri As | Insulin analogues, process for their preparation |
| DK437786D0 (da) * | 1986-09-12 | 1986-09-12 | Nordisk Gentofte | Insulinprecursorer |
-
1988
- 1988-07-20 JP JP63506781A patent/JPH03506023A/ja active Pending
- 1988-07-20 FI FI910286A patent/FI910286A0/fi not_active Application Discontinuation
- 1988-07-20 KR KR1019900700589A patent/KR900701842A/ko not_active Ceased
- 1988-07-20 AU AU22636/88A patent/AU616205B2/en not_active Ceased
- 1988-07-20 US US07/640,308 patent/US5149777A/en not_active Expired - Fee Related
- 1988-07-20 WO PCT/DK1988/000124 patent/WO1990001038A1/en not_active Ceased
- 1988-07-20 EP EP88907258A patent/EP0425482B1/en not_active Expired - Lifetime
- 1988-07-20 AT AT88907258T patent/ATE93238T1/de not_active IP Right Cessation
- 1988-08-01 ES ES888802408A patent/ES2010299A6/es not_active Expired
-
1990
- 1990-12-19 NO NO90905472A patent/NO905472L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2263688A (en) | 1990-02-19 |
| WO1990001038A1 (en) | 1990-02-08 |
| US5149777A (en) | 1992-09-22 |
| AU616205B2 (en) | 1991-10-24 |
| FI910286A7 (fi) | 1991-01-18 |
| KR900701842A (ko) | 1990-12-04 |
| NO905472L (no) | 1991-03-20 |
| JPH03506023A (ja) | 1991-12-26 |
| EP0425482B1 (en) | 1993-08-18 |
| EP0425482A1 (en) | 1991-05-08 |
| FI910286A0 (fi) | 1991-01-18 |
| NO905472D0 (no) | 1990-12-19 |
| ATE93238T1 (de) | 1993-09-15 |
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