ES8708251A1 - Un metodo de producir insulina humana - Google Patents
Un metodo de producir insulina humanaInfo
- Publication number
- ES8708251A1 ES8708251A1 ES557227A ES557227A ES8708251A1 ES 8708251 A1 ES8708251 A1 ES 8708251A1 ES 557227 A ES557227 A ES 557227A ES 557227 A ES557227 A ES 557227A ES 8708251 A1 ES8708251 A1 ES 8708251A1
- Authority
- ES
- Spain
- Prior art keywords
- preparation
- insulin
- human insulin
- precursors
- insulin precursors
- 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
- 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 title abstract 6
- 101000976075 Homo sapiens Insulin Proteins 0.000 title abstract 5
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound 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 5
- 239000002243 precursor Substances 0.000 title abstract 5
- 102000004877 Insulin Human genes 0.000 title abstract 3
- 108090001061 Insulin Proteins 0.000 title abstract 3
- 229940125396 insulin Drugs 0.000 title abstract 3
- 238000000034 method Methods 0.000 title 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 abstract 2
- 239000004475 Arginine Substances 0.000 abstract 1
- 239000004472 Lysine Substances 0.000 abstract 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 abstract 1
- 108091028043 Nucleic acid sequence Proteins 0.000 abstract 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 abstract 1
- 238000012258 culturing Methods 0.000 abstract 1
- 230000002255 enzymatic effect Effects 0.000 abstract 1
- 239000001963 growth medium Substances 0.000 abstract 1
- 238000011084 recovery Methods 0.000 abstract 1
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
- C12N15/80—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/37—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi
- C07K14/39—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi from yeasts
-
- 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
-
- 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)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Mycology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Diabetes (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Endocrinology (AREA)
- Toxicology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Management, Administration, Business Operations System, And Electronic Commerce (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
METODO DE PRODUCIR INSULINA HUMANA. COMPRENDE: A) CULTIVAR UNA CEPA DE LEVADURA, TRANSFORMADA CON UN VEHICULO DE EXPRESION QUE COMPRENDE UNA SECUENCIA DE ADN QUE CODIFICA UN PRECURSOR DE INSULINA DE FORMULA B-X-Y-A, EN UN MEDIO ADECUADO; B) RECUPERAR EL PRECURSOR DE LA INSULINA DEL MEDIO DE CULTIVO Y CONVERTIRLO EN INSULINA HUMANA TRATANDOLO CON UNA DISOLUCION ACUOSA DE TRIPSINA Y CARBOXIPEPTIDASA B. SIENDO: B Y A, LA CADENA B- Y A- DE LA INSULINA HUMANA; Y X E Y, INDIVIDUALMENTE LISINA O ARGININA.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK129385A DK129385A (da) | 1985-03-22 | 1985-03-22 | Peptider og fremstilling deraf |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ES8708251A1 true ES8708251A1 (es) | 1987-10-01 |
| ES557227A0 ES557227A0 (es) | 1987-10-01 |
Family
ID=8103207
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES553231A Expired ES8802402A1 (es) | 1985-03-22 | 1986-03-21 | Un metodo para producir precursores de insulina humana. |
| ES557227A Expired ES8708251A1 (es) | 1985-03-22 | 1986-11-28 | Un metodo de producir insulina humana |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES553231A Expired ES8802402A1 (es) | 1985-03-22 | 1986-03-21 | Un metodo para producir precursores de insulina humana. |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP0195691B1 (es) |
| JP (3) | JPH0648993B2 (es) |
| AT (1) | ATE69266T1 (es) |
| AU (1) | AU586855B2 (es) |
| CA (1) | CA1340823C (es) |
| DE (1) | DE3682303D1 (es) |
| DK (1) | DK129385A (es) |
| ES (2) | ES8802402A1 (es) |
| FI (1) | FI87801C (es) |
| GR (1) | GR860764B (es) |
| IE (1) | IE58842B1 (es) |
| MX (1) | MX163837B (es) |
| NO (1) | NO172646C (es) |
| NZ (1) | NZ215570A (es) |
| PT (1) | PT82241B (es) |
| ZA (1) | ZA861953B (es) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK58285D0 (da) * | 1984-05-30 | 1985-02-08 | Novo Industri As | Peptider samt fremstilling og anvendelse deraf |
| EP0208418B1 (en) * | 1985-06-12 | 1991-10-30 | Lubrizol Genetics Inc. | Modified zein |
| 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 |
| US5426036A (en) * | 1987-05-05 | 1995-06-20 | Hoechst Aktiengesellschaft | Processes for the preparation of foreign proteins in streptomycetes |
| DE3837271A1 (de) * | 1988-11-03 | 1990-05-10 | Hoechst Ag | Verfahren zur selektiven spaltung von fusionsproteinen |
| CA1340772C (en) * | 1987-12-30 | 1999-09-28 | Patricia Tekamp-Olson | Expression and secretion of heterologous protiens in yeast employing truncated alpha-factor leader sequences |
| DK336188D0 (da) * | 1988-06-20 | 1988-06-20 | Nordisk Gentofte | Propeptider |
| EP0347781B1 (de) * | 1988-06-23 | 1994-02-16 | Hoechst Aktiengesellschaft | Mini-Proinsulin, seine Herstellung und Verwendung |
| US6875589B1 (en) | 1988-06-23 | 2005-04-05 | Hoechst Aktiengesellschaft | Mini-proinsulin, its preparation and use |
| ES2081826T3 (es) * | 1988-11-03 | 1996-03-16 | Hoechst Ag | Procedimiento para la preparacion de un producto previo de insulina en estreptomicetos. |
| US5716927A (en) * | 1988-12-23 | 1998-02-10 | Novo Nordisk A/S | Insulin analogs having a modified B-chain |
| DE3844211A1 (de) * | 1988-12-29 | 1990-07-05 | Hoechst Ag | Neue insulinderivate, verfahren zu deren herstellung, ihre verwendung und eine sie enthaltende pharmazeutische zubereitung |
| IL93282A (en) * | 1989-02-09 | 1995-08-31 | Lilly Co Eli | Insulin analogues |
| DK134189D0 (da) * | 1989-03-20 | 1989-03-20 | Nordisk Gentofte | Insulinforbindelser |
| CA2051375C (en) * | 1989-05-04 | 2000-09-12 | Dennis J. Henner | Process and compositions for the isolation of human relaxin |
| NZ239652A (en) * | 1990-09-05 | 1992-09-25 | Hoechst Ag | Hydrolysis of preproinsulin to insulin and analogues using clostripain and optionally carboxypeptidase |
| TW224471B (es) * | 1991-11-26 | 1994-06-01 | Lilly Co Eli | |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| US6001604A (en) * | 1993-12-29 | 1999-12-14 | Bio-Technology General Corp. | Refolding of proinsulins without addition of reducing agents |
| ATE350053T1 (de) * | 1994-12-29 | 2007-01-15 | Ferring Int Ct Sa | Herstellung von humaninsulin |
| KR0150565B1 (ko) * | 1995-02-15 | 1998-08-17 | 김정재 | 유전자 조환에 의한 사람 인슐린 전구체의 제조 및 이를 이용한 인슐린의 제조방법 |
| IL118127A0 (en) * | 1995-05-05 | 1996-09-12 | Lilly Co Eli | Single chain insulin with high bioactivity |
| GB9513967D0 (en) * | 1995-07-08 | 1995-09-06 | Univ Leicester | Insulin |
| KR100381494B1 (ko) * | 1997-06-30 | 2003-07-22 | 바이오 테크놀로지 제네랄 코오포레이션 | 인간인슐린의제조방법 |
| WO1999009816A1 (de) * | 1997-08-22 | 1999-03-04 | Roche Diagnostics Gmbh | Verfahren zur gewinnung von insulin precursorproteinen |
| DE19930676B4 (de) | 1999-07-02 | 2006-01-19 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur Stabilisierung von Insulin, Insulinderivaten und/oder deren Vorläufer in komplexen Mischungen bei deren Lagerung in wäßrigen Lösungsmitteln |
| AU4935701A (en) | 2000-03-24 | 2001-10-08 | Genentech Inc | Use of insulin for the treatment of cartilagenous disorders |
| US6926898B2 (en) | 2000-04-12 | 2005-08-09 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| AR025646A1 (es) | 2000-09-13 | 2002-12-04 | Beta Lab Sa | Cepa de levaduras metilotroficas recombinantes productoras de un precursor de insulina, construcciones de adn y metodo para obtener la cepa. |
| US7638618B2 (en) | 2001-02-20 | 2009-12-29 | Sanofi-Aventis Deutschland Gmbh | Nucleic acids encoding a hirudin and pro-insulin as superscretable peptides and for parallel improvement of the exported forms of one or more polypeptides of interest |
| US7202059B2 (en) | 2001-02-20 | 2007-04-10 | Sanofi-Aventis Deutschland Gmbh | Fusion proteins capable of being secreted into a fermentation medium |
| US7312192B2 (en) * | 2001-09-07 | 2007-12-25 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| WO2005003296A2 (en) | 2003-01-22 | 2005-01-13 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| CA2841097A1 (en) | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin and g-csf fusion proteins |
| ES2570937T3 (es) | 2008-08-07 | 2016-05-23 | Biocon Ltd | Un proceso para la preparación de compuestos de insulina |
| AR072563A1 (es) * | 2009-07-15 | 2010-09-08 | Beta Lab Sa | Un procedimiento para obtener insulina aspartica que utiliza una cepa de levaduras de pichia pastoris |
| PL239062B1 (pl) * | 2016-01-22 | 2021-11-02 | Inst Biotechnologii I Antybiotykow | Sposób wytwarzania insuliny i jej pochodnych |
| BR112019004314A2 (pt) * | 2016-09-06 | 2019-05-28 | Chemical & Biopharmaceutical Laboratories Of Patras S A | derivados pró-insulina |
| KR102666154B1 (ko) | 2018-08-08 | 2024-05-20 | 주식회사 대웅제약 | 지속형 인슐린 아날로그 및 그 복합체 |
| KR102646845B1 (ko) | 2018-08-08 | 2024-03-14 | 주식회사 대웅제약 | 클로스트리파인을 이용한 지속형 인슐린 아날로그 복합체의 활성형 제조방법 |
| CN113226284B (zh) * | 2018-09-25 | 2024-12-03 | 美药星制药股份有限公司 | 高度纯化的重组人胰岛素（rhi）api及其生产方法 |
| KR20200080747A (ko) * | 2018-12-27 | 2020-07-07 | 주식회사 폴루스 | 인슐린 전구체의 인슐린 효소 전환용 조성물 및 이를 이용하여 인슐린 전구체를 인슐린으로 전환하는 방법 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PH16156A (en) * | 1980-03-27 | 1983-07-18 | Lilly Co Eli | Process for producing an insulin precursor |
| NZ199391A (en) * | 1981-01-02 | 1985-12-13 | Genentech Inc | Chimeric polypeptides comprising a proinsulin sequence,and preparation by recombinant dna technique;production of human insulin |
| DE3209184A1 (de) * | 1982-03-13 | 1983-09-15 | Hoechst Ag, 6230 Frankfurt | Verfahren zur umwandlung von praeproinsulinanaloga zu insulinen |
| DK172738B1 (da) * | 1983-04-07 | 1999-06-21 | Chiron Corp | Fremgangsmåde til at udtrykke modent insulin og DNA-struktur til anvendelse ved fremgangsmåden |
| DK58285D0 (da) * | 1984-05-30 | 1985-02-08 | Novo Industri As | Peptider samt fremstilling og anvendelse deraf |
-
1985
- 1985-03-22 DK DK129385A patent/DK129385A/da not_active Application Discontinuation
-
1986
- 1986-03-17 ZA ZA861953A patent/ZA861953B/xx unknown
- 1986-03-20 JP JP61060995A patent/JPH0648993B2/ja not_active Expired - Lifetime
- 1986-03-20 MX MX1947A patent/MX163837B/es unknown
- 1986-03-20 CA CA000504650A patent/CA1340823C/en not_active Expired - Fee Related
- 1986-03-21 ES ES553231A patent/ES8802402A1/es not_active Expired
- 1986-03-21 NZ NZ215570A patent/NZ215570A/xx unknown
- 1986-03-21 FI FI861198A patent/FI87801C/fi not_active IP Right Cessation
- 1986-03-21 GR GR860764A patent/GR860764B/el unknown
- 1986-03-21 AT AT86302133T patent/ATE69266T1/de not_active IP Right Cessation
- 1986-03-21 IE IE73786A patent/IE58842B1/en not_active IP Right Cessation
- 1986-03-21 AU AU55005/86A patent/AU586855B2/en not_active Ceased
- 1986-03-21 NO NO861120A patent/NO172646C/no not_active IP Right Cessation
- 1986-03-21 EP EP86302133A patent/EP0195691B1/en not_active Expired - Lifetime
- 1986-03-21 DE DE8686302133T patent/DE3682303D1/de not_active Expired - Lifetime
- 1986-03-21 PT PT82241A patent/PT82241B/pt not_active IP Right Cessation
- 1986-11-28 ES ES557227A patent/ES8708251A1/es not_active Expired
-
1993
- 1993-05-24 JP JP5121394A patent/JPH088871B2/ja not_active Expired - Lifetime
-
1995
- 1995-07-14 JP JP7178875A patent/JP2553326B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP0195691A1 (en) | 1986-09-24 |
| AU5500586A (en) | 1986-09-25 |
| FI861198A0 (fi) | 1986-03-21 |
| DK129385D0 (da) | 1985-03-22 |
| JPH0648993B2 (ja) | 1994-06-29 |
| ES8802402A1 (es) | 1988-05-16 |
| CA1340823C (en) | 1999-11-16 |
| GR860764B (en) | 1986-07-21 |
| EP0195691B1 (en) | 1991-11-06 |
| ATE69266T1 (de) | 1991-11-15 |
| JP2553326B2 (ja) | 1996-11-13 |
| FI87801C (fi) | 1993-02-25 |
| FI861198L (fi) | 1986-09-23 |
| ZA861953B (en) | 1986-11-26 |
| FI87801B (fi) | 1992-11-13 |
| JPH0823985A (ja) | 1996-01-30 |
| JPS61221200A (ja) | 1986-10-01 |
| NO172646B (no) | 1993-05-10 |
| PT82241B (pt) | 1988-11-30 |
| DK129385A (da) | 1986-09-23 |
| AU586855B2 (en) | 1989-07-27 |
| PT82241A (en) | 1986-04-01 |
| JPH088871B2 (ja) | 1996-01-31 |
| ES553231A0 (es) | 1988-05-16 |
| NO861120L (no) | 1986-09-23 |
| JPH06133777A (ja) | 1994-05-17 |
| NO172646C (no) | 1993-08-18 |
| MX163837B (es) | 1992-06-25 |
| IE860737L (en) | 1986-09-22 |
| IE58842B1 (en) | 1993-11-17 |
| ES557227A0 (es) | 1987-10-01 |
| NZ215570A (en) | 1989-07-27 |
| DE3682303D1 (de) | 1991-12-12 |
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