NO301483B1 - Fremgangsmåte for fremstilling av humaninsulinanaloger - Google Patents
Fremgangsmåte for fremstilling av humaninsulinanaloger Download PDFInfo
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- NO301483B1 NO301483B1 NO912438A NO912438A NO301483B1 NO 301483 B1 NO301483 B1 NO 301483B1 NO 912438 A NO912438 A NO 912438A NO 912438 A NO912438 A NO 912438A NO 301483 B1 NO301483 B1 NO 301483B1
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- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- HHMSPIAOYISBOU-IYQBICMXSA-N insulin rabbit 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](CO)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 HHMSPIAOYISBOU-IYQBICMXSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 238000002103 osmometry Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940070353 protamines Drugs 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000007261 sc medium Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 239000007222 ypd medium Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 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
- C07K14/575—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Emergency Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Obesity (AREA)
- Pharmacology & Pharmacy (AREA)
- Hematology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Fats And Perfumes (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK721588A DK721588D0 (da) | 1988-12-23 | 1988-12-23 | Humaninsulinanaloger |
DK477789A DK477789D0 (da) | 1989-09-28 | 1989-09-28 | Nye polypeptider |
PCT/DK1989/000296 WO1990007522A1 (en) | 1988-12-23 | 1989-12-15 | Human insulin analogues |
Publications (3)
Publication Number | Publication Date |
---|---|
NO912438D0 NO912438D0 (no) | 1991-06-21 |
NO912438L NO912438L (no) | 1991-08-21 |
NO301483B1 true NO301483B1 (no) | 1997-11-03 |
Family
ID=26067619
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO912438A NO301483B1 (no) | 1988-12-23 | 1991-06-21 | Fremgangsmåte for fremstilling av humaninsulinanaloger |
Country Status (17)
Country | Link |
---|---|
US (1) | US5164366A (de) |
EP (3) | EP0837072B1 (de) |
JP (1) | JPH04502465A (de) |
KR (1) | KR910700262A (de) |
CN (1) | CN1043719A (de) |
AT (3) | ATE178908T1 (de) |
AU (1) | AU641631B2 (de) |
CA (1) | CA2006578A1 (de) |
DE (4) | DE68928917T2 (de) |
ES (1) | ES2134669T3 (de) |
FI (1) | FI913037A0 (de) |
HU (1) | HUT56857A (de) |
IL (1) | IL92853A0 (de) |
NO (1) | NO301483B1 (de) |
NZ (1) | NZ231936A (de) |
WO (1) | WO1990007522A1 (de) |
YU (1) | YU243689A (de) |
Families Citing this family (146)
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DK336188D0 (da) * | 1988-06-20 | 1988-06-20 | Nordisk Gentofte | Propeptider |
US6875589B1 (en) * | 1988-06-23 | 2005-04-05 | Hoechst Aktiengesellschaft | Mini-proinsulin, its preparation and use |
US5514646A (en) * | 1989-02-09 | 1996-05-07 | Chance; Ronald E. | Insulin analogs modified at position 29 of the B chain |
US5126249A (en) * | 1989-05-09 | 1992-06-30 | Eli Lilly And Company | Enzymatic removal of a protein amino-terminal sequence |
DK155690D0 (da) * | 1990-06-28 | 1990-06-28 | Novo Nordisk As | Nye peptider |
DK10191D0 (da) * | 1991-01-22 | 1991-01-22 | Novo Nordisk As | Hidtil ukendte peptider |
US5304473A (en) * | 1991-06-11 | 1994-04-19 | Eli Lilly And Company | A-C-B proinsulin, method of manufacturing and using same, and intermediates in insulin production |
DK72793D0 (da) * | 1993-06-21 | 1993-06-21 | Novo Nordisk As | Nyt produkt |
US6869930B1 (en) * | 1993-09-17 | 2005-03-22 | Novo Nordisk A/S | Acylated insulin |
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 |
AU3562195A (en) * | 1994-10-04 | 1996-04-26 | Novo Nordisk A/S | Preparations containing aspb28 human insulin and nicotinamide |
US5597893A (en) * | 1994-10-31 | 1997-01-28 | Eli Lilly And Company | Preparation of stable insulin analog crystals |
US5631347A (en) * | 1995-06-07 | 1997-05-20 | Eli Lilly And Company | Reducing gelation of a fatty acid-acylated protein |
CN1069649C (zh) * | 1996-01-25 | 2001-08-15 | 中国科学院上海生物化学研究所 | [b9谷氨酸,b10门冬氨酸]人胰岛素 |
US5948751A (en) * | 1996-06-20 | 1999-09-07 | Novo Nordisk A/S | X14-mannitol |
DE19726167B4 (de) * | 1997-06-20 | 2008-01-24 | Sanofi-Aventis Deutschland Gmbh | Insulin, Verfahren zu seiner Herstellung und es enthaltende pharmazeutische Zubereitung |
HUP0004169A3 (en) | 1997-10-24 | 2001-06-28 | Lilly Co Eli | Insoluble insulin compositions and process for production thereof |
ES2230727T3 (es) * | 1997-11-12 | 2005-05-01 | Alza Corporation | Procedimiento de administracion dermal de polipeptidos. |
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 |
US7169889B1 (en) | 1999-06-19 | 2007-01-30 | Biocon Limited | Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin |
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US7022674B2 (en) * | 1999-12-16 | 2006-04-04 | Eli Lilly And Company | Polypeptide compositions with improved stability |
EP1265630B1 (de) | 2000-03-24 | 2006-06-07 | Genentech, Inc. | Verwendung von insulin zur behandlung von knorpelkrankheiten |
US6867183B2 (en) | 2001-02-15 | 2005-03-15 | Nobex Corporation | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
US7060675B2 (en) | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
US7202059B2 (en) | 2001-02-20 | 2007-04-10 | Sanofi-Aventis Deutschland Gmbh | Fusion proteins capable of being secreted into a fermentation medium |
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 |
US6852694B2 (en) * | 2001-02-21 | 2005-02-08 | Medtronic Minimed, Inc. | Stabilized insulin formulations |
DE10114178A1 (de) | 2001-03-23 | 2002-10-10 | Aventis Pharma Gmbh | Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität |
US6835802B2 (en) * | 2001-06-04 | 2004-12-28 | Nobex Corporation | Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties |
US6713452B2 (en) | 2001-06-04 | 2004-03-30 | Nobex Corporation | Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
US6828297B2 (en) | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
US7713932B2 (en) | 2001-06-04 | 2010-05-11 | Biocon Limited | Calcitonin drug-oligomer conjugates, and uses thereof |
US6858580B2 (en) * | 2001-06-04 | 2005-02-22 | Nobex Corporation | Mixtures of drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
US6828305B2 (en) | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of growth hormone drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
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US6913903B2 (en) | 2001-09-07 | 2005-07-05 | Nobex Corporation | Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
US7166571B2 (en) | 2001-09-07 | 2007-01-23 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
US7196059B2 (en) | 2001-09-07 | 2007-03-27 | Biocon Limited | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
US7312192B2 (en) | 2001-09-07 | 2007-12-25 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
US6770625B2 (en) | 2001-09-07 | 2004-08-03 | Nobex Corporation | Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith |
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PT3300721T (pt) | 2003-11-20 | 2019-06-06 | Novo Nordisk As | Formulações peptidicas contendo propileno glicol que sao ideais para a produção e para utilizacao em dispositivos de injeção |
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JPS55138393A (en) * | 1979-04-13 | 1980-10-29 | Shionogi & Co Ltd | Semisynthesis of insulin |
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-
1989
- 1989-12-15 JP JP2501698A patent/JPH04502465A/ja active Pending
- 1989-12-15 KR KR1019900701869A patent/KR910700262A/ko not_active Application Discontinuation
- 1989-12-15 HU HU90984A patent/HUT56857A/hu unknown
- 1989-12-15 AU AU48344/90A patent/AU641631B2/en not_active Ceased
- 1989-12-15 WO PCT/DK1989/000296 patent/WO1990007522A1/en active Application Filing
- 1989-12-20 US US07/453,445 patent/US5164366A/en not_active Expired - Fee Related
- 1989-12-21 AT AT97121214T patent/ATE178908T1/de not_active IP Right Cessation
- 1989-12-21 DE DE68928917T patent/DE68928917T2/de not_active Expired - Fee Related
- 1989-12-21 DE DE0861851T patent/DE861851T1/de active Pending
- 1989-12-21 DE DE68928810T patent/DE68928810T2/de not_active Expired - Fee Related
- 1989-12-21 ES ES97121214T patent/ES2134669T3/es not_active Expired - Lifetime
- 1989-12-21 AT AT89313460T patent/ATE170875T1/de active
- 1989-12-21 AT AT97121213T patent/ATE175974T1/de active
- 1989-12-21 EP EP97121213A patent/EP0837072B1/de not_active Expired - Lifetime
- 1989-12-21 DE DE68928971T patent/DE68928971T2/de not_active Expired - Fee Related
- 1989-12-21 EP EP97121214A patent/EP0861851B1/de not_active Expired - Lifetime
- 1989-12-21 NZ NZ231936A patent/NZ231936A/en unknown
- 1989-12-21 EP EP89313460A patent/EP0375437B1/de not_active Expired - Lifetime
- 1989-12-22 IL IL92853A patent/IL92853A0/xx unknown
- 1989-12-22 CA CA002006578A patent/CA2006578A1/en not_active Abandoned
- 1989-12-22 YU YU02436/89A patent/YU243689A/xx unknown
- 1989-12-23 CN CN89109575A patent/CN1043719A/zh active Pending
-
1991
- 1991-06-20 FI FI913037A patent/FI913037A0/fi not_active Application Discontinuation
- 1991-06-21 NO NO912438A patent/NO301483B1/no unknown
Also Published As
Publication number | Publication date |
---|---|
DE68928810D1 (de) | 1998-10-15 |
DE861851T1 (de) | 1999-04-22 |
EP0837072A3 (de) | 1998-08-19 |
IL92853A0 (en) | 1990-09-17 |
ATE178908T1 (de) | 1999-04-15 |
YU243689A (en) | 1991-10-31 |
DE68928917D1 (de) | 1999-03-04 |
FI913037A0 (fi) | 1991-06-20 |
JPH04502465A (ja) | 1992-05-07 |
DE68928810T2 (de) | 1999-03-18 |
NO912438L (no) | 1991-08-21 |
EP0861851A1 (de) | 1998-09-02 |
NO912438D0 (no) | 1991-06-21 |
HUT56857A (en) | 1991-10-28 |
ATE170875T1 (de) | 1998-09-15 |
AU641631B2 (en) | 1993-09-30 |
EP0375437B1 (de) | 1998-09-09 |
AU4834490A (en) | 1990-08-01 |
CA2006578A1 (en) | 1990-06-23 |
EP0837072A2 (de) | 1998-04-22 |
DE68928971T2 (de) | 1999-12-02 |
EP0375437A2 (de) | 1990-06-27 |
DE68928917T2 (de) | 1999-08-05 |
ATE175974T1 (de) | 1999-02-15 |
NZ231936A (en) | 1992-04-28 |
WO1990007522A1 (en) | 1990-07-12 |
EP0861851B1 (de) | 1999-04-14 |
EP0837072B1 (de) | 1999-01-20 |
KR910700262A (ko) | 1991-03-14 |
EP0375437A3 (de) | 1991-09-11 |
ES2134669T3 (es) | 1999-10-01 |
CN1043719A (zh) | 1990-07-11 |
DE68928971D1 (de) | 1999-05-27 |
US5164366A (en) | 1992-11-17 |
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