PT90484A - Processo para a oxidacao bioquimica de esteroides e para a preparacao por engenharia genetica de celulas para esse fim - Google Patents
Processo para a oxidacao bioquimica de esteroides e para a preparacao por engenharia genetica de celulas para esse fimInfo
- Publication number
- PT90484A PT90484A PT90484A PT9048489A PT90484A PT 90484 A PT90484 A PT 90484A PT 90484 A PT90484 A PT 90484A PT 9048489 A PT9048489 A PT 9048489A PT 90484 A PT90484 A PT 90484A
- Authority
- PT
- Portugal
- Prior art keywords
- steroids
- cholesterol
- host cells
- cells
- preparation
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y106/00—Oxidoreductases acting on NADH or NADPH (1.6)
- C12Y106/02—Oxidoreductases acting on NADH or NADPH (1.6) with a heme protein as acceptor (1.6.2)
- C12Y106/02004—NADPH-hemoprotein reductase (1.6.2.4), i.e. NADP-cytochrome P450-reductase
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0007—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa
- C07J5/0023—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa substituted in position 16
- C07J5/003—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group including 16-alkylidene substitutes
- C07J5/0038—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group including 16-alkylidene substitutes by an alkyl group
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
- C07J13/005—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 16 (17)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
- C07J13/007—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 17 (20)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J21/005—Ketals
- C07J21/006—Ketals at position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0007—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa
- C07J5/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa
- C07J7/002—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/004—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa
- C07J7/0045—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/008—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21
- C07J7/009—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21 by only one oxygen atom doubly bound
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0006—Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
- C12N9/0036—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on NADH or NADPH (1.6)
- C12N9/0038—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on NADH or NADPH (1.6) with a heme protein as acceptor (1.6.2)
- C12N9/0042—NADPH-cytochrome P450 reductase (1.6.2.4)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0071—Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0095—Oxidoreductases (1.) acting on iron-sulfur proteins as donor (1.18)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P33/00—Preparation of steroids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
- C12Y101/01—Oxidoreductases acting on the CH-OH group of donors (1.1) with NAD+ or NADP+ as acceptor (1.1.1)
- C12Y101/01053—3-Alpha (or 20-beta)-hydroxysteroid dehydrogenase (1.1.1.53)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y114/00—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14)
- C12Y114/15—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14) with reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen (1.14.15)
- C12Y114/15004—Steroid 11-beta-monooxygenase (1.14.15.4)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y114/00—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14)
- C12Y114/15—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14) with reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen (1.14.15)
- C12Y114/15006—Cholesterol monooxygenase (side-chain-cleaving) (1.14.15.6), i.e. cytochrome P450scc
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y114/00—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14)
- C12Y114/99—Miscellaneous (1.14.99)
- C12Y114/99009—Steroid 17-alpha-monooxygenase (1.14.99.9), i.e. cytochrome-P450-steroid-17-alpha-hydroxylase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y118/00—Oxidoreductases acting on iron-sulfur proteins as donors (1.18)
- C12Y118/01—Oxidoreductases acting on iron-sulfur proteins as donors (1.18) with NAD+ or NADP+ as acceptor (1.18.1)
- C12Y118/01002—Ferredoxin-NADP+ reductase (1.18.1.2)
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Physics & Mathematics (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Plant Pathology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Steroid Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP88200904 | 1988-05-06 | ||
EP88202080 | 1988-09-23 |
Publications (2)
Publication Number | Publication Date |
---|---|
PT90484A true PT90484A (pt) | 1989-11-30 |
PT90484B PT90484B (pt) | 1994-08-31 |
Family
ID=26115083
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PT90484A PT90484B (pt) | 1988-05-06 | 1989-05-05 | Processo para a oxidacao bioquimica de esteroides e para a preparacao por engenharia genetica de celulas para esse fim |
Country Status (16)
Country | Link |
---|---|
JP (2) | JP2963711B2 (pt) |
KR (1) | KR100256025B1 (pt) |
CN (1) | CN1038667A (pt) |
AT (1) | ATE201235T1 (pt) |
AU (1) | AU635494B2 (pt) |
CA (1) | CA1340616C (pt) |
DE (1) | DE68929296T2 (pt) |
DK (1) | DK175573B1 (pt) |
ES (1) | ES2157883T3 (pt) |
FI (1) | FI109605B (pt) |
HU (1) | HU217411B (pt) |
IL (1) | IL90207A (pt) |
NO (1) | NO314267B1 (pt) |
NZ (1) | NZ229032A (pt) |
PT (1) | PT90484B (pt) |
WO (1) | WO1989010963A1 (pt) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1042567A (zh) * | 1988-09-23 | 1990-05-30 | 吉斯特-布罗卡迪斯公司 | 类固醇多步氧化方法和所用的遗传工程细胞 |
DE69122016T2 (de) * | 1990-09-26 | 1997-04-30 | Sumitomo Chemical Co | Mitochondriales P450 |
US5420027A (en) * | 1991-01-10 | 1995-05-30 | Board Of Regents, The University Of Texas System | Methods and compositions for the expression of biologically active fusion proteins comprising a eukaryotic cytochrome P450 fused to a reductase in bacteria |
US5240831A (en) * | 1991-01-10 | 1993-08-31 | Board Of Regents, The University Of Texas | Methods and compositions for the expression of biologically active eukaryotic cytochrome p45os in bacteria |
GB9615032D0 (en) | 1996-07-17 | 1996-09-04 | Univ Dundee | Enzyme system |
US9255256B2 (en) | 1996-07-17 | 2016-02-09 | Btg International Limited | Expression of functional cytochorome P450 monooxygenase system in enterobacteria |
FR2820145B1 (fr) * | 2001-01-31 | 2004-01-23 | Aventis Pharma Sa | Souche de levure produisant des steroides de facon autonome |
EP2386634A4 (en) * | 2009-01-07 | 2012-07-18 | Mitsubishi Chem Corp | ENZYMATIC STEROL LATERAL CHAIN CLEAVAGE PROTEIN AND USE THEREOF |
KR20160019451A (ko) | 2013-06-17 | 2016-02-19 | 사노피 | 시토크롬 p450 모노옥시게나제 생체촉매작용을 위한 전세포 시스템 |
CA2936954A1 (en) * | 2014-01-20 | 2015-07-23 | Sanofi | Novel cytochrome p450 polypeptide with increased enzymatic activity |
JP5800040B2 (ja) * | 2014-01-29 | 2015-10-28 | 三菱化学株式会社 | ステロール側鎖切断酵素蛋白質およびその利用 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4720454A (en) * | 1984-04-18 | 1988-01-19 | White Perrin C | Genetic probe used in the detection of adrenal hyperplasia |
-
1989
- 1989-05-05 PT PT90484A patent/PT90484B/pt not_active IP Right Cessation
- 1989-05-05 IL IL9020789A patent/IL90207A/xx unknown
- 1989-05-06 CN CN89104208A patent/CN1038667A/zh active Pending
- 1989-05-08 DE DE68929296T patent/DE68929296T2/de not_active Expired - Lifetime
- 1989-05-08 CA CA000599041A patent/CA1340616C/en not_active Expired - Lifetime
- 1989-05-08 NZ NZ229032A patent/NZ229032A/en unknown
- 1989-05-08 JP JP1505707A patent/JP2963711B2/ja not_active Expired - Lifetime
- 1989-05-08 AU AU35759/89A patent/AU635494B2/en not_active Expired
- 1989-05-08 HU HU289/89A patent/HU217411B/hu unknown
- 1989-05-08 KR KR1019900700022A patent/KR100256025B1/ko not_active IP Right Cessation
- 1989-05-08 AT AT89201173T patent/ATE201235T1/de not_active IP Right Cessation
- 1989-05-08 WO PCT/NL1989/000032 patent/WO1989010963A1/en active IP Right Grant
- 1989-05-08 ES ES89201173T patent/ES2157883T3/es not_active Expired - Lifetime
-
1990
- 1990-11-05 FI FI905464A patent/FI109605B/fi not_active IP Right Cessation
- 1990-11-05 DK DK199002648A patent/DK175573B1/da not_active IP Right Cessation
- 1990-11-05 NO NO19904791A patent/NO314267B1/no not_active IP Right Cessation
-
1999
- 1999-03-23 JP JP11078556A patent/JPH11308991A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
KR100256025B1 (ko) | 2000-05-01 |
CN1038667A (zh) | 1990-01-10 |
NZ229032A (en) | 1992-06-25 |
NO904791L (no) | 1991-01-04 |
WO1989010963A1 (en) | 1989-11-16 |
HU217411B (hu) | 2000-01-28 |
JP2963711B2 (ja) | 1999-10-18 |
DE68929296D1 (de) | 2001-06-21 |
ES2157883T3 (es) | 2001-09-01 |
DK264890D0 (da) | 1990-11-05 |
FI905464A0 (fi) | 1990-11-05 |
KR900702022A (ko) | 1990-12-05 |
CA1340616C (en) | 1999-06-29 |
IL90207A (en) | 1994-07-31 |
HUT54413A (en) | 1991-02-28 |
AU3575989A (en) | 1989-11-29 |
DE68929296T2 (de) | 2001-12-06 |
NO904791D0 (no) | 1990-11-05 |
HU893289D0 (en) | 1990-12-28 |
NO314267B1 (no) | 2003-02-24 |
JPH11308991A (ja) | 1999-11-09 |
IL90207A0 (en) | 1989-12-15 |
ATE201235T1 (de) | 2001-06-15 |
DK175573B1 (da) | 2004-12-13 |
PT90484B (pt) | 1994-08-31 |
JPH04500303A (ja) | 1992-01-23 |
FI109605B (fi) | 2002-09-13 |
AU635494B2 (en) | 1993-03-25 |
DK264890A (da) | 1990-11-05 |
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