NO904791L - Fremgangsmaate for biokjemisk oksydasjon av steroider samtgenetisk omvandlede celler for anvendelse deri. - Google Patents

Fremgangsmaate for biokjemisk oksydasjon av steroider samtgenetisk omvandlede celler for anvendelse deri.

Info

Publication number
NO904791L
NO904791L NO90904791A NO904791A NO904791L NO 904791 L NO904791 L NO 904791L NO 90904791 A NO90904791 A NO 90904791A NO 904791 A NO904791 A NO 904791A NO 904791 L NO904791 L NO 904791L
Authority
NO
Norway
Prior art keywords
steroids
oxidation
cholesterol
host cells
biochemically
Prior art date
Application number
NO90904791A
Other languages
English (en)
Other versions
NO314267B1 (no
NO904791D0 (no
Inventor
Herman Slijkhuis
Gerardus Cornelis Maria Selten
Eric Bastiaan Smaal
Original Assignee
Roussel Uclaf
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Roussel Uclaf filed Critical Roussel Uclaf
Publication of NO904791D0 publication Critical patent/NO904791D0/no
Publication of NO904791L publication Critical patent/NO904791L/no
Publication of NO314267B1 publication Critical patent/NO314267B1/no

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
    • 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
    • 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
    • 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)

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  • 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)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Endocrinology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)
NO19904791A 1988-05-06 1990-11-05 Anvendelse av ekspresjonskassett i multigensystemer, ekspresjonskassett, rekombinant vertscelle, fremgangsmåte for fremstilling av enblanding av eksogeneproteiner, fremgangsmåte for selektiv biokjemisk oksydasjon, samtfremgangsmåtefor osydas NO314267B1 (no)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP88200904 1988-05-06
EP88202080 1988-09-23
PCT/NL1989/000032 WO1989010963A1 (en) 1988-05-06 1989-05-08 Process for the biochemical oxidation of steroids and genetically engineered cells to be used therefor

Publications (3)

Publication Number Publication Date
NO904791D0 NO904791D0 (no) 1990-11-05
NO904791L true NO904791L (no) 1991-01-04
NO314267B1 NO314267B1 (no) 2003-02-24

Family

ID=26115083

Family Applications (1)

Application Number Title Priority Date Filing Date
NO19904791A NO314267B1 (no) 1988-05-06 1990-11-05 Anvendelse av ekspresjonskassett i multigensystemer, ekspresjonskassett, rekombinant vertscelle, fremgangsmåte for fremstilling av enblanding av eksogeneproteiner, fremgangsmåte for selektiv biokjemisk oksydasjon, samtfremgangsmåtefor osydas

Country Status (16)

Country Link
JP (2) JP2963711B2 (no)
KR (1) KR100256025B1 (no)
CN (1) CN1038667A (no)
AT (1) ATE201235T1 (no)
AU (1) AU635494B2 (no)
CA (1) CA1340616C (no)
DE (1) DE68929296T2 (no)
DK (1) DK175573B1 (no)
ES (1) ES2157883T3 (no)
FI (1) FI109605B (no)
HU (1) HU217411B (no)
IL (1) IL90207A (no)
NO (1) NO314267B1 (no)
NZ (1) NZ229032A (no)
PT (1) PT90484B (no)
WO (1) WO1989010963A1 (no)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
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
US9255256B2 (en) 1996-07-17 2016-02-09 Btg International Limited Expression of functional cytochorome P450 monooxygenase system in enterobacteria
GB9615032D0 (en) 1996-07-17 1996-09-04 Univ Dundee Enzyme system
FR2820145B1 (fr) * 2001-01-31 2004-01-23 Aventis Pharma Sa Souche de levure produisant des steroides de facon autonome
WO2010079594A1 (ja) * 2009-01-07 2010-07-15 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
SG11201509965YA (en) * 2013-06-17 2016-01-28 Sanofi Sa Whole-cell system for cytochrome p450 monooxygenases biocatalysis
KR20160108540A (ko) * 2014-01-20 2016-09-19 사노피 증가된 효소 활성을 갖는 신규한 시토크롬 p450 폴리펩티드
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)

* Cited by examiner, † Cited by third party
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

Also Published As

Publication number Publication date
HUT54413A (en) 1991-02-28
IL90207A0 (en) 1989-12-15
DK264890A (da) 1990-11-05
KR900702022A (ko) 1990-12-05
JPH11308991A (ja) 1999-11-09
KR100256025B1 (ko) 2000-05-01
FI905464A0 (fi) 1990-11-05
DK264890D0 (da) 1990-11-05
AU3575989A (en) 1989-11-29
PT90484A (pt) 1989-11-30
JP2963711B2 (ja) 1999-10-18
HU217411B (hu) 2000-01-28
NO314267B1 (no) 2003-02-24
CA1340616C (en) 1999-06-29
AU635494B2 (en) 1993-03-25
CN1038667A (zh) 1990-01-10
FI109605B (fi) 2002-09-13
PT90484B (pt) 1994-08-31
DE68929296T2 (de) 2001-12-06
NZ229032A (en) 1992-06-25
ES2157883T3 (es) 2001-09-01
NO904791D0 (no) 1990-11-05
WO1989010963A1 (en) 1989-11-16
JPH04500303A (ja) 1992-01-23
ATE201235T1 (de) 2001-06-15
HU893289D0 (en) 1990-12-28
IL90207A (en) 1994-07-31
DK175573B1 (da) 2004-12-13
DE68929296D1 (de) 2001-06-21

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