ATE323158T1 - Verwendung von vernetzten kristallen als neue form von immobilisierung von enzymen - Google Patents

Verwendung von vernetzten kristallen als neue form von immobilisierung von enzymen

Info

Publication number
ATE323158T1
ATE323158T1 AT98105856T AT98105856T ATE323158T1 AT E323158 T1 ATE323158 T1 AT E323158T1 AT 98105856 T AT98105856 T AT 98105856T AT 98105856 T AT98105856 T AT 98105856T AT E323158 T1 ATE323158 T1 AT E323158T1
Authority
AT
Austria
Prior art keywords
cross
clecs
crystals
enzyme
new form
Prior art date
Application number
AT98105856T
Other languages
English (en)
Inventor
Manuel A Navia
Clair Nancy L St
Original Assignee
Vertex Pharma
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 Vertex Pharma filed Critical Vertex Pharma
Application granted granted Critical
Publication of ATE323158T1 publication Critical patent/ATE323158T1/de

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531Production of immunochemical test materials
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06104Dipeptides with the first amino acid being acidic
    • C07K5/06113Asp- or Asn-amino acid
    • C07K5/06121Asp- or Asn-amino acid the second amino acid being aromatic or cycloaliphatic
    • C07K5/0613Aspartame
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N11/00Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/16Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/18Carboxylic ester hydrolases (3.1.1)
    • C12N9/20Triglyceride splitting, e.g. by means of lipase
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/24Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2462Lysozyme (3.2.1.17)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/52Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
    • C12N9/54Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea bacteria being Bacillus
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/6448Elastases, e.g. pancreatic elastase (3.4.21.36); leukocyte elastase (3.4.31.37)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/78Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C12N9/80Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/78Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C12N9/80Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
    • C12N9/82Asparaginase (3.5.1.1)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001Enzyme electrodes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001Enzyme electrodes
    • C12Q1/002Electrode membranes
    • C12Q1/003Functionalisation
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/37Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Analytical Chemistry (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Liquid Crystal Substances (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Crystals, And After-Treatments Of Crystals (AREA)
  • Piezo-Electric Or Mechanical Vibrators, Or Delay Or Filter Circuits (AREA)
AT98105856T 1990-08-03 1991-07-30 Verwendung von vernetzten kristallen als neue form von immobilisierung von enzymen ATE323158T1 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US56228090A 1990-08-03 1990-08-03

Publications (1)

Publication Number Publication Date
ATE323158T1 true ATE323158T1 (de) 2006-04-15

Family

ID=24245600

Family Applications (2)

Application Number Title Priority Date Filing Date
AT91914256T ATE240391T1 (de) 1990-08-03 1991-07-30 Verwendung von vernetzten kristallen als neuem verfahren zur immobilisierung von enzymen
AT98105856T ATE323158T1 (de) 1990-08-03 1991-07-30 Verwendung von vernetzten kristallen als neue form von immobilisierung von enzymen

Family Applications Before (1)

Application Number Title Priority Date Filing Date
AT91914256T ATE240391T1 (de) 1990-08-03 1991-07-30 Verwendung von vernetzten kristallen als neuem verfahren zur immobilisierung von enzymen

Country Status (25)

Country Link
EP (2) EP0550450B1 (de)
JP (2) JPH05508549A (de)
AT (2) ATE240391T1 (de)
AU (1) AU662104B2 (de)
BR (1) BR9106732A (de)
CA (1) CA2087730C (de)
CZ (1) CZ12393A3 (de)
DE (2) DE69133521T2 (de)
DK (2) DK0861888T3 (de)
ES (2) ES2263187T3 (de)
FI (1) FI120099B (de)
HU (2) HUT65904A (de)
IE (1) IE912767A1 (de)
IL (1) IL99046A (de)
LT (1) LT3366B (de)
LV (1) LV10304B (de)
MD (1) MD1592B2 (de)
NO (1) NO930360L (de)
PT (1) PT98564B (de)
RU (1) RU2124052C1 (de)
SG (1) SG70966A1 (de)
SK (1) SK283185B6 (de)
TJ (1) TJ210R3 (de)
UA (1) UA27035C2 (de)
WO (1) WO1992002617A1 (de)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5932212A (en) * 1996-05-24 1999-08-03 Altus Biologics, Inc. Crosslinked protein crystal formulations and their use as catalysts in organic solvents
WO1998013119A1 (en) * 1996-09-24 1998-04-02 Altus Biologics Inc. Crosslinked protein crystals as universal separation media
US6140475A (en) * 1997-04-11 2000-10-31 Altus Biologics Inc. Controlled dissolution crosslinked protein crystals
ATE397013T1 (de) 1997-09-05 2008-06-15 Altus Pharmaceuticals Inc Kohlenhydrat-vernetzte glykoproteinkristalle
US6500933B1 (en) 1997-09-05 2002-12-31 Altus Biologics Inc. Methods of preparing carbohydrate crosslinked glycoprotein crystals
US6979561B1 (en) 1998-10-09 2005-12-27 Gilead Sciences, Inc. Non-homogeneous systems for the resolution of enantiomeric mixtures
GB9823334D0 (en) 1998-10-23 1998-12-23 Darwin Discovery Ltd Enzyme coupling
EP1372703A2 (de) * 2001-02-16 2004-01-02 Ibex Technologies Matrixstabilisierte enzymkristalle und ihre verwendung
US7241272B2 (en) 2001-11-13 2007-07-10 Baxter International Inc. Method and composition for removing uremic toxins in dialysis processes
DK1699921T3 (da) * 2004-01-01 2010-02-01 Council Scient Ind Res Fremgangsmåde til fremstilling af tværbundne proteinkrystaller
DE602005009677D1 (de) 2004-03-22 2008-10-23 Solvay Pharm Gmbh Orale pharmazeutische zusammensetzungen von produkten mit lipase, insbesondere von pankreatin, mit tensiden
ES2352086T3 (es) 2004-10-14 2011-02-15 Cystic Fibrosis Foundation Therapeutics, Inc. Composiciones que contienen lipasa, proteasa y amilasa para el tratamiento de la insuficiencia pancreática.
RU2413532C2 (ru) 2005-07-29 2011-03-10 Зольвай Фармасьютиклз Гмбх Способ получения стерилизованного порошкообразного панкреатина
US9198871B2 (en) 2005-08-15 2015-12-01 Abbott Products Gmbh Delayed release pancreatin compositions
US11266607B2 (en) 2005-08-15 2022-03-08 AbbVie Pharmaceuticals GmbH Process for the manufacture and use of pancreatin micropellet cores
US10072256B2 (en) 2006-05-22 2018-09-11 Abbott Products Gmbh Process for separating and determining the viral load in a pancreatin sample
JP5248676B2 (ja) 2009-05-22 2013-07-31 サンヨー食品株式会社 不斉酸化反応を有する蛋白質複合体およびその製造方法
DK2478005T3 (en) * 2009-09-15 2015-02-16 Ajinomoto Althea Inc Protein a crystals and cross bound crystals and methods of use thereof
US9303255B2 (en) 2010-08-26 2016-04-05 Aisin Seiki Kabushiki Kaisha Electrode having enzyme crystals immobilized thereon, method for producing electrode having enzyme crystals immobilized thereon, and biological fuel cell and biosensor provided with electrode having enzyme crystals immobilized thereon
EP3003358B1 (de) * 2013-06-07 2021-03-24 Allena Pharmaceuticals Inc. Dialysezusammensetzungen und -vorrichtungen
WO2016126970A1 (en) 2015-02-04 2016-08-11 Abbvie Inc. Pharmaceutical compositions and methods of use thereof to treat pancreatic enzyme insufficiency
US12564623B2 (en) 2017-06-15 2026-03-03 The University Of Chicago Methods and compositions for treating cancer
IL300080A (en) 2020-08-18 2023-03-01 Onchilles Pharma Inc Processed porcine pancreatic elastase proteins
JP7148016B2 (ja) * 2020-10-19 2022-10-05 不二製油株式会社 酵素固定化用担体及びそれを用いた固定化酵素
EP4504961A1 (de) * 2022-04-07 2025-02-12 Need4Health B.V. Verfahren zur bestimmung der insulindosierung

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Publication number Priority date Publication date Assignee Title
US3664926A (en) 1970-02-26 1972-05-23 Merck & Co Inc Crystallization of l-asparaginase
DE2801238C2 (de) 1977-01-27 1986-06-05 (Zaidanhojin) Sagami Chemical Research Center, Tokio/Tokyo Verfahren zur Herstellung von Salzen aus L,L-Dipeptiden und Phenylalaninestern
US4373023A (en) * 1980-10-14 1983-02-08 Massachusetts Institute Of Technology Process for neutralizing heparin
EP0367302A3 (de) * 1982-04-23 1991-06-19 Wako Pure Chemical Industries, Ltd. Verfahren zur Halbsynthese von menschlichem Insulin, dabei zu verwendende, vernetzte, wasserlösliche Achromobacter Protease I und Verfahren zu dessen Herstellung
US4411996A (en) * 1982-06-30 1983-10-25 Nabisco Brands, Inc. Process for isomerizing glucose
AU3889685A (en) * 1984-01-20 1985-08-09 Eye Products Ltd. Partnership Method for cleaning contact lenses
FR2566798B1 (fr) * 1984-06-27 1986-12-12 Centre Nat Rech Scient Membrane porteuse de la luciferase pour le dosage de l'atp et son procede de production
US4650758A (en) * 1984-09-21 1987-03-17 Cetus Corporation Stabilization of enzymes useful in the production of glucosone and other enzymatic processes
JPS6317691A (ja) * 1986-07-09 1988-01-25 Agency Of Ind Science & Technol アスパルテ−ム製造用固定化酵素
FI85285C (fi) * 1988-05-13 1992-03-25 Stabra Ag Tvaerbundet, vattenoloesligt glukosisomeras och foerfarande foer framstaellning daerav.
US5010006A (en) * 1988-08-11 1991-04-23 Her Majesty The Queen In Right Of Canada As Represented By The National Research Council Of Canada Lipase immdoilized by cross-linking with inert protein for glyceride synthesis

Also Published As

Publication number Publication date
LV10304A (lv) 1994-10-20
EP0550450A1 (de) 1993-07-14
MD1592B2 (ro) 2001-01-31
IL99046A0 (en) 1992-07-15
SG70966A1 (en) 2000-03-21
CA2087730C (en) 1999-07-20
JP2004000230A (ja) 2004-01-08
LT3366B (en) 1995-07-25
DK0861888T3 (da) 2006-08-14
UA27035C2 (uk) 2000-02-28
HK1012411A1 (en) 1999-07-30
IE912767A1 (en) 1992-02-12
FI930454L (fi) 1993-02-02
FI930454A0 (fi) 1993-02-02
BR9106732A (pt) 1993-08-17
LTIP1077A (en) 1995-04-25
RU2124052C1 (ru) 1998-12-27
AU662104B2 (en) 1995-08-24
DE69133521T2 (de) 2006-12-07
DE69133258T2 (de) 2004-03-18
FI120099B (fi) 2009-06-30
DE69133521D1 (de) 2006-05-24
JPH05508549A (ja) 1993-12-02
PT98564A (pt) 1992-06-30
WO1992002617A1 (en) 1992-02-20
CZ12393A3 (en) 1993-10-13
IE20040113A1 (en) 2004-05-05
EP0550450B1 (de) 2003-05-14
HU9300275D0 (en) 1993-04-28
AU8315491A (en) 1992-03-02
TJ210R3 (en) 1998-11-14
EP0861888B1 (de) 2006-04-12
HK1023362A1 (en) 2000-09-08
SK283185B6 (sk) 2003-03-04
DE69133258D1 (de) 2003-06-18
CA2087730A1 (en) 1992-02-04
DK0550450T3 (da) 2003-09-08
EP0861888A1 (de) 1998-09-02
HUT65904A (en) 1994-07-28
HU211521A9 (en) 1995-11-28
ES2263187T3 (es) 2006-12-01
LV10304B (en) 1995-06-20
NO930360D0 (no) 1993-02-02
ATE240391T1 (de) 2003-05-15
PT98564B (pt) 1999-01-29
NO930360L (no) 1993-04-02
IL99046A (en) 1998-09-24
ES2199933T3 (es) 2004-03-01
SK5993A3 (en) 1993-07-07

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