CA2087730A1 - Utilisation de cristaux reticules, nouvelle forme d'immobilisation des enzymes - Google Patents

Utilisation de cristaux reticules, nouvelle forme d'immobilisation des enzymes

Info

Publication number
CA2087730A1
CA2087730A1 CA2087730A CA2087730A CA2087730A1 CA 2087730 A1 CA2087730 A1 CA 2087730A1 CA 2087730 A CA2087730 A CA 2087730A CA 2087730 A CA2087730 A CA 2087730A CA 2087730 A1 CA2087730 A1 CA 2087730A1
Authority
CA
Canada
Prior art keywords
clecs
crystals
enzyme
novel form
enzyme immobilization
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.)
Granted
Application number
CA2087730A
Other languages
English (en)
Other versions
CA2087730C (fr
Inventor
Manuel A. Navia
Nancy L. St. Clair
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Vertex Pharmaceuticals Inc
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of CA2087730A1 publication Critical patent/CA2087730A1/fr
Application granted granted Critical
Publication of CA2087730C publication Critical patent/CA2087730C/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531—Production of immunochemical test materials
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06104—Dipeptides with the first amino acid being acidic
    • C07K5/06113—Asp- or Asn-amino acid
    • C07K5/06121—Asp- or Asn-amino acid the second amino acid being aromatic or cycloaliphatic
    • C07K5/0613—Aspartame
    • 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
    • C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • 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
    • C12N9/14—Hydrolases (3)
    • 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
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/18—Carboxylic ester hydrolases (3.1.1)
    • C12N9/20—Triglyceride splitting, e.g. by means of lipase
    • 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
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2462—Lysozyme (3.2.1.17)
    • 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
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
    • C12N9/54—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea bacteria being Bacillus
    • 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
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6448—Elastases, e.g. pancreatic elastase (3.4.21.36); leukocyte elastase (3.4.31.37)
    • 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
    • C12N9/14—Hydrolases (3)
    • C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C12N9/80—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
    • 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
    • C12N9/14—Hydrolases (3)
    • C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C12N9/80—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
    • C12N9/82—Asparaginase (3.5.1.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001—Enzyme electrodes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001—Enzyme electrodes
    • C12Q1/002—Electrode membranes
    • C12Q1/003—Functionalisation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/37—Measuring 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)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biophysics (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Pathology (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Cell Biology (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)
CA002087730A 1990-08-03 1991-07-30 Utilisation de cristaux reticules, nouvelle forme d'immobilisation des enzymes Expired - Lifetime CA2087730C (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US56228090A 1990-08-03 1990-08-03
US562,280 1990-08-03

Publications (2)

Publication Number Publication Date
CA2087730A1 true CA2087730A1 (fr) 1992-02-04
CA2087730C CA2087730C (fr) 1999-07-20

Family

ID=24245600

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002087730A Expired - Lifetime CA2087730C (fr) 1990-08-03 1991-07-30 Utilisation de cristaux reticules, nouvelle forme d'immobilisation des enzymes

Country Status (26)

Country Link
EP (2) EP0550450B1 (fr)
JP (2) JPH05508549A (fr)
AT (2) ATE240391T1 (fr)
AU (1) AU662104B2 (fr)
BR (1) BR9106732A (fr)
CA (1) CA2087730C (fr)
CZ (1) CZ12393A3 (fr)
DE (2) DE69133521T2 (fr)
DK (2) DK0861888T3 (fr)
ES (2) ES2199933T3 (fr)
FI (1) FI120099B (fr)
HK (2) HK1023362A1 (fr)
HU (2) HUT65904A (fr)
IE (1) IE912767A1 (fr)
IL (1) IL99046A (fr)
LT (1) LT3366B (fr)
LV (1) LV10304B (fr)
MD (1) MD1592B2 (fr)
NO (1) NO930360L (fr)
PT (1) PT98564B (fr)
RU (1) RU2124052C1 (fr)
SG (1) SG70966A1 (fr)
SK (1) SK283185B6 (fr)
TJ (1) TJ210R3 (fr)
UA (1) UA27035C2 (fr)
WO (1) WO1992002617A1 (fr)

Families Citing this family (23)

* 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
AU4738197A (en) * 1996-09-24 1998-04-17 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
AU8772498A (en) 1997-09-05 1999-03-29 Altus Biologics Inc. Carbohydrate crosslinked glycoprotein crystals
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
WO2002070646A2 (fr) * 2001-02-16 2002-09-12 Ibex Technologies Cristaux d'enzymes à stabilisation matricielle et modalités d'utilisation
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
BRPI0509148B8 (pt) 2004-03-22 2021-05-25 Abbott Products Gmbh composições farmacêuticas orais de produtos contendo lipase, em particular de pancreatina contendo tensoativos, seus usos e respectivos processos de fabricação
PT2198880T (pt) 2004-10-14 2017-01-04 Lilly Co Eli Composições contendo lipase, protease e amilase para o tratamento de insuficiência pancreática
JP5140586B2 (ja) 2005-07-29 2013-02-06 アボット プロダクツ ゲゼルシャフト ミット ベシュレンクテル ハフツング 滅菌パンクレアチン粉末の製法
US11266607B2 (en) 2005-08-15 2022-03-08 AbbVie Pharmaceuticals GmbH Process for the manufacture and use of pancreatin micropellet cores
US9198871B2 (en) 2005-08-15 2015-12-01 Abbott Products Gmbh Delayed release pancreatin compositions
US10072256B2 (en) 2006-05-22 2018-09-11 Abbott Products Gmbh Process for separating and determining the viral load in a pancreatin sample
US8852904B2 (en) * 2009-05-22 2014-10-07 Sanyo Foods Co., Ltd. Protein complex having activity catalyzing asymmetric oxidation reaction and process for producing the same
US8921531B2 (en) * 2009-09-15 2014-12-30 Althea Technologies, Inc. Protein a crystals and cross-linked 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
DK3003358T3 (da) 2013-06-07 2021-06-21 Allena Pharmaceuticals Inc Sammensætninger og anordninger til dialyse
US20180028454A1 (en) 2015-02-04 2018-02-01 Abbvie Inc. Pharmaceutical compositions and methods of use thereof to treat pancreatic enzyme insufficiency
EP4292606A3 (fr) * 2017-06-15 2024-02-21 The University of Chicago Compositions pour le traitement du cancer
WO2023194615A1 (fr) * 2022-04-07 2023-10-12 Need4Health B.V. Procédé pour déterminer le dosage d'insuline

Family Cites Families (10)

* Cited by examiner, † Cited by third party
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
DE3381980D1 (de) * 1982-04-23 1990-12-13 Wako Pure Chem Ind Ltd Verfahren zur halbsynthese von menschlichem insulin und dazu zu verwendende alkalische protease.
US4411996A (en) * 1982-06-30 1983-10-25 Nabisco Brands, Inc. Process for isomerizing glucose
EP0168487A1 (fr) * 1984-01-20 1986-01-22 Eye Products Limited Partnership Procede de nettoyage de lentilles de contact
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.

Also Published As

Publication number Publication date
SG70966A1 (en) 2000-03-21
BR9106732A (pt) 1993-08-17
DK0861888T3 (da) 2006-08-14
EP0861888B1 (fr) 2006-04-12
AU8315491A (en) 1992-03-02
IE912767A1 (en) 1992-02-12
ES2263187T3 (es) 2006-12-01
HK1012411A1 (en) 1999-07-30
JPH05508549A (ja) 1993-12-02
RU2124052C1 (ru) 1998-12-27
HU211521A9 (en) 1995-11-28
NO930360D0 (no) 1993-02-02
AU662104B2 (en) 1995-08-24
EP0861888A1 (fr) 1998-09-02
ATE323158T1 (de) 2006-04-15
ATE240391T1 (de) 2003-05-15
MD1592B2 (ro) 2001-01-31
JP2004000230A (ja) 2004-01-08
LV10304A (lv) 1994-10-20
UA27035C2 (uk) 2000-02-28
FI930454A0 (fi) 1993-02-02
IL99046A (en) 1998-09-24
SK5993A3 (en) 1993-07-07
HK1023362A1 (en) 2000-09-08
CZ12393A3 (en) 1993-10-13
TJ210R3 (en) 1998-11-14
DE69133521D1 (de) 2006-05-24
PT98564A (pt) 1992-06-30
DE69133258T2 (de) 2004-03-18
LT3366B (en) 1995-07-25
IE20040113A1 (en) 2004-05-05
LV10304B (en) 1995-06-20
ES2199933T3 (es) 2004-03-01
PT98564B (pt) 1999-01-29
CA2087730C (fr) 1999-07-20
DK0550450T3 (da) 2003-09-08
SK283185B6 (sk) 2003-03-04
FI120099B (fi) 2009-06-30
HU9300275D0 (en) 1993-04-28
HUT65904A (en) 1994-07-28
WO1992002617A1 (fr) 1992-02-20
IL99046A0 (en) 1992-07-15
EP0550450B1 (fr) 2003-05-14
FI930454A (fi) 1993-02-02
DE69133521T2 (de) 2006-12-07
EP0550450A1 (fr) 1993-07-14
NO930360L (no) 1993-04-02
LTIP1077A (en) 1995-04-25
DE69133258D1 (de) 2003-06-18

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