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)
  • Investigating Or Analysing Biological Materials (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Piezo-Electric Or Mechanical Vibrators, Or Delay Or Filter Circuits (AREA)
  • Crystals, And After-Treatments Of Crystals (AREA)
  • Liquid Crystal Substances (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 (25)

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) DE69133258T2 (fr)
DK (2) DK0861888T3 (fr)
ES (2) ES2263187T3 (fr)
FI (1) FI120099B (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 (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 (fr) * 1996-09-24 1998-04-02 Altus Biologics Inc. Cristaux proteiniques reticules utilises comme supports de separation universels
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
JP2004523240A (ja) * 2001-02-16 2004-08-05 アイベックス テクノロジーズ マトリックス安定化酵素結晶および使用方法
US7241272B2 (en) 2001-11-13 2007-07-10 Baxter International Inc. Method and composition for removing uremic toxins in dialysis processes
US20090035828A1 (en) * 2004-01-01 2009-02-05 Tholath Emilia Abraham Method For the Preparation of Cross Linked Protein Crystals
CA2560613C (fr) 2004-03-22 2015-11-24 Solvay Pharmaceuticals Gmbh Compositions pharmaceutiques par voie orale a base de lipases, en particulier de pancreatine, contenant des tensioacitfs
WO2006044529A1 (fr) 2004-10-14 2006-04-27 Altus Pharmaceuticals Inc. Compositions contenant de la lipase, de la protease et de l'amylase pour le traitement de l'insuffisance pancreatique
KR101555058B1 (ko) 2005-07-29 2015-09-22 애보트 래버러토리즈 게엠베하 살균된 판크레아틴 분말의 제조방법
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
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
BR112012005869A2 (pt) 2009-09-15 2017-01-31 Althea Tech Inc cristais da proteína a, cristais reticulados e métodos de utilização dos mesmos
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
WO2016126970A1 (fr) 2015-02-04 2016-08-11 Abbvie Inc. Compositions pharmaceutiques et méthodes d'utilisation de celles-ci pour traiter une insuffisance liée aux enzymes pancréatiques
EP4292606B1 (fr) 2017-06-15 2025-11-12 The University of Chicago Compositions pour le traitement du cancer
EP4199947A4 (fr) 2020-08-18 2024-10-16 Onchilles Pharma, Inc. Protéines d'élastase pancréatique porcine modifiées
WO2022085419A1 (fr) * 2020-10-19 2022-04-28 不二製油グループ本社株式会社 Support d'immobilisation d'enzyme et enzyme immobilisée qui utilise celui-ci
EP4504961A1 (fr) * 2022-04-07 2025-02-12 Need4Health B.V. Procédé pour déterminer le dosage d'insuline

Family Cites Families (11)

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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 (fr) * 1982-04-23 1991-06-19 Wako Pure Chemical Industries, Ltd. Procédé pour la semi-synthèse d'insuline humaine protéase I d'Achromobacter réticulée soluble dans l'eau pour sa mise en oeuvre et procédé pour la préparation de celle-ci
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.
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
CZ12393A3 (en) 1993-10-13
UA27035C2 (uk) 2000-02-28
DE69133258D1 (de) 2003-06-18
SK283185B6 (sk) 2003-03-04
AU662104B2 (en) 1995-08-24
FI120099B (fi) 2009-06-30
HU9300275D0 (en) 1993-04-28
PT98564B (pt) 1999-01-29
BR9106732A (pt) 1993-08-17
LTIP1077A (en) 1995-04-25
FI930454A0 (fi) 1993-02-02
DE69133521D1 (de) 2006-05-24
ATE240391T1 (de) 2003-05-15
IL99046A (en) 1998-09-24
RU2124052C1 (ru) 1998-12-27
LT3366B (en) 1995-07-25
IE912767A1 (en) 1992-02-12
EP0550450B1 (fr) 2003-05-14
MD1592B2 (ro) 2001-01-31
EP0861888A1 (fr) 1998-09-02
WO1992002617A1 (fr) 1992-02-20
HK1012411A1 (en) 1999-07-30
FI930454L (fi) 1993-02-02
PT98564A (pt) 1992-06-30
JP2004000230A (ja) 2004-01-08
AU8315491A (en) 1992-03-02
DE69133521T2 (de) 2006-12-07
SG70966A1 (en) 2000-03-21
ES2199933T3 (es) 2004-03-01
TJ210R3 (en) 1998-11-14
SK5993A3 (en) 1993-07-07
CA2087730C (fr) 1999-07-20
DK0550450T3 (da) 2003-09-08
HUT65904A (en) 1994-07-28
LV10304A (lv) 1994-10-20
LV10304B (en) 1995-06-20
IL99046A0 (en) 1992-07-15
HU211521A9 (en) 1995-11-28
JPH05508549A (ja) 1993-12-02
NO930360L (no) 1993-04-02
NO930360D0 (no) 1993-02-02
IE20040113A1 (en) 2004-05-05
ATE323158T1 (de) 2006-04-15
EP0550450A1 (fr) 1993-07-14
DE69133258T2 (de) 2004-03-18
DK0861888T3 (da) 2006-08-14
ES2263187T3 (es) 2006-12-01
EP0861888B1 (fr) 2006-04-12
HK1023362A1 (en) 2000-09-08

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