UA27035C2 - Кристал білка, зшитого багатофуhкціоhальhим зшивальним агеhтом (варіаhти), пристрій, що містить кристал білка та спосіб отримаhhя аспартаму - Google Patents

Кристал білка, зшитого багатофуhкціоhальhим зшивальним агеhтом (варіаhти), пристрій, що містить кристал білка та спосіб отримаhhя аспартаму

Info

Publication number
UA27035C2
UA27035C2 UA93002104A UA93002104A UA27035C2 UA 27035 C2 UA27035 C2 UA 27035C2 UA 93002104 A UA93002104 A UA 93002104A UA 93002104 A UA93002104 A UA 93002104A UA 27035 C2 UA27035 C2 UA 27035C2
Authority
UA
Ukraine
Prior art keywords
crystal
protein
linked
appliance
variants
Prior art date
Application number
UA93002104A
Other languages
English (en)
Russian (ru)
Inventor
Мен'юел А. Нейвіа
Меньюел А. Нейвиа
Ненсі Л. Ст.Клер
Ненси Л Ст.Клер
Original Assignee
Вертекс Фармас'Ютікалс Інкорпорейтід
Вертекс Фармасьютикалс Инкорпорейтид
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 Вертекс Фармас'Ютікалс Інкорпорейтід, Вертекс Фармасьютикалс Инкорпорейтид filed Critical Вертекс Фармас'Ютікалс Інкорпорейтід
Publication of UA27035C2 publication Critical patent/UA27035C2/uk

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

Abstract

Кристал білка має стійкість до екзогенного протеолізу. Він зберігає принаймні 91% його вихідної активності після інкубування протягом принаймні трьох годин у присутності пронази (Pronase™). Винахід стосується іммобілізації ферментів, їх використання й способу одержання аспартаму, що використовує зшитий білковий кристал.
UA93002104A 1990-08-03 1991-07-30 Кристал білка, зшитого багатофуhкціоhальhим зшивальним агеhтом (варіаhти), пристрій, що містить кристал білка та спосіб отримаhhя аспартаму UA27035C2 (uk)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US56228090A 1990-08-03 1990-08-03
PCT/US1991/005415 WO1992002617A1 (en) 1990-08-03 1991-07-30 Use of crosslinked crystals as a novel form of enzyme immobilization

Publications (1)

Publication Number Publication Date
UA27035C2 true UA27035C2 (uk) 2000-02-28

Family

ID=24245600

Family Applications (1)

Application Number Title Priority Date Filing Date
UA93002104A UA27035C2 (uk) 1990-08-03 1991-07-30 Кристал білка, зшитого багатофуhкціоhальhим зшивальним агеhтом (варіаhти), пристрій, що містить кристал білка та спосіб отримаhhя аспартаму

Country Status (26)

Country Link
EP (2) EP0861888B1 (uk)
JP (2) JPH05508549A (uk)
AT (2) ATE323158T1 (uk)
AU (1) AU662104B2 (uk)
BR (1) BR9106732A (uk)
CA (1) CA2087730C (uk)
CZ (1) CZ12393A3 (uk)
DE (2) DE69133258T2 (uk)
DK (2) DK0861888T3 (uk)
ES (2) ES2199933T3 (uk)
FI (1) FI120099B (uk)
HK (2) HK1023362A1 (uk)
HU (2) HUT65904A (uk)
IE (1) IE912767A1 (uk)
IL (1) IL99046A (uk)
LT (1) LT3366B (uk)
LV (1) LV10304B (uk)
MD (1) MD1592B2 (uk)
NO (1) NO930360L (uk)
PT (1) PT98564B (uk)
RU (1) RU2124052C1 (uk)
SG (1) SG70966A1 (uk)
SK (1) SK283185B6 (uk)
TJ (1) TJ210R3 (uk)
UA (1) UA27035C2 (uk)
WO (1) WO1992002617A1 (uk)

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
DK1009759T3 (da) * 1997-09-05 2008-08-04 Altus Pharmaceuticals Inc Carbohydrat-tværbundne glycoproteinkrystaller
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 (en) * 2001-02-16 2004-01-02 Ibex Technologies Matrix stabilized enzyme crystals and methods of use
US7241272B2 (en) 2001-11-13 2007-07-10 Baxter International Inc. Method and composition for removing uremic toxins in dialysis processes
JP4799422B2 (ja) * 2004-01-01 2011-10-26 カウンシル・オブ・サイエンティフィック・アンド・インダストリアル・リサーチ 架橋タンパク質結晶の調製方法
CN1933850B (zh) 2004-03-22 2011-01-12 索尔瓦药物有限公司 含表面活性剂的、含脂肪酶产品尤其是胰酶的口服药物组合物
EP1809320B1 (en) 2004-10-14 2010-07-21 Altus Pharmaceuticals Inc. Compositions containing lipase; protease and amylase for treating pancreatic insufficiency
PL1913138T3 (pl) 2005-07-29 2017-07-31 Abbott Laboratories Gmbh Sposoby wytwarzania pankreatyny w proszku o niskiej zawartości wirusa
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
CA2774212C (en) * 2009-09-15 2018-01-30 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
ES2875060T3 (es) 2013-06-07 2021-11-08 Allena Pharmaceuticals Inc Composiciones y dispositivos para diálisis
US20180028454A1 (en) 2015-02-04 2018-02-01 Abbvie Inc. Pharmaceutical compositions and methods of use thereof to treat pancreatic enzyme insufficiency
EP3638293B1 (en) * 2017-06-15 2023-10-04 The University of Chicago Compositions for treating cancer
WO2023194615A1 (en) * 2022-04-07 2023-10-12 Need4Health B.V. Method for determining insulin dosage

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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
DE2857828C2 (uk) 1977-01-27 1990-06-07 Toyo Soda Mfg. Co., Ltd., Shinnanyo, Yamaguchi, Jp
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
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.

Also Published As

Publication number Publication date
EP0861888B1 (en) 2006-04-12
BR9106732A (pt) 1993-08-17
EP0861888A1 (en) 1998-09-02
PT98564B (pt) 1999-01-29
DE69133258D1 (de) 2003-06-18
DE69133521T2 (de) 2006-12-07
LT3366B (en) 1995-07-25
HU9300275D0 (en) 1993-04-28
HK1023362A1 (en) 2000-09-08
LV10304B (en) 1995-06-20
SK283185B6 (sk) 2003-03-04
FI930454A (fi) 1993-02-02
AU662104B2 (en) 1995-08-24
PT98564A (pt) 1992-06-30
ATE323158T1 (de) 2006-04-15
TJ210R3 (en) 1998-11-14
ES2263187T3 (es) 2006-12-01
ES2199933T3 (es) 2004-03-01
HK1012411A1 (en) 1999-07-30
NO930360D0 (no) 1993-02-02
JPH05508549A (ja) 1993-12-02
LV10304A (lv) 1994-10-20
SK5993A3 (en) 1993-07-07
NO930360L (no) 1993-04-02
EP0550450B1 (en) 2003-05-14
DK0861888T3 (da) 2006-08-14
HU211521A9 (en) 1995-11-28
LTIP1077A (en) 1995-04-25
ATE240391T1 (de) 2003-05-15
HUT65904A (en) 1994-07-28
IL99046A0 (en) 1992-07-15
DE69133258T2 (de) 2004-03-18
RU2124052C1 (ru) 1998-12-27
MD1592B2 (ro) 2001-01-31
SG70966A1 (en) 2000-03-21
CZ12393A3 (en) 1993-10-13
JP2004000230A (ja) 2004-01-08
DK0550450T3 (da) 2003-09-08
CA2087730A1 (en) 1992-02-04
EP0550450A1 (en) 1993-07-14
DE69133521D1 (de) 2006-05-24
FI120099B (fi) 2009-06-30
IE20040113A1 (en) 2004-05-05
FI930454A0 (fi) 1993-02-02
IE912767A1 (en) 1992-02-12
IL99046A (en) 1998-09-24
CA2087730C (en) 1999-07-20
WO1992002617A1 (en) 1992-02-20
AU8315491A (en) 1992-03-02

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