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CA2242488A1 - Conjugaison de polypeptides - Google Patents

Conjugaison de polypeptides Download PDF

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Publication number
CA2242488A1
CA2242488A1 CA002242488A CA2242488A CA2242488A1 CA 2242488 A1 CA2242488 A1 CA 2242488A1 CA 002242488 A CA002242488 A CA 002242488A CA 2242488 A CA2242488 A CA 2242488A CA 2242488 A1 CA2242488 A1 CA 2242488A1
Authority
CA
Canada
Prior art keywords
molecules
polypeptide
kda
polymeric carrier
carrier molecule
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.)
Abandoned
Application number
CA002242488A
Other languages
English (en)
Inventor
Henrik Bisgard-Frantzen
Arne Agerlin Olsen
Annette Prento
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.)
Novozymes AS
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 CA2242488A1 publication Critical patent/CA2242488A1/fr
Abandoned legal-status Critical Current

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Classifications

    • 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
    • C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
    • C12N11/08—Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a synthetic polymer
    • C12N11/089—Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a synthetic polymer obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q9/00—Preparations for removing hair or for aiding hair removal
    • A61Q9/02—Shaving preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66—Enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/88—Polyamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/02—Preparations for cleaning the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/06—Preparations for styling the hair, e.g. by temporary shaping or colouring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/10—Preparations for permanently dyeing the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/12—Preparations containing hair conditioners
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16—Organic compounds
    • C11D3/38—Products with no well-defined composition, e.g. natural products
    • C11D3/384—Animal products
    • C11D3/3845—Antibodies
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16—Organic compounds
    • C11D3/38—Products with no well-defined composition, e.g. natural products
    • C11D3/386—Preparations containing enzymes, e.g. protease or amylase
    • 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
    • C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
    • 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
    • C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
    • C12N11/08—Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a synthetic polymer
    • C12N11/082—Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a synthetic polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • C12N11/087—Acrylic polymers
    • 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
    • C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
    • C12N11/10—Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a carbohydrate
    • 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
    • C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/57—Compounds covalently linked to a(n inert) carrier molecule, e.g. conjugates, pro-fragrances

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Birds (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Detergent Compositions (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Cosmetics (AREA)
  • Immobilizing And Processing Of Enzymes And Microorganisms (AREA)

Abstract

L'invention porte sur des conjugués de polypeptides à allergénicité réduite comportant une molécule support polymérique à laquelle son fixées deux ou plus de deux molécules de polypeptides. L'invention porte également sur un procédé de production desdits conjugués, sur des compositions les contenant, et sur leur utilisation dans un grand nombre d'applications industrielles telles que des produits pour soins personnel et des détergents.
CA002242488A 1996-02-15 1997-02-07 Conjugaison de polypeptides Abandoned CA2242488A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DK15496 1996-02-15
DK0154/96 1996-02-15

Publications (1)

Publication Number Publication Date
CA2242488A1 true CA2242488A1 (fr) 1997-08-21

Family

ID=8090373

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002242488A Abandoned CA2242488A1 (fr) 1996-02-15 1997-02-07 Conjugaison de polypeptides

Country Status (6)

Country Link
EP (1) EP0894128A1 (fr)
JP (1) JP2000506119A (fr)
CN (1) CN1273589C (fr)
AU (1) AU725287B2 (fr)
CA (1) CA2242488A1 (fr)
WO (1) WO1997030148A1 (fr)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100361933B1 (ko) 1993-09-08 2003-02-14 라 졸라 파마슈티칼 컴파니 화학적으로정의된비중합성결합가플랫폼분자및그것의콘주게이트
US6416756B1 (en) 1997-01-10 2002-07-09 Novozymes A/S Modified protease having 5 to 13 covalently coupled polymeric molecules for skin care
WO1998030682A1 (fr) * 1997-01-10 1998-07-16 Novo Nordisk A/S Enzyme couplee a des molecules polymeres pour les soins de la peau
US6908757B1 (en) 1998-03-26 2005-06-21 The Procter & Gamble Company Serine protease variants having amino acid deletions and substitutions
US6495136B1 (en) 1998-03-26 2002-12-17 The Procter & Gamble Company Proteases having modified amino acid sequences conjugated to addition moieties
CN1301305A (zh) 1998-03-26 2001-06-27 宝洁公司 具有氨基酸取代的丝氨酸蛋白酶变体
US6936249B1 (en) 1998-04-15 2005-08-30 Genencor International, Inc. Proteins producing an altered immunogenic response and methods of making and using the same
US6838269B1 (en) 1998-04-15 2005-01-04 Genencor International, Inc. Proteins producing an altered immunogenic response and methods of making and using the same
US6835550B1 (en) * 1998-04-15 2004-12-28 Genencor International, Inc. Mutant proteins having lower allergenic response in humans and methods for constructing, identifying and producing such proteins
US6642011B2 (en) 1998-04-15 2003-11-04 Genencor International, Inc. Human protease and use of such protease for pharmaceutical applications and for reducing the allergenicity of non-human proteins
US6468955B1 (en) 1998-05-01 2002-10-22 The Proctor & Gamble Company Laundry detergent and/or fabric care compositions comprising a modified enzyme
AU7275498A (en) * 1998-05-01 1999-11-23 Procter & Gamble Company, The Laundry detergent and/or fabric care compositions comprising a modified enzyme
US6638526B1 (en) 1998-06-23 2003-10-28 Novozymes A/S Polypeptides conjugated to copolymers of ethylene oxide and propylene oxide to reduce allergenicity
AU768765B2 (en) * 1998-06-23 2004-01-08 Novozymes A/S A polypeptide-polymer conjugate
CA2333491A1 (fr) * 1998-07-17 2000-01-27 Novozymes A/S Conjugue polypeptide-polymeres a efficacite de lavage amelioree
JP2002527059A (ja) * 1998-10-13 2002-08-27 ノボザイムス アクティーゼルスカブ 低められた免疫応答を有する修飾されたポリペプチド
US6461849B1 (en) 1998-10-13 2002-10-08 Novozymes, A/S Modified polypeptide
US7312062B2 (en) 1998-11-27 2007-12-25 Novozymes A/S Lipolytic enzyme variants
CA2353379C (fr) * 1998-11-27 2011-01-04 Novozymes A/S Variants d'enzyme lipolytique
US6946128B1 (en) 1999-07-22 2005-09-20 The Procter & Gamble Company Protease conjugates having sterically protected epitope regions
KR20020021395A (ko) 1999-07-22 2002-03-20 데이비드 엠 모이어 입체적으로 보호된 ｃｌｉｐ 부위를 갖는 프로테아제콘쥬게이트
WO2001007575A2 (fr) 1999-07-22 2001-02-01 The Procter & Gamble Company Variants de protease subtilisine possedant des suppressions et des substitutions d'acides amines dans certaines regions de sites antigeniques
BR0012660A (pt) 1999-07-22 2002-04-09 Procter & Gamble Variante de protease tipo subtilisina; composição de limpeza; e composição de cuidado pessoal
DE10009252A1 (de) 2000-03-01 2001-09-06 Henkel Kgaa Wärmendes Hautreinigungsgel
JP2003535208A (ja) 2000-06-08 2003-11-25 ラ ホヤ ファーマシューティカル カンパニー 高分子量ポリエチレン・オキシドを含む多価プラットホーム分子
DE10047481A1 (de) * 2000-09-26 2002-04-25 Henkel Kgaa Wasch- und Reinigungsmittel
ITMI20010347A1 (it) 2001-02-21 2002-08-21 Grisotech S A Complessi di immunoglobuline e polisaccaridi per assorbimento orale etrans-mucosale
CA2441595C (fr) 2001-03-23 2012-07-03 Genencor International, Inc. Proteines provoquant une reaction immunogene modifiee, et methodes de production et d'utilisation desdites proteines
US7332320B2 (en) 2001-12-31 2008-02-19 Genencor International, Inc. Protease producing an altered immunogenic response and methods of making and using the same
DE10209821A1 (de) 2002-03-06 2003-09-25 Biotechnologie Ges Mittelhesse Kopplung von Proteinen an ein modifiziertes Polysaccharid
WO2003099242A1 (fr) * 2002-05-29 2003-12-04 Henkel Kommanditgesellschaft Auf Aktien Agents cosmetiques comprenant une disulfidisomerase proteinique
DE10227238A1 (de) * 2002-06-19 2004-01-15 Wella Ag Hochaffine kosmetische Mittel
CN1668332A (zh) * 2002-07-09 2005-09-14 桑多斯股份公司 包含苯酚的含高浓度人生长激素的液体制剂
DE10242076A1 (de) * 2002-09-11 2004-03-25 Fresenius Kabi Deutschland Gmbh HAS-Allergen-Konjugate
ES2314238T3 (es) 2002-10-08 2009-03-16 Fresenius Kabi Deutschland Gmbh Conjugados de oligosacaridos farmaceuticamente activos.
WO2005014655A2 (fr) 2003-08-08 2005-02-17 Fresenius Kabi Deutschland Gmbh Conjugues d'amidon d'hydroxyalkyle et de proteine
WO2005077319A2 (fr) * 2004-02-12 2005-08-25 Unilever Plc Compositions de traitement capillaire
EP2039460A3 (fr) * 2004-11-02 2014-07-02 HID Global GmbH Dispositif de pose, dispositif d'établissement de contact, système d'avance, unité de pose et d'établissement de contact, installation de production, procédé de fabrication et ensemble transpondeur
WO2007123271A2 (fr) * 2006-04-21 2007-11-01 Kao Corporation Composition d'agent de lutte contre un biofilm
DK2197919T3 (da) 2007-08-27 2014-07-07 Ratiopharm Gmbh Flydende formulering af g-csf-konjugat
US8021436B2 (en) * 2007-09-27 2011-09-20 The Procter & Gamble Company Cleaning and/or treatment compositions comprising a xyloglucan conjugate
EP2070950A1 (fr) 2007-12-14 2009-06-17 Fresenius Kabi Deutschland GmbH Dérivés hydroxyalkylés de l'amidon et leur procédé de préparation
SG11201403324TA (en) * 2011-12-20 2014-07-30 Pfizer Improved processes for preparing peptide conjugates and linkers
WO2014067933A1 (fr) * 2012-10-31 2014-05-08 C-Lecta Gmbh Préparation de support bioactif pour une sécurité améliorée dans les produits de soin et les aliments

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4179337A (en) * 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
GB8430252D0 (en) * 1984-11-30 1985-01-09 Beecham Group Plc Compounds
DE3541186A1 (de) * 1985-11-21 1987-05-27 Boehringer Mannheim Gmbh Wasserloesliche, stabilisierte peroxidasederivate, verfahren zu ihrer herstellung und verwendung zur bestimmung von wasserstoffperoxid
US5006333A (en) * 1987-08-03 1991-04-09 Ddi Pharmaceuticals, Inc. Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols
US5133968A (en) * 1990-08-20 1992-07-28 Kanebo, Ltd. Modified protease, method of producing the same and cosmetic products containing the modified protease
US5230891A (en) * 1990-08-20 1993-07-27 Kanebo Limited Modified protease, method of producing the same and cosmetic products containing the modified protease
EP0796324A1 (fr) * 1994-12-07 1997-09-24 Novo Nordisk A/S Polypeptide a allergenicite reduite
WO1996040791A1 (fr) * 1995-06-07 1996-12-19 Novo Nordisk A/S Modification de polypeptides

Also Published As

Publication number Publication date
AU725287B2 (en) 2000-10-12
CN1211278A (zh) 1999-03-17
JP2000506119A (ja) 2000-05-23
CN1273589C (zh) 2006-09-06
AU1540697A (en) 1997-09-02
WO1997030148A1 (fr) 1997-08-21
EP0894128A1 (fr) 1999-02-03

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EEER Examination request
FZDE Discontinued
FZDE Discontinued

Effective date: 20051128

FZDE Discontinued

Effective date: 20051128

FZDE Discontinued

Effective date: 20051128

FZDE Discontinued

Effective date: 20051128