CA2492437A1 - Nouveaux conjugues d'effecteurs, procedes permettant de les produire et utilisation pharmaceutique de ceux-ci - Google Patents

Nouveaux conjugues d'effecteurs, procedes permettant de les produire et utilisation pharmaceutique de ceux-ci Download PDF

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Publication number
CA2492437A1
CA2492437A1 CA002492437A CA2492437A CA2492437A1 CA 2492437 A1 CA2492437 A1 CA 2492437A1 CA 002492437 A CA002492437 A CA 002492437A CA 2492437 A CA2492437 A CA 2492437A CA 2492437 A1 CA2492437 A1 CA 2492437A1
Authority
CA
Canada
Prior art keywords
dione
dihydroxy
tetramethyl
methyl
oxacyclohexadec
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
CA002492437A
Other languages
English (en)
Inventor
Markus Berger
Gerhard Siemeister
Ulrich Klar
Joerg Willuda
Andreas Menrad
Klaus Bosslet
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.)
Individual
Original Assignee
Schering AG
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
Priority claimed from DE10234975A external-priority patent/DE10234975A1/de
Priority claimed from DE10305098A external-priority patent/DE10305098A1/de
Application filed by Schering AG filed Critical Schering AG
Publication of CA2492437A1 publication Critical patent/CA2492437A1/fr
Abandoned legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6807—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense
    • A61K47/6809—Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
    • 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
    • A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/36—Oxygen or sulfur atoms
    • C07D207/40—2,5-Pyrrolidine-diones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Rheumatology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Psychiatry (AREA)
  • Cell Biology (AREA)
  • Cardiology (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biochemistry (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)

Abstract

L'invention concerne des conjugués d'épothilones et des dérivés d'épothilone (en tant qu'effecteurs) avec des biomolécules adéquates (en tant qu'unités de reconnaissance). Le procédé de production consiste à faire réagir les effecteurs avec des lieurs appropriés ; les composés qui sont produits étant conjugués avec les unités de reconnaissance. La présente invention concerne également l'utilisation pharmaceutique de ces conjugués pour traiter des troubles prolifératifs ou associés à l'angiogenèse.
CA002492437A 2002-07-31 2003-07-31 Nouveaux conjugues d'effecteurs, procedes permettant de les produire et utilisation pharmaceutique de ceux-ci Abandoned CA2492437A1 (fr)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
DE10234975.4 2002-07-31
DE10234975A DE10234975A1 (de) 2002-07-31 2002-07-31 Neue Effektor-Konjugate, Verfahren zu ihrer Herstellung und ihre pharmazeutische Verwendung
DE10305098.1 2003-02-07
DE10305098A DE10305098A1 (de) 2003-02-07 2003-02-07 Neue Effektor-Konjugate, Verfahren zu ihrer Herstellung und ihre pharmazeutische Verwendung
US45167303P 2003-03-05 2003-03-05
US60/451,673 2003-03-05
PCT/EP2003/008483 WO2004012735A2 (fr) 2002-07-31 2003-07-31 Nouveaux conjugues d'effecteurs, procedes permettant de les produire et utilisation pharmaceutique de ceux-ci

Publications (1)

Publication Number Publication Date
CA2492437A1 true CA2492437A1 (fr) 2004-02-12

Family

ID=31498923

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002492437A Abandoned CA2492437A1 (fr) 2002-07-31 2003-07-31 Nouveaux conjugues d'effecteurs, procedes permettant de les produire et utilisation pharmaceutique de ceux-ci

Country Status (16)

Country Link
EP (1) EP1524979A2 (fr)
JP (1) JP2006505627A (fr)
KR (1) KR20050026033A (fr)
AU (1) AU2003253365A1 (fr)
BR (1) BR0313043A (fr)
CA (1) CA2492437A1 (fr)
CO (1) CO5700741A2 (fr)
EC (1) ECSP055626A (fr)
HR (1) HRP20050186A2 (fr)
IL (1) IL166039A0 (fr)
IS (1) IS7708A (fr)
MX (1) MXPA05001282A (fr)
NO (1) NO20051038L (fr)
NZ (1) NZ537870A (fr)
PL (1) PL374528A1 (fr)
WO (1) WO2004012735A2 (fr)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4579351B2 (ja) 1996-12-03 2010-11-10 スローン−ケッタリング インスティトュート フォア キャンサー リサーチ エポチロンの合成とその中間体及びその類似物並びにその使用
IL144370A0 (en) * 1999-02-11 2002-05-23 Schering Ag Epothilon derivatives, method for the production and the use thereof as pharmaceuticals
US6921769B2 (en) 2002-08-23 2005-07-26 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
US7649006B2 (en) 2002-08-23 2010-01-19 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
PT1506203E (pt) 2002-08-23 2007-04-30 Sloan Kettering Inst Cancer Síntese de epotilonas, seus intermediários, seus análogos e suas utilizações
GB0221312D0 (en) 2002-09-13 2002-10-23 Novartis Ag Organic compounds
JP2006510626A (ja) * 2002-12-05 2006-03-30 シエーリング アクチエンゲゼルシャフト 増殖疾患の処理における部位特異的供給のためのエポチロン類似体
DE10256982A1 (de) 2002-12-05 2004-06-24 Schering Ag Neue Effektor-Konjugate, Verfahren zu Ihrer Herstellung und Ihre Pharmazeutische Verwendung
DK1718340T3 (da) * 2004-01-30 2008-03-03 Bayer Schering Pharma Ag Nye effektorkonjugater, fremgangsmåde til deres fremstilling og deres farmaceutiske anvendelse
US7541330B2 (en) 2004-06-15 2009-06-02 Kosan Biosciences Incorporated Conjugates with reduced adverse systemic effects
US8288557B2 (en) 2004-07-23 2012-10-16 Endocyte, Inc. Bivalent linkers and conjugates thereof
PE20080102A1 (es) * 2006-05-25 2008-02-11 Bristol Myers Squibb Co Conjugados de analogos de aziridinil-epotilona y composiciones farmaceuticas que comprenden los mismos
AR061181A1 (es) 2006-05-25 2008-08-13 Bristol Myers Squibb Co Compuestos de aziridinil-epotilona
CN101678124A (zh) 2007-03-14 2010-03-24 恩多塞特公司 结合配体连接的微管溶素递药缀合物
CN101754969A (zh) 2007-05-25 2010-06-23 百时美施贵宝公司 制备埃坡霉素化合物和类似物的方法
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
CN101784565B (zh) 2007-06-25 2014-12-10 恩多塞特公司 含有亲水性间隔区接头的共轭物
CA2703491C (fr) 2007-10-25 2017-06-13 Endocyte, Inc. Tubulysines et leurs procedes de preparation
IT1401451B1 (it) * 2010-06-10 2013-07-26 Chemi Spa Nuovo processo di preparazione di 2-idrossi-4-fenil-3,4-diidro-2h-cromen-6-il-metanolo e (r)-2-[3-(diisopropilammino)-1-fenilpropil]-4-(idrossimetil)fenolo.
WO2013126797A1 (fr) 2012-02-24 2013-08-29 Purdue Research Foundation Ciblage du récepteur de la cholécystokinine de type b pour imagerie et thérapie
US20140080175A1 (en) 2012-03-29 2014-03-20 Endocyte, Inc. Processes for preparing tubulysin derivatives and conjugates thereof
AU2013331440A1 (en) 2012-10-16 2015-04-30 Endocyte, Inc. Drug delivery conjugates containing unnatural amino acids and methods for using
HUE070615T2 (hu) * 2016-10-17 2025-06-28 Pfizer Anti-EDB antitestek és antitest-gyógyszer konjugátumok
KR102377416B1 (ko) * 2017-06-30 2022-03-21 엘지디스플레이 주식회사 표시장치

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK130984A (da) * 1983-03-07 1984-09-08 Smithkline Beckman Corp Leukotrien-antagonister
IL107400A0 (en) * 1992-11-10 1994-01-25 Cortech Inc Bradykinin antagonists
US5942555A (en) * 1996-03-21 1999-08-24 Surmodics, Inc. Photoactivatable chain transfer agents and semi-telechelic photoactivatable polymers prepared therefrom
US20020058286A1 (en) * 1999-02-24 2002-05-16 Danishefsky Samuel J. Synthesis of epothilones, intermediates thereto and analogues thereof
AU2001243372A1 (en) * 2000-03-01 2001-09-12 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
AU2001295195B2 (en) * 2000-04-28 2007-02-01 Kosan Biosciences, Inc. Myxococcus host cells for the production of epothilones
US6441213B1 (en) * 2000-05-18 2002-08-27 National Starch And Chemical Investment Holding Corporation Adhesion promoters containing silane, carbamate or urea, and donor or acceptor functionality
WO2001092255A2 (fr) * 2000-05-26 2001-12-06 Kosan Biosciences, Inc. Derives d'epothilone, procedes de production et methodes d'utilisation
DE10041221A1 (de) * 2000-08-22 2002-03-14 Deutsches Krebsforsch Verfahren zur Herstellung von wasserlöslichen Saccharidkonjugaten und Saccharidmimetika durch Diels-Alder-Reaktion und ihre Verwendung als Therapeutika oder Diagnostika
GB0116143D0 (en) * 2001-07-02 2001-08-22 Amersham Pharm Biotech Uk Ltd Chemical capture reagent

Also Published As

Publication number Publication date
JP2006505627A (ja) 2006-02-16
KR20050026033A (ko) 2005-03-14
IS7708A (is) 2005-02-23
AU2003253365A1 (en) 2004-02-23
HRP20050186A2 (en) 2005-10-31
WO2004012735A3 (fr) 2004-05-27
BR0313043A (pt) 2005-06-14
PL374528A1 (en) 2005-10-31
NZ537870A (en) 2007-03-30
WO2004012735A2 (fr) 2004-02-12
IL166039A0 (en) 2006-01-15
EP1524979A2 (fr) 2005-04-27
ECSP055626A (es) 2005-04-18
MXPA05001282A (es) 2005-04-28
CO5700741A2 (es) 2006-11-30
NO20051038L (no) 2005-04-06

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Legal Events

Date Code Title Description
EEER Examination request
FZDE Discontinued