BE2011C028I2 - Macrocyclic analogs and methods of their use and preparation - Google Patents

Macrocyclic analogs and methods of their use and preparation

Info

Publication number
BE2011C028I2
BE2011C028I2 BE2011C028C BE2011C028C BE2011C028I2 BE 2011C028 I2 BE2011C028 I2 BE 2011C028I2 BE 2011C028 C BE2011C028 C BE 2011C028C BE 2011C028 C BE2011C028 C BE 2011C028C BE 2011C028 I2 BE2011C028 I2 BE 2011C028I2
Authority
BE
Belgium
Prior art keywords
preparation
methods
macrocyclic analogs
analogs
macrocyclic
Prior art date
Application number
BE2011C028C
Other languages
French (fr)
Original Assignee
Eisai R&D Man Co Ltd
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22219026&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=BE2011C028(I2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Eisai R&D Man Co Ltd filed Critical Eisai R&D Man Co Ltd
Publication of BE2011C028I2 publication Critical patent/BE2011C028I2/en

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Classifications

    • 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
    • C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicinal Preparation (AREA)
  • Steroid Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Saccharide Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention provides a compound having the formula: that is useful as an intermediate in the preparation of certain pharmaceutically active halichondrin analogs.
BE2011C028C 1998-06-17 2011-09-02 Macrocyclic analogs and methods of their use and preparation BE2011C028I2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US8968298P 1998-06-17 1998-06-17
PCT/US1999/013677 WO1999065894A1 (en) 1998-06-17 1999-06-16 Macrocyclic analogs and methods of their use and preparation
EP99928746A EP1087960B1 (en) 1998-06-17 1999-06-16 Macrocyclic analogs and methods of their use and preparation

Publications (1)

Publication Number Publication Date
BE2011C028I2 true BE2011C028I2 (en) 2018-08-24

Family

ID=22219026

Family Applications (1)

Application Number Title Priority Date Filing Date
BE2011C028C BE2011C028I2 (en) 1998-06-17 2011-09-02 Macrocyclic analogs and methods of their use and preparation

Country Status (22)

Country Link
US (4) US6214865B1 (en)
EP (4) EP2277873B1 (en)
JP (1) JP4454151B2 (en)
KR (1) KR100798600B1 (en)
CN (1) CN1216051C (en)
AT (1) ATE502932T1 (en)
AU (1) AU762998B2 (en)
BE (1) BE2011C028I2 (en)
BR (1) BRPI9911326B8 (en)
CA (3) CA2632433C (en)
CY (2) CY1111516T1 (en)
DE (2) DE69943296D1 (en)
DK (1) DK1087960T3 (en)
FR (1) FR11C0038I2 (en)
HU (1) HU227912B1 (en)
IL (1) IL139960A0 (en)
LU (1) LU91854I2 (en)
NO (5) NO328280B1 (en)
NZ (1) NZ508597A (en)
PT (1) PT1087960E (en)
WO (1) WO1999065894A1 (en)
ZA (1) ZA200007159B (en)

Families Citing this family (99)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL139960A0 (en) 1998-06-17 2002-02-10 Eisai Co Ltd Macrocylic analogs and methods of their use and preparation
US8097648B2 (en) * 1998-06-17 2012-01-17 Eisai R&D Management Co., Ltd. Methods and compositions for use in treating cancer
US6653341B1 (en) 1998-06-17 2003-11-25 Eisai Co., Ltd. Methods and compositions for use in treating cancer
DE10037310A1 (en) 2000-07-28 2002-02-07 Asta Medica Ag New indole derivatives and their use as medicines
EP1531846A4 (en) * 2002-02-27 2006-04-19 Us Gov Health & Human Serv LIGAND CONJUGATES, ADAPTER AND CYTOTOXIC AGENT, RELATED COMPOSITIONS AND RELATED METHODS OF USE
US7192972B2 (en) 2002-03-22 2007-03-20 Eisai Co., Ltd. Hemiasterlin derivatives and uses thereof
US20050075395A1 (en) * 2003-05-28 2005-04-07 Gary Gordon Continuous dosing regimen
CA2526385C (en) * 2003-05-29 2008-07-22 Abbott Laboratories Continuous dosing regimen with abt-751
US20070196418A1 (en) * 2003-07-29 2007-08-23 Michael Lewis Drug delivery methods and devices
CN101899026B (en) 2004-06-03 2016-08-03 卫材R&D管理有限公司 Intermediates for the preparation of analogues of halichondrin B
CN109180615A (en) * 2004-06-03 2019-01-11 卫材R&D管理有限公司 Intermediates for the preparation of analogs of halichondrin B
US20060045846A1 (en) * 2004-08-30 2006-03-02 Horstmann Thomas E Reagents and methods for labeling terminal olefins
WO2006076100A2 (en) * 2004-12-09 2006-07-20 Eisai Co. Ltd. Tubulin isotype screening in cancer therapy using halichondrin b analogs
BRPI0817909B1 (en) * 2007-10-03 2022-06-21 Eisai R&D Management Co., Ltd Methods of obtaining and preparing a diastereomerically pure composition, compounds, and method of producing said compounds
JP6001857B2 (en) * 2008-04-04 2016-10-05 エーザイ・アール・アンド・ディー・マネジメント株式会社 Halichondrin B analog
SI2415470T1 (en) 2009-03-30 2016-12-30 Eisai R&D Management Co., Ltd. Liposome composition
JP5622719B2 (en) 2009-03-30 2014-11-12 エーザイ・アール・アンド・ディー・マネジメント株式会社 Method for producing liposome composition
RU2476216C1 (en) * 2009-03-30 2013-02-27 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Liposomal composition
WO2010119890A1 (en) * 2009-04-14 2010-10-21 日産化学工業株式会社 Method for producing tetrahydropyran compound and intermediate thereof
TH121482A (en) 2009-08-19 2013-02-28 นางสาวปัณณพัฒน์ เหลืองธาตุทอง Quinoline derivative-containing pharmaceutical composition
BR112012018232B8 (en) 2010-01-26 2023-01-10 Eisai R&D Man Co Ltd FURO [3,2-B] PYRAN DERIVATIVE COMPOUNDS USEFUL IN THE SYNTHESIS OF HALICONDRIN B ANALOGS AND ER-80402 AND ERIBULIN SYNTHESIS METHODS
ES2731653T3 (en) 2011-03-18 2019-11-18 Eisai R&D Man Co Ltd Methods and uses to predict the response to eribulin
WO2012147900A1 (en) 2011-04-28 2012-11-01 Eisai R&D Management Co., Ltd. Microreactor process for halichondrin b analog synthesis
EP3444363B1 (en) 2011-06-03 2020-11-25 Eisai R&D Management Co., Ltd. Biomarkers for prediciting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds
EP2785687B1 (en) 2011-11-30 2019-02-20 Sandoz AG Process for preparation of (3r)-2,4-di-leaving group-3-methylbut-1-ene
EP2791123B1 (en) 2011-12-16 2018-07-18 Sandoz AG Process for preparation of 3-((2s,5s)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl) propanol derivatives and intermediates useful thereof
AU2012363334B2 (en) * 2011-12-29 2017-02-02 Alphora Research Inc. 2-((2s,3s,4r,5r)-5-((s)-3-amino-2-hydroxyprop-1-yl)-4-methoxy-3-(phenylsulfonylmethyl) tetrahydrofuran-2-yl)acetaldehyde derivatives and process for their preparation
CN104334562A (en) * 2012-03-30 2015-02-04 阿方拉研究股份有限公司 Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein
WO2014087230A1 (en) 2012-12-04 2014-06-12 Eisai R&D Management Co., Ltd. Use of eribulin in the treatment of breast cancer
WO2014183211A1 (en) 2013-05-15 2014-11-20 Alphora Research Inc. 3-((2s,5s)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl)propanol derivatives, their preparation and intermediates useful thereof
ES2705698T3 (en) 2013-06-26 2019-03-26 Eisai R&D Man Co Ltd Combination therapy for cancer treatment comprising eribulin and lenvatinib
AU2014286880B2 (en) * 2013-07-03 2017-12-14 Sandoz Ag Synthetic process for preparation of macrocyclic C1-keto analogs of Halichondrin B and intermediates useful therein including intermediates containing -SO2-(p-TOLYL) groups
CN103483352A (en) * 2013-10-18 2014-01-01 李友香 Medicinal bulk drug for resisting tumors
HUE049387T2 (en) 2013-11-04 2020-09-28 Eisai R&D Man Co Ltd Macrocyclization reactions and intermediates useful in the synthesis of analogs of halichondrin b
SG10201805024YA (en) 2013-12-06 2018-07-30 Eisai R&D Man Co Ltd Methods useful in the synthesis of halichondrin b analogs
CN104860978A (en) * 2014-02-20 2015-08-26 正大天晴药业集团股份有限公司 Synthesis intermediates of halichondrin B analog
TW201617326A (en) * 2014-03-06 2016-05-16 Ａｌｐｈｏｒａ研發股份有限公司 Crystalline derivatives of (S)-1-((2R,3R,4S,5S)-5-allyl-3-methoxy-4-(tosylmethyl)tetrahydrofuran-2-yl)-3-aminopropan-2-ol
KR20170039096A (en) * 2014-05-28 2017-04-10 에자이 알앤드디 매니지먼트 가부시키가이샤 Use of eribulin in the treatment of cancer
US10556910B2 (en) * 2014-06-30 2020-02-11 President And Fellows Of Harvard College Synthesis of halichondrin analogs and uses thereof
KR20230043234A (en) 2014-08-28 2023-03-30 에자이 알앤드디 매니지먼트 가부시키가이샤 High-purity quinoline derivative and method for manufacturing same
WO2016038624A1 (en) 2014-09-09 2016-03-17 Cipla Limited "process for the preparation of macrocyclic ketone analogs of halichondrin b or pharmaceutically acceptable salts and intermediates thereof"
CN105713031B (en) * 2014-12-05 2021-05-07 正大天晴药业集团股份有限公司 Intermediate for preparing eribulin and preparation method thereof
LT3263106T (en) 2015-02-25 2024-01-10 Eisai R&D Management Co., Ltd. METHOD OF REDUCING BITTERNESS OF QUINOLINE DERIVATIVES
JP6951248B2 (en) * 2015-03-04 2021-10-20 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． Combination of PD-1 antagonist and eribulin to treat cancer
KR102662228B1 (en) 2015-03-04 2024-05-02 머크 샤프 앤드 돔 코포레이션 Combination of PD-1 antagonists and VEGFR/FGFR/RET tyrosine kinase inhibitors to treat cancer
US10344038B2 (en) 2015-04-30 2019-07-09 President And Fellows Of Harvard College Chromium-mediated coupling and application to the synthesis of halichondrins
MX380284B (en) * 2015-05-07 2025-03-12 Eisai R&D Man Co Ltd Macrocyclization reactions and intermediates and other fragments useful in the synthesis of halichondrin macrolides
US10597401B2 (en) 2015-05-08 2020-03-24 Albany Molecular Research, Inc. Methods and intermediates for the preparation of omacetaxine and cephalotaxine derivatives thereof
MX373231B (en) 2015-06-16 2020-05-08 Eisai R&D Man Co Ltd ANTICANCER AGENT.
CA2994925C (en) 2015-08-20 2023-08-29 Eisai R&D Management Co., Ltd. Tumor therapeutic agent
US10676481B2 (en) 2016-02-12 2020-06-09 Eisai R&D Management Co., Ltd. Intermediates in the synthesis of eribulin and related methods of synthesis
EP3449921B1 (en) 2016-04-28 2023-05-31 Eisai R&D Management Co., Ltd. Eribulin for inhibiting tumor growth
EP3464297B1 (en) 2016-05-26 2023-10-25 Dr. Reddy's Laboratories Ltd. Process for preparation of eribulin and intermediates thereof
SG11201811671XA (en) 2016-06-30 2019-01-30 Eisai R&D Man Co Ltd Prins reaction and intermediates useful in the synthesis of halichondrin macrolides and analogs thereof
JP2019530706A (en) 2016-10-14 2019-10-24 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． Combination of PD-1 antagonist and eribulin for treating urothelial cancer
JP6978758B2 (en) 2016-11-11 2021-12-08 プレジデント アンド フェローズ オブ ハーバード カレッジ Palladium-mediated ketolization
WO2018096478A2 (en) 2016-11-23 2018-05-31 Dr. Reddy’S Laboratories Limited Process for preparation of eribulin and intermediates thereof
KR101880939B1 (en) 2017-01-02 2018-08-17 연성정밀화학(주) Intermediate for Preparing Eribulin Mesylate and Process for Preapring the Same
CN110139866B (en) * 2017-01-02 2022-05-17 研成精密化学株式会社 Intermediates for the preparation of eribulin mesylate and methods for preparing the same
KR101991710B1 (en) 2017-12-14 2019-06-21 연성정밀화학(주) Intermediate for Preparing Eribulin Mesylate and Process for Preparing the Same
CN108341828B (en) * 2017-01-24 2021-04-06 江苏恒瑞医药股份有限公司 Process for the preparation of eribulin and intermediates thereof
CN108341738B (en) * 2017-01-24 2022-10-21 江苏恒瑞医药股份有限公司 Process for the preparation of eribulin and intermediates thereof
US12303505B2 (en) 2017-02-08 2025-05-20 Eisai R&D Management Co., Ltd. Tumor-treating pharmaceutical composition
JP7168580B2 (en) 2017-04-05 2022-11-09 プレジデント アンド フェローズ オブ ハーバード カレッジ Macrocycles and uses thereof
US9938288B1 (en) 2017-04-05 2018-04-10 President And Fellows Of Harvard College Macrocyclic compound and uses thereof
BR112019023064A2 (en) 2017-05-16 2020-06-09 Eisai R&D Man Co Ltd treatment of hepatocellular carcinoma
IL295588B2 (en) 2017-07-06 2024-03-01 Harvard College Synthesis of the Lichondrins
US11498892B2 (en) 2017-07-06 2022-11-15 President And Fellows Of Harvard College Fe/Cu-mediated ketone synthesis
US20190046513A1 (en) 2017-08-10 2019-02-14 Huya Bioscience International, Llc Combination therapies of hdac inhibitors and tubulin inhibitors
CN109694379B (en) * 2017-10-24 2020-09-11 江苏恒瑞医药股份有限公司 Intermediate for preparing eribulin and preparation method thereof
JP6967811B2 (en) * 2017-11-09 2021-11-17 ヨンスン ファイン ケミカル カンパニー，リミテッド Eribulin mesylate production intermediate and its production method
ES2974243T3 (en) 2017-11-15 2024-06-26 Harvard College Macrocyclic compounds and their uses
WO2019097073A1 (en) 2017-11-20 2019-05-23 Basilea Pharmaceutica International AG Pharmaceutical combinations for use in the treatment of neoplastic diseases
WO2019102490A1 (en) 2017-11-21 2019-05-31 Natco Pharma Limited Intermediates for the preparation of eribulin thereof
KR20250057138A (en) 2018-01-03 2025-04-28 에자이 알앤드디 매니지먼트 가부시키가이샤 Prins reaction and compounds useful in the synthesis of halichondrin macrolides and analogs thereof
WO2019211877A1 (en) 2018-05-03 2019-11-07 Cipla Limited Process for the preparation of macrocyclic ketone analogs of halichondrin b
WO2020008382A1 (en) * 2018-07-04 2020-01-09 Dr. Reddy’S Laboratories Limited Process for preparation of eribulin and intermediates thereof
EP3823973A4 (en) * 2018-07-20 2022-09-21 Dr. Reddy's Laboratories Limited PURIFICATION PROCESSES FOR THE MANUFACTURE OF ERIBULIN AND INTERMEDIATE PRODUCTS THEREOF
US20210340156A1 (en) * 2018-10-09 2021-11-04 Dr. Reddy's Laboratories Limited Process for preparation of eribulin and intermediates thereof
US12522611B2 (en) * 2018-11-28 2026-01-13 Natco Pharma Limited Process for the preparation of high pure Eribulin and its Mesylate salt
WO2020132636A1 (en) 2018-12-20 2020-06-25 Auransa Inc. Analogues of pentamidine and uses therefor
US11447499B2 (en) 2019-06-14 2022-09-20 Rk Pharma Inc. Process for the preparation of eribulin mesylate intermediate
JP7574232B2 (en) 2019-06-21 2024-10-28 カウンスィル 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 Chemoenzymatic process for the preparation of homopropargylic alcohols
US11083705B2 (en) 2019-07-26 2021-08-10 Eisai R&D Management Co., Ltd. Pharmaceutical composition for treating tumor
US12036204B2 (en) 2019-07-26 2024-07-16 Eisai R&D Management Co., Ltd. Pharmaceutical composition for treating tumor
JP7657213B2 (en) 2019-11-07 2025-04-04 エーザイ・アール・アンド・ディー・マネジメント株式会社 Anti-mesothelin eribulin antibody-drug conjugates and methods of use
CN113135876B (en) * 2020-01-16 2024-05-17 南通诺泰生物医药技术有限公司 Preparation method of eribulin and intermediate thereof
AU2021210079A1 (en) * 2020-01-22 2022-08-25 Jiangsu Hengrui Medicine Co., Ltd. Drug conjugate of Eribulin derivative, preparation method therefor and application thereof in medicine
KR102377262B1 (en) 2020-05-11 2022-03-22 연성정밀화학(주) Crystalline Eribulin Salt
IL279168B (en) 2020-12-02 2022-04-01 Finetech Pharmaceutical Ltd Process for the preparation of eribulin
CN113354659B (en) 2021-06-08 2022-04-08 江苏慧聚药业股份有限公司 Synthesis of eribulin mesylate
CA3225975A1 (en) * 2021-07-22 2023-01-26 Shanghai Senhui Medicine Co., Ltd. Drug conjugate of eribulin derivative
WO2023212746A2 (en) * 2022-04-30 2023-11-02 William Marsh Rice University A unified strategy for the total syntheses of eribulin and a macrolactam analogue of halichondrin b
KR20250133788A (en) * 2023-01-17 2025-09-08 시스트이뮨, 인코포레이티드 Eribulin drug conjugate
TW202513596A (en) 2023-06-09 2025-04-01 大陸商徠特康（蘇州）生物製藥有限公司 Anti-HER2 antibody, antibody-drug conjugate and drug combination, drug kit, preparation method and use thereof
CN118834221B (en) * 2023-08-08 2025-10-21 浙江星月药物科技有限公司 A halichondrin B analogue
WO2025081063A2 (en) 2023-10-13 2025-04-17 Eisai R&D Management Co., Ltd. Antibody-drug conjugate metabolites
WO2025106586A1 (en) * 2023-11-13 2025-05-22 Luxvitae Therapeutics Inc. Macrocyclic ketone compounds and applications thereof
WO2025228172A1 (en) * 2024-04-28 2025-11-06 上海拓济医药有限责任公司 Eribulin derivative and antibody-drug conjugate thereof, and medical use thereof

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5338865A (en) * 1992-03-12 1994-08-16 President And Fellows Of Harvard College Synthesis of halichondrin B and norhalichondrin B
US5436238A (en) 1992-03-12 1995-07-25 President And Fellows Of Harvard College Halichondrins and related compounds
GB9206244D0 (en) * 1992-03-23 1992-05-06 Pharma Mar Sa Cytotoxic compound from a marine sponge
US5426194A (en) * 1993-01-19 1995-06-20 Arizona Board Of Regents, A Body Corporate Acting On Behalf Of Arizona State University Isolation and structure of Halistatin 1
IL139960A0 (en) 1998-06-17 2002-02-10 Eisai Co Ltd Macrocylic analogs and methods of their use and preparation
US6653341B1 (en) * 1998-06-17 2003-11-25 Eisai Co., Ltd. Methods and compositions for use in treating cancer
CN101899026B (en) 2004-06-03 2016-08-03 卫材R&D管理有限公司 Intermediates for the preparation of analogues of halichondrin B
BRPI0817909B1 (en) * 2007-10-03 2022-06-21 Eisai R&D Management Co., Ltd Methods of obtaining and preparing a diastereomerically pure composition, compounds, and method of producing said compounds
JP5134686B2 (en) * 2007-11-16 2013-01-30 エーザイ・アール・アンド・ディー・マネジメント株式会社 Novel intermediates for the synthesis of halichondrin B analogues and novel desulfonylation reactions for use in said intermediates
JP6001857B2 (en) 2008-04-04 2016-10-05 エーザイ・アール・アンド・ディー・マネジメント株式会社 Halichondrin B analog
BR112012018232B8 (en) * 2010-01-26 2023-01-10 Eisai R&D Man Co Ltd FURO [3,2-B] PYRAN DERIVATIVE COMPOUNDS USEFUL IN THE SYNTHESIS OF HALICONDRIN B ANALOGS AND ER-80402 AND ERIBULIN SYNTHESIS METHODS

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Publication number Publication date
US8148554B2 (en) 2012-04-03
HU227912B1 (en) 2012-05-29
PT1087960E (en) 2011-06-17
ATE502932T1 (en) 2011-04-15
EP1087960B1 (en) 2011-03-23
CA2335300A1 (en) 1999-12-23
NO2011018I1 (en) 2011-09-26
ZA200007159B (en) 2001-12-04
JP2002518384A (en) 2002-06-25
KR20010083050A (en) 2001-08-31
NO331183B1 (en) 2011-10-24
EP2272840B1 (en) 2012-08-22
NO20093217L (en) 2001-02-15
CN1312804A (en) 2001-09-12
HK1035534A1 (en) 2001-11-30
US6469182B1 (en) 2002-10-22
NZ508597A (en) 2004-01-30
KR100798600B1 (en) 2008-01-28
US20110172446A1 (en) 2011-07-14
WO1999065894A1 (en) 1999-12-23
EP1087960A1 (en) 2001-04-04
BRPI9911326B8 (en) 2021-05-25
HUP0103357A2 (en) 2002-01-28
NO2022019I1 (en) 2022-06-03
BR9911326A (en) 2001-04-03
US6365759B1 (en) 2002-04-02
EP2277873B1 (en) 2012-05-30
JP4454151B2 (en) 2010-04-21
EP2277873A1 (en) 2011-01-26
CY2011010I1 (en) 2014-04-09
US6214865B1 (en) 2001-04-10
EP2272839B1 (en) 2012-08-22
FR11C0038I1 (en) 2011-10-14
CA2755266A1 (en) 1999-12-23
AU762998C (en) 2000-01-05
CA2632433C (en) 2012-02-07
DE69943296D1 (en) 2011-05-05
FR11C0038I2 (en) 2013-01-11
BR9911326B1 (en) 2015-01-06
AU762998B2 (en) 2003-07-10
EP2272839A1 (en) 2011-01-12
NO20006316L (en) 2001-02-15
NO2011026I1 (en) 2012-01-09
CA2632433A1 (en) 1999-12-23
DE122011100031I1 (en) 2011-12-15
RU2245335C2 (en) 2005-01-27
CY2011010I2 (en) 2014-04-09
NO2011026I2 (en) 2012-06-11
IL139960A0 (en) 2002-02-10
AU4573999A (en) 2000-01-05
DK1087960T3 (en) 2011-06-14
CA2755266C (en) 2014-08-12
CY1111516T1 (en) 2014-04-09
LU91854I2 (en) 2011-10-17
EP1087960A4 (en) 2004-12-01
NO328280B1 (en) 2010-01-25
CA2335300C (en) 2008-10-07
HUP0103357A3 (en) 2002-10-28
CN1216051C (en) 2005-08-24
EP2272840A1 (en) 2011-01-12
NO20006316D0 (en) 2000-12-12

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