AU2003275364A1 - Synergistic methods and compositions for treating cancer - Google Patents
Synergistic methods and compositions for treating cancer Download PDFInfo
- Publication number
- AU2003275364A1 AU2003275364A1 AU2003275364A AU2003275364A AU2003275364A1 AU 2003275364 A1 AU2003275364 A1 AU 2003275364A1 AU 2003275364 A AU2003275364 A AU 2003275364A AU 2003275364 A AU2003275364 A AU 2003275364A AU 2003275364 A1 AU2003275364 A1 AU 2003275364A1
- Authority
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- Australia
- Prior art keywords
- methyl
- hydroxy
- phenyl
- pyridin
- ethylamino
- 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
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- 238000000034 method Methods 0.000 title claims description 37
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41541602P | 2002-10-02 | 2002-10-02 | |
| US60/415,416 | 2002-10-02 | ||
| PCT/US2003/031091 WO2004030627A2 (en) | 2002-10-02 | 2003-10-01 | Synergistic methods and compositions for treating cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2003275364A1 true AU2003275364A1 (en) | 2004-04-23 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
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| AU2003275364A Abandoned AU2003275364A1 (en) | 2002-10-02 | 2003-10-01 | Synergistic methods and compositions for treating cancer |
| AU2003282892A Abandoned AU2003282892A1 (en) | 2002-10-02 | 2003-10-01 | Synergistic methods and compositions for treating cancer |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2003282892A Abandoned AU2003282892A1 (en) | 2002-10-02 | 2003-10-01 | Synergistic methods and compositions for treating cancer |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US20040106605A1 (enExample) |
| EP (2) | EP1551411A2 (enExample) |
| JP (2) | JP2006503866A (enExample) |
| AU (2) | AU2003275364A1 (enExample) |
| CA (2) | CA2500714A1 (enExample) |
| TW (2) | TW200501960A (enExample) |
| WO (2) | WO2004030625A2 (enExample) |
Families Citing this family (71)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP0977563B1 (en) * | 1996-12-03 | 2005-10-12 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US20020058286A1 (en) * | 1999-02-24 | 2002-05-16 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto and analogues thereof |
| WO2003002609A2 (en) * | 2001-06-28 | 2003-01-09 | Domantis Limited | Dual-specific ligand and its use |
| US20050271663A1 (en) * | 2001-06-28 | 2005-12-08 | Domantis Limited | Compositions and methods for treating inflammatory disorders |
| NZ571508A (en) | 2002-05-24 | 2010-05-28 | Schering Corp | Neutralizing human anti-IGFR antibody |
| US7696320B2 (en) | 2004-08-24 | 2010-04-13 | Domantis Limited | Ligands that have binding specificity for VEGF and/or EGFR and methods of use therefor |
| US9321832B2 (en) * | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
| AU2003244817B2 (en) * | 2002-06-28 | 2010-08-26 | Domantis Limited | Antigen-binding immunoglobulin single variable domains and dual-specific constructs |
| US7649006B2 (en) | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| WO2004018478A2 (en) * | 2002-08-23 | 2004-03-04 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US6921769B2 (en) | 2002-08-23 | 2005-07-26 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| AU2003290330A1 (en) * | 2002-12-27 | 2004-07-22 | Domantis Limited | Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand |
| BRPI0415395A (pt) * | 2003-10-15 | 2006-12-12 | Osi Pharm Inc | composto, métodos para inibir a atividade da proteìna quinase e para tratar um paciente que tenha uma condição que seja mediada pela atividade da proteìna quinase, e, composição |
| JP2007510434A (ja) | 2003-11-12 | 2007-04-26 | シェーリング コーポレイション | 多重遺伝子発現のためのプラスミドシステム |
| US8017321B2 (en) | 2004-01-23 | 2011-09-13 | The Regents Of The University Of Colorado, A Body Corporate | Gefitinib sensitivity-related gene expression and products and methods related thereto |
| ATE514434T1 (de) | 2004-02-25 | 2011-07-15 | Dana Farber Cancer Inst Inc | Hemmer des insulinartigen wachstumsfaktor- rezeptors-1 zur hemmung von tumorzellwachstum |
| AR048518A1 (es) | 2004-04-02 | 2006-05-03 | Osi Pharm Inc | Inhibidores heterobiciclicos de proteina quinasas sustituidos con anillos 6,6 -biciclicos |
| WO2005117553A2 (en) * | 2004-05-27 | 2005-12-15 | The Regents Of The University Of Colorado | Methods for prediction of clinical outcome to epidermal growth factor receptor inhibitors by cancer patients |
| AU2005249205A1 (en) * | 2004-06-03 | 2005-12-15 | F. Hoffmann-La Roche Ag | Treatment with gemcitabine and an EGFR-inhibitor |
| US7811562B2 (en) | 2004-12-03 | 2010-10-12 | Schering Corporation | Biomarkers for pre-selection of patients for anti-IGF1R therapy |
| AU2006218404A1 (en) * | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | N-phenyl benzamide derivatives as sirtuin modulators |
| DE602006016085D1 (de) * | 2005-03-16 | 2010-09-23 | Genentech Inc | Biologische marker prediktiv für das ansprechen von krebs auf inhibitoren der kinase des rezeptors für epidermalen wachstumsfaktor |
| US8383357B2 (en) * | 2005-03-16 | 2013-02-26 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to epidermal growth factor receptor kinase inhibitors |
| KR20080019249A (ko) | 2005-06-15 | 2008-03-03 | 쉐링 코포레이션 | 안정한 항체 제형 |
| ES2431050T3 (es) * | 2005-08-04 | 2013-11-22 | Sirtris Pharmaceuticals, Inc. | Benzotiazoles y tiazolopiridinas como moduladores de la sirtuína |
| US8088928B2 (en) | 2005-08-04 | 2012-01-03 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US7855289B2 (en) | 2005-08-04 | 2010-12-21 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US8093401B2 (en) * | 2005-08-04 | 2012-01-10 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US8580814B2 (en) * | 2006-04-03 | 2013-11-12 | Sunesis Pharmaceuticals, Inc. | Methods of using (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4- oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid for treatment of cancer |
| US8062838B2 (en) * | 2005-09-20 | 2011-11-22 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| JP2009519011A (ja) * | 2005-12-01 | 2009-05-14 | ドマンティス リミテッド | インターロイキン１受容体１型に結合する非競合ドメイン抗体フォーマット |
| US8575164B2 (en) * | 2005-12-19 | 2013-11-05 | OSI Pharmaceuticals, LLC | Combination cancer therapy |
| US7589087B2 (en) | 2006-03-31 | 2009-09-15 | Janssen Pharmaceutica, N.V. | Benzoimidazol-2-yl pyridines as modulators of the histamine H4receptor |
| ME01143B (me) | 2006-03-31 | 2013-03-20 | Janssen Pharmaceutica Nv | BENZOIMIDAZOL-2-IL PIRIMIDINI l PIRAZINI KAO MODULATORI HISTAMINSKOG H4 RECEPTORA |
| EP2338488A1 (en) * | 2006-05-26 | 2011-06-29 | Bayer HealthCare, LLC | Drug combinations with substituted diaryl ureas for the treatment of cancer |
| CA2673095C (en) * | 2006-12-20 | 2016-03-15 | Nerviano Medical Sciences S.R.L. | Indazole derivatives as kinase inhibitors for the treatment of cancer |
| TW200833711A (en) * | 2006-12-22 | 2008-08-16 | Genentech Inc | Antibodies to insulin-like growth factor receptor |
| TW200900070A (en) * | 2007-02-27 | 2009-01-01 | Osi Pharm Inc | Combination cancer therapy |
| EP2134860A1 (en) * | 2007-04-13 | 2009-12-23 | OSI Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to kinase inhibitors |
| EA200901301A1 (ru) * | 2007-06-06 | 2010-06-30 | Домантис Лимитед | Полипептиды, вариабельные домены антител и антагонисты |
| CL2008001822A1 (es) * | 2007-06-20 | 2009-03-13 | Sirtris Pharmaceuticals Inc | Compuestos derivados de tiazolo[5,4-b]piridina; composicion farmaceutica que comprende a dichos compuestos; y uso del compuesto en el tratamiento de la resistencia a la insulina, sindrome metabolico, diabetes, entre otras. |
| AU2008307634A1 (en) * | 2007-10-03 | 2009-04-09 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| AU2008307579A1 (en) * | 2007-10-03 | 2009-04-09 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| WO2009058348A1 (en) * | 2007-11-01 | 2009-05-07 | Sirtris Pharmaceuticals, Inc. | Amide derivatives as sirtuin modulators |
| WO2009061453A1 (en) * | 2007-11-08 | 2009-05-14 | Sirtris Pharmaceuticals, Inc. | Solubilized thiazolopyridines |
| WO2009079001A1 (en) | 2007-12-18 | 2009-06-25 | Janssen Pharmaceutica N.V. | Bicyclic heteroaryl-substituted imidazoles as modulators of the histamine h4 receptor |
| ES2402138T3 (es) * | 2007-12-28 | 2013-04-29 | Deutsches Krebsforschungszentrum, Stiftung Des Öffentlichen Rechts | Terapia contra el cáncer con un parvovirus combinado con quimioterapia |
| JP2011510018A (ja) * | 2008-01-18 | 2011-03-31 | オーエスアイ・フアーマスーテイカルズ・インコーポレーテツド | 癌治療のためのイミダゾピラジノール誘導体 |
| RU2008106419A (ru) * | 2008-02-21 | 2009-08-27 | Закрытое акционерное общество "Ива фарм" (RU) | Лекарственные средства на основе олигоядерных координационных соединений d-металлов, способ терапевтического воздействия на организм пациента и способ повышения терапевтической эффективности фармакологически активного вещества |
| CN101925528B (zh) | 2008-03-27 | 2012-11-28 | 三菱电机株式会社 | 电梯控制系统 |
| EP2283020B8 (en) * | 2008-05-19 | 2012-12-12 | OSI Pharmaceuticals, LLC | Substituted imidazopyr-and imidazotri-azines |
| US9371311B2 (en) | 2008-06-30 | 2016-06-21 | Janssen Pharmaceutica Nv | Benzoimidazol-2-yl pyrimidine derivatives |
| BRPI0922435A2 (pt) | 2008-12-19 | 2018-09-11 | Sirtris Pharmaceuticals Inc | "composto de tiazolopiridina moduladores de sirtuina, composição farmacêutica compreendendo o mesmo e seu uso." |
| WO2010099137A2 (en) * | 2009-02-26 | 2010-09-02 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the emt status of tumor cells in vivo |
| JP2012520893A (ja) | 2009-03-18 | 2012-09-10 | オーエスアイ・ファーマシューティカルズ，エルエルシー | Ｅｇｆｒ阻害薬及びｉｇｆ−１ｒ阻害剤の投与を含む組み合わせ癌治療 |
| MX2011011025A (es) | 2009-04-20 | 2011-11-02 | Osi Pharmaceuticals Llc | Preparacion de c-piracin-metilaminas. |
| WO2010129740A1 (en) * | 2009-05-07 | 2010-11-11 | Osi Pharmaceuticals, Inc. | Use of osi-906 for treating adrenocortical carcinoma |
| WO2010146059A2 (en) | 2009-06-16 | 2010-12-23 | F. Hoffmann-La Roche Ag | Biomarkers for igf-1r inhibitor therapy |
| EP2542893A2 (en) * | 2010-03-03 | 2013-01-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| JP5607241B2 (ja) | 2010-05-21 | 2014-10-15 | ケミリア・エービー | 新規ピリミジン誘導体 |
| WO2012117396A1 (en) * | 2011-03-01 | 2012-09-07 | Novotyr Therapeutics Ltd | Tyrphostin derivative in combination with cytotoxic compounds for treating cancer |
| WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
| EP2688883B1 (en) | 2011-03-24 | 2016-05-18 | Noviga Research AB | Pyrimidine derivatives |
| EP2702173A1 (en) | 2011-04-25 | 2014-03-05 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
| US9834575B2 (en) | 2013-02-26 | 2017-12-05 | Triact Therapeutics, Inc. | Cancer therapy |
| BR112015021463A8 (pt) | 2013-03-06 | 2019-11-19 | Janssen Pharmaceutica Nv | moduladores de benzoimidazol-2-il pirimidina do receptor histamínico h4,seu uso e composição faramacêutica |
| US9770454B2 (en) | 2013-07-14 | 2017-09-26 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. | IGF-1R signaling pathway inhibitors useful in the treatment of neurodegenerative diseases |
| EP3044593A4 (en) | 2013-09-09 | 2017-05-17 | Triact Therapeutics, Inc. | Cancer therapy |
| KR20170109589A (ko) * | 2015-02-05 | 2017-09-29 | 티르노보 리미티드 | 암 치료를 위한 irs/stat3 이중 조절제 및 항암제의 조합물 |
| GB201617627D0 (en) * | 2016-10-18 | 2016-11-30 | Cellcentric Ltd | Pharmaceutical compounds |
| KR102582752B1 (ko) * | 2016-12-13 | 2023-09-22 | 프린스턴 드러그 디스커버리 인크 | 단백질 키나아제 억제제 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2643903A1 (fr) * | 1989-03-03 | 1990-09-07 | Union Pharma Scient Appl | Nouveaux derives de benzimidazole, leurs procedes de preparation, intermediaires de synthese, compositions pharmaceutiques les contenant, utiles notamment pour le traitement des maladies cardiovasculaires, et des ulceres duodenaux |
| WO2000035455A1 (en) * | 1998-12-15 | 2000-06-22 | Telik, Inc. | Heteroaryl-aryl ureas as igf-1 receptor antagonists |
| EP1509230B1 (en) * | 2002-06-05 | 2007-01-03 | Cedars-Sinai Medical Center | Gefitinib (iressa) for the treatment of cancer |
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2003
- 2003-09-30 TW TW092127035A patent/TW200501960A/zh unknown
- 2003-10-01 US US10/676,214 patent/US20040106605A1/en not_active Abandoned
- 2003-10-01 US US10/677,067 patent/US20040072760A1/en not_active Abandoned
- 2003-10-01 JP JP2004541936A patent/JP2006503866A/ja not_active Withdrawn
- 2003-10-01 CA CA002500714A patent/CA2500714A1/en not_active Abandoned
- 2003-10-01 WO PCT/US2003/030933 patent/WO2004030625A2/en not_active Ceased
- 2003-10-01 EP EP03759640A patent/EP1551411A2/en not_active Withdrawn
- 2003-10-01 TW TW092127209A patent/TW200410689A/zh unknown
- 2003-10-01 CA CA002500729A patent/CA2500729A1/en not_active Abandoned
- 2003-10-01 AU AU2003275364A patent/AU2003275364A1/en not_active Abandoned
- 2003-10-01 AU AU2003282892A patent/AU2003282892A1/en not_active Abandoned
- 2003-10-01 JP JP2004541997A patent/JP2006503867A/ja not_active Withdrawn
- 2003-10-01 WO PCT/US2003/031091 patent/WO2004030627A2/en not_active Ceased
- 2003-10-01 EP EP03774511A patent/EP1556051A2/en not_active Withdrawn
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| EP1551411A2 (en) | 2005-07-13 |
| CA2500729A1 (en) | 2004-04-15 |
| AU2003282892A1 (en) | 2004-04-23 |
| TW200410689A (en) | 2004-07-01 |
| JP2006503866A (ja) | 2006-02-02 |
| JP2006503867A (ja) | 2006-02-02 |
| US20040106605A1 (en) | 2004-06-03 |
| TW200501960A (en) | 2005-01-16 |
| US20040072760A1 (en) | 2004-04-15 |
| WO2004030625A2 (en) | 2004-04-15 |
| WO2004030625A3 (en) | 2004-06-24 |
| WO2004030627A3 (en) | 2004-07-01 |
| CA2500714A1 (en) | 2004-04-15 |
| WO2004030627A2 (en) | 2004-04-15 |
| EP1556051A2 (en) | 2005-07-27 |
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