JP4541882B2 - Ｓｍａｃタンパク質のアポトーシスタンパク質阻害物質（ｉａｐ）との結合に対するペプチド阻害剤 - Google Patents
Ｓｍａｃタンパク質のアポトーシスタンパク質阻害物質（ｉａｐ）との結合に対するペプチド阻害剤 Download PDFInfo
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- JP4541882B2 JP4541882B2 JP2004518651A JP2004518651A JP4541882B2 JP 4541882 B2 JP4541882 B2 JP 4541882B2 JP 2004518651 A JP2004518651 A JP 2004518651A JP 2004518651 A JP2004518651 A JP 2004518651A JP 4541882 B2 JP4541882 B2 JP 4541882B2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
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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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
- C07D207/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- 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
- C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
- C07D207/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- 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
- C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
- C07D207/10—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 no 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
-
- 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
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- 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
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- 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
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
-
- 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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Genetics & Genomics (AREA)
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- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39315002P | 2002-07-02 | 2002-07-02 | |
| PCT/EP2003/007005 WO2004005248A1 (en) | 2002-07-02 | 2003-07-01 | Peptide inhibitors of smac protein binding to inhibitor of apoptosis proteins (iap) |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2006501181A JP2006501181A (ja) | 2006-01-12 |
| JP2006501181A5 JP2006501181A5 (enExample) | 2006-08-31 |
| JP4541882B2 true JP4541882B2 (ja) | 2010-09-08 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2004518651A Expired - Fee Related JP4541882B2 (ja) | 2002-07-02 | 2003-07-01 | Ｓｍａｃタンパク質のアポトーシスタンパク質阻害物質（ｉａｐ）との結合に対するペプチド阻害剤 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US20060128632A1 (enExample) |
| EP (1) | EP1519918A1 (enExample) |
| JP (1) | JP4541882B2 (enExample) |
| CN (1) | CN100384819C (enExample) |
| AU (1) | AU2003249920A1 (enExample) |
| BR (1) | BR0312408A (enExample) |
| CA (1) | CA2491041A1 (enExample) |
| WO (1) | WO2004005248A1 (enExample) |
Families Citing this family (77)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US7291615B2 (en) | 2003-05-01 | 2007-11-06 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| CN1933847A (zh) * | 2004-01-16 | 2007-03-21 | 密歇根大学董事会 | Smac肽模拟物及其应用 |
| BRPI0507482A (pt) * | 2004-02-05 | 2007-07-17 | Novartis Ag | combinação de (a) um inibidor de dna topoisomerase e (b) um inibidor de iap |
| CA2558615C (en) | 2004-03-23 | 2013-10-29 | Genentech, Inc. | Azabicyclo-octane inhibitors of iap |
| EP2253614B1 (en) * | 2004-04-07 | 2012-09-19 | Novartis AG | Inhibitors of IAP |
| MXPA06014969A (es) * | 2004-07-02 | 2007-02-08 | Genentech Inc | Inhibidores de iap. |
| EP1773766B1 (en) | 2004-07-15 | 2014-04-02 | Tetralogic Pharmaceuticals Corporation | Iap binding compounds |
| ATE477254T1 (de) * | 2004-12-20 | 2010-08-15 | Genentech Inc | Pyrrolidine als inhibitoren von iap |
| BRPI0607988A2 (pt) * | 2005-02-25 | 2009-10-27 | Tetralogic Pharmaceuticals | composto, composição farmacêutica, e método para induzir apoptose em uma célula |
| DE102005017116A1 (de) * | 2005-04-13 | 2006-10-26 | Novartis Ag | Hemmstoffe für Inhibitoren von Apoptose Proteinen (IAP) |
| US7772177B2 (en) | 2005-05-18 | 2010-08-10 | Aegera Therapeutics, Inc. | BIR domain binding compounds |
| AU2006254538A1 (en) | 2005-05-25 | 2006-12-07 | 2Curex Aps | Compounds modifying apoptosis |
| US8318717B2 (en) | 2005-05-25 | 2012-11-27 | 2Curex | Compounds modifying apoptosis |
| US20100256046A1 (en) * | 2009-04-03 | 2010-10-07 | Tetralogic Pharmaceuticals Corporation | Treatment of proliferative disorders |
| JP2009512719A (ja) | 2005-10-25 | 2009-03-26 | アエゲラ セラピューティクス インコーポレイテッド | Ｉａｐｂｉｒドメイン結合化合物 |
| CN101374829A (zh) * | 2005-12-19 | 2009-02-25 | 健泰科生物技术公司 | Iap的抑制剂 |
| ES2684120T3 (es) | 2005-12-20 | 2018-10-01 | Novartis Ag | Combinación de un inhibidor de IAP y un taxano |
| CA2634743C (en) * | 2005-12-23 | 2014-07-29 | Zealand Pharma A/S | Modified lysine-mimetic compounds |
| TWI543988B (zh) | 2006-03-16 | 2016-08-01 | 科學製藥股份有限公司 | 結合於細胞凋亡抑制蛋白（ｉａｐ）之桿狀病毒ｉａｐ重複序列（ｂｉｒ）區域之化合物 |
| AU2007250443B2 (en) * | 2006-05-16 | 2013-06-13 | Pharmascience Inc. | IAP BIR domain binding compounds |
| WO2008014252A2 (en) | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Iap inhibitors |
| US20100144650A1 (en) * | 2006-07-24 | 2010-06-10 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| AR063943A1 (es) * | 2006-07-24 | 2009-03-04 | Tetralogic Pharmaceuticals Cor | Dipeptidos antagonistas de iap, una composicion farmaceutica que los comprende y el uso de los mismos para el tratamiento del cancer. |
| WO2008014238A2 (en) * | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| WO2008014240A2 (en) * | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| WO2008014236A1 (en) * | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| PE20110224A1 (es) | 2006-08-02 | 2011-04-05 | Novartis Ag | PROCEDIMIENTO PARA LA SINTESIS DE UN PEPTIDOMIMETICO DE Smac INHIBIDOR DE IAP, Y COMPUESTOS INTERMEDIARIOS PARA LA SINTESIS DEL MISMO |
| RU2009117701A (ru) | 2006-10-12 | 2010-11-20 | Новартис АГ (CH) | Производные пирролидина в качестве ингибиторов iap |
| JP5394249B2 (ja) | 2006-11-28 | 2014-01-22 | ノバルティス アーゲー | Ｉａｐ阻害剤とｆｌｔ３阻害剤の組合せ剤 |
| JP2010513561A (ja) * | 2006-12-19 | 2010-04-30 | ジェネンテック， インコーポレイテッド | Ｉａｐのイミダゾピリジンインヒビター |
| ES2558856T3 (es) | 2006-12-21 | 2016-02-09 | Zealand Pharma A/S | Síntesis de compuestos de pirrolidina |
| AU2008240153B2 (en) * | 2007-04-12 | 2013-01-31 | Joyant Pharmaceuticals, Inc. | SMAC mimetic dimers and trimers useful as anti-cancer agents |
| CN101687787A (zh) | 2007-04-30 | 2010-03-31 | 健泰科生物技术公司 | Iap的抑制剂 |
| JP2010528587A (ja) * | 2007-05-07 | 2010-08-26 | テトラロジック ファーマシューティカルズ コーポレーション | アポトーシス阻害タンパク質のアンタゴニストに対する感受性のバイオマーカーとしてＴＮＦα遺伝子の発現を用いる方法 |
| KR20100110870A (ko) * | 2008-01-11 | 2010-10-13 | 제넨테크, 인크. | Ｉａｐ의 억제제 |
| NZ590550A (en) | 2008-08-02 | 2013-05-31 | Genentech Inc | Inhibitors of Apoptosis (IAP) for treating cancer |
| US20110218211A1 (en) * | 2008-08-16 | 2011-09-08 | Genentech, Inc. | Azaindole inhibitors of iap |
| US8283372B2 (en) | 2009-07-02 | 2012-10-09 | Tetralogic Pharmaceuticals Corp. | 2-(1H-indol-3-ylmethyl)-pyrrolidine dimer as a SMAC mimetic |
| TW201109335A (en) | 2009-08-04 | 2011-03-16 | Takeda Pharmaceutical | Heterocyclic compounds |
| CN105646471A (zh) | 2009-08-12 | 2016-06-08 | 诺华股份有限公司 | 细胞凋亡蛋白抑制剂的固体口服制剂和晶形 |
| US20120196793A1 (en) * | 2009-09-18 | 2012-08-02 | Firestone Brant G | Biomarkers for iap inhibitor compounds |
| CN102050867A (zh) * | 2009-11-10 | 2011-05-11 | 上海艾力斯医药科技有限公司 | 四肽类似物、制备方法及其应用 |
| EP2534170B1 (en) | 2010-02-12 | 2017-04-19 | Pharmascience Inc. | Iap bir domain binding compounds |
| EP3608317A1 (en) | 2012-01-12 | 2020-02-12 | Yale University | Compounds & methods for the enhanced degradation of targeted proteins & other polypeptides by an e3 ubiquitin ligase |
| US8859541B2 (en) * | 2012-02-27 | 2014-10-14 | Boehringer Ingelheim International Gmbh | 6-alkynylpyridines |
| GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| GB201311888D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| CA2974651A1 (en) | 2014-01-24 | 2015-07-30 | Children's Hospital Of Eastern Ontario Research Institute Inc. | Smc combination therapy for the treatment of cancer |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| US10071164B2 (en) | 2014-08-11 | 2018-09-11 | Yale University | Estrogen-related receptor alpha based protac compounds and associated methods of use |
| HK1247204A1 (zh) | 2015-01-20 | 2018-09-21 | Arvinas Operations, Inc. | 用於雄激素受体的靶向降解的化合物和方法 |
| US12312316B2 (en) | 2015-01-20 | 2025-05-27 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
| GB201506872D0 (en) * | 2015-04-22 | 2015-06-03 | Ge Oil & Gas Uk Ltd | Novel compounds |
| EP3302482A4 (en) | 2015-06-05 | 2018-12-19 | Arvinas, Inc. | Tank-binding kinase-1 protacs and associated methods of use |
| WO2017011590A1 (en) * | 2015-07-13 | 2017-01-19 | Arvinas, Inc. | Alanine-based modulators of proteolysis and associated methods of use |
| US10772962B2 (en) | 2015-08-19 | 2020-09-15 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of bromodomain-containing proteins |
| BR112018008918A8 (pt) | 2015-11-02 | 2019-02-26 | Univ Yale | compostos de quimera proteólise dirigida e métodos para preparação e uso dos mesmos |
| JP7286539B2 (ja) | 2016-11-01 | 2023-06-05 | アルビナス・オペレーションズ・インコーポレイテッド | タウタンパク質標的化ｐｒｏｔａｃ、および関連使用方法 |
| DK3689868T3 (da) | 2016-12-01 | 2024-01-02 | Arvinas Operations Inc | Tetrahydronaphthalen- og tetrahydroisoquinolinderivater som østrogenreceptordegraderende midler |
| CN110753693A (zh) | 2016-12-23 | 2020-02-04 | 阿尔维纳斯运营股份有限公司 | Egfr蛋白水解靶向嵌合分子和相关使用方法 |
| AU2017382436C1 (en) | 2016-12-23 | 2021-05-27 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of Rapidly Accelerated Fibrosarcoma polypeptides |
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| EP3658235A1 (en) * | 2017-07-25 | 2020-06-03 | Hepagene Therapeutics, Inc. | Dimeric peptide inhibitors of apoptosis proteins |
| EP3658158A4 (en) * | 2017-07-27 | 2021-04-14 | The National Institute for Biotechnology in the Negev Ltd. | SMAC / YLDIABLO INHIBITORS TO TREAT CANCER |
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Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5801012A (en) * | 1996-09-17 | 1998-09-01 | Northwestern University | Methods and compositions for generating angiostatin |
| EP1210362A2 (en) * | 1999-09-01 | 2002-06-05 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Identification of peptides that facilitate uptake and cytoplasmic and/or nuclear transport of proteins, dna and viruses |
| US6992063B2 (en) * | 2000-09-29 | 2006-01-31 | The Trustees Of Princeton University | Compositions and method for regulating apoptosis |
| WO2002030959A2 (en) * | 2000-10-13 | 2002-04-18 | Abbott Laboratories | Peptides derived from smac (diablo) and methods of use therefor |
| DE10105041A1 (de) * | 2001-02-05 | 2002-08-14 | Tell Pharm Ag Hergiswil | Tripeptide und Tripeptid-Derivate für die Behandlung neurodegenerativer Krankheiten |
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- 2003-07-01 WO PCT/EP2003/007005 patent/WO2004005248A1/en not_active Ceased
- 2003-07-01 EP EP03762570A patent/EP1519918A1/en not_active Withdrawn
- 2003-07-01 CN CNB038156571A patent/CN100384819C/zh not_active Expired - Fee Related
- 2003-07-01 BR BR0312408-8A patent/BR0312408A/pt not_active IP Right Cessation
- 2003-07-01 US US10/519,042 patent/US20060128632A1/en not_active Abandoned
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| CA2491041A1 (en) | 2004-01-15 |
| BR0312408A (pt) | 2005-04-19 |
| WO2004005248A1 (en) | 2004-01-15 |
| US20060052311A1 (en) | 2006-03-09 |
| CN100384819C (zh) | 2008-04-30 |
| US20060128632A1 (en) | 2006-06-15 |
| CN1665784A (zh) | 2005-09-07 |
| AU2003249920A1 (en) | 2004-01-23 |
| EP1519918A1 (en) | 2005-04-06 |
| JP2006501181A (ja) | 2006-01-12 |
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