ES2262518T5 - Antagonistas de tek. - Google Patents
Antagonistas de tek. Download PDFInfo
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- ES2262518T5 ES2262518T5 ES00938207T ES00938207T ES2262518T5 ES 2262518 T5 ES2262518 T5 ES 2262518T5 ES 00938207 T ES00938207 T ES 00938207T ES 00938207 T ES00938207 T ES 00938207T ES 2262518 T5 ES2262518 T5 ES 2262518T5
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- tek
- polypeptide
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- C07—ORGANIC CHEMISTRY
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- Peptides Or Proteins (AREA)
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| US137889P | 1999-06-07 |
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| NZ (1) | NZ516258A (enExample) |
| PT (1) | PT1187918E (enExample) |
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| AU782067B2 (en) | 1999-12-20 | 2005-06-30 | Immunex Corporation | TWEAK receptor |
| EP1427829A4 (en) * | 2001-08-31 | 2005-10-12 | Abmaxis Inc | MULTIVALENT PROTEIN CONJUGATE WITH SEVERAL LIGANDEN BINDING RECORDORDOMAS |
| US7205275B2 (en) | 2001-10-11 | 2007-04-17 | Amgen Inc. | Methods of treatment using specific binding agents of human angiopoietin-2 |
| US7521053B2 (en) | 2001-10-11 | 2009-04-21 | Amgen Inc. | Angiopoietin-2 specific binding agents |
| US7138370B2 (en) | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
| US7658924B2 (en) | 2001-10-11 | 2010-02-09 | Amgen Inc. | Angiopoietin-2 specific binding agents |
| CN1315536C (zh) * | 2002-09-13 | 2007-05-16 | 李进 | 肿瘤抗原疫苗及其制备方法和疫苗组合物 |
| JP2007525187A (ja) * | 2003-05-16 | 2007-09-06 | レセプター・バイオロジクス・インコーポレイテッド | イントロン融合タンパク質、ならびにその同定方法および使用方法 |
| RS53476B (sr) | 2003-07-18 | 2014-12-31 | Amgen Fremont Inc. | Sredstva za specifično vezivanje faktora rasta hepatocita |
| US20060286102A1 (en) * | 2004-05-14 | 2006-12-21 | Pei Jin | Cell surface receptor isoforms and methods of identifying and using the same |
| EP1778264A2 (en) * | 2004-06-25 | 2007-05-02 | Licentia, Ltd. | Tie receptor and tie ligand materials and methods for modulating female fertility |
| US7507748B2 (en) * | 2004-07-22 | 2009-03-24 | Amgen Inc. | Substituted aryl-amine derivatives and methods of use |
| WO2006066071A2 (en) * | 2004-12-17 | 2006-06-22 | Mayo Foundation For Medical Education And Research | Prognosis of renal cell carcinoma |
| HRP20110859T1 (hr) | 2004-12-21 | 2011-12-31 | Medimmune Limited | Protutijela usmjerena na angiopoietin-2 i njihova upotreba |
| US20090170769A1 (en) * | 2005-05-13 | 2009-07-02 | Pei Jin | Cell surface receptor isoforms and methods of identifying and using the same |
| AR059066A1 (es) | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| PE20121506A1 (es) | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
| AU2008219166B2 (en) | 2007-02-16 | 2013-05-16 | Amgen Inc. | Nitrogen-containing heterocyclyl ketones and their use as c-Met inhibitors |
| TWI595005B (zh) | 2007-08-21 | 2017-08-11 | 安健股份有限公司 | 人類ｃ－ｆｍｓ抗原結合蛋白質 |
| US8574577B2 (en) | 2008-01-03 | 2013-11-05 | The Scripps Research Institute | VEGF antibodies comprising modular recognition domains |
| US8454960B2 (en) | 2008-01-03 | 2013-06-04 | The Scripps Research Institute | Multispecific antibody targeting and multivalency through modular recognition domains |
| GEP20156390B (en) | 2008-01-03 | 2015-11-10 | Scripps Research Inst | Antibody targeting through a modular recognition domain |
| US8557242B2 (en) | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | ERBB2 antibodies comprising modular recognition domains |
| US8557243B2 (en) | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | EFGR antibodies comprising modular recognition domains |
| EP2247305A4 (en) | 2008-01-28 | 2012-11-14 | Medimmune Ltd | STABILIZED ANGIOPOIETIN-2 ANTIBODIES AND USES THEREOF |
| JO2913B1 (en) | 2008-02-20 | 2015-09-15 | امجين إنك, | Antibodies directed towards angiopoietin-1 and angiopoietin-2 proteins and their uses |
| AU2009262199B2 (en) | 2008-06-27 | 2012-08-09 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
| WO2012009705A1 (en) | 2010-07-15 | 2012-01-19 | Zyngenia, Inc. | Ang-2 binding complexes and uses thereof |
| MY161199A (en) | 2011-03-23 | 2017-04-14 | Amgen Inc | Fused tricyclic dual inhibitors of cdk 4/6 and flt3 |
| CN106432506A (zh) | 2011-05-24 | 2017-02-22 | 泽恩格尼亚股份有限公司 | 多价和单价多特异性复合物及其用途 |
| US9745288B2 (en) | 2011-08-16 | 2017-08-29 | Indiana University Research And Technology Corporation | Compounds and methods for treating cancer by inhibiting the urokinase receptor |
| AU2012299195B9 (en) * | 2011-08-19 | 2018-05-10 | Regeneron Pharmaceuticals, Inc | Anti-Tie2 antibodies uses thereof |
| US10316105B2 (en) | 2011-08-19 | 2019-06-11 | Regeneron Pharmaceuticals, Inc. | Anti-TIE2 antibodies and uses thereof |
| AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
| US9505749B2 (en) | 2012-08-29 | 2016-11-29 | Amgen Inc. | Quinazolinone compounds and derivatives thereof |
| GB201223053D0 (en) * | 2012-12-20 | 2013-02-06 | Medical Res Council | Receptor |
| EP3424530A1 (en) | 2013-03-15 | 2019-01-09 | Zyngenia, Inc. | Multivalent and monovalent multispecific complexes and their uses |
| TW201605896A (zh) | 2013-08-30 | 2016-02-16 | 安美基股份有限公司 | Gitr抗原結合蛋白 |
| BR112018068103A2 (pt) | 2016-03-08 | 2019-01-15 | Janssen Biotech Inc | anticorpos gitr, métodos e usos |
| MX2019000514A (es) | 2016-07-14 | 2019-07-12 | Scholar Rock Inc | Anticuerpos de tgfb, métodos, y usos. |
| EP3558955B1 (en) | 2016-12-22 | 2021-08-11 | Amgen Inc. | Benzisothiazole, isothiazolo[3,4-b]pyridine, quinazoline, phthalazine, pyrido[2,3-d]pyridazine and pyrido[2,3-d]pyrimidine derivatives as kras g12c inhibitors for treating lung, pancreatic or colorectal cancer |
| JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
| EP3679040B1 (en) | 2017-09-08 | 2022-08-03 | Amgen Inc. | Inhibitors of kras g12c and methods of using the same |
| AU2019262589B2 (en) | 2018-05-04 | 2022-07-07 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| ES2995514T3 (en) | 2018-05-04 | 2025-02-10 | Amgen Inc | Kras g12c inhibitors and methods of using the same |
| MX2020011907A (es) | 2018-05-10 | 2021-01-29 | Amgen Inc | Inhibidores de kras g12c para el tratamiento de cancer. |
| ES2938987T3 (es) | 2018-06-01 | 2023-04-18 | Amgen Inc | Inhibidores de KRAS G12c y métodos de uso de los mismos |
| MX2020012204A (es) | 2018-06-11 | 2021-03-31 | Amgen Inc | Inhibidores de kras g12c para tratar el cáncer. |
| CA3100390A1 (en) | 2018-06-12 | 2020-03-12 | Amgen Inc. | Kras g12c inhibitors encompassing piperazine ring and use thereof in the treatment of cancer |
| CN108888756A (zh) * | 2018-07-25 | 2018-11-27 | 韩曙 | C16多肽和血管生成素Ang1的应用和应用二者的药物 |
| JP7516029B2 (ja) | 2018-11-16 | 2024-07-16 | アムジエン・インコーポレーテツド | Ｋｒａｓ ｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法 |
| WO2020106640A1 (en) | 2018-11-19 | 2020-05-28 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| JP7377679B2 (ja) | 2018-11-19 | 2023-11-10 | アムジエン・インコーポレーテツド | がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法 |
| MA54546A (fr) | 2018-12-20 | 2022-03-30 | Amgen Inc | Amides d'hétéroaryle utiles en tant qu'inhibiteurs de kif18a |
| CA3123871A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
| JP7676308B2 (ja) | 2018-12-20 | 2025-05-14 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤として有用なヘテロアリールアミド |
| WO2020132651A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
| WO2020180768A1 (en) | 2019-03-01 | 2020-09-10 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
| MX2021010323A (es) | 2019-03-01 | 2021-12-10 | Revolution Medicines Inc | Compuestos bicíclicos de heterociclilo y usos de este. |
| EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
| PH12021552922A1 (en) | 2019-05-21 | 2022-04-04 | Amgen Inc | Solid state forms |
| PE20220231A1 (es) * | 2019-06-25 | 2022-02-07 | Gilead Sciences Inc | Proteinas de fusion flt3l-fc y metodos de uso |
| AU2020324406A1 (en) | 2019-08-02 | 2022-03-17 | Amgen Inc. | KIF18A inhibitors |
| JP7756070B2 (ja) | 2019-08-02 | 2025-10-17 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤としてのピリジン誘導体 |
| JP7640521B2 (ja) | 2019-08-02 | 2025-03-05 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤として有用なヘテロアリールアミド |
| MX2022001295A (es) | 2019-08-02 | 2022-02-22 | Amgen Inc | Inhibidores de kif18a. |
| EP4031542B1 (en) | 2019-09-18 | 2025-10-15 | Merck Sharp & Dohme LLC | Small molecule inhibitors of kras g12c mutant |
| AU2020369569A1 (en) | 2019-10-24 | 2022-04-14 | Amgen Inc. | Pyridopyrimidine derivatives useful as KRAS G12C and KRAS G12D inhibitors in the treatment of cancer |
| UA129778C2 (uk) | 2019-10-28 | 2025-07-30 | Мерк Шарп Енд Доум Елелсі | Низькомолекулярні інгібітори g12c-мутантного kras |
| CN119424423A (zh) | 2019-10-31 | 2025-02-14 | 大鹏药品工业株式会社 | 4-氨基丁-2-烯酰胺衍生物及其盐 |
| AU2020379731A1 (en) | 2019-11-04 | 2022-05-05 | Revolution Medicines, Inc. | Ras inhibitors |
| CA3159561A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2021091956A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
| MX2022005525A (es) | 2019-11-08 | 2022-06-08 | Revolution Medicines Inc | Compuestos de heteroarilo bicíclicos y usos de estos. |
| AR120456A1 (es) | 2019-11-14 | 2022-02-16 | Amgen Inc | Síntesis mejorada del compuesto inhibidor de g12c de kras |
| US12466825B2 (en) | 2019-11-14 | 2025-11-11 | Amgen Inc. | Synthesis of KRAS G12C inhibitor compound |
| EP4065231A1 (en) | 2019-11-27 | 2022-10-05 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| WO2021106231A1 (en) | 2019-11-29 | 2021-06-03 | Taiho Pharmaceutical Co., Ltd. | A compound having inhibitory activity against kras g12d mutation |
| US12365706B2 (en) | 2019-12-18 | 2025-07-22 | Merck Sharp & Dohme Llc | Macrocyclic peptides as potent inhibitors of K-RAS G12D mutant |
| MX2022008305A (es) | 2020-01-07 | 2022-08-08 | Revolution Medicines Inc | Dosificacion de inhibidores de shp2 y metodos de tratamiento del cancer. |
| US20230181536A1 (en) | 2020-04-24 | 2023-06-15 | Taiho Pharmaceutical Co., Ltd. | Anticancer combination therapy with n-(1-acryloyl-azetidin-3-yl)-2-((1h-indazol-3-yl)amino)methyl)-1h-imidazole-5-carboxamide inhibitor of kras-g12c |
| US20230174518A1 (en) | 2020-04-24 | 2023-06-08 | Taiho Pharmaceutical Co., Ltd. | Kras g12d protein inhibitors |
| TW202214253A (zh) | 2020-06-18 | 2022-04-16 | 美商銳新醫藥公司 | 延遲、預防及治療對ｒａｓ抑制劑之後天抗性之方法 |
| KR20230031926A (ko) | 2020-07-15 | 2023-03-07 | 다이호야쿠힌고교 가부시키가이샤 | 종양의 치료에 사용되는 피리미딘 화합물을 포함하는 조합 |
| CA3187757A1 (en) | 2020-09-03 | 2022-03-24 | Ethan AHLER | Use of sos1 inhibitors to treat malignancies with shp2 mutations |
| PE20231207A1 (es) | 2020-09-15 | 2023-08-17 | Revolution Medicines Inc | Derivados indolicos como inhibidores de ras en el tratamiento del cancer |
| CN117396472A (zh) | 2020-12-22 | 2024-01-12 | 上海齐鲁锐格医药研发有限公司 | Sos1抑制剂及其用途 |
| US12036286B2 (en) | 2021-03-18 | 2024-07-16 | Seagen Inc. | Selective drug release from internalized conjugates of biologically active compounds |
| MX2023013085A (es) | 2021-05-05 | 2023-11-16 | Revolution Medicines Inc | Inhibidores de ras. |
| PE20240089A1 (es) | 2021-05-05 | 2024-01-16 | Revolution Medicines Inc | Inhibidores de ras para el tratamiento del cancer |
| CN117500811A (zh) | 2021-05-05 | 2024-02-02 | 锐新医药公司 | 共价ras抑制剂及其用途 |
| WO2022250170A1 (en) | 2021-05-28 | 2022-12-01 | Taiho Pharmaceutical Co., Ltd. | Small molecule inhibitors of kras mutated proteins |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| TW202340214A (zh) | 2021-12-17 | 2023-10-16 | 美商健臻公司 | 做為shp2抑制劑之吡唑并吡𠯤化合物 |
| EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| JP2025509217A (ja) | 2022-03-07 | 2025-04-11 | アムジエン・インコーポレーテツド | ４－メチル－２－プロパン－２－イル－ピリジン－３－カルボニトリルを調製するための方法 |
| CN119136806A (zh) | 2022-03-08 | 2024-12-13 | 锐新医药公司 | 用于治疗免疫难治性肺癌的方法 |
| CN120504682A (zh) | 2022-06-10 | 2025-08-19 | 锐新医药公司 | 大环ras抑制剂 |
| IL320217A (en) | 2022-10-14 | 2025-06-01 | Black Diamond Therapeutics Inc | Methods for treating cancer using isoquinoline or 6-azaquinoline derivatives |
| KR20250164828A (ko) | 2023-03-30 | 2025-11-25 | 레볼루션 메디슨즈, 인크. | Ras gtp 가수분해 유도를 위한 조성물 및 이의 용도 |
| AU2024253668A1 (en) | 2023-04-07 | 2025-11-13 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| WO2024211712A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| CN121100123A (zh) | 2023-04-14 | 2025-12-09 | 锐新医药公司 | Ras抑制剂的结晶形式 |
| US20240352038A1 (en) | 2023-04-14 | 2024-10-24 | Revolution Medicines, Inc. | Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| WO2025034702A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Rmc-6291 for use in the treatment of ras protein-related disease or disorder |
| TW202515582A (zh) | 2023-08-24 | 2025-04-16 | 日商大塚製藥股份有限公司 | 西區嘧啶(cedazuridine)之固定劑量組合 |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| TW202535891A (zh) | 2023-10-20 | 2025-09-16 | 美商默沙東有限責任公司 | Ｋｒａｓ蛋白之小分子抑制劑 |
| WO2025137507A1 (en) | 2023-12-22 | 2025-06-26 | Regor Pharmaceuticals, Inc. | Sos1 inhibitors and uses thereof |
| WO2025196639A1 (en) | 2024-03-21 | 2025-09-25 | Seagen Inc. | Cd25 antibodies, antibody-drug conjugates, and uses thereof |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0584082B1 (en) * | 1991-01-31 | 2000-05-31 | Cor Therapeutics, Inc. | Domains of extracellular region of human platelet derived growth factor receptor polypeptides |
| JPH07506242A (ja) | 1992-01-09 | 1995-07-13 | ヘルシンキ ユニバーシティ ホルディング リミテッド | Ｔｉｅ，新規内皮細胞受容体チロシンキナーゼ |
| US5955291A (en) | 1992-01-09 | 1999-09-21 | Alitalo; Kari | Antibodies recognizing tie receptor tyrosine kinase and uses thereof |
| WO1994000469A1 (en) | 1992-06-26 | 1994-01-06 | Immunex Corporation | Novel tyrosine kinase |
| US5681714A (en) | 1992-07-30 | 1997-10-28 | Mount Sinai Hospital Corporation | Nucleic acid encoding tek receptor tyrosine kinase |
| JPH06315382A (ja) | 1993-05-06 | 1994-11-15 | Toshio Suda | Ｔｉｅ−２受容体をコードするｄｎａ及びｔｉｅ−２受容体 |
| AU8143094A (en) * | 1993-11-12 | 1995-05-29 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | (tie-2), a novel receptor tyrosine kinase |
| AUPM379494A0 (en) * | 1994-02-10 | 1994-03-03 | Ludwig Institute For Cancer Research | Immunointeractive molecules - ii |
| US5814464A (en) * | 1994-10-07 | 1998-09-29 | Regeneron Pharma | Nucleic acids encoding TIE-2 ligand-2 |
| WO1996020403A1 (en) | 1994-12-23 | 1996-07-04 | Ludwig Institute For Cancer Research | Assay, receptor proteins and ligands |
| EP0821728B1 (en) * | 1995-04-06 | 2004-08-11 | Regeneron Pharmaceuticals, Inc. | Tie-2 ligands, methods of making and uses thereof |
| US6033903A (en) * | 1995-06-02 | 2000-03-07 | Applied Research Systems, ARS Holding N.V. | Method of expressing and secreting soluble extracellular domains of human gonadotropin hormone receptors |
| ATE299936T1 (de) * | 1996-05-02 | 2005-08-15 | Mochida Pharm Co Ltd | Fas antigen-derivate |
| WO1998018914A1 (en) * | 1996-10-31 | 1998-05-07 | Duke University | Soluble tie2 receptor |
| US6376653B1 (en) | 1998-09-28 | 2002-04-23 | Smithkline Beecham Plc | Tie2 antagonist antibodies |
-
2000
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- 2000-06-07 AU AU53282/00A patent/AU783960B2/en not_active Ceased
- 2000-06-07 PT PT00938207T patent/PT1187918E/pt unknown
- 2000-06-07 CA CA002374851A patent/CA2374851A1/en not_active Abandoned
- 2000-06-07 WO PCT/US2000/015706 patent/WO2000075323A1/en not_active Ceased
- 2000-06-07 US US09/590,656 patent/US6413932B1/en not_active Expired - Fee Related
- 2000-06-07 IL IL14648200A patent/IL146482A0/xx unknown
- 2000-06-07 AT AT00938207T patent/ATE324444T1/de not_active IP Right Cessation
- 2000-06-07 DE DE60027564T patent/DE60027564T3/de not_active Expired - Lifetime
- 2000-06-07 EP EP00938207A patent/EP1187918B9/en not_active Expired - Lifetime
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2006
- 2006-05-02 US US11/416,613 patent/US20070025993A1/en not_active Abandoned
- 2006-07-07 CY CY20061100953T patent/CY1105078T1/el unknown
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| AU783960B2 (en) | 2006-01-05 |
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| CA2374851A1 (en) | 2000-12-14 |
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| DK1187918T4 (da) | 2009-02-23 |
| NZ516258A (en) | 2004-02-27 |
| ES2262518T3 (es) | 2006-12-01 |
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| DE60027564T2 (de) | 2007-05-10 |
| JP4587626B2 (ja) | 2010-11-24 |
| EP1187918A1 (en) | 2002-03-20 |
| JP2003501090A (ja) | 2003-01-14 |
| IL146482A0 (en) | 2002-07-25 |
| EP1187918B2 (en) | 2009-01-14 |
| AU5328200A (en) | 2000-12-28 |
| US20070025993A1 (en) | 2007-02-01 |
| WO2000075323A1 (en) | 2000-12-14 |
| DE60027564T3 (de) | 2009-07-23 |
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