JP2005534623A - Erbファミリーの阻害剤並びにraf及び/又はras阻害剤を投与することを含む癌の治療法 - Google Patents
Erbファミリーの阻害剤並びにraf及び/又はras阻害剤を投与することを含む癌の治療法 Download PDFInfo
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- JP2005534623A JP2005534623A JP2003583483A JP2003583483A JP2005534623A JP 2005534623 A JP2005534623 A JP 2005534623A JP 2003583483 A JP2003583483 A JP 2003583483A JP 2003583483 A JP2003583483 A JP 2003583483A JP 2005534623 A JP2005534623 A JP 2005534623A
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- 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
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- 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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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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
- A61K31/495—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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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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
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- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
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| US37080702P | 2002-04-08 | 2002-04-08 | |
| PCT/US2003/010747 WO2003086467A1 (en) | 2002-04-08 | 2003-04-08 | Cancer treatment method comprising administering an erb-family inhibitor and a raf and/or ras inhibitor |
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| JP2005534623A true JP2005534623A (ja) | 2005-11-17 |
| JP2005534623A5 JP2005534623A5 (enExample) | 2006-07-06 |
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| US (1) | US20050176740A1 (enExample) |
| EP (1) | EP1492568A1 (enExample) |
| JP (1) | JP2005534623A (enExample) |
| AU (1) | AU2003221684A1 (enExample) |
| WO (1) | WO2003086467A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015182625A1 (ja) * | 2014-05-26 | 2015-12-03 | 国立大学法人京都大学 | Ras活性阻害薬及びその用途 |
| JP2017511341A (ja) * | 2014-04-04 | 2017-04-20 | アストラゼネカ・アクチエボラーグAstrazeneca Aktiebolag | Nras変異癌の処置における使用のためのegfr阻害剤とmek阻害剤の組合せ |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005011607A2 (en) | 2003-08-01 | 2005-02-10 | Smithkline Beecham Corporation | Treatment of cancers expressing p95 erbb2 |
| TWI441646B (zh) | 2005-01-21 | 2014-06-21 | Genentech Inc | 帕妥珠單抗(pertuzumab)用於製備治療人類病患癌症之藥物的用途 |
| MY152164A (en) | 2005-02-23 | 2014-08-15 | Genentech Inc | Extending time to disease progression or survival in cancer patients |
| EP1871347B1 (en) | 2005-04-19 | 2016-08-03 | Novartis AG | Pharmaceutical composition |
| SI2132573T1 (sl) | 2007-03-02 | 2014-07-31 | Genentech, Inc. | Napovedovanje odziva na inhibitor dimerizacije HER na osnovi nizke ekspresije HER3 |
| EP2592156B1 (en) | 2007-06-08 | 2016-04-20 | Genentech, Inc. | Gene expression markers of tumor resistance to HER2 inhibitor treatment |
| US9551033B2 (en) | 2007-06-08 | 2017-01-24 | Genentech, Inc. | Gene expression markers of tumor resistance to HER2 inhibitor treatment |
| TWI472339B (zh) | 2008-01-30 | 2015-02-11 | Genentech Inc | 包含結合至her2結構域ii之抗體及其酸性變異體的組合物 |
| US8252805B2 (en) | 2008-05-07 | 2012-08-28 | Teva Pharmaceutical Industries Ltd. | Forms of lapatinib ditosylate and processes for preparation thereof |
| BRPI0812682A2 (pt) | 2008-06-16 | 2010-06-22 | Genentech Inc | tratamento de cáncer de mama metastático |
| JP5624114B2 (ja) | 2009-03-20 | 2014-11-12 | ジェネンテック, インコーポレイテッド | 抗her抗体 |
| CN102459223B (zh) | 2009-05-15 | 2014-11-05 | 诺华股份有限公司 | 5-吡啶-3-基-1,3-二氢-吲哚-2-酮衍生物及其作为醛固酮合成酶和/或cyp11b1调节剂的用途 |
| MX2011012199A (es) | 2009-05-15 | 2011-12-08 | Novartis Ag | Derivados de benzoxazolona como inhibidores de la sintasa de aldosterona. |
| CN102421448A (zh) | 2009-05-29 | 2012-04-18 | 霍夫曼-拉罗奇有限公司 | Her2信号传导调控剂在表达her2的胃癌患者中 |
| RU2587619C2 (ru) | 2010-02-18 | 2016-06-20 | Дженентек, Инк. | Антагонисты неурегулина и применение их в лечении злокачественного новообразования |
| WO2011146568A1 (en) | 2010-05-19 | 2011-11-24 | Genentech, Inc. | Predicting response to a her inhibitor |
| US8709419B2 (en) * | 2010-08-17 | 2014-04-29 | Hoffmann-La Roche, Inc. | Combination therapy |
| EP2643353A1 (en) | 2010-11-24 | 2013-10-02 | Novartis AG | Multispecific molecules |
| WO2012075327A1 (en) | 2010-12-02 | 2012-06-07 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Methods for treating a tumor using an antibody that specifically binds grp94 |
| US9295669B2 (en) | 2010-12-14 | 2016-03-29 | Hoffman La-Roche Inc. | Combination therapy for proliferative disorders |
| EP2655413B1 (en) | 2010-12-23 | 2019-01-16 | F.Hoffmann-La Roche Ag | Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery |
| KR20140057326A (ko) | 2011-08-17 | 2014-05-12 | 제넨테크, 인크. | 뉴레귤린 항체 및 그의 용도 |
| WO2013063229A1 (en) | 2011-10-25 | 2013-05-02 | The Regents Of The University Of Michigan | Her2 targeting agent treatment in non-her2-amplified cancers having her2 expressing cancer stem cells |
| CA2857114A1 (en) | 2011-11-30 | 2013-06-06 | Genentech, Inc. | Erbb3 mutations in cancer |
| US9376715B2 (en) | 2011-12-09 | 2016-06-28 | Roche Molecular Systems, Inc | Methods for detecting mutations in the catalytic subunit of the phosphoinositol-3 kinase (PIK3CA) gene |
| BR112014024017A8 (pt) | 2012-03-27 | 2017-07-25 | Genentech Inc | Métodos de tratamento de um tipo de câncer, de tratamento do carcinoma, para selecionar uma terapia e para quantificação e inibidor de her3 |
| MX363188B (es) | 2012-11-30 | 2019-03-13 | Hoffmann La Roche | Identificación de pacientes con necesidad de coterapia del inhibidor de pd-l1. |
| WO2014170910A1 (en) | 2013-04-04 | 2014-10-23 | Natco Pharma Limited | Process for the preparation of lapatinib |
| CA2935804A1 (en) | 2014-01-14 | 2015-07-23 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identification, assessment, prevention, and treatment of melanoma using pd-l1 isoforms |
| CA2963091A1 (en) | 2014-10-06 | 2016-04-14 | Dana-Farber Cancer Institute, Inc. | Angiopoietin-2 biomarkers predictive of anti-immune checkpoint response |
| MX2017006864A (es) | 2014-12-23 | 2017-08-28 | Genentech Inc | Composiciones y métodos para tratar y diagnosticar cánceres resistentes a la quimioterapia. |
| WO2017194554A1 (en) | 2016-05-10 | 2017-11-16 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Combinations therapies for the treatment of cancer |
| MX2018014047A (es) | 2016-05-17 | 2019-06-20 | Genentech Inc | Firmas de genes estromales para el diagnóstico y uso en inmunoterapia. |
| EP3797173A2 (en) | 2018-05-21 | 2021-03-31 | Nanostring Technologies, Inc. | Molecular gene signatures and methods of using same |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH1112279A (ja) * | 1997-06-27 | 1999-01-19 | Microbial Chem Res Found | Ras蛋白の阻害活性を有する新規なアグライアスタチン立体異性体とそれらの製造法 |
| WO1999010325A1 (en) * | 1997-08-06 | 1999-03-04 | Glaxo Group Limited | Benzylidene-1,3-dihydro-indol-2-one derivatives as receptor tyrosine kinase inhibitors, particularly of raf kinases |
| JP2002500225A (ja) * | 1998-01-12 | 2002-01-08 | グラクソ グループ リミテッド | プロテインチロシンキナーゼ阻害剤としての二環式ヘテロ芳香族化合物 |
| WO2002024680A1 (en) * | 2000-09-21 | 2002-03-28 | Smithkline Beecham P.L.C. | Imidazole derivatives as raf kinase inhibitors |
| WO2003022840A1 (en) * | 2001-09-05 | 2003-03-20 | Smithkline Beecham Plc | Pyridine derivatives as raf kinase inhibitors |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR004010A1 (es) * | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
| AR007857A1 (es) * | 1996-07-13 | 1999-11-24 | Glaxo Group Ltd | Compuestos heterociclicos fusionados como inhibidores de proteina tirosina quinasa, sus metodos de preparacion, intermediarios uso en medicina ycomposiciones farmaceuticas que los contienen. |
| HRP970371A2 (en) * | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| CA2260058A1 (en) * | 1996-07-13 | 1998-01-22 | Kathryn Jane Smith | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors |
| ATE290882T1 (de) * | 2001-01-16 | 2005-04-15 | Glaxo Group Ltd | Pharmazeutische mischung gegen krebs, die ein 4- chinazolinamin in kombination mit paclitaxel, carboplatin or vinorelbine enthält |
-
2003
- 2003-04-08 JP JP2003583483A patent/JP2005534623A/ja active Pending
- 2003-04-08 US US10/510,542 patent/US20050176740A1/en not_active Abandoned
- 2003-04-08 WO PCT/US2003/010747 patent/WO2003086467A1/en not_active Ceased
- 2003-04-08 EP EP03718262A patent/EP1492568A1/en not_active Withdrawn
- 2003-04-08 AU AU2003221684A patent/AU2003221684A1/en not_active Abandoned
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH1112279A (ja) * | 1997-06-27 | 1999-01-19 | Microbial Chem Res Found | Ras蛋白の阻害活性を有する新規なアグライアスタチン立体異性体とそれらの製造法 |
| WO1999010325A1 (en) * | 1997-08-06 | 1999-03-04 | Glaxo Group Limited | Benzylidene-1,3-dihydro-indol-2-one derivatives as receptor tyrosine kinase inhibitors, particularly of raf kinases |
| JP2002500225A (ja) * | 1998-01-12 | 2002-01-08 | グラクソ グループ リミテッド | プロテインチロシンキナーゼ阻害剤としての二環式ヘテロ芳香族化合物 |
| WO2002024680A1 (en) * | 2000-09-21 | 2002-03-28 | Smithkline Beecham P.L.C. | Imidazole derivatives as raf kinase inhibitors |
| WO2003022840A1 (en) * | 2001-09-05 | 2003-03-20 | Smithkline Beecham Plc | Pyridine derivatives as raf kinase inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| H.HE, THE CANCER JOURNAL, vol. V7 N3, JPN5004013911, 2001, pages 191 - 202, ISSN: 0001356778 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017511341A (ja) * | 2014-04-04 | 2017-04-20 | アストラゼネカ・アクチエボラーグAstrazeneca Aktiebolag | Nras変異癌の処置における使用のためのegfr阻害剤とmek阻害剤の組合せ |
| WO2015182625A1 (ja) * | 2014-05-26 | 2015-12-03 | 国立大学法人京都大学 | Ras活性阻害薬及びその用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003086467A1 (en) | 2003-10-23 |
| US20050176740A1 (en) | 2005-08-11 |
| AU2003221684A1 (en) | 2003-10-27 |
| EP1492568A1 (en) | 2005-01-05 |
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