JP2014509593A - ＥｒｂＢ経路阻害剤に対する耐性の克服 - Google Patents
ＥｒｂＢ経路阻害剤に対する耐性の克服 Download PDFInfo
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- Chemical Kinetics & Catalysis (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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| US61/452,974 | 2011-03-15 | ||
| US61/452,976 | 2011-03-15 | ||
| PCT/US2012/029292 WO2012125864A2 (en) | 2011-03-15 | 2012-03-15 | Overcoming resistance to erbb pathway inhibitors |
Publications (2)
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| JP2014509593A true JP2014509593A (ja) | 2014-04-21 |
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Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
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| HRP20131113T1 (hr) * | 2007-02-16 | 2014-01-17 | Merrimack Pharmaceuticals, Inc. | Protutijela protiv erbb3 i njihova uporaba |
| JP2013522237A (ja) | 2010-03-11 | 2013-06-13 | メリマック ファーマシューティカルズ インコーポレーティッド | トリプルネガティブおよび基底様乳癌の治療におけるｅｒｂｂ３阻害剤の使用 |
| US8691231B2 (en) | 2011-06-03 | 2014-04-08 | Merrimack Pharmaceuticals, Inc. | Methods of treatment of tumors expressing predominantly high affinity EGFR ligands or tumors expressing predominantly low affinity EGFR ligands with monoclonal and oligoclonal anti-EGFR antibodies |
| US9828635B2 (en) | 2011-10-06 | 2017-11-28 | Aveo Pharmaceuticals, Inc. | Predicting tumor response to anti-ERBB3 antibodies |
| MX350957B (es) | 2011-11-23 | 2017-09-27 | Medimmune Llc | Moleculas de union especificas para her3 y usos de las mismas. |
| US9956276B2 (en) * | 2012-01-19 | 2018-05-01 | Duke University | Vaccines against antigens involved in therapy resistance and methods of using same |
| AR094403A1 (es) * | 2013-01-11 | 2015-07-29 | Hoffmann La Roche | Terapia de combinación de anticuerpos anti-her3 |
| WO2015048008A2 (en) * | 2013-09-24 | 2015-04-02 | Medimmune, Llc | Binding molecules specific for her3 and uses thereof |
| TW201601753A (zh) * | 2013-09-30 | 2016-01-16 | 第一三共股份有限公司 | 蛋白質生物標記及其用途 |
| WO2015066543A1 (en) * | 2013-11-01 | 2015-05-07 | Board Of Regents, The University Of Texas System | Targeting her2 and her3 with bispecific antibodies in cancerous cells |
| WO2015100459A2 (en) | 2013-12-27 | 2015-07-02 | Merrimack Pharmaceuticals, Inc. | Biomarker profiles for predicting outcomes of cancer therapy with erbb3 inhibitors and/or chemotherapies |
| SG11201607109QA (en) | 2014-02-28 | 2016-09-29 | Merus Nv | Antibodies that bind egfr and erbb3 |
| SI3110849T1 (sl) * | 2014-02-28 | 2021-01-29 | Merus N.V. | Protitelo, ki veže ERBB-2 in ERBB-3 |
| WO2015157634A1 (en) | 2014-04-11 | 2015-10-15 | Kolltan Pharmaceuticals, Inc. | Anti-erbb antibodies and methods of use thereof |
| MX2016014862A (es) | 2014-05-14 | 2017-02-27 | Hoffmann La Roche | Her3 / her2 anticuerpos biespecificos que se unen a la horquilla beta de her3 y al dominio ii de her2. |
| MA39599A (fr) | 2014-05-14 | 2016-10-05 | Merrimack Pharmaceuticals Inc | Dosage et administration d'agents thérapeutiques anti-egfr |
| CA2954279C (en) | 2014-07-07 | 2023-11-14 | Duke University | Vaccines against an oncogenic isoform of esr1 and methods of using the same |
| WO2016007499A1 (en) | 2014-07-07 | 2016-01-14 | Duke University | Vaccines against an oncogenic isoform of her2 (erbb2) and methods of using the same |
| CA2959775A1 (en) | 2014-09-08 | 2016-03-17 | Yeda Research And Development Co. Ltd. | Compositions and methods for treating cancer resistant to a tyrosine kinase inhibitor (tki) |
| CA2959716A1 (en) | 2014-09-08 | 2016-03-17 | Yeda Research And Development Co. Ltd. | Anti-her3 antibodies and uses of same |
| HK1248539A1 (zh) * | 2015-04-17 | 2018-10-19 | 梅里麦克制药股份有限公司 | 借助塞里班土单抗的组合治疗 |
| WO2016179103A1 (en) | 2015-05-01 | 2016-11-10 | National Taiwan University | Pink1 c-terminal domain polypeptide and methods using the same in cancer treatment |
| US10184006B2 (en) | 2015-06-04 | 2019-01-22 | Merrimack Pharmaceuticals, Inc. | Biomarkers for predicting outcomes of cancer therapy with ErbB3 inhibitors |
| WO2017035482A1 (en) * | 2015-08-27 | 2017-03-02 | Merrimack Pharmaceuticals, Inc | Combination therapies for treatment of heregulin positive cancers |
| BR112018008068A2 (en) | 2015-10-23 | 2018-11-13 | Merus N.V. | binding molecules that inhibit cancer growth |
| EP3176183A1 (en) | 2015-12-02 | 2017-06-07 | Yeda Research and Development Co. Ltd | Compositions and methods for treating cancer not resistant to a tyrosine kinase inhibitor (tki) |
| CN108697779B (zh) | 2016-01-07 | 2023-09-19 | 杜克大学 | 癌症疫苗和递送方法 |
| US10487143B2 (en) | 2016-10-05 | 2019-11-26 | Duke University | Vaccines against HER3 antigens and methods of using the same |
| US11224665B2 (en) | 2016-10-05 | 2022-01-18 | Duke University | Mitochondrial antiviral signaling (MAVS) protein compositions and methods of using the same |
| CA3058343A1 (en) | 2017-03-31 | 2018-10-04 | Merus N.V. | Erbb-2 and erbb-3 binding bispecific antibodies for use in the treatment of cells that have an nrg1 fusion gene |
| US12195551B2 (en) | 2017-05-17 | 2025-01-14 | Merus N.V. | Combination of an ErbB-2/ErbB-3 bispecific antibody with endocrine therapy for breast cancer |
| HUE071182T2 (hu) | 2017-08-09 | 2025-08-28 | Merus Nv | EGFR és CMET kötõ antitestek |
| WO2019088348A1 (ko) * | 2017-11-06 | 2019-05-09 | 한국과학기술원 | Egfr 저해제 저항성 암 치료제 |
| AU2020371040B2 (en) * | 2019-10-24 | 2025-10-09 | Merus N.V. | Means and methods for treating subjects with HER2 and HER3 positive cancer |
| AR127893A1 (es) * | 2021-12-10 | 2024-03-06 | Servier Lab | Terapia del cáncer dirigida a egfr |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US5968511A (en) | 1996-03-27 | 1999-10-19 | Genentech, Inc. | ErbB3 antibodies |
| US7390632B2 (en) | 1999-09-30 | 2008-06-24 | Tumor Biology Investment Group, Inc. | Soluble ErbB3 receptor isoforms |
| US7612042B2 (en) | 2001-05-31 | 2009-11-03 | Tumor Biology Investment Group, Inc. | Methods for inhibiting heregulin and treating cancer |
| EP1283053A1 (en) | 2001-08-09 | 2003-02-12 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibitors of HER3 activity |
| CN100424175C (zh) | 2002-03-26 | 2008-10-08 | 上海泽生科技开发有限公司 | ErbB-3 用于肿瘤治疗的方法和组合物 |
| US7332580B2 (en) | 2002-04-05 | 2008-02-19 | The Regents Of The University Of California | Bispecific single chain Fv antibody molecules and methods of use thereof |
| US7332585B2 (en) | 2002-04-05 | 2008-02-19 | The Regents Of The California University | Bispecific single chain Fv antibody molecules and methods of use thereof |
| AR056857A1 (es) | 2005-12-30 | 2007-10-24 | U3 Pharma Ag | Anticuerpos dirigidos hacia her-3 (receptor del factor de crecimiento epidérmico humano-3) y sus usos |
| HRP20131113T1 (hr) * | 2007-02-16 | 2014-01-17 | Merrimack Pharmaceuticals, Inc. | Protutijela protiv erbb3 i njihova uporaba |
| PL2132229T3 (pl) | 2007-03-01 | 2016-12-30 | Kompozycje rekombinowanych przeciwciał anty-receptor czynnika wzrostu naskórka | |
| JP2010526797A (ja) | 2007-05-11 | 2010-08-05 | エンゾン ファーマシューティカルズ，インコーポレーテッド | Ｈｅｒ３のモジュレーションのためのｒｎａアンタゴニスト化合物 |
| MX2010011145A (es) | 2008-04-11 | 2011-04-11 | Merrimack Pharmaceuticals Inc | Enlazadores de la albumina de suero humana y conjugados de la misma. |
| CN102282168A (zh) | 2008-11-18 | 2011-12-14 | 梅里麦克制药股份有限公司 | 人血清白蛋白接头以及其结合物 |
| CN102356092B (zh) * | 2009-03-20 | 2014-11-05 | 霍夫曼-拉罗奇有限公司 | 双特异性抗-her抗体 |
| US8362215B2 (en) | 2009-04-29 | 2013-01-29 | Trellis Bioscience, Llc | Antibodies immunoreactive with heregulin-coupled HER3 |
| DK2516469T3 (en) | 2009-12-22 | 2016-05-02 | Roche Glycart Ag | ANTI-HER3 antibodies and uses thereof |
| WO2011136911A2 (en) | 2010-04-09 | 2011-11-03 | Aveo Pharmaceuticals, Inc. | Anti-erbb3 antibodies |
| ES2692379T3 (es) * | 2010-11-01 | 2018-12-03 | Symphogen A/S | Anticuerpos anti-HER3 y composiciones |
| US20140056898A1 (en) * | 2011-02-24 | 2014-02-27 | Bo Zhang | Combination therapies comprising anti-erbb3 agents |
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- 2012-03-15 US US14/004,848 patent/US20150231238A1/en not_active Abandoned
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| CA2828043A1 (en) | 2012-09-20 |
| SG192775A1 (en) | 2013-09-30 |
| WO2012125864A3 (en) | 2012-12-27 |
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| BR112013022887A2 (pt) | 2016-12-06 |
| AU2012229062A1 (en) | 2013-04-11 |
| MX2013010444A (es) | 2014-03-21 |
| KR20140023921A (ko) | 2014-02-27 |
| EP2686015A2 (en) | 2014-01-22 |
| CN103429262A (zh) | 2013-12-04 |
| WO2012125864A2 (en) | 2012-09-20 |
| US20150231238A1 (en) | 2015-08-20 |
| EA201301025A1 (ru) | 2014-01-30 |
| EP2815765A1 (en) | 2014-12-24 |
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