AU2003273964B2 - Pharmaceutical compositions directed to Erb-B1 receptors - Google Patents
Pharmaceutical compositions directed to Erb-B1 receptors Download PDFInfo
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- AU2003273964B2 AU2003273964B2 AU2003273964A AU2003273964A AU2003273964B2 AU 2003273964 B2 AU2003273964 B2 AU 2003273964B2 AU 2003273964 A AU2003273964 A AU 2003273964A AU 2003273964 A AU2003273964 A AU 2003273964A AU 2003273964 B2 AU2003273964 B2 AU 2003273964B2
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C—CHEMISTRY; METALLURGY
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C07—ORGANIC CHEMISTRY
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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- C07K—PEPTIDES
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- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
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- C07K—PEPTIDES
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Landscapes
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| PCT/EP2003/011164 WO2004032960A1 (en) | 2002-10-10 | 2003-10-09 | Pharmaceutical compositions directed to erb-b1 receptors |
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| AU2003273964A1 AU2003273964A1 (en) | 2004-05-04 |
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|---|---|---|---|---|
| US7060808B1 (en) * | 1995-06-07 | 2006-06-13 | Imclone Systems Incorporated | Humanized anti-EGF receptor monoclonal antibody |
| US20030224001A1 (en) * | 1998-03-19 | 2003-12-04 | Goldstein Neil I. | Antibody and antibody fragments for inhibiting the growth of tumors |
| ZA200007412B (en) * | 1998-05-15 | 2002-03-12 | Imclone Systems Inc | Treatment of human tumors with radiation and inhibitors of growth factor receptor tyrosine kinases. |
| WO2000069459A1 (en) * | 1999-05-14 | 2000-11-23 | Imclone Systems Incorporated | Treatment of refractory human tumors with epidermal growth factor receptor antagonists |
| AU9500201A (en) * | 2000-08-09 | 2002-02-18 | Imclone Systems Inc | Treatment of hyperproliferative diseases with epidermal growth factor receptor antagonists |
| RU2292904C2 (ru) * | 2001-01-09 | 2007-02-10 | Мерк Патент Гмбх | Комбинированная терапия, использующая ингибиторы рецептора тирозинкиназы и ингибиторы ангиогенезиса |
| US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
| US20080008704A1 (en) * | 2001-03-16 | 2008-01-10 | Mark Rubin | Methods of treating colorectal cancer with anti-epidermal growth factor antibodies |
| JP4414142B2 (ja) | 2001-05-11 | 2010-02-10 | ルードヴィッヒ インスティテュート フォー キャンサー リサーチ | 特異的結合タンパク質およびその使用 |
| US20100056762A1 (en) | 2001-05-11 | 2010-03-04 | Old Lloyd J | Specific binding proteins and uses 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 |
| US9321832B2 (en) | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
| 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 |
| CA2501818C (en) * | 2002-10-10 | 2012-03-27 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Pharmaceutical compositions directed to erb-b1 receptors |
| TWI229650B (en) * | 2002-11-19 | 2005-03-21 | Sharp Kk | Substrate accommodating tray |
| DE10254601A1 (de) | 2002-11-22 | 2004-06-03 | Ganymed Pharmaceuticals Ag | Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung |
| RU2402569C2 (ru) * | 2004-03-19 | 2010-10-27 | Имклоун Элэлси | Человеческие антитела к рецептору эпидермального фактора роста |
| EA012622B1 (ru) | 2004-06-01 | 2009-10-30 | Домэнтис Лимитед | Биспецифичные гибридные антитела с увеличенным периодом полувыведения из сыворотки |
| SG10201403526YA (en) | 2005-07-25 | 2014-10-30 | Emergent Product Dev Seattle | B-cell reduction using cd37-specific and cd20-specific binding molecules |
| JP2009518025A (ja) * | 2005-12-06 | 2009-05-07 | ドマンティス リミテッド | 細胞表面標的に対して結合特異性を有する二重特異性リガンドおよびその使用方法 |
| MX2008008564A (es) | 2006-01-04 | 2009-01-29 | Merck Patent Gmbh | Terapeutica combinada con anticuerpos anti-egfr y anti-her2. |
| US20110165150A1 (en) * | 2006-01-18 | 2011-07-07 | Merck Patent Gmbh | Isolated organ perfusion combination therapy of cancer |
| US7498142B2 (en) * | 2006-01-31 | 2009-03-03 | Yeda Research And Development Co., Ltd. | Methods of identifying combinations of antibodies with an improved anti-tumor activity and compositions and methods using the antibodies |
| CN101484807A (zh) | 2006-03-31 | 2009-07-15 | 麻省理工学院 | 表达突变型egf受体的肿瘤的治疗 |
| CA2652926A1 (en) * | 2006-05-26 | 2007-12-06 | Bayer Healthcare Llc | Drug combinations with substituted diaryl ureas for the treatment of cancer |
| AU2007257692B2 (en) | 2006-06-12 | 2013-11-14 | Aptevo Research And Development Llc | Single-chain multivalent binding proteins with effector function |
| CA2670315A1 (en) | 2006-11-21 | 2008-11-20 | The Regents Of The University Of California | Anti-egfr family antibodies, bispecific anti-egfr family antibodies and methods of use thereof |
| CN104013956B (zh) | 2007-01-25 | 2018-12-18 | 达娜-法勃肿瘤研究所公司 | 抗egfr抗体在治疗egfr突变体介导的疾病中的用途 |
| AU2013200209B9 (en) * | 2007-03-01 | 2015-07-09 | Symphogen A/S | Recombinant anti-epidermal growth factor receptor antibody compositions |
| KR101805140B1 (ko) | 2007-03-01 | 2017-12-05 | 심포젠 에이/에스 | 재조합 항-표피 성장 인자 수용체 항체 조성물 |
| CA2680854C (en) | 2007-03-15 | 2017-02-14 | Ludwig Institute For Cancer Research | Treatment method using egfr antibodies and src inhibitors and related formulations |
| CN108424454B (zh) | 2007-08-14 | 2022-05-31 | 路德维格癌症研究所有限公司 | 靶向egf受体的单克隆抗体175及其衍生物和用途 |
| WO2009030239A1 (en) * | 2007-09-06 | 2009-03-12 | Genmab A/S | Novel methods and antibodies for treating cancer |
| EP2193149A1 (en) * | 2007-10-02 | 2010-06-09 | Merck Patent GmbH | Crystalline egfr - matuzumab complex and matuzumab mimetics obtained thereof |
| WO2009070753A2 (en) * | 2007-11-28 | 2009-06-04 | The Scripps Research Institute | Bivalent single chain fv antibody compositions that specifically bind to integrin receptor on a metastatic cell in a mammalian subject |
| US9266967B2 (en) | 2007-12-21 | 2016-02-23 | Hoffmann-La Roche, Inc. | Bivalent, bispecific antibodies |
| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| US8574577B2 (en) | 2008-01-03 | 2013-11-05 | The Scripps Research Institute | VEGF antibodies comprising modular recognition domains |
| US8557242B2 (en) | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | ERBB2 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 |
| US8557243B2 (en) | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | EFGR antibodies comprising modular recognition domains |
| WO2009088805A2 (en) * | 2008-01-03 | 2009-07-16 | The Scripps Research Institute | Antibody targeting through a modular recognition domain |
| ES2368700T3 (es) | 2008-04-11 | 2011-11-21 | Emergent Product Development Seattle, Llc | Agente inmunoterapéutico para cd37 y combinación con un agente quimioterapéutico bifuncional del mismo. |
| RU2540146C2 (ru) * | 2008-08-29 | 2015-02-10 | Симфоген А/С | Композиции рекомбинантных антител против рецептора эпидермального фактора роста |
| US8883149B2 (en) | 2008-09-15 | 2014-11-11 | Yeda Research And Development Co. Ltd. | Antibody combinations and use of same for treating cancer |
| CA2779436A1 (en) | 2008-10-31 | 2010-05-06 | Biogen Idec Ma Inc. | Light targeting molecules and uses thereof |
| NZ594665A (en) | 2009-03-20 | 2013-08-30 | Genentech Inc | Bispecific anti-her antibodies |
| CA2756244A1 (en) | 2009-04-02 | 2010-10-07 | Roche Glycart Ag | Multispecific antibodies comprising full length antibodies and single chain fab fragments |
| ES2537100T3 (es) | 2009-04-07 | 2015-06-02 | Roche Glycart Ag | Anticuerpos biespecíficos trivalentes |
| US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| AU2010296018B2 (en) | 2009-09-16 | 2016-05-05 | Genentech, Inc. | Coiled coil and/or tether containing protein complexes and uses thereof |
| CN104984322B (zh) * | 2009-10-14 | 2020-09-11 | 阿寇达医疗有限公司 | 神经调节蛋白在治疗外周神经损伤中的应用 |
| JP6184695B2 (ja) | 2009-12-04 | 2017-08-23 | ジェネンテック, インコーポレイテッド | 多重特異性抗体、抗体アナログ、組成物、及び方法 |
| AR080793A1 (es) | 2010-03-26 | 2012-05-09 | Roche Glycart Ag | Anticuerpos biespecificos |
| KR20130060223A (ko) | 2010-05-04 | 2013-06-07 | 메리맥 파마슈티컬즈, 인크. | 상피세포 성장인자 수용체(egfr)에 대한 항체 및 이의 용도 |
| NZ604003A (en) | 2010-05-27 | 2015-04-24 | Genmab As | Monoclonal antibodies against her2 |
| CN103153339B (zh) | 2010-05-27 | 2021-05-04 | 根马布股份公司 | 针对her2表位的单克隆抗体 |
| WO2012009705A1 (en) | 2010-07-15 | 2012-01-19 | Zyngenia, Inc. | Ang-2 binding complexes and uses thereof |
| US9464136B2 (en) * | 2010-08-20 | 2016-10-11 | Massachusetts Institute Of Technology | Antibody-based constructs directed against tyrosine kinase receptors |
| EP2609111B1 (en) | 2010-08-24 | 2017-11-01 | F. Hoffmann-La Roche AG | Bispecific antibodies comprising a disulfide stabilized-fv fragment |
| US9155802B2 (en) | 2010-11-01 | 2015-10-13 | Symphogen A/S | Pan-HER antibody composition |
| WO2012085111A1 (en) | 2010-12-23 | 2012-06-28 | F. Hoffmann-La Roche Ag | Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery |
| EP2668209B8 (en) | 2011-01-24 | 2021-08-11 | Gilead Sciences, Inc. | Antibodies selective for cells presenting egfr at high density |
| BR112013019975A2 (pt) | 2011-02-28 | 2017-08-01 | Hoffmann La Roche | proteínas de ligação de antígeno, composição farmacêutica, uso de uma proteína de ligação de antígeno, método para o tratamento de um paciente e método para a preparação de uma proteína de ligação de antígeno, ácido nucleico, vetor e célula hospedeira" |
| CA2824824A1 (en) | 2011-02-28 | 2012-09-07 | F. Hoffmann-La Roche Ag | Monovalent antigen binding proteins |
| AU2012245116A1 (en) | 2011-04-20 | 2013-11-07 | Genmab A/S | Bispecific antibodies against HER2 and CD3 |
| WO2012156975A1 (en) | 2011-05-16 | 2012-11-22 | Yeda Research And Development Co. Ltd. | COMBINATIONS OF ANTI ErbB ANTIBODIES FOR THE TREATMENT OF CANCER |
| ES2704038T3 (es) | 2011-05-24 | 2019-03-13 | Zyngenia Inc | Complejos multiespecíficos multivalentes y monovalentes y sus usos |
| 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 |
| EP2812357B1 (en) | 2012-02-10 | 2020-11-04 | F.Hoffmann-La Roche Ag | Single-chain antibodies and other heteromultimers |
| HK1202431A1 (en) | 2012-05-02 | 2015-10-02 | Symphogen A/S | Humanized pan-her antibody compositions |
| JP6309002B2 (ja) | 2012-06-27 | 2018-04-11 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 標的に特異的に結合する少なくとも1つの結合実体を含む抗体Fc領域結合体を作製するための方法およびその使用 |
| EP2867253B1 (en) | 2012-06-27 | 2016-09-14 | F. Hoffmann-La Roche AG | Method for selection and production of tailor-made highly selective and multi-specific targeting entities containing at least two different binding entities and uses thereof |
| WO2014064682A1 (en) * | 2012-10-24 | 2014-05-01 | Yeda Research And Development Co. Ltd. | Combinations of epidermal growth factor receptor targeting antibodies for treating cancer |
| HK1209434A1 (en) | 2012-11-13 | 2016-04-01 | Astellas Pharma Inc. | Agents for treatment of claudin expressing cancer diseases |
| WO2014127785A1 (en) | 2013-02-20 | 2014-08-28 | Ganymed Pharmaceuticals Ag | Combination therapy involving antibodies against claudin 18.2 for treatment of cancer |
| US10150800B2 (en) | 2013-03-15 | 2018-12-11 | Zyngenia, Inc. | EGFR-binding modular recognition domains |
| KR102089591B1 (ko) | 2013-07-29 | 2020-03-18 | 삼성전자주식회사 | 항 EGFR scFv 단편 및 이를 포함하는 항 c-Met/항 EGFR 이중 특이 항체 |
| RU2016115866A (ru) | 2013-10-11 | 2017-11-16 | Ф. Хоффманн-Ля Рош Аг | Мультиспецифические антитела с обменянными доменами и одинаковыми вариабельными доменами легкой цепи |
| CA2930307A1 (en) | 2013-11-13 | 2015-05-21 | Zymeworks Inc. | Monovalent antigen binding constructs targeting egfr and/or her2 and uses thereof |
| EP3074424B1 (en) | 2013-11-27 | 2025-02-12 | Zymeworks BC Inc. | Bispecific antigen-binding constructs targeting her2 |
| MA39599A (fr) | 2014-05-14 | 2016-10-05 | Merrimack Pharmaceuticals Inc | Dosage et administration d'agents thérapeutiques anti-egfr |
| SG11201703309PA (en) * | 2014-10-31 | 2017-05-30 | Baylor College Medicine | Survivin specific t-cell receptor targeting tumor but not t cells |
| WO2016065456A1 (en) * | 2014-10-31 | 2016-05-06 | Formation Biologics Inc. | Egfr antibody-based combination therapy |
| WO2016082044A1 (en) | 2014-11-27 | 2016-06-02 | Zymeworks Inc. | Methods of using bispecific antigen-binding constructs targeting her2 |
| JP6721590B2 (ja) | 2014-12-03 | 2020-07-15 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 多重特異性抗体 |
| WO2017053469A2 (en) | 2015-09-21 | 2017-03-30 | Aptevo Research And Development Llc | Cd3 binding polypeptides |
| WO2017055399A1 (en) | 2015-10-02 | 2017-04-06 | F. Hoffmann-La Roche Ag | Cellular based fret assay for the determination of simultaneous binding |
| SI3356411T1 (sl) | 2015-10-02 | 2021-09-30 | F. Hoffmann-La Roche Ag | Bispecifična protitelesa, specifična za PD1 in TIM3 |
| US11958913B2 (en) * | 2017-01-09 | 2024-04-16 | Biomunex Pharmaceuticals | Polypeptide linker for preparing multispecific antibodies |
| MX2019011770A (es) | 2017-04-03 | 2020-01-09 | Hoffmann La Roche | Inmunoconjugados de un anticuerpo anti-pd-1 con un mutante il-2 o con il-15. |
| DK3606955T3 (da) | 2017-04-05 | 2025-01-13 | Hoffmann La Roche | Bispecifikke antistoffer, der specifikt binder sig til PD1 og LAG3 |
| US12048745B2 (en) | 2018-05-01 | 2024-07-30 | Augusta University Research Institute, Inc. | Methods for detecting and reversing immune therapy resistance |
| TW202304994A (zh) | 2021-04-02 | 2023-02-01 | 美商泰尼歐生物公司 | 促效性抗il-2r抗體及使用方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5558864A (en) * | 1991-03-06 | 1996-09-24 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Humanized and chimeric anti-epidermal growth factor receptor monoclonal antibodies |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4943533A (en) * | 1984-03-01 | 1990-07-24 | The Regents Of The University Of California | Hybrid cell lines that produce monoclonal antibodies to epidermal growth factor receptor |
| US4968603A (en) | 1986-12-31 | 1990-11-06 | The Regents Of The University Of California | Determination of status in neoplastic disease |
| WO1989006692A1 (en) | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
| AU4128089A (en) * | 1988-09-15 | 1990-03-22 | Rorer International (Overseas) Inc. | Monoclonal antibodies specific to human epidermal growth factor receptor and therapeutic methods employing same |
| US5705157A (en) * | 1989-07-27 | 1998-01-06 | The Trustees Of The University Of Pennsylvania | Methods of treating cancerous cells with anti-receptor antibodies |
| DE122004000008I1 (de) | 1991-06-14 | 2005-06-09 | Genentech Inc | Humanisierter Heregulin Antikörper. |
| FI941572A7 (fi) * | 1991-10-07 | 1994-05-27 | Oncologix Inc | Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenete lmä |
| JPH05320513A (ja) * | 1992-05-26 | 1993-12-03 | Toray Dow Corning Silicone Co Ltd | 粘土状オルガノポリシロキサン組成物 |
| KR100269879B1 (ko) | 1992-06-30 | 2000-10-16 | 폴 에이치. 피셔 | 항-이알비비-2모노클로날항체의 조합물 및 그 사용방법 |
| RU2158127C2 (ru) * | 1994-12-23 | 2000-10-27 | Варнер-Ламберт Компани | Способы ингибирования тирозинкиназы рецептора эпидермального фактора роста, азотсодержащие трициклические соединения, фармацевтическая композиция, предназначенная для введения ингибитора тирозинкиназы рецептора эпидермального фактора роста, например, erb-b2, erb-b3 или erb-b4, и противозачаточная композиция |
| WO1996040210A1 (en) * | 1995-06-07 | 1996-12-19 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth of tumors |
| CA2372053C (en) * | 1999-04-28 | 2008-09-02 | Board Of Regents, The University Of Texas System | Compositions and methods for cancer treatment by selectively inhibiting vegf |
| US20020103345A1 (en) * | 2000-05-24 | 2002-08-01 | Zhenping Zhu | Bispecific immunoglobulin-like antigen binding proteins and method of production |
| RU2292904C2 (ru) * | 2001-01-09 | 2007-02-10 | Мерк Патент Гмбх | Комбинированная терапия, использующая ингибиторы рецептора тирозинкиназы и ингибиторы ангиогенезиса |
| CN100488563C (zh) * | 2001-02-19 | 2009-05-20 | 默克专利有限公司 | 免疫原性降低的经修饰抗egfr抗体 |
| CA2501818C (en) * | 2002-10-10 | 2012-03-27 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Pharmaceutical compositions directed to erb-b1 receptors |
-
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- 2003-10-09 DK DK03757931.5T patent/DK1549344T3/en active
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-
2010
- 2010-09-21 JP JP2010211122A patent/JP2010280727A/ja active Pending
-
2015
- 2015-04-06 CY CY20151100329T patent/CY1116167T1/el unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5558864A (en) * | 1991-03-06 | 1996-09-24 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Humanized and chimeric anti-epidermal growth factor receptor monoclonal antibodies |
Non-Patent Citations (2)
| Title |
|---|
| Modjtahedi, H. et al. Cell. Biophys. 1993, vol. 22, pp. 129-146 * |
| YE, D et al. Oncogene. Vol.18(3): 731-738 * |
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