JP5497887B2 - 二重特異性抗ＥｒｂＢ−２／抗ｃ−Ｍｅｔ抗体 - Google Patents
二重特異性抗ＥｒｂＢ−２／抗ｃ−Ｍｅｔ抗体 Download PDFInfo
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Families Citing this family (167)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| JP2011513427A (ja) * | 2008-03-06 | 2011-04-28 | ジェネンテック， インコーポレイテッド | ｃ−ｍｅｔ及びＥＧＦＲアンタゴニストの併用療法 |
| BRPI1014089A2 (pt) | 2009-04-02 | 2016-04-19 | Roche Glycart Ag | anticorpos multiespecíficos que compreendem anticorpos de comprimento completo e fragmentos fab de cadeia simples |
| DK2417156T3 (en) | 2009-04-07 | 2015-03-02 | Roche Glycart Ag | Trivalent, bispecific antibodies |
| US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| US9493578B2 (en) | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
| CA2781519A1 (en) | 2009-09-16 | 2011-03-24 | Genentech, Inc. | Coiled coil and/or tether containing protein complexes and uses thereof |
| TW201138821A (en) | 2010-03-26 | 2011-11-16 | Roche Glycart Ag | Bispecific antibodies |
| CA2806252C (en) | 2010-07-29 | 2019-05-14 | Xencor, Inc. | Antibodies with modified isoelectric points |
| RU2612903C2 (ru) | 2010-08-02 | 2017-03-13 | Ридженерон Фармасьютикалз, Инк. | Мыши, у которых вырабатываются связывающие белки, содержащие vl-домены |
| CA2807278A1 (en) | 2010-08-24 | 2012-03-01 | F. Hoffmann - La Roche Ag | Bispecific antibodies comprising a disulfide stabilized - fv fragment |
| EP3264089A1 (en) | 2010-08-31 | 2018-01-03 | Genentech, Inc. | Biomarkers and methods of treatment |
| SG188324A1 (en) | 2010-09-03 | 2013-04-30 | Academia Sinica | Anti-c-met antibody and methods of use thereof |
| RU2604490C2 (ru) | 2010-11-05 | 2016-12-10 | Займворкс Инк. | ДИЗАЙН УСТОЙЧИВОГО ГЕТЕРОДИМЕРНОГО АНТИТЕЛА С МУТАЦИЯМИ В Fc ДОМЕНЕ |
| WO2012085111A1 (en) | 2010-12-23 | 2012-06-28 | F. Hoffmann-La Roche Ag | Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery |
| JP5764677B2 (ja) | 2011-02-28 | 2015-08-19 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 抗原結合タンパク質 |
| CN103403025B (zh) | 2011-02-28 | 2016-10-12 | 弗·哈夫曼-拉罗切有限公司 | 单价抗原结合蛋白 |
| BR112013023653A2 (pt) | 2011-03-17 | 2016-12-13 | Univ Ramot | anticorpo biespecífico, método de preparação do anticorpo, e composição farmacêutica |
| DK2694972T3 (en) * | 2011-04-04 | 2017-10-02 | Pierian Holdings Inc | PROCEDURES FOR PREVENTING AND IMPROVING GASTRIC CANCER SURVIVAL |
| PT2748201T (pt) * | 2011-08-23 | 2018-02-08 | Roche Glycart Ag | Moléculas de ligação ao antigénio biespecíficas que ativam as células t |
| KR101886983B1 (ko) | 2011-08-23 | 2018-08-08 | 로슈 글리카트 아게 | 2 개의 ｆａｂ 단편을 포함하는 fc-부재 항체 및 이용 방법 |
| JP5925893B2 (ja) * | 2011-08-23 | 2016-05-25 | ロシュ グリクアート アーゲー | 二重特異性抗原結合分子 |
| WO2013026837A1 (en) * | 2011-08-23 | 2013-02-28 | Roche Glycart Ag | Bispecific t cell activating antigen binding molecules |
| WO2013026839A1 (en) | 2011-08-23 | 2013-02-28 | Roche Glycart Ag | Bispecific antibodies specific for t-cell activating antigens and a tumor antigen and methods of use |
| WO2013033008A2 (en) * | 2011-08-26 | 2013-03-07 | Merrimack Pharmaceuticals, Inc. | Tandem fc bispecific antibodies |
| KR20130037153A (ko) * | 2011-10-05 | 2013-04-15 | 삼성전자주식회사 | 항 ｃ-Ｍｅｔ 항체 및 그의 용도 |
| US12466897B2 (en) | 2011-10-10 | 2025-11-11 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
| GB2504139B (en) | 2012-07-20 | 2014-12-31 | Argen X Bv | Antibodies to highly conserved targets produced by the immunisation of Camelidae species |
| KR102052774B1 (ko) | 2011-11-04 | 2019-12-04 | 자임워크스 인코포레이티드 | Ｆｃ 도메인 내의 돌연변이를 갖는 안정한 이종이합체 항체 설계 |
| KR101963230B1 (ko) | 2011-12-26 | 2019-03-29 | 삼성전자주식회사 | 복수개의 단일 항체를 포함하는 단백질 복합체 |
| WO2013119966A2 (en) | 2012-02-10 | 2013-08-15 | Genentech, Inc. | Single-chain antibodies and other heteromultimers |
| US9062120B2 (en) | 2012-05-02 | 2015-06-23 | Janssen Biotech, Inc. | Binding proteins having tethered light chains |
| TW201843172A (zh) * | 2012-06-25 | 2018-12-16 | 美商再生元醫藥公司 | 抗－ｅｇｆｒ抗體及其用途 |
| US9499634B2 (en) | 2012-06-25 | 2016-11-22 | Zymeworks Inc. | Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells |
| RU2639287C2 (ru) | 2012-06-27 | 2017-12-20 | Ф. Хоффманн-Ля Рош Аг | Способ отбора и получения высокоселективных и мультиспецифичных нацеливающих групп с заданными свойствами, включающих по меньшей мере две различные связывающие группировки, и их применения |
| KR20150030744A (ko) | 2012-06-27 | 2015-03-20 | 에프. 호프만-라 로슈 아게 | 표적에 특이적으로 결합하는 하나 이상의 결합 단위를 포함하는 항체 Ｆｃ－영역 접합체의 제조 방법 및 그의 용도 |
| JP6581505B2 (ja) | 2012-10-03 | 2019-09-25 | ザイムワークス，インコーポレイテッド | 重鎖および軽鎖ポリペプチドの対を定量化する方法 |
| KR101911438B1 (ko) | 2012-10-31 | 2018-10-24 | 삼성전자주식회사 | 이중 특이 항원 결합 단백질 복합체 및 이중 특이 항체의 제조 방법 |
| EP2914628A1 (en) * | 2012-11-01 | 2015-09-09 | Max-Delbrück-Centrum für Molekulare Medizin | An antibody that binds cd269 (bcma) suitable for use in the treatment of plasma cell diseases such as multiple myeloma and autoimmune diseases |
| EP2914629A1 (en) | 2012-11-05 | 2015-09-09 | MAB Discovery GmbH | Method for the production of multispecific antibodies |
| EP2727941A1 (en) | 2012-11-05 | 2014-05-07 | MAB Discovery GmbH | Method for the production of multispecific antibodies |
| US20170275367A1 (en) | 2012-11-21 | 2017-09-28 | Janssen Biotech, Inc. | Bispecific EGFR/C-Met Antibodies |
| US9695228B2 (en) | 2012-11-21 | 2017-07-04 | Janssen Biotech, Inc. | EGFR and c-Met fibronectin type III domain binding molecules |
| PL2922872T3 (pl) * | 2012-11-21 | 2019-03-29 | Janssen Biotech, Inc. | Bispecyficzne przeciwciała przeciwko egfr/c-met |
| KR102545617B1 (ko) | 2012-11-28 | 2023-06-20 | 자임워크스 비씨 인코포레이티드 | 가공된 면역글로불린 중쇄-경쇄 쌍 및 이들의 용도 |
| US9914785B2 (en) | 2012-11-28 | 2018-03-13 | Zymeworks Inc. | Engineered immunoglobulin heavy chain-light chain pairs and uses thereof |
| US9701759B2 (en) | 2013-01-14 | 2017-07-11 | Xencor, Inc. | Heterodimeric proteins |
| US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
| US10131710B2 (en) | 2013-01-14 | 2018-11-20 | Xencor, Inc. | Optimized antibody variable regions |
| US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
| HRP20191865T1 (hr) | 2013-01-14 | 2020-01-10 | Xencor, Inc. | Novi heterodimerni proteini |
| US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
| US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
| WO2014113510A1 (en) | 2013-01-15 | 2014-07-24 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
| RU2015140915A (ru) * | 2013-02-26 | 2017-04-03 | Роше Гликарт Аг | Биспецифические антигенсвязывающие молекулы, активирующие т-клетки |
| MX2015011712A (es) | 2013-03-06 | 2016-04-04 | Merrimack Pharmaceuticals Inc | Anticerpos biespecificos fc en fila anti-c-met. |
| CA3093606A1 (en) | 2013-03-15 | 2014-09-18 | Xencor, Inc. | Heterodimeric proteins for induction of t cells |
| US10106624B2 (en) | 2013-03-15 | 2018-10-23 | Xencor, Inc. | Heterodimeric proteins |
| US10519242B2 (en) | 2013-03-15 | 2019-12-31 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
| US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| KR102049990B1 (ko) * | 2013-03-28 | 2019-12-03 | 삼성전자주식회사 | c-Met 항체 및 VEGF 결합 단편이 연결된 융합 단백질 |
| KR102049991B1 (ko) * | 2013-03-28 | 2019-12-02 | 삼성전자주식회사 | 항 c-Met/항 Her2 이중 특이 항체 |
| KR102067613B1 (ko) * | 2013-03-28 | 2020-01-20 | 삼성전자주식회사 | 항 c-Met 항체 및 항 her2 항체를 포함하는 병용 투여용 조성물 |
| KR102074421B1 (ko) * | 2013-03-29 | 2020-02-10 | 삼성전자주식회사 | 항 c-Met/항 EGFR 이중 특이 항체 |
| US9388243B2 (en) | 2013-05-29 | 2016-07-12 | Samsung Electronics Co., Ltd. | Method of target membrane protein depletion |
| KR102190220B1 (ko) * | 2013-05-29 | 2020-12-14 | 삼성전자주식회사 | 타겟 특이적 세포막 단백질 제거용 조성물 |
| US9879081B2 (en) * | 2013-06-25 | 2018-01-30 | Samsung Electronics Co., Ltd. | Protein complex, bispecific antibody including the protein complex, and method of preparation thereof |
| KR102236367B1 (ko) * | 2013-07-26 | 2021-04-05 | 삼성전자주식회사 | DARPin을 포함하는 이중 특이 키메라 단백질 |
| 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 |
| IL244623B (en) | 2013-10-14 | 2022-08-01 | Janssen Biotech Inc | Cysteine engineered fibronectin type iii domain binding molecules |
| EA039356B1 (ru) * | 2013-10-18 | 2022-01-18 | Янссен Байотек, Инк. | БИСПЕЦИФИЧЕСКИЕ К EGFR/c-Met АНТИТЕЛА |
| US9717715B2 (en) | 2013-11-15 | 2017-08-01 | Samsung Electronics Co., Ltd. | Method of combination therapy using an anti-C-Met antibody |
| CA2924268C (en) * | 2013-11-21 | 2021-05-18 | F. Hoffmann-La Roche Ag | Anti-alpha-synuclein antibodies and methods of use |
| MX376384B (es) | 2013-11-27 | 2025-03-07 | Zymeworks Bc Inc | Construcciones de union a antigenos biespecificas dirigidas a her2. |
| KR102178323B1 (ko) | 2013-11-29 | 2020-11-13 | 삼성전자주식회사 | 항 c-Met/항 Ang2 이중 특이 항체 |
| US10370692B2 (en) | 2013-12-20 | 2019-08-06 | Hoffmann-La Roche Inc. | Recombinant polypeptide production methods |
| TW201609805A (zh) | 2013-12-23 | 2016-03-16 | 美國禮來大藥廠 | 結合ｅｇｆｒ及ｍｅｔ之多功能抗體 |
| BR112016015589A2 (pt) * | 2014-01-06 | 2017-10-31 | Hoffmann La Roche | módulos de trânsito monovalentes para a barreira hematoencefálica |
| KR102194142B1 (ko) * | 2014-01-20 | 2020-12-23 | 삼성전자주식회사 | 항 c-Met/항 EGFR 이중 특이 항체 및 c-Src 저해제를 포함하는 병용 투여용 약학 조성물 |
| KR20160125965A (ko) * | 2014-02-28 | 2016-11-01 | 아스테라스 세이야쿠 가부시키가이샤 | 신규 인간 tlr2 및 인간 tlr4에 결합하는 이중 특이적 항체 |
| RU2016141307A (ru) | 2014-03-21 | 2018-04-24 | Регенерон Фармасьютикалз, Инк. | Отличные от человека животные, которые вырабатывают однодоменные связывающие белки |
| RU2723940C2 (ru) * | 2014-03-21 | 2020-06-18 | Экс-Боди, Инк. | Биспецифические антигенсвязывающие полипептиды |
| WO2015143406A2 (en) | 2014-03-21 | 2015-09-24 | Regeneron Pharmaceuticals, Inc. | Vl antigen binding proteins exhibiting distinct binding characteristics |
| EP3122900A1 (en) | 2014-03-24 | 2017-02-01 | F. Hoffmann-La Roche AG | Cancer treatment with c-met antagonists and correlation of the latter with hgf expression |
| EP3954713A3 (en) | 2014-03-28 | 2022-03-30 | Xencor, Inc. | Bispecific antibodies that bind to cd38 and cd3 |
| KR102526945B1 (ko) | 2014-04-30 | 2023-04-27 | 막스-델부뤽-센트럼 퓌어 몰레쿨라레 메디친 인 데어 헬름홀츠-게마인샤프트 | Ｃｄ269에 대한 인간화 항체 |
| KR102223502B1 (ko) | 2014-05-09 | 2021-03-05 | 삼성전자주식회사 | 항 c-Met/항 EGFR/항 Her3 다중 특이 항체 및 이의 이용 |
| KR102401595B1 (ko) * | 2014-05-09 | 2022-05-24 | 삼성전자주식회사 | 항 HER2 scFv 단편 및 이를 포함하는 항 c-Met/항 HER2 이중 특이 항체 |
| US9975960B2 (en) * | 2014-05-09 | 2018-05-22 | Samsung Electronics Co., Ltd. | Anti-HER2 antibody and anti-c-Met/anti-HER2 bispecific antibodies comprising the same |
| US20170233489A1 (en) * | 2014-05-26 | 2017-08-17 | Samsung Electronics Co., Ltd. | Composition for combination therapy comprising anti-her2 antibody and anti-c-met antibody |
| EA201692476A1 (ru) | 2014-05-28 | 2017-07-31 | Займворкс Инк. | Модифицированные антигенсвязывающие полипептидные конструкции и их применение |
| KR102259232B1 (ko) * | 2014-08-25 | 2021-05-31 | 삼성전자주식회사 | 항 c-Met/항 Ang2 이중 특이 항체 |
| CN105888672B (zh) * | 2014-09-02 | 2018-07-27 | 北京中煤矿山工程有限公司 | 一种斜冻结孔用外夹式下冻结管装置 |
| EP3215524B1 (en) | 2014-11-06 | 2021-01-13 | F.Hoffmann-La Roche Ag | Fc-region variants with modified fcrn- and protein a-binding properties |
| CN107074955B (zh) | 2014-11-20 | 2021-06-22 | 豪夫迈·罗氏有限公司 | 针对FolR1和CD3的T细胞活化性双特异性抗原结合分子 |
| RS60615B1 (sr) | 2014-11-20 | 2020-08-31 | Hoffmann La Roche | Zajednički laki lanci i postupci upotrebe |
| LT3789402T (lt) | 2014-11-20 | 2022-09-26 | F. Hoffmann-La Roche Ag | Kompleksinė terapija, naudojant t ląsteles aktyvinančias bispecifines antigeną surišančias molekules ir pd-1 ašį surišančius antagonistus |
| CN116333153A (zh) | 2014-11-26 | 2023-06-27 | 森科股份有限公司 | 结合cd3和肿瘤抗原的异二聚体抗体 |
| EP3223907A2 (en) | 2014-11-26 | 2017-10-04 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and cd38 |
| US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
| PL3227332T3 (pl) | 2014-12-03 | 2020-06-15 | F. Hoffmann-La Roche Ag | Wielospecyficzne przeciwciała |
| WO2016105450A2 (en) | 2014-12-22 | 2016-06-30 | Xencor, Inc. | Trispecific antibodies |
| US10227411B2 (en) | 2015-03-05 | 2019-03-12 | Xencor, Inc. | Modulation of T cells with bispecific antibodies and FC fusions |
| US11111314B2 (en) | 2015-03-19 | 2021-09-07 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
| IL302486A (en) | 2015-06-24 | 2023-06-01 | Hoffmann La Roche | Antibodies against the transnephrine receptor with adapted affinity |
| CN107849137B (zh) * | 2015-10-02 | 2021-11-26 | 豪夫迈·罗氏有限公司 | 双特异性抗ceaxcd3 t细胞活化性抗原结合分子 |
| JP6657392B2 (ja) | 2015-10-02 | 2020-03-04 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 二重特異性抗ヒトｃｄ２０／ヒトトランスフェリン受容体抗体及び使用方法 |
| AR106189A1 (es) | 2015-10-02 | 2017-12-20 | Hoffmann La Roche | ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO |
| CA3000869A1 (en) | 2015-10-08 | 2017-04-13 | Zymeworks Inc. | Antigen-binding polypeptide constructs comprising kappa and lambda light chains and uses thereof |
| US11235063B2 (en) | 2015-11-03 | 2022-02-01 | Merck Patent Gmbh | Bi-specific antibodies for enhanced tumor selectivity and inhibition and uses thereof |
| KR20180085800A (ko) | 2015-12-07 | 2018-07-27 | 젠코어 인코포레이티드 | Cd3 및 psma에 결합하는 이종이합체성 항체 |
| CR20180365A (es) | 2015-12-16 | 2018-09-28 | Amgen Inc | PROTEÍNAS DE UNIÓN AL ANTÍGENO BISPECÍFICO DE ANTI-TL1A/ANTI-TNF-a Y SUS USOS |
| IL263542B2 (en) | 2016-06-14 | 2024-10-01 | Xencor Inc | Bispecific antibodies inhibit immunological checkpoint |
| SG11201811062XA (en) | 2016-06-21 | 2019-01-30 | Janssen Biotech Inc | Cysteine engineered fibronectin type iii domain binding molecules |
| KR20190020341A (ko) | 2016-06-28 | 2019-02-28 | 젠코어 인코포레이티드 | 소마토스타틴 수용체 2에 결합하는 이종이량체 항체 |
| US10793632B2 (en) | 2016-08-30 | 2020-10-06 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| CN110214148A (zh) | 2016-10-14 | 2019-09-06 | Xencor股份有限公司 | 含有IL-15/IL-15Rα Fc融合蛋白和PD-1抗体片段的双特异性异源二聚体融合蛋白 |
| TWI782930B (zh) | 2016-11-16 | 2022-11-11 | 美商再生元醫藥公司 | 抗ｍｅｔ抗體，結合ｍｅｔ之雙特異性抗原結合分子及其使用方法 |
| EP3554561B1 (en) | 2016-12-14 | 2023-06-28 | Janssen Biotech, Inc. | Cd137 binding fibronectin type iii domains |
| WO2018111976A1 (en) | 2016-12-14 | 2018-06-21 | Janssen Biotech, Inc. | Pd-l1 binding fibronectin type iii domains |
| JP7104703B2 (ja) | 2016-12-14 | 2022-07-21 | ヤンセン バイオテツク，インコーポレーテツド | Ｃｄ８ａ結合フィブロネクチンｉｉｉ型ドメイン |
| WO2018118616A1 (en) * | 2016-12-22 | 2018-06-28 | Eli Lilly And Company | Methods for producing fabs and igg bispecific antibodies |
| MY200973A (en) | 2017-04-11 | 2024-01-26 | Inhibrx Inc | Multispecific Polypeptide Constructs Having Constrained Cd3 Binding And Methods Of Using The Same |
| KR102078292B1 (ko) | 2017-05-30 | 2020-02-19 | 주식회사 종근당 | 신규한 항 c-Met 항체 및 이의 용도 |
| AU2018291497A1 (en) | 2017-06-30 | 2020-01-16 | Xencor, Inc. | Targeted heterodimeric Fc fusion proteins containing IL-15/IL-15Ra and antigen binding domains |
| US10981992B2 (en) | 2017-11-08 | 2021-04-20 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| AU2018366199A1 (en) | 2017-11-08 | 2020-05-28 | Xencor, Inc. | Bispecific and monospecific antibodies using novel anti-PD-1 sequences |
| MX2020006322A (es) | 2017-12-19 | 2020-09-18 | Xencor Inc | Proteinas de fusion il-2 fc modificadas. |
| WO2019122409A1 (en) | 2017-12-22 | 2019-06-27 | Argenx Bvba | Bispecific antigen binding construct |
| GB201802487D0 (en) | 2018-02-15 | 2018-04-04 | Argenx Bvba | Cytokine combination therapy |
| US11780926B2 (en) * | 2018-03-22 | 2023-10-10 | Universität Stuttgart | Multivalent binding molecules |
| CN112469477A (zh) | 2018-04-04 | 2021-03-09 | Xencor股份有限公司 | 与成纤维细胞活化蛋白结合的异源二聚体抗体 |
| IL323061A (en) * | 2018-04-11 | 2025-10-01 | Inhibrx Biosciences Inc | Multispecific polypeptide constructs with forced CD3 binding and related methods and uses |
| EP3781598A1 (en) | 2018-04-18 | 2021-02-24 | Xencor, Inc. | Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains |
| AU2019256539A1 (en) | 2018-04-18 | 2020-11-26 | Xencor, Inc. | PD-1 targeted heterodimeric fusion proteins containing IL-15/IL-15Ra Fc-fusion proteins and PD-1 antigen binding domains and uses thereof |
| CN112789294A (zh) | 2018-07-24 | 2021-05-11 | 印希比股份有限公司 | 含有受限cd3结合结构域和受体结合区的多特异性多肽构建体及其使用方法 |
| SG11202103192RA (en) | 2018-10-03 | 2021-04-29 | Xencor Inc | Il-12 heterodimeric fc-fusion proteins |
| CA3115089A1 (en) | 2018-10-11 | 2020-04-16 | Inhibrx, Inc. | Dll3 single domain antibodies and therapeutic compositions thereof |
| AU2020232605A1 (en) | 2019-03-01 | 2021-10-21 | Xencor, Inc. | Heterodimeric antibodies that bind ENPP3 and CD3 |
| KR102239781B1 (ko) * | 2019-04-08 | 2021-04-13 | 주식회사 녹십자 | Gpnmb 및 cd3에 특이적으로 결합하는 이중특이적 항체 및 이의 용도 |
| BR112021019959A2 (pt) * | 2019-04-17 | 2022-02-08 | Novo Nordisk As | Anticorpo biespecífico, e, formulação farmacêutica |
| KR20220063185A (ko) | 2019-09-16 | 2022-05-17 | 리제너론 파마슈티칼스 인코포레이티드 | 면역-pet 영상화를 위한 방사성 표지된 met 결합 단백질 |
| WO2021076574A2 (en) | 2019-10-14 | 2021-04-22 | Aro Biotherapeutics Company | Fn3 domain-sirna conjugates and uses thereof |
| WO2021076543A1 (en) | 2019-10-14 | 2021-04-22 | Aro Biotherapeutics Company | Epcam binding fibronectin type iii domains |
| EP4045061A4 (en) | 2019-10-14 | 2024-04-17 | ARO Biotherapeutics Company | FIBRONECTIN TYPE III DOMAINS BINDING TO CD137 |
| WO2021231976A1 (en) | 2020-05-14 | 2021-11-18 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3 |
| KR102607909B1 (ko) | 2020-08-19 | 2023-12-01 | 젠코어 인코포레이티드 | 항-cd28 조성물 |
| JP2024511319A (ja) | 2021-03-09 | 2024-03-13 | ゼンコア インコーポレイテッド | Ｃｄ３及びｃｌｄｎ６に結合するヘテロ二量体抗体 |
| JP2024509274A (ja) | 2021-03-10 | 2024-02-29 | ゼンコア インコーポレイテッド | Ｃｄ３及びｇｐｃ３に結合するヘテロ二量体抗体 |
| JP2024517610A (ja) | 2021-04-14 | 2024-04-23 | アロ・バイオセラピューティクス・カンパニー | Ｃｄ７１に結合するフィブロネクチンｉｉｉ型ドメイン |
| BR112023021318A2 (pt) | 2021-04-14 | 2023-12-19 | Aro Biotherapeutics Company | Conjugados de domínio fn3-sirna e usos dos mesmos |
| WO2023069888A1 (en) | 2021-10-18 | 2023-04-27 | Tavotek Biotherapeutics (Hong Kong) Limited | ANTI-EGFR ANTIBODIES, ANTI-cMET ANTIBODIES, ANTI-VEGF ANTIBODIES, MULTISPECIFIC ANTIBODIES, AND USES THEREOF |
| CN118742325A (zh) | 2022-01-28 | 2024-10-01 | 上海岸阔医药科技有限公司 | 预防或治疗与抗肿瘤剂相关的疾病或病症的方法 |
| WO2023155905A1 (zh) | 2022-02-21 | 2023-08-24 | 上海岸阔医药科技有限公司 | 化合物及其用途 |
| EP4604988A1 (en) | 2022-10-21 | 2025-08-27 | Diagonal Therapeutics Inc. | Heteromeric agonistic antibodies to il-18 receptor |
| JP2025539837A (ja) * | 2022-11-24 | 2025-12-09 | 江▲蘇▼恒瑞医▲薬▼股▲フン▼有限公司 | Ｈｇｆｒとｅｇｆｒに特異的に結合する二重特異性抗体を含む医薬組成物 |
| AU2024252640A1 (en) | 2023-04-07 | 2025-10-02 | Diagonal Therapeutics Inc. | Bispecific agonistic antibodies to activin a receptor like type 1 (alk1) |
| US20240383990A1 (en) | 2023-04-07 | 2024-11-21 | Diagonal Therapeutics Inc. | Hinge-modified bispecific antibodies |
| WO2024243048A1 (en) | 2023-05-19 | 2024-11-28 | Diagonal Therapeutics Inc. | Bispecific agonistic antibodies to il12 receptor |
| TW202502822A (zh) * | 2023-07-07 | 2025-01-16 | 大陸商四川科倫博泰生物醫藥股份有限公司 | Ｅｇｆｒ／ｃ－ｍｅｔ雙特異性結合蛋白及其用途 |
| TW202502823A (zh) * | 2023-07-07 | 2025-01-16 | 大陸商四川科倫博泰生物醫藥股份有限公司 | Ｅｇｆｒ／ｃ－ｍｅｔ雙特異性結合蛋白及其用途 |
| WO2025025434A1 (zh) * | 2023-08-02 | 2025-02-06 | 百泰生物药业有限公司 | EGFR/c-Met双特异性抗体及其应用 |
| WO2025090519A1 (en) | 2023-10-23 | 2025-05-01 | Diagonal Therapeutics Inc. | Heteromeric agonistic antibodies to il-18 receptor |
| WO2025103450A1 (en) * | 2023-11-15 | 2025-05-22 | Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | Antibody-drug conjugates targeting egfr/c-met and preparation methods and uses thereof |
| WO2025213061A2 (en) | 2024-04-04 | 2025-10-09 | Ethyreal Bio, Inc. | Anti-tshr antibodies and uses thereof |
Family Cites Families (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CU22545A1 (es) | 1994-11-18 | 1999-03-31 | Centro Inmunologia Molecular | Obtención de un anticuerpo quimérico y humanizado contra el receptor del factor de crecimiento epidérmico para uso diagnóstico y terapéutico |
| US4968603A (en) | 1986-12-31 | 1990-11-06 | The Regents Of The University Of California | Determination of status in neoplastic disease |
| AU600575B2 (en) | 1987-03-18 | 1990-08-16 | Sb2, Inc. | Altered antibodies |
| US5204244A (en) | 1987-10-27 | 1993-04-20 | Oncogen | Production of chimeric antibodies by homologous recombination |
| US5202238A (en) | 1987-10-27 | 1993-04-13 | Oncogen | Production of chimeric antibodies by homologous recombination |
| JP3040121B2 (ja) | 1988-01-12 | 2000-05-08 | ジェネンテク，インコーポレイテッド | 増殖因子レセプターの機能を阻害することにより腫瘍細胞を処置する方法 |
| WO1991006305A1 (en) | 1989-11-07 | 1991-05-16 | Bristol-Myers Squibb Company | Oligomeric immunoglobulins |
| WO1992004053A1 (en) | 1990-08-31 | 1992-03-19 | Bristol-Myers Sqibb Company | Homoconjugated immunoglobulins |
| DK0531472T3 (da) | 1991-03-06 | 2003-12-01 | Merck Patent Gmbh | Humaniserede monoklonale antistoffer |
| DE4118120A1 (de) | 1991-06-03 | 1992-12-10 | Behringwerke Ag | Tetravalente bispezifische rezeptoren, ihre herstellung und verwendung |
| US6511663B1 (en) | 1991-06-11 | 2003-01-28 | Celltech R&D Limited | Tri- and tetra-valent monospecific antigen-binding proteins |
| EP0590058B1 (en) | 1991-06-14 | 2003-11-26 | Genentech, Inc. | HUMANIZED Heregulin ANTIBODy |
| US5747654A (en) | 1993-06-14 | 1998-05-05 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant disulfide-stabilized polypeptide fragments having binding specificity |
| US6476198B1 (en) | 1993-07-13 | 2002-11-05 | The Scripps Research Institute | Multispecific and multivalent antigen-binding polypeptide molecules |
| WO1995009917A1 (en) | 1993-10-07 | 1995-04-13 | The Regents Of The University Of California | Genetically engineered bispecific tetravalent antibodies |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US5686292A (en) | 1995-06-02 | 1997-11-11 | Genentech, Inc. | Hepatocyte growth factor receptor antagonist antibodies and uses thereof |
| AU6267896A (en) * | 1995-06-07 | 1996-12-30 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth oftumors |
| US7060808B1 (en) * | 1995-06-07 | 2006-06-13 | Imclone Systems Incorporated | Humanized anti-EGF receptor monoclonal antibody |
| US6750334B1 (en) | 1996-02-02 | 2004-06-15 | Repligen Corporation | CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor |
| WO1999009055A2 (en) | 1997-08-18 | 1999-02-25 | Innogenetics N.V. | Interferon-gamma-binding molecules for treating septic shock, cachexia, immune diseases and skin disorders |
| JP4334141B2 (ja) | 1998-04-20 | 2009-09-30 | グリカート バイオテクノロジー アクチェンゲゼルシャフト | 抗体依存性細胞傷害性を改善するための抗体のグリコシル化操作 |
| DE19819846B4 (de) | 1998-05-05 | 2016-11-24 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Multivalente Antikörper-Konstrukte |
| JP4113670B2 (ja) * | 1998-06-22 | 2008-07-09 | イムノメディクス， インコーポレイテッド | プレターゲッティング診断およびプレターゲッティング治療のための二重特異性抗体の使用 |
| US6897044B1 (en) | 1999-01-28 | 2005-05-24 | Biogen Idec, Inc. | Production of tetravalent antibodies |
| CA2369292C (en) | 1999-04-09 | 2010-09-21 | Kyowa Hakko Kogyo Co. Ltd. | Method of modulating the activity of functional immune molecules |
| GEP20104998B (en) | 1999-06-25 | 2010-06-10 | Genentech Inc | Humanized antibody which binds erbb2 and blocks activation by ligand receptor of erbb2 (variants) and use of the composition comprising these antibodies methods for treating cancer |
| DK1272647T3 (en) | 2000-04-11 | 2014-12-15 | Genentech Inc | Multivalent antibodies and uses thereof |
| FR2807767B1 (fr) | 2000-04-12 | 2005-01-14 | Lab Francais Du Fractionnement | Anticorps monoclonaux anti-d |
| EP1293514B1 (en) | 2001-09-14 | 2006-11-29 | Affimed Therapeutics AG | Multimeric single chain tandem Fv-antibodies |
| ATE430580T1 (de) | 2001-10-25 | 2009-05-15 | Genentech Inc | Glycoprotein-zusammensetzungen |
| US20040093621A1 (en) | 2001-12-25 | 2004-05-13 | Kyowa Hakko Kogyo Co., Ltd | Antibody composition which specifically binds to CD20 |
| 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 |
| PL224786B1 (pl) | 2003-01-22 | 2017-01-31 | Glycart Biotechnology Ag | Wyizolowany kwas nukleinowy, ssaczy wektor ekspresyjny, komórki gospodarza, fuzja polipeptydowa i sposób jej wytwarzania, sposoby in vitro i ex vivo modyfikowania profilu glikozylacji polipeptydu wytwarzanego przez komórki gospodarza |
| BRPI0407446A (pt) | 2003-02-13 | 2006-01-31 | Pharmacia Corp | Anticorpos para c-met para o tratamento de cânceres |
| ITMI20031127A1 (it) | 2003-06-05 | 2004-12-06 | Uni Degli Studi Del Piemont E Orientale Am | Anticorpi anti-hgf-r e loro uso |
| WO2005000898A2 (en) | 2003-06-27 | 2005-01-06 | Biogen Idec Ma Inc. | Use of hydrophobic-interaction-chromatography or hinge-region modifications for the production of homogeneous antibody-solutions |
| KR20060041205A (ko) | 2003-07-01 | 2006-05-11 | 이뮤노메딕스, 인코오포레이티드 | 양특이성 항체들의 다가 담체들 |
| US20050054048A1 (en) | 2003-07-29 | 2005-03-10 | Luigi Grasso | Antibodies and methods for generating genetically altered antibodies with enhanced effector function |
| HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
| NZ545776A (en) | 2003-08-22 | 2009-05-31 | Biogen Idec Inc | Improved antibodies having altered effector function and methods for making the same |
| CA2534959A1 (en) | 2003-09-05 | 2005-03-31 | Genentech, Inc. | Antibodies with altered effector functions |
| ME01775B (me) | 2003-11-05 | 2011-02-28 | Glycart Biotechnology Ag | Cd20 antitijela sa povećanim afinitetom vezivanja za fc receptor i efektornom funkcijom |
| WO2005063816A2 (en) | 2003-12-19 | 2005-07-14 | Genentech, Inc. | Monovalent antibody fragments useful as therapeutics |
| WO2005117973A2 (en) * | 2004-05-05 | 2005-12-15 | Merrimack Pharmaceuticals, Inc. | Bispecific binding agents for modulating biological activity |
| SV2006002143A (es) | 2004-06-16 | 2006-01-26 | Genentech Inc | Uso de un anticuerpo para el tratamiento del cancer resistente al platino |
| JP2008512352A (ja) | 2004-07-17 | 2008-04-24 | イムクローン システムズ インコーポレイティド | 新規な四価の二重特異性抗体 |
| US7476724B2 (en) | 2004-08-05 | 2009-01-13 | Genentech, Inc. | Humanized anti-cmet antibodies |
| AU2005335714B2 (en) | 2004-11-10 | 2012-07-26 | Macrogenics, Inc. | Engineering Fc antibody regions to confer effector function |
| EP2402374A1 (en) * | 2005-02-07 | 2012-01-04 | GlycArt Biotechnology AG | Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof |
| EP1868648B1 (en) * | 2005-03-25 | 2015-04-15 | Genentech, Inc. | Methods and compositions for modulating hyperstabilized c-met |
| JP5620626B2 (ja) | 2005-03-31 | 2014-11-05 | 中外製薬株式会社 | 会合制御によるポリペプチド製造方法 |
| JP5255435B2 (ja) | 2005-04-26 | 2013-08-07 | メディミューン，エルエルシー | ヒンジドメイン操作による抗体エフェクター機能の調節 |
| EP1877441A2 (en) | 2005-04-26 | 2008-01-16 | Bioren, Inc. | Method of producing human igg antibodies with enhanced effector functions |
| TWI323734B (en) | 2005-08-19 | 2010-04-21 | Abbott Lab | Dual variable domain immunoglobulin and uses thereof |
| WO2007031875A2 (en) | 2005-08-26 | 2007-03-22 | Glycart Biotechnology Ag | Modified antigen binding molecules with altered cell signaling activity |
| US7951918B2 (en) | 2006-03-17 | 2011-05-31 | Biogen Idec Ma Inc. | Stabilized polypeptide compositions |
| TW200815470A (en) | 2006-03-30 | 2008-04-01 | Novartis Ag | Compositions and methods of use for antibodies of c-Met |
| US20070274985A1 (en) | 2006-05-26 | 2007-11-29 | Stefan Dubel | Antibody |
| WO2008140493A2 (en) | 2006-11-21 | 2008-11-20 | The Regents Of The University Of Californina | Anti-egfr family antibodies, bispecific anti-egfr family antibodies and methods of use thereof |
| US20080226635A1 (en) | 2006-12-22 | 2008-09-18 | Hans Koll | Antibodies against insulin-like growth factor I receptor and uses thereof |
| HRP20131113T1 (hr) * | 2007-02-16 | 2014-01-17 | Merrimack Pharmaceuticals, Inc. | Protutijela protiv erbb3 i njihova uporaba |
| EP2014681A1 (en) | 2007-07-12 | 2009-01-14 | Pierre Fabre Medicament | Novel antibodies inhibiting c-met dimerization, and uses thereof |
| EP2626371A1 (en) * | 2007-07-31 | 2013-08-14 | MedImmune, LLC | Multispecific epitope binding proteins and uses thereof |
| 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 |
| US8242247B2 (en) | 2007-12-21 | 2012-08-14 | Hoffmann-La Roche Inc. | Bivalent, bispecific antibodies |
| JP2011513427A (ja) | 2008-03-06 | 2011-04-28 | ジェネンテック， インコーポレイテッド | ｃ−ｍｅｔ及びＥＧＦＲアンタゴニストの併用療法 |
| US20090226455A1 (en) | 2008-03-06 | 2009-09-10 | Genentech, Inc. | Combination therapy with c-met and her antagonists |
| US20100260668A1 (en) * | 2008-04-29 | 2010-10-14 | Abbott Laboratories | Dual Variable Domain Immunoglobulins and Uses Thereof |
| CN102076355B (zh) * | 2008-04-29 | 2014-05-07 | Abbvie公司 | 双重可变结构域免疫球蛋白及其用途 |
| SG191639A1 (en) * | 2008-06-03 | 2013-07-31 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
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| EP2417160A1 (en) | 2012-02-15 |
| CN102361883A (zh) | 2012-02-22 |
| JP2012522525A (ja) | 2012-09-27 |
| CA2757426A1 (en) | 2010-10-14 |
| EP2417164A1 (en) | 2012-02-15 |
| CN102361884A (zh) | 2012-02-22 |
| TW201039848A (en) | 2010-11-16 |
| BRPI1014474A2 (pt) | 2017-06-27 |
| JP2012522523A (ja) | 2012-09-27 |
| BRPI1014449A2 (pt) | 2017-06-27 |
| US20100254989A1 (en) | 2010-10-07 |
| AU2010233995A1 (en) | 2011-09-08 |
| JP5612663B2 (ja) | 2014-10-22 |
| US20130273054A1 (en) | 2013-10-17 |
| IL214885A0 (en) | 2011-11-30 |
| IL214847A0 (en) | 2011-11-30 |
| MX2011010169A (es) | 2011-10-11 |
| SG175080A1 (en) | 2011-11-28 |
| WO2010115551A1 (en) | 2010-10-14 |
| US20100254988A1 (en) | 2010-10-07 |
| AU2010233993A1 (en) | 2011-09-08 |
| SG175078A1 (en) | 2011-11-28 |
| KR20110124368A (ko) | 2011-11-16 |
| KR20110126748A (ko) | 2011-11-23 |
| AR076194A1 (es) | 2011-05-26 |
| US20130156772A1 (en) | 2013-06-20 |
| WO2010115553A1 (en) | 2010-10-14 |
| MX2011010158A (es) | 2011-10-17 |
| AR076195A1 (es) | 2011-05-26 |
| CA2757669A1 (en) | 2010-10-14 |
| TW201039849A (en) | 2010-11-16 |
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