CN108341873B - 表皮生长因子受体3(her3)的抗体 - Google Patents
表皮生长因子受体3(her3)的抗体 Download PDFInfo
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- CN108341873B CN108341873B CN201810122569.3A CN201810122569A CN108341873B CN 108341873 B CN108341873 B CN 108341873B CN 201810122569 A CN201810122569 A CN 201810122569A CN 108341873 B CN108341873 B CN 108341873B
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| AR094403A1 (es) * | 2013-01-11 | 2015-07-29 | Hoffmann La Roche | Terapia de combinación de anticuerpos anti-her3 |
| EP2997134B1 (en) | 2013-05-14 | 2020-06-24 | Board of Regents, The University of Texas System | Human application of engineered chimeric antigen receptor (car) t-cells |
| EP3004168A4 (en) | 2013-05-24 | 2017-03-01 | Board of Regents, The University of Texas System | Chimeric antigen receptor-targeting monoclonal antibodies |
| EP3046468A4 (en) * | 2013-09-18 | 2017-06-21 | Sloan-kettering Institute For Cancer Research | Methods and compositions for imaging disorders using polyspecific agents |
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| MX369513B (es) | 2014-02-14 | 2019-11-11 | Univ Texas | Receptores de antígenos quiméricos y métodos de realización. |
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| JP6967853B2 (ja) * | 2014-02-28 | 2021-11-17 | メルス ナムローゼ フェンノートシャップ | ErbB−2およびErbB−3に結合する抗体 |
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| WO2016011343A1 (en) | 2014-07-17 | 2016-01-21 | The Trustees Of The University Of Pennsylvania | Her3 peptides and dendritic cell vaccines |
| WO2016054114A1 (en) | 2014-09-29 | 2016-04-07 | The Regents Of The University Of California | Compositions for expanding regulatory t cells (treg), and treating autoimmune and inflammatory diseases and conditions |
| EP3215534B1 (en) | 2014-11-05 | 2020-04-15 | Board of Regents, The University of Texas System | Chimeric antigen receptors (car) to selectively target protein complexes |
| ES2784900T3 (es) * | 2014-12-12 | 2020-10-01 | Massachusetts Gen Hospital | Tratamiento de metástasis cerebrales del cáncer de mama |
| JP2018527286A (ja) * | 2015-07-17 | 2018-09-20 | ブライアン ジェイ ツェルニキCZERNIECKI, Brian, J. | 免疫に基づく療法のための、免疫原性mhcクラスiiペプチドの同定 |
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| JP2018536682A (ja) | 2015-12-11 | 2018-12-13 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | Egfr及び/またはerbb3遮断に耐性のある腫瘍の成長を低減または防止するための方法 |
| CN106692969B (zh) * | 2016-12-08 | 2021-08-10 | 北海康成(北京)医药科技有限公司 | 抗erbb3抗体及其用途 |
| US11780925B2 (en) | 2017-03-31 | 2023-10-10 | Merus N.V. | ErbB-2 and ErbB3 binding bispecific antibodies for use in the treatment of cells that have an NRG1 fusion gene |
| BR112019024230A2 (pt) | 2017-05-17 | 2020-06-09 | Merus N.V. | combinação de um anticorpo bispecífico erbb-2 / erbb-3 com terapia endócrina para câncer de mama |
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| US20210246223A1 (en) * | 2018-06-22 | 2021-08-12 | Crd Pharmaceuticals Inc | ANTI-HER3 Antibody and uses thereof |
| CN112955137B (zh) | 2018-09-10 | 2025-05-13 | 米拉蒂治疗股份有限公司 | 组合疗法 |
| US20220313840A1 (en) * | 2019-06-04 | 2022-10-06 | Academia Sinica | Ligands targed to epidermal growth factor receptors and compositions for use in treating tumors |
| CN118742573A (zh) * | 2022-03-03 | 2024-10-01 | 四川科伦博泰生物医药股份有限公司 | Her3结合蛋白及其用途 |
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|---|---|---|---|---|
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| DE3378250D1 (en) | 1982-04-22 | 1988-11-24 | Ici Plc | Continuous release formulations |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| JPS60500673A (ja) | 1983-03-08 | 1985-05-09 | コモンウエルス セラム ラボラトリ−ズ コミツシヨン | 抗原活性を有するアミノ酸配列 |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| DE3572982D1 (en) | 1984-03-06 | 1989-10-19 | Takeda Chemical Industries Ltd | Chemically modified lymphokine and production thereof |
| US5128326A (en) | 1984-12-06 | 1992-07-07 | Biomatrix, Inc. | Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same |
| US5374548A (en) | 1986-05-02 | 1994-12-20 | Genentech, Inc. | Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor |
| MX9203291A (es) | 1985-06-26 | 1992-08-01 | Liposome Co Inc | Metodo para acoplamiento de liposomas. |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US4881175A (en) | 1986-09-02 | 1989-11-14 | Genex Corporation | Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides |
| US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
| EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| US5013653A (en) | 1987-03-20 | 1991-05-07 | Creative Biomolecules, Inc. | Product and process for introduction of a hinge region into a fusion protein to facilitate cleavage |
| US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
| ATE120761T1 (de) | 1987-05-21 | 1995-04-15 | Creative Biomolecules Inc | Multifunktionelle proteine mit vorbestimmter zielsetzung. |
| US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| US5132405A (en) | 1987-05-21 | 1992-07-21 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| US4880078A (en) | 1987-06-29 | 1989-11-14 | Honda Giken Kogyo Kabushiki Kaisha | Exhaust muffler |
| US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
| US5336603A (en) | 1987-10-02 | 1994-08-09 | Genentech, Inc. | CD4 adheson variants |
| US5476996A (en) | 1988-06-14 | 1995-12-19 | Lidak Pharmaceuticals | Human immune system in non-human animal |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| KR900005995A (ko) | 1988-10-31 | 1990-05-07 | 우메모또 요시마사 | 변형 인터류킨-2 및 그의 제조방법 |
| WO1990005144A1 (en) | 1988-11-11 | 1990-05-17 | Medical Research Council | Single domain ligands, receptors comprising said ligands, methods for their production, and use of said ligands and receptors |
| CA2006596C (en) | 1988-12-22 | 2000-09-05 | Rika Ishikawa | Chemically-modified g-csf |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5108921A (en) | 1989-04-03 | 1992-04-28 | Purdue Research Foundation | Method for enhanced transmembrane transport of exogenous molecules |
| ATE92107T1 (de) | 1989-04-29 | 1993-08-15 | Delta Biotechnology Ltd | N-terminale fragmente von menschliches serumalbumin enthaltenden fusionsproteinen. |
| US6291158B1 (en) | 1989-05-16 | 2001-09-18 | Scripps Research Institute | Method for tapping the immunological repertoire |
| US5112946A (en) | 1989-07-06 | 1992-05-12 | Repligen Corporation | Modified pf4 compositions and methods of use |
| FR2650598B1 (fr) | 1989-08-03 | 1994-06-03 | Rhone Poulenc Sante | Derives de l'albumine a fonction therapeutique |
| WO1991005548A1 (en) | 1989-10-10 | 1991-05-02 | Pitman-Moore, Inc. | Sustained release composition for macromolecular proteins |
| WO1991006570A1 (en) | 1989-10-25 | 1991-05-16 | The University Of Melbourne | HYBRID Fc RECEPTOR MOLECULES |
| CA2071867A1 (en) | 1989-11-06 | 1991-05-07 | Edith Mathiowitz | Method for producing protein microspheres |
| US5183884A (en) | 1989-12-01 | 1993-02-02 | United States Of America | Dna segment encoding a gene for a receptor related to the epidermal growth factor receptor |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| ATE356869T1 (de) | 1990-01-12 | 2007-04-15 | Amgen Fremont Inc | Bildung von xenogenen antikörpern |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| US5349053A (en) | 1990-06-01 | 1994-09-20 | Protein Design Labs, Inc. | Chimeric ligand/immunoglobulin molecules and their uses |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| US6172197B1 (en) | 1991-07-10 | 2001-01-09 | Medical Research Council | Methods for producing members of specific binding pairs |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| WO1993012227A1 (en) | 1991-12-17 | 1993-06-24 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| CA2089661C (en) | 1990-08-29 | 2007-04-03 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
| KR100246529B1 (ko) | 1990-12-14 | 2000-04-01 | 스티븐 에이. 서윈. 엠.디. | 수용체 관련된 신호 변환 경로를 위한 키메라 사슬 |
| DE69232706T2 (de) | 1991-05-01 | 2002-11-28 | Henry M. Jackson Foundation For The Advancement Of Military Medicine, Rockville | Verfahren zur behandlung infektiöser respiratorischer erkrankungen |
| EP2224006A1 (en) | 1991-12-02 | 2010-09-01 | MedImmune Limited | Production of anti-self antibodies from antibody segment repertoires and displayed on phage |
| ES2227512T3 (es) | 1991-12-02 | 2005-04-01 | Medical Research Council | Produccion de anticuerpos contra auto-antigenos a partir de repertorios de segmentos de anticuerpos fijados en un fago. |
| US5622929A (en) | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
| FR2686901A1 (fr) | 1992-01-31 | 1993-08-06 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides antithrombotiques, leur preparation et compositions pharmaceutiques les contenant. |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
| US5912015A (en) | 1992-03-12 | 1999-06-15 | Alkermes Controlled Therapeutics, Inc. | Modulated release from biocompatible polymers |
| US5447851B1 (en) | 1992-04-02 | 1999-07-06 | Univ Texas System Board Of | Dna encoding a chimeric polypeptide comprising the extracellular domain of tnf receptor fused to igg vectors and host cells |
| AU4116793A (en) | 1992-04-24 | 1993-11-29 | Board Of Regents, The University Of Texas System | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
| ATE452975T1 (de) | 1992-08-21 | 2010-01-15 | Univ Bruxelles | Immunoglobuline ohne leichte ketten |
| US6765087B1 (en) | 1992-08-21 | 2004-07-20 | Vrije Universiteit Brussel | Immunoglobulins devoid of light chains |
| US5958708A (en) | 1992-09-25 | 1999-09-28 | Novartis Corporation | Reshaped monoclonal antibodies against an immunoglobulin isotype |
| CA2103323A1 (en) | 1992-11-24 | 1994-05-25 | Gregory D. Plowman | Her4 human receptor tyrosine kinase |
| US5934272A (en) | 1993-01-29 | 1999-08-10 | Aradigm Corporation | Device and method of creating aerosolized mist of respiratory drug |
| AU6819494A (en) | 1993-04-26 | 1994-11-21 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| ATE204325T1 (de) | 1993-04-29 | 2001-09-15 | Unilever Nv | Herstellung von antikörpern oder funktionstüchtig gemachten teilen davon, abgeleitet von schweren ketten von immunglobulinen von camelidae |
| EP0714409A1 (en) | 1993-06-16 | 1996-06-05 | Celltech Therapeutics Limited | Antibodies |
| SE9400088D0 (sv) | 1994-01-14 | 1994-01-14 | Kabi Pharmacia Ab | Bacterial receptor structures |
| US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
| US5834252A (en) | 1995-04-18 | 1998-11-10 | Glaxo Group Limited | End-complementary polymerase reaction |
| US5837458A (en) | 1994-02-17 | 1998-11-17 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
| JPH10503371A (ja) | 1994-07-29 | 1998-03-31 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 新規化合物 |
| US6132764A (en) | 1994-08-05 | 2000-10-17 | Targesome, Inc. | Targeted polymerized liposome diagnostic and treatment agents |
| AU4755696A (en) | 1995-01-05 | 1996-07-24 | Board Of Regents Acting For And On Behalf Of The University Of Michigan, The | Surface-modified nanoparticles and method of making and using same |
| US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
| US6019968A (en) | 1995-04-14 | 2000-02-01 | Inhale Therapeutic Systems, Inc. | Dispersible antibody compositions and methods for their preparation and use |
| US6121022A (en) | 1995-04-14 | 2000-09-19 | Genentech, Inc. | Altered polypeptides with increased half-life |
| US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
| JP2000507912A (ja) | 1995-08-31 | 2000-06-27 | アルカームズ コントロールド セラピューティックス,インコーポレイテッド | 作用剤の徐放性組成物 |
| JP2000506165A (ja) | 1996-03-04 | 2000-05-23 | ザ ペン ステイト リサーチ ファウンデーション | 細胞インターナリゼーションを増強するための物質および方法 |
| AU728657B2 (en) | 1996-03-18 | 2001-01-18 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| EP1728802A3 (en) * | 1996-03-27 | 2006-12-13 | Genentech, Inc. | ErbB3 antibodies |
| US5968511A (en) * | 1996-03-27 | 1999-10-19 | Genentech, Inc. | ErbB3 antibodies |
| US5985309A (en) | 1996-05-24 | 1999-11-16 | Massachusetts Institute Of Technology | Preparation of particles for inhalation |
| US5874064A (en) | 1996-05-24 | 1999-02-23 | Massachusetts Institute Of Technology | Aerodynamically light particles for pulmonary drug delivery |
| US5855913A (en) | 1997-01-16 | 1999-01-05 | Massachusetts Instite Of Technology | Particles incorporating surfactants for pulmonary drug delivery |
| US6056973A (en) | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
| WO1998023289A1 (en) | 1996-11-27 | 1998-06-04 | The General Hospital Corporation | MODULATION OF IgG BINDING TO FcRn |
| ES2236832T3 (es) | 1997-01-16 | 2005-07-16 | Massachusetts Institute Of Technology | Preparacion de particulas para inhalacion. |
| US6136558A (en) | 1997-02-10 | 2000-10-24 | Genentech, Inc. | Heregulin variants |
| US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| EP0983303B1 (en) | 1997-05-21 | 2006-03-08 | Biovation Limited | Method for the production of non-immunogenic proteins |
| AU736707B2 (en) | 1997-06-11 | 2001-08-02 | Anaphore, Inc. | Trimerising module |
| EP1958962A3 (en) | 1997-06-12 | 2013-05-01 | Novartis International Pharmaceutical Ltd. | Artificial antibody polypeptides |
| US5989463A (en) | 1997-09-24 | 1999-11-23 | Alkermes Controlled Therapeutics, Inc. | Methods for fabricating polymer-based controlled release devices |
| DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| WO1999019488A1 (en) | 1997-10-15 | 1999-04-22 | Children's Medical Center Corporation | Novel human egf receptors and use thereof |
| GB9722131D0 (en) | 1997-10-20 | 1997-12-17 | Medical Res Council | Method |
| SE512663C2 (sv) | 1997-10-23 | 2000-04-17 | Biogram Ab | Inkapslingsförfarande för aktiv substans i en bionedbrytbar polymer |
| US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
| PT2180007E (pt) | 1998-04-20 | 2013-11-25 | Roche Glycart Ag | Engenharia de glicosilação de anticorpos para melhorar a citotoxicidade celular dependente de anticorpos |
| JP2002518432A (ja) | 1998-06-24 | 2002-06-25 | アドバンスト インハレーション リサーチ,インコーポレイテッド | 吸入器から放出される大多孔性粒子 |
| US6818418B1 (en) | 1998-12-10 | 2004-11-16 | Compound Therapeutics, Inc. | Protein scaffolds for antibody mimics and other binding proteins |
| KR101155191B1 (ko) | 1999-01-15 | 2012-06-13 | 제넨테크, 인크. | 효과기 기능이 변화된 폴리펩티드 변이체 |
| ES2568899T3 (es) | 1999-04-09 | 2016-05-05 | Kyowa Hakko Kirin Co., Ltd. | Procedimiento para controlar la actividad de una molécula inmunofuncional |
| DE19932688B4 (de) | 1999-07-13 | 2009-10-08 | Scil Proteins Gmbh | Design von Beta-Faltblatt-Proteinen des gamma-II-kristallins antikörperähnlichen |
| ES2327382T3 (es) | 1999-07-20 | 2009-10-29 | Morphosys Ag | Metodos para presentar (poli)peptidos/proteinas en particulas de bacteriofagos a traves de enlaces disulfuro. |
| WO2001014424A2 (en) | 1999-08-24 | 2001-03-01 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
| AU2001266557A1 (en) | 2000-04-12 | 2001-10-23 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| EP1328626B1 (en) | 2000-05-26 | 2013-04-17 | National Research Council Of Canada | Single-domain brain-targeting antibody fragments derived from llama antibodies |
| ES2405944T3 (es) | 2000-11-30 | 2013-06-04 | Medarex, Inc. | Ácidos nucleicos que codifican las secuencias de inmunoglobulina humana reorganizadas a partir de ratones transcromoscómicos transgénicos zadas |
| EP2762140B1 (en) * | 2001-02-19 | 2017-03-22 | Novartis AG | Treatment of solid brain tumours with a rapamycin derivative |
| US20050048512A1 (en) | 2001-04-26 | 2005-03-03 | Avidia Research Institute | Combinatorial libraries of monomer domains |
| US20040175756A1 (en) | 2001-04-26 | 2004-09-09 | Avidia Research Institute | Methods for using combinatorial libraries of monomer domains |
| US20050053973A1 (en) | 2001-04-26 | 2005-03-10 | Avidia Research Institute | Novel proteins with targeted binding |
| WO2002092780A2 (en) | 2001-05-17 | 2002-11-21 | Diversa Corporation | Novel antigen binding molecules for therapeutic, diagnostic, prophylactic, enzymatic, industrial, and agricultural applications, and methods for generating and screening thereof |
| DE60237282D1 (de) | 2001-06-28 | 2010-09-23 | Domantis Ltd | Doppelspezifischer ligand und dessen verwendung |
| ITMI20011483A1 (it) | 2001-07-11 | 2003-01-11 | Res & Innovation Soc Coop A R | Uso di composti come antagonisti funzionali ai recettori centrali deicannabinoidi |
| EP1283053A1 (en) | 2001-08-09 | 2003-02-12 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibitors of HER3 activity |
| ES2326964T3 (es) | 2001-10-25 | 2009-10-22 | Genentech, Inc. | Composiciones de glicoproteina. |
| US7771951B2 (en) | 2001-12-03 | 2010-08-10 | Amgen Fremont Inc. | Antibody categorization based on binding characteristics |
| WO2003064383A2 (en) | 2002-02-01 | 2003-08-07 | Ariad Gene Therapeutics, Inc. | Phosphorus-containing compounds & uses thereof |
| US20030157579A1 (en) | 2002-02-14 | 2003-08-21 | Kalobios, Inc. | Molecular sensors activated by disinhibition |
| US7335478B2 (en) | 2002-04-18 | 2008-02-26 | Kalobios Pharmaceuticals, Inc. | Reactivation-based molecular interaction sensors |
| AU2003217912A1 (en) | 2002-03-01 | 2003-09-16 | Xencor | Antibody optimization |
| EP2135879A3 (en) | 2002-06-28 | 2010-06-23 | Domantis Limited | Ligand |
| NZ540196A (en) | 2002-11-08 | 2008-09-26 | Ablynx Nv | Camelidae antibodies against imminoglobulin E and use thereof for the treatment of allergic disorders |
| CA2511910A1 (en) | 2002-12-27 | 2004-07-15 | Domantis Limited | Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand |
| WO2004072266A2 (en) | 2003-02-13 | 2004-08-26 | Kalobios Inc. | Antibody affinity engineering by serial epitope-guided complementarity replacement |
| US20090005257A1 (en) | 2003-05-14 | 2009-01-01 | Jespers Laurent S | Process for Recovering Polypeptides that Unfold Reversibly from a Polypeptide Repertoire |
| DE10324447A1 (de) | 2003-05-28 | 2004-12-30 | Scil Proteins Gmbh | Generierung künstlicher Bindungsproteine auf der Grundlage von Ubiquitin |
| DK1639011T3 (da) | 2003-06-30 | 2009-02-16 | Domantis Ltd | Pegylerede enkelt-domæne antistoffer (dAb) |
| KR101019763B1 (ko) | 2003-07-25 | 2011-03-04 | 파나소닉 주식회사 | 전송 품질 평가를 가진 다중 반송파 송/수신용 장치 및방법 |
| US7399865B2 (en) | 2003-09-15 | 2008-07-15 | Wyeth | Protein tyrosine kinase enzyme inhibitors |
| JP4782700B2 (ja) | 2004-01-20 | 2011-09-28 | カロバイオス ファーマシューティカルズ インコーポレイティッド | 最低限必須な結合決定基を用いた抗体特異性の移入 |
| US20060008844A1 (en) | 2004-06-17 | 2006-01-12 | Avidia Research Institute | c-Met kinase binding proteins |
| EP1844073A1 (en) | 2005-01-31 | 2007-10-17 | Ablynx N.V. | Method for generating variable domain sequences of heavy chain antibodies |
| GB0503546D0 (en) * | 2005-02-21 | 2005-03-30 | Hellenic Pasteur Inst | Antibody |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| AU2006287765B2 (en) * | 2005-09-07 | 2011-12-08 | Merck Serono Sa | P13K inhibitors for the treatment of endometriosis |
| CA2621502A1 (en) | 2005-09-07 | 2007-03-15 | Medimmune, Inc. | Toxin conjugated eph receptor antibodies |
| KR101866623B1 (ko) | 2005-11-28 | 2018-07-04 | 젠맵 에이/에스 | 재조합 1가 항체 및 그의 제조 방법 |
| 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 |
| SG172692A1 (en) | 2006-06-12 | 2011-07-28 | Symphogen As | Pan-cell surface receptor- specific therapeutics |
| US7825127B2 (en) | 2006-12-28 | 2010-11-02 | Takeda Pharmaceutical Company, Limited | Method for treating cancer |
| BRPI0808055A2 (pt) | 2007-02-16 | 2013-07-30 | Merrimack Pharmaceuticals Inc | anticorpo monoclonal isolado ou porÇço do mesmo que se liga ao antÍgeno, composiÇço, Ácido nucleico isolado, vetor de expressço, cÉlula hospedeira, hibridoma, kit, uso de um anticorpo monoclonal isolado ou porÇço do mesmo que se liga ao antÍgeno, mÉtodo para diagnosticar um cÂncer associado com erbb3 em um paciente, e, anticorpo |
| US20080245375A1 (en) * | 2007-04-05 | 2008-10-09 | Medtronic Vascular, Inc. | Benign Prostatic Hyperplasia Treatments |
| EP2205242B1 (en) | 2007-09-12 | 2015-04-15 | Genentech, Inc. | Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents, and methods of use |
| JP5348725B2 (ja) | 2007-10-25 | 2013-11-20 | ジェネンテック, インコーポレイテッド | チエノピリミジン化合物の製造方法 |
| UY31800A (es) | 2008-05-05 | 2009-11-10 | Smithkline Beckman Corp | Metodo de tratamiento de cancer usando un inhibidor de cmet y axl y un inhibidor de erbb |
| NZ594665A (en) * | 2009-03-20 | 2013-08-30 | Genentech Inc | Bispecific anti-her antibodies |
| CA2759792A1 (en) * | 2009-04-29 | 2010-11-04 | Trellis Bioscience, Inc. | Improved antibodies immunoreactive with heregulin-coupled her3 |
| SG178509A1 (en) | 2009-08-21 | 2012-04-27 | Merrimack Pharmaceuticals Inc | Antibodies against the ectodomain of erbb3 and uses thereof |
| LT2719708T (lt) * | 2009-11-13 | 2018-02-12 | Daiichi Sankyo Europe Gmbh | Medžiaga ir būdai, skirti su her-3 susijusių ligų gydymui arba prevencijai |
| MX2012007340A (es) * | 2009-12-22 | 2012-08-01 | Roche Glycart Ag | Anticuerpos anti/her3 y usos de los mismos. |
| ES2519348T3 (es) | 2010-02-18 | 2014-11-06 | Genentech, Inc. | Antagonistas de neurregulina y uso de los mismos en el tratamiento del cáncer |
| PL2544680T3 (pl) | 2010-03-11 | 2015-08-31 | Merrimack Pharmaceuticals Inc | Zastosowanie inhibitorów ERBB1 w leczeniu potrójnie ujemnego raka gruczołu sutkowego |
| CN105968206B (zh) * | 2010-04-09 | 2020-01-17 | Aveo制药公司 | 抗erbb3抗体 |
| US20130108547A1 (en) | 2010-05-13 | 2013-05-02 | Fox Chase Cancer Center | Recombinantly Produced Antibodies Targeting ErbB Signaling Molecules and Methods of Use Thereof for the Diagnosis and Treatment of Disease |
| EP2571901B1 (en) * | 2010-05-20 | 2019-01-02 | Ablynx N.V. | Biological materials related to her3 |
| UY33492A (es) | 2010-07-09 | 2012-01-31 | Abbott Lab | Inmunoglobulinas con dominio variable dual y usos de las mismas |
| WO2012019024A2 (en) | 2010-08-04 | 2012-02-09 | Immunogen, Inc. | Her3-binding molecules and immunoconjugates thereof |
| US20120156130A1 (en) * | 2010-08-06 | 2012-06-21 | Thore Hettmann | Use of her3 binding agents in prostate treatment |
| MY162825A (en) * | 2010-08-20 | 2017-07-31 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) |
| TW201302793A (zh) | 2010-09-03 | 2013-01-16 | Glaxo Group Ltd | 新穎之抗原結合蛋白 |
| US9155802B2 (en) | 2010-11-01 | 2015-10-13 | Symphogen A/S | Pan-HER antibody composition |
| ITRM20100577A1 (it) | 2010-11-02 | 2012-05-03 | Takis Srl | Immunoterapia contro il recettore erbb-3 |
| AR083705A1 (es) | 2010-11-04 | 2013-03-13 | Abbott Lab | Inmunoglobulinas con dominio variable dual y usos de las mismas |
| JPWO2012176779A1 (ja) * | 2011-06-20 | 2015-02-23 | 協和発酵キリン株式会社 | 抗erbB3抗体 |
| US10300140B2 (en) * | 2011-07-28 | 2019-05-28 | I2 Pharmaceuticals, Inc. | Sur-binding proteins against ERBB3 |
| AU2012294326A1 (en) * | 2011-08-10 | 2013-03-21 | Merrimack Pharmaceuticals, Inc. | Treatment of advanced solid tumors using combination of anti-ErbB3 immunotherapy and selected chemotherapy |
| WO2013071058A1 (en) * | 2011-11-09 | 2013-05-16 | The Uab Research Foundation | Her3 antibodies and uses thereof |
| EP3608340A1 (en) * | 2011-11-23 | 2020-02-12 | Medlmmune, LLC | Binding molecules specific for her3 and uses thereof |
| US20130273029A1 (en) * | 2011-12-05 | 2013-10-17 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) directed to domain ii of her3 |
| WO2013084147A2 (en) * | 2011-12-05 | 2013-06-13 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) |
| WO2015157634A1 (en) * | 2014-04-11 | 2015-10-15 | Kolltan Pharmaceuticals, Inc. | Anti-erbb antibodies and methods of use thereof |
-
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