JP6141639B2 - 抗体 - Google Patents
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- JP6141639B2 JP6141639B2 JP2012514528A JP2012514528A JP6141639B2 JP 6141639 B2 JP6141639 B2 JP 6141639B2 JP 2012514528 A JP2012514528 A JP 2012514528A JP 2012514528 A JP2012514528 A JP 2012514528A JP 6141639 B2 JP6141639 B2 JP 6141639B2
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| EP2436397B1 (en) | 2009-05-29 | 2017-05-10 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical composition containing antagonist of egf family ligand as component |
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| US10266599B2 (en) | 2010-12-07 | 2019-04-23 | Cancer Research Technology Limited | Antibodies which bind to the human CC chemokine receptor 4 and uses thereof |
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| EP2670426B1 (en) | 2011-01-31 | 2017-05-10 | The General Hospital Corporation | Multimodal trail molecules and uses in cellular therapies |
| CN103857421B (zh) * | 2011-06-13 | 2017-09-22 | Tla指标免疫疗法公司 | 治疗癌症的方法和在其中使用的结合试剂 |
| US9726666B2 (en) | 2011-06-13 | 2017-08-08 | Tla Targeted Immunotherapies Ab | Diagnosing and treating inflammatory diseases |
| ES2758884T3 (es) | 2011-06-24 | 2020-05-06 | Stephen D Gillies | Proteínas de fusión de inmunoglobulina a través de cadena ligera y métodos de uso de ellas |
| TWI593705B (zh) * | 2011-12-28 | 2017-08-01 | Chugai Pharmaceutical Co Ltd | Humanized anti-epiregulin antibody and cancer therapeutic agent containing the antibody as an active ingredient |
| HK1207655A1 (en) * | 2012-05-04 | 2016-02-05 | Dana-Farber Cancer Institute, Inc. | Affinity matured anti-ccr4 humanized monoclonal antibodies and methods of use |
| JP6310845B2 (ja) * | 2012-07-06 | 2018-04-11 | 学校法人 聖マリアンナ医科大学 | Ｈｔｌｖ−１関連脊髄症患者の治療方法および治療剤 |
| US9862932B2 (en) | 2012-07-24 | 2018-01-09 | The General Hospital Corporation | Oncolytic virus therapy for resistant tumors |
| US9605074B2 (en) * | 2012-08-30 | 2017-03-28 | The General Hospital Corporation | Multifunctional nanobodies for treating cancer |
| GB2512857A (en) | 2013-04-09 | 2014-10-15 | Cancer Res Technology | Cancer biomarker |
| TW201542591A (zh) * | 2013-06-24 | 2015-11-16 | Chugai Pharmaceutical Co Ltd | 含有以人源化抗Ｅｐｉｒｅｇｕｌｉｎ抗體爲有效成分的腺癌以外的非小細胞肺癌之治療劑 |
| US10407508B2 (en) | 2013-07-08 | 2019-09-10 | Nanjing Legend Biotech., Ltd. | Compositions and methods for increasing protein half-life in a serum |
| RU2016146993A (ru) * | 2014-05-21 | 2018-06-21 | Пфайзер Инк. | Комбинация антитела к CCR4 и агониста 4-1BB для лечения рака |
| US9616114B1 (en) | 2014-09-18 | 2017-04-11 | David Gordon Bermudes | Modified bacteria having improved pharmacokinetics and tumor colonization enhancing antitumor activity |
| WO2016057488A1 (en) * | 2014-10-06 | 2016-04-14 | Dana-Farber Cancer Institute, Inc. | Humanized cc chemokine receptor 4 (ccr4) antibodies and methods of use thereof |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| GB201521447D0 (en) * | 2015-12-04 | 2016-01-20 | Ucb Biopharma Sprl | De novo antibody design |
| CA3026474A1 (en) | 2016-06-20 | 2017-12-28 | Kymab Limited | Anti-pd-l1 and il-2 cytokines |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
| CN116420679B (zh) * | 2018-03-26 | 2025-10-03 | 瑞泽恩制药公司 | 用于测试治疗剂的人源化啮齿动物 |
| CN110759996B (zh) * | 2018-07-27 | 2022-09-06 | 深圳康体生命科技有限公司 | 一种gfp抗体 |
| CN111135310B (zh) * | 2019-12-24 | 2021-05-07 | 江苏省人民医院（南京医科大学第一附属医院） | 一种定制化t细胞表位疫苗的双靶向纳米药、其制备方法及应用 |
| CN114891117B (zh) * | 2022-04-26 | 2023-09-05 | 深圳市体内生物医药科技有限公司 | 一种靶向ccr8的嵌合抗原受体t细胞及其制备方法和应用 |
| WO2024092031A1 (en) * | 2022-10-25 | 2024-05-02 | Seismic Therapeutic, Inc. | VARIANT IgG FC POLYPEPTIDES AND USES THEREOF |
| CN116693679B (zh) * | 2023-01-18 | 2025-11-11 | 中国人民解放军陆军军医大学 | 抗金黄色葡萄球菌α-溶血素的全人源单克隆抗体Hm0699及其应用 |
| CN117187180B (zh) * | 2023-11-03 | 2024-01-26 | 四川大学 | 一种Th17细胞及其培养方法和应用及其诱导液 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2437213A1 (fr) | 1978-09-28 | 1980-04-25 | Cm Ind | Produits cytotoxiques formes par liaison covalente de la chaine a de la ricine avec un anticorps et leur procede de preparation |
| US4736866B1 (en) | 1984-06-22 | 1988-04-12 | Transgenic non-human mammals | |
| WO1990010457A1 (en) | 1989-03-14 | 1990-09-20 | New York University | Method of treating hiv infections using immunotoxins |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| EP1136556B1 (en) | 1991-11-25 | 2005-06-08 | Enzon, Inc. | Method of producing multivalent antigen-binding proteins |
| US5965132A (en) | 1992-03-05 | 1999-10-12 | Board Of Regents, The University Of Texas System | Methods and compositions for targeting the vasculature of solid tumors |
| WO1993017715A1 (en) | 1992-03-05 | 1993-09-16 | Board Of Regents, The University Of Texas System | Diagnostic and/or therapeutic agents, targeted to neovascular endothelial cells |
| US5776427A (en) | 1992-03-05 | 1998-07-07 | Board Of Regents, The University Of Texas System | Methods for targeting the vasculature of solid tumors |
| US6488930B1 (en) * | 1999-01-15 | 2002-12-03 | Millennium Pharmaceuticals, Inc. | Anti-CCR4 antibodies and methods of use therefor |
| AU2004201168A1 (en) | 1999-01-15 | 2004-04-22 | Millennium Pharmaceuticals, Inc. | Anti-CCR4 antibodies and methods of use therefor |
| US6703020B1 (en) | 1999-04-28 | 2004-03-09 | Board Of Regents, The University Of Texas System | Antibody conjugate methods for selectively inhibiting VEGF |
| 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 |
| EP1050307A1 (en) | 1999-05-06 | 2000-11-08 | Applied Research Systems ARS Holding N.V. | CCR4 antagonists in sepsis |
| JP3926153B2 (ja) | 2000-03-03 | 2007-06-06 | 協和醗酵工業株式会社 | 遺伝子組換え抗体およびその抗体断片 |
| US6946292B2 (en) * | 2000-10-06 | 2005-09-20 | Kyowa Hakko Kogyo Co., Ltd. | Cells producing antibody compositions with increased antibody dependent cytotoxic activity |
| US20020182624A1 (en) | 2001-02-28 | 2002-12-05 | Eos Biotechnology, Inc. | Chemokine receptors and disease |
| WO2003018635A1 (fr) * | 2001-08-31 | 2003-03-06 | Kyowa Hakko Kogyo Co., Ltd. | Anticorps greffes cdr humains et fragments de ces anticorps |
| JPWO2005035582A1 (ja) | 2003-10-08 | 2007-11-22 | 協和醗酵工業株式会社 | Ｃｃｒ４に特異的に結合する抗体組成物 |
| US8491902B2 (en) * | 2003-12-04 | 2013-07-23 | Kyowa Hakko Kirin Co., Ltd. | Medicament comprising recombinant antibody against chemokine receptor CCR4 |
| GB0718167D0 (en) * | 2007-09-18 | 2007-10-31 | Cancer Rec Tech Ltd | Cancer marker and therapeutic target |
| US8962806B2 (en) | 2007-12-28 | 2015-02-24 | Dana-Farber Cancer Institute, Inc. | Humanized monoclonal antibodies and methods of use |
| GB0909906D0 (en) | 2009-06-09 | 2009-07-22 | Affitech As | Antibodies |
| US8802442B2 (en) | 2011-11-30 | 2014-08-12 | Eric B. Wheeldon | Apparatus and method for the remote sensing of blood in human feces and urine |
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| CN102482355B (zh) | 2014-12-17 |
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| US20130236535A1 (en) | 2013-09-12 |
| US20130196379A1 (en) | 2013-08-01 |
| US20160208003A1 (en) | 2016-07-21 |
| CN104436191A (zh) | 2015-03-25 |
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| EP2440579A2 (en) | 2012-04-18 |
| WO2010142952A2 (en) | 2010-12-16 |
| GB0909906D0 (en) | 2009-07-22 |
| JP2012529280A (ja) | 2012-11-22 |
| CN102482355A (zh) | 2012-05-30 |
| US9145461B2 (en) | 2015-09-29 |
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