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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| US30276810P | 2010-02-09 | 2010-02-09 | |
| US61/302,768 | 2010-02-09 | ||
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| US20120141501A1 (en) | 2009-05-29 | 2012-06-07 | Forerunner Pharma Research Co. Ltd | 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 |
| EP2670426B1 (en) | 2011-01-31 | 2017-05-10 | The General Hospital Corporation | Multimodal trail molecules and uses in cellular therapies |
| US9726666B2 (en) | 2011-06-13 | 2017-08-08 | Tla Targeted Immunotherapies Ab | Diagnosing and treating inflammatory diseases |
| DK2717941T3 (da) * | 2011-06-13 | 2020-07-13 | Tla Targeted Immunotherapies Ab | Behandling af cancer |
| US11492383B2 (en) | 2011-06-24 | 2022-11-08 | Stephen D. Gillies | Light chain immunoglobulin fusion proteins and methods of use thereof |
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| EP3511343A1 (en) * | 2012-05-04 | 2019-07-17 | Dana Farber Cancer Institute, Inc. | Affinity matured anti-ccr4 humanized monoclonal antibodies and methods of use |
| EP2870973B1 (en) * | 2012-07-06 | 2022-08-31 | St. Marianna University School of Medicine | Remedy for htlv-1-associated myelopathy patients |
| EP2877572B1 (en) | 2012-07-24 | 2018-11-28 | The General Hospital Corporation | Oncolytic virus therapy for resistant tumors |
| EP2890720B1 (en) * | 2012-08-30 | 2019-07-17 | The General Hospital Corporation | Compositions and methods for treating cancer |
| GB2512857A (en) | 2013-04-09 | 2014-10-15 | Cancer Res Technology | Cancer biomarker |
| EP3015115A4 (en) * | 2013-06-24 | 2017-02-22 | Chugai Seiyaku Kabushiki Kaisha | Therapeutic agent comprising humanized anti-epiregulin antibody as active ingredient for non-small-cell lung carcinoma excluding adenocarcinoma |
| CN105555310B (zh) | 2013-07-08 | 2019-07-23 | 南京传奇生物科技有限公司 | 一种提高蛋白血清半衰期的组合物和方法 |
| US10023649B2 (en) * | 2014-05-21 | 2018-07-17 | Pfizer Inc. | Method of treating cancer with a combination of an anti-CCR4 antibody and a 4-1BB agonist |
| US9616114B1 (en) | 2014-09-18 | 2017-04-11 | David Gordon Bermudes | Modified bacteria having improved pharmacokinetics and tumor colonization enhancing antitumor activity |
| EP3204418B1 (en) * | 2014-10-06 | 2020-03-25 | 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 |
| TW201803905A (zh) | 2016-06-20 | 2018-02-01 | 克馬伯有限公司 | 用於免疫腫瘤學之多重專一性抗體 |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| JP7328243B2 (ja) * | 2018-03-26 | 2023-08-16 | 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 | 治療薬を試験するためのヒト化げっ歯類 |
| 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 |
| AU2023367781A1 (en) | 2022-10-25 | 2025-06-05 | 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 |
| EP0617706B1 (en) | 1991-11-25 | 2001-10-17 | Enzon, Inc. | Multivalent antigen-binding proteins |
| US5776427A (en) | 1992-03-05 | 1998-07-07 | Board Of Regents, The University Of Texas System | Methods for targeting the vasculature of solid tumors |
| ES2193143T3 (es) | 1992-03-05 | 2003-11-01 | Univ Texas | Uso de inmunoconjugados para la diagnosis y/o terapia de tumores vascularizaos. |
| 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 |
| 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 |
| US6342219B1 (en) | 1999-04-28 | 2002-01-29 | Board Of Regents, The University Of Texas System | Antibody compositions for selectively inhibiting VEGF |
| EP1050307A1 (en) | 1999-05-06 | 2000-11-08 | Applied Research Systems ARS Holding N.V. | CCR4 antagonists in sepsis |
| AU3607301A (en) | 2000-03-03 | 2001-09-12 | Kyowa Hakko Kogyo Kk | Gene recombinant antibody and its fragment |
| US6946292B2 (en) * | 2000-10-06 | 2005-09-20 | Kyowa Hakko Kogyo Co., Ltd. | Cells producing antibody compositions with increased antibody dependent cytotoxic activity |
| JP2004535157A (ja) | 2001-02-28 | 2004-11-25 | プロテイン デザイン ラブス， インコーポレイテッド | ケモカイン受容体と疾患 |
| BRPI0212266B8 (pt) * | 2001-08-31 | 2021-05-25 | Kyowa Hakko Kirin Co Ltd | anticorpos humanizados anti-ccr4, método de produção dos mesmos, medicamento, e agentes terapêuticos e de diagnóstico |
| EP1688436A4 (en) | 2003-10-08 | 2009-12-02 | Kyowa Hakko Kirin Co Ltd | ANTIBODY COMPOSITION THAT IS ABLE TO SPECIFY CCR4 SPECIFICALLY |
| ATE486611T1 (de) * | 2003-12-04 | 2010-11-15 | Kyowa Hakko Kirin Co Ltd | Einen genetisch modifizierten antikörper gegen chemokin-rezeptor-ccr4 enthaltendes medikament |
| GB0718167D0 (en) | 2007-09-18 | 2007-10-31 | Cancer Rec Tech Ltd | Cancer marker and therapeutic target |
| WO2009086514A1 (en) | 2007-12-28 | 2009-07-09 | 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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| CN102482355A (zh) | 2012-05-30 |
| US20130236535A1 (en) | 2013-09-12 |
| US20100310464A1 (en) | 2010-12-09 |
| CN102482355B (zh) | 2014-12-17 |
| EA201171464A1 (ru) | 2012-07-30 |
| US20160208003A1 (en) | 2016-07-21 |
| GB0909906D0 (en) | 2009-07-22 |
| JP2012529280A (ja) | 2012-11-22 |
| WO2010142952A2 (en) | 2010-12-16 |
| CN104436191A (zh) | 2015-03-25 |
| US8461304B2 (en) | 2013-06-11 |
| EP2440579A2 (en) | 2012-04-18 |
| US20130196379A1 (en) | 2013-08-01 |
| US9145461B2 (en) | 2015-09-29 |
| WO2010142952A3 (en) | 2011-08-18 |
| US8822664B2 (en) | 2014-09-02 |
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