CN101189261B - 高亲和力Melan-A T细胞受体 - Google Patents
高亲和力Melan-A T细胞受体 Download PDFInfo
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| US7994298B2 (en) | 2004-09-24 | 2011-08-09 | Trustees Of Dartmouth College | Chimeric NK receptor and methods for treating cancer |
| WO2008039818A2 (en) * | 2006-09-26 | 2008-04-03 | Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Modified t cell receptors and related materials and methods |
| EP2087000A2 (en) * | 2006-09-29 | 2009-08-12 | Immunocore Ltd. | T cell therapies |
| US8119772B2 (en) | 2006-09-29 | 2012-02-21 | California Institute Of Technology | MART-1 T cell receptors |
| GB0816096D0 (en) * | 2008-09-04 | 2008-10-15 | Medigene Ltd | Diabetes t cell receptors |
| GB0911566D0 (en) | 2009-07-03 | 2009-08-12 | Immunocore Ltd | T cell receptors |
| WO2011059836A2 (en) | 2009-10-29 | 2011-05-19 | Trustees Of Dartmouth College | T cell receptor-deficient t cell compositions |
| US9273283B2 (en) | 2009-10-29 | 2016-03-01 | The Trustees Of Dartmouth College | Method of producing T cell receptor-deficient T cells expressing a chimeric receptor |
| US12492376B2 (en) | 2009-10-29 | 2025-12-09 | The Trustees Of Dartmouth College | T-cell receptor-deficient T cell compositions |
| CA3080181A1 (en) * | 2011-03-04 | 2012-09-13 | Shire Human Genetic Therapies, Inc. | Peptide linkers for polypeptide compositions and methods for using same |
| US9833476B2 (en) | 2011-08-31 | 2017-12-05 | The Trustees Of Dartmouth College | NKP30 receptor targeted therapeutics |
| RU2665548C2 (ru) * | 2012-05-03 | 2018-08-30 | Фред Хатчинсон Кансэр Рисёч Сентер | Способ получения клеток, экспрессирующих т-клеточный рецептор |
| WO2013169691A1 (en) | 2012-05-07 | 2013-11-14 | Trustees Of Dartmouth College | Anti-b7-h6 antibody, fusion proteins, and methods of using the same |
| AU2013308409A1 (en) | 2012-08-31 | 2015-03-26 | University Of Birmingham | Target peptides for immunotherapy and diagnostics |
| EP2892544A4 (en) | 2012-09-05 | 2016-11-02 | Univ Virginia Patent Found | TARGET PEPTIDES FOR THERAPY AND DIAGNOSIS OF COLORECTAL CARCINOMAS |
| EP3071594A4 (en) * | 2013-11-22 | 2017-05-03 | The Board of Trustees of the University of Illionis | Engineered high-affinity human t cell receptors |
| EP3137100B1 (en) | 2014-04-15 | 2023-12-20 | University Of Virginia Patent Foundation | Isolated t cell receptors and methods of use therefor |
| EP2944652A1 (en) * | 2014-05-13 | 2015-11-18 | Technische Universität München | Glypican-3-specific T-cell receptors and their uses for immunotherapy of hepatocellular carcinoma |
| WO2016014725A1 (en) * | 2014-07-22 | 2016-01-28 | The University Of Notre Dame Du Lac | Molecular constructs and uses thereof |
| GB201417803D0 (en) * | 2014-10-08 | 2014-11-19 | Adaptimmune Ltd | T cell receptors |
| GB201506642D0 (en) | 2015-04-20 | 2015-06-03 | Ucl Business Plc | T cell receptor |
| NL2014935B1 (en) | 2015-06-08 | 2017-02-03 | Applied Immune Tech Ltd | T cell receptor like antibodies having fine specificity. |
| GB201516272D0 (en) * | 2015-09-15 | 2015-10-28 | Adaptimmune Ltd And Immunocore Ltd | TCR Libraries |
| GB201516277D0 (en) | 2015-09-15 | 2015-10-28 | Adaptimmune Ltd And Immunocore Ltd | TCR libraries |
| US11827688B2 (en) | 2016-06-02 | 2023-11-28 | Immunocore Limited | Dosing regimen for GP100-specific TCR—anti-CD3 SCFV fusion protein |
| GB201617714D0 (en) | 2016-10-19 | 2016-11-30 | Ucl Business Plc | T Cell receptor |
| BR112019018863A8 (pt) * | 2017-03-15 | 2023-05-02 | Hutchinson Fred Cancer Res | Tcrs de alta afinidade específicos para mage-a1 e usos dos mesmos |
| EP4327819A3 (en) * | 2017-06-30 | 2024-05-29 | Academisch Ziekenhuis Leiden (H.O.D.N. Leids Universitair Medisch Centrum) | Treatment of haematological malignancies |
| EP3692058A1 (en) | 2017-10-06 | 2020-08-12 | Oslo Universitetssykehus HF | Chimeric antigen receptors |
| CN112646024B (zh) * | 2019-10-10 | 2023-03-24 | 香雪生命科学技术（广东）有限公司 | 一种识别kras突变的t细胞受体及其编码序列 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004044004A2 (en) * | 2002-11-09 | 2004-05-27 | Avidex Limited | T cell receptor display |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4317940B2 (ja) | 2001-08-31 | 2009-08-19 | イミュノコア・リミテッド | 物質 |
| US7751825B2 (en) | 2002-06-27 | 2010-07-06 | Qualcomm Incorporated | Controlling geographic location information of devices operating in wireless communication systems |
| US7569664B2 (en) | 2002-10-09 | 2009-08-04 | Immunocore Limited | Single chain recombinant T cell receptors |
| EP1567553A2 (en) * | 2002-12-03 | 2005-08-31 | Avidex Ltd. | Complexes of receptors |
| WO2005114215A2 (en) * | 2004-05-19 | 2005-12-01 | Avidex Ltd | Method of improving t cell receptors |
| DE602005011617D1 (de) | 2004-05-19 | 2009-01-22 | Medigene Ltd | Hochaffiner ny-eso-t-zellen-rezeptor |
-
2005
- 2005-06-01 GB GBGB0511124.0A patent/GB0511124D0/en not_active Ceased
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004044004A2 (en) * | 2002-11-09 | 2004-05-27 | Avidex Limited | T cell receptor display |
Non-Patent Citations (2)
| Title |
|---|
| LEFRANC, M.P.等.IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains.《Developmental and Comparative Immunology》.2005,第29卷(第3期),第185－203页. * |
| LI, Y等.Directed evolution of human T-cell receptors with picomolar affinities by phage display.《Nature Biotechnology》.2005,第23卷(第3期),第349-354页. * |
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| AU2006253941A2 (en) | 2008-03-06 |
| EP1893642A2 (en) | 2008-03-05 |
| MX2007014919A (es) | 2009-02-16 |
| US20080292549A1 (en) | 2008-11-27 |
| WO2006129085A3 (en) | 2007-02-01 |
| CA2610786A1 (en) | 2006-12-07 |
| ZA200710009B (en) | 2008-09-25 |
| US8217144B2 (en) | 2012-07-10 |
| WO2006129085A2 (en) | 2006-12-07 |
| EA012507B1 (ru) | 2009-10-30 |
| CN101189261A (zh) | 2008-05-28 |
| AU2006253941B2 (en) | 2012-04-12 |
| EA200702677A1 (ru) | 2008-06-30 |
| BRPI0611326A2 (pt) | 2010-08-31 |
| GB0511124D0 (en) | 2005-07-06 |
| AU2006253941A1 (en) | 2006-12-07 |
| JP2008545426A (ja) | 2008-12-18 |
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