JP7325959B2 - 腫瘍特異的細胞の枯渇のための抗ＣＤ２５ ＦＣγ受容体二重特異性抗体 - Google Patents
腫瘍特異的細胞の枯渇のための抗ＣＤ２５ ＦＣγ受容体二重特異性抗体 Download PDFInfo
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- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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- Peptides Or Proteins (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1605947.9 | 2016-04-07 | ||
| GB201605947 | 2016-04-07 | ||
| PCT/EP2017/056469 WO2017174331A1 (en) | 2016-04-07 | 2017-03-17 | Anti cd25 fc gamma receptor bispecific antibodies for tumor specific cell depletion |
Publications (3)
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| WO2017011592A1 (en) | 2015-07-13 | 2017-01-19 | Modular Genetics, Inc. | Generation of acyl alcohols |
| RU2759970C2 (ru) | 2016-04-07 | 2021-11-19 | Кансер Ресёрч Текнолоджи Лимитед | БИСПЕЦИФИЧЕСКИЕ АНТИТЕЛА К CD25 И Fc ГАММА-РЕЦЕПТОРУ ДЛЯ ЭЛИМИНАЦИИ ОПУХОЛЕСПЕЦИФИЧЕСКИХ КЛЕТОК |
| KR102576042B1 (ko) | 2016-10-11 | 2023-09-07 | 아게누스 인코포레이티드 | 항-lag-3 항체 및 이의 사용 방법 |
| US11879014B2 (en) | 2017-03-17 | 2024-01-23 | Tusk Therapeutics Ltd. | Method of treating cancer or depleting regulatory T cells in a subject by administering a human IGG1 anti-CD25 antibody |
| CN110914302A (zh) | 2017-06-01 | 2020-03-24 | 赛托姆克斯治疗学股份有限公司 | 可活化抗pdl1抗体及其使用方法 |
| GB201712032D0 (en) | 2017-07-26 | 2017-09-06 | Bioinvent Int Ab | Antibodies and uses thereof |
| CN120617499A (zh) * | 2018-01-10 | 2025-09-12 | 生物发明国际公司 | 抗体的新型组合和用途 |
| BR112020016374A2 (pt) * | 2018-02-13 | 2020-12-15 | Precision Biologics, Inc. | Métodos e composições para direcionar células treg |
| SG11202008733YA (en) * | 2018-03-13 | 2020-10-29 | Tusk Therapeutics Ltd | Anti-cd25 for tumour specific cell depletion |
| EP3566718A1 (en) * | 2018-05-07 | 2019-11-13 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz | A pharmazeutical combination (treg depleting agent, checkpoint inhibitor, tlr9 agonist) for use in the treatment of cancer |
| EP3830129A4 (en) * | 2018-07-30 | 2022-05-04 | Invenra, Inc. | MULTISPECIFIC TREG-BINDING MOLECULES |
| CN113272330B (zh) * | 2019-03-02 | 2024-07-26 | 南通壹宸生物医药科技有限公司 | 一种双特异抗体 |
| WO2021145946A1 (en) * | 2020-01-13 | 2021-07-22 | Invenra Inc. | Multispecific treg binding molecules |
| EP4103611B1 (en) * | 2020-02-13 | 2024-03-27 | UCB Biopharma SRL | Bispecific antibodies binding hvem and cd9 |
| EP4151655A1 (en) | 2020-05-14 | 2023-03-22 | Jiangsu Hengrui Pharmaceuticals Co., Ltd. | Anti-cd25 antibodies, antigen-binding fragments thereof, and medical uses thereof |
| EP4243860A4 (en) * | 2020-11-13 | 2024-10-16 | iBio, Inc. | ANTI-CD25 ANTIBODIES |
| WO2022117572A2 (en) | 2020-12-02 | 2022-06-09 | Oncurious Nv | An ltbr agonist in combination therapy against cancer |
| US20240352136A1 (en) | 2021-09-02 | 2024-10-24 | Hoffmann-La Roche Inc. | Antibodies for the treatment of aml |
| TW202336033A (zh) * | 2022-03-07 | 2023-09-16 | 瑞典商生物創新國際有限公司 | 抗體之新穎組合及用途 |
| WO2023208990A1 (en) | 2022-04-26 | 2023-11-02 | F. Hoffmann-La Roche Ag | Combination therapy for the treatment of cancer comprising a fas axis antagonist and a t-reg cell depleting agent antagonist, |
| WO2023245021A2 (en) * | 2022-06-14 | 2023-12-21 | Invenra Inc. | Multispecific binding agents that target cd25 and/or ctla4 and uses thereof |
| WO2024088987A1 (en) | 2022-10-26 | 2024-05-02 | F. Hoffmann-La Roche Ag | Combination therapy for the treatment of cancer |
| KR20240113400A (ko) * | 2023-01-11 | 2024-07-22 | 한국과학기술원 | 종양 내 Treg의 바이오마커를 포함하는 진단용 조성물 및 약학 조성물 |
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| CN120917143A (zh) | 2023-03-29 | 2025-11-07 | 第一三共株式会社 | 抗cd25抗体及抗cd25抗体-药物偶联物 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008535883A (ja) | 2005-04-15 | 2008-09-04 | ノバルティス アクチエンゲゼルシャフト | 免疫治療におけるｃｄ２５抗体の使用 |
| WO2010030002A1 (ja) | 2008-09-12 | 2010-03-18 | 国立大学法人三重大学 | 外来性ｇｉｔｒリガンド発現細胞 |
| WO2014145907A1 (en) | 2013-03-15 | 2014-09-18 | Xencor, Inc. | Targeting t cells with heterodimeric proteins |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0316282B8 (pt) * | 2002-11-15 | 2021-05-25 | Genmab As | anticorpo humano isolado monoclonal, composição, imunoconjugado, molécula biespecífica ou multiespecífica, método e conjunto de diagnóstico para detectar a presença de antígeno cd25 ou uma célula que expressa cd25, e, vetor de expressão |
| AU2007342338A1 (en) * | 2006-09-20 | 2008-07-17 | The Johns Hopkins University | Combinatorial therapy of cancer and infectious diseases with anti-B7-H1 antibodies |
| RU2759970C2 (ru) | 2016-04-07 | 2021-11-19 | Кансер Ресёрч Текнолоджи Лимитед | БИСПЕЦИФИЧЕСКИЕ АНТИТЕЛА К CD25 И Fc ГАММА-РЕЦЕПТОРУ ДЛЯ ЭЛИМИНАЦИИ ОПУХОЛЕСПЕЦИФИЧЕСКИХ КЛЕТОК |
| GB201712032D0 (en) * | 2017-07-26 | 2017-09-06 | Bioinvent Int Ab | Antibodies and uses thereof |
| SG11202008733YA (en) * | 2018-03-13 | 2020-10-29 | Tusk Therapeutics Ltd | Anti-cd25 for tumour specific cell depletion |
| WO2023208990A1 (en) * | 2022-04-26 | 2023-11-02 | F. Hoffmann-La Roche Ag | Combination therapy for the treatment of cancer comprising a fas axis antagonist and a t-reg cell depleting agent antagonist, |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008535883A (ja) | 2005-04-15 | 2008-09-04 | ノバルティス アクチエンゲゼルシャフト | 免疫治療におけるｃｄ２５抗体の使用 |
| WO2010030002A1 (ja) | 2008-09-12 | 2010-03-18 | 国立大学法人三重大学 | 外来性ｇｉｔｒリガンド発現細胞 |
| WO2014145907A1 (en) | 2013-03-15 | 2014-09-18 | Xencor, Inc. | Targeting t cells with heterodimeric proteins |
| US20140294759A1 (en) | 2013-03-15 | 2014-10-02 | Seung Chu | Targeting regulatory t cells with heterodimeric proteins |
Non-Patent Citations (5)
| Title |
|---|
| Cancer Vaccines, 2009, Vol.1174, pp.99-106 |
| Eur. J. Immunol., 2010, Vol.40, pp.3325-3335 |
| JOHN H SAMPSON; ET AL，A PILOT STUDY OF IL-2Rα BLOCKADE DURING LYMPHOPENIA DEPLETES REGULATORY T-CELLS AND CORRELATES WITH ENHANCED IMMUNITY IN PATIENTS WITH GLIOBLASTOMA，PLOS ONE，2012年02月27日，VOL:7, NR:2，PAGE(S):E31046/1-11，https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0031046&type=printable |
| Science Translational Medicine, 2012, Vol.4, No.134, Article No.134ra62, pp.1-9 |
| Trends in Immunology, 2015, Vol.36, No.6, pp.325-336 |
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| US20230265200A1 (en) | 2023-08-24 |
| IL262129B1 (en) | 2025-03-01 |
| IL262129A (en) | 2018-11-29 |
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| CL2018002828A1 (es) | 2019-03-08 |
| CL2019003498A1 (es) | 2020-05-29 |
| EP3440109B1 (en) | 2025-07-23 |
| EP3440109A1 (en) | 2019-02-13 |
| PL3440109T3 (pl) | 2025-12-01 |
| BR112018070636A2 (pt) | 2019-02-05 |
| RU2018135247A3 (OSRAM) | 2021-01-20 |
| ES3046543T3 (en) | 2025-12-02 |
| EP3440109C0 (en) | 2025-07-23 |
| AU2017247880B2 (en) | 2024-07-11 |
| KR20220032642A (ko) | 2022-03-15 |
| RU2018135247A (ru) | 2020-05-12 |
| CN109476739A (zh) | 2019-03-15 |
| US20190135925A1 (en) | 2019-05-09 |
| CA3020204A1 (en) | 2017-10-12 |
| JP2019513725A (ja) | 2019-05-30 |
| MX2018012319A (es) | 2019-06-06 |
| IL262129B2 (en) | 2025-07-01 |
| RU2759970C2 (ru) | 2021-11-19 |
| AU2017247880A1 (en) | 2018-11-15 |
| KR20190017735A (ko) | 2019-02-20 |
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