ES2742456T3 - Regímenes de tratamiento utilizando anticuerpos anti-NKG2A - Google Patents
Regímenes de tratamiento utilizando anticuerpos anti-NKG2A Download PDFInfo
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- ES2742456T3 ES2742456T3 ES15763016T ES15763016T ES2742456T3 ES 2742456 T3 ES2742456 T3 ES 2742456T3 ES 15763016 T ES15763016 T ES 15763016T ES 15763016 T ES15763016 T ES 15763016T ES 2742456 T3 ES2742456 T3 ES 2742456T3
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112012021576A2 (pt) | 2010-02-26 | 2016-10-25 | Novo Nordisk As | composições estáveis contendo anticorpo. |
| CN103635487B (zh) | 2011-06-17 | 2016-10-12 | 诺沃—诺迪斯克有限公司 | 选择性消除侵蚀性细胞 |
| DK3193929T3 (da) | 2014-09-16 | 2019-08-19 | Innate Pharma | Behandlingsregimer ved anvendelse af anti-nkg2a-antistoffer |
| CN113929782B (zh) | 2014-09-16 | 2024-06-21 | 依奈特制药公司 | 对淋巴细胞中抑制途径的中和 |
| RU2721271C2 (ru) | 2014-10-23 | 2020-05-18 | Иннейт Фарма | Лечение раковых заболеваний с применением анти-nkg2a средств |
| KR20190080992A (ko) | 2015-05-21 | 2019-07-08 | 하푼 테라퓨틱스, 인크. | 삼중특이성 결합 단백질 및 사용 방법 |
| US10736963B2 (en) | 2015-07-24 | 2020-08-11 | Innate Pharma | Methods for detecting tissue infiltrating NK cells |
| RS61901B1 (sr) | 2016-01-21 | 2021-06-30 | Innate Pharma | Neutralizacija inhibitornih puteva u limfocitima |
| US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
| KR20230173745A (ko) | 2016-10-21 | 2023-12-27 | 이나뜨 파르마 에스.에이. | 항-kir3dl2 작용제에 의한 치료 |
| SG10202107880XA (en) | 2017-05-12 | 2021-09-29 | Harpoon Therapeutics Inc | Mesothelin binding proteins |
| JP2020527144A (ja) * | 2017-07-10 | 2020-09-03 | イナート・ファルマ・ソシエテ・アノニムＩｎｎａｔｅ Ｐｈａｒｍａ Ｐｈａｒｍａ Ｓ．Ａ． | 癌を処置するためのヒトｓｉｇｌｅｃ−９に対する抗体およびヒトｎｋｇ２ａに対する抗体を使用する組み合わせ療法 |
| PL3694529T3 (pl) | 2017-10-13 | 2024-12-16 | Harpoon Therapeutics, Inc. | Trójswoiste białka i sposoby zastosowania |
| IL315737A (en) | 2017-10-13 | 2024-11-01 | Harpoon Therapeutics Inc | B-cell maturation antigen-binding proteins |
| KR20200133233A (ko) * | 2018-03-13 | 2020-11-26 | 이나뜨 파르마 | 두부경부암의 치료 |
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| CN113286817B (zh) | 2018-09-25 | 2025-01-28 | 哈普恩治疗公司 | Dll3结合蛋白及使用方法 |
| EP3878869A4 (en) * | 2018-11-07 | 2023-04-19 | Shanghai Hyamab Biotech Co., Ltd. | NKG2A ANTIBODIES, METHOD OF PRODUCTION THEREOF AND USE THEREOF |
| US11274150B2 (en) | 2018-11-16 | 2022-03-15 | Bristol-Myers Squibb Company | Anti-human natural killer cell inhibitory receptor group 2A protein (NKG2A) antibodies |
| JP2022528000A (ja) * | 2019-03-29 | 2022-06-07 | ドレン バイオ， インコーポレイテッド | 大顆粒リンパ球およびナチュラルキラー細胞レベルを低減する方法 |
| CN114174538A (zh) | 2019-05-30 | 2022-03-11 | 百时美施贵宝公司 | 适合于免疫肿瘤学疗法的多肿瘤基因特征 |
| KR20220016155A (ko) | 2019-05-30 | 2022-02-08 | 브리스톨-마이어스 스큅 컴퍼니 | 면역-종양학 (i-o) 요법에 적합한 대상체를 확인하는 방법 |
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| WO2021024020A1 (en) | 2019-08-06 | 2021-02-11 | Astellas Pharma Inc. | Combination therapy involving antibodies against claudin 18.2 and immune checkpoint inhibitors for treatment of cancer |
| EP4054591A1 (en) | 2019-11-04 | 2022-09-14 | Astrazeneca AB | Combination therapy for treating cancer |
| CN113583127A (zh) * | 2020-04-30 | 2021-11-02 | 迈威(上海)生物科技股份有限公司 | 一种靶向nkg2a和pd-l1的双特异性抗体及应用 |
| KR20230010228A (ko) * | 2020-05-08 | 2023-01-18 | 시애틀 칠드런즈 호스피탈 디/비/에이 시애틀 칠드런즈 리서치 인스티튜트 | 자연 살해 세포를 표적으로 하는 키메라 항원 수용체 (cars) |
| KR20230035576A (ko) | 2020-07-07 | 2023-03-14 | 비온테크 에스이 | Hpv 양성 암 치료용 rna |
| CA3190660A1 (en) | 2020-08-31 | 2022-03-03 | George C. Lee | Cell localization signature and immunotherapy |
| US11795228B2 (en) | 2020-09-30 | 2023-10-24 | Dren Bio, Inc. | Anti-CD94 antibodies and methods of use thereof |
| WO2022120179A1 (en) | 2020-12-03 | 2022-06-09 | Bristol-Myers Squibb Company | Multi-tumor gene signatures and uses thereof |
| US11883432B2 (en) | 2020-12-18 | 2024-01-30 | Century Therapeutics, Inc. | Chimeric antigen receptor system with adaptable receptor specificity |
| WO2022135666A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Treatment schedule for cytokine proteins |
| TW202245808A (zh) | 2020-12-21 | 2022-12-01 | 德商拜恩迪克公司 | 用於治療癌症之治療性ｒｎａ |
| WO2022135667A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Therapeutic rna for treating cancer |
| CA3196999A1 (en) | 2020-12-28 | 2022-07-07 | Masano HUANG | Methods of treating tumors |
| SMT202500208T1 (it) | 2020-12-28 | 2025-07-22 | Bristol Myers Squibb Co | Composizioni anticorpali e metodi per il loro uso |
| EP4314068A1 (en) | 2021-04-02 | 2024-02-07 | The Regents Of The University Of California | Antibodies against cleaved cdcp1 and uses thereof |
| EP4347651A1 (en) | 2021-06-01 | 2024-04-10 | Les Laboratoires Servier | Anti-nkg2a antibodies and compositions |
| AU2022312698A1 (en) | 2021-07-13 | 2024-01-25 | BioNTech SE | Multispecific binding agents against cd40 and cd137 in combination therapy for cancer |
| TW202333802A (zh) | 2021-10-11 | 2023-09-01 | 德商拜恩迪克公司 | 用於肺癌之治療性rna(二) |
| KR20240159621A (ko) | 2022-03-18 | 2024-11-05 | 브리스톨-마이어스 스큅 컴퍼니 | 폴리펩티드를 단리하는 방법 |
| WO2023235847A1 (en) | 2022-06-02 | 2023-12-07 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
| CN120418289A (zh) | 2022-12-14 | 2025-08-01 | 安斯泰来制药欧洲有限公司 | 结合cldn18.2和cd3的双特异性结合剂与免疫检查点抑制剂的联合疗法 |
| EP4649173A1 (en) | 2023-01-13 | 2025-11-19 | Akrivia Biomedics Limited | Method of profiling diseases |
| WO2024196952A1 (en) | 2023-03-20 | 2024-09-26 | Bristol-Myers Squibb Company | Tumor subtype assessment for cancer therapy |
| WO2025038763A1 (en) | 2023-08-15 | 2025-02-20 | Bristol-Myers Squibb Company | Ceramic hydroxyapatite chromatography flow through method |
| WO2025121445A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and agents stabilizing or increasing expression of cldn18.2 |
| WO2025120867A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and anti-vegfr2 antibodies |
| WO2025120866A1 (en) | 2023-12-08 | 2025-06-12 | Astellas Pharma Inc. | Combination therapy involving bispecific binding agents binding to cldn18.2 and cd3 and agents stabilizing or increasing expression of cldn18.2 |
| US20250215087A1 (en) | 2023-12-29 | 2025-07-03 | Bristol-Myers Squibb Company | Combination therapy of kras inhibitor and treg depleting agent |
| WO2025250011A1 (en) | 2024-05-29 | 2025-12-04 | Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis | Treatment for cancer |
Family Cites Families (16)
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| GB9725764D0 (en) | 1997-12-04 | 1998-02-04 | Isis Innovation | HLA-E binding |
| US20030095965A1 (en) | 2001-05-02 | 2003-05-22 | Katrien Van Beneden | Antibodies to Ly49E and CD94/NKG2 receptors |
| CN101107269B (zh) * | 2004-12-28 | 2012-10-31 | 依奈特制药公司 | 抗nkg2a的单克隆抗体 |
| EP3026063A1 (en) | 2004-12-28 | 2016-06-01 | Innate Pharma S.A. | Monoclonal antibodies against nkg2a |
| MX2008015830A (es) | 2006-06-30 | 2009-01-09 | Novo Nordisk As | Anticuerpos anti-nkg2a y usos de los mismos. |
| BRPI0908508A2 (pt) | 2008-01-24 | 2016-03-22 | Novo Nordisk As | anticorpo monoclonal nkg2a anti-humano humanizado |
| US20110033389A1 (en) | 2009-04-29 | 2011-02-10 | Zhifeng Chen | Modified antibodies for passive immunotherapy |
| BR112012021576A2 (pt) | 2010-02-26 | 2016-10-25 | Novo Nordisk As | composições estáveis contendo anticorpo. |
| CN103635487B (zh) | 2011-06-17 | 2016-10-12 | 诺沃—诺迪斯克有限公司 | 选择性消除侵蚀性细胞 |
| EP3186282A1 (en) | 2014-08-28 | 2017-07-05 | Academisch Ziekenhuis Leiden h.o.d.n. LUMC | Cd94/nkg2a and/or cd94/nkg2b antibody, vaccine combinations |
| DK3193929T3 (da) | 2014-09-16 | 2019-08-19 | Innate Pharma | Behandlingsregimer ved anvendelse af anti-nkg2a-antistoffer |
| CN113929782B (zh) | 2014-09-16 | 2024-06-21 | 依奈特制药公司 | 对淋巴细胞中抑制途径的中和 |
| RU2721271C2 (ru) | 2014-10-23 | 2020-05-18 | Иннейт Фарма | Лечение раковых заболеваний с применением анти-nkg2a средств |
| RS61901B1 (sr) | 2016-01-21 | 2021-06-30 | Innate Pharma | Neutralizacija inhibitornih puteva u limfocitima |
| KR20200133233A (ko) | 2018-03-13 | 2020-11-26 | 이나뜨 파르마 | 두부경부암의 치료 |
| AU2019270277B9 (en) | 2018-05-15 | 2024-12-05 | Innate Pharma | Treatment of cancer |
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