TWI824258B - 包含il-2蛋白及cd80蛋白之融合蛋白及其用途 - Google Patents
包含il-2蛋白及cd80蛋白之融合蛋白及其用途 Download PDFInfo
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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| CA3026474A1 (en) * | 2016-06-20 | 2017-12-28 | Kymab Limited | Anti-pd-l1 and il-2 cytokines |
| KR102201086B1 (ko) * | 2018-09-17 | 2021-01-11 | (주)지아이이노베이션 | Il-2 단백질 및 cd80 단백질을 포함하는 융합단백질 및 이의 용도 |
| JP7543404B2 (ja) * | 2019-11-20 | 2024-09-02 | ジーアイ・セル・インコーポレイテッド | T細胞培養用培地組成物及びこれを用いたt細胞の培養方法 |
| PL4063491T3 (pl) * | 2019-11-20 | 2025-03-31 | Gi Cell, Inc. | Kompozycja do hodowli komórek naturalnych zabójców i sposób otrzymywania komórek naturalnych zabójców z jej zastosowaniem |
| JP7488337B2 (ja) * | 2019-11-27 | 2024-05-21 | ジーアイ・セル・インコーポレイテッド | Il-2タンパク質及びcd80タンパク質を含む融合タンパク質及びnk細胞を含む抗癌治療用組成物 |
| US20230014358A1 (en) * | 2019-11-27 | 2023-01-19 | Gi Cell, Inc. | Composition for anticancer treatment, comprising nk cells and fusion protein which comprises il-2 protein and cd80 protein |
| CN115989238A (zh) * | 2020-03-18 | 2023-04-18 | Gi医诺微新 | 包含il-2蛋白和cd80蛋白片段或其变体的融合蛋白及其用途 |
| PL4122447T3 (pl) | 2020-03-18 | 2025-11-24 | Gi Innovation, Inc. | Preparat białka fuzyjnego zawierający białka il-2 i cd80 |
| WO2021187922A1 (ko) | 2020-03-18 | 2021-09-23 | (주)지아이이노베이션 | Il-2 단백질 및 cd80 단백질을 포함하는 융합단백질 및 항암제를 포함하는 암 치료용 약학 조성물 |
| US11746137B2 (en) * | 2020-03-31 | 2023-09-05 | Hanmi Pharm. Co., Ltd. | Immunostimulating IL-2 analogs |
| US20230235011A1 (en) * | 2020-05-25 | 2023-07-27 | Beijing Beyond Biotechnology Co., Ltd | Fc-cd80 fusion protein and conjugates thereof and their uses |
| KR102373965B1 (ko) * | 2020-06-05 | 2022-03-15 | (주)지아이이노베이션 | Il-2 단백질 및 cd80 단백질을 포함하는 융합단백질을 포함하는 방사선 치료 증진용 약학적 조성물 |
| WO2022005174A1 (ko) * | 2020-06-30 | 2022-01-06 | (주)지아이이노베이션 | 항-lag-3 항체 및 il-2를 포함하는 융합단백질 및 이의 용도 |
| EP4175979A2 (en) * | 2020-07-02 | 2023-05-10 | Inhibrx, Inc. | Polypeptides comprising modified il-2 polypeptides and uses thereof |
| WO2022045849A1 (ko) * | 2020-08-31 | 2022-03-03 | 주식회사 지아이셀 | Il15 단백질, il15 수용체 알파 단백질, fc 도메인 및 il2 단백질을 포함하는 융합단백질 및 이의 용도 |
| TWI815194B (zh) | 2020-10-22 | 2023-09-11 | 美商基利科學股份有限公司 | 介白素2-Fc融合蛋白及使用方法 |
| US20240043544A1 (en) * | 2020-12-08 | 2024-02-08 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Anti-egfr chimeric antigen receptors |
| JP2024518013A (ja) * | 2021-03-10 | 2024-04-24 | イミュノウェイク インコーポレイテッド | 免疫調節分子及びその使用 |
| WO2022057696A2 (zh) * | 2021-09-08 | 2022-03-24 | 中南大学湘雅医院 | 一种重组蛋白的编码序列、重组蛋白及其单克隆抗体的制备方法 |
| KR20230168273A (ko) * | 2022-06-03 | 2023-12-13 | (주)지아이이노베이션 | 항-tigit 항체를 포함하는 이중 특이적 항체 및 이의 용도 |
| EP4545562A4 (en) | 2022-06-22 | 2025-10-01 | Gi Innovation Inc | FUSION PROTEIN COMPRISING AN ANTI-CD73 ANTIBODY AND IL-2, AND USE THEREOF |
| TW202421176A (zh) | 2022-09-20 | 2024-06-01 | 南韓商Gi生物群系公司 | 植物乳桿菌菌株的組合療法以及使用其的癌症治療方法 |
| EP4591873A1 (en) * | 2022-09-20 | 2025-07-30 | Gi Biome Inc. | Combined therapy of lactobacillus plantarum strain, and cancer treatment method using same |
| CN115850436A (zh) * | 2022-10-14 | 2023-03-28 | 海徕科(北京)生物技术有限公司 | 白介素2突变体及其应用 |
| WO2025063755A1 (ko) * | 2023-09-20 | 2025-03-27 | 주식회사 에스엘바이젠 | 항암 dna 백신 및 면역반응-증진용 융합단백질을 포함하는 신규 암 치료제 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017079117A1 (en) * | 2015-11-02 | 2017-05-11 | Five Prime Therapeutics, Inc. | Cd80 extracellular domain polypeptides and their use in cancer treatment |
| WO2017220989A1 (en) * | 2016-06-20 | 2017-12-28 | Kymab Limited | Anti-pd-l1 and il-2 cytokines |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0119621A1 (en) * | 1983-03-21 | 1984-09-26 | F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft | Interleukin-2 |
| CN86104525A (zh) * | 1985-07-31 | 1987-02-25 | 武田药品工业株式会社 | 人类白细胞介素-2的分析方法和试剂 |
| US5229109A (en) | 1992-04-14 | 1993-07-20 | Board Of Regents, The University Of Texas System | Low toxicity interleukin-2 analogues for use in immunotherapy |
| DZ2788A1 (fr) * | 1998-05-15 | 2003-12-01 | Bayer Ag | Agonistes et antagonistes selectifs à IL-2. |
| US6955807B1 (en) | 1998-05-15 | 2005-10-18 | Bayer Pharmaceuticals Corporation | IL-2 selective agonists and antagonists |
| GB9810999D0 (en) | 1998-05-21 | 1998-07-22 | Goken Joop | Materials and methods relating to the expression of genes |
| US7829084B2 (en) | 2001-01-17 | 2010-11-09 | Trubion Pharmaceuticals, Inc. | Binding constructs and methods for use thereof |
| JP2005507870A (ja) | 2001-08-13 | 2005-03-24 | ユニバーシティ・オブ・サザン・カリフォルニア | 低毒性のインターロイキン−2突然変異体 |
| EP1454138B1 (en) | 2001-12-04 | 2012-01-18 | Merck Patent GmbH | Immunocytokines with modulated selectivity |
| CU23229A1 (es) | 2002-05-10 | 2007-09-26 | Ct Ingenieria Genetica Biotech | ANTAGONISTA QUIMéRICO ANTH1 |
| RU2006135112A (ru) * | 2004-03-05 | 2008-04-10 | Чирон Корпорейшн (Us) | Тест-система in vitro для прогнозирования устойчивости пациента к терапевтическим средствам |
| FI2402754T4 (fi) * | 2006-03-06 | 2023-10-06 | Ei-kiinteärakenteisia rekombinantteja polymeerejä ja niiden käyttötapoja | |
| CA2656700A1 (en) | 2006-07-06 | 2008-01-10 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Compositions and methods for enhancing the efficacy of il-2 mediated immune responses |
| WO2009023270A2 (en) * | 2007-08-15 | 2009-02-19 | Amunix, Inc. | Compositions and methods for modifying properties of biologically active polypeptides |
| CU23923B1 (es) | 2010-11-12 | 2013-07-31 | Ct De Inmunología Molecular | Polipéptidos derivados de la il-2 con actividad agonista |
| EP2673294B1 (en) | 2011-02-10 | 2016-04-27 | Roche Glycart AG | Mutant interleukin-2 polypeptides |
| EA201892619A1 (ru) | 2011-04-29 | 2019-04-30 | Роше Гликарт Аг | Иммуноконъюгаты, содержащие мутантные полипептиды интерлейкина-2 |
| US8956619B2 (en) * | 2011-10-25 | 2015-02-17 | University Of Maryland, Baltimore County | Soluble CD80 as a therapeutic to reverse immune supression in cancer patients |
| WO2014144960A2 (en) | 2013-03-15 | 2014-09-18 | Abbvie Biotherapeutics Inc. | Fc variants |
| MY193723A (en) | 2014-08-29 | 2022-10-27 | Hoffmann La Roche | Combination therapy of tumor-targeted il-2 variant immunocytokines and antibodies against human pd-l1 |
| KR102687530B1 (ko) * | 2016-05-04 | 2024-07-25 | 암젠 인크 | T-조절 세포의 증식을 위한 인터류킨-2 뮤테인 |
| US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
| MX2019011770A (es) * | 2017-04-03 | 2020-01-09 | Hoffmann La Roche | Inmunoconjugados de un anticuerpo anti-pd-1 con un mutante il-2 o con il-15. |
| KR102201086B1 (ko) * | 2018-09-17 | 2021-01-11 | (주)지아이이노베이션 | Il-2 단백질 및 cd80 단백질을 포함하는 융합단백질 및 이의 용도 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017079117A1 (en) * | 2015-11-02 | 2017-05-11 | Five Prime Therapeutics, Inc. | Cd80 extracellular domain polypeptides and their use in cancer treatment |
| WO2017220989A1 (en) * | 2016-06-20 | 2017-12-28 | Kymab Limited | Anti-pd-l1 and il-2 cytokines |
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