ES2905663T3 - Terapia de combinación para el cáncer - Google Patents
Terapia de combinación para el cáncer Download PDFInfo
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- ES2905663T3 ES2905663T3 ES17755458T ES17755458T ES2905663T3 ES 2905663 T3 ES2905663 T3 ES 2905663T3 ES 17755458 T ES17755458 T ES 17755458T ES 17755458 T ES17755458 T ES 17755458T ES 2905663 T3 ES2905663 T3 ES 2905663T3
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- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N2005/1085—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy characterised by the type of particles applied to the patient
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C07K—PEPTIDES
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- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C—CHEMISTRY; METALLURGY
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
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- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
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Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
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| HK1225742A1 (zh) | 2013-08-22 | 2017-09-15 | Acceleron Pharma, Inc. | TGF-β受体II型变体及其用途 |
| EP4218792A1 (en) | 2015-08-04 | 2023-08-02 | Acceleron Pharma Inc. | Composition for treating myeloproliferative disorders |
| DK3628049T3 (da) | 2017-05-04 | 2023-08-14 | Acceleron Pharma Inc | Tgf-beta-receptortype-ii-fusionsproteiner og anvendelser deraf |
| EP3768316A4 (en) * | 2018-03-23 | 2022-06-01 | The University Of Western Australia | Method for immunotherapy drug treatment |
| WO2019211489A1 (en) * | 2018-05-04 | 2019-11-07 | Merck Patent Gmbh | COMBINED INHIBITION OF PD-1/PD-L1, TGFβ AND DNA-PK FOR THE TREATMENT OF CANCER |
| JP2021523096A (ja) * | 2018-05-15 | 2021-09-02 | メルク パテント ゲーエムベーハー | 未治療対象において癌を治療する際に使用するための標的ｔｇｆ−β阻害のための投与計画 |
| CN112566634A (zh) * | 2018-06-13 | 2021-03-26 | 默克专利有限公司 | Iii期nsclc治疗和与治疗相关的病理状况缓解 |
| BR112020026902A2 (pt) * | 2018-07-02 | 2021-03-30 | Merck Patent Gmbh | Terapia combinada com inibição direcionada de tgf-b para o tratamento de câncer de pulmão de células não pequenas avançado |
| CA3105750A1 (en) * | 2018-07-09 | 2020-01-16 | Precigen, Inc. | Fusion constructs and methods of using thereof |
| TW202039558A (zh) * | 2018-11-30 | 2020-11-01 | 大陸商江蘇恆瑞醫藥股份有限公司 | 抗ｃｄ４０抗體、其抗原結合片段及其醫藥用途 |
| CR20210416A (es) | 2019-01-30 | 2021-09-14 | Scholar Rock Inc | INHIBIDORES ESPECIFICOS DEL COMPLEJO DE LTBP DE TGFß Y USOS DE LOS MISMOS |
| EP3693974A1 (en) * | 2019-02-07 | 2020-08-12 | Koninklijke Philips N.V. | Identifying responsiveness to radio-immuno combination therapy |
| EP3929215A4 (en) * | 2019-06-10 | 2022-06-22 | Shandong Boan Biotechnology Co., Ltd. | BIFUNCTIONAL FUSION PROTEIN AGAINST PDL1 AND TGF? AND ITS USE |
| WO2020263312A1 (en) * | 2019-06-28 | 2020-12-30 | Gensun Biopharma, Inc. | ANTITUMOR ANTAGONIST CONSISTING OF A MUTATED TGFβ1 - RII EXTRACELLULAR DOMAIN AND AN IMMUNOGLOBULIN SCAFFOLD |
| CN112442132A (zh) * | 2019-09-05 | 2021-03-05 | 复旦大学 | 靶向肿瘤的重组双功能融合蛋白及其应用 |
| CN114980903A (zh) * | 2019-09-12 | 2022-08-30 | 圣诺制药公司 | 共递送TGF-β SIRNA和PDL1 SIRNA用于治疗癌症 |
| CN112574314A (zh) * | 2019-09-30 | 2021-03-30 | 和铂医药(苏州)有限公司 | 一种融合蛋白及其应用 |
| US11802145B2 (en) | 2019-10-21 | 2023-10-31 | Nanjing Leads Biolabs Co., Ltd. | Recombinant protein targeting PD-1 and TGFß |
| KR20220095205A (ko) * | 2019-11-01 | 2022-07-06 | 아레스 트레이딩 에스.아. | 암의 치료를 위한 방사선요법과 PD-1, TGFβ 및 ATM의 조합 억제 |
| JP2023502585A (ja) * | 2019-11-05 | 2023-01-25 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌の治療のための、ＰＤ－１、ＴＧＦβ、及びＴＩＧＩＴの組み合わせ阻害 |
| KR20220113382A (ko) * | 2019-12-11 | 2022-08-12 | 우시 바이올로직스 아일랜드 리미티드 | PD-L1 및 TGFβ에 대한 이작용성 항체 |
| WO2021123432A1 (en) | 2019-12-20 | 2021-06-24 | Ares Trading S.A. | Igg:tgfbetarii fusion protein composition |
| EP3838260A1 (en) | 2019-12-20 | 2021-06-23 | Ares Trading S.A. | Igg:tgf rii fusion protein composition |
| JP7719779B2 (ja) | 2020-01-11 | 2025-08-06 | スカラー ロック インコーポレイテッド | ＴＧＦβ阻害剤およびその使用 |
| CA3166328A1 (en) | 2020-01-11 | 2021-07-15 | Scholar Rock, Inc. | Tgf-beta inhibitors and use thereof |
| CN115175942B (zh) * | 2020-02-25 | 2025-05-30 | 上海药明生物技术有限公司 | 一种双功能融合蛋白及其用途 |
| CN115461362A (zh) * | 2020-04-14 | 2022-12-09 | 葛兰素史密斯克莱知识产权发展有限公司 | 基于ICOS抗体和PD-L1抗体TGF-β受体融合蛋白的癌症组合疗法 |
| WO2021209458A1 (en) | 2020-04-14 | 2021-10-21 | Ares Trading S.A. | Combination treatment of cancer |
| WO2022011256A1 (en) | 2020-07-10 | 2022-01-13 | Precigen, Inc. | Fusion constructs and methods of using thereof |
| CN113968903A (zh) * | 2020-07-24 | 2022-01-25 | 迈威(上海)生物科技股份有限公司 | TGF-β RII突变体及其融合蛋白 |
| CN116323657B (zh) * | 2020-09-24 | 2023-12-08 | 上海齐鲁制药研究中心有限公司 | 同时靶向PD-L1和TGFβ的双功能分子及其医药用途 |
| CN116801906A (zh) | 2020-11-02 | 2023-09-22 | 阿雷斯贸易股份有限公司 | 癌症的联合治疗 |
| AU2021370991A1 (en) * | 2020-11-02 | 2023-06-22 | Ares Trading S.A. | Combination treatment of cancer |
| WO2022204581A2 (en) | 2021-03-26 | 2022-09-29 | Scholar Rock, Inc. | Tgf-beta inhibitors and use thereof |
| EP4333900A2 (en) | 2021-05-03 | 2024-03-13 | Merck Patent GmbH | Her2 targeting fc antigen binding fragment-drug conjugates |
| EP4346905A1 (en) | 2021-05-25 | 2024-04-10 | Merck Patent GmbH | Egfr targeting fc antigen binding fragment-drug conjugates |
| EP4348260A2 (en) | 2021-06-03 | 2024-04-10 | Scholar Rock, Inc. | Tgf-beta inhibitors and therapeutic use thereof |
| US20240279338A1 (en) | 2021-06-07 | 2024-08-22 | Ares Trading S.A. | Combination Treatment of Cancer |
| GB202215997D0 (en) * | 2022-10-28 | 2022-12-14 | Io Biotech Aps | Therapy |
| TW202434643A (zh) | 2023-01-09 | 2024-09-01 | 大陸商北京拓界生物醫藥科技有限公司 | ＴＧＦβ１結合分子、ＧＡＲＰ－ＴＧＦβ１結合分子及其醫藥用途 |
| WO2024187051A1 (en) | 2023-03-07 | 2024-09-12 | Scholar Rock, Inc. | Tgf-beta inhibitors for use for treating resistant or unresponsive cancer in patients |
| WO2025240343A1 (en) | 2024-05-13 | 2025-11-20 | Scholar Rock, Inc. | Tgf-beta inhibitors for treating cancer |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| MXPA02007733A (es) | 2000-02-11 | 2004-09-10 | Merck Patent Gmbh | Mejoramiento de la vida media circulante de proteinas de fusion basadas en anticuerpos. |
| PL206701B1 (pl) | 2001-03-07 | 2010-09-30 | Merck Patent Gmbh | Immunoglobulinowe białko fuzyjne, kodujący je kwas nukleinowy, replikujący wektor ekspresji zawierający taki kwas nukleinowy, eukariotyczna komórka gospodarza zawierająca taki wektor ekspresji oraz sposób zwiększania ekspresji takiego białka fuzyjnego |
| WO2002079415A2 (en) | 2001-03-30 | 2002-10-10 | Lexigen Pharmaceuticals Corp. | Reducing the immunogenicity of fusion proteins |
| HRP20080053A2 (hr) | 2005-07-01 | 2009-08-31 | Medarex | Ljudska monoklonska protutijela na ligand 1 za programiranu smrt stanice (pd-l1) |
| CA3120172A1 (en) | 2008-12-09 | 2010-07-08 | Genentech, Inc. | Anti-pd-l1 antibodies and their use to enhance t-cell function |
| MX349096B (es) * | 2011-11-28 | 2017-07-11 | Merck Patent Gmbh | Anticuerpos anti-pd-l1 y sus usos. |
| CA2947354C (en) * | 2012-04-30 | 2024-03-19 | Biocon Limited | Targeted/immunomodulatory fusion proteins and methods for making same |
| SG10201603055WA (en) * | 2012-05-31 | 2016-05-30 | Genentech Inc | Methods Of Treating Cancer Using PD-L1 Axis Binding Antagonists And VEGF Antagonists |
| NZ721364A (en) * | 2014-02-10 | 2023-04-28 | Merck Patent Gmbh | Targeted tgfβ inhibition |
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