AU2018205233A1 - Dosing regimens and dosage forms for targeted TGFβ inhibition - Google Patents
Dosing regimens and dosage forms for targeted TGFβ inhibition Download PDFInfo
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- AU2018205233A1 AU2018205233A1 AU2018205233A AU2018205233A AU2018205233A1 AU 2018205233 A1 AU2018205233 A1 AU 2018205233A1 AU 2018205233 A AU2018205233 A AU 2018205233A AU 2018205233 A AU2018205233 A AU 2018205233A AU 2018205233 A1 AU2018205233 A1 AU 2018205233A1
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- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
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Landscapes
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| US201762443698P | 2017-01-07 | 2017-01-07 | |
| US62/443,698 | 2017-01-07 | ||
| US201762581978P | 2017-11-06 | 2017-11-06 | |
| US62/581,978 | 2017-11-06 | ||
| PCT/US2018/012604 WO2018129331A1 (en) | 2017-01-07 | 2018-01-05 | Dosing regimens and dosage forms for targeted tgf-b inhibition |
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| AU2018205233A1 true AU2018205233A1 (en) | 2019-07-11 |
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| HK1225740A1 (zh) | 2013-08-22 | 2017-09-15 | Acceleron Pharma Inc. | TGF-β受体II型变体及其用途 |
| EP3331550B1 (en) | 2015-08-04 | 2022-11-02 | Acceleron Pharma Inc. | Composition for treating myeloproliferative disorders |
| SI3628049T1 (sl) | 2017-05-04 | 2023-10-30 | Acceleron Pharma Inc. | Fuzijske beljakovine receptorja TGF-beta tipa II in njihova uporaba |
| AU2019288765A1 (en) * | 2018-06-22 | 2021-01-07 | Merck Patent Gmbh | Dosing regimens for targeted TGF-β inhibition for use in treating biliary tract cancer |
| 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 |
| SG11202100208VA (en) | 2018-07-09 | 2021-02-25 | Precigen Inc | Fusion constructs and methods of using thereof |
| JP7436477B2 (ja) * | 2018-11-09 | 2024-02-21 | ジエンス ヘンルイ メデイシンカンパニー リミテッド | ＴＧＦ－β受容体融合タンパク質医薬組成物およびその使用 |
| MX2021009175A (es) | 2019-01-30 | 2021-09-14 | Scholar Rock Inc | Inhibidores especificos del complejo de ltbp de tgf? y usos de los mismos. |
| AU2020290119B2 (en) * | 2019-06-10 | 2024-07-18 | Shandong Boan Biotechnology Co., Ltd. | Bifunctional fusion protein against PDL1 and TGFβ and use thereof |
| 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 |
| WO2021081321A1 (en) * | 2019-10-24 | 2021-04-29 | Amgen Inc. | Systems and approaches for drug delivery |
| WO2021084124A1 (en) * | 2019-11-01 | 2021-05-06 | Ares Trading S.A. | COMBINED INHIBITION OF PD-1, TGFβ AND ATM TOGETHER WITH RADIOTHERAPY FOR THE TREATMENT OF CANCER |
| EP4054617A4 (en) * | 2019-11-05 | 2023-12-27 | Acceleron Pharma Inc. | Treatments for systemic sclerosis |
| US20230035169A1 (en) * | 2019-12-11 | 2023-02-02 | WuXi Biologics Ireland Limited | BI-FUNCTIONAL ANTIBODY AGAINST PD-L1 AND TGF-Beta |
| CN115135302A (zh) * | 2019-12-20 | 2022-09-30 | 阿雷斯贸易股份有限公司 | IgG:TGFβRII融合蛋白组合物 |
| CN111118064B (zh) * | 2019-12-24 | 2022-10-25 | 华南理工大学 | 一种精子生成障碍动物模型及其制备方法与应用 |
| MX2022008609A (es) | 2020-01-11 | 2022-11-10 | Scholar Rock Inc | Inhibidores de tgf¿ y uso de los mismos. |
| AU2021205440A1 (en) | 2020-01-11 | 2022-09-01 | Scholar Rock,Inc. | TGF-beta inhibitors and use thereof |
| CN115135675A (zh) * | 2020-02-18 | 2022-09-30 | 南京金斯瑞生物科技有限公司 | 融合蛋白及其用途 |
| EP4093779A4 (en) * | 2020-02-25 | 2024-03-06 | Wuxi Biologics Ireland Limited | BIFUNCTIONAL FUSION PROTEIN AND USES THEREOF |
| WO2022011256A1 (en) | 2020-07-10 | 2022-01-13 | Precigen, Inc. | Fusion constructs and methods of using thereof |
| 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 |
| US20240148903A1 (en) | 2021-03-08 | 2024-05-09 | Nanjing GenScript Biotech Co., Ltd. | Delivery of antibody by using dual viral vector system |
| WO2022204581A2 (en) | 2021-03-26 | 2022-09-29 | Scholar Rock, Inc. | Tgf-beta inhibitors and use thereof |
| WO2022256723A2 (en) | 2021-06-03 | 2022-12-08 | Scholar Rock, Inc. | Tgf-beta inhibitors and therapeutic use thereof |
| CA3231649A1 (en) * | 2021-11-19 | 2023-05-25 | Cecilia Anna Wilhelmina Geuijen | Multispecific binding moieties comprising pd-1 and tgf-brii binding domains |
| 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 (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5785682A (en) * | 1995-03-22 | 1998-07-28 | Abbott Laboratories | Pre-filled syringe drug delivery system |
| JP6066732B2 (ja) * | 2010-03-05 | 2017-01-25 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 標的免疫調節抗体および融合タンパク質に基づく組成物および方法 |
| US20130110045A1 (en) * | 2011-10-31 | 2013-05-02 | Ming-Yuan Wu | Single use intravenous therapy administering device with needle safety covers |
| PT3489254T (pt) * | 2012-04-30 | 2022-12-30 | Biocon Ltd | Proteínas de fusão direcionadas/imunomoduladoras e seus métodos de fabrico |
| WO2014193898A1 (en) * | 2013-05-31 | 2014-12-04 | Merck Sharp & Dohme Corp. | Combination therapies for cancer |
| SI3105246T1 (sl) * | 2014-02-10 | 2021-11-30 | Merck Patent Gmbh | Ciljana inhibicija TGF BETA |
| CN114920840A (zh) * | 2014-10-14 | 2022-08-19 | 诺华股份有限公司 | 针对pd-l1的抗体分子及其用途 |
| CA2975147C (en) * | 2015-01-31 | 2025-06-10 | The Trustees Of The University Of Pennsylvania | COMPOSITIONS AND METHODS OF ADMINISTRATION OF THERAPEUTIC MOLECULES TO T CELLS |
| EP3277716B1 (en) * | 2015-04-03 | 2020-06-24 | XOMA Technology Ltd. | Treatment of cancer using inhibitors of tgf-beta and pd-1 |
| MX2017014381A (es) * | 2015-05-12 | 2018-03-02 | Genentech Inc | Metodos terapeuticos y diagnosticos para cancer. |
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