CA2952293A1 - Mic-1 fusion proteins and uses thereof - Google Patents
Mic-1 fusion proteins and uses thereof Download PDFInfo
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- CA2952293A1 CA2952293A1 CA2952293A CA2952293A CA2952293A1 CA 2952293 A1 CA2952293 A1 CA 2952293A1 CA 2952293 A CA2952293 A CA 2952293A CA 2952293 A CA2952293 A CA 2952293A CA 2952293 A1 CA2952293 A1 CA 2952293A1
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| EP14173664.5 | 2014-06-24 | ||
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| CA2952293A1 true CA2952293A1 (en) | 2015-12-30 |
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| JP5977814B2 (ja) | 2011-04-08 | 2016-08-24 | アムジエン・インコーポレーテツド | 増殖分化因子１５（ｇｄｆ−１５）を使用して代謝障害を治療または改善する方法 |
| LT3027642T (lt) | 2013-07-31 | 2020-10-12 | Amgen Inc. | Augimo ir diferenciacijos faktoriaus 15(gdf-15) konstruktai |
| US10588980B2 (en) | 2014-06-23 | 2020-03-17 | Novartis Ag | Fatty acids and their use in conjugation to biomolecules |
| US20190000923A1 (en) | 2015-12-22 | 2019-01-03 | Novartis Ag | Methods of treating or ameliorating metabolic disorders using growth differentiation factor 15 (gdf-15) |
| US10336812B2 (en) * | 2016-05-10 | 2019-07-02 | Janssen Biotech, Inc. | GDF15 fusion proteins and uses thereof |
| KR102433503B1 (ko) * | 2016-05-24 | 2022-08-18 | 노보 노르디스크 에이/에스 | Mic-1 화합물 및 이것의 사용 |
| GB201615844D0 (en) * | 2016-09-16 | 2016-11-02 | Genagon Therapeutics Ab | Agents for use in therapy |
| EP3551214B1 (en) | 2016-12-06 | 2024-03-13 | St Vincent's Hospital Sydney Limited | Treatment of obesity and eating disorders |
| GB201700553D0 (en) * | 2017-01-12 | 2017-03-01 | Genagon Therapeutics Ab | Therapeutic agents |
| GB201700567D0 (en) | 2017-01-12 | 2017-03-01 | Genagon Therapeutics Ab | Therapeutic agents |
| WO2018193033A1 (en) | 2017-04-20 | 2018-10-25 | Novo Nordisk A/S | Methods of purification of albumin fusion proteins |
| TWI710377B (zh) * | 2017-05-23 | 2020-11-21 | 丹麥商諾佛 儂迪克股份有限公司 | Ｍｉｃ－１化合物及其用途 |
| JP2020533302A (ja) | 2017-09-10 | 2020-11-19 | ノヴォ ノルディスク アー／エス | 肥満の治療において使用するためのｍｉｃ−１およびｇｌｐ−１ |
| WO2019190752A1 (en) | 2018-03-30 | 2019-10-03 | Alexion Pharmaceuticals, Inc. | Manufacturing of glycoproteins |
| TWI724392B (zh) | 2018-04-06 | 2021-04-11 | 美商美國禮來大藥廠 | 生長分化因子15促效劑化合物及其使用方法 |
| US12054527B2 (en) | 2018-04-09 | 2024-08-06 | Amgen Inc. | Growth differentiation factor 15 fusion proteins |
| EP3833974A2 (en) | 2018-08-10 | 2021-06-16 | Novartis AG | Gfral extracellular domains and methods of use |
| WO2020033867A2 (en) | 2018-08-10 | 2020-02-13 | Alexion Pharmaceuticals, Inc. | Methods of treating neurofibromatosis type 1 and related conditions with alkaline phosphatase |
| MY205905A (en) | 2018-10-22 | 2024-11-20 | Janssen Pharmaceutica Nv | Glucagon like peptide 1 (glp1)-growth differentiation factor 15 (gdf15) fusion proteins and uses thereof |
| ES3061099T3 (en) | 2019-10-04 | 2026-03-31 | Amgen Inc | Use of gdf15 for treating cardiometabolic syndrome and other conditions |
| CA3161302A1 (en) * | 2019-11-26 | 2021-06-03 | Yuhan Corporation | Long-acting gdf15 fusion protein and pharmaceutical composition comprising same |
| CA3161266A1 (en) * | 2019-12-09 | 2021-06-17 | Alexion Pharmaceuticals, Inc. | Alkaline phosphatase polypeptides and methods of use thereof |
| KR102899743B1 (ko) * | 2019-12-11 | 2025-12-12 | 주식회사 엘지화학 | O-글리코실화 가능한 폴리펩타이드 영역 및 gdf15를 포함하는 융합 폴리펩타이드 |
| EP4081241A4 (en) * | 2019-12-24 | 2024-05-01 | Juvena Therapeutics, Inc. | REGENERATIVE POLYPEPTIDES AND USES THEREOF |
| WO2021136223A1 (en) | 2019-12-31 | 2021-07-08 | Beijing Ql Biopharmaceutical Co., Ltd. | Fusion proteins of glp-1 and gdf15 and conjugates thereof |
| WO2021194257A1 (ko) * | 2020-03-25 | 2021-09-30 | (주) 업테라 | 세포 투과성 펩티드 이량체, 이의 제조방법 및 이를 이용한 카고 전달 시스템 |
| KR102195740B1 (ko) * | 2020-03-25 | 2020-12-28 | 서울대학교산학협력단 | 세포 투과성 펩티드 이량체, 이의 제조방법 및 이를 이용한 카고 전달 시스템 |
| US12611447B2 (en) | 2020-09-04 | 2026-04-28 | Alexion Pharmaceuticals, Inc. | Methods for treating bone mineralization disorders |
| EP4237438A4 (en) | 2020-10-27 | 2024-11-27 | Beijing QL Biopharmaceutical Co., Ltd. | GDF15 FUSION PROTEINS AND THEIR USE |
| CN112694520B (zh) * | 2020-12-02 | 2023-01-17 | 图凌(杭州)生物医药有限公司 | 一种人工多肽hm、其抗体及在病理检测中的应用 |
| AU2022218782B2 (en) | 2021-02-12 | 2026-06-25 | Alexion Pharmaceuticals, Inc. | Alkaline phosphatase polypeptides and methods of use thereof |
| WO2022219495A1 (en) | 2021-04-12 | 2022-10-20 | Novartis Ag | 2-((4-((s)-2-(4-chloro-2-fluorophenyl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((s)-oxetan-2-yl)methyl)-1h-imidazole derivatives as activators of the glp1 receptor for the treatment of obesity |
| JP2025505198A (ja) | 2022-02-10 | 2025-02-21 | ノバルティス アーゲー | 肥満の治療のためのｇｌｐ１受容体の活性化因子としての２－（（４－（（ｓ）－２－（４－クロロ－２－フルオロフェニル）－２－メチルベンゾ［ｄ］［１，３］ジオキソール－４－イル）ピペリジン－１－イル）メチル）－１－（（（ｓ）－オキセタン－２－イル）メチル）－１ｈ－イミダゾール誘導体 |
| EP4389762A1 (en) | 2022-12-23 | 2024-06-26 | Ospedale San Raffaele S.r.l. | Inhibitors of dux4 activity and their use in therapy. |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6926898B2 (en) | 2000-04-12 | 2005-08-09 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| CN1241946C (zh) | 2002-07-01 | 2006-02-15 | 美国福源集团 | 对多种细胞具刺激增生作用的人血清白蛋白重组融合蛋白 |
| DK2441466T3 (da) | 2004-04-13 | 2014-10-27 | St Vincents Hosp Sydney | MIC-1-inhiberende middel |
| PL1751184T3 (pl) * | 2004-05-13 | 2010-02-26 | Lilly Co Eli | Białka fuzyjne FGF-21 |
| MX2007001180A (es) * | 2004-07-26 | 2007-04-13 | Asterion Ltd | Enlazantes. |
| CA2695374A1 (en) | 2007-08-15 | 2009-02-19 | Amunix, Inc. | Compositions and methods for modifying properties of biologically active polypeptides |
| KR20140125803A (ko) * | 2012-01-26 | 2014-10-29 | 암젠 인크 | 성장 분화 인자 15(gdf-15) 폴리펩타이드들 |
| JP6254146B2 (ja) | 2012-03-27 | 2017-12-27 | エヌジーエム バイオファーマシューティカルス，インコーポレーテッド | 代謝障害を治療するための組成物および方法 |
| CA2899170C (en) | 2013-01-30 | 2022-08-02 | Ngm Biopharmaceuticals, Inc. | Compositions and methods of use in treating metabolic disorders |
| LT3027642T (lt) | 2013-07-31 | 2020-10-12 | Amgen Inc. | Augimo ir diferenciacijos faktoriaus 15(gdf-15) konstruktai |
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2015
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- 2015-06-17 RU RU2017101436A patent/RU2017101436A/ru unknown
- 2015-06-17 CN CN201580033507.XA patent/CN106459222A/zh not_active Withdrawn
- 2015-06-17 MX MX2016016063A patent/MX2016016063A/es unknown
- 2015-06-17 BR BR112016029848A patent/BR112016029848A2/pt not_active Application Discontinuation
- 2015-06-17 JP JP2016574944A patent/JP6696915B2/ja not_active Expired - Fee Related
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- 2015-06-17 CA CA2952293A patent/CA2952293A1/en not_active Withdrawn
- 2015-06-17 KR KR1020167037059A patent/KR20170020383A/ko not_active Withdrawn
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| US20160015784A1 (en) | 2016-01-21 |
| JP6696915B2 (ja) | 2020-05-20 |
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| EP3160496B1 (en) | 2021-03-03 |
| MX2016016063A (es) | 2017-03-10 |
| RU2017101436A3 (enExample) | 2019-02-13 |
| WO2015197446A1 (en) | 2015-12-30 |
| KR20170020383A (ko) | 2017-02-22 |
| CN106459222A (zh) | 2017-02-22 |
| US20160129083A1 (en) | 2016-05-12 |
| EP3160496A1 (en) | 2017-05-03 |
| BR112016029848A2 (pt) | 2017-10-24 |
| AR100945A1 (es) | 2016-11-09 |
| AU2015279525A1 (en) | 2016-12-15 |
| IL249327A0 (en) | 2017-02-28 |
| TW201613958A (en) | 2016-04-16 |
| ZA201608214B (en) | 2018-11-28 |
| RU2017101436A (ru) | 2018-07-24 |
| US9272019B2 (en) | 2016-03-01 |
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