CN107810201A - 使用klotho变体多肽的方法和组合物 - Google Patents
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- CN107810201A CN107810201A CN201580075428.5A CN201580075428A CN107810201A CN 107810201 A CN107810201 A CN 107810201A CN 201580075428 A CN201580075428 A CN 201580075428A CN 107810201 A CN107810201 A CN 107810201A
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462087516P | 2014-12-04 | 2014-12-04 | |
| US62/087,516 | 2014-12-04 | ||
| PCT/IB2015/059294 WO2016088059A1 (en) | 2014-12-04 | 2015-12-02 | Methods and compositions using klotho variant polypeptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107810201A true CN107810201A (zh) | 2018-03-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201580075428.5A Pending CN107810201A (zh) | 2014-12-04 | 2015-12-02 | 使用klotho变体多肽的方法和组合物 |
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| Country | Link |
|---|---|
| US (2) | US10654909B2 (enExample) |
| EP (1) | EP3227319B1 (enExample) |
| JP (1) | JP2017537926A (enExample) |
| KR (1) | KR20170084332A (enExample) |
| CN (1) | CN107810201A (enExample) |
| AU (1) | AU2015356643B2 (enExample) |
| BR (1) | BR112017011398A2 (enExample) |
| CA (1) | CA2969307A1 (enExample) |
| EA (1) | EA201791238A1 (enExample) |
| MX (2) | MX2017007303A (enExample) |
| TW (1) | TW201628641A (enExample) |
| WO (1) | WO2016088059A1 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112695049A (zh) * | 2020-08-20 | 2021-04-23 | 山东兴瑞生物科技有限公司 | 修饰间充质干细胞的融合基因、质粒、修饰得到干细胞及制备方法 |
| CN112915193A (zh) * | 2021-03-05 | 2021-06-08 | 南方医科大学南方医院 | Kp-1在制备治疗慢性肺病的药物中的用途 |
| CN112915192A (zh) * | 2021-03-05 | 2021-06-08 | 南方医科大学南方医院 | Kp-1在制备治疗慢性肝病的药物中的用途 |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3031839B1 (fr) | 2015-01-19 | 2020-03-13 | Areva Stockage D'energie | Systeme electrique comprenant un empilement de cellules electrochimiques et procede de pilotage de ce systeme |
| EP3253403B1 (en) | 2015-02-06 | 2021-09-01 | The Regents of The University of California | Methods and compositions for improved cognition |
| EP3551212A4 (en) | 2016-11-22 | 2020-11-04 | Klotho Therapeutics, Inc. | NEW RECOMBINATED KLOTHO PROTEINS AND COMPOSITIONS AND METHODS INCLUDING THEM |
| CA3069143A1 (en) | 2017-07-06 | 2019-01-10 | Yale University | Compositions and methods for treating or preventing endocrine fgf-linked diseases |
| CN111712519A (zh) * | 2017-12-13 | 2020-09-25 | 耶鲁大学 | 用于治疗或预防内分泌fgf23-相关疾病的组合物和方法 |
| WO2019140250A1 (en) * | 2018-01-12 | 2019-07-18 | New York University | SOLUBLE α-KLOTH PROTEINS, PROTEIN FRAGMENTS, AND USES THEREOF |
| EP3883958A4 (en) * | 2018-11-21 | 2022-09-07 | University of Pittsburgh - Of the Commonwealth System of Higher Education | METHODS AND MATERIALS FOR REDUCING AGE-RELATED STRIATED MUSCLES AND COGNITIVE DEGRADATION |
| US20240384250A1 (en) * | 2021-09-03 | 2024-11-21 | The Uab Research Foundation | Fibroblast growth factor 23 modulating compounds |
| WO2024168241A2 (en) * | 2023-02-10 | 2024-08-15 | The Trustees Of Indiana University | Stabilized fgf23 fusion proteins, compositions and a targeted therapy for hyperphosphatemia |
| EP4434534A1 (en) | 2023-03-22 | 2024-09-25 | ADvantage Therapeutics, Inc. | Klotho mrna |
| WO2025101851A1 (en) * | 2023-11-10 | 2025-05-15 | Regeneron Pharmaceuticals, Inc. | Engineered alpha klotho polypeptides and uses thereof |
| US20250376667A1 (en) * | 2024-06-07 | 2025-12-11 | Regeneron Pharmaceuticals, Inc. | Engineered alpha klotho polypeptides and uses thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102015760A (zh) * | 2008-01-28 | 2011-04-13 | 诺瓦提斯公司 | 使用klotho-fgf融合多肽的方法和组合物 |
| WO2011092234A1 (en) * | 2010-01-29 | 2011-08-04 | Novartis Ag | Methods and compositions using fgf23 fusion polypeptides |
| WO2013027191A1 (en) * | 2011-08-25 | 2013-02-28 | Novartis Ag | Methods and compositions using fgf23 fusion polypeptides |
Family Cites Families (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL71691A (en) | 1984-04-27 | 1991-04-15 | Yeda Res & Dev | Production of interferon-ypsilon |
| US5128326A (en) | 1984-12-06 | 1992-07-07 | Biomatrix, Inc. | Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same |
| US5266561A (en) | 1988-01-11 | 1993-11-30 | Amylin Pharmaceuticals, Inc. | Treatment of type 2 diabetes mellitus |
| SE509359C2 (sv) * | 1989-08-01 | 1999-01-18 | Cemu Bioteknik Ab | Användning av stabiliserade protein- eller peptidkonjugat för framställning av ett läkemedel |
| EP0550436A1 (en) | 1989-11-06 | 1993-07-14 | Alkermes Controlled Therapeutics, Inc. | Protein microspheres and methods of using them |
| JPH06507782A (ja) | 1990-06-15 | 1994-09-08 | サイオス ノバ インコーポレイテッド | アルツハイマー病のアミロイド形成開症状を示すヒト以外の組換え哺乳動物 |
| US5408038A (en) | 1991-10-09 | 1995-04-18 | The Scripps Research Institute | Nonnatural apolipoprotein B-100 peptides and apolipoprotein B-100-apolipoprotein A-I fusion peptides |
| FR2686899B1 (fr) * | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| US5912015A (en) | 1992-03-12 | 1999-06-15 | Alkermes Controlled Therapeutics, Inc. | Modulated release from biocompatible polymers |
| US5420112A (en) | 1992-06-12 | 1995-05-30 | Lewis; Michael E. | Prevention and treatment of peripheral neuropathy |
| US5541094A (en) | 1992-09-25 | 1996-07-30 | E. I. Du Pont De Nemours And Company | Glyoxylic acid/aminomethylphosphonic acid mixtures prepared using a microbial transformant |
| US5877399A (en) | 1994-01-27 | 1999-03-02 | Johns Hopkins University | Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease |
| US6187992B1 (en) | 1994-12-05 | 2001-02-13 | Merck & Co., Inc. | Transgenic mouse having a disrupted amyloid precursor protein gene |
| WO1997007788A2 (en) | 1995-08-31 | 1997-03-06 | Alkermes Controlled Therapeutics, Inc. | Composition for sustained release of an agent |
| US6194177B1 (en) | 1996-02-20 | 2001-02-27 | Applied Research Systems Ars Holding N.V. | DNA encoding a hybrid heterodimeric protein |
| JP3258027B2 (ja) | 1996-03-15 | 2002-02-18 | サマーセット・ファーマシューティカルズ・インコーポレイテッド | セレジリン投与による末梢ニューロパシーの予防および治療方法 |
| US6358752B1 (en) | 1996-09-27 | 2002-03-19 | Cornell Research Foundation, Inc. | Liposome-enhanced test device and method |
| EP0945506B1 (en) | 1996-12-26 | 2007-02-28 | Kyowa Hakko Kogyo Co., Ltd. | Proteine avec une activite de suppression du vieillissement |
| US6127598A (en) | 1997-07-25 | 2000-10-03 | The Regents Of The University Of California | NKX-2.2 and NKX-6.1 transgenic mouse models for diabetes, depression, and obesity |
| US5989463A (en) | 1997-09-24 | 1999-11-23 | Alkermes Controlled Therapeutics, Inc. | Methods for fabricating polymer-based controlled release devices |
| SE512663C2 (sv) | 1997-10-23 | 2000-04-17 | Biogram Ab | Inkapslingsförfarande för aktiv substans i en bionedbrytbar polymer |
| WO1999051773A1 (en) | 1998-04-03 | 1999-10-14 | Phylos, Inc. | Addressable protein arrays |
| US7060479B2 (en) | 1999-12-08 | 2006-06-13 | Serono Genetics Institute, S.A. | Full-length human cDNAs encoding potentially secreted proteins |
| US20030055231A1 (en) | 1998-10-28 | 2003-03-20 | Jian Ni | 12 human secreted proteins |
| JP4585693B2 (ja) | 1999-04-22 | 2010-11-24 | リポサイエンス、インコーポレイテッド | Ii型糖尿病を発現する危険性のnmrによる決定方法 |
| WO2001001251A1 (en) | 1999-06-30 | 2001-01-04 | Microsoft Corporation | Restoration of a computer to a previous state |
| US6569832B1 (en) | 1999-11-12 | 2003-05-27 | Novo Nordisk A/S | Inhibition of beta cell degeneration |
| US6716626B1 (en) | 1999-11-18 | 2004-04-06 | Chiron Corporation | Human FGF-21 nucleic acids |
| US6406853B1 (en) | 1999-12-23 | 2002-06-18 | The Regents Of The University Of California | Interventions to mimic the effects of calorie restriction |
| CA2398603A1 (en) | 2000-02-15 | 2001-08-23 | Amgen, Inc. | Fibroblast growth factor-23 molecules and uses thereof |
| US20060160181A1 (en) | 2000-02-15 | 2006-07-20 | Amgen Inc. | Fibroblast Growth Factor-23 molecules and uses thereof |
| JP2006238894A (ja) | 2000-02-15 | 2006-09-14 | Amgen Inc | 線維芽細胞成長因子−23分子およびその使用 |
| JP2003531583A (ja) | 2000-03-08 | 2003-10-28 | カイロン コーポレイション | ヒトfgf−23遺伝子および遺伝子発現産物 |
| AU2001273323B2 (en) | 2000-07-19 | 2005-11-10 | Advanced Research & Technology Institute | Novel fibroblast growth factor (FGF23) and methods for use |
| CA2436661A1 (en) | 2001-01-30 | 2002-08-08 | Regeneron Pharmaceuticals, Inc. | Novel nucleic acid and polypeptide molecules |
| US7588757B2 (en) | 2001-03-14 | 2009-09-15 | Genzyme Corporation | Methods of treating Parkinson's disease using recombinant adeno-associated virus virions |
| AU2002302581A1 (en) | 2001-04-26 | 2002-11-11 | Geneprot, Inc. | Human fibroblast growth factor-related compositions |
| EP1327443A1 (en) | 2001-12-21 | 2003-07-16 | Kyowa Hakko Kogyo Co., Ltd. | Therapeutic or preventing agent for the diseases caused by a decrease in the expression level of the klotho protein |
| US20050004348A1 (en) | 2002-12-23 | 2005-01-06 | Miyamoto Ken-Ichi | Novel type II Na/Pi cotransporters and type II Na/Pi cotransporter expression regulatory factors |
| JP2007531707A (ja) | 2003-10-15 | 2007-11-08 | ピーディーエル バイオファーマ, インコーポレイテッド | IGの重鎖定常領域の位置250、314および/または428の変異誘発によるFc融合タンパク質血清半減期の改変 |
| US20170233446A1 (en) | 2008-01-28 | 2017-08-17 | Novartis Ag | Methods and compositions using klotho-fgf fusion polypeptides |
| US20110015345A1 (en) | 2008-03-19 | 2011-01-20 | Ambrx, Inc. | Modified FGF-23 Polypeptides and Their Uses |
| KR101651703B1 (ko) | 2008-10-10 | 2016-08-26 | 암젠 인크 | Fgf21 돌연변이체 및 이의 용도 |
| US8461111B2 (en) | 2009-05-20 | 2013-06-11 | Florida State University Research Foundation | Fibroblast growth factor mutants having improved functional half-life and methods of their use |
| US20110195077A1 (en) | 2010-01-29 | 2011-08-11 | Novartis Ag | Methods and compositions using fgf23 fusion ppolypeptides |
| CH707030B1 (de) | 2011-10-21 | 2015-03-13 | Abbvie Inc | Kombinationsbehandlung von DAAs zur Verwendung in der Behandlung von HCV |
| US10588980B2 (en) | 2014-06-23 | 2020-03-17 | Novartis Ag | Fatty acids and their use in conjugation to biomolecules |
-
2015
- 2015-12-02 EA EA201791238A patent/EA201791238A1/ru unknown
- 2015-12-02 BR BR112017011398A patent/BR112017011398A2/pt not_active IP Right Cessation
- 2015-12-02 KR KR1020177017910A patent/KR20170084332A/ko not_active Ceased
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- 2015-12-02 EP EP15816527.4A patent/EP3227319B1/en not_active Not-in-force
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- 2015-12-02 CA CA2969307A patent/CA2969307A1/en not_active Abandoned
- 2015-12-02 WO PCT/IB2015/059294 patent/WO2016088059A1/en not_active Ceased
- 2015-12-02 MX MX2017007303A patent/MX2017007303A/es unknown
- 2015-12-02 JP JP2017529778A patent/JP2017537926A/ja active Pending
- 2015-12-02 US US15/532,634 patent/US10654909B2/en active Active
- 2015-12-03 TW TW104140597A patent/TW201628641A/zh unknown
-
2017
- 2017-06-05 MX MX2021000030A patent/MX2021000030A/es unknown
-
2020
- 2020-02-26 US US16/802,511 patent/US20200362015A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102015760A (zh) * | 2008-01-28 | 2011-04-13 | 诺瓦提斯公司 | 使用klotho-fgf融合多肽的方法和组合物 |
| WO2011092234A1 (en) * | 2010-01-29 | 2011-08-04 | Novartis Ag | Methods and compositions using fgf23 fusion polypeptides |
| WO2013027191A1 (en) * | 2011-08-25 | 2013-02-28 | Novartis Ag | Methods and compositions using fgf23 fusion polypeptides |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112695049A (zh) * | 2020-08-20 | 2021-04-23 | 山东兴瑞生物科技有限公司 | 修饰间充质干细胞的融合基因、质粒、修饰得到干细胞及制备方法 |
| CN112915193A (zh) * | 2021-03-05 | 2021-06-08 | 南方医科大学南方医院 | Kp-1在制备治疗慢性肺病的药物中的用途 |
| CN112915192A (zh) * | 2021-03-05 | 2021-06-08 | 南方医科大学南方医院 | Kp-1在制备治疗慢性肝病的药物中的用途 |
| CN112915193B (zh) * | 2021-03-05 | 2022-09-13 | 南方医科大学南方医院 | Kp-1在制备治疗慢性肺病的药物中的用途 |
| CN112915192B (zh) * | 2021-03-05 | 2022-10-25 | 南方医科大学南方医院 | Kp-1在制备治疗慢性肝病的药物中的用途 |
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| CA2969307A1 (en) | 2016-06-09 |
| KR20170084332A (ko) | 2017-07-19 |
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| AU2015356643B2 (en) | 2019-01-24 |
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| AU2015356643A1 (en) | 2017-06-22 |
| BR112017011398A2 (pt) | 2018-04-03 |
| US20200362015A1 (en) | 2020-11-19 |
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