CN110981941A - 生物模拟肽和生物可降解的递送平台 - Google Patents
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| US9802984B2 (en) * | 2013-06-07 | 2017-10-31 | The Johns Hopkins University | Biomimetic peptide and biodegradable delivery platform for the treatment of angiogenesis- and lymphangiogenesis-dependent diseases |
| US20170216363A1 (en) | 2014-08-07 | 2017-08-03 | The Johns Hopkins University | Nanoparticle modification of human adipose-derived mesenchymal stem cells for treating brain cancer and other neurological diseases |
| KR101748120B1 (ko) * | 2015-07-13 | 2017-06-16 | 서울대학교산학협력단 | 나노입자-유리체 기반 단백질 복합체를 유효성분으로 포함하는 혈관신생억제용 조성물 및 이의 용도 |
| MX2018006194A (es) * | 2015-11-19 | 2018-12-06 | Asclepix Therapeutics Llc | Peptidos con propiedades antiangiogenicas, antilinfangiogenicas y antiedemicas y formulaciones de nanoparticulas. |
| MX2019003895A (es) | 2016-10-04 | 2019-10-07 | Asclepix Therapeutics Inc | Compuestos y metodos para activar la señalizacion tie2. |
| CA3063140A1 (en) * | 2017-05-08 | 2018-11-15 | Asclepix Therapeutics, Inc. | Biodegradable microparticles for sustained delivery of anti-angiogenic peptide |
| US11674959B2 (en) | 2017-08-03 | 2023-06-13 | The Johns Hopkins University | Methods for identifying and preparing pharmaceutical agents for activating Tie1 and/or Tie2 receptors |
| US12059476B2 (en) | 2017-10-10 | 2024-08-13 | The Johns Hopkins University | Biodegradable biomimetic particles |
| US11697804B2 (en) | 2018-10-01 | 2023-07-11 | The Johns Hopkins University | Transcriptionally targeted and CpG-free plasmid for theranostic gene therapy |
| CN113507925A (zh) * | 2019-02-06 | 2021-10-15 | 北卡罗来纳大学教堂山分校 | 用于抑制术后粘连的组合物和方法 |
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| US12605463B2 (en) | 2019-04-12 | 2026-04-21 | The Johns Hopkins University | Tolerogenic artificial antigen-presenting cells |
| CN113144213B (zh) * | 2021-03-23 | 2023-04-07 | 西安交通大学医学院第一附属医院 | 一种多级pH响应基因-药物共递送的纳米药物、制备方法及其应用 |
| WO2024044745A2 (en) * | 2022-08-26 | 2024-02-29 | Asclepix Therapeutics, Inc. | Formulations for intraocular delivery of peptides derived from type iv collagen |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20110206760A1 (en) * | 2008-07-21 | 2011-08-25 | Compugen Ltd. | Angiopoietin derived peptides |
| US20120114759A1 (en) * | 2009-05-15 | 2012-05-10 | The Johns Hopkins University | Peptide/particle delivery systems |
| US20120232012A1 (en) * | 2005-09-12 | 2012-09-13 | The Johns Hopkins University | Compositions having antiangiogenic activity and uses thereof |
| US20120270770A1 (en) * | 2010-08-03 | 2012-10-25 | Jesse Michael Jaynes | Anti-angiogenic peptides and their uses |
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| CA2636424A1 (en) * | 2006-01-09 | 2007-10-25 | The Regents Of The University Of California | Immunostimulatory combinations of tnfrsf, tlr, nlr, rhr, purinergic receptor, and cytokine receptor agonists for vaccines and tumor immunotherapy |
| ITMI20060625A1 (it) * | 2006-03-31 | 2007-10-01 | Istituto Naz Per La Ricerca | Peptide antiangiogenico e suoi impieghi terapeutici |
| CA2666709A1 (en) * | 2006-11-10 | 2008-05-29 | Genentech, Inc. | Method for treating age-related macular degeneration |
| WO2008085828A2 (en) | 2007-01-03 | 2008-07-17 | The Johns Hopkins University | Peptide modulators of angiogenesis and use thereof |
| CN102083423A (zh) * | 2008-05-06 | 2011-06-01 | 葛兰素集团有限公司 | 生物活性剂的囊封方法 |
| US12371522B2 (en) | 2011-10-12 | 2025-07-29 | The Johns Hopkins University | Bioreducible poly (beta-amino ester)s for siRNA delivery |
| CN102791294A (zh) * | 2009-12-16 | 2012-11-21 | 布里格姆妇女医院股份有限公司 | 用于多种药物递送的粒子 |
| US20120192339A1 (en) | 2010-07-28 | 2012-08-02 | Honeywell International Inc. | Flexible Body Armor Vest with Breast Plate |
| EP2649095B1 (en) * | 2010-12-10 | 2021-10-06 | Aleksander S. Popel | Mimetic peptides derived from collagen type iv and their use for treating angiogenesis- and lymphangiogenesis- dependent diseases |
| JP5747312B2 (ja) | 2011-02-24 | 2015-07-15 | コニカミノルタ株式会社 | 活性光線硬化型インクジェットインク及び画像形成方法 |
| US20150272900A1 (en) | 2012-10-26 | 2015-10-01 | The Johns Hopkins University | Layer-By-Layer Approach to Co-Deliver DNA and siRNA via AuNPs: A Potential Platform for Modifying Release Kinetics |
| US9802984B2 (en) * | 2013-06-07 | 2017-10-31 | The Johns Hopkins University | Biomimetic peptide and biodegradable delivery platform for the treatment of angiogenesis- and lymphangiogenesis-dependent diseases |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120232012A1 (en) * | 2005-09-12 | 2012-09-13 | The Johns Hopkins University | Compositions having antiangiogenic activity and uses thereof |
| US20110206760A1 (en) * | 2008-07-21 | 2011-08-25 | Compugen Ltd. | Angiopoietin derived peptides |
| US20120114759A1 (en) * | 2009-05-15 | 2012-05-10 | The Johns Hopkins University | Peptide/particle delivery systems |
| US20120270770A1 (en) * | 2010-08-03 | 2012-10-25 | Jesse Michael Jaynes | Anti-angiogenic peptides and their uses |
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