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1. 发明申请

WO2008060557A2 EFFICIENT NUCLEAR DELIVERY OF ANTISENSE OLIGONUCLEOTIDES 审中-公开
标题翻译：反式寡核苷酸的有效核输送
公开(公告)号：WO2008060557A2
公开(公告)日：2008-05-22
申请号：PCT/US2007/023894
申请日：2007-11-14
申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA , TEWARI, Manorama , KIM, Younghoon , DISCHER, Dennis
发明人： TEWARI, Manorama , KIM, Younghoon , DISCHER, Dennis
IPC分类号： A61K48/00
CPC分类号： C12N15/88 , A61K9/1273 , A61K48/00 , C12N15/111 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2320/32 , C12N2310/3521
摘要： Provided is a biocompatible polyethylene oxide (PEO)-based polymersome system for the delivery of oligonucleotides, including antisense RNA, siRNA and RNAi, to a cell or tissue target, and method of use therefore, wherein the method comprises encapsulating the oligonucleotide in a biodegradable neutral, nano-transforming polymersome delivery vehicle and delivering the encapsulated oligonucleotide to the cell or tissue target in vitro or in vivo., particularly for treating a disease, such cancer or cellular hyperproliferation. The degradable polymersome, and the oligonucleotides stably encapsulated therein are taken up passively by cells and delivered into endolysosomes, wherein the polymersomes decompose at a known rate at a known pH, thereby releasing encapsulated oligonucleotides in a controlled manner within the cell and facilitating delivery of antisense oligonucleotide or siRNA or RNAi into the nucleus of the cell target.
摘要翻译：提供用于将寡核苷酸（包括反义RNA，siRNA和RNAi）递送至细胞或组织靶标的生物相容性聚环氧乙烷（PEO）基聚合物体系统及其使用方法，其中所述方法包括将寡核苷酸包封在可生物降解的中性纳米转化聚合物体递送载体中，并将包封的寡核苷酸体外或体内递送至细胞或组织靶标，特别是用于治疗疾病如癌症或细胞过度增殖。可降解聚合物囊泡和其中稳定包封的寡核苷酸被细胞被动吸收并递送到内溶酶体中，其中聚合物囊泡以已知的速率在已知pH下分解，从而以受控方式在细胞内释放包封的寡核苷酸并促进反义寡核苷酸或siRNA或RNAi进入细胞靶标的细胞核。

2. 发明申请

WO2007075502A9 THERMO-RESPONSIVE BLOCK CO-POLYMERS, AND USE THEREOF 审中-公开
标题翻译：热响应嵌段共聚物及其用途
公开(公告)号：WO2007075502A9
公开(公告)日：2007-08-16
申请号：PCT/US2006048103
申请日：2006-12-15
申请人： UNIV PENNSYLVANIA , QIN SHUHUI , YANG SHU , DISCHER DENNIS , GENG YAN
发明人： QIN SHUHUI , YANG SHU , DISCHER DENNIS , GENG YAN
IPC分类号： A61K9/50
CPC分类号： A61K9/1273 , A61K47/34 , C08F293/005 , C08F2438/03
摘要： Provided are thermo-responsive polymersomes, which display cold-controlled encapsulation near the physiological temperatures, and have a PDI less than 1.2. Morphology of the thermo- responsive polymersomes is a function of the weight fraction of the hydrophilic block in the block copolymer and the number average molecular weight (Mn) of the block copolymer. When the lower critical solution temperature (LCST) is at, or slightly above physiological temperature, the thermo-responsive block displays hydrophobic properties, such that the block copolymer self-assembles in aqueous solution to form a polymersome with the thermo- responsive block occupying the core of the polymersome and the hydrophilic block occupying the corona of the polymersome. Below the LCST, the thermo-responsive block displays hydrophilic properties, such that the polymersome dissociates, providing fast release of an active agent encapsulated therein.
摘要翻译：提供的是热响应性聚合物囊泡，其显示接近生理温度的冷控制囊封，并且具有小于1.2的PDI。热敏聚合物囊泡的形态是嵌段共聚物中亲水嵌段的重量分数和嵌段共聚物的数均分子量（Mn）的函数。当较低临界溶解温度（LCST）处于或略高于生理温度时，热响应性嵌段显示疏水性，使得嵌段共聚物在水溶液中自组装形成聚合物体，热响应性嵌段占据聚合物囊泡的核心和占据聚合物囊泡的冠部的亲水嵌段。在LCST以下，热响应性嵌段显示出亲水性，使得聚合物囊泡解离，从而提供封装在其中的活性剂的快速释放。

3. 发明申请

WO2006071769A1 CONTROLLED RELEASE FROM BLOCK CO-POLYMER WORM MICELLES 审中-公开
标题翻译：从块状聚合物麦克风控制释放
公开(公告)号：WO2006071769A1
公开(公告)日：2006-07-06
申请号：PCT/US2005/046770
申请日：2005-12-28
申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA , DISCHER, Dennis , GENG, Yan
发明人： DISCHER, Dennis , GENG, Yan
IPC分类号： A61K9/10
CPC分类号： A61K9/1075 , A61K31/56
摘要： Provided is a method of controlling the release of at least one encapsulated active agent from a worm-like micelle, wherein each worm-like micelle comprises one or more amphiphilic block copolymers that self assemble in aqueous solution, without organic solvent or post assembly polymerization; wherein at least one of said amphiphilic molecules is a hydrophilic block copolymer and at least one of said amphiphilic molecules is a hydrophobic block copolymer which is hydrolyticaly unstable in the pH range of about 5 to about 7. The loaded worm-like micelles of the present invention are particularly suited for the stable and controlled transport, delivery and storage of materials, either in vivo or in vitro .
摘要翻译：本发明提供一种控制从蠕虫状胶束释放至少一种封装的活性剂的方法，其中每个蠕虫状胶束包含一种或多种在水溶液中自组装而无有机溶剂或后装配聚合的两亲性嵌段共聚物; 其中所述两亲分子中的至少一个是亲水性嵌段共聚物，并且所述两亲分子中的至少一个是在约5至约7的pH范围内水解不稳定的疏水性嵌段共聚物。本发明的负载的蠕虫状胶束本发明特别适用于体内或体外的材料的稳定和受控的运输，递送和储存。

4. 发明申请

WO2008060557A3 EFFICIENT NUCLEAR DELIVERY OF ANTISENSE OLIGONUCLEOTIDES 审中-公开
标题翻译：有效的核交付反义寡核苷酸
公开(公告)号：WO2008060557A3
公开(公告)日：2008-11-27
申请号：PCT/US2007023894
申请日：2007-11-14
申请人： UNIV PENNSYLVANIA , TEWARI MANORAMA , KIM YOUNGHOON , DISCHER DENNIS
发明人： TEWARI MANORAMA , KIM YOUNGHOON , DISCHER DENNIS
IPC分类号： A61K48/00
CPC分类号： C12N15/88 , A61K9/1273 , A61K48/00 , C12N15/111 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2320/32 , C12N2310/3521
摘要： Provided is a biocompatible polyethylene oxide (PEO)-based polymersome system for the delivery of oligonucleotides, including antisense RNA, siRNA and RNAi, to a cell or tissue target, and method of use therefore, wherein the method comprises encapsulating the oligonucleotide in a biodegradable neutral, nano-transforming polymersome delivery vehicle and delivering the encapsulated oligonucleotide to the cell or tissue target in vitro or in vivo., particularly for treating a disease, such cancer or cellular hyperproliferation. The degradable polymersome, and the oligonucleotides stably encapsulated therein are taken up passively by cells and delivered into endolysosomes, wherein the polymersomes decompose at a known rate at a known pH, thereby releasing encapsulated oligonucleotides in a controlled manner within the cell and facilitating delivery of antisense oligonucleotide or siRNA or RNAi into the nucleus of the cell target.
摘要翻译：提供了一种用于向细胞或组织靶标递送包括反义RNA，siRNA和RNAi的寡核苷酸的生物相容性聚环氧乙烷（PEO）基聚合物体系，以及因此使用的方法，其中所述方法包括将寡核苷酸包封在可生物降解中性的纳米转化聚合物组递送载体，并将包封的寡核苷酸在体外或体内递送至细胞或组织靶，特别是用于治疗疾病，例如癌症或细胞过度增殖。稳定包被的可降解聚合物和寡核苷酸被细胞无源地吸收并递送到内溶体中，其中聚合物囊泡以已知的速率以已知的pH分解，从而以受控的方式在细胞内释放包封的寡核苷酸并促进反义寡核苷酸或siRNA或RNAi进入细胞靶的细胞核。

5. 发明申请

WO2012109267A3 NOVEL PEPTIDES AND METHODS USING SAME 审中-公开
标题翻译：新颖的肽和使用它的方法
公开(公告)号：WO2012109267A3
公开(公告)日：2012-10-11
申请号：PCT/US2012024174
申请日：2012-02-07
申请人： UNIV PENNSYLVANIA , DISCHER DENNIS E , NUNEZ PIA L RODRIGUEZ , PANTANO DIEGO A
发明人： DISCHER DENNIS E , NUNEZ PIA L RODRIGUEZ , PANTANO DIEGO A
IPC分类号： C07H21/04 , C12N5/00 , C12N5/02
CPC分类号： A61K47/48246 , A61K38/00 , A61K38/177 , C07K7/06 , C07K7/08 , C07K14/001 , C07K14/70596
摘要： Disclosed is a method of modulating the phagocytic activity of at least one phagocyte in a subject. A method of providing a composition resistant to phagocytosis to a subject is further disclosed. A method of treating, ameliorating or preventing an inflammatory disease in a subject is also disclosed.
摘要翻译：公开了调节受试者中至少一种吞噬细胞的吞噬活性的方法。进一步公开了向受试者提供抗吞噬作用的组合物的方法。还公开了治疗，改善或预防受试者的炎性疾病的方法。

6. 发明申请

WO2007075502A3 THERMO-RESPONSIVE BLOCK CO-POLYMERS, AND USE THEREOF 审中-公开
标题翻译：热反应块共聚物及其用途
公开(公告)号：WO2007075502A3
公开(公告)日：2008-11-20
申请号：PCT/US2006048103
申请日：2006-12-15
申请人： UNIV PENNSYLVANIA , QIN SHUHUI , YANG SHU , DISCHER DENNIS , GENG YAN
发明人： QIN SHUHUI , YANG SHU , DISCHER DENNIS , GENG YAN
IPC分类号： C04B35/56
CPC分类号： A61K9/1273 , A61K47/34 , C08F293/005 , C08F2438/03
摘要： Provided are thermo-responsive polymersomes, which display cold-controlled encapsulation near the physiological temperatures, and have a PDI less than 1.2. Morphology of the thermo- responsive polymersomes is a function of the weight fraction of the hydrophilic block in the block copolymer and the number average molecular weight (Mn) of the block copolymer. When the lower critical solution temperature (LCST) is at, or slightly above physiological temperature, the thermo-responsive block displays hydrophobic properties, such that the block copolymer self-assembles in aqueous solution to form a polymersome with the thermo- responsive block occupying the core of the polymersome and the hydrophilic block occupying the corona of the polymersome. Below the LCST, the thermo-responsive block displays hydrophilic properties, such that the polymersome dissociates, providing fast release of an active agent encapsulated therein.
摘要翻译：提供的是热响应聚合物囊泡，其在生理温度附近显示冷控制的包封，并且PDI小于1.2。热响应性聚合物的形态是嵌段共聚物中亲水嵌段的重量分数和嵌段共聚物的数均分子量（Mn）的函数。当低临界溶解温度（LCST）处于或略高于生理温度时，热响应性嵌段显示疏水性质，使得嵌段共聚物在水溶液中自组装形成聚合物体，其中热响应性嵌段占据聚合物的核心和占聚合物的电晕的亲水性嵌段。在LCST之下，热响应块显示出亲水性质，使得聚合物组分解，提供封装在其中的活性剂的快速释放。

7. 发明申请

WO2012109267A2 NOVEL PEPTIDES AND METHODS USING SAME 审中-公开
标题翻译：新颖的肽和使用它的方法
公开(公告)号：WO2012109267A2
公开(公告)日：2012-08-16
申请号：PCT/US2012/024174
申请日：2012-02-07
申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA , DISCHER, Dennis, E. , NUNEZ, Pia, L., Rodriguez , PANTANO, Diego, A.
发明人： DISCHER, Dennis, E. , NUNEZ, Pia, L., Rodriguez , PANTANO, Diego, A.
IPC分类号： A61K38/10
CPC分类号： A61K47/48246 , A61K38/00 , A61K38/177 , C07K7/06 , C07K7/08 , C07K14/001 , C07K14/70596
摘要： The present invention includes a method of modulating the phagocytic activity of at least one phagocyte in a subject. The present invention also includes a method of providing a composition resistant to phagocytosis to a subject. The present invention further includes a method of treating, ameliorating or preventing an inflammatory disease in a subject.
摘要翻译：本发明包括调节受试者中至少一种吞噬细胞的吞噬活性的方法。本发明还包括向受试者提供抗吞噬作用的组合物的方法。本发明还包括治疗，改善或预防受试者的炎性疾病的方法。

8. 发明申请

WO2010118335A1 LIGAND-SPECIFIC INHIBITION OF ATTACHMENT OF IMMUNE CELLS TO IMPLANTABLE BIOMATERIALS 审中-公开
标题翻译：将免疫细胞连接到可植入生物材料的特异性抑制
公开(公告)号：WO2010118335A1
公开(公告)日：2010-10-14
申请号：PCT/US2010/030558
申请日：2010-04-09
申请人： THE CHILDREN'S HOSPITAL OF PHILADELPHIA , THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA , STACHELEK, Stanley, J. , DISCHER, Dennis , LEVY, Robert, J. , UEDA, Masako , TSAI, Richard
发明人： STACHELEK, Stanley, J. , DISCHER, Dennis , LEVY, Robert, J. , UEDA, Masako , TSAI, Richard
IPC分类号： A61L33/00 , B05D3/00
CPC分类号： A61L31/10 , A61L27/34 , A61L27/54 , A61L31/022 , A61L31/048 , A61L33/128 , A61L2300/252 , A61L2300/432 , A61L2300/606 , A61L2300/802 , C08L89/00
摘要： Methods for protecting biomaterϊals comprise attaching CD47 or Ig domain thereof to the surface of the biomaterial, thereby inhibiting or reducing immune cell attachment and/or immune cell-mediated damage to the biomaterial. Also provided are kits for practicing these methods and the protected biomaterials.
摘要翻译：用于保护生物体的方法包括将CD47或Ig结构域连接到生物材料的表面，从而抑制或减少对生物材料的免疫细胞附着和/或免疫细胞介导的损伤。还提供了用于实施这些方法和受保护的生物材料的试剂盒。

9. 发明申请

WO2008133654A2 METHOD OF TREATING A TUMOR AND BIODISTRIBUTION OF A DRUG DELIVERED BY WORM-LIKE FILOMICELLES 审中-公开
标题翻译：治疗肿瘤的方法和由类似细胞膜递送的药物的生物分布
公开(公告)号：WO2008133654A2
公开(公告)日：2008-11-06
申请号：PCT/US2007023777
申请日：2007-11-14
申请人： UNIV PENNSYLVANIA , DALHAIMER PAUL , DISCHER DENNIS E , CAI SHENSHEN , GENG YAN
发明人： DALHAIMER PAUL , DISCHER DENNIS E , CAI SHENSHEN , GENG YAN
IPC分类号： A61K9/51
CPC分类号： A61K9/1075 , A61K9/0024 , A61K9/1273 , A61K9/1274 , A61K9/5146 , A61K31/337
摘要： Provided are filomicelle nanocarrier systems for the controlled transport and bioselective delivery of encapsulatable, cytotoxic active agents contained therein, particularly anticancer agents. Further provided are methods for controlling destabilization of the filomicelle membrane and the resulting hydrolysis-triggered, controlled release of the active agent(s) encapsulated therein by controlling the blend ratio (mol%) of hydrolysable PEO-block copolymer of the hydrophilic component(s) and of the more hydrophobic PEO-block copolymer component(s), wherein bioselective release of the encapsulated cytotoxic agents is distributed intracellularly, and wherein lowered dosage of the drug was delivered to the non-tumor organs. Thus, the filomicelle system offers enhanced tumor-selective biodistribution of a drug, and a reduced toxicity of the encapsulated drug to other organs.
摘要翻译：提供了用于受控运输和生物选择性递送其中包含的可密封的细胞毒性活性剂，特别是抗癌剂的微粒纳米载体系统。进一步提供了通过控制亲水组分（s）的可水解PEO嵌段共聚物的共混比（mol％）来控制薄膜的去稳定化和所包含的活性剂的水解触发的控制释放的方法）和更疏水的PEO-嵌段共聚物组分，其中包封的细胞毒性剂的生物选择性释放在细胞内分布，并且其中药物的较低剂量被递送至非肿瘤器官。因此，filomicelle系统提供药物的增强的肿瘤选择性生物分布，以及包封的药物对其他器官的毒性降低。

10. 发明申请

WO2007075502A2 THERMO-RESPONSIVE BLOCK CO-POLYMERS, AND USE THEREOF 审中-公开
标题翻译：热反应块共聚物及其用途
公开(公告)号：WO2007075502A2
公开(公告)日：2007-07-05
申请号：PCT/US2006/048103
申请日：2006-12-15
申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA , QIN, Shuhui , YANG, Shu , DISCHER, Dennis , GENG, Yan
发明人： QIN, Shuhui , YANG, Shu , DISCHER, Dennis , GENG, Yan
IPC分类号： A61K9/50
CPC分类号： A61K9/1273 , A61K47/34 , C08F293/005 , C08F2438/03
摘要： Provided are thermo-responsive polymersomes, which display cold-controlled encapsulation near the physiological temperatures, and have a PDI less than 1.2. Morphology of the thermo- responsive polymersomes is a function of the weight fraction of the hydrophilic block in the block copolymer and the number average molecular weight (Mn) of the block copolymer. When the lower critical solution temperature (LCST) is at, or slightly above physiological temperature, the thermo-responsive block displays hydrophobic properties, such that the block copolymer self-assembles in aqueous solution to form a polymersome with the thermo- responsive block occupying the core of the polymersome and the hydrophilic block occupying the corona of the polymersome. Below the LCST, the thermo-responsive block displays hydrophilic properties, such that the polymersome dissociates, providing fast release of an active agent encapsulated therein.
摘要翻译：提供的是热响应聚合物囊泡，其在生理温度附近显示冷控制的包封，并且PDI小于1.2。热响应性聚合物的形态是嵌段共聚物中亲水嵌段的重量分数和嵌段共聚物的数均分子量（Mn）的函数。当低临界溶解温度（LCST）处于或略高于生理温度时，热响应性嵌段显示疏水性质，使得嵌段共聚物在水溶液中自组装形成聚合物体，其中热响应性嵌段占据聚合物的核心和占聚合物的电晕的亲水性嵌段。在LCST之下，热响应块显示出亲水性质，使得聚合物组分解，提供封装在其中的活性剂的快速释放。

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