公开(公告)号：US11613590B2

公开(公告)日：2023-03-28

申请号：US16631418

申请日：2018-07-17

申请人： Nucleus Therapeutics Pty. Ltd. ,  Yale University

发明人： James Campbell ,  Valentina Dubljevic ,  James Hansen ,  Zahra Rattray ,  Jiangbing Zhou

IPC分类号： C07K16/00 ,  A61K39/395 ,  C07K16/44 ,  A61P35/00 ,  A61K39/00 ,  A61K31/502

摘要： The present disclosure relates to cell penetrating anti-DNA binding proteins. Compositions comprising these binding proteins may be may be useful for delivering agents to cells and treating diseases such as cancer.

公开(公告)号：US11590242B2

公开(公告)日：2023-02-28

申请号：US16310372

申请日：2017-06-15

申请人： Yale University

发明人： Jiangbing Zhou ,  James Hansen

IPC分类号： A61K47/69 ,  A61P35/00 ,  A61K47/68 ,  A61K31/502 ,  A61K31/704

摘要： DNA-targeted nanocarriers for encapsulating an active agent and delivering it to extracellular DNA are provided. The nanocarriers, for example, polymeric particles, liposomes, and multilamellar vesicles have targeting moiety that targets DNA conjugated thereto. The targeting moiety that targets DNA is typically an antibody, or variant, fragment, or fusion protein derived therefrom that binds to DNA or nucleosomes. The targeting moiety can be a circulating autoantibody that binds DNA such as those commonly found in patients with SLE. In some embodiments, the targeting moiety is antibody 3E10 or a variant, fragment, or fusion protein derived therefrom. Pharmaceutical compositions, methods of use, and dosage regimens are also provided.

公开(公告)号：US20190247515A1

公开(公告)日：2019-08-15

申请号：US16310372

申请日：2017-06-15

申请人： Yale University

发明人： Jiangbing Zhou ,  James Hansen

IPC分类号： A61K47/69 ,  A61K31/502 ,  A61P35/00 ,  A61K47/68 ,  A61K31/704

CPC分类号： A61K47/6937 ,  A61K31/502 ,  A61K31/704 ,  A61K47/6843 ,  A61K47/6935 ,  A61P35/00

摘要： DNA-targeted nanocarriers for encapsulating an active agent and delivering it to extracellular DNA are provided. The nanocarriers, for example, polymeric particles, liposomes, and multilamellar vesicles have targeting moiety that targets DNA conjugated thereto. The targeting moiety that targets DNA is typically an antibody, or variant, fragment, or fusion protein derived therefrom that binds to DNA or nucleosomes. The targeting moiety can be a circulating autoantibody that binds DNA such as those commonly found in patients with SLE. In some embodiments, the targeting moiety is antibody 3E10 or a variant, fragment, or fusion protein derived therefrom. Pharmaceutical compositions, methods of use, and dosage regimens are also provided.

公开(公告)号：US09272043B2

公开(公告)日：2016-03-01

申请号：US14293733

申请日：2014-06-02

申请人： Yale University

发明人： W. Mark Saltzman ,  Zhaozhong Jiang ,  Jiangbing Zhou ,  Jie Liu

IPC分类号： A61K9/50 ,  A61K9/14 ,  C08G63/685 ,  C12N15/87 ,  A61K47/34 ,  A61K31/7088 ,  A61K9/107

CPC分类号： C08G63/6852 ,  A61K9/1075 ,  A61K31/337 ,  A61K31/7088 ,  A61K31/711 ,  A61K38/1774 ,  A61K38/1793 ,  A61K38/44 ,  A61K47/34 ,  A61K48/0041 ,  C08G63/88 ,  C12N15/87 ,  C12N15/88 ,  C12P13/001 ,  C12Y113/12007

摘要： Poly(amine-co-ester) polymers, methods of forming active agent-load nanoparticles therefrom, and methods of using the nanoparticles for drug delivery are disclosed. The nanoparticles can be coated with an agent that reduces surface charge, an agent that increases cell-specific targeting, or a combination thereof. Typically, the loaded nanoparticles are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the nanoparticles are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.

摘要翻译： 公开了聚（胺 - 共酯）聚合物，其中形成活性剂负载纳米颗粒的方法，以及使用该纳米颗粒用于药物递送的方法。 纳米颗粒可以用减少表面电荷的试剂，增加细胞特异性靶向的试剂或其组合来涂覆。 通常，加载的纳米颗粒在药物递送下毒性较小，效率更高，或与其它转染试剂相比较，其组合。 在一些实施方案中，纳米颗粒适合于体内递送，并且可以全身施用于受试者以治疗疾病或病症。

公开(公告)号：US20150073041A1

公开(公告)日：2015-03-12

申请号：US14547051

申请日：2014-11-18

申请人： Yale University

发明人： W. Mark Saltzman ,  Junwei Zhang ,  Jiangbing Zhou ,  Zhaozhong Jiang

IPC分类号： A61K47/48

CPC分类号： A61K47/593 ,  A61K9/1075 ,  A61K9/5146 ,  A61K31/7088 ,  A61K47/34 ,  C08G63/685 ,  C12N15/87

摘要： Polyamine-co-ester-co-ortho ester) polymers, methods of forming active agent-load nanoparticles therefrom, and methods of using the nanoparticles for drug delivery are disclosed. The nanoparticles can be coated with an agent that reduces surface charge, an agent that increases cell-specific targeting, or a combination thereof. Typically, the loaded nanoparticles are less toxic, more efficient at drug delivery, or a combination thereof compared to a control or other transfection reagents.

摘要翻译： 多胺 - 共 - 酯 - 共 - 原酸酯）聚合物，形成活性剂负载纳米颗粒的方法，以及使用该纳米颗粒用于药物递送的方法。 纳米颗粒可以用减少表面电荷的试剂，增加细胞特异性靶向的试剂或其组合来涂覆。 通常，与对照或其它转染试剂相比，负载的纳米颗粒毒性较小，在药物递送时效率更高，或其组合。

公开(公告)号：US20200214989A1

公开(公告)日：2020-07-09

申请号：US16624803

申请日：2018-06-21

申请人： Yale University

发明人： Jiangbing Zhou ,  Xin Yang ,  Chao Ma

IPC分类号： A61K9/51 ,  A61K9/14 ,  A61K31/56 ,  A61P35/04 ,  A61P3/10 ,  A23L33/10

摘要： Supramolecular particle compositions based on medicinal natural products (MNPs), their synthetic analogs and derivatives, and methods to prepare and use them are provided. Five classes of MNPs and their derivatives including diterpene resin acid, phytosterol, lupane-type pentacyclic triterpene, oleanane-type pentacyclic tritepene, and lanostane-type triterpene form functional nano- or micro-structures that are stable to strong acidic environment and effectively penetrate the gastrointestinal tract. Therapeutic, prophylactic, or diagnostic agents that generally have poor intestinal permeability are converted to bioavailable forms when delivered with these supramolecular particles. Among many others, small compound chemotherapeutic agents and peptide therapeutics encapsulated therein have a much greater plasma concentration following oral administration, and effectively controls and treat symptoms associated with tumors or diabetes.

公开(公告)号：US10682422B2

公开(公告)日：2020-06-16

申请号：US15527285

申请日：2015-11-18

申请人： Yale University

发明人： W. Mark Saltzman ,  Junwei Zhang ,  Jiangbing Zhou ,  Zhaozhong Jiang

IPC分类号： A61K48/00 ,  A61K47/69 ,  C12N15/113 ,  C08G63/685 ,  C12N15/11 ,  A61K9/51 ,  A61K47/59 ,  A61K31/7088 ,  A61K47/34 ,  C12N15/87 ,  A61K9/107

摘要： Poly(amine-co-ester-co-ortho ester) polymers, methods of forming active agent-load nanoparticles therefrom, and methods of using the nanoparticles for drug delivery are disclosed. The nanoparticles can be coated with an agent that reduces surface charge, an agent that increases cell-specific targeting, or a combination thereof. Typically, the loaded nanoparticles are less toxic, more efficient at drug delivery, or a combination thereof compared to a control or other transfection reagents.

公开(公告)号：US20190330317A1

公开(公告)日：2019-10-31

申请号：US16310326

申请日：2017-06-15

申请人： Yale University

发明人： James Hansen ,  Jiangbing Zhou

IPC分类号： C07K16/18 ,  A61K47/68 ,  A61K47/69 ,  A61K9/14 ,  A61K31/704 ,  A61K49/00 ,  A61K47/65 ,  A61K9/51

摘要： Guanosine-targeted nanocarriers for encapsulating an active agent and delivering it to extracellular guanosine and DNA are provided. The nanocarriers, for example, polymeric particles, liposomes, and multilamellar vesicles have targeting moiety that targets guanosine attached, linked, or conjugated thereto. The targeting moiety that targets guanosine is typically an antibody, or variant, fragment, or fusion protein derived therefrom that binds to guanosine. The targeting moiety can be a circulating autoantibody that binds guanosine such as those commonly found in patients with SLE. Cytoplasmic delivery vehicles that do not localize into endosomes or lysosomes are also provided. The delivery agent is typically an antibody, or variant, fragment, or fusion protein derived therefrom that binds to guanosine. In some embodiments, the targeting moiety or delivery agent is antibody 4H2 or a variant, fragment, or fusion protein derived therefrom. Pharmaceutical compositions, methods of use, and dosage regimens are also provided.

公开(公告)号：US09567430B2

公开(公告)日：2017-02-14

申请号：US14988538

申请日：2016-01-05

申请人： Yale University

发明人： W. Mark Saltzman ,  Zhaozhong Jiang ,  Jiangbing Zhou ,  Jie Liu

IPC分类号： A61K9/50 ,  A61K9/14 ,  C08G63/685 ,  C12N15/87 ,  A61K47/34 ,  A61K31/7088 ,  A61K9/107 ,  A61K31/711 ,  A61K48/00 ,  C12N15/88 ,  C12P13/00

CPC分类号： C08G63/6852 ,  A61K9/1075 ,  A61K31/337 ,  A61K31/7088 ,  A61K31/711 ,  A61K38/1774 ,  A61K38/1793 ,  A61K38/44 ,  A61K47/34 ,  A61K48/0041 ,  C08G63/88 ,  C12N15/87 ,  C12N15/88 ,  C12P13/001 ,  C12Y113/12007

摘要： Poly(amine-co-ester) polymers, methods of forming active agent-load nanoparticles therefrom, and methods of using the nanoparticles for drug delivery are disclosed. The nanoparticles can be coated with an agent that reduces surface charge, an agent that increases cell-specific targeting, or a combination thereof. Typically, the loaded nanoparticles are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the nanoparticles are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.

摘要翻译： 公开了聚（胺 - 共酯）聚合物，其中形成活性剂负载纳米颗粒的方法，以及使用该纳米颗粒用于药物递送的方法。 纳米颗粒可以用减少表面电荷的试剂，增加细胞特异性靶向的试剂或其组合来涂覆。 通常，加载的纳米颗粒在药物递送下毒性较小，效率更高，或与其它转染试剂相比较，其组合。 在一些实施方案中，纳米颗粒适合于体内递送，并且可以全身施用于受试者以治疗疾病或病症。

公开(公告)号：US20150118311A1

公开(公告)日：2015-04-30

申请号：US14397830

申请日：2013-05-06

申请人： Yale University

发明人： Jiangbing Zhou ,  Toral R. Patel ,  Joseph M. Piepmeier ,  William Mark Saltzman

IPC分类号： A61K9/51 ,  A61K31/428 ,  A61K9/00 ,  A61K31/337

CPC分类号： A61K9/513 ,  A61K9/0019 ,  A61K9/0085 ,  A61K9/19 ,  A61K9/5153 ,  A61K31/17 ,  A61K31/337 ,  A61K31/428 ,  A61K31/4745 ,  A61K31/495

摘要： Brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery (CED) have been developed. In the preferred embodiment, these are loaded with FDA-approved compounds, identified through library screening to target brain cancer stem cells (BSCSs). The particles are formed by emulsifying a polymer-drug solution, then removing solvent and centrifuging at a first force to remove the larger particles, then collecting the smaller particles using a second higher force to sediment the smaller particles having a diameter of less than 100 nm, more preferably less than 90 nanometers average diameter, able to penetrate brain interstitial spaces.

摘要翻译： 已经开发了可以装载药物并针对颅内对流增强递送（CED）进行优化的穿透脑的聚合物纳米颗粒。 在优选实施方案中，它们装载经FDA批准的化合物，通过文库筛选鉴定靶向脑癌干细胞（BSCS）。 颗粒通过乳化聚合物药物溶液，然后除去溶剂并以第一力离心以除去较大的颗粒，然后使用第二较高的力收集较小的颗粒以沉淀直径小于100nm的较小颗粒 ，更优选小于90纳米的平均直径，能够穿透脑间质空间。