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公开(公告)号：US20100136058A1
公开(公告)日：2010-06-03
申请号：US12462496
申请日：2009-08-04
申请人： Yunping Luo , Rong Xiang , Ralph A. Reisfeld
发明人： Yunping Luo , Rong Xiang , Ralph A. Reisfeld
CPC分类号： A61K48/0008 , A61K39/0011 , A61K48/005 , A61K2039/522 , A61K2039/523 , A61K2039/53 , A61K2039/55527 , A61K2039/6031 , C12N2510/02 , Y02A50/484
摘要： A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a polynucleotide construct operably encoding an a Fra-1 protein, such as a polyubiquitinated human Fra-1 protein, and IL-18, such as human IL-18, in a pharmaceutically acceptable carrier. In a preferred embodiment, the polynucleotide construct is operably incorporated in an attenuated bacterial vector, such as an attenuated Salmonella typhimurium, particularly a doubly attenuated aroA- dam- S. typhimurium. Transformed host cells, methods of inhibiting tumor growth, of vaccinating a patient against cancer, and of delivering genetic material to a mammalian cell in vivo are also described.
摘要翻译： 适用于引发针对癌细胞的免疫应答的DNA疫苗包括在药学上可操作地编码Fra-1蛋白（例如多聚遍在蛋白化的人Fra-1蛋白）和IL-18（例如人IL-18）的多核苷酸构建体 可接受的载体 在优选的实施方案中，多核苷酸构建体可操作地掺入减毒的细菌载体中，例如减毒的鼠伤寒沙门氏菌，特别是双重减毒的aroA-鼠伤寒沙门氏菌。 还描述了转化的宿主细胞，抑制肿瘤生长的方法，使患者接种癌症的疫苗，以及将体内遗传物质递送至哺乳动物细胞。
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公开(公告)号：US09629922B2
公开(公告)日：2017-04-25
申请号：US13820413
申请日：2011-09-02
申请人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
发明人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
CPC分类号： A61K31/58 , A61K9/127 , A61K9/1271 , A61K9/1272 , A61K31/4164 , A61K31/704 , A61K47/28 , A61K47/6911 , A61K47/6913 , B82Y5/00
摘要： The present invention provides an aqueous tumor-targeting liposome nanoparticle composition comprising an aqueous dispersion of liposome nanoparticles. The nanoparticles preferably encapsulate an anti-cancer chemotherapeutic agent, which can be added to a pre-formed liposome composition or can be incorporated in the liposomes during the formation of the liposomes. The liposome nanoparticles comprise a legumain-targeting lipid admixed with one or more other micelle or vesicle-forming lipid materials in the form of nanoparticulate liposomes dispersed in an aqueous carrier. A preferred tumor-targeting liposome nanoparticle composition comprises (a) a legumain-targeting lipid component, (b) a zwitterionic lipid component; (c) an amino-substituted lipid component; (d) a neutral lipid component; and (e) polyethylene glycol-conjugated lipid component. The legumain-targeting lipid component comprising a hydrophobic lipid portion covalenetly attached to a legumain-binding moiety.
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公开(公告)号：US09616137B2
公开(公告)日：2017-04-11
申请号：US13224399
申请日：2011-09-02
申请人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
发明人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
CPC分类号： A61K31/58 , A61K9/127 , A61K9/1271 , A61K9/1272 , A61K31/4164 , A61K31/704 , A61K47/28 , A61K47/6911 , A61K47/6913 , B82Y5/00
摘要： The present invention provides an aqueous tumor-targeting liposome nanoparticle composition comprising an aqueous dispersion of liposome nanoparticles. The nanoparticles preferably encapsulate an anti-cancer chemotherapeutic agent, which can be added to a pre-formed liposome composition or can be incorporated in the liposomes during the formation of the liposomes. The liposome nanoparticles comprise a legumain-targeting lipid admixed with one or more other micelle or vesicle-forming lipid materials in the form of nanoparticulate liposomes dispersed in an aqueous carrier. A preferred tumor-targeting liposome nanoparticle composition comprises (a) a legumain-targeting lipid component, (b) a zwitterionic lipid component; (c) an amino-substituted lipid component; (d) a neutral lipid component; and (e) polyethylene glycol-conjugated lipid component. The legumain-targeting lipid component comprising a hydrophobic lipid portion covalently attached to a legumain-binding moiety.
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公开(公告)号：US07569552B2
公开(公告)日：2009-08-04
申请号：US10574752
申请日：2004-10-07
申请人： Yunping Luo , Rong Xiang , Ralph A. Reisfeld
发明人： Yunping Luo , Rong Xiang , Ralph A. Reisfeld
CPC分类号： A61K48/0008 , A61K39/0011 , A61K48/005 , A61K2039/522 , A61K2039/523 , A61K2039/53 , A61K2039/55527 , A61K2039/6031 , C12N2510/02 , Y02A50/484
摘要： A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a polynucleotide construct operably encoding an a Fra-1 protein, such as a polyubiquitinated human Fra-1 protein, and IL-18, such as human IL-18, in a pharmaceutically acceptable carrier. In a preferred embodiment, the polynucleotide construct is operably incorporated in an attenuated bacterial vector, such as an attenuated Salmonella typhimurium, particularly a doubly attenuated aroA− dam− S. typhimurium. Transformed host cells, methods of inhibiting tumor growth, of vaccinating a patient against cancer, and of delivering genetic material to a mammalian cell in vivo are also described.
摘要翻译： 适用于引发针对癌细胞的免疫应答的DNA疫苗包括在药学上可操作地编码Fra-1蛋白（例如多聚泛素化的人Fra-1蛋白）和IL-18（例如人IL-18）的多核苷酸构建体 可接受的载体 在优选的实施方案中，多核苷酸构建体可操作地掺入减毒的细菌载体中，例如减毒的鼠伤寒沙门氏菌，特别是双重减毒的aroA-鼠伤寒沙门氏菌。 还描述了转化的宿主细胞，抑制肿瘤生长的方法，使患者接种癌症的疫苗，以及将体内遗传物质递送至哺乳动物细胞。
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公开(公告)号：US20130330399A1
公开(公告)日：2013-12-12
申请号：US13820413
申请日：2011-09-02
申请人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
发明人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
CPC分类号： A61K31/58 , A61K9/127 , A61K9/1271 , A61K9/1272 , A61K31/4164 , A61K31/704 , A61K47/28 , A61K47/6911 , A61K47/6913 , B82Y5/00
摘要： The present invention provides an aqueous tumor-targeting liposome nanoparticle composition comprising an aqueous dispersion of liposome nanoparticles. The nanoparticles preferably encapsulate an anti-cancer chemotherapeutic agent, which can be added to a pre-formed liposome composition or can be incorporated in the liposomes during the formation of the liposomes. The liposome nanoparticles comprise a legumain-targeting lipid admixed with one or more other micelle or vesicle-forming lipid materials in the form of nanoparticulate liposomes dispersed in an aqueous carrier. A preferred tumor-targeting liposome nanoparticle composition comprises (a) a legumain-targeting lipid component, (b) a zwitterionic lipid component; (c) an amino-substituted lipid component; (d) a neutral lipid component; and (e) polyethylene glycol-conjugated lipid component. The legumain-targeting lipid component comprising a hydrophobic lipid portion covalenetly attached to a legumain-binding moiety.
摘要翻译： 本发明提供了包含脂质体纳米颗粒的水分散体的含水肿瘤靶向脂质体纳米颗粒组合物。 纳米颗粒优选包封抗癌化学治疗剂，其可以加入到预形成的脂质体组合物中，或者可以在形成脂质体期间掺入脂质体中。 脂质体纳米颗粒包含与分散在水性载体中的纳米颗粒脂质体形式的一种或多种其它胶束或形成囊泡的脂质材料混合的豆粕靶向脂质。 优选的肿瘤靶向脂质体纳米颗粒组合物包含（a）脂肪组织靶向脂质组分，（b）两性离子脂质组分; （c）氨基取代的脂质成分; （d）中性脂质组分; 和（e）聚乙二醇缀合的脂质组分。 所述脂肪组分包含疏水性脂质部分，其与共轭结合部分共价连接。
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公开(公告)号：US20120058177A1
公开(公告)日：2012-03-08
申请号：US13224399
申请日：2011-09-02
申请人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
发明人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo , Debbie Liao , Ze Liu , Tingmei Chen , Si Chen , Dan Lu
IPC分类号： A61K9/127 , A61P35/00 , A61K31/704 , B82Y5/00
CPC分类号： A61K31/58 , A61K9/127 , A61K9/1271 , A61K9/1272 , A61K31/4164 , A61K31/704 , A61K47/28 , A61K47/6911 , A61K47/6913 , B82Y5/00
摘要： The present invention provides an aqueous tumor-targeting liposome nanoparticle composition comprising an aqueous dispersion of liposome nanoparticles. The nanoparticles preferably encapsulate an anti-cancer chemotherapeutic agent, which can be added to a pre-formed liposome composition or can be incorporated in the liposomes during the formation of the liposomes. The liposome nanoparticles comprise a legumain-targeting lipid admixed with one or more other micelle or vesicle-forming lipid materials in the form of nanoparticulate liposomes dispersed in an aqueous carrier. A preferred tumor-targeting liposome nanoparticle composition comprises (a) a legumain-targeting lipid component, (b) a zwitterionic lipid component; (c) an amino-substituted lipid component; (d) a neutral lipid component; and (e) polyethylene glycol-conjugated lipid component. The legumain-targeting lipid component comprising a hydrophobic lipid portion covalenetly attached to a legumain-binding moiety.
摘要翻译： 本发明提供了包含脂质体纳米颗粒的水分散体的含水肿瘤靶向脂质体纳米颗粒组合物。 纳米颗粒优选包封抗癌化学治疗剂，其可以加入到预形成的脂质体组合物中，或者可以在形成脂质体期间掺入脂质体中。 脂质体纳米颗粒包含与分散在水性载体中的纳米颗粒脂质体形式的一种或多种其它胶束或形成囊泡的脂质材料混合的豆粕靶向脂质。 优选的肿瘤靶向脂质体纳米颗粒组合物包含（a）脂肪组织靶向脂质组分，（b）两性离子脂质组分; （c）氨基取代的脂质成分; （d）中性脂质组分; 和（e）聚乙二醇缀合的脂质组分。 所述脂肪组分包含疏水性脂质部分，其与共轭结合部分共价连接。
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公开(公告)号：US08053421B2
公开(公告)日：2011-11-08
申请号：US12462496
申请日：2009-08-04
申请人： Yunping Luo , Rong Xiang , Ralph A. Reisfeld
发明人： Yunping Luo , Rong Xiang , Ralph A. Reisfeld
CPC分类号： A61K48/0008 , A61K39/0011 , A61K48/005 , A61K2039/522 , A61K2039/523 , A61K2039/53 , A61K2039/55527 , A61K2039/6031 , C12N2510/02 , Y02A50/484
摘要： A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a polynucleotide construct operably encoding an a Fra-1 protein, such as a polyubiquitinated human Fra-1 protein, and IL-18, such as human IL-18, in a pharmaceutically acceptable carrier. In a preferred embodiment, the polynucleotide construct is operably incorporated in an attenuated bacterial vector, such as an attenuated Salmonella typhimurium, particularly a doubly attenuated aroA− dam− S. typhimurium. Transformed host cells, methods of inhibiting tumor growth, of vaccinating a patient against cancer, and of delivering genetic material to a mammalian cell in vivo are also described.
摘要翻译： 适用于引发针对癌细胞的免疫应答的DNA疫苗包括在药学上可操作地编码Fra-1蛋白（例如多聚泛素化的人Fra-1蛋白）和IL-18（例如人IL-18）的多核苷酸构建体 可接受的载体 在优选的实施方案中，多核苷酸构建体可操作地掺入减毒的细菌载体中，例如减毒的鼠伤寒沙门氏菌，特别是双重减毒的aroA-鼠伤寒沙门氏菌。 还描述了转化的宿主细胞，抑制肿瘤生长的方法，使患者接种癌症的疫苗，以及将体内遗传物质递送至哺乳动物细胞。
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8.发明申请DNA COMPOSITION FOR ELICITING AN IMMUNE RESPONSE AGAINST TUMOR-ASSOCIATED MACROPHAGES 审中-公开针对肿瘤相关巨噬细胞的免疫反应的DNA组合物公开(公告)号：US20090275642A1
公开(公告)日：2009-11-05
申请号：US12311379
申请日：2007-10-05
申请人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo
发明人： Ralph A. Reisfeld , Rong Xiang , Yunping Luo
CPC分类号： C12N9/6472 , A61K39/00 , A61K39/0011 , A61K2039/521 , A61K2039/5254 , A61K2039/53 , A61K2039/542 , A61K2039/645 , C12N9/50
摘要： The present invention provides a DNA composition comprising a DNA minigene construct that encodes for a polypeptide comprising a plurality of immunogenic fragments of a cysteine endopeptidase that is expressed in tumor-associated cells. The immunogenic fragments are joined together serially by a linker peptide between each successive fragment in the polypeptide. The polypeptide is capable of eliciting an immune response against the tumor-associated cells, is expressible in immune cells, and is incorporated in a pharmaceutically acceptable carrier.
摘要翻译： 本发明提供一种DNA组合物，其包含编码包含在肿瘤相关细胞中表达的半胱氨酸内肽酶的多个免疫原性片段的多肽的DNA小基因构建体。 免疫原性片段通过多肽中每个连续片段之间的接头肽连续连接在一起。 多肽能够引发针对肿瘤相关细胞的免疫应答，可在免疫细胞中表达，并且被掺入药学上可接受的载体中。
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9.发明授权DNA composition encoding an immunogenic VEGF receptor peptide and methods of use thereof 有权编码免疫原性VEGF受体肽的DNA组合物及其使用方法公开(公告)号：US08241637B2
公开(公告)日：2012-08-14
申请号：US13280855
申请日：2011-10-25
CPC分类号： A61K39/0005 , A61K39/0011 , A61K2039/522 , A61K2039/53 , A61K2039/542 , Y02A50/484
摘要： A method of inhibiting endothelial cell proliferation in a mammal is provided. The method comprises the step of administering to the mammal an effective immunological response eliciting amount of a DNA composition comprising a DNA construct operably encoding a VEGF receptor polypeptide and a pharmaceutically acceptable carrier therefor, whereby said mammal exhibits an immune response elicited by vaccine and specific to proliferating endothelial cells. The methods of this invention inhibit vascular endothelial cell proliferation in the tumor micro-environment. Angiogenesis inhibition and subsequent decrease in tumor growth and dissemination is achieved.
摘要翻译： 提供了抑制哺乳动物内皮细胞增殖的方法。 该方法包括向哺乳动物施用有效的免疫应答引发量的DNA组合物的步骤，该组合物包含可操作地编码VEGF受体多肽的DNA构建体及其药学上可接受的载体，由此所述哺乳动物表现出由疫苗引起的免疫应答， 增殖性内皮细胞。 本发明的方法抑制肿瘤微环境中的血管内皮细胞增殖。 实现血管发生抑制和随后肿瘤生长和传播的减少。
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10.发明授权DNA composition encoding an immunogenic VEGF receptor peptide and methods of use thereof 有权编码免疫原性VEGF受体肽的DNA组合物及其使用方法公开(公告)号：US08048428B2
公开(公告)日：2011-11-01
申请号：US11507298
申请日：2006-08-21
CPC分类号： A61K39/0005 , A61K39/0011 , A61K2039/522 , A61K2039/53 , A61K2039/542 , Y02A50/484
摘要： A DNA composition effective for inhibiting endothelial cell proliferation comprises a DNA construct operably encoding a vascular endothelial growth factor (VEGF) receptor polypeptide, which can be a full length VEGF receptor protein or an immunogenic fragment thereof. This invention provides DNA compositions that encode VEGF receptor-2 (KDR), VEGF receptor-1 (Flt-1), or Flk-1 (the murine homolog of KDR), as well as methods of using such a DNA composition to inhibit vascular endothelial cell proliferation in the tumor micro-environment. Angiogenesis inhibition and subsequent decrease in tumor growth and dissemination is achieved.
摘要翻译： 有效抑制内皮细胞增殖的DNA组合包括可操作地编码血管内皮生长因子（VEGF）受体多肽的DNA构建体，其可以是全长VEGF受体蛋白质或其免疫原性片段。 本发明提供编码VEGF受体-2（KDR），VEGF受体-1（Flt-1）或Flk-1（KDR的鼠同源物）的DNA组合物，以及使用这种DNA组合物抑制血管的方法 内皮细胞增殖在肿瘤微环境中。 实现血管发生抑制和随后肿瘤生长和传播的减少。
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