公开(公告)号：US09579283B2

公开(公告)日：2017-02-28

申请号：US14113371

申请日：2012-04-27

申请人： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Cheryl L. Willman

发明人： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Cheryl L. Willman

IPC分类号： A61K9/127 ,  A61K31/704 ,  A61K31/711 ,  A61K45/06 ,  A61K47/48 ,  C07K14/47 ,  C12N15/88 ,  A61K33/24 ,  A61K39/05 ,  C12N15/113 ,  A61K38/00 ,  A61K48/00

CPC分类号： A61K9/1271 ,  A61K31/704 ,  A61K31/711 ,  A61K33/24 ,  A61K38/00 ,  A61K39/05 ,  A61K45/06 ,  A61K47/62 ,  A61K47/6901 ,  A61K48/0016 ,  C07K14/47 ,  C12N15/1135 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2810/40

摘要： The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

摘要翻译： 本发明涉及用于特异性靶向肝细胞和其它癌细胞的原细胞，其包含具有支持的脂质双层的纳米多孔二氧化硅核心; 至少一种促进癌细胞死亡的药物（例如传统的小分子，大分子货物（例如siRNA或蛋白质毒素如蓖麻毒素A链或白喉毒素A链）和/或组蛋白包装的质粒DNA 设置在纳米多孔硅芯内（优选超螺旋以更有效地将DNA包装到原细胞中），其任选地用核定位序列修饰以帮助定位癌细胞核内的原细胞，以及表达参与治疗的肽的能力 （凋亡/细胞死亡）或作为报告物，靶向肽靶向待治疗的组织中的癌细胞，使得原细胞与靶细胞的结合是特异性和增强的，并且促进内体逃逸的融合肽 原细胞和包封的DNA。根据本发明的原细胞可用于治疗癌症，特别是包括肝细胞（肝）癌症 选择性结合肝细胞组织或在癌症诊断中起作用的新型结合肽（c-MET肽），包括癌症治疗和药物发现。

公开(公告)号：US20190262469A1

公开(公告)日：2019-08-29

申请号：US15757254

申请日：2016-09-02

申请人： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Oscar Negrete ,  Dan C Wilkinson ,  Brian S Wilkinson ,  David Patrick Padilla

发明人： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Oscar Negrete ,  Dan C Wilkinson ,  Brian S Wilkinson ,  David Patrick Padilla

IPC分类号： A61K47/69 ,  A61K31/337 ,  A61P31/04

摘要： The present disclosure relates to protocells that are useful in the treatment and prevention of viral infections, including but not limited to infections caused by a Hendra virus and Nipah virus (NiV). The present disclosure relates to protocells that are useful in the treatment of bacterial infections, including antibiotic-resistant bacterial infections. The protocells are coated with a lipid bi- or multilayer comprising at least one moiety that targets a viral cellular receptor and at least one moiety that ruptures a virally-infected cell membrane. The present disclosure further relates to novel mesoporous metal oxide nanoparticles and related protocells that are useful in the treatment and/or prevention of a wide variety of disorders, including a cancer or a bacterial or viral infection. Such nanoparticles and protocells can be functionalized to allow for synergistic loading of a wide variety of active ingredients.

公开(公告)号：US20180049984A1

公开(公告)日：2018-02-22

申请号：US15474810

申请日：2017-03-30

申请人： Charles Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Joshua Santarpia ,  Adrienne Celeste Greene ,  Oscar Negrete ,  Steven Branda ,  Ayse Muniz ,  Jacob Ongundi Agola ,  Kimberly Butler

发明人： Charles Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Joshua Santarpia ,  Adrienne Celeste Greene ,  Oscar Negrete ,  Steven Branda ,  Ayse Muniz ,  Jacob Ongundi Agola ,  Kimberly Butler

IPC分类号： A61K9/127 ,  C12N9/22 ,  A61K9/51 ,  A61K49/00

CPC分类号： A61K9/1274 ,  A61K9/501 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/7088 ,  A61K45/06 ,  A61K48/005 ,  A61K49/005 ,  C12N9/22 ,  C12N15/8206 ,  C12N2310/11 ,  C12N2310/20

摘要： The present disclosure relates to the delivery of polynucleotides and/or oligonucleotides using silica delivery platforms, e.g., silica carriers or protocells. In particular, in the present disclosure, polynucleotides in the form of plasmids expressing siRNA may be administered as cargo in the silica delivery platform to a patient or subject to inhibit and/or treat cancer in a patient. In one aspect, the silica delivery platform that have been charged with cargo comprising plasmid DNA (in particular, CRISPR ds plasmid DNA) which expresses siRNA, shRNA, mRNA and other RNA which may be used to administer these plasmids to patients in order to effect inhibition of cancer cells (especially including apoptosis of those cancer cells) and effective and/or prophylaxis of cancer, as well as numerous pathogens, including viruses, bacteria, fungi, and/or other disease states and/or conditions. In another aspect, the silica delivery platform comprises a biological package (e.g., plasmid nucleic acid, such as a for a CRISPR/Cas system) that interacts with a genomic sequence to either activate or inhibit gene expression. Such vehicles can be employed to control gene activation and repression in a host (e.g., a patient) and/or a pathogen.

公开(公告)号：US20180028686A1

公开(公告)日：2018-02-01

申请号：US15474800

申请日：2017-03-30

申请人： Charles Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Joshua Santarpia ,  Adrienne Celeste Greene ,  Oscar Negrete ,  Steven Branda ,  Ayse Muniz ,  Jacob Ongundi Agola ,  Kimberly Butler

发明人： Charles Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Joshua Santarpia ,  Adrienne Celeste Greene ,  Oscar Negrete ,  Steven Branda ,  Ayse Muniz ,  Jacob Ongundi Agola ,  Kimberly Butler

IPC分类号： A61K48/00 ,  A61K9/50 ,  A61K31/7088 ,  A61K45/06

CPC分类号： A61K9/1274 ,  A61K9/501 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/7088 ,  A61K45/06 ,  A61K48/005 ,  A61K49/005 ,  C12N9/22 ,  C12N15/8206 ,  C12N2310/11 ,  C12N2310/20

摘要： The present disclosure relates to the delivery of polynucleotides and/or oligonucleotides using silica delivery platforms, e.g., silica carriers or protocells. In particular, in the present disclosure, polynucleotides in the form of plasmids expressing siRNA may be administered as cargo in the silica delivery platform to a patient or subject to inhibit and/or treat cancer in a patient. In one aspect, the silica delivery platform that have been charged with cargo comprising plasmid DNA (in particular, CRISPR ds plasmid DNA) which expresses siRNA, shRNA, mRNA and other RNA which may be used to administer these plasmids to patients in order to effect inhibition of cancer cells (especially including apoptosis of those cancer cells) and effective and/or prophylaxis of cancer, as well as numerous pathogens, including viruses, bacteria, fungi, and/or other disease states and/or conditions. In another aspect, the silica delivery platform comprises a biological package (e.g., plasmid nucleic acid, such as a for a CRISPR/Cas system) that interacts with a genomic sequence to either activate or inhibit gene expression. Such vehicles can be employed to control gene activation and repression in a host (e.g., a patient) and/or a pathogen.

公开(公告)号：US20140079774A1

公开(公告)日：2014-03-20

申请号：US14113371

申请日：2012-04-27

申请人： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carleen Erin Ashley

发明人： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carleen Erin Ashley

IPC分类号： A61K9/127 ,  A61K45/06 ,  A61K31/704 ,  A61K31/711

CPC分类号： A61K9/1271 ,  A61K31/704 ,  A61K31/711 ,  A61K33/24 ,  A61K38/00 ,  A61K39/05 ,  A61K45/06 ,  A61K47/62 ,  A61K47/6901 ,  A61K48/0016 ,  C07K14/47 ,  C12N15/1135 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2810/40

摘要： The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

摘要翻译： 本发明涉及用于特异性靶向肝细胞和其它癌细胞的原细胞，其包含具有支持的脂质双层的纳米多孔二氧化硅核心; 促进癌细胞死亡的至少一种试剂（例如传统的小分子，大分子货物（例如siRNA或蛋白质毒素如蓖麻毒素A链或白喉毒素A链）和/或组蛋白包装的质粒DNA 设置在纳米多孔硅芯内（优选超螺旋以更有效地将DNA包装到原细胞中），其任选地用核定位序列修饰以帮助定位癌细胞核内的原细胞，以及表达参与治疗的肽的能力 （凋亡/细胞死亡）或作为报告物，靶向肽靶向待治疗的组织中的癌细胞，使得原细胞与靶细胞的结合是特异性和增强的，并且促进内体逃逸的融合肽 原细胞和包封的DNA。根据本发明的原细胞可用于治疗癌症，特别是包括肝细胞（肝）癌症 选择性结合肝细胞组织或在癌症诊断中起作用的新型结合肽（c-MET肽），包括癌症治疗和药物发现。

公开(公告)号：US20140301951A1

公开(公告)日：2014-10-09

申请号：US14253030

申请日：2014-04-15

申请人： Juewen Liu ,  C. Jeffrey Brinker ,  Carlee Ashley ,  Eric C. Carnes

发明人： Juewen Liu ,  C. Jeffrey Brinker ,  Carlee Ashley ,  Eric C. Carnes

IPC分类号： A61K9/127 ,  A61K39/395 ,  A61K33/06 ,  A61K49/00 ,  A61K33/00 ,  A61K33/24 ,  A61K38/16 ,  A61K31/713

CPC分类号： A61K9/127 ,  A61K9/1272 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/713 ,  A61K33/00 ,  A61K33/06 ,  A61K33/24 ,  A61K38/16 ,  A61K39/3955 ,  A61K49/005

摘要： Various exemplary embodiments provide protocell nanostructures and methods for constructing and using the protocell nanostructures. In one embodiment, the protocell nanostructures can include a core-shell structure including a porous particle core surrounded by a shell of lipid bilayer(s). The protocell can be internalized in a bioactive cell. Various cargo components, for example, drugs, can be loaded in and released from the porous particle core of the protocell(s) and then delivered within the bioactive cell.

摘要翻译： 各种示例性实施方案提供了用于构建和使用原细胞纳米结构的原细胞纳米结构和方法。 在一个实施方案中，原细胞纳米结构可以包括核 - 壳结构，其包括被脂质双层的壳包围的多孔颗粒核。 原细胞可以内化在生物活性细胞中。 可以将各种货物组分，例如药物装载在原细胞的多孔颗粒核心中并从其释放，然后在生物活性细胞内递送。

公开(公告)号：US08734816B2

公开(公告)日：2014-05-27

申请号：US13143164

申请日：2010-01-05

申请人： Juewen Liu ,  Jeffrey C. Brinker ,  Carlee Ashley ,  Eric C. Carnes

发明人： Juewen Liu ,  Jeffrey C. Brinker ,  Carlee Ashley ,  Eric C. Carnes

IPC分类号： A61K9/127 ,  A61K9/51

CPC分类号： A61K9/127 ,  A61K9/1272 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/713 ,  A61K33/00 ,  A61K33/06 ,  A61K33/24 ,  A61K38/16 ,  A61K39/3955 ,  A61K49/005

摘要： Various exemplary embodiments provide protocell nanostructures and methods for constructing and using the protocell nanostructures. In one embodiment, the protocell nanostructures can include a core-shell structure including a porous particle core surrounded by a shell of lipid bilayer(s). The protocell can be internalized in a bioactive cell. Various cargo components, for example, drugs, can be loaded in and released from the porous particle core of the protocell(s) and then delivered within the bioactive cell.

摘要翻译： 各种示例性实施方案提供了用于构建和使用原细胞纳米结构的原细胞纳米结构和方法。 在一个实施方案中，原细胞纳米结构可以包括核 - 壳结构，其包括被脂质双层的壳包围的多孔颗粒核。 原细胞可以内化在生物活性细胞中。 可以将各种货物组分，例如药物装载在原细胞的多孔颗粒核心中并从其释放，然后在生物活性细胞内递送。