公开(公告)号：WO2013056132A3

公开(公告)日：2013-06-13

申请号：PCT/US2012060072

申请日：2012-10-12

Applicant: STC UNM ,  SANDIA CORP

Inventor： ASHLEY CARLEE ERIN ,  BRINKER C JEFFREY ,  CARNES ERIC C ,  FEKRAZAD MOHAMMAD HOUMAN ,  FELTON LINDA A ,  NEGRETE OSCAR ,  PADILLA DAVID PATRICK ,  WILKINSON BRIAN S ,  WILKINSON DAN C ,  WILLMAN CHERYL L

IPC: A61K9/16 ,  A61K31/7088 ,  A61K31/7105 ,  A61K38/17 ,  A61K47/48 ,  A61K48/00 ,  A61K49/08

CPC classification number: A61K47/48823 ,  A61K9/0014 ,  A61K9/107 ,  A61K9/1271 ,  A61K9/5078 ,  A61K31/192 ,  A61K31/465 ,  A61K31/506 ,  A61K31/513 ,  A61K31/704 ,  A61K31/7088 ,  A61K31/7105 ,  A61K31/713 ,  A61K33/24 ,  A61K38/00 ,  A61K38/17 ,  A61K38/45 ,  A61K38/47 ,  A61K45/06 ,  A61K47/483 ,  A61K47/48561 ,  A61K47/48815 ,  A61K47/48861 ,  A61K47/6923 ,  A61K48/0008 ,  A61K49/0082 ,  A61K49/0423 ,  B82Y5/00 ,  C07K7/06 ,  C07K2319/00 ,  C12N15/113 ,  C12N15/1131 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2810/40 ,  C12Y204/02036 ,  C12Y302/02022 ,  A61K2300/00

Abstract: 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.

Abstract translation: 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，并且促进内源性逃逸的融合肽 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：EP2765997A4

公开(公告)日：2015-06-24

申请号：EP12840155

申请日：2012-10-12

Applicant: STC UNM ,  SANDIA CORP

Inventor： ASHLEY CARLEE ERIN ,  BRINKER C JEFFREY ,  CARNES ERIC C ,  FEKRAZAD MOHAMMAD HOUMAN ,  FELTON LINDA A ,  NEGRETE OSCAR ,  PADILLA DAVID PATRICK ,  WILKINSON BRIAN S ,  WILKINSON DAN C ,  WILLMAN CHERYL L

IPC: A61K9/16 ,  A61K9/107 ,  A61K9/127 ,  A61K9/50 ,  A61K31/7088 ,  A61K31/7105 ,  A61K31/713 ,  A61K38/17 ,  A61K45/06 ,  A61K47/48 ,  A61K48/00 ,  A61K49/04 ,  A61K49/08 ,  B82Y5/00 ,  C07K7/06 ,  C12N15/88

CPC classification number: A61K47/48823 ,  A61K9/0014 ,  A61K9/107 ,  A61K9/1271 ,  A61K9/5078 ,  A61K31/192 ,  A61K31/465 ,  A61K31/506 ,  A61K31/513 ,  A61K31/704 ,  A61K31/7088 ,  A61K31/7105 ,  A61K31/713 ,  A61K33/24 ,  A61K38/00 ,  A61K38/17 ,  A61K38/45 ,  A61K38/47 ,  A61K45/06 ,  A61K47/483 ,  A61K47/48561 ,  A61K47/48815 ,  A61K47/48861 ,  A61K47/6923 ,  A61K48/0008 ,  A61K49/0082 ,  A61K49/0423 ,  B82Y5/00 ,  C07K7/06 ,  C07K2319/00 ,  C12N15/113 ,  C12N15/1131 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2810/40 ,  C12Y204/02036 ,  C12Y302/02022 ,  A61K2300/00

Abstract: 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.

公开(公告)号：AU2012323937A1

公开(公告)日：2014-06-05

申请号：AU2012323937

申请日：2012-10-12

Applicant: STC UNM ,  SANDIA CORP

Inventor： ASHLEY CARLEE ERIN ,  BRINKER C JEFFREY ,  CARNES ERIC C ,  FEKRAZAD MOHAMMAD HOUMAN ,  FELTON LINDA A ,  NEGRETE OSCAR ,  PADILLA DAVID PATRICK ,  WILKINSON BRIAN S ,  WILKINSON DAN C ,  WILLMAN CHERYL L

IPC: A61K9/16 ,  A61K31/7088 ,  A61K31/7105 ,  A61K38/17 ,  A61K47/48 ,  A61K48/00 ,  A61K49/08

Abstract: 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.

公开(公告)号：SG11201401499XA

公开(公告)日：2014-09-26

申请号：SG11201401499X

申请日：2012-10-12

Applicant: STC UNM ,  SANDIA CORP

Inventor： ASHLEY CARLEE ERIN ,  BRINKER C JEFFREY ,  CARNES ERIC C ,  FEKRAZAD MOHAMMAD HOUMAN ,  FELTON LINDA A ,  NEGRETE OSCAR ,  PADILLA DAVID PATRICK ,  WILKINSON BRIAN S ,  WILKINSON DAN C ,  WILLMAN CHERYL L

IPC: A61K31/7088 ,  A61K9/16 ,  A61K31/7105 ,  A61K38/17 ,  A61K47/48 ,  A61K48/00 ,  A61K49/08

Abstract: 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.

公开(公告)号：CA2852064A1

公开(公告)日：2013-04-18

申请号：CA2852064

申请日：2012-10-12

Applicant: STC UNM ,  SANDIA CORP

Inventor： ASHLEY CARLEE ERIN ,  BRINKER C JEFFREY ,  CARNES ERIC C ,  FEKRAZAD MOHAMMAD HOUMAN ,  FELTON LINDA A ,  NEGRETE OSCAR ,  PADILLA DAVID PATRICK ,  WILKINSON BRIAN S ,  WILKINSON DAN C ,  WILLMAN CHERYL L

IPC: A61K9/16 ,  A61K31/7088 ,  A61K31/7105 ,  A61K38/17 ,  A61K47/48 ,  A61K48/00 ,  A61K49/08

Abstract: 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.

公开(公告)号：MX2014004415A

公开(公告)日：2015-06-05

申请号：MX2014004415

申请日：2012-10-12

Applicant: STC UNM

Inventor： ASHLEY CARLEE ERIN ,  BRINKER C JEFFREY ,  CARNES ERIC C ,  FEKRAZAD MOHAMMAD HOUMAN ,  FELTON LINDA A ,  NEGRETE OSCAR ,  PADILLA DAVID PATRICK ,  WILKINSON BRIAN S ,  WILKINSON DAN C ,  WILLMAN CHERYL L

IPC: A61K9/16 ,  A61K31/7088 ,  A61K31/7105 ,  A61K38/17 ,  A61K47/48 ,  A61K48/00 ,  A61K49/08

Abstract: La presente invención se refiere a protocélulas específicamente dirigidas a la células de cáncer hepatocelular y a otras células cancerosas, las cuales comprenden un núcleo de sílice nanoporoso que soporta una bicapa lipídica; al menos un agente que facilita la muerte de la célula cancerosa (como la tradicional molécula pequeña), una carga macromolecular (por ejemplo, ARNsi o una toxina proteica como la cadena A de la toxina ricina o la cadena A de la toxina diftérica) y/o un ADN plasmídico empaquetado con histona dispuesto dentro del núcleo de sílice nanoporoso (de preferencia, superenrollado para empaquetar con más eficiencia el ADN en las protocélulas), que opcionalmente puede modificarse con una secuencia de localización nuclear que ayude a localizar las protocélulas dentro del núcleo de la célula cancerosa y con la capacidad de expresar péptidos que participan en el tratamiento (apoptosis/muerte celular) de la célula cancerosa o como un reportero, un péptido dirigido cuyo objetivo son las células cancerosas en el tejido que se va a tratar, de manera que la unión de las protocélulas con las células objetivo sea específica y mejorada; y un péptido fusogénico que promueve el escape endosómico de las protocélulas y el ADN encapsulado. Las protocélulas según la presente invención se pueden usar para tratar el cáncer, en especial el cáncer hepatocelular (de hígado), utilizando novedosos péptidos de unión (péptidos c-MET) que se unen de manera selectiva al tejido hepatocelular, o para funcionar en el diagnóstico de cáncer, incluido el tratamiento oncológico o también en el desarrollo de medicamentos.