公开(公告)号：US20170232115A1

公开(公告)日：2017-08-17

申请号：US15380962

申请日：2016-12-15

Applicant: STC.UNM ,  Sandia Corporation

Inventor： Carlee Erin Ashley ,  C. Jeffrey Brinker ,  Eric C. Carnes ,  Mohammed Houman Fekrazad ,  Linda A. Felton ,  Oscar Negrete ,  David Patrick Padilla ,  Brian S. Wilkinson ,  Dan C. Wilkinson ,  Cheryl L. Willman

IPC: A61K49/00 ,  A61K33/24 ,  A61K31/513 ,  C12N15/113 ,  A61K38/45 ,  A61K31/506 ,  A61K38/47 ,  A61K31/465 ,  A61K31/192 ,  A61K31/704 ,  A61K48/00

CPC classification number: A61K48/0008 ,  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 ,  A61K47/6923 ,  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：US20190091150A1

公开(公告)日：2019-03-28

申请号：US16025557

申请日：2018-07-02

Applicant: STC.UNM ,  Sandia Corporation

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

IPC: A61K9/127 ,  A61K31/704 ,  A61K33/24 ,  A61K47/69 ,  C07K14/47 ,  A61K45/06 ,  A61K47/62 ,  C12N15/88 ,  A61K39/05 ,  C12N15/113 ,  A61K31/711 ,  A61K48/00 ,  A61K38/00

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：US09480653B2

公开(公告)日：2016-11-01

申请号：US14627739

申请日：2015-02-20

Applicant: STC.UNM ,  SANDIA CORPORATION

Inventor： C. Jeffrey Brinker ,  Carlee Erin Ashley ,  Xingmao Jiang ,  Juewen Liu ,  David S. Peabody ,  Walker Richard Wharton ,  Eric Carnes ,  Bryce Chackerian ,  Cheryl L. Willman

IPC: A61K9/56 ,  A61K9/127 ,  A61K9/51 ,  A61K49/00 ,  A61K31/575 ,  A61K31/513 ,  A61K33/24 ,  A61K31/704

CPC classification number: A61K9/127 ,  A61K9/1277 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/513 ,  A61K31/575 ,  A61K31/704 ,  A61K33/24 ,  A61K49/005

Abstract: Various embodiments provide materials and methods for synthesizing protocells for use in targeted delivery of cargo components to cancer cells. In one embodiment, the lipid bilayer can be fused to the porous particle core to form a protocell. The lipid bilayer can be modified with targeting ligands or other ligands to achieve targeted delivery of cargo components that are loaded within the protocell to a target cell, e.g., a type of cancer. Shielding materials can be conjugated to the surface of the lipid bilayer to reduce undesired non-specific binding.

公开(公告)号：US20150320681A1

公开(公告)日：2015-11-12

申请号：US14797487

申请日：2015-07-13

Applicant: STC.UNM ,  SANDIA CORPORATION

Inventor： C. Jeffrey Brinker ,  Carlee Erin Ashley ,  Xingmao Jiang ,  Juewen Liu ,  David S. Peabody ,  Walker Richard Wharton ,  Eric Carnes ,  Bryce Chackerian ,  Cheryl L. Willman

IPC: A61K9/127 ,  A61K33/24 ,  A61K31/704 ,  A61K31/513 ,  A61K49/00 ,  A61K31/575

CPC classification number: A61K9/127 ,  A61K9/1277 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/513 ,  A61K31/575 ,  A61K31/704 ,  A61K33/24 ,  A61K49/005

Abstract: Various embodiments provide materials and methods for synthesizing protocells for use in targeted delivery of cargo components to cancer cells. In one embodiment, the lipid bilayer can be fused to the porous particle core to form a protocell. The lipid bilayer can be modified with targeting ligands or other ligands to achieve targeted delivery of cargo components that are loaded within the protocell to a target cell, e.g., a type of cancer. Shielding materials can be conjugated to the surface of the lipid bilayer to reduce undesired non-specific binding.

公开(公告)号：US20150164798A1

公开(公告)日：2015-06-18

申请号：US14627739

申请日：2015-02-20

Applicant: STC.UNM ,  SANDIA CORPORATION

Inventor： C. Jeffrey Brinker ,  Carlee Erin Ashley ,  Xingmao Jiang ,  Juewen Liu ,  David S. Peabody ,  Walker Richard Wharton ,  Eric Carnes ,  Bryce Chackerian ,  Cheryl L. Willman

IPC: A61K9/127 ,  A61K31/704

CPC classification number: A61K9/127 ,  A61K9/1277 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/513 ,  A61K31/575 ,  A61K31/704 ,  A61K33/24 ,  A61K49/005

Abstract: Various embodiments provide materials and methods for synthesizing protocells for use in targeted delivery of cargo components to cancer cells. In one embodiment, the lipid bilayer can be fused to the porous particle core to form a protocell. The lipid bilayer can be modified with targeting ligands or other ligands to achieve targeted delivery of cargo components that are loaded within the protocell to a target cell, e.g., a type of cancer. Shielding materials can be conjugated to the surface of the lipid bilayer to reduce undesired non-specific binding.

Abstract translation: 各种实施方案提供用于合成原细胞以用于向癌细胞靶向递送货物组分的材料和方法。 在一个实施方案中，脂质双层可以与多孔颗粒核心融合以形成原细胞。 脂质双层可以用靶向配体或其他配体进行修饰，以实现载体在原细胞内的货物组分的靶向递送到靶细胞，例如一种类型的癌症。 屏蔽材料可以结合到脂质双层的表面以减少不期望的非特异性结合。

公开(公告)号：US10022327B2

公开(公告)日：2018-07-17

申请号：US14970998

申请日：2015-12-16

Applicant: STC.UNM ,  SANDIA CORPORATION

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

IPC: A61K9/127 ,  A61K31/704 ,  A61K31/711 ,  A61K33/24 ,  A61K39/05 ,  C12N15/113 ,  C07K14/47 ,  C12N15/88 ,  A61K45/06 ,  A61K47/62 ,  A61K47/69 ,  A61K38/00 ,  A61K48/00

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：US20160106671A1

公开(公告)日：2016-04-21

申请号：US14970998

申请日：2015-12-16

Applicant: STC.UNM ,  SANDIA CORPORATION

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

IPC: A61K9/127 ,  C12N15/113 ,  A61K39/05 ,  A61K31/711 ,  A61K31/704 ,  A61K33/24

CPC classification number: 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

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：US20150272885A1

公开(公告)日：2015-10-01

申请号：US14350674

申请日：2012-10-12

Applicant: STC.UNM ,  SANDIA CORPORATION

Inventor： Carlee Erin Ashley ,  C. Jeffrey Brinker ,  Eric C. Carnes ,  Mohammad Houman Fekrazad ,  Linda A. Felton ,  Oscar Negrete ,  David Patrick Padilla ,  Brian S. Wilkinson ,  Dan C. Wilkinson ,  Cheryl L. Willman

IPC: A61K9/127 ,  A61K45/06 ,  A61K31/704 ,  A61K31/513 ,  A61K31/713 ,  A61K38/17

CPC classification number: A61K48/0008 ,  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 ,  A61K47/6923 ,  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：US20150010475A1

公开(公告)日：2015-01-08

申请号：US14369741

申请日：2012-12-31

Applicant: STC. UNM ,  SANDIA CORPORATION

Inventor： C. Jeffrey Brinker ,  David S. Peabody ,  Walker Kip Wharton ,  Bryce Chackerian ,  Carlee Erin Ashley ,  Cheryl L. Willman ,  Eric C. Carnes ,  Katherine Epler ,  Robert Eric Castillo

IPC: A61K47/48 ,  C12N15/113 ,  C12N15/11 ,  C07K7/06 ,  A61K31/704

CPC classification number: A61K31/704 ,  A61K47/62 ,  A61K47/64 ,  A61K47/6911 ,  C07K7/06 ,  C12N15/111 ,  C12N15/113

Abstract: The present invention relates to the use of which are attached or anchored phospholipid biolayers further modified by CRLF-2 and CD 19 binding peptides which may be used for delivering pharmaceutical cargos, to cells expressing CRLF-2 and CD 19, thereby treating cancer, in particular, acute lymphoblastic leukemia (ALL), including (B-precursor acute lymphoblastic leukemia (B-ALL). Novel CRLF-2 binding peptides and CLRF-2 and CD19-binding viral-like particles (VLPs) useful in the treatment of cancer, including ALL are also provided.

Abstract translation: 本发明涉及其用途，其可用于将可用于递送药物载体的CRLF-2和CD19结合肽进一步修饰的磷脂生物层结合到表达CRLF-2和CD19的细胞中，从而治疗癌症 特别是急性淋巴细胞白血病（ALL），包括（B-前体急性成淋巴细胞白血病（B-ALL）），用于治疗癌症的新型CRLF-2结合肽和CLRF-2和CD19结合病毒样颗粒（VLP） ，也包括ALL。

公开(公告)号：US20170298449A1

公开(公告)日：2017-10-19

申请号：US15638926

申请日：2017-06-30

Applicant: STC.UNM ,  ST. JUDE CHILDREN'S RESEARCH HOSPITAL ,  THE CHILDREN'S HOSPITAL OF PHILADELPHIA ON BEHALF OF CHILDREN'S ONCOLOGY GROUP

Inventor： Cheryl L. Willman ,  Stephen P. Hunger ,  Charles Mullighan ,  I-Ming Chen ,  Kathryn G. Roberts ,  Huining Kang ,  Richard C. Harvey

IPC: C12Q1/68

CPC classification number: C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/158

Abstract: The invention provides arrays, systems, devices, methods, computer-readable media and kits that enable expression-based classification of B-precursor acute lymphoblastic leukemia (ALL) as being either responsive or non-responsive to tyrosine kinase inhibitor mono or co-therapy.