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1. 发明申请

US20180049984A1 Carriers for Plasmid and RNP Delivery in the Treatment of Cancer and Other Disease States 审中-公开
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.

2. 发明申请

US20180028686A1 Protocells for Plasmid and RNP Delivery in the Treatment of Cancer and Other Disease States 审中-公开
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.

3. 发明申请

US20190262469A1 PROTOCELLS TO TREAT MICROBIAL INFECTION AND FOR SYNERGISTIC DELIVERY 审中-公开
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.

4. 发明授权

US08828736B2 Microelectroporation device for genomic screening 有权
标题翻译：用于基因组筛选的微电极装置
公开(公告)号：US08828736B2
公开(公告)日：2014-09-09
申请号：US13173180
申请日：2011-06-30
申请人： Thomas D. Perroud , Ronald F. Renzi , Oscar Negrete , Mark R. Claudnic
发明人： Thomas D. Perroud , Ronald F. Renzi , Oscar Negrete , Mark R. Claudnic
IPC分类号： G01N25/08 , C12M1/42 , B01L3/00
CPC分类号： B01L3/502761 , B01L2200/0668 , B01L2300/0645 , B01L2300/0864 , C12M35/02 , Y10T436/2575
摘要： We have developed an microelectroporation device that combines microarrays of oligonucleotides, microfluidic channels, and electroporation for cell transfection and high-throughput screening applications (e.g. RNA interference screens). Microarrays allow the deposition of thousands of different oligonucleotides in microscopic spots. Microfluidic channels and microwells enable efficient loading of cells into the device and prevent cross-contamination between different oligonucleotides spots. Electroporation allows optimal transfection of nucleic acids into cells (especially hard-to-transfect cells such as primary cells) by minimizing cell death while maximizing transfection efficiency. This invention has the advantage of a higher throughput and lower cost, while preventing cross-contamination compared to conventional screening technologies. Moreover, this device does not require bulky robotic liquid handling equipment and is inherently safer given that it is a closed system.
摘要翻译：我们开发了一种微电极装置，其结合寡核苷酸微阵列，微流体通道和电穿孔用于细胞转染和高通量筛选应用（例如RNA干扰筛选）。微阵列允许在微观斑点中沉积数千种不同的寡核苷酸。微流体通道和微孔能够有效地将细胞装载到装置中并防止不同寡核苷酸斑点之间的交叉污染。电穿孔允许通过最大限度地减少细胞死亡同时使转染效率最大化将核酸最佳地转染到细胞（特别是难转染细胞，如原代细胞）中。本发明具有较高的生产能力和较低的成本，同时防止与常规筛选技术相比的交叉污染。此外，该装置不需要庞大的机器人液体处理设备，并且由于它是封闭的系统，所以固有地更安全。

5. 发明授权

US09549976B1 Affinity selection of Nipah and Hendra virus-related vaccine candidates from a complex random peptide library displayed on bacteriophage virus-like particles 有权
标题翻译：从噬菌体病毒样颗粒中显示的复杂随机肽库的Nipah和Hendra病毒相关疫苗候选物的亲和力选择
公开(公告)号：US09549976B1
公开(公告)日：2017-01-24
申请号：US14081629
申请日：2013-11-15
申请人： David S. Peabody , Bryce Chackerian , Carlee Ashley , Eric Carnes , Oscar Negrete
发明人： David S. Peabody , Bryce Chackerian , Carlee Ashley , Eric Carnes , Oscar Negrete
IPC分类号： A61K39/00 , A61K39/155 , A61K49/00 , A61K39/385 , C12Q1/70 , C12N7/00 , G01N33/569
CPC分类号： A61K39/155 , A61K39/12 , A61K2039/5256 , A61K2039/5258 , C12N2760/18234 , G01N33/56983
摘要： The invention relates to virus-like particles of bacteriophage MS2 (MS2 VLPs) displaying peptide epitopes or peptide mimics of epitopes of Nipah Virus envelope glycoprotein that elicit an immune response against Nipah Virus upon vaccination of humans or animals. Affinity selection on Nipah Virus-neutralizing monoclonal antibodies using random sequence peptide libraries on MS2 VLPs selected peptides with sequence similarity to peptide sequences found within the envelope glycoprotein of Nipah itself, thus identifying the epitopes the antibodies recognize. The selected peptide sequences themselves are not necessarily identical in all respects to a sequence within Nipah Virus glycoprotein, and therefore may be referred to as epitope mimics VLPs displaying these epitope mimics can serve as vaccine. On the other hand, display of the corresponding wild-type sequence derived from Nipah Virus and corresponding to the epitope mapped by affinity selection, may also be used as a vaccine.
摘要翻译：本发明涉及噬菌体MS2（MS2 VLP）的病毒样颗粒，其显示了尼泊尔病毒包膜糖蛋白的表位的肽表位或肽模拟物，其在接种人或动物时引起针对尼帕病毒的免疫应答。在Nipah病毒中和单克隆抗体上的亲和力选择，使用MS2 VLP上的随机序列肽文库，选择与Nipah本身的包膜糖蛋白内发现的肽序列具有序列相似性的肽，从而鉴定抗体识别的表位。所选择的肽序列本身在所有方面不一定与尼帕病毒糖蛋白内的序列相同，因此可以称为表位模拟物，显示这些表位模拟物的VLP可以用作疫苗。另一方面，从Nipah Virus得到的相应野生型序列的显示与通过亲和力选择映射的表位对应，也可以用作疫苗。

6. 发明申请

US20120004144A1 MICROELECTROPORATION DEVICE FOR GENOMIC SCREENING 有权
标题翻译：用于基因检测的微电子设备
公开(公告)号：US20120004144A1
公开(公告)日：2012-01-05
申请号：US13173180
申请日：2011-06-30
申请人： Thomas D. Perroud , Ronald F. Renzi , Oscar Negrete , Mark R. Claudnic
发明人： Thomas D. Perroud , Ronald F. Renzi , Oscar Negrete , Mark R. Claudnic
IPC分类号： C40B60/12
CPC分类号： B01L3/502761 , B01L2200/0668 , B01L2300/0645 , B01L2300/0864 , C12M35/02 , Y10T436/2575
摘要： We have developed an microelectroporation device that combines microarrays of oligonucleotides, microfluidic channels, and electroporation for cell transfection and high-throughput screening applications (e.g. RNA interference screens). Microarrays allow the deposition of thousands of different oligonucleotides in microscopic spots. Microfluidic channels and microwells enable efficient loading of cells into the device and prevent cross-contamination between different oligonucleotides spots. Electroporation allows optimal transfection of nucleic acids into cells (especially hard-to-transfect cells such as primary cells) by minimizing cell death while maximizing transfection efficiency. This invention has the advantage of a higher throughput and lower cost, while preventing cross-contamination compared to conventional screening technologies. Moreover, this device does not require bulky robotic liquid handling equipment and is inherently safer given that it is a closed system.
摘要翻译：我们开发了一种微电极装置，其结合寡核苷酸微阵列，微流体通道和电穿孔用于细胞转染和高通量筛选应用（例如RNA干扰筛选）。微阵列允许在微观斑点中沉积数千种不同的寡核苷酸。微流体通道和微孔能够有效地将细胞装载到装置中并防止不同寡核苷酸斑点之间的交叉污染。电穿孔允许通过最大限度地减少细胞死亡同时使转染效率最大化将核酸最佳地转染到细胞（特别是难转染细胞，如原代细胞）中。本发明具有较高的生产能力和较低的成本，同时防止与常规筛选技术相比的交叉污染。此外，该装置不需要庞大的机器人液体处理设备，并且由于它是封闭的系统，所以固有地更安全。

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