公开(公告)号：US09315825B2

公开(公告)日：2016-04-19

申请号：US13247306

申请日：2011-09-28

申请人： James M Wilson ,  Anna P Tretiakova ,  Jenny Agnes Greig

发明人： James M Wilson ,  Anna P Tretiakova ,  Jenny Agnes Greig

IPC分类号： A01N63/00 ,  C12N15/86 ,  C12N7/00 ,  C12N9/22 ,  A61K48/00 ,  C07K14/47

CPC分类号： A61K48/0066 ,  C07K7/08 ,  C07K14/00 ,  C07K14/4702 ,  C07K2319/09 ,  C07K2319/715 ,  C07K2319/80 ,  C07K2319/81 ,  C07K2319/92 ,  C12N7/00 ,  C12N9/22 ,  C12N15/86 ,  C12N2750/14143 ,  C12N2750/14151 ,  C12N2800/30 ,  C12N2800/40 ,  C12N2800/80 ,  C12N2830/002 ,  C12N2830/003 ,  C12N2830/005 ,  C12N2830/006 ,  C12N2830/20 ,  C12N2840/203 ,  C12Y301/21004

摘要： The present invention relates to gene therapy systems designed for the delivery of a therapeutic product to a subject using replication-defective virus composition(s) engineered with a built-in safety mechanism for ablating the therapeutic gene product, either permanently or temporarily, in response to a pharmacological agent—preferably an oral formulation, e.g., a pill. The invention is based, in part, on the applicants' development of an integrated approach, referred to herein as “PITA” (Pharmacologically Induced Transgene Ablation), for ablating a transgene or negatively regulating transgene expression. In this approach, replication-deficient viruses are used to deliver a transgene encoding a therapeutic product (an RNA or a protein) so that it is expressed in the subject, but can be reversibly or irreversibly turned off by administering the pharmacological agent; e.g., by administration of a small molecule that induces expression of an ablator specific for the transgene or its RNA transcript.

摘要翻译： 本发明涉及基因治疗系统，其被设计用于使用使用内置安全机制工程改造的复制缺陷病毒组合物将治疗产品递送给受试者，所述安全机制永久地或临时地用于消融治疗性基因产物 药物剂 - 优选口服制剂，例如丸剂。 本发明部分地基于申请人开发一种综合方法，在本文中称为“PITA”（药理诱导的转基因消融），用于消融转基因或负调控转基因表达。 在该方法中，使用复制缺陷病毒递送编码治疗产物（RNA或蛋白质）的转基因，使其在受试者中表达，但通过施用药理学试剂可逆地或不可逆地截止; 例如通过施用诱导特异于转基因或其RNA转录物的消融体表达的小分子。

公开(公告)号：US09343231B2

公开(公告)日：2016-05-17

申请号：US14033479

申请日：2013-09-22

申请人： Liang Chai ,  Alan Rae ,  James M Wilson

发明人： Liang Chai ,  Alan Rae ,  James M Wilson

IPC分类号： H01G4/12 ,  H01G4/008 ,  H01G4/005 ,  H01G4/30

CPC分类号： H01G4/10 ,  H01G4/005 ,  H01G4/008 ,  H01G4/12 ,  H01G4/1209 ,  H01G4/30 ,  Y10T29/43 ,  Y10T29/435

摘要： A capacitor, and methods of its manufacture, having improved capacitance efficiency which results from increasing the effective area of an electrode surface are disclosed. An improved “three-dimensional” capacitor may be constructed with electrode layers having three-dimensional aspects at the point of interface with a dielectric such that portions of the electrode extend into the dielectric layer.

摘要翻译： 公开了一种电容器及其制造方法，其具有由于增加电极表面的有效面积而提高的电容效率。 可以在与电介质的界面点处具有三维方面的电极层来构造改进的“三维”电容器，使得电极的一部分延伸到电介质层中。

公开(公告)号：US08603459B2

公开(公告)日：2013-12-10

申请号：US13337608

申请日：2011-12-27

申请人： James M Wilson ,  Guangping Gao ,  Soumitra Roy

发明人： James M Wilson ,  Guangping Gao ,  Soumitra Roy

IPC分类号： A61K35/76 ,  C12N15/11 ,  C12N15/63 ,  C12N15/33

CPC分类号： A61K39/235 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/525 ,  A61K2039/5256 ,  A61K2039/57 ,  C07K14/005 ,  C12N7/00 ,  C12N15/86 ,  C12N2710/10022 ,  C12N2710/10321 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10362 ,  C12N2710/20022 ,  C12N2740/16122 ,  C12N2740/17022 ,  C12N2750/14122 ,  C12N2760/14134 ,  C12N2760/16134 ,  C12N2760/20122 ,  C12N2830/002 ,  C12N2830/55

摘要： A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

公开(公告)号：US08685387B2

公开(公告)日：2014-04-01

申请号：US12744441

申请日：2008-11-24

申请人： Soumitra Roy ,  James M Wilson ,  Luc H Vandenberghe

发明人： Soumitra Roy ,  James M Wilson ,  Luc H Vandenberghe

IPC分类号： A61K35/76 ,  C12N7/01 ,  C12N15/00 ,  C12N15/34 ,  A61K48/00

CPC分类号： C12N15/86 ,  A61K48/00 ,  A61K2039/525 ,  A61K2039/5256 ,  C07K14/005 ,  C12N7/00 ,  C12N2710/10321 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10361 ,  C12N2760/16122

摘要： A recombinant vector comprises simian adenovirus SAdV-39, -25.2, -26, -30, -37, and -38 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus SAdV-39, -25.2, -26, -30, -37, and -383 gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

摘要翻译： 重组载体包含猿猴腺病毒SAdV-39，-25.2，-26，-30，-37和-38序列，以及在调控序列控制下的异源基因。 还公开了表达猿猴腺病毒SAdV-39，-25.2，-26，-30，-37和-383基因的细胞系。 提供了使用载体和细胞系的方法。

公开(公告)号：US08524446B2

公开(公告)日：2013-09-03

申请号：US12962793

申请日：2010-12-08

申请人： Guangping Gao ,  James M Wilson ,  Mauricio R. Alvira

发明人： Guangping Gao ,  James M Wilson ,  Mauricio R. Alvira

IPC分类号： C12Q1/70 ,  C12Q1/68 ,  C07H21/04

CPC分类号： C12N15/86 ,  A61K38/177 ,  A61K38/4846 ,  A61K48/00 ,  C07K14/005 ,  C12N7/00 ,  C12N2750/14121 ,  C12N2750/14122 ,  C12N2750/14143 ,  C12N2750/14151 ,  C12N2750/14152 ,  C12N2750/14162 ,  C12N2750/14171 ,  C12N2830/008 ,  C12N2830/48 ,  C12N2830/85 ,  C12N2830/90 ,  C12Q1/701 ,  C12Q2600/158 ,  C12Y304/21022

摘要： A method for detecting and isolating AAV sequences in a sample of DNA obtained from tissue or cells is provided, which sample contains DNA and proviral AAV. The method involves subjecting the sample containing DNA to amplification via polymerase chain reaction (PCR) using a first set of primers which specifically amplify a first AAV region. The first AAV region is characterized by having at least 250 nucleotides of AAV capsid nucleic acid sequence, a variable sequence flanked by a sequence of at least 18 nucleotides at the 5′ end of the first AAV region and a sequence of at least 18 nucleotides at the 3′ end of the first AAV region. Each of the 5′ and 3′ at least 18 nucleotides is the same over at least 9 consecutive nucleotides relative to corresponding sequences in an alignment of at least two AAV serotypes. Each of the sets of primers consist of a 5′ primer and a 3′ primer. The method is further useful for identifying AAV sequences in the sample by the presence of amplified proviral AAV sequences.

摘要翻译： 提供了从组织或细胞获得的DNA样品中检测和分离AAV序列的方法，该样品含有DNA和前病毒AAV。 该方法包括使用特异性扩增第一AAV区域的第一组引物通过聚合酶链反应（PCR）使含有DNA的样品进行扩增。 第一个AAV区的特征在于具有AAV衣壳核酸序列的至少250个核苷酸，在第一AAV区的5'末端侧接至少18个核苷酸的序列的可变序列和至少18个核苷酸的序列 第一个AAV区域的3'端。 相对于至少两种AAV血清型的比对中的相应序列，5'和3'至少18个核苷酸中的每一个在至少9个连续核苷酸上相同。 每组引物由5'引物和3'引物组成。 该方法进一步用于通过扩增的前病毒AAV序列的存在来鉴定样品中的AAV序列。

公开(公告)号：US07838277B2

公开(公告)日：2010-11-23

申请号：US12011377

申请日：2008-01-25

申请人： Guangping Gao ,  James M Wilson

发明人： Guangping Gao ,  James M Wilson

IPC分类号： C12N7/01 ,  A61K39/235

CPC分类号： C07K14/005 ,  A61K38/00 ,  A61K39/00 ,  C12N2710/10322

摘要： Chimpanzee serotype C68 proteins, peptides, and polypeptide are provided. Also provided are novel adenoviruses derived from these proteins, as well as compositions containing these proteins and methods of using same for immunization and therapy. Further, a rapid method for screening recombinant transformants using a visually detectable method is described.

摘要翻译： 提供黑猩猩血清型C68蛋白，肽和多肽。 还提供了衍生自这些蛋白质的新型腺病毒，以及含有这些蛋白质的组合物及其用于免疫和治疗的方法。 此外，描述了使用视觉可检测方法筛选重组转化体的快速方法。

公开(公告)号：US07022519B2

公开(公告)日：2006-04-04

申请号：US10251157

申请日：2002-09-20

申请人： Guangping Gao ,  James M Wilson

发明人： Guangping Gao ,  James M Wilson

IPC分类号： C12N5/10 ,  C12N15/63

CPC分类号： G01R31/275 ,  C12N15/86 ,  C12N2710/10344 ,  C12N2750/14143 ,  C12N2750/14151 ,  C12N2840/20 ,  G01R31/013 ,  G01R31/316

摘要： A method for producing recombinant adeno-associated virus in the absence of contaminating helper virus or wild-type virus involves culturing a mammalian host cell containing an rAd/AAV hybrid virus, an AAV rep sequence and an AAV cap sequence under the control of regulatory sequences directing expression thereof. The rAd/AAV hybrid virus contains a rAAV construct to be packaged into an AAV virion in an backbone containing the adenoviral sequences necessary to express E1a and E1b gene products and to permit replication of the hybrid virus. The method of the invention permits replication of the hybrid virus and production of rAAV virion in this host cell in the absence of a helper virus and obviates a subsequent purification step to purify rAAV from contaminating virus.

公开(公告)号：US10920244B2

公开(公告)日：2021-02-16

申请号：US13266599

申请日：2010-04-29

申请人： Christie L Bell ,  James M Wilson

发明人： Christie L Bell ,  James M Wilson

IPC分类号： C12N15/864 ,  C12N15/86 ,  C12N7/01 ,  C12N15/35 ,  C12N15/40 ,  A61K48/00

摘要： An artificial AAV capsid comprising a heterologous conducting airway targeting sequence is provided. The artificial AAV is useful as a targeting moiety, for delivery of heterologous molecules which are associated therewith. The artificial AAV is also useful in the generation of AAV vectors having the artificial capsid. Also described are methods of modifying the native tropism and transduction efficiency of vectors by improving and/or ablating their ability to transduce conducting airway cells. Methods of targeting conducting airway cells and delivering therapeutic and other molecules thereto are also provided.

公开(公告)号：US08524219B2

公开(公告)日：2013-09-03

申请号：US12744375

申请日：2008-11-24

申请人： Soumitra Roy ,  James M Wilson ,  Luc H Vandenberghe

发明人： Soumitra Roy ,  James M Wilson ,  Luc H Vandenberghe

IPC分类号： A61K35/76 ,  A61K48/00 ,  C12N7/01 ,  C12N15/00 ,  C12N15/34

CPC分类号： A61K35/761 ,  A61K38/162 ,  C07K14/005 ,  C12N7/00 ,  C12N15/86 ,  C12N2710/10321 ,  C12N2710/10322 ,  C12N2710/10332 ,  C12N2710/10343 ,  C12N2710/10351 ,  C12N2810/6018 ,  Y02A50/463

摘要： A recombinant vector comprises simian adenovirus 28, simian adenovirus 27, simian adenovirus 32, simian adenovirus 33, and/or simian adenovirus 35 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses one or more simian adenovirus-28, -27, -32, -33, or -35 genes is also disclosed. Methods of using the vectors and cell lines are provided.

公开(公告)号：US08105574B2

公开(公告)日：2012-01-31

申请号：US11820439

申请日：2007-06-19

申请人： James M Wilson ,  Guangping Gao ,  Soumitra Roy

发明人： James M Wilson ,  Guangping Gao ,  Soumitra Roy

IPC分类号： C12N15/00 ,  C12N15/34 ,  C12N15/11 ,  C12N15/63

CPC分类号： A61K39/235 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/525 ,  A61K2039/5256 ,  A61K2039/57 ,  C07K14/005 ,  C12N7/00 ,  C12N15/86 ,  C12N2710/10022 ,  C12N2710/10321 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10362 ,  C12N2710/20022 ,  C12N2740/16122 ,  C12N2740/17022 ,  C12N2750/14122 ,  C12N2760/14134 ,  C12N2760/16134 ,  C12N2760/20122 ,  C12N2830/002 ,  C12N2830/55

摘要： A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

摘要翻译： 重组载体包含猿猴腺病毒序列和在调节序列控制下的异源基因。 还公开了表达猿腺病毒基因的细胞系。 提供了使用载体和细胞系的方法。