公开(公告)号：US20050260588A1

公开(公告)日：2005-11-24

申请号：US10513191

申请日：2003-05-01

申请人： Charles Conrad ,  Yin Chen

发明人： Charles Conrad ,  Yin Chen

IPC分类号： C12N15/74 ,  C12P21/06 ,  C12Q1/68

CPC分类号： C12N15/74

摘要： An expression vector for altering expression of a target nucleic acid sequence in a host cell by production of single-stranded cDNA (ssDNA) in the host cell in vivo. The expression vector is comprised of a cassette comprising a sequence of interest, an inverted tandem repeat, and a primer binding site 3′ to the inverted tandem repeat, and a reverse transcriptase/RNAse H coding gene, and may be transfected into the host cell. Transcription of the cassette by the host cell produces an RNA template which is reverse transcribed with the product of the RT coding gene to produce ssDNA of a specified sequence. The ssDNA is modified to remove flanking vector sequences by taking advantage of the “stem-loop” structure of the ssDNA, which forms as a result of the inverted tandem repeat that allows the ssDNA to fold back on itself, forming a double stranded DNA stem. The double-stranded stem may contain one or more restriction endonuclease recognition sites and the loop, which remains as ssDNA, can be any desired nucleotide sequence. This design allows the double-stranded stem of the stem-loop intermediate to be cleaved by the desired corresponding restriction endonuclease(s) and the loop portion is then released as a linearized, single-stranded piece of DNA. The resulting ssDNA binds to an endogenous target nucleic acid sequence to alter the expression of that sequence for such therapeutic purposes as gene activation or inactivation using duplex or triplex binding of nucleic acids, site-directed mutagenesis, interruption of cellular function by binding to specific cellular proteins, or interfering with RNA splicing functions.

摘要翻译： 用于通过在体内在宿主细胞中产生单链cDNA（ssDNA）来改变宿主细胞中靶核酸序列的表达的表达载体。 表达载体由包含感兴趣序列，反向串联重复序列和反向串联重复序列的引物结合位点3'和逆转录酶/ RNA酶H编码基因的盒组成，并且可以转染入宿主细胞 。 由宿主细胞转录盒产生RNA模板，其与RT编码基因的产物逆转录以产生指定序列的ssDNA。 通过利用ssDNA的“茎 - 环”结构，ssDNA被修饰以去除侧翼载体序列，其由反向串联重复的结果形成，其允许ssDNA自身折叠，形成双链DNA干 。 双链茎可以含有一个或多个限制性内切核酸酶识别位点，并且作为ssDNA保留的环可以是任何所需的核苷酸序列。 该设计允许茎环中间体的双链茎被所需的相应的限制性内切核酸酶切割，然后将环部分作为线性化的单链DNA片段释放。 所得的ssDNA结合内源靶核酸序列以改变该序列的表达，用于诸如基因激活或灭活的治疗目的，使用核酸的双链或三重结合，定点突变，通过结合特异性细胞中断细胞功能 蛋白质或干扰RNA剪接功能。

公开(公告)号：US20070160581A1

公开(公告)日：2007-07-12

申请号：US11586797

申请日：2006-10-26

申请人： Charles Conrad ,  Yin Chen

发明人： Charles Conrad ,  Yin Chen

IPC分类号： A61K48/00 ,  C12N15/86 ,  C12N5/08

CPC分类号： A61K48/005

摘要： Methods and compositions comprising a DNA expression cassette for producing ss-cDNA inside a host cell (in vivo). The expression system optionally contains a reverse transcriptase/RNAse H coding gene, and a restriction endonuclease gene. The cassette carries cloning sites in two distinct locations for cloning and expressing a sequence of interest. The mRNA then serves as a template for reverse transcriptase and synthesis of the ss-cDNA. In one embodiment, the ss-cDNA folds and forms a dsDNA “stem-loop” structure which can be designed to contain restriction endonuclease recognition site the stem portion for cutting off the ssDNA loop containing the SOI having minimal flanking sequence attached. In another embodiment, the mRNA template folds prior to reverse transcription and serves as a termination signal for the RT. Again, a ss-cDNA is formed having only minimal flanking sequence. The data shows the usefulness of this system for producing ss-DNA inside a host/target cell.

摘要翻译： 包含用于在宿主细胞内（体内）产生ss-cDNA的DNA表达盒的方法和组合物。 表达系统任选地含有逆转录酶/ RNA酶H编码基因和限制性内切核酸酶基因。 该盒携带在两个不同位置的克隆位点用于克隆和表达感兴趣的序列。 然后，mRNA用作逆转录酶和ss-cDNA合成的模板。 在一个实施方案中，ss-cDNA折叠并形成dsDNA“茎 - 环”结构，其可被设计为含有限制性内切核酸酶识别位点，用于切断含有附着有最小侧翼序列的SOI的ssDNA环的茎部分。 在另一个实施方案中，mRNA模板在逆转录之前折叠并用作RT的终止信号。 再次，形成仅具有最小侧翼序列的ss-cDNA。 数据显示该系统在宿主/靶细胞内产生ss-DNA的有用性。

公开(公告)号：US09018213B2

公开(公告)日：2015-04-28

申请号：US14236208

申请日：2012-07-31

申请人： Guisen Zhang ,  Yin Chen ,  Xiangqing Xu ,  Xin Liu ,  Song Zhao ,  Bifeng Liu ,  Minquan Yu ,  Yinli Qiu

发明人： Guisen Zhang ,  Yin Chen ,  Xiangqing Xu ,  Xin Liu ,  Song Zhao ,  Bifeng Liu ,  Minquan Yu ,  Yinli Qiu

IPC分类号： A61K31/496 ,  A61K31/453 ,  A61K31/454 ,  C07D311/94 ,  C07D405/12 ,  C07D417/12 ,  C07D417/14 ,  C07D413/14 ,  C07D311/80 ,  C07D409/12

CPC分类号： C07D311/94 ,  A61K31/453 ,  A61K31/454 ,  A61K31/496 ,  C07D311/80 ,  C07D405/12 ,  C07D409/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14

摘要： Disclosed are alicyclic[c]benzopyrone derivatives and use thereof. The alicyclic[c]benzopyrone derivatives are compounds represented by formula I or their salts. The present compounds not only significantly improve high activity induced by MK-801, but also effectively improve clambering symptom induced by Apomorphine and do not cause EPS within effective dose. These in vitro targets and in vivo pharmacological models are closely related to diseases of the nervous system caused by dopamine dysfunction, especially schizophrenia. Therefore the present compounds can be used for the treatment of central nervous system diseases, especially schizophrenia. ED50 is lower and effect is stronger in two animal models i.e. high activity induced by MK-801 and clambering symptom induced by Apomorphine, while ED50 is higher and therapeutic index is greater in animal models of catalepsy.

摘要翻译： 公开了脂环族[c]苯并吡喃酮衍生物及其用途。 脂环式[c]苯并吡喃酮衍生物是由式I表示的化合物或其盐。 本发明化合物不仅显着改善了MK-801诱导的高活性，而且有效地改善了阿扑吗啡引起的痉挛症状，不会有效剂量引起EPS。 这些体外靶标和体内药理学模型与由多巴胺功能障碍，特别是精神分裂症引起的神经系统疾病密切相关。 因此，本发明化合物可用于治疗中枢神经系统疾病，特别是精神分裂症。 ED50较低，两种动物模型中效果更强，即由MK-801诱导的高活性和阿扑吗啡引起的痉挛症状，而ED50较高，而在僵住症的动物模型中治疗指数更高。

公开(公告)号：US08828958B2

公开(公告)日：2014-09-09

申请号：US11664052

申请日：2005-09-28

申请人： Yin Chen ,  Xin Xing Tan

发明人： Yin Chen ,  Xin Xing Tan

IPC分类号： C07H21/04 ,  C12N15/11 ,  C12N15/00

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/111 ,  C12N2310/16 ,  C12N2320/11 ,  C12N2320/30 ,  C12N2330/31 ,  C12N2330/50

摘要： The current invention is directed to oligonucleotide sequences isolated from a sequence designated rbl-1 [SEQ ID NO. 19] that either kill or inhibit growth, or prevent the production of endogenously expressed toxin, of microorganisms. These ssDNA sequences, identified through use of a screening method, appear to act as modulators of essential growth functions which may act at the level of triplex formation, antisense inhibition, or as aptamers that alter gene function. The sequences, referred to as minimum functional regions, or MFRs, are useful inter alia as therapeutic agents for treatment of sepsis and other pathologies caused by microorganisms such as sepsis and/or in which microorganisms are contributory agents.

摘要翻译： 本发明涉及从命名为rbl-1 [SEQ ID NO.1]的序列分离的寡核苷酸序列。 19]可以杀死或抑制微生物的生长，或阻止生成内源性表达的毒素。 通过使用筛选方法鉴定的这些ssDNA序列似乎可以作为必需生长功能的调节剂，其可以在三重形成，反义抑制水平或作为改变基因功能的适体的作用下起作用。 称为最小功能区域或MFR的序列尤其可用作治疗败血症的治疗剂和由诸如败血症和/或其中微生物是贡献剂的微生物引起的其它病症。

公开(公告)号：US20140171442A1

公开(公告)日：2014-06-19

申请号：US14236208

申请日：2012-07-31

申请人： Guisen Zhang ,  Yin Chen ,  Xiangqing Xu ,  Xin Liu ,  Song Zhao ,  Bifeng Liu ,  Miquan Yu ,  Yinli Qiu

发明人： Guisen Zhang ,  Yin Chen ,  Xiangqing Xu ,  Xin Liu ,  Song Zhao ,  Bifeng Liu ,  Miquan Yu ,  Yinli Qiu

IPC分类号： C07D311/94 ,  C07D413/14 ,  C07D417/12 ,  C07D409/12

CPC分类号： C07D311/94 ,  A61K31/453 ,  A61K31/454 ,  A61K31/496 ,  C07D311/80 ,  C07D405/12 ,  C07D409/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14

摘要： Disclosed are alicyclic[c]benzopyrone derivatives and use thereof. The alicyclic[c]benzopyrone derivatives are compounds represented by formula I or their salts. The present compounds not only significantly improve high activity induced by MK-801, but also effectively improve clambering symptom induced by Apomorphine and do not cause EPS within effective dose. These in vitro targets and in vivo pharmacological models are closely related to diseases of the nervous system caused by dopamine dysfunction, especially schizophrenia. Therefore the present compounds can be used for the treatment of central nervous system diseases, especially schizophrenia. ED50 is lower and effect is stronger in two animal models i.e. high activity induced by MK-801 and clambering symptom induced by Apomorphine, while ED50 is higher and therapeutic index is greater in animal models of catalepsy.

摘要翻译： 公开了脂环族[c]苯并吡喃酮衍生物及其用途。 脂环式[c]苯并吡喃酮衍生物是由式I表示的化合物或其盐。 本发明化合物不仅显着改善了MK-801诱导的高活性，而且有效地改善了阿扑吗啡引起的痉挛症状，不会有效剂量引起EPS。 这些体外靶标和体内药理学模型与由多巴胺功能障碍，特别是精神分裂症引起的神经系统疾病密切相关。 因此，本发明化合物可用于治疗中枢神经系统疾病，特别是精神分裂症。 ED50较低，两种动物模型中效果更强，即由MK-801诱导的高活性和阿扑吗啡引起的痉挛症状，而ED50较高，而在僵住症的动物模型中治疗指数更高。

公开(公告)号：US20140113911A1

公开(公告)日：2014-04-24

申请号：US14009581

申请日：2012-04-06

申请人： Guisen Zhang ,  Yin Chen ,  Xiangqing Xu ,  Bifeng Liu ,  Xin Liu ,  Song Zhao ,  Shicheng Liu ,  Minquan Yu ,  Heng Zhang ,  Xinghua Liu

发明人： Guisen Zhang ,  Yin Chen ,  Xiangqing Xu ,  Bifeng Liu ,  Xin Liu ,  Song Zhao ,  Shicheng Liu ,  Minquan Yu ,  Heng Zhang ,  Xinghua Liu

IPC分类号： C07D417/12 ,  C07D413/14

CPC分类号： C07D417/12 ,  A61K31/454 ,  A61K31/496 ,  C07D405/12 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： The present invention relates to the field of pharmaceutical chemistry, and in particular, to a benzopyrone derivative and a use thereof. The benzopyrone derivative is compound having a structure of formula (I) or a pharmaceutically acceptable salt thereof. It has been found by experiments that, this type of compounds is useful in prevention or treatment of neuropsychical diseases.

摘要翻译： 本发明涉及药物化学领域，特别涉及苯并吡喃酮衍生物及其应用。 苯并吡喃酮衍生物是具有式（I）结构的化合物或其药学上可接受的盐。 通过实验发现，这种类型的化合物可用于预防或治疗神经精神疾病。

公开(公告)号：US20070040211A1

公开(公告)日：2007-02-22

申请号：US11209145

申请日：2005-08-22

申请人： Shao Ku ,  Yin Chen ,  Wenpin Lu ,  Tahui Wang

发明人： Shao Ku ,  Yin Chen ,  Wenpin Lu ,  Tahui Wang

IPC分类号： H01L29/792

CPC分类号： H01L29/7923 ,  H01L29/1045

摘要： A multi-bit memory cell includes a substrate; a multi-bit charge-trapping cell over the substrate, the multi-bit charge-trapping cell having a first lateral side and a second lateral side; a source region in the substrate, a portion of the source region being under the first side of the multi-bit charge-trapping cell; a drain region in the substrate, a portion of the drain region being under the second side of the multi-bit charge-trapping cell; and a channel region in the substrate between the source region and the drain region. The channel region has one of a p-type doping and an n-type doping, and the doping is configured to provide a highest doping concentration near the central portion of the channel region.

摘要翻译： 多位存储单元包括基板; 位于衬底上的多位电荷俘获电池，所述多位电荷俘获电池具有第一侧面和第二侧面; 源区域，源区域中的一部分位于多位电荷捕获单元的第一侧之下; 所述衬底中的漏极区域，所述漏极区域的一部分位于所述多位电荷俘获电池的第二侧的下方; 以及在源极区域和漏极区域之间的衬底中的沟道区域。 沟道区具有p型掺杂和n型掺杂之一，并且掺杂被配置为在沟道区的中心部分附近提供最高的掺杂浓度。

公开(公告)号：US09315496B2

公开(公告)日：2016-04-19

申请号：US14009581

申请日：2012-04-06

申请人： Guisen Zhang ,  Yin Chen ,  Xiangqing Xu ,  Bifeng Liu ,  Xin Liu ,  Song Zhao ,  Shicheng Liu ,  Minquan Yu ,  Heng Zhang ,  Xinghua Liu

发明人： Guisen Zhang ,  Yin Chen ,  Xiangqing Xu ,  Bifeng Liu ,  Xin Liu ,  Song Zhao ,  Shicheng Liu ,  Minquan Yu ,  Heng Zhang ,  Xinghua Liu

IPC分类号： A61K31/496 ,  A61K31/454 ,  C07D405/12 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14

CPC分类号： C07D417/12 ,  A61K31/454 ,  A61K31/496 ,  C07D405/12 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： The present invention relates to the field of pharmaceutical chemistry, and in particular, to a benzopyrone derivative and a use thereof. The benzopyrone derivative is compound having a structure of formula (I) or a pharmaceutically acceptable salt thereof. It has been found by experiments that, this type of compounds is useful in prevention or treatment of neuropsychical diseases.

摘要翻译： 本发明涉及药物化学领域，特别涉及苯并吡喃酮衍生物及其应用。 苯并吡喃酮衍生物是具有式（I）结构的化合物或其药学上可接受的盐。 通过实验发现，这种类型的化合物可用于预防或治疗神经精神疾病。

公开(公告)号：US20080206154A1

公开(公告)日：2008-08-28

申请号：US11664052

申请日：2005-09-28

申请人： Yin Chen ,  Xin Xing Tan

发明人： Yin Chen ,  Xin Xing Tan

IPC分类号： A61K31/713 ,  C07H21/02 ,  C12N15/66 ,  A61P31/00 ,  C07H21/04 ,  C12N5/00

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/111 ,  C12N2310/16 ,  C12N2320/11 ,  C12N2320/30 ,  C12N2330/31 ,  C12N2330/50

摘要： The current invention is directed to oligonucleotide sequences isolated from a sequence designated rbl-1 [SEQ ID NO. 19] that either kill or inhibit growth, or prevent the production of endogenously expressed toxin, of microorganisms. These ssDNA sequences, identified through use of a screening method, appear to act as modulators of essential growth functions which may act at the level of triplex formation, antisense inhibition, or as aptamers that alter gene function. The sequences, referred to as minimum functional regions, or MFRs, are useful inter alia as therapeutic agents for treatment of sepsis and other pathologies caused by microorganisms such as sepsis and/or in which microorganisms are contributory agents.

摘要翻译： 本发明涉及从命名为rbl-1 [SEQ ID NO.1]的序列分离的寡核苷酸序列。 19]可以杀死或抑制微生物的生长，或阻止生成内源性表达的毒素。 通过使用筛选方法鉴定的这些ssDNA序列似乎可以作为必需生长功能的调节剂，其可以在三重生成，反义抑制水平或作为改变基因功能的适体的作用下起作用。 称为最小功能区域或MFR的序列尤其可用作治疗败血症的治疗剂和由诸如败血症和/或其中微生物是贡献剂的微生物引起的其它病症。

公开(公告)号：US20070020635A1

公开(公告)日：2007-01-25

申请号：US10574254

申请日：2004-06-03

申请人： Yin Chen ,  Xin Tan

发明人： Yin Chen ,  Xin Tan

IPC分类号： C12Q1/68 ,  C40B40/02 ,  C40B40/08 ,  C07H21/04 ,  A61K48/00 ,  C12N15/74

CPC分类号： C12N15/113 ,  C07H21/04 ,  C12N15/1034 ,  C12N15/111 ,  C12N15/74 ,  C12N2310/11 ,  C12N2310/111 ,  C12N2310/127 ,  C12N2320/11 ,  C12N2330/31 ,  C12Q1/6837 ,  C12Q2565/531

摘要： A selectively inducible, single-stranded DNA (ssDNA) expression library, a method for constructing a ssDNA expression library, a method for screening ssDNA using the expression library, and a method for identifying ssDNA molecules that alter expression of bacterial and fungal gene(s) related to cell growth and toxin production and secretion. The screening library is used to, among other things, identify ODNs effective in stopping cell growth, killing bacteria or fungi, or preventing bacteria and/or fungi from synthesizing and secreting their toxins, and/or to discover ODNs effective in eukaryotic (e.g., mammalian) cells for targeted alteration of gene function. The library is also useful for identifying ssDNAs or ODNs that are used as therapeutic agents for, for instance, providing a method for treatment of bacterial infections such as sepsis.

摘要翻译： 选择性诱导型单链DNA（ssDNA）表达文库，构建ssDNA表达文库的方法，使用表达文库筛选ssDNA的方法以及鉴定改变细菌和真菌基因表达的ssDNA分子的方法 ）与细胞生长和毒素生成和分泌有关。 除了别的以外，筛选文库用于鉴别有效阻止细胞生长，杀死细菌或真菌，或阻止细菌和/或真菌合成和分泌其毒素的ODN，和/或发现在真核生物中有效的ODN（例如， 哺乳动物）细胞用于靶向改变基因功能。 该文库也可用于鉴定用作治疗剂的ssDNA或ODN，例如提供治疗细菌感染如败血症的方法。