公开(公告)号：US09272022B2

公开(公告)日：2016-03-01

申请号：US13435932

申请日：2012-03-30

申请人： Paul Chang ,  Sejal K. Vyas ,  Anthony Leung ,  Phillip A. Sharp

发明人： Paul Chang ,  Sejal K. Vyas ,  Anthony Leung ,  Phillip A. Sharp

IPC分类号： A61K38/47 ,  A61K39/395 ,  C12N15/113 ,  C07K16/40 ,  A61K31/713 ,  A61K38/45 ,  C07H21/02 ,  C12Q1/68 ,  G01N33/68

CPC分类号： C12N15/1137 ,  A61K31/713 ,  A61K38/45 ,  A61K38/47 ,  A61K39/395 ,  A61K39/3955 ,  C07H21/02 ,  C07K16/40 ,  C12N15/113 ,  C12N2310/14 ,  C12N2320/12 ,  C12Q1/6886 ,  G01N33/6893 ,  G01N2333/91142 ,  G01N2500/02

摘要： The invention provides methods for treating or decreasing the likelihood of developing a stress-granule related disorder and/or cancer by administering one or more poly-ADP-ribose polymerase (PARP) inhibitors, one or more PARP activators, one or more poly-ADP-ribose glycosylase (PARG) activators, and/or one or more poly-ADP-ribose glycohydrolase ARH3 activators. The invention also provides corresponding methods of decreasing stress granule formation and/or proliferation in a cell or a population of cells. The invention further provides methods of increasing the number of stress granules and proliferation in a cell or a population of cells by administering one or more PARP activators, one or more PARP inhibitors, one or more PARG inhibitors, and/or one or more ARH3 inhibitors. The invention also provides methods for screening for agents for treating or decreasing the likelihood of developing a stress granule-related disorder or cancer, and methods for determining the propensity for developing a stress granule-related disorder or cancer, as well as compositions and kits containing one or more PARP inhibitors, one or more PARP activators, one or more PARG activators, and one or more ARH3 activators.

摘要翻译： 本发明提供了通过施用一种或多种聚ADP-核糖聚合酶（PARP）抑制剂，一种或多种PARP激活剂，一种或多种聚ADP来治疗或降低发展应激颗粒相关病症和/或癌症的可能性的方法 核糖糖酵解酶（PARG）激活剂和/或一种或多种聚ADP-核糖糖水解酶ARH3激活剂。 本发明还提供减少细胞或细胞群体中应激颗粒形成和/或增殖的相应方法。 本发明还提供了通过施用一种或多种PARP激活剂，一种或多种PARP抑制剂，一种或多种PARG抑制剂和/或一种或多种ARH3抑制剂来增加细胞或细胞群体中的应激颗粒数量和增殖的方法 。 本发明还提供筛选用于治疗或降低发展应激颗粒相关病症或癌症的可能性的药剂的方法，以及用于确定发展应激颗粒相关病症或癌症倾向的方法，以及含有 一种或多种PARP抑制剂，一种或多种PARP活化剂，一种或多种PARG活化剂和一种或多种ARH3活化剂。

公开(公告)号：US20110097329A1

公开(公告)日：2011-04-28

申请号：US12822995

申请日：2010-06-24

申请人： Paul Chang ,  Sejal Vyas ,  Anthony Leung ,  Phillip A. Sharp

发明人： Paul Chang ,  Sejal Vyas ,  Anthony Leung ,  Phillip A. Sharp

IPC分类号： A61K39/395 ,  C12N5/02 ,  A61P35/00 ,  C12Q1/48 ,  C12Q1/68

CPC分类号： C12N15/1137 ,  A61K31/713 ,  A61K38/45 ,  A61K38/47 ,  A61K39/395 ,  A61K39/3955 ,  C07H21/02 ,  C07K16/40 ,  C12N15/113 ,  C12N2310/14 ,  C12N2320/12 ,  C12Q1/6886 ,  G01N33/6893 ,  G01N2333/91142 ,  G01N2500/02

摘要： The invention provides methods for treating or decreasing the likelihood of developing a stress-granule related disorder and/or cancer by administering one or more poly-ADP-ribose polymerase (PARP) inhibitors, one or more PARP activators, one or more poly-ADP-ribose glycosylase (PARG) activators, and/or one or more poly-ADP-ribose glycohydrolase ARH3 activators. The invention also provides corresponding methods of decreasing stress granule formation and/or proliferation in a cell or a population of cells. The invention further provides methods of increasing the number of stress granules and proliferation in a cell or a population of cells by administering one or more PARP activators, one or more PARP inhibitors, one or more PARG inhibitors, and/or one or more ARH3 inhibitors. The invention also provides methods for screening for agents for treating or decreasing the likelihood of developing a stress granule-related disorder or cancer, and methods for determining the propensity for developing a stress granule-related disorder or cancer, as well as compositions and kits containing one or more PARP inhibitors, one or more PARP activators, one or more PARG activators, and one or more ARH3 activators.

摘要翻译： 本发明提供了通过施用一种或多种聚ADP-核糖聚合酶（PARP）抑制剂，一种或多种PARP激活剂，一种或多种聚ADP来治疗或降低发展应激颗粒相关病症和/或癌症的可能性的方法 核糖糖酵解酶（PARG）激活剂和/或一种或多种聚ADP-核糖糖水解酶ARH3激活剂。 本发明还提供减少细胞或细胞群体中应激颗粒形成和/或增殖的相应方法。 本发明还提供了通过施用一种或多种PARP激活剂，一种或多种PARP抑制剂，一种或多种PARG抑制剂和/或一种或多种ARH3抑制剂来增加细胞或细胞群体中的应激颗粒数量和增殖的方法 。 本发明还提供筛选用于治疗或降低发展应激颗粒相关病症或癌症的可能性的药剂的方法，以及用于确定发展应激颗粒相关病症或癌症倾向的方法，以及含有 一种或多种PARP抑制剂，一种或多种PARP活化剂，一种或多种PARG活化剂和一种或多种ARH3活化剂。

公开(公告)号：US20130156776A1

公开(公告)日：2013-06-20

申请号：US13435932

申请日：2012-03-30

申请人： Paul Chang ,  Sejal . Vyas ,  Anthony Leung ,  Phillip A. Sharp

发明人： Paul Chang ,  Sejal . Vyas ,  Anthony Leung ,  Phillip A. Sharp

IPC分类号： A61K38/47 ,  A61K31/713 ,  A61K39/395 ,  C12Q1/68 ,  C07H21/02 ,  C12N15/113 ,  G01N33/68 ,  A61K38/45 ,  C07K16/40

CPC分类号： C12N15/1137 ,  A61K31/713 ,  A61K38/45 ,  A61K38/47 ,  A61K39/395 ,  A61K39/3955 ,  C07H21/02 ,  C07K16/40 ,  C12N15/113 ,  C12N2310/14 ,  C12N2320/12 ,  C12Q1/6886 ,  G01N33/6893 ,  G01N2333/91142 ,  G01N2500/02

摘要： The invention provides methods for treating or decreasing the likelihood of developing a stress-granule related disorder and/or cancer by administering one or more poly-ADP-ribose polymerase (PARP) inhibitors, one or more PARP activators, one or more poly-ADP-ribose glycosylase (PARG) activators, and/or one or more poly-ADP-ribose glycohydrolase ARH3 activators. The invention also provides corresponding methods of decreasing stress granule formation and/or proliferation in a cell or a population of cells. The invention further provides methods of increasing the number of stress granules and proliferation in a cell or a population of cells by administering one or more PARP activators, one or more PARP inhibitors, one or more PARG inhibitors, and/or one or more ARH3 inhibitors. The invention also provides methods for screening for agents for treating or decreasing the likelihood of developing a stress granule-related disorder or cancer, and methods for determining the propensity for developing a stress granule-related disorder or cancer, as well as compositions and kits containing one or more PARP inhibitors, one or more PARP activators, one or more PARG activators, and one or more ARH3 activators.

摘要翻译： 本发明提供了通过施用一种或多种聚ADP-核糖聚合酶（PARP）抑制剂，一种或多种PARP激活剂，一种或多种聚ADP来治疗或降低发展应激颗粒相关病症和/或癌症的可能性的方法 核糖糖酵解酶（PARG）激活剂和/或一种或多种聚ADP-核糖糖水解酶ARH3激活剂。 本发明还提供减少细胞或细胞群体中应激颗粒形成和/或增殖的相应方法。 本发明还提供了通过施用一种或多种PARP激活剂，一种或多种PARP抑制剂，一种或多种PARG抑制剂和/或一种或多种ARH3抑制剂来增加细胞或细胞群体中的应激颗粒数量和增殖的方法 。 本发明还提供筛选用于治疗或降低发展应激颗粒相关病症或癌症的可能性的药剂的方法，以及用于确定发展应激颗粒相关病症或癌症倾向的方法，以及含有 一种或多种PARP抑制剂，一种或多种PARP活化剂，一种或多种PARG活化剂和一种或多种ARH3活化剂。

公开(公告)号：US08435961B2

公开(公告)日：2013-05-07

申请号：US12821967

申请日：2010-06-23

申请人： Paul Chang ,  Anthony Leung ,  Phillip A. Sharp

发明人： Paul Chang ,  Anthony Leung ,  Phillip A. Sharp

IPC分类号： A61K31/70 ,  A61K31/00 ,  A61K39/395

CPC分类号： C12N15/111 ,  C07K2319/61 ,  C12N9/1077 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2320/50

摘要： The invention provides methods for increasing the activity of an inhibitory RNA (RNAi) in a subject requiring administering one or more poly-ADP-ribose polymerase (PARP) inhibitors and/or one or more PARG activators to the subject. The invention also provides methods for increasing the activity of an inhibitory RNA in a cell or cell population requiring contacting a cell or cell population with one or more PARP inhibitors and/or one or more PARG activators. The invention further provides compositions and kits containing one or more PARP inhibitors and/or one or more PARG activators.

摘要翻译： 本发明提供了在需要给受试者施用一种或多种聚ADP-核糖聚合酶（PARP）抑制剂和/或一种或多种PARG活化剂的受试者中提高抑制性RNA（RNAi）的活性的方法。 本发明还提供了增加细胞或细胞群体中抑制性RNA的活性的方法，其需要使细胞或细胞群体与一种或多种PARP抑制剂和/或一种或多种PARG活化剂接触。 本发明还提供了含有一种或多种PARP抑制剂和/或一种或多种PARG活化剂的组合物和试剂盒。

公开(公告)号：US20110097328A1

公开(公告)日：2011-04-28

申请号：US12821967

申请日：2010-06-23

申请人： Paul Chang ,  Anthony Leung ,  Phillip A. Sharp

发明人： Paul Chang ,  Anthony Leung ,  Phillip A. Sharp

IPC分类号： A61K39/395 ,  A61K31/7088 ,  C12N5/02

CPC分类号： C12N15/111 ,  C07K2319/61 ,  C12N9/1077 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2320/50

摘要： The invention provides methods for increasing the activity of an inhibitory RNA (RNAi) in a subject requiring administering one or more poly-ADP-ribose polymerase (PARP) inhibitors and/or one or more PARG activators to the subject. The invention also provides methods for increasing the activity of an inhibitory RNA in a cell or cell population requiring contacting a cell or cell population with one or more PARP inhibitors and/or one or more PARG activators. The invention further provides compositions and kits containing one or more PARP inhibitors and/or one or more PARG activators.

摘要翻译： 本发明提供了在需要给受试者施用一种或多种聚ADP-核糖聚合酶（PARP）抑制剂和/或一种或多种PARG活化剂的受试者中提高抑制性RNA（RNAi）的活性的方法。 本发明还提供了增加细胞或细胞群体中抑制性RNA的活性的方法，其需要使细胞或细胞群体与一种或多种PARP抑制剂和/或一种或多种PARG活化剂接触。 本发明还提供了含有一种或多种PARP抑制剂和/或一种或多种PARG活化剂的组合物和试剂盒。

公开(公告)号：US09012138B2

公开(公告)日：2015-04-21

申请号：US13043917

申请日：2011-03-09

申请人： Thomas Tuschl ,  Phillip D. Zamore ,  Phillip A. Sharp ,  David P. Bartel

发明人： Thomas Tuschl ,  Phillip D. Zamore ,  Phillip A. Sharp ,  David P. Bartel

IPC分类号： C12Q1/68 ,  C07H21/02 ,  C07H21/04 ,  C12N15/10 ,  C12N15/11 ,  C12N15/113 ,  A61K38/00

CPC分类号： C12N15/113 ,  A01K67/0336 ,  A01K2207/05 ,  A01K2217/075 ,  A01K2227/703 ,  A01K2267/03 ,  A61K38/00 ,  C07H21/02 ,  C12N15/1079 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/53 ,  C12N2330/30 ,  C12Q1/66 ,  C12N2310/3521

摘要： The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response. This specific targeting of a particular gene function is useful in functional genomic and therapeutic applications.

公开(公告)号：US07008780B2

公开(公告)日：2006-03-07

申请号：US09852370

申请日：2001-05-10

申请人： Joel L. Pomerantz ,  Phillip A. Sharp ,  Carl O. Pabo

发明人： Joel L. Pomerantz ,  Phillip A. Sharp ,  Carl O. Pabo

IPC分类号： C12P21/02

CPC分类号： C07K14/4702 ,  A01K2217/05 ,  C07K2319/00 ,  C12N9/22 ,  C12N15/1055

摘要： Chimeric proteins containing composite DNA-binding regions are disclosed together with DNA constructs encoding them, compositions containing them and applications in which they are useful.

公开(公告)号：US06326166B1

公开(公告)日：2001-12-04

申请号：US08973131

申请日：1998-03-16

申请人： Joel L. Pomerantz ,  Phillip A. Sharp ,  Carl O. Pabo

发明人： Joel L. Pomerantz ,  Phillip A. Sharp ,  Carl O. Pabo

IPC分类号： C12P2102

CPC分类号： C07K14/4702 ,  C07K2319/00

摘要： Chineric proteins containing composite DNA-binding regions are disclosed together with DNA constructs encoding them, compositions containing them and applications in which they are useful.

摘要翻译： 与编码它们的DNA构建体，含有它们的组合物和它们有用的应用一起公开含有复合DNA结合区的Chineric蛋白质。

公开(公告)号：US08742092B2

公开(公告)日：2014-06-03

申请号：US12897756

申请日：2010-10-04

申请人： Thomas Tuschl ,  Phillip A. Sharp ,  Phillip D. Zamore ,  David P. Bartel

发明人： Thomas Tuschl ,  Phillip A. Sharp ,  Phillip D. Zamore ,  David P. Bartel

IPC分类号： C07H21/04 ,  A61K48/00

CPC分类号： C12N15/113 ,  A01K67/0336 ,  A01K2207/05 ,  A01K2217/075 ,  A01K2227/703 ,  A01K2267/03 ,  A61K38/00 ,  C07H21/02 ,  C12N15/1079 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/53 ,  C12N2330/30 ,  C12Q1/66 ,  C12N2310/3521

摘要： The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response. This specific targeting of a particular gene function is useful in functional genomic and therapeutic applications.

公开(公告)号：US20120122111A1

公开(公告)日：2012-05-17

申请号：US13043917

申请日：2011-03-09

申请人： Thomas Tuschl ,  Phillip D. Zamore ,  Phillip A. Sharp ,  David P. Bartel

发明人： Thomas Tuschl ,  Phillip D. Zamore ,  Phillip A. Sharp ,  David P. Bartel

IPC分类号： C12Q1/68

CPC分类号： C12N15/113 ,  A01K67/0336 ,  A01K2207/05 ,  A01K2217/075 ,  A01K2227/703 ,  A01K2267/03 ,  A61K38/00 ,  C07H21/02 ,  C12N15/1079 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/53 ,  C12N2330/30 ,  C12Q1/66 ,  C12N2310/3521

摘要： The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response. This specific targeting of a particular gene function is useful in functional genomic and therapeutic applications.