公开(公告)号：WO2011000108A1

公开(公告)日：2011-01-06

申请号：PCT/CA2010/001031

申请日：2010-06-30

申请人： PROTIVA BIOTHERAPEUTICS, INC. ,  LEE, Amy C. H. ,  JUDGE, Adam ,  ROBBINS, Marjorie ,  YAWORSKI, Ed ,  MACLACHLAN, Ian

发明人： LEE, Amy C. H. ,  JUDGE, Adam ,  ROBBINS, Marjorie ,  YAWORSKI, Ed ,  MACLACHLAN, Ian

IPC分类号： C12N15/113 ,  A61K31/713 ,  A61K47/22 ,  A61K9/14 ,  C07H21/02 ,  C07K14/775

CPC分类号： A61K9/1272 ,  A61K9/0019 ,  A61K31/713 ,  A61K47/543 ,  C07D317/20 ,  C07D317/24 ,  C07D317/28 ,  C07D319/06 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2320/32 ,  Y10S977/80 ,  Y10S977/816 ,  C12N2310/3521

摘要： The present invention provides compositions and methods for the delivery of interfering RNAs that silence APOB expression to liver cells. In particular, the nucleic acid-lipid particles provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo . The compositions of the present invention are highly potent, thereby allowing effective knock-down of APOB at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

摘要翻译： 本发明提供了将APOB表达沉默到肝细胞的干扰RNA的递送的组合物和方法。 特别地，核酸 - 脂质颗粒提供了核酸的有效包封以及将体内核酸封装在细胞体内的有效递送。 本发明的组合物是非常有效的，从而允许在相对低的剂量下有效击倒APOB。 此外，与本领域先前已知的组合物和方法相比，本发明的组合物和方法毒性低，并提供更大的治疗指数。

公开(公告)号：WO2008019486A1

公开(公告)日：2008-02-21

申请号：PCT/CA2007/001413

申请日：2007-08-15

申请人： PROTIVA BIOTHERAPEUTICS, INC. ,  MACLACHLAN, Ian ,  ROBBINS, Marjorie ,  JUDGE, Adam

发明人： MACLACHLAN, Ian ,  ROBBINS, Marjorie ,  JUDGE, Adam

IPC分类号： A61K48/00 ,  A61K31/712 ,  A61P37/06 ,  C12N15/88 ,  C07H21/00 ,  C07K14/705

CPC分类号： C12N15/1138 ,  C12N15/117 ,  C12N2310/17 ,  C12N2310/321 ,  C12N2310/3521

摘要： The present invention provides methods of modulating the activation of certain Toll-like receptors (TLRs) such as TLR7/8 using chemically modified nucleic acid molecules. The present invention also provides methods of using such modified nucleic acid molecules to treat diseases or disorders associated with TLR7/8 activation such as systemic lupus erythematosus. The present invention further provides compositions comprising a combination of modified nucleic acid molecules and nucleic acid molecules that silence expression of one or more target sequences. Methods of using such compositions to reduce or abolish target gene expression without inducing cytokine production are also provided.

摘要翻译： 本发明提供使用化学修饰的核酸分子调节某些Toll样受体（TLR）如TLR7 / 8的活化的方法。 本发明还提供了使用这些修饰的核酸分子来治疗与TLR7 / 8激活相关的疾病或病症的系统如系统性红斑狼疮的方法。 本发明还提供了包含修饰的核酸分子和沉默一个或多个靶序列的表达的核酸分子的组合的组合物。 还提供了使用这些组合物来减少或消除靶基因表达而不诱导细胞因子产生的方法。

公开(公告)号：WO2011011447A1

公开(公告)日：2011-01-27

申请号：PCT/US2010/042648

申请日：2010-07-20

申请人： PROTIVA BIOTHERAPEUTICS, INC. ,  TRUSTEES OF BOSTON UNIVERSITY ,  UNITED STATES ARMY MEDICAL RESEARCH AND MATERIEL COMMAND ,  GEISBERT, Thomas W. ,  LEE, Amy C.H. ,  ROBBINS, Marjorie ,  SOOD, Vandana ,  JUDGE, Adam ,  HENSLEY, Lisa E. ,  MACLACHLAN, Ian

发明人： GEISBERT, Thomas W. ,  LEE, Amy C.H. ,  ROBBINS, Marjorie ,  SOOD, Vandana ,  JUDGE, Adam ,  HENSLEY, Lisa E. ,  MACLACHLAN, Ian

IPC分类号： C12N15/113

CPC分类号： C12N15/1131 ,  A61K9/127 ,  A61K9/1271 ,  A61K31/713 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2320/31 ,  C12N2330/51 ,  C12N2760/14111 ,  C12N2310/3521

摘要： The present invention provides compositions comprising therapeutic nucleic acids ( e.g ., interfering RNA such as siRNA) that target Ebola virus (EBOV) gene expression and methods of using such compositions to silence EBOV gene expression. More particularly, the invention provides unmodified and chemically modified interfering RNA which silence EBOV gene expression and methods of use thereof, e.g ., for preventing or treating EBOV infections caused by one or more EBOV species such as Zaire EBOV. The invention also provides serum-stable nucleic acid-lipid particles comprising one or more interfering RNA molecules, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. Methods of silencing EBOV gene expression by administering one or more interfering RNA molecules to a mammalian subject are also provided.

摘要翻译： 本发明提供了包含针对埃博拉病毒（EBOV）基因表达的治疗性核酸（例如干扰RNA，例如siRNA）和使用这种组合物沉默EBOV基因表达的方法的组合物。 更具体地说，本发明提供了未修饰和化学修饰的干扰RNA，其使EBOV基因表达沉默，及其使用方法，例如用于预防或治疗由一种或多种EBOV物质如扎伊尔EBOV引起的EBOV感染。 本发明还提供包含一种或多种干扰RNA分子，阳离子脂质和非阳离子脂质的血清稳定的核酸 - 脂质颗粒，其可进一步包含抑制颗粒聚集的共轭脂质。 还提供了通过向哺乳动物受试者施用一种或多种干扰RNA分子来沉默EBOV基因表达的方法。

公开(公告)号：WO2007056861A1

公开(公告)日：2007-05-24

申请号：PCT/CA2006/001882

申请日：2006-11-17

申请人： PROTIVA BIOTHERAPEUTICS, INC. ,  MACLACHLAN, Ian ,  ROBBINS, Marjorie

发明人： MACLACHLAN, Ian ,  ROBBINS, Marjorie

IPC分类号： C07H21/02 ,  A61K31/713 ,  A61K47/30 ,  A61K48/00 ,  A61K9/127 ,  A61P31/16 ,  C12N15/09 ,  C12N15/44 ,  C12N15/87 ,  C12Q1/68 ,  C12Q1/70 ,  G01N33/569

CPC分类号： A61K48/00 ,  A61K9/0019 ,  A61K9/0043 ,  A61K9/1271 ,  A61K9/1272 ,  A61K31/00 ,  A61K31/713 ,  A61K47/30 ,  A61K47/50 ,  A61K47/59 ,  A61K47/6907 ,  A61K47/6911 ,  A61K47/6921 ,  C07K14/005 ,  C12N15/1131 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2760/16122 ,  C12N2310/3521

摘要： The present invention provides siRNA molecules that target influenza virus gene expression and methods of using such siRNA molecules to silence influenza virus gene expression. The present invention also provides nucleic acid-lipid particles that target influenza virus gene expression comprising a siRNA that silences influenza virus gene expression, a cationic lipid, and a non-cationic lipid.

摘要翻译： 本发明提供靶向流感病毒基因表达的siRNA分子和使用这种siRNA分子沉默流感病毒基因表达的方法。 本发明还提供靶向流感病毒基因表达的核酸 - 脂质颗粒，其包含沉默流感病毒基因表达的siRNA，阳离子脂质和非阳离子脂质。

公开(公告)号：WO2010105372A1

公开(公告)日：2010-09-23

申请号：PCT/CA2010/000444

申请日：2010-03-19

申请人： PROTIVA BIOTHERAPEUTICS, INC. ,  ROBBINS, Marjorie ,  MACLACHLAN, Ian

发明人： ROBBINS, Marjorie ,  MACLACHLAN, Ian

IPC分类号： A61K31/713 ,  A61K47/44 ,  A61K48/00 ,  A61K9/127 ,  A61P31/14 ,  C12N15/113 ,  C07H21/02 ,  C12N15/51

CPC分类号： C12N15/1131 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/3521 ,  C12N2310/3525 ,  C12N2310/3533 ,  C12N2310/3531

摘要： The present invention provides compositions comprising therapeutic nucleic acids such as interfering RNA that target hepatitis C virus (HCV) gene expression, lipid particles comprising one or more (e.g., a cocktail) of the therapeutic nucleic acids, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles (e.g., for the treatment of acute or chronic hepatitis C caused by one or more HCV genotypes).

摘要翻译： 本发明提供包含治疗性核酸的组合物，例如靶向丙型肝炎病毒（HCV）基因表达的干扰RNA，包含治疗性核酸的一种或多种（例如混合物）的脂质颗粒，制备脂质颗粒的方法和 递送和/或施用脂质颗粒的方法（例如，用于治疗由一种或多种HCV基因型引起的急性或慢性丙型肝炎）。

公开(公告)号：WO2011141703A1

公开(公告)日：2011-11-17

申请号：PCT/GB2011/000721

申请日：2011-05-12

申请人： PROTIVA BIOTHERAPEUTICS INC. ,  HEYES, James ,  WOOD, Mark ,  MARTIN, Alan ,  LEE, Amy, C., H. ,  JUDGE, Adam ,  ROBBINS, Marjorie ,  MACLACHLAN, Ian

发明人： HEYES, James ,  WOOD, Mark ,  MARTIN, Alan ,  LEE, Amy, C., H. ,  JUDGE, Adam ,  ROBBINS, Marjorie ,  MACLACHLAN, Ian

IPC分类号： C12N15/113 ,  C12N15/88 ,  A61K31/713 ,  C07C229/08 ,  C07D317/28

CPC分类号： A61K31/713 ,  C12N15/111 ,  C12N15/113 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32

摘要： The present invention provides compositions and methods for the delivery of interfering RNAs such as siRNAs that silence APOB expression in cells such as liver cells. In particular, the nucleic acid-lipid particles provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells such as liver cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of APOB at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

摘要翻译： 本发明提供了用于递送干扰RNA的组合物和方法，例如使细胞如肝细胞中的APOB表达沉默的siRNA。 特别地，核酸 - 脂质颗粒提供了核酸的有效包封以及将体内核酸封装到细胞例如肝细胞的有效递送。 本发明的组合物是非常有效的，从而允许在相对低的剂量下有效击倒APOB。 此外，与本领域先前已知的组合物和方法相比，本发明的组合物和方法毒性低，并提供更大的治疗指数。