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    NUCLEIC ACID BINDING COMPOUNDS AND METHODS OF USE
    1.
    发明申请
    NUCLEIC ACID BINDING COMPOUNDS AND METHODS OF USE 有权
    核酸结合化合物及其使用方法

    公开(公告)号：US20100266677A1

    公开(公告)日：2010-10-21

    申请号：US12670772

    申请日：2008-07-28

    申请人： Benjamin L. Miller ,  Brian R. McNaughton ,  Peter C. Gareiss ,  Joseph Wedekind ,  Charles Thornton ,  Krzysztof Sobczak

    发明人： Benjamin L. Miller ,  Brian R. McNaughton ,  Peter C. Gareiss ,  Joseph Wedekind ,  Charles Thornton ,  Krzysztof Sobczak

    IPC分类号： A61K9/127 ,  C07K5/10 ,  C07K5/08 ,  C07K5/06 ,  A61K38/05 ,  C12Q1/68 ,  A61K38/06 ,  A61K38/07 ,  A61K38/08 ,  C12Q1/70 ,  C07H21/02

    CPC分类号： C07K5/0806 ,  A61K38/00 ,  C07K1/047 ,  C07K5/081 ,  C07K5/0812 ,  C07K5/0815 ,  C07K5/0821

    摘要： The present invention relates to homo- and hetero-dimer compounds formed by a disulfide, sulfinyl thio, or olefin bond between two monomers. A method of making a homo- or hetero-dimer compound is also disclosed. The present invention also relates to monomer compounds capable of forming homo- or hetero-dimer compounds, as well as oligomers formed via linkage of one or more dimers. Also disclosed are methods of inhibiting the activity of target RNA molecules, particularly those having a secondary structure that include a stem or stem-loop formation. Dimer compounds capable of inhibiting the activity of an HIV-I RNA frameshifting stem-loop and a (CUG)n expanded repeat stem-loop are disclosed, as are methods of treating diseases associated with these target RNA molecules. The dimer compounds can also be used for selectively detecting presence of the target RNA molecule in a sample.

    摘要翻译： 本发明涉及由两个单体之间的二硫键，亚硫酰基硫基或烯烃键形成的均聚物和异二聚体化合物。 还公开了制备均聚物或异二聚体化合物的方法。 本发明还涉及能够形成均聚物或异二聚体化合物的单体化合物，以及通过连接一个或多个二聚体形成的低聚物。 还公开了抑制靶RNA分子的活性的方法，特别是具有包括茎或茎 - 环形成的二级结构的那些。 公开了能够抑制HIV-1 RNA干扰茎环和（CUG）n扩增的重复茎环的活性的二聚体化合物，以及治疗与这些靶RNA分子相关疾病的方法。 二聚体化合物也可用于选择性地检测样品中靶RNA分子的存在。

    SUPERCHARGED PROTEINS FOR CELL PENETRATION
    3.
    发明申请
    SUPERCHARGED PROTEINS FOR CELL PENETRATION 有权
    超细胞蛋白用于细胞穿透

    公开(公告)号：US20120100569A1

    公开(公告)日：2012-04-26

    申请号：US13318032

    申请日：2010-04-28

    申请人： David R. Liu ,  Brian R. McNaughton ,  James Joseph Cronican ,  David B. Thompson

    发明人： David R. Liu ,  Brian R. McNaughton ,  James Joseph Cronican ,  David B. Thompson

    IPC分类号： C12Q1/02 ,  C12N5/02 ,  C07K14/00 ,  C12N9/96

    CPC分类号： C07K14/43595 ,  C07K7/06 ,  C07K7/08 ,  C07K14/001 ,  C07K2319/01 ,  C12N5/0602 ,  C12N2501/40 ,  C12N2501/60 ,  C12N2740/13043

    摘要： Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to “supercharge” the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof. The inventive complexes or pharmaceutical compositions thereof may be used to treat proliferative diseases, infectious diseases, cardiovascular diseases, inborn errors in metabolism, genetic diseases, etc.

    摘要翻译： 提供了将组合物，制剂，系统和用于将超荷电蛋白或者超荷电蛋白和药剂（例如核酸，肽，蛋白质，小分子）的复合物递送至细胞的相关方法。 这样的系统和方法包括使用超荷电蛋白。 例如，超正电荷的蛋白质可以通过静电相互作用与核酸（其通常具有净负电荷）相关联。 在一些实施方案中，这样的系统和方法包括改变蛋白质的一级序列以便“增加”蛋白质（例如，产生超正电荷的蛋白质）。 在一些实施方案中，包含超荷电蛋白和一种或多种待递送的试剂的复合物可用作治疗剂。 在一些实施方案中，将复合物和/或其药物组合物施用于有需要的受试者。 本发明的复合物或其药物组合物可用于治疗增殖性疾病，感染性疾病，心血管疾病，代谢中的先天错误，遗传疾病等。

    SUPERCHARGED PROTEINS FOR CELL PENETRATION
    4.
    发明申请
    SUPERCHARGED PROTEINS FOR CELL PENETRATION 审中-公开
    超细胞蛋白用于细胞穿透

    公开(公告)号：US20110112040A1

    公开(公告)日：2011-05-12

    申请号：US12989829

    申请日：2009-04-28

    申请人： David R. Liu ,  Brian R. Mcnaughton ,  James Joseph Cronican ,  David B. Thompson

    发明人： David R. Liu ,  Brian R. Mcnaughton ,  James Joseph Cronican ,  David B. Thompson

    IPC分类号： A61K38/14 ,  C12N5/00 ,  C12Q1/02 ,  C07K14/00 ,  C12N15/63

    CPC分类号： A61K38/17

    摘要： Compositions, systems and related methods for delivering a supercharged protein or a complex of a supercharged protein and therapeutic agent (e g, nucleic acid, peptide, small molecule) to cells are disclosed. Superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. The systems and methods may involve altering the primary sequence of a protein in order to “supercharge” the protein (e g, to generate a superpositively-charged protein). The compositions may be used to treat proliferative diseases, infectious diseases, cardiovascular diseases, inborn errors in metabolism, genetic diseases, etc.

    摘要翻译： 公开了用于将超荷电蛋白或超荷电蛋白和治疗剂（例如，核酸，肽，小分子）的复合物递送至细胞的组合物，系统和相关方法。 带正电荷的蛋白质可能通过静电相互作用与核酸（通常具有净负电荷）相关联。 所述系统和方法可以涉及改变蛋白质的一级序列以便“增加”蛋白质（例如产生超正电荷的蛋白质）。 该组合物可用于治疗增殖性疾病，感染性疾病，心血管疾病，代谢中的先天错误，遗传疾病等。

    Supercharged proteins for cell penetration
    5.
    发明授权
    Supercharged proteins for cell penetration 有权
    用于细胞穿透的超荷电蛋白

    公开(公告)号：US09221886B2

    公开(公告)日：2015-12-29

    申请号：US13318032

    申请日：2010-04-28

    申请人： David R. Liu ,  Brian R. McNaughton ,  James Joseph Cronican ,  David B. Thompson

    发明人： David R. Liu ,  Brian R. McNaughton ,  James Joseph Cronican ,  David B. Thompson

    IPC分类号： C12N15/09 ,  C12N9/96 ,  C12N5/00 ,  A61K38/43 ,  C07H21/04 ,  C07K1/00 ,  C07K14/435 ,  C07K7/06 ,  C07K7/08 ,  C07K14/00

    CPC分类号： C07K14/43595 ,  C07K7/06 ,  C07K7/08 ,  C07K14/001 ,  C07K2319/01 ,  C12N5/0602 ,  C12N2501/40 ,  C12N2501/60 ,  C12N2740/13043

    摘要： Compositions, preparations, systems, and related methods for delivering a supercharged protein, or a complex of a supercharged protein and an agent (e.g., nucleic acids, peptides, proteins, small molecules) to cells are provided. Such systems and methods include the use of supercharged proteins. For example, superpositively charged proteins may be associated with nucleic acids (which typically have a net negative charge) via electrostatic interactions. In some embodiments, such systems and methods involve altering the primary sequence of a protein in order to “supercharge” the protein (e.g., to generate a superpositively-charged protein). In some embodiments, complexes comprising supercharged proteins and one or more agents to be delivered are useful as therapeutic agents. In some embodiments, complexes and/or pharmaceutical compositions thereof are administered to a subject in need thereof. The inventive complexes or pharmaceutical compositions thereof may be used to treat proliferative diseases, infectious diseases, cardiovascular diseases, inborn errors in metabolism, genetic diseases, etc.

    摘要翻译： 提供了将组合物，制剂，系统和用于将超荷电蛋白或者超荷电蛋白和药剂（例如核酸，肽，蛋白质，小分子）的复合物递送至细胞的相关方法。 这样的系统和方法包括使用超荷电蛋白。 例如，超正电荷的蛋白质可以通过静电相互作用与核酸（其通常具有净负电荷）相关联。 在一些实施方案中，这样的系统和方法包括改变蛋白质的一级序列以便“增加”蛋白质（例如，产生超正电荷的蛋白质）。 在一些实施方案中，包含超荷电蛋白和一种或多种待递送的试剂的复合物可用作治疗剂。 在一些实施方案中，将复合物和/或其药物组合物施用于有需要的受试者。 本发明的复合物或其药物组合物可用于治疗增殖性疾病，感染性疾病，心血管疾病，代谢中的先天错误，遗传疾病等。

    Nucleic acid binding compounds and methods of use
    6.
    发明授权
    Nucleic acid binding compounds and methods of use 有权
    核酸结合化合物和使用方法

    公开(公告)号：US09212205B2

    公开(公告)日：2015-12-15

    申请号：US12670772

    申请日：2008-07-28

    申请人： Benjamin L. Miller ,  Brian R. McNaughton ,  Peter C. Gareiss ,  Joseph Wedekind ,  Charles Thornton ,  Krzysztof Sobczak

    发明人： Benjamin L. Miller ,  Brian R. McNaughton ,  Peter C. Gareiss ,  Joseph Wedekind ,  Charles Thornton ,  Krzysztof Sobczak

    IPC分类号： C07K5/08 ,  A61K38/00 ,  C07K1/113 ,  C07K5/083 ,  C07K5/087 ,  C07K5/09 ,  C07K5/097 ,  C07K1/04

    CPC分类号： C07K5/0806 ,  A61K38/00 ,  C07K1/047 ,  C07K5/081 ,  C07K5/0812 ,  C07K5/0815 ,  C07K5/0821

    摘要： The present invention relates to homo- and hetero-dimer compounds formed by a disulfide, sulfinyl thio, or olefin bond between two monomers. A method of making a homo- or hetero-dimer compound is also disclosed. The present invention also relates to monomer compounds capable of forming homo- or hetero-dimer compounds, as well as oligomers formed via linkage of one or more dimers. Also disclosed are methods of inhibiting the activity of target RNA molecules, particularly those having a secondary structure that include a stem or stem-loop formation. Dimer compounds capable of inhibiting the activity of an HIV-I RNA frameshifting stem-loop and a (CUG)n expanded repeat stem-loop are disclosed, as are methods of treating diseases associated with these target RNA molecules. The dimer compounds can also be used for selectively detecting presence of the target RNA molecule in a sample.

    摘要翻译： 本发明涉及由两个单体之间的二硫键，亚硫酰基硫基或烯烃键形成的均聚物和异二聚体化合物。 还公开了制备均聚物或异二聚体化合物的方法。 本发明还涉及能够形成均聚物或异二聚体化合物的单体化合物，以及通过连接一个或多个二聚体形成的低聚物。 还公开了抑制靶RNA分子的活性的方法，特别是具有包括茎或茎 - 环形成的二级结构的那些。 公开了能够抑制HIV-1 RNA干扰茎环和（CUG）n扩增的重复茎环的活性的二聚体化合物，以及治疗与这些靶RNA分子相关疾病的方法。 二聚体化合物也可用于选择性地检测样品中靶RNA分子的存在。