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    COMPOSITIONS AND METHODS FOR TREATING OTITIS MEDIA AND OTHER CONDITIONS WITH INHIBITORS OF CYLD
    1.
    发明申请
    COMPOSITIONS AND METHODS FOR TREATING OTITIS MEDIA AND OTHER CONDITIONS WITH INHIBITORS OF CYLD 有权
    用于治疗OTITIS媒体的组合物和方法及其与CYLD抑制剂的其他条件

    公开(公告)号：US20150065561A1

    公开(公告)日：2015-03-05

    申请号：US14391890

    申请日：2013-04-09

    申请人： Georgia State University Research Foundation, Inc.

    发明人： Jian-Dong Li

    IPC分类号： C12N15/113 ,  A61K31/4174 ,  C12Q1/68 ,  A61K31/277 ,  A61K31/7064 ,  A61K31/685 ,  A61K31/4015 ,  A61K31/44

    CPC分类号： C12N15/1137 ,  A61K31/277 ,  A61K31/4015 ,  A61K31/4174 ,  A61K31/44 ,  A61K31/685 ,  A61K31/7064 ,  A61K31/713 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/141 ,  C12Q1/68 ,  C12Y301/04017 ,  C12Y304/19012

    摘要： The present invention is based, in part, on our studies of molecular pathways that include the deubiquitinase CYLD. Accordingly, the present invention features, inter alia, nucleic acid constructs that express CYLD or a biologically active variant thereof (e.g., a variant including the catalytic domain), nucleic acids that inhibit the expression of a negative regulator of CYLD (e.g., PDE4B or LNK2), nucleic acids that modulate the expression of downstream CYLD targets (e.g., Akt, by inhibiting or promoting the expression of the downstream target), compositions including one or more of these types of constructs (e.g., pharmaceutical compositions), kits including one or more of the compositions described herein and instructions for use, screening methods to identify therapeutic agents {e.g., anti-inflammatory agents) that upregulate CYLD, downregulate a negative regulatory of CYLD, or modulate (e.g., inhibit) a downstream CYLD target (e.g., Akt), and various methods of treatment including the administration of the nucleic acids described above, protein biotherapeutics, and/or small molecules, alone or in combination, to address cancer, inflammation, and fibrosis. The compositions described herein can be used in the preparation of a medicament (e.g., used in the preparation of a medicament to treat cancer, inflammation, fibrosis, or one or more of the more specific conditions described herein).

    摘要翻译： 本发明部分基于我们对包括去泛素酶CYLD的分子途径的研究。 因此，本发明尤其涉及表达CYLD或其生物活性变体（例如，包含催化结构域的变体）的核酸构建体，抑制CYLD负调节子表达的核酸（例如，PDE4B或 LNK2），调节下游CYLD靶标表达的核酸（例如Akt，通过抑制或促进下游靶标的表达），包括这些类型的构建体（例如药物组合物）中的一种或多种的组合物，包括一种 或更多的本文所述的组合物和使用说明书，筛选方法来鉴定上调CYLD的治疗剂（例如抗炎剂），下调CYLD的负调节，或调节（例如，抑制）下游CYLD靶标（例如， ，Akt）和各种治疗方法，包括单独施用上述核酸，蛋白质生物治疗剂和/或小分子， 结合，以解决癌症，炎症和纤维化。 本文所述的组合物可用于制备药物（例如，用于制备治疗癌症，炎症，纤维化或本文所述的更具体病症中的一种或多种的药物）。

    Phosphodiesterase 4D7 as prostate cancer marker
    2.
    发明授权
    Phosphodiesterase 4D7 as prostate cancer marker 有权
    磷酸二酯酶4D7作为前列腺癌标志物

    公开(公告)号：US08753892B2

    公开(公告)日：2014-06-17

    申请号：US13320283

    申请日：2010-05-11

    申请人： Ralf Hoffmann ,  Miles Douglas Houslay ,  David James Peter Henderson

    发明人： Ralf Hoffmann ,  Miles Douglas Houslay ,  David James Peter Henderson

    IPC分类号： G01N33/68

    CPC分类号： G01N33/68 ,  C12N9/16 ,  C12N15/1137 ,  C12N15/115 ,  C12N2310/113 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/16 ,  C12Q1/44 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Y301/04017 ,  G01N33/57434 ,  G01N2333/916 ,  G01N2800/52 ,  G01N2800/54 ,  Y10S436/813

    摘要： The present invention relates to phosphodiesterase 4D7 (PDE4D7) for use as a marker for prostate cancer, and the use of PDE4D7 as a marker for diagnosing, detecting, monitoring or prognosticating prostate cancer or the progression of prostate cancer. The present invention also relates to a composition for diagnosing, detecting, monitoring or prognosticating prostate cancer or the progression of prostate cancer, a corresponding method and immunoassay, a method for diagnosing, monitoring or prognosticating hormone-resistant prostate cancer vs. hormone-sensitive prostate cancer, a corresponding immunoassay, a method of data acquisition, an immunoassay for diagnosing, detecting, monitoring or prognosticating prostate cancer or the progression of prostate cancer, a method of identifying an individual for eligibility for prostate cancer therapy, an immunoassay for stratifying an individual or cohort of individuals with a prostate cancer disease, an immunoassay for stratifying an individual with prostate cancer, as well as a pharmaceutical composition comprising a compound directly stimulating or modulating the activity of PDE4D7, a compound indirectly stimulating or modulating the activity of PDE4D7, the PDE4D7 protein or a biologically active equivalent thereof, a nucleic acid encoding and expressing PDE4D7, a miRNA inhibitor specific for PDE4D7 miRNAs, a demethylation agent and/or a phosphodiesterase displacement factor.

    摘要翻译： 本发明涉及用作前列腺癌标志物的磷酸二酯酶4D7（PDE4D7），以及使用PDE4D7作为诊断，检测，监测或预测前列腺癌或前列腺癌进展的标志物。 本发明还涉及用于诊断，检测，监测或预测前列腺癌或前列腺癌进展的组合物，相应的方法和免疫测定，用于诊断，监测或预测激素抵抗性前列腺癌与激素敏感前列腺的方法 癌症，相应的免疫测定，数据采集方法，用于诊断，检测，监测或预测前列腺癌的免疫测定或前列腺癌的进展，鉴定个体对前列腺癌治疗的资格的方法，用于分层个体的免疫测定 或具有前列腺癌疾病的个体队列，用于分层患有前列腺癌的个体的免疫测定，以及包含直接刺激或调节PDE4D7活性的化合物的药物组合物，间接刺激或调节PDE4D7活性的化合物 PDE4D7蛋白或生物学 其活性成分，编码并表达PDE4D7的核酸，PDE4D7 miRNA特异性的miRNA抑制剂，去甲基化剂和/或磷酸二酯酶置换因子。

    NEURONAL PAIN PATHWAY
    3.
    发明申请
    NEURONAL PAIN PATHWAY 有权
    神经痛痛途径

    公开(公告)号：US20120295853A1

    公开(公告)日：2012-11-22

    申请号：US13569510

    申请日：2012-08-08

    申请人： Richard Ambron ,  Ying-Ju Sung ,  Donald W. Landry ,  Shi-Xian Deng

    发明人： Richard Ambron ,  Ying-Ju Sung ,  Donald W. Landry ,  Shi-Xian Deng

    IPC分类号： A61K31/55 ,  A61P25/00 ,  A61P25/04 ,  A61K38/02

    CPC分类号： A61K38/06 ,  A61K9/0014 ,  A61K9/7023 ,  A61K31/352 ,  A61K31/4422 ,  A61K31/55 ,  A61K38/02 ,  A61K38/07 ,  A61K38/465 ,  A61K47/64 ,  C12N9/1205 ,  C12Y301/04017

    摘要： The present invention relates to the discovery of a novel molecular pathway involved in long-term hyperexcitability of sensory neurons, which, in higher animals, is associated with persistent pain. It is based on the discovery that, following injury to an axon of a neuron, an increase in nitric oxide synthase activity results in increased nitric oxide production, which, in turn, activates guanylyl cyclase, thereby increasing levels of cGMP. Increased cGMP results in activation of protein kinase G (“PKG”), which then is retrogradely transported along the axon to the neuron cell body, where it phosphorylates MAPKerk.

    摘要翻译： 本发明涉及发现涉及感觉神经元的长期兴奋性的新型分子途径，其在高等动物中与持续性疼痛相关。 基于这样的发现，在神经元轴突损伤之后，一氧化氮合酶活性的增加导致一氧化氮产生增加，这反过来激活鸟苷酸环化酶，从而增加cGMP的水平。 增加的cGMP导致蛋白激酶G（PKG）的激活，其然后沿着轴突逆行转运到神经元细胞体，其中磷酸化MAPKerk。

    NEURONAL PAIN PATHWAY
    4.
    发明申请
    NEURONAL PAIN PATHWAY 审中-公开
    神经痛痛途径

    公开(公告)号：US20150320761A1

    公开(公告)日：2015-11-12

    申请号：US14813990

    申请日：2015-07-30

    申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

    发明人： Richard Ambron ,  Ying-Ju Sung ,  Donald W. Landry ,  Shi-Xian Deng

    IPC分类号： A61K31/55 ,  A61K9/00 ,  A61K47/48

    CPC分类号： A61K38/06 ,  A61K9/0014 ,  A61K9/7023 ,  A61K31/352 ,  A61K31/4422 ,  A61K31/55 ,  A61K38/02 ,  A61K38/07 ,  A61K38/465 ,  A61K47/64 ,  C12N9/1205 ,  C12Y301/04017

    摘要： The present invention relates to the discovery of a novel molecular pathway involved in long-term hyperexcitability of sensory neurons, which, in higher animals, is associated with persistent pain. It is based on the discovery that, following injury to an axon of a neuron, an increase in nitric oxide synthase activity results in increased nitric oxide production, which, in turn, activates guanylyl cyclase, thereby increasing levels of cGMP. Increased cGMP results in activation of protein kinase G (“PKG”), which then is retrogradely transported along the axon to the neuron cell body, where it phosphorylates MAPKerk.

    摘要翻译： 本发明涉及发现涉及感觉神经元的长期兴奋性的新型分子途径，其在高等动物中与持续性疼痛相关。 基于这样的发现，在神经元轴突损伤之后，一氧化氮合酶活性的增加导致一氧化氮产生增加，这反过来激活鸟苷酸环化酶，从而增加cGMP的水平。 增加的cGMP导致蛋白激酶G（“PKG”）的激活，其然后沿着轴突逆行转运到神经元细胞体，其中磷酸化MAPKerk。

    Neuronal pain pathway
    7.
    发明申请
    Neuronal pain pathway 有权
    神经元疼痛途径

    公开(公告)号：US20060216339A1

    公开(公告)日：2006-09-28

    申请号：US11385455

    申请日：2006-03-21

    申请人： Richard Ambron ,  Ying-Ju Sung ,  Donald Landry ,  Shi-Xian Deng

    发明人： Richard Ambron ,  Ying-Ju Sung ,  Donald Landry ,  Shi-Xian Deng

    IPC分类号： A61K38/10 ,  A61K38/08 ,  A61K38/05 ,  A61K9/70

    CPC分类号： A61K38/06 ,  A61K9/0014 ,  A61K9/7023 ,  A61K31/352 ,  A61K31/4422 ,  A61K31/55 ,  A61K38/02 ,  A61K38/07 ,  A61K38/465 ,  A61K47/64 ,  C12N9/1205 ,  C12Y301/04017

    摘要： The present invention relates to the discovery of a novel molecular pathway involved in long-term hyperexcitability of sensory neurons, which, in higher animals, is associated with persistent pain. It is based on the discovery that, following injury to an axon of a neuron, an increase in nitric oxide synthase activity results in increased nitric oxide production, which, in turn, activates guanylyl cyclase, thereby increasing levels of cGMP. Increased cGMP results in activation of protein kinase G (“PKG”), which then is retrogradely transported along the axon to the neuron cell body, where it phosphorylates MAPKerk.

    摘要翻译： 本发明涉及发现涉及感觉神经元的长期兴奋性的新型分子途径，其在高等动物中与持续性疼痛相关。 它是基于这样的发现：在神经元轴突损伤之后，一氧化氮合酶活性的增加导致一氧化氮产生增加，这反过来激活鸟苷酸环化酶，从而增加cGMP的水平。 增加的cGMP导致蛋白激酶G（“PKG”）的激活，其然后沿着轴突逆行转运到神经元细胞体，其中磷酸化MAPKerk。

    RNA Interference Mediated Inhibition of Cyclic Nucleotide Type 4 Phosphodiesterase (PDE4B) Gene Expression Using Short Interfering Nucleic Acid (siNA)
    9.
    发明申请
    RNA Interference Mediated Inhibition of Cyclic Nucleotide Type 4 Phosphodiesterase (PDE4B) Gene Expression Using Short Interfering Nucleic Acid (siNA) 审中-公开

    公开(公告)号：US20100120895A1

    公开(公告)日：2010-05-13

    申请号：US12598573

    申请日：2008-05-02

    申请人： India Vasant Jadhav ,  Ivan Richards ,  Walter Strapps ,  Chandra Vargeese

    发明人： India Vasant Jadhav ,  Ivan Richards ,  Walter Strapps ,  Chandra Vargeese

    IPC分类号： A61K31/7105 ,  C07H21/02 ,  A61P11/06 ,  A61P11/16

    CPC分类号： C12N15/1137 ,  C12N2310/14 ,  C12N2310/317 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/332 ,  C12N2310/53 ,  C12Y301/04017 ,  C12N2310/3521

    摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression and/or activity, including PDE4B1, PDE4B2, and PDE4B3 gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions, including but not limited to IL-6, IL-7, IL-8, IL-15, TNF-alpha and matrix metalloproteinases (MMPs), such as MMP-I, MMP-2, MMP-3, MMP-9 and MMP-12. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA), and multifunctional siNA molecules capable of mediating RNA interference (RNAi) against cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, antisense and others that can inhibit the function of endogenous RNA molecules or RNAi pathway components (RNAi inhibitors), such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PDE4B gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC) including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce inflammatory, respiratory, and autoimmune diseases, traits, and conditions, and/or other disease states associated with PDE4B gene expression or activity in a subject or organism.