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    Compositions of treating hepatitis virus infections with N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination therapy
    3.
    发明授权
    Compositions of treating hepatitis virus infections with N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination therapy 失效
    联合治疗用N-取代-1,5-二脱氧-1,5-亚氨基-D-葡萄糖醇化合物治疗肝炎病毒感染的组合物

    公开(公告)号：US07612093B2

    公开(公告)日：2009-11-03

    申请号：US11300464

    申请日：2005-12-15

    申请人： Gary S. Jacob ,  Timothy M. Block ,  Raymond A. Dwek

    发明人： Gary S. Jacob ,  Timothy M. Block ,  Raymond A. Dwek

    IPC分类号： A61K31/445 ,  A61K31/505 ,  A61K31/675

    CPC分类号： C07D211/46 ,  A61K31/445 ,  A61K45/06

    摘要： Provided are methods and compositions for treating hepatitis virus infections in mammals, especially humans. The methods comprise (1) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination with nucleoside antiviral agents, nucleotide antiviral agents, mixtures thereof, or immunomodulating/immunostimulating agents, or (2) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination with nucleoside antiviral agents, nucleotide antiviral agents, or mixtures thereof, and immunomodulating/immunostimulating agents.

    摘要翻译： 提供用于治疗哺乳动物，特别是人类的肝炎病毒感染的方法和组合物。 方法包括（1）与核苷抗病毒剂，核苷酸抗病毒剂，其混合物或免疫调节/免疫刺激剂组合施用N-取代的-1,5-二脱氧-1,5-亚氨基-D-葡萄糖醇化合物，或（2 ）与核苷抗病毒剂，核苷酸抗病毒剂或其混合物以及免疫调节/免疫刺激剂组合施用N-取代的-1,5-二脱氧-1,5-亚氨基-D-葡萄糖醇化合物。

    Method of inhibiting hepatitis B virus
    4.
    发明授权
    Method of inhibiting hepatitis B virus 失效
    抑制乙型肝炎病毒的方法

    公开(公告)号：US6037351A

    公开(公告)日：2000-03-14

    申请号：US676153

    申请日：1996-07-11

    申请人： Timothy M. Block ,  Baruch S. Blumberg ,  Raymond A. Dwek

    发明人： Timothy M. Block ,  Baruch S. Blumberg ,  Raymond A. Dwek

    IPC分类号： C07D211/46 ,  A61K31/445 ,  A61P31/12 ,  A61P31/20

    CPC分类号： A61K31/445

    摘要： A method is disclosed for the treatment of hepatitis B virus (HBV) infections which comprises administering to the infected host an N-alkyl derivative of 1,5-dideoxy-1,5-imino-D-glucitol in which the alkyl group contains from 3 to 6 carbon atoms.

    摘要翻译： PCT No.PCT / US94 / 14548 Sec。 371日期1996年7月11日 102（e）日期1996年7月11日PCT 1994年12月23日PCT PCT。 WO95 / 19172 PCT出版物 日期1995年7月20日公开了用于治疗乙型肝炎病毒（HBV）感染的方法，其包括向感染的宿主施用1,5-二脱氧-1,5-亚氨基-D-葡萄糖醇的N-烷基衍生物，其中 该烷基含有3至6个碳原子。

    Methods of Treating hepatitis virus infections with N-substituted-1,5-dideoxy-1,5-imino-d-glucitol compounds in combination therapy
    7.
    发明授权
    Methods of Treating hepatitis virus infections with N-substituted-1,5-dideoxy-1,5-imino-d-glucitol compounds in combination therapy 有权
    联合治疗用N-取代-1,5-二脱氧-1,5-亚氨基-d-葡萄糖醇化合物治疗肝炎病毒感染的方法

    公开(公告)号：US06689759B1

    公开(公告)日：2004-02-10

    申请号：US09355446

    申请日：2000-01-19

    申请人： Gary S. Jacob ,  Timothy M. Block ,  Raymond A. Dwek

    发明人： Gary S. Jacob ,  Timothy M. Block ,  Raymond A. Dwek

    IPC分类号： A61K3100

    CPC分类号： A61K31/51 ,  A61K31/675 ,  A61K31/7052 ,  A61K2300/00

    摘要： Provided are methods and compositions for treating hepatitis virus infections in mammals, especially humans. The methods comprise (1) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination with nucleoside antiviral agents, nucleotide antiviral agents, mixtures thereof, or immunomodulating/immunostimulating agents, or (2) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination with nucleoside antivirals agents, nucleotide antiviral agents, or mixtures thereof, and immunomodulating/immunostimulating agents.

    摘要翻译： 提供用于治疗哺乳动物，特别是人类的肝炎病毒感染的方法和组合物。 方法包括（1）与核苷抗病毒剂，核苷酸抗病毒剂，其混合物或免疫调节/免疫刺激剂组合施用N-取代的-1,5-二脱氧-1,5-亚氨基-D-葡萄糖醇化合物，或（2 ）与核苷抗病毒剂，核苷酸抗病毒剂或其混合物以及免疫调节/免疫刺激剂组合施用N-取代的-1,5-二脱氧-1,5-亚氨基-D-葡萄糖醇化合物。

    Imino sugar derivatives demonstrate potent antiviral activity and reduced toxicity
    9.
    发明授权
    Imino sugar derivatives demonstrate potent antiviral activity and reduced toxicity 有权
    亚氨基糖衍生物表现出强大的抗病毒活性和降低的毒性

    公开(公告)号：US09040488B2

    公开(公告)日：2015-05-26

    申请号：US13061734

    申请日：2009-09-02

    申请人： Timothy M. Block ,  Jinhong Chang ,  Xiaodong Xu

    发明人： Timothy M. Block ,  Jinhong Chang ,  Xiaodong Xu

    IPC分类号： C07D211/46 ,  A61K31/445 ,  A61K31/47 ,  A61K31/7056

    CPC分类号： A61K31/47 ,  A61K31/7056 ,  C07D211/46 ,  Y02A50/393 ,  A61K2300/00

    摘要： Imino sugars, such as deoxynojirimycin (DNJ), are glucose analogues that selectively inhibit cellular α-glucosidase I and II (enzymes that process N-linked glycans in glycoprotein) and exhibit broad spectrum antiviral activities against many enveloped viruses. Previously we have reported a novel DNJ derivative, OSL-95II, with antiviral activity and reduced cytotoxicity. In order to develop imino sugars with more potent antiviral activity as well as improved toxicity profile, OSL-95II was modified by diversifying the nitrogen linked alkylated side chain. The antiviral activities were initially tested in bovine viral diarrhea virus (BVDV) infected MDBK cells, yielding several imino sugar derivatives with novel structure and superior antiviral activity and toxicity profile. Furthermore, these new compounds were shown to be active against Dengue virus (DV) and West Nile virus (WNV) infection in BHK cells where potent anti-DV activity having submicromolar EC50 values and SI of greater than 900. These compounds represent a new generation of iminio sugars and their analogues, having application in the clinical treatment of infection of DV and other members of flaviviridae.

    摘要翻译： 诸如脱氧野尻霉素（DNJ）的亚氨基糖是选择性抑制细胞α-葡萄糖苷酶I和II（在糖蛋白中加工N-连接聚糖的酶）并且对许多包膜病毒展现广谱抗病毒活性的葡萄糖类似物。 以前我们已经报道了具有抗病毒活性和降低的细胞毒性的新型DNJ衍生物OSL-95II。 为了开发具有更强的抗病毒活性和改善的毒性特征的亚氨基糖，OSL-95II通过使氮连接的烷基化侧链多样化而被修饰。 首先在牛病毒性腹泻病毒（BVDV）感染的MDBK细胞中测试抗病毒活性，产生几种具有新结构和优良抗病毒活性和毒性特征的亚氨基糖衍生物。 此外，这些新化合物被证明对BHK细胞中登革热病毒（DV）和西尼罗病毒（WNV）感染具有活性，其中具有亚微摩尔EC 50值和SI大于900的有效抗DV活性。这些化合物代表新一代 的亚氨基糖及其类似物，可用于临床治疗DV和其他黄病毒成分的感染。

    SERINE PROTEASE INHIBITOR KAZAL ANTIBODIES
    10.
    发明申请
    SERINE PROTEASE INHIBITOR KAZAL ANTIBODIES 审中-公开
    丝氨酸蛋白酶抑制剂KAZAL抗体

    公开(公告)号：US20140308657A1

    公开(公告)日：2014-10-16

    申请号：US13991943

    申请日：2011-12-07

    申请人： Xuanyong Lu ,  Timothy M. Block

    发明人： Xuanyong Lu ,  Timothy M. Block

    IPC分类号： G01N33/569 ,  C07K16/38

    CPC分类号： G01N33/56983 ,  C07K16/38 ,  C07K2317/34 ,  C12Q1/37 ,  G01N33/57438 ,  G01N33/5761 ,  G01N33/5767 ,  G01N2800/50

    摘要： This invention describes a relevant etiology of cancer and a novel anti-cancer therapeutic strategy, based on the discovery that a protein named serine protease inhibitor (SPIK/SPINK/PSTI) was up-regulated by hepatitis B and C virus infections consequently suppressing the cell apoptosis. Accordingly, this invention provides an inhibitor of SPIK and/or a technology of suppression of over-expression of SPIK in cells. The inhibitors include: 1) chemical compounds, which can inhibit SPIK transcripts, protein activity, and gene expression, 2) SPIK siRNA (RNAi gene silence or dsRNA of SPIK, 3) DNA anti-sense and anti-SPIK antibody. Further, this invention provides a method of using the inhibitor as an anti-cancer agent to re-instate cancer cell apoptosis (e.g., serine protease dependent cell apoptosis). Also provided is an anti-SPIK antibody specific for an epitope comprising the first nine amino acids of intact SPIK. Further, a diagnostic kit is provided comprising at least one antibody specific for an epitope comprising the first nine amino acids of intact SPIK to diagnose patients exhibiting disease symptoms or at risk for developing a disease, wherein the disease is HBV infection, HCV infection, hepatitis, cancer or hepatic cancer.

    摘要翻译： 本发明描述了癌症的相关病因和新型抗癌治疗策略，基于以下发现：称为丝氨酸蛋白酶抑制剂（SPIK / SPINK / PSTI）的蛋白质被乙型和丙型肝炎病毒感染上调，从而抑制细胞 凋亡。 因此，本发明提供了SPIK抑制剂和/或抑制细胞中SPIK过度表达的技术。 抑制剂包括：1）可抑制SPIK转录物，蛋白质活性和基因表达的化合物，2）SPIK siRNA（SPIK的RNAi基因沉默或dsRNA，3）DNA反义和抗SPIK抗体。 此外，本发明提供了使用该抑制剂作为抗癌剂来重新制备癌细胞凋亡（如丝氨酸蛋白酶依赖性细胞凋亡）的方法。 还提供了对包含完整SPIK的前9个氨基酸的表位特异的抗SPIK抗体。 此外，提供了诊断试剂盒，其包含至少一种特异于包含完整SPIK的前九个氨基酸的表位的抗体，以诊断表现出疾病症状或处于发展疾病的风险的患者，其中所述疾病是HBV感染，HCV感染，肝炎 ，癌症或肝癌。