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    TARGETING TUMOR CELLS WITH CHEMOTHERAPEUTIC AGENTS CONJUGATED TO MATRIPTASE ANTIBODIES
    144.
    发明申请
    TARGETING TUMOR CELLS WITH CHEMOTHERAPEUTIC AGENTS CONJUGATED TO MATRIPTASE ANTIBODIES 审中-公开
    靶向肿瘤细胞与化学治疗药物结合到基质抗体

    公开(公告)号：WO2011063127A1

    公开(公告)日：2011-05-26

    申请号：PCT/US2010/057235

    申请日：2010-11-18

    Applicant: UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY ,  LIN, Siang-Yo ,  BERTINO, Joseph, R.

    Inventor： LIN, Siang-Yo ,  BERTINO, Joseph, R.

    IPC: A61K39/00 ,  C07K17/00 ,  C12N5/07

    CPC classification number: A61K31/704 ,  A61K31/454 ,  A61K39/395 ,  A61K45/06 ,  A61K47/48384 ,  A61K47/48646 ,  A61K47/6803 ,  A61K47/6871 ,  A61K2039/505 ,  C07K16/30 ,  C07K16/40 ,  A61K2300/00

    Abstract: The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as doxorubicin (DOX) are introduced, which are equipotent to anticancer agents used in free form but exhibit significantly reduced cardiotoxicity and almost no adverse effects on normal bone marrow-derived mesenchymal stromal cells that do not express matriptase. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

    Abstract translation: 本发明涉及具有细胞毒性剂的matriptase抗体的片段酶抗体和免疫偶联物，以及其用于杀死或抑制表达表达表皮细胞的癌细胞如多发性骨髓瘤和乳腺癌的生长的用途。 特别地，引入了包含matriptase单克隆抗体和抗癌剂如多柔比星（DOX）的免疫缀合物，其与游离形式使用的抗癌剂相当，但显示出显着降低的心脏毒性并且对正常骨髓来源的间充质基质细胞几乎没有不利影响 不表达matriptase。 本发明还提供包含这些新的免疫缀合物的组合物和它们用于治疗包括表达matriptase的细胞的恶性肿瘤的用途。 此外，将matriptase抗体或matriptase抗体和细胞毒性剂的免疫缀合物与免疫调节剂（例如沙利度胺或其类似物）的给药组合施用提供了对这些癌症的更有效的治疗。

    TYPE 5 ADENYLYL CYCLASE INHIBITORS FOR PROVIDING CARDIAC PROTECTION
    148.
    发明申请
    TYPE 5 ADENYLYL CYCLASE INHIBITORS FOR PROVIDING CARDIAC PROTECTION 审中-公开
    5型腺苷酸环化酶抑制剂，用于提供心脏保护

    公开(公告)号：WO2009099676A1

    公开(公告)日：2009-08-13

    申请号：PCT/US2009/000836

    申请日：2009-02-09

    Applicant: UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY ,  VATNER, Stephen, F. ,  IWATSUBO, Kosaku

    Inventor： VATNER, Stephen, F. ,  IWATSUBO, Kosaku

    IPC: A61K31/7076 ,  A61P9/00

    CPC classification number: A61K31/7076

    Abstract: The invention provides a method of treating a cardiac disease by administering a pharmaceutically effective amount of at least one compound capable of inhibiting AC5 to a patient. The compound capable of inhibiting AC5 may be administered singly or in combination with another agent, such as, for instance a β-blocker. In some embodiments, the AC5 inhibiting compound is 9-β-D-arabinofuranosyladenine (AraAde). The compound may be administered in an amount of about 1 to about 200 mg/kg/day, about 1 to about 100 mg/kg/day, about 10 to about 80 mg/kg/day, about 12 to about 40 mg/kg/day or about 15 to about 25 mg/kg/day. In some embodiments, the compound is administered parenterally. The cardiac disease may be, for instance, myocardial infarction (MI) or heart failure (HF). The compound capable of inhibiting AC5 may be administered alone or in conjunction with one or more other active agents. Likewise, the invention provides a method of treating a heart attack, a method of inhibiting myocardial apoptosis, and a method of treating heart failure by administering a pharmaceutically effective amount of at least one compound capable of inhibiting AC5 to a patient in the same manner.

    Abstract translation: 本发明提供了一种治疗心脏病的方法，其通过向患者施用药学上有效量的至少一种能够抑制AC5的化合物。 能够抑制AC5的化合物可以单独施用或与另一种试剂例如β-阻滞剂组合施用。 在一些实施方案中，抑制AC5的化合物是9-β-D-阿拉伯呋喃糖基腺嘌呤（AraAde）。 化合物可以以约1至约200mg / kg /天，约1至约100mg / kg /天，约10至约80mg / kg /天，约12至约40mg / kg的量施用 /天或约15至约25mg / kg /天。 在一些实施方案中，所述化合物肠胃外给药。 心脏病可以是例如心肌梗死（MI）或心力衰竭（HF）。 能够抑制AC5的化合物可以单独施用或与一种或多种其它活性剂一起施用。 同样，本发明提供了治疗心脏病发作的方法，抑制心肌细胞凋亡的方法，以及通过以相同的方式向患者施用药学上有效量的至少一种能够抑制AC5的化合物来治疗心力衰竭的方法。

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