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    Anti-lymphotoxin-beta receptor antibodies as anti-tumor agents
    2.
    发明申请
    Anti-lymphotoxin-beta receptor antibodies as anti-tumor agents 失效
    抗淋巴毒素-β受体抗体作为抗肿瘤剂

    公开(公告)号：US20050281811A1

    公开(公告)日：2005-12-22

    申请号：US11185373

    申请日：2005-07-19

    申请人： Jeffrey Browning ,  Werner Meier ,  Christopher Benjamin

    发明人： Jeffrey Browning ,  Werner Meier ,  Christopher Benjamin

    IPC分类号： A61K38/00 ,  A61K38/19 ,  A61K39/395 ,  C07K14/525 ,  C07K14/715 ,  C07K16/24 ,  C07K16/28

    CPC分类号： A61K38/191 ,  A61K39/395 ,  A61K2039/505 ,  C07K14/525 ,  C07K14/715 ,  C07K16/2866 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2319/00 ,  C07K2319/30 ,  Y10S424/809 ,  A61K2300/00

    摘要： This invention relates to compositions and methods useful for activating LT-β receptor signaling, which in turn elicits potent anti-proliferative effects on tumor cells. More particularly, this invention relates to lymphotoxin heteromeric complexes formed between lymphotoxin-α and multiple subunits of lymphotoxin-β, which induce cytotoxic effects on tumor cells in the presence of lymphotoxin-β receptor activating agents. Also within the scope of this invention are antibodies directed against the lymphotoxin-β receptor which act as lymphotoxin-β receptor activating agents alone or in combination with other lymphotoxin-β receptor activating agents either in the presence or absence of lymphotoxin-α/β complexes. A screening method for selecting such antibodies is provided. This invention also relates to compositions and methods using cross-linked anti-lymphotoxin-β receptor antibodies either alone or in the presence of other lymphotoxin-β receptor activating agents to potentiate tumor cell cytotoxicity.

    摘要翻译： 本发明涉及用于激活LT-β受体信号传导的组合物和方法，其又引起对肿瘤细胞的有效的抗增殖作用。 更具体地，本发明涉及在淋巴毒素-α与淋巴毒素-β的多个亚基之间形成的淋巴毒素异聚体复合物，其在淋巴毒素-β受体活化剂存在下诱导对肿瘤细胞的细胞毒性作用。 也在本发明范围内的是针对淋巴毒素-β受体的抗体，其单独或与其它淋巴毒素-β受体活化剂组合起作用，即在存在或不存在淋巴毒素-α/β复合物的情况下作为淋巴毒素-β受体活化剂 。 提供了选择这种抗体的筛选方法。 本发明还涉及使用交联的抗淋巴毒素-β受体抗体单独或在其它淋巴毒素-β受体活化剂存在下增强肿瘤细胞毒性的组合物和方法。

    Methods of designing and producing novel compounds having improved binding affinity for CD154 or other trimeric proteins
    8.
    发明申请
    Methods of designing and producing novel compounds having improved binding affinity for CD154 or other trimeric proteins 审中-公开
    设计和生产具有改善的对CD154或其他三聚蛋白的结合亲和力的新化合物的方法

    公开(公告)号：US20060172346A1

    公开(公告)日：2006-08-03

    申请号：US11317536

    申请日：2005-12-23

    申请人： Zhongli Zheng ,  Frederick Taylor ,  Christopher Benjamin ,  Yen-Ming Hsu

    发明人： Zhongli Zheng ,  Frederick Taylor ,  Christopher Benjamin ,  Yen-Ming Hsu

    IPC分类号： G01N33/567 ,  C07K16/28

    CPC分类号： C07K16/2875 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/70575 ,  C07K2319/00 ,  G01N33/56972 ,  G01N2333/70575 ,  G01N2333/70578 ,  G01N2500/10 ,  G01N2500/20

    摘要： The present invention relates to methods for designing and producing novel CD40:CD154 binding interrupter compounds and methods using these compounds to treat conditions associated with inappropriate CD154 activation in a subject. This invention also relates to novel methods for screening candidate compounds for the properties of specifically binding CD154 and interrupting CD40:CD154 interaction. This invention further relates to methods of improving the binding affinity, or the ability to block CD40/CD154 interaction, of a synthetic molecule for a trimeric protein, such as CD154. These methods comprise converting a first synthetic molecule that cannot promote lattice or aggregate formation of its target trimeric protein to a second synthetic molecule that can promote lattice or aggregate formation of its target trimeric protein. This invention also relates to a two-dimensional lattice or aggregate comprising a plurality of trimeric CD154 on a cell surface or in solution, wherein the lattice or aggregate is formed by bivalent anti-CD154 antibodies associated with trimeric CD154 molecules.

    摘要翻译： 本发明涉及用于设计和生产新型CD40：CD154结合中断剂化合物的方法和使用这些化合物治疗与受试者中不适当的CD154活化相关的病症的方法。 本发明还涉及用于筛选特异性结合CD154和中断CD40：CD154相互作用的性质的候选化合物的新方法。 本发明还涉及提高合成分子对三聚蛋白如CD154的结合亲和力或阻断CD40 / CD154相互作用的能力的方法。 这些方法包括将不能促进其目标三聚体蛋白的晶格或聚集体形成的第一合成分子转化成可以促进其目标三聚体蛋白质的晶格或聚集体形成的第二合成分子。 本发明还涉及在细胞表面或溶液中包含多个三聚体CD154的二维晶格或聚集体，其中所述晶格或聚集体由与三聚体CD154分子相关的二价抗CD154抗体形成。