SUPERANTIBODY SYNTHESIS AND USE IN DETECTION, PREVENTION AND TREATMENT OF DISEASE
    1.
    发明申请
    SUPERANTIBODY SYNTHESIS AND USE IN DETECTION, PREVENTION AND TREATMENT OF DISEASE 审中-公开
    超敏反应合成及用于检测,预防和治疗疾病

    公开(公告)号:US20120064593A1

    公开(公告)日:2012-03-15

    申请号:US13215952

    申请日:2011-08-23

    IPC分类号: C12N9/96 C07K19/00 C12N13/00

    摘要: Superantibodies having enhanced autophilic, catalytic, and/or membrane-penetrating properties are prepared by affinity-based conjugation of a photoactivatable organic molecule to a target immunoglobulin. The photoactivatable organic molecule bears a chromophoric aromatic hydrocarbon moiety, which has affinity for the immunoglobulin. Upon photolysis, the organic molecule is covalently linked to the immunoglobulin. A preferred organic molecule is a peptide and a preferred aromatic hydrocarbon moiety is a tryptophan residue. The photoactivatable organic molecule need not bear a purine, pyrimidine or azido group to effect binding to the immunoglobulin and/or photoactivation. Autophilic superantibodies can promote apoptosis of target cells and/or enhance therapeutic efficacies in the treatment of patients with diseases or disorders responsive to antibody therapy. Exemplary of such diseases are atherosclerosis and cardiovascular disease. Membrane-penetrating superantibodies can prevent apoptosis by binding to intracellular anti-caspase signal proteins. Compositions containing the superantibodies, as well as methods of making and using them, are disclosed.

    摘要翻译: 具有增强的自亲性,催化和/或膜穿透性质的超抗体通过可光活化的有机分子与靶免疫球蛋白的亲和基偶联来制备。 可光活化的有机分子具有对免疫球蛋白具有亲和性的发色芳烃部分。 光解后,有机分子与免疫球蛋白共价连接。 优选的有机分子是肽,优选的芳族烃部分是色氨酸残基。 可光活化的有机分子不需要携带嘌呤,嘧啶或叠氮基以实现与免疫球蛋白的结合和/或光活化。 自噬性超抗体可以促进靶细胞的凋亡和/或增强治疗对抗体治疗反应的疾病或病症的患者的治疗功效。 这些疾病的示例是动脉粥样硬化和心血管疾病。 膜穿透性超抗体可以通过结合细胞内抗半胱天冬酶信号蛋白来预防凋亡。 公开了含有超抗体的组合物,以及制备和使用它们的方法。

    TRANS-MEMBRANE-ANTIBODY INDUCED INHIBITION OF APOPTOSIS
    8.
    发明申请
    TRANS-MEMBRANE-ANTIBODY INDUCED INHIBITION OF APOPTOSIS 审中-公开
    转移膜抗体诱导抑制作用

    公开(公告)号:US20090274710A1

    公开(公告)日:2009-11-05

    申请号:US12421398

    申请日:2009-04-09

    IPC分类号: A61K39/395 C07K16/18

    摘要: Cell suicide (apoptosis) is associated with pathogenesis, for example, it is the major cause for the loss of neurons in Alzheimer's disease. Caspase-3 is critically involved in the pathway of apoptosis. Superantibody (SAT)-trans-membrane technology has been used to produce antibodies against the caspase enzyme in an effort to inhibit apoptosis in living cells. The advantage of using trans-membrane antibodies as apoptosis inhibitors is their specific target recognition in the cell and their lower toxicity compared to conventional apoptosis inhibitors. It is shown that a MTS-transport-peptide modified monoclonal anti-caspase-3 antibody reduces actinomycin D-induced apoptosis and cleavage of spectrin in living cells. These results indicate that antibodies conjugated to a membrane transporter peptide have a therapeutic potential to inhibit apoptosis in a variety of diseases.

    摘要翻译: 细胞自杀(凋亡)与发病机制相关,例如,它是阿尔茨海默病中神经元丧失的主要原因。 Caspase-3严重参与凋亡途径。 已经使用超抗体(SAT) - 跨膜技术产生抗半胱天冬酶的抗体,以抑制活细胞凋亡。 使用跨膜抗体作为细胞凋亡抑制剂的优点是其与细胞凋亡抑制剂相比在细胞中的特异性靶标识别及其较低的毒性。 显示MTS转运肽修饰的单克隆抗半胱天冬酶-3抗体降低放线菌素D诱导的细胞凋亡和活细胞中血影蛋白的裂解。 这些结果表明,与膜转运蛋白肽缀合的抗体具有抑制多种疾病细胞凋亡的治疗潜力。

    SUPERANTIBODY SYNTHESIS AND USE IN DETECTION, PREVENTION AND TREATMENT OF DISEASE
    9.
    发明申请
    SUPERANTIBODY SYNTHESIS AND USE IN DETECTION, PREVENTION AND TREATMENT OF DISEASE 审中-公开
    超敏反应合成及用于检测,预防和治疗疾病

    公开(公告)号:US20090208418A1

    公开(公告)日:2009-08-20

    申请号:US11912992

    申请日:2005-04-29

    摘要: Superantibodies having enhanced autophilic, catalytic, and/or membrane-penetrating properties are prepared by affinity-based conjugation of a photoactivatable organic molecule to a target immunoglobulin. The photoactivatable organic molecule bears a chromophoric aromatic hydrocarbon moiety, which has affinity for the immunoglobulin. Upon photolysis, the organic molecule is covalently linked to the immunoglobulin. A preferred organic molecule is a peptide and a preferred aromatic hydrocarbon moiety is a tryptophan residue. The photoactivatable organic molecule need not bear a purine, pyrimidine or azido group to effect binding to the immunoglobulin and/or photoactivation. The superantibodies can enhance the potency and expand the targeting range of target antibodies. Autophilic superantibodies can promote apoptosis of target cells and/or enhance therapeutic efficacies in the treatment of patients with diseases or disorders responsive to antibody therapy. Exemplary of such diseases are atherosclerosis and cardiovascular disease. Membrane-penetrating superantibodies can prevent apoptosis by binding to intracellular anti-caspase signal proteins. Compositions containing the superantibodies, as well as methods of making and using them, are disclosed.

    摘要翻译: 具有增强的自亲性,催化和/或膜穿透性质的超抗体通过可光活化的有机分子与靶免疫球蛋白的亲和基偶联来制备。 可光活化的有机分子具有对免疫球蛋白具有亲和性的发色芳烃部分。 光解后,有机分子与免疫球蛋白共价连接。 优选的有机分子是肽,优选的芳族烃部分是色氨酸残基。 可光活化的有机分子不需要携带嘌呤,嘧啶或叠氮基以实现与免疫球蛋白的结合和/或光活化。 超抗体可增强靶向抗体的效力并扩大靶向范围。 自噬性超抗体可以促进靶细胞的凋亡和/或增强治疗对抗体治疗反应的疾病或病症的患者的治疗功效。 这些疾病的示例是动脉粥样硬化和心血管疾病。 膜穿透性超抗体可以通过结合细胞内抗半胱天冬酶信号蛋白来预防凋亡。 公开了含有超抗体的组合物,以及制备和使用它们的方法。