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    Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug
    41.
    发明授权
    Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug 有权
    用于增加化疗药物靶标特异性毒性的方法和组合物

    公开(公告)号：US07470429B2

    公开(公告)日：2008-12-30

    申请号：US10066782

    申请日：2002-02-06

    申请人： Gary L. Griffiths ,  Hans J. Hansen

    发明人： Gary L. Griffiths ,  Hans J. Hansen

    IPC分类号： A61K39/00

    CPC分类号： B82Y5/00 ,  A61K47/6815 ,  A61K47/6863 ,  A61K47/6867 ,  A61K47/6879 ,  A61K47/6895 ,  A61K47/6899

    摘要： A method for increasing the target-specific toxicity of a drug is effected by pretargeting an enzyme to a mammalian target site, and then administering a cytotoxic drug known to act at the target site, or a prodrug form thereof which is converted to the drug in situ, which drug is also detoxified to form an intermediate of lower toxicity using said mammal's ordinary metabolic processes, whereby the detoxified intermediate is reconverted to its more toxic form by the pretargeted enzyme and thus has enhanced cytotoxicity at the target site. Further enhancement can be achieved by pretargeting an enzyme which converts the prodrug to the cytotoxic drug at the target site. Kits for use with the method also are provided. The method and kits permit lower doses of cytotoxic agents, maximize target site activity and minimize systemic side effects.

    摘要翻译： 通过将酶靶向到哺乳动物靶位点，然后施用已知在靶位点起作用的细胞毒性药物或其转化为药物的前药形式，来实现增加药物的靶特异性毒性的方法 使用所述哺乳动物的普通代谢过程，所述药物也被解毒以形成具有较低毒性的中间体，由此所述解毒中间体被所述预靶向酶再转化为其更具毒性的形式，因此在靶位点具有增强的细胞毒性。 可以通过预靶向在靶位点将前药转化为细胞毒性药物的酶来实现进一步增强。 还提供了与该方法一起使用的套件。 该方法和试剂盒允许较低剂量的细胞毒剂，最大限度地提高目标部位活性并最大程度减少全身副作用。

    Composite Probes and Use Thereof in Super Resolution Methods
    48.
    发明申请
    Composite Probes and Use Thereof in Super Resolution Methods 有权
    复合探针及其在超分辨率方法中的应用

    公开(公告)号：US20120309045A1

    公开(公告)日：2012-12-06

    申请号：US13519737

    申请日：2010-12-28

    申请人： Jay R. Knutson ,  Gary L. Griffiths

    发明人： Jay R. Knutson ,  Gary L. Griffiths

    IPC分类号： C07K7/06 ,  C12N13/00 ,  B29C59/16 ,  G01N21/21 ,  G01N21/59 ,  G01N21/64 ,  F21V9/16

    CPC分类号： C07K2/00 ,  C09B11/24 ,  C09B23/086 ,  G01N21/6428 ,  G01N21/6458 ,  G01N2021/6432 ,  G01N2021/6441 ,  Y10T436/21

    摘要： Composite probes for super resolution optical techniques using super resolution via transiently activated quenchers (STAQ) include a donor moiety and an acceptor moiety joined by a linker, wherein the acceptor moiety, when excited by incident radiation, is excited to a state which, for example, absorbs in the donor emission region, such that the acceptor moiety in its excited state quenches at least a portion of the donor moiety emission. Other transiently activated quenching mechanisms and moieties could accomplish the same task by reducing donor population. Also disclosed are methods for irradiating a selected region of a target material including the composite probe, wherein the composite probe enables improved resolution by point spread function modification and/or nanoscale chemical reactions.

    摘要翻译： 用于通过瞬时激活猝灭剂（STAQ）使用超分辨率的超分辨率光学技术的复合探针包括通过接头连接的供体部分和受体部分，其中受体部分在被入射辐射激发时被激发到例如 ，在受体发射区吸收，使得其激发态的受体部分猝灭供体部分发射的至少一部分。 其他瞬时激活的猝灭机制和部分可以通过减少供体群体来完成相同的任务。 还公开了用于照射包括复合探针的靶材料的选定区域的方法，其中复合探针通过点扩散功能修饰和/或纳米级化学反应提高了分辨率。

    Site-specific labeling of disulfide-containing targeting vectors
    49.
    发明授权
    Site-specific labeling of disulfide-containing targeting vectors 有权
    二硫化物靶向载体的位点特异性标记

    公开(公告)号：US06576746B2

    公开(公告)日：2003-06-10

    申请号：US09417109

    申请日：1999-10-13

    申请人： William J. McBride ,  Gary L. Griffiths

    发明人： William J. McBride ,  Gary L. Griffiths

    IPC分类号： C07K1600

    CPC分类号： G01N33/531 ,  A61K47/6889 ,  A61K51/1093 ,  Y10S435/81

    摘要： A method of producing a diagnostic or therapeutic conjugate of a protein, polypeptide or peptide containing at least one disulfide bond which is necessary to maintain its biological activity, and bearing at least one thiol-containing moiety linked thereto through a hydrazone or hydrazine linkage, is effected by contacting said protein, polypeptide or peptide with a thiol-reactive diagnostic or therapeutic agent, either preformed or generated in situ, to form a stable diagnostic or therapeutic conjugate of the protein, polypeptide or peptide without substantial cleavage of the disulfide bond. Diagnostic and therapeutic conjugates produced using the foregoing method, as well as kits for carrying out the method are provided.

    摘要翻译： 产生含有维持其生物学活性所必需的至少一个二硫键的蛋白质，多肽或肽的诊断或治疗性缀合物的方法，以及通过腙或肼键连接至少一个含硫醇的部分， 通过将所述蛋白质，多肽或肽与硫醇反应性诊断或治疗剂接触，其通过预先形成或原位产生，以形成蛋白质，多肽或肽的稳定的诊断或治疗缀合物，而不显着切割二硫键。 提供了使用上述方法制备的诊断和治疗缀合物，以及用于实施该方法的试剂盒。