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1.发明申请Methods of selecting and producing modified toxins, conjugates containing modified toxins, and uses thereof 审中-公开选择和产生修饰毒素的方法，含有修饰毒素的缀合物及其用途公开(公告)号：US20090092578A1
公开(公告)日：2009-04-09
申请号：US12004025
申请日：2007-12-18
IPC分类号： A61K38/20 , C12P21/02 , A61K38/16 , C12N15/74 , C12N15/70 , A61K39/395 , C12N15/31 , C07K14/195
CPC分类号： C07K16/1203 , A61K47/6415 , C07K14/25 , C07K2319/01 , C07K2319/55 , C12N15/01 , C12N15/1034 , G01N2333/25 , G01N2333/415
摘要： Methods for selecting and identifying modified toxins and conjugates thereof are provided. The methods are select for toxins that exhibit reduced toxicity to the host cell in which they are expressed. Methods of increasing production of toxins, such as the modified toxins, or conjugates thereof, also are provided. In particular, in the methods the toxins, or conjugates thereof, are produced in the presence of an inhibitor molecule. Also provided, are modified toxins and conjugates thereof. Such conjugates can be used in the treatment of various disease or disorders associated with proliferation, migration, and physiological activity of cells involved in immune or inflammatory responses.
摘要翻译： 提供了选择和鉴定修饰毒素及其缀合物的方法。 这些方法是选择对宿主细胞表现出降低的毒性的毒素。 还提供了增加毒素生产的方法，例如修饰的毒素或其缀合物。 特别地，在该方法中，毒素或其结合物在抑制剂分子的存在下产生。 还提供了修饰的毒素及其缀合物。 这种缀合物可以用于治疗与涉及免疫或炎症反应的细胞的增殖，迁移和生理活性相关的各种疾病或病症。
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2.发明申请Methods and compositions for treating secondary tissue damage and other inflammatory conditions and disorders 审中-公开用于治疗次级组织损伤和其他炎性病症和障碍的方法和组合物公开(公告)号：US20110160126A1
公开(公告)日：2011-06-30
申请号：US12932472
申请日：2011-02-24
CPC分类号： C07K14/521 , A61K38/00 , A61K47/6415 , A61K47/642 , A61K47/6425 , A61K2039/505 , C07H21/04 , C07K14/415 , C07K16/2866 , C07K17/00 , C07K2317/77 , C07K2319/00 , C07K2319/33 , C07K2319/55
摘要： Methods for treatment of diseases, including human immunideficiency virus infection, are provided. The disease are treated by administering conjugates containing as a ligand a chemokine receptor targeting agents, such as a chemokine, and a targeted agent, such as a toxin.
摘要翻译： 提供了治疗包括人免疫缺陷病毒感染在内的疾病的方法。 通过施用含有趋化因子受体靶向剂（例如趋化因子）和靶向药物（例如毒素）作为配体的缀合物来治疗该疾病。
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3.发明授权Nucleic acid molecules encoding cytotoxic conjugates that contain a chemokine receptor targeting agent 失效编码含有趋化因子受体靶向剂的细胞毒性偶联物的核酸分子公开(公告)号：US07192736B2
公开(公告)日：2007-03-20
申请号：US09792793
申请日：2001-02-22
CPC分类号： C07K14/521 , A61K47/62 , A61K47/642 , A61K47/6425 , A61K47/6811 , A61K2039/505 , C07H21/04 , C07K7/06 , C07K14/415 , C07K2318/20 , C07K2319/00 , C07K2319/01 , C07K2319/55
摘要： Nucleic acid moleucles that encode conjugates containing as a ligand a chemokine receptor targeting agent, such as a chemokine, and a targeted agent, such as a toxin are provided. These conjugates are used to treat inflammatory responses associated with activation, proliferation and migration of immune effector cells, including leukocyte cell types, neutrophils, macrophages, and eosinophils.
摘要翻译： 提供了编码含有趋化因子受体靶向剂（如趋化因子）和靶向药物（如毒素）作为配体的结合物的核酸痣。 这些缀合物用于治疗与免疫效应细胞（包括白细胞细胞类型，嗜中性粒细胞，巨噬细胞和嗜酸性粒细胞）的激活，增殖和迁移相关的炎性反应。
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公开(公告)号：US07166702B1
公开(公告)日：2007-01-23
申请号：US09453851
申请日：1999-12-02
CPC分类号： C07K14/521 , A61K47/62 , A61K47/642 , A61K47/6425 , A61K47/6811 , A61K2039/505 , C07H21/04 , C07K7/06 , C07K14/415 , C07K2318/20 , C07K2319/00 , C07K2319/01 , C07K2319/55
摘要： Conjugates containing as a ligand chemokine receptor targeting agents, such as chemokines, and a targeted agent, such as a toxin are provided. These conjugates are used to treat inflammatory responses associated with activation, proliferation and migration of immune effector cells, including leukocyte cell types, neutrophils, macrophages, and eosinophils. The conjugates provided herein are used to lessen or inhibit these processes to prevent or at least lessen the resulting secondary effects. In particular, the conjugates can be used to target toxins to receptors on secondary tissue damage-promoting cells. The ligand moiety can be selected to deliver the cell toxin to such secondary tissue damage-promoting cells as mononuclear phagocytes, leukocytes, natural killer cells, dendritic cells, and T and B lymphocytes, thereby suppressing the proliferation, migration, or physiological activity of such cells. Among preferred conjugates are fusion proteins having a chemokine, or a biologically active fragment thereof, as the ligand moiety linked to a cell toxin via a peptide linker of from 2 to about 60 amino acid residues.
摘要翻译： 提供含有作为配体趋化因子受体靶向剂（如趋化因子）和靶向药物（如毒素）的缀合物。 这些缀合物用于治疗与免疫效应细胞（包括白细胞细胞类型，嗜中性粒细胞，巨噬细胞和嗜酸性粒细胞）的激活，增殖和迁移相关的炎性反应。 本文提供的缀合物用于减少或抑制这些过程以防止或至少减轻所得到的二次效应。 特别地，缀合物可用于将毒素靶向次级组织损伤促进细胞上的受体。 可以选择配体部分以将细胞毒素递送至作为单核吞噬细胞，白细胞，天然杀伤细胞，树突状细胞和T和B淋巴细胞的次级组织损伤促进细胞，从而抑制这些细胞的增殖，迁移或生理活性 细胞。 优选的缀合物是具有趋化因子或其生物活性片段的融合蛋白，作为通过2至约60个氨基酸残基的肽接头与细胞毒素连接的配体部分。
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5.发明授权Methods and compositions for treating secondary tissue damage and other inflammatory conditions and disorders 失效用于治疗次级组织损伤和其他炎性病症和障碍的方法和组合物公开(公告)号：US07157418B1
公开(公告)日：2007-01-02
申请号：US09360242
申请日：1999-07-22
CPC分类号： C07K14/521 , A61K47/62 , A61K47/642 , A61K47/6425 , A61K47/6811 , A61K2039/505 , C07H21/04 , C07K7/06 , C07K14/415 , C07K2318/20 , C07K2319/00 , C07K2319/01 , C07K2319/55
摘要： Conjugates containing as a ligand a chemokine receptor targeting agents, such as chemokines, and a targeted agent, such as a toxin are provided. These conjugates are used to treat inflammatory responses associated with activation, proliferation and migration of immune effector cells, including leukocyte cell types, neutrophiles, macrophages, and eosinophils. The conjugates provided herein are used to lessen or inhibit these processes to prevent or at least lessen the resulting secondary effects. In particular, the conjugates are used to target toxins to receptors on secondary tissue damage-promoting cells. The ligand moiety can be selected to deliver the cell toxin to such secondary tissue damage-promoting cells as mononuclear phagocytes, leukocytes, natural killer cells, dendritic cells, and T and B lymphocytes, thereby suppressing the proliferation, migration, or physiological activity of such cells. Among preferred conjugates are fusion proteins having a chemokine, or a biologically active fragment thereof, as the ligand moiety linked to a cell toxin via a peptide linker of from 2 to about 60 amino acid residues.
摘要翻译： 提供了含有作为配体趋化因子受体靶向剂（如趋化因子）和靶向药物如毒素的缀合物。 这些缀合物用于治疗与免疫效应细胞（包括白细胞细胞类型，嗜中性细胞，巨噬细胞和嗜酸性粒细胞）的激活，增殖和迁移相关的炎性反应。 本文提供的缀合物用于减少或抑制这些过程以防止或至少减轻所得到的二次效应。 特别地，缀合物用于将毒素靶向次级组织损伤促进细胞上的受体。 可以选择配体部分以将细胞毒素递送至作为单核吞噬细胞，白细胞，天然杀伤细胞，树突状细胞和T和B淋巴细胞的次级组织损伤促进细胞，从而抑制这些细胞的增殖，迁移或生理活性 细胞。 优选的缀合物是具有趋化因子或其生物活性片段的融合蛋白，作为通过2至约60个氨基酸残基的肽接头与细胞毒素连接的配体部分。
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