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1. 发明授权

US5601825A Therapeutic conjugates of toxins and drugs 失效
标题翻译：毒素和药物的治疗共轭物
公开(公告)号：US5601825A
公开(公告)日：1997-02-11
申请号：US452131
申请日：1995-05-26
申请人： Hans J. Hansen , Gary L. Griffiths , Anastasia Lentine-Jones , David M. Goldenberg
发明人： Hans J. Hansen , Gary L. Griffiths , Anastasia Lentine-Jones , David M. Goldenberg
IPC分类号： A61K38/00 , A61K31/00 , A61K38/22 , A61K38/43 , A61K39/395 , A61K47/48 , A61K51/10 , A61K51/12 , A61P31/00 , A61P35/00 , A61P35/02 , C07K14/435 , C07K16/06 , C07K16/10 , C07K16/18 , C07K16/30 , G01N33/534 , G01N33/68 , C07K16/20 , C07K19/00
CPC分类号： A61K51/10 , A61K47/48523 , A61K47/48569 , A61K51/1018 , A61K51/1048 , A61K51/1093 , A61K51/1282 , C07K16/065 , C07K16/1063 , C07K16/30 , G01N33/534 , G01N33/6857 , A61K2121/00 , A61K2123/00 , A61K38/00
摘要： Provided are conjugates useful in cancer or infectious disease therapy. The conjugate is a drug or modified toxin which is a native toxin devoid of a functioning receptor binding domain and a protein which reacts with a substance associated with a targeted cell or pathogen. The targeted substance internalizes the conjugate into the cell cytoplasm, and the kills the cell. The protein prior to conjugation has at least one mercapto group which becomes a site for conjugation to the toxin or drug. Also provided are methods of therapy, methods for producing the conjugate and pharmaceuticals compositions of the conjugates.
摘要翻译：提供可用于癌症或感染性疾病治疗的缀合物。缀合物是药物或修饰的毒素，其是没有功能受体结合结构域的天然毒素和与靶向细胞或病原体相关的物质发生反应的蛋白质。靶向物质将结合物内化为细胞质，杀死细胞。缀合前的蛋白质具有至少一个巯基，其成为与毒素或药物缀合的位点。还提供了治疗方法，生产缀合物的方法和缀合物的药物组合物。

2. 发明授权

US5541297A Therapeutic conjugates of toxins and drugs 失效
标题翻译：毒素和药物的治疗共轭物
公开(公告)号：US5541297A
公开(公告)日：1996-07-30
申请号：US882177
申请日：1992-05-11
申请人： Hans J. Hansen , Gary L. Griffiths , Anastasia Lentine-Jones , David M. Goldenberg
发明人： Hans J. Hansen , Gary L. Griffiths , Anastasia Lentine-Jones , David M. Goldenberg
IPC分类号： A61K38/00 , A61K31/00 , A61K38/22 , A61K38/43 , A61K39/395 , A61K47/48 , A61K51/10 , A61K51/12 , A61P31/00 , A61P35/00 , A61P35/02 , C07K14/435 , C07K16/06 , C07K16/10 , C07K16/18 , C07K16/30 , G01N33/534 , G01N33/68 , C07K16/46
CPC分类号： A61K51/10 , A61K47/48523 , A61K47/48569 , A61K51/1018 , A61K51/1048 , A61K51/1093 , A61K51/1282 , C07K16/065 , C07K16/1063 , C07K16/30 , G01N33/534 , G01N33/6857 , A61K2121/00 , A61K2123/00 , A61K38/00
摘要： Provided are conjugates useful in cancer or infectious disease therapy. The conjugate is a drug or modified toxin which is a native toxin devoid of a functioning receptor binding domain and a protein which reacts with a substance associated with a targeted cell or pathogen. The targeted substance internalizes the conjugate into the cell cytoplasm, and the kills the cell. The protein prior to conjugation has at least one mercapto group which becomes a site for conjugation to the toxin or drug. Also provided are methods of therapy, methods for producing the conjugate and pharmaceuticals compositions of the conjugates.
摘要翻译：提供可用于癌症或感染性疾病治疗的缀合物。缀合物是药物或修饰的毒素，其是没有功能受体结合结构域的天然毒素和与靶向细胞或病原体相关的物质发生反应的蛋白质。靶向物质将结合物内化为细胞质，杀死细胞。缀合前的蛋白质具有至少一个巯基，其成为与毒素或药物缀合的位点。还提供了治疗方法，生产缀合物的方法和缀合物的药物组合物。

3. 发明授权

US5328679A Methods for technetium/rhenium labeling of proteins 失效
标题翻译：蛋白质锝/铼标记方法
公开(公告)号：US5328679A
公开(公告)日：1994-07-12
申请号：US760466
申请日：1991-09-17
申请人： Hans J. Hansen , Gary L. Griffiths , Anastasia Lentine-Jones
发明人： Hans J. Hansen , Gary L. Griffiths , Anastasia Lentine-Jones
IPC分类号： A61K51/10 , A61K51/12 , A61K49/02 , A61K39/395 , A61K43/00 , C07K15/28
CPC分类号： A61K51/1048 , A61K51/10 , A61K51/1282 , A61K2123/00
摘要： A method for radiolabeling a protein with a radioisotope of technetium or rhenium is disclosed which comprises the steps of contacting a solution of a protein containing a plurality of adjacent free sulfhydryl groups, or in particular cases, intact protein containing at least one disulfide group, with stannous ions, and then with radiopertechnetate or radioperrhenate, the amount of stannous ion being sufficient to substantially completely reduce the radiopertechnetate or radioperrhenate, and recovering radiolabeled protein.A rapid and quantitative method for producing a sterile, injectable solution of Tc-99m-labeled monovalent antibody fragment is also disclosed which comprises the step of mixing a sterile solution containing a monovalent antibody fragment having at least one free sulfhydryl group, stannous chloride and excess tartrate, at mildly acidic pH, or a sucrose-stabilized lyophilizate of such solution, with a sterile solution of Tc-99m-pertechnetate, whereby substantially quantitative labeling of the antibody fragment with Tc-99m is effected in about 5 minutes at ambient temperature, the resultant sterile solution of Tc-99m-labeled monovalent antibody fragment being suitable for immediate injection into a patient for scintigraphic imaging.
摘要翻译：公开了用锝或铼的放射性同位素放射性标记蛋白质的方法，其包括将含有多个相邻游离巯基的蛋白质溶液或特别是含有至少一个二硫基的完整蛋白质溶液与亚锡离子，然后用锝铁或无铼酸盐，亚锡离子的量足以基本上完全降低玄武岩或无纶珍珠岩，并回收放射性标记的蛋白质。还公开了用于生产Tc-99m标记的单价抗体片段的无菌注射溶液的快速和定量的方法，其包括将含有至少一个游离巯基，氯化亚锡和过量的一价抗体片段的无菌溶液混合的步骤用温和酸性pH的酒石酸盐或这种溶液的蔗糖稳定的冻干物，用Tc-99m-高锝酸盐的无菌溶液，由此在约5分钟内在环境温度下对Tc-99m的抗体片段进行基本上定量的标记，所得到的Tc-99m标记的单价抗体片段的无菌溶液适于立即注射到患者中用于闪烁照相成像。

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