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公开(公告)号：US5206344A
公开(公告)日：1993-04-27
申请号：US142467
申请日：1988-01-11
CPC分类号： A61K47/48215 , A61K38/2013 , A61K38/215 , A61K47/48476 , C07K1/1077 , Y10S930/141
摘要： Muteins of IL-2 in which one of the amino acids of the mature native sequence of IL-2 is replaced by a cysteine residue are prepared and conjugated through the replaced cysteine residue to a polymer selected from polyethylene glycol homopolymers or polyoxyethylated polyols, wherein said homopolymers are unsubstituted or substituted at one end with an alkyl group. These muteins are made via host expression of mutant genes encoding the muteins that have been changed from the genes for the parent proteins by site-directed mutagenesis. In addition, other species of IL-2 may be conjugated via the cysteine residue at position 125 of the mature IL-2 protein that is not necessary for the biological activity of the IL-2.
摘要翻译： 制备其中IL-2的成熟天然序列的一个氨基酸被半胱氨酸残基取代的IL-2的突变蛋白，并通过所述替换的半胱氨酸残基与选自聚乙二醇均聚物或聚氧乙烯化多元醇的聚合物缀合，其中所述 均聚物是未取代的或在一端被烷基取代。 这些突变蛋白是通过宿主表达编码突变蛋白的突变基因，通过定点突变从母体蛋白的基因中改变的突变蛋白。 此外，IL-2的其它物质可以通过成熟IL-2蛋白的125位的半胱氨酸残基而被结合，这对于IL-2的生物活性是不必要的。
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公开(公告)号：US4902502A
公开(公告)日：1990-02-20
申请号：US299235
申请日：1989-01-23
IPC分类号： A61K47/48
CPC分类号： A61K47/48215
摘要： The present invention is a process for preparing a pharmaceutical composition comprising a biologically active conjugated protein. It comprises a polyethylene glycol or a polyoxyethylated polyol conjugated to IL-2. This protein is conjugated to reduce its immunogenicity, and increase it solubility, and increase its circulating in vivo half-life.
摘要翻译： 本发明是一种制备包含生物活性共轭蛋白质的药物组合物的方法。 它包含与IL-2缀合的聚乙二醇或聚氧乙烯化多元醇。 这种蛋白质被缀合以降低其免疫原性，并增加其溶解度，并增加其体内循环体内的半衰期。
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公开(公告)号：US5089261A
公开(公告)日：1992-02-18
申请号：US415046
申请日：1989-09-29
IPC分类号： A61K47/48
CPC分类号： A61K47/48215
摘要： The present invention is a process for preparing a pharmaceutical composition comprising a biologically active conjugated protein. It comprises a polyethylene glycol or a polyoxyethylated polyol conjugated to IL-2. This protein is conjugated to reduce its immunogenicity, and increase its solubility, and increase its circulating in vivo half-life.
摘要翻译： 本发明是一种制备包含生物活性共轭蛋白质的药物组合物的方法。 它包含与IL-2缀合的聚乙二醇或聚氧乙烯化多元醇。 该蛋白质被缀合以降低其免疫原性，并增加其溶解度，并增加其体内循环体内的半衰期。
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公开(公告)号：US4789630A
公开(公告)日：1988-12-06
申请号：US896677
申请日：1986-08-20
IPC分类号： G01N33/545 , C12Q1/28 , C12Q1/68 , G01N21/82 , G01N33/535 , G01N33/543 , G01N33/58 , G01N33/53
CPC分类号： C12Q1/28 , C12Q1/68 , G01N33/581 , C12Q2326/12 , Y10S435/803 , Y10S435/81 , Y10S435/96 , Y10S435/975
摘要： Useful for visualizing biological materials in a solid phase, on a gel, or in a liquid phase is a solid salt of the meriquinone of benzidine or a substituted benzidine. An immobilized or dissolved complex of a polymeric anion and the meriquinone of benzidine or a substituted benzidine having controllable solubility may also be employed. Preferred are meriquinone salts and complexes of 3,3,5,5'-tetramethylbenzidine. For visualization, the benzidine or substituted benzidine is oxidized to its meriquinone at pH 3 to 7 in the presence of an effective anion or polymeric anion, an oxidation catalyst, and an effective amount of oxidant to form a solid salt or immobilized complex of the meriquinone under conditions where the meriquinone solubility lies below about 10.sup.-5 M.
摘要翻译： 可用于在固相，凝胶或液相中可视化生物材料是联苯胺或取代的联苯胺的固醇的固体盐。 还可以使用固定或溶解的聚合阴离子的复合物和具有可控的溶解度的联苯胺或取代的联苯胺的金刚酮。 优选3,3,5,5'-四甲基联苯胺的季戊四醇盐和络合物。 为了可视化，联苯胺或取代的联苯胺在有效阴离子或聚合阴离子，氧化催化剂和有效量的氧化剂的存在下，在pH 3至7下被氧化成其三聚物，以形成固体盐或固定的复合物 在meriquinone溶解度低于约10 -5 M的条件下。
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