公开(公告)号：US07105653B2

公开(公告)日：2006-09-12

申请号：US10826809

申请日：2004-04-17

申请人： Armen B. Shanafelt ,  Jeffrey M. Greve ,  Gary Jesmok ,  Kenneth Lembach ,  Gayle D. Wetzel

发明人： Armen B. Shanafelt ,  Jeffrey M. Greve ,  Gary Jesmok ,  Kenneth Lembach ,  Gayle D. Wetzel

IPC分类号： C12N5/10 ,  C12N15/26 ,  C12N15/63

CPC分类号： C07K14/55 ,  A61K38/00

摘要： The invention is directed to a polypeptide comprising a human IL-2 mutein numbered in accordance with wild-type IL-2 wherein said human IL-2 is substituted at at least one of positions 20, 88 or 126, whereby said mutein preferentially activates T cells over NK cells. D20H and I, N88G, I, and R, in particular have a relative T cell-differential activity much greater than native IL-2, with predicted associated reduced in vivo toxicity. The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.

摘要翻译： 本发明涉及包含根据野生型IL-2编号的人IL-2突变蛋白的多肽，其中所述人IL-2在20,88或126位中的至少一个被取代，其中所述突变蛋白优先激活T 细胞在NK细胞上。 D20H和I，N88G，I和R特别具有比天然IL-2大得多的相对T细胞差异活性，预测相关的体内毒性降低。 本发明还包括编码本发明的突变蛋白的多核苷酸，含有多核苷酸的载体，转化的宿主细胞，包含突变蛋白的药物组合物和治疗方法。