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52. 发明授权

US06894031B1 Pituitary tumor transforming gene (PTTG) carboxy-terminal peptides and methods of use thereof to inhibit neoplastic cellular proliferation and/or transformation 失效
标题翻译：垂体肿瘤转化基因（PTTG）羧基末端肽及其用于抑制肿瘤细胞增殖和/或转化的方法
公开(公告)号：US06894031B1
公开(公告)日：2005-05-17
申请号：US09569956
申请日：2000-05-12
申请人： Gregory A. Horwitz , Xun Zhang , Shlomo Melmed
发明人： Gregory A. Horwitz , Xun Zhang , Shlomo Melmed
IPC分类号： A01K67/027 , A61K38/00 , A61K48/00 , C07K14/47 , C07K14/82 , A01N43/04 , A01N63/00 , C07H21/04 , C12N15/00 , C12N15/63
CPC分类号： A01K67/027 , A01K2217/05 , A61K38/00 , A61K48/00 , C07K14/47 , C07K14/82 , C12N2799/022 , Y10S435/81 , Y10S435/975
摘要： Disclosed is a method of inhibiting neoplastic cellular proliferation and/or transformation of mammalian cells, including cells of human origin, in vitro or in vivo. The inventive method involves the use of a pituitary tumor transforming gene carboxy-terminal peptide (PTTG-C), which has the ability to regulate endogenous pituitary, tumor transforming gene (PTTG) expression and/or function in a dominant negative manner. In some embodiments, the invention is directed to gene-based treatments that deliver PTTG-C-related polynucleotides to mammalian cells, whether in vitro or in vivo, to inhibit the endogenous expression of PTTG. Other embodiments are directed to peptide-based treatments that deliver PTTG-C peptide molecules to the cells, which inhibit endogenous PTTG expression and/or PTTG function. Additional embodiments directed to a method of inhibiting tumor angiogenesis, in vivo, are also disclosed. Also disclosed are compositions useful for inhibiting neoplastic cellular proliferation and/or transformation and tumor angiogenesis, including compositions comprising a PTTG carboxy-terminal peptide or comprising a chimeric or fusion protein that contains a first PTTG carboxy-terminal peptide segment and a second cellular uptake-enhancing and/or importation-competent peptide segment. Also disclosed are compositions comprising a PTTG carboxy-terminal-related polynucleotide, including compositions comprising expression vectors containing the PTTG-C-related polynucleotides. Kits comprising the inventive compositions are also disclosed for the treatment of neoplastic cellular proliferation in vitro or in vivo. Isolated PTTG-C peptides and PTTG-C-related polynucleotides are also disclosed, as are anti-PTTG-C-specific antibodies.
摘要翻译：公开了在体外或体内抑制哺乳动物细胞（包括人源的细胞）的肿瘤细胞增殖和/或转化的方法。本发明的方法涉及使用垂体肿瘤转化基因羧基末端肽（PTTG-C），其具有以显性负性方式调节内源性垂体，肿瘤转化基因（PTTG）表达和/或功能的能力。在一些实施方案中，本发明涉及将PTTG-C相关多核苷酸递送至哺乳动物细胞的基于基因的治疗，无论是在体外还是在体内，以抑制PTTG的内源性表达。其它实施方案涉及将PTTG-C肽分子递送至抑制内源PTTG表达和/或PTTG功能的细胞的基于肽的治疗。还公开了针对体内抑制肿瘤血管发生的方法的另外的实施方案。还公开了可用于抑制肿瘤细胞增殖和/或转化和肿瘤血管发生的组合物，包括包含PTTG羧基末端肽或包含嵌合或融合蛋白的组合物，其包含第一PTTG羧基末端肽段和第二细胞吸收 - 增强和/或进口能力的肽段。还公开了包含PTTG羧基末端相关多核苷酸的组合物，包括含有含有PTTG-C相关多核苷酸的表达载体的组合物。还公开了包含本发明组合物的试剂盒用于在体外或体内治疗肿瘤细胞增殖。还公开了分离的PTTG-C肽和PTTG-C相关多核苷酸，抗PTTG-C特异性抗体也是如此。

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