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    • 1. 发明申请
    • CHIMERIC MOLECULES
    • CHIMERIC分子
    • US20120164155A1
    • 2012-06-28
    • US13380272
    • 2010-06-22
    • Elizabeth Grgacic
    • Elizabeth Grgacic
    • A61K39/21C07H21/04G01N33/566A61P31/14C07K16/10C07K19/00A61P37/04
    • C12N7/00A61K39/12A61K39/145A61K2039/5256A61K2039/5258A61K2039/53A61K2039/55505C07K2319/00C12N2740/16134C12N2740/17023C12N2740/17034C12N2760/16122C12N2760/16134Y02A50/386Y02A50/41Y02A50/412Y02A50/414
    • The invention relates to chimeric proteins comprising an antigen and a trimer forming portion or a trimer and virus-like particle forming portion of foamy virus envelope protein (FV TM). The trimer or trimer and virus-like particle forming portion comprises i) full length foamy virus transmembrane protein; ii) foamy virus transmembrane protein absent a functional cytoplasmic domain; iii) foamy virus transmembrane protein absent a functional cytoplasmic domain and transmembrane domain; iv) foamy virus ectodomain comprising N-terminal heptad repeat region and cysteine rich region between N-terminal heptad repeat region and C-terminal α-helical region; v) N-terminal heptad repeat region; vi) a functional variant of any one of i) to v); or vii) any one of i) to vi) lacking an FV fusion peptide domain. In particular, the antigen is an antigen of a virus envelope protein, such as HIV gp 120. Soluble and membrane bound forms of trimeric and higher oligomeric forms of the chimeric proteins are provided as well as nucleic acid molecules encoding and expressing same, viral-like particles comprising same, compositions including pharmaceutical compositions, host cells and kits. Methods are described for producing immune responses including antibodies determined by the chimeric protein or VLP, as well as methods of screening using the chimeric protein, VLP and/or antibodies.
    • 本发明涉及包含抗原和三聚体形成部分或形成泡沫病毒包膜蛋白(FV TM)的三聚体和病毒样颗粒形成部分的嵌合蛋白。 三聚体或三聚体和病毒样颗粒形成部分包括i)全长泡沫病毒跨膜蛋白; ii)泡沫病毒跨膜蛋白不存在功能性细胞质结构域; iii)泡沫病毒跨膜蛋白没有功能性细胞质结构域和跨膜结构域; iv)包含N-末端七肽重复区和N末端七重复区和C-末端α-螺旋区之间的半胱氨酸富集区的泡沫病毒胞外域; v)N-末端七肽重复区; vi)i)至v)中任一项的功能变体; 或vii)i)至vi)中的任何一个缺乏FV融合肽结构域。 特别地,抗原是病毒包膜蛋白(例如HIV gp120)的抗原。提供嵌合蛋白质的三聚体和更高级寡聚体形式的可溶性和膜结合形式以及编码和表达嵌合蛋白的核酸分子, 包含其的类似颗粒,包括药物组合物,宿主细胞和试剂盒的组合物。 描述了用于产生包括由嵌合蛋白或VLP测定的抗体的免疫应答的方法,以及使用嵌合蛋白,VLP和/或抗体进行筛选的方法。