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    • 4. 发明申请
    • Method for Shielding Functional Sites or Epitopes on Proteins
    • 屏蔽蛋白质功能位点或表位的方法
    • US20100092505A1
    • 2010-04-15
    • US11887604
    • 2006-03-31
    • Elisabetta BianchiAntonello Pessi
    • Elisabetta BianchiAntonello Pessi
    • A61K39/385C07K17/00A61P37/04
    • C07K14/005A61K39/00A61K47/60C12N2740/16122
    • Methods of site-specifically shielding one or more binding sites within a polypeptide are disclosed, comprising attaching at least one small molecular weight, water-soluble polymer to said polypeptide such that the binding site is masked by said polymer. The shielding of a binding site (e.g., epitope) as per the disclosed methods acts to either eliminate or substantially reduce the biological response induced by the interaction between said binding site and its cognate receptor, helping to refocus the biological response toward unmasked portions of the polypeptide. Pharmaceutical products generated as per the methods described herein (e.g., polymer-modified antigens and vaccine compositions comprising them), as well as the use thereof, induce a specific immune response against unmasked portions of the polypeptides when directly introduced into living vertebrate tissue, preferably a mammalian host such as a human or a non-human mammal of commercial or domestic veterinary importance, generating selective immunoprotection in said mammal.
    • 公开了特异性屏蔽多肽内的一个或多个结合位点的方法,包括将至少一种小分子量的水溶性聚合物连接到所述多肽上,使得结合位点被所述聚合物掩蔽。 根据所公开的方法,结合位点(例如,表位)的屏蔽用于消除或显着降低由所述结合位点与其同源受体之间的相互作用诱导的生物反应,有助于将生物反应重新聚焦到未被掩蔽的部分 多肽。 根据本文所述的方法(例如,聚合物修饰的抗原和包含它们的疫苗组合物)产生的药物产品及其用途当直接引入活的脊椎动物组织时诱导针对多肽的未掩蔽部分的特异性免疫应答 哺乳动物宿主,例如商业或家庭兽医重要的人或非人哺乳动物,在所述哺乳动物中产生选择性免疫保护。
    • 8. 发明申请
    • Stable Peptide Mimetic of Hiv Gp41 Fusion Intermediate
    • 稳定肽模拟的HIF Gp41融合中间体
    • US20070224212A1
    • 2007-09-27
    • US11628483
    • 2005-05-27
    • Elisabetta BianchiAntonello PessiRomas GeleziunasDavid Bramhill
    • Elisabetta BianchiAntonello PessiRomas GeleziunasDavid Bramhill
    • C12Q1/70
    • C07K14/005A61K38/00A61K39/00A61K39/12C12N2740/15022C12N2740/16122C12N2740/16134G01N2333/16G01N2500/02
    • Methods of covalently-stabilizing alpha-helical, chimeric peptides constrained within a homotrimeric or heterotrimeric coiled-coil structure are disclosed. The coiled-coil structures made by the methods disclosed within this specification mimic all or a portion of the internal, trimeric coiled-coil motif contained within the fusogenic conformation of an enveloped virus membrane-fusion protein, particularly the internal coiled-coil domain of the HIV gp41 ectodomain. The HIV-derived, chimeric peptides disclosed comprise a non-HIV, soluble, trimeric form of a coiled-coil fused in helical phase to all or a portion of the N-helix of HIV gp41 and are covalently-stabilized in a homotrimeric or heterotrimeric coiled-coil structure through the formation of disulfide or chemoselective bonds between said peptides. The covalently-stabilized, HIV-derived, homotrimeric or heterotrimeric coiled-coil structures made by the methods disclosed herein represent a close mimetic of a HIV gp41 fusion intermediate and are potent inhibitors of HIV infectivity. These HIV-derived chimeric peptides may provide for therapeutic treatment against HIV infection by inhibiting the virus-host cell membrane fusion process.
    • 公开了限制在同三聚体或异三聚体卷曲螺旋结构内的共价稳定的α-螺旋嵌合肽的方法。 通过本说明书中公开的方法制备的盘绕线圈结构模拟包含在包膜病毒膜 - 融合蛋白的融合构象内的内部三聚体卷曲螺旋基序的全部或一部分,特别是内部卷曲螺旋结构域 HIV gp41胞外域。 所公开的HIV衍生的嵌合肽包含螺旋状螺旋状的非HIV,可溶性三聚体形式,其与HIV gp41的全部或部分N-螺旋融合,并且以同三聚或异三聚体共价稳定 通过在所述肽之间形成二硫键或化学选择性键来进行卷曲螺旋结构。 由本文公开的方法制备的共价稳定的HIV衍生的同源三聚体或异三聚体卷曲螺旋结构代表HIV gp41融合中间体的密切模拟物,并且是HIV感染性的有效抑制剂。 这些HIV衍生的嵌合肽可以通过抑制病毒宿主细胞膜融合过程来提供针对HIV感染的治疗性治疗。