Lipidized interferon and methods of treating viral hepatitis
    2.
    发明授权
    Lipidized interferon and methods of treating viral hepatitis 有权
    脂质干扰素和治疗病毒性肝炎的方法

    公开(公告)号:US08486384B2

    公开(公告)日:2013-07-16

    申请号:US12446487

    申请日:2007-10-29

    IPC分类号: A61K38/21 A61K38/00 C07K14/56

    CPC分类号: A61K38/21 A61K47/543

    摘要: The present invention is directed to methods and compositions useful in increasing in mammals the absorption and retention of polypeptides. The invention provides lipid-conjugated interferon having increased liver uptake and increased plasma half-life.

    摘要翻译: 本发明涉及用于增加哺乳动物吸收和保留多肽的方法和组合物。 本发明提供具有增加的肝摄取和增加的血浆半衰期的脂质缀合的干扰素。

    Methods and compositions for lipidization of hydrophilic molecules
    3.
    发明授权
    Methods and compositions for lipidization of hydrophilic molecules 失效
    亲水分子脂化的方法和组合物

    公开(公告)号:US06225445B1

    公开(公告)日:2001-05-01

    申请号:US09120118

    申请日:1998-07-22

    IPC分类号: C07K100

    摘要: Fatty acid derivatives of sulfhydryl-containing compounds (for example, sulfhydryl-containing peptides or proteins) comprising fatty acid-conjugated products with a disulfide linkage are employed for delivery of the compounds to mammalian cells. This modification markedly increases the absorption of the compounds by mammalian cells relative to the rate of absorption of the unconjugated compounds, as well as prolonging blood and tissue retention of the compounds. Moreover, the disulfide linkage in the conjugate is quite labile in the cells and thus facilitates intracellular release of the intact compounds from the fatty acid moieties.

    摘要翻译: 使用包含具有二硫键的脂肪酸缀合产物的含巯基化合物(例如,含巯基肽或蛋白质)的脂肪酸衍生物用于将化合物递送至哺乳动物细胞。 该修饰显着增加了哺乳动物细胞相对于未缀合化合物的吸收速率的吸收,以及延长了化合物的血液和组织滞留。 此外,缀合物中的二硫键在细胞中是非常不稳定的,因此促进完整化合物从脂肪酸部分的细胞内释放。

    Method and compositions for lipidization of hydrophilic molecules
    4.
    发明授权
    Method and compositions for lipidization of hydrophilic molecules 失效
    亲水分子脂化的方法和组合物

    公开(公告)号:US6093692A

    公开(公告)日:2000-07-25

    申请号:US936898

    申请日:1997-09-25

    IPC分类号: A61K38/28

    CPC分类号: A61K47/48038

    摘要: Fatty acid derivatives of disulfide-containing compounds (for example, disulfide-containing peptides or proteins) comprising fatty acid-conjugated products with a disulfide linkage are employed for delivery of the compounds to mammalian cells. This modification markedly increases the absorption of the compounds by mammalian cells relative to the rate of absorption of the unconjugated compounds, as well as prolonging blood and tissue retention of the compounds. Moreover, the disulfide linkage in the conjugate is quite labile in vivo and thus facilitates intracellular or extracellular release of the intact compounds from the fatty acid moieties.

    摘要翻译: 使用包含具有二硫键的脂肪酸共轭产物的含二硫化物的化合物(例如,含二硫化物的肽或蛋白质)的脂肪酸衍生物用于将化合物递送至哺乳动物细胞。 该修饰显着增加了哺乳动物细胞相对于未缀合化合物的吸收速率的吸收,以及延长了化合物的血液和组织滞留。 此外,缀合物中的二硫键在体内是非常不稳定的,因此促进完整化合物从脂肪酸部分的胞内或细胞外释放。

    Compositions and methods for enhanced transepithelial and
transendothelial transport or active agents
    6.
    发明授权
    Compositions and methods for enhanced transepithelial and transendothelial transport or active agents 失效
    增强的跨上皮和跨内皮转运或活性剂的组合物和方法

    公开(公告)号:US5254342A

    公开(公告)日:1993-10-19

    申请号:US768508

    申请日:1991-09-30

    CPC分类号: A61K47/483

    摘要: Compositions and methods for use in enhancement of transmembrane and transcellular transport of an active agent, in particular a peptide or protein, in which at least one carrier for transmembrane or transcellular transport of an active agent which is a ligand for a cell-surface receptor is used to form a ligand/active agent conjugate and at least one transfer enhancement agent which enhances transcytosis of the resultant cell-surface receptor/ligand complex is administered to accelerate transcytosis. As an example, the effects of brefeldin A and monensin on transferrin (Tf) transcellular transport, Tf receptor (TfR) distribution and TfR-mediated endocytosis in filter-grown MDCK cells are described. The transfer enhancement agents markedly enhanced the transcytosis of ligand/active agent complexes in both the apical-to-basal and the basal-to-apical directions, but did not increase the transcytosis of agents which were not bound to a cell-surface receptor ligand as carrier. Furthermore, this enhanced transcytosis was abolished by competition with excess unlabeled Tf, confirming that it was a TfR-mediated process.

    摘要翻译: 用于增强活性剂,特别是肽或蛋白质的跨膜和跨细胞转运的组合物和方法,其中至少一种作为细胞表面受体配体的活性剂的跨膜或跨细胞转运载体是 用于形成配体/活性剂缀合物,并且施用增强所得细胞表面受体/配体复合物的转胞吞作用的至少一种转移增强剂以加速转胞吞作用。 作为例子,描述了布非司定A和莫能菌素对过滤生长MDCK细胞中转铁蛋白(Tf)跨细胞转运,Tf受体(TfR)分布和TfR介导的内吞作用的影响。 转移增强剂显着增强了配体/活性剂复合物在顶端到基底和基底到顶端方向的转胞吞作用,但不增加不结合细胞表面受体配体的试剂的胞吞作用 作为承运人。 此外,通过与过量的未标记的Tf的竞争来消除这种增强的转胞吞作用,证实它是TfR介导的过程。

    Fusion proteins with cleavable spacers and uses thereof
    10.
    发明授权
    Fusion proteins with cleavable spacers and uses thereof 有权
    具有可切割间隔物的融合蛋白及其用途

    公开(公告)号:US07956158B2

    公开(公告)日:2011-06-07

    申请号:US12058648

    申请日:2008-03-28

    申请人: Wei-Chiang Shen

    发明人: Wei-Chiang Shen

    IPC分类号: A61K38/12 A61K38/00

    摘要: A polypeptide comprising a first protein domain, a second protein domain, and a dithiocyclopeptide spacer containing at least one protease cleavage site, wherein the dithiocyclopeptide is exogenous relative to the first or second protein domain, and wherein the first and second protein domains are operably linked by the dithiocyclopeptide. Also disclosed are methods of producing the polypeptide and delivering the protein domains into a cell.

    摘要翻译: 一种多肽,其包含第一蛋白结构域,第二蛋白质结构域和含有至少一个蛋白酶切割位点的二硫环环间隔物,其中所述二硫环环肽相对于所述第一或第二蛋白质结构域是外源的,并且其中所述第一和第二蛋白质结构域可操作地连接 通过二硫环多肽。 还公开了产生多肽并将蛋白质结构域递送到细胞中的方法。