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    Proproteins and Methods of Use Thereof
    74.
    发明申请
    Proproteins and Methods of Use Thereof 有权
    Proproteins及其使用方法

    公开(公告)号：US20130101555A1

    公开(公告)日：2013-04-25

    申请号：US13721528

    申请日：2012-12-20

    申请人： CytomX Therapeutics, Inc.

    发明人： Nancy E. Stagliano ,  James W. West ,  Kathryn Kamath ,  Paul H. Bessette ,  Jason Sagert

    IPC分类号： C07K19/00

    CPC分类号： C07K14/56 ,  A61K38/00 ,  A61K47/64 ,  A61K47/65 ,  C07K14/00 ,  C07K14/555 ,  C07K14/565 ,  C07K14/57 ,  C07K14/705 ,  C07K16/00 ,  C07K19/00 ,  C07K2319/10 ,  C07K2319/31 ,  C07K2319/33 ,  C07K2319/50 ,  C07K2319/70 ,  C07K2319/90 ,  C12N15/1037 ,  G01N33/6866

    摘要： The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.

    摘要翻译： 本公开内容提供了蛋白质和可激活的前蛋白组合物。 前蛋白含有功能蛋白（即其全长蛋白质或其功能片段），其与抑制功能蛋白与其靶标或结合配偶体的结合的肽掩模偶联。 可激活的蛋白质包含与肽掩模偶联的功能性蛋白质，并进一步与可活化接头偶联，其中在非活化状态下，肽掩模抑制功能性蛋白质与其靶标或结合配偶体的结合，并且在活化状态下 肽掩模不抑制功能蛋白与其靶或结合配偶体的结合。 前体蛋白可以提供如果不抑制结合其结合配偶体的功能性蛋白质在非处理部位的结合，则可以提供降低的毒性和不良副作用。 前体蛋白可进一步提供改善的生物分布特征。 含有肽掩模的前体蛋白可以显示比不含肽掩模的相应功能蛋白质更长的体内或血清半衰期。 本公开进一步提供筛选，制备和使用这些蛋白质的方法。

    ACTIVATABLE CYTOKINE CONSTRUCTS AND COMBINATION METHODS
    79.
    发明公开
    ACTIVATABLE CYTOKINE CONSTRUCTS AND COMBINATION METHODS 审中-公开

    公开(公告)号：US20230192798A1

    公开(公告)日：2023-06-22

    申请号：US17938536

    申请日：2022-10-06

    申请人： CytomX Therapeutics, Inc.

    发明人： Alexey Yevgenyevich Berezhnoy ,  Nicole G. Lapuyade ,  Na Cai ,  Michael B. Winter ,  Kenneth Wong ,  Madan M. Paidhungat ,  Dylan L. Daniel ,  Erwan Le Scolan

    IPC分类号： C07K14/56 ,  C07K16/28 ,  A61P35/00

    CPC分类号： C07K14/56 ,  C07K16/2896 ,  A61P35/00

    摘要： Provided herein are methods of treating a subject by administering a combination of an activatable cytokine construct (ACC) and a PD-1/PD-L1 pathway inhibitor in which the ACC includes: a first monomer construct including an optional first peptide mask (PM1), an optional third cleavable moiety (CM3), a first mature cytokine protein (CP1), a first cleavable moiety (CM1), and a first dimerization domain (DD1), wherein the CM1 is positioned between the CP1 and the DD1; and a second monomer construct including an optional second peptide mask (PM2), an optional forth cleavable moiety (CM4), a second mature cytokine protein (CP2), a second cleavable moiety (CM2), and a second dimerization domain (DD2), wherein the CM2 is positioned between the CP2 and the DD2; wherein the DD1 and the DD2 bind to each other thereby forming a dimer of the first monomer construct and the second monomer construct; and where the ACC is characterized by a reduction in at least one activity of the CP1 and/or CP2 as compared to a control level of the at least one activity of the CP1 and/or CP2.