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    B7-H4 fusion proteins and methods of use thereof
    1.
    发明授权
    B7-H4 fusion proteins and methods of use thereof 有权
    B7-H4融合蛋白及其使用方法

    公开(公告)号：US09011853B2

    公开(公告)日：2015-04-21

    申请号：US13392811

    申请日：2010-08-31

    申请人： Solomon Langermann ,  Linda Liu ,  Joseph R. Podojil ,  Stephen D. Miller ,  Shannon Marshall

    发明人： Solomon Langermann ,  Linda Liu ,  Joseph R. Podojil ,  Stephen D. Miller ,  Shannon Marshall

    IPC分类号： A61K38/16 ,  C07K14/705 ,  C07K16/46 ,  G01N33/68 ,  A61K38/17 ,  C07K16/28

    CPC分类号： C07K14/70532 ,  A61K9/0019 ,  A61K38/00 ,  A61K38/1709 ,  A61K39/44 ,  C07K16/2827 ,  C07K2317/50 ,  C07K2317/56 ,  C07K2317/72 ,  C07K2319/30 ,  C07K2319/32 ,  G01N33/6863 ,  G01N33/6866 ,  G01N33/6869 ,  G01N2800/52

    摘要： Fusion proteins containing B7-H4 polypeptides are disclosed. The B7-H4 fusion proteins can include full-length B7-H4 polypeptides, or can contain a fragment of a full-length B7-H4 polypeptide, including some or all of the extracellular domain of the B7-H4 polypeptide. Methods for using the fusion proteins to downregulate T cell activation and for the treatment of inflammatory and autoimmune diseases and disorders are also disclosed. The B7-H4 fusion proteins are useful for treating inflammation by inhibiting or reducing differentiation, proliferation, activity, and/or cytokine production and/or secretion by ThI, ThI 7, Th22, and/or other cells that secrete, or cause other cells to secrete, inflammatory molecules, including, but not limited to, IL-1β, TNF-α, TGF-beta, IFN-γ, IL-17, IL-6, IL-23, IL-22, IL-21, and MMPs; or enhancing IL-IO secretion by Tregs, increasing the differentiation of Tregs, increasing the number of Tregs, or combinations thereof.

    摘要翻译： 公开了含有B7-H4多肽的融合蛋白。 B7-H4融合蛋白可以包括全长B7-H4多肽，或可以含有全长B7-H4多肽的片段，包括B7-H4多肽的一些或全部细胞外结构域。 还公开了使用融合蛋白来下调T细胞活化和治疗炎性和自身免疫性疾病和病症的方法。 B7-H4融合蛋白可用于通过抑制或减少Th1，Th17，Th22和/或分泌或引起其他细胞的其他细胞的分化，增殖，活性和/或细胞因子产生和/或分泌来治疗炎症 包括但不限于IL-1和bgr; TNF-α，TGF-β，IFN-γ，IL-17，IL-6，IL-23，IL-22，IL-21， 和MMPs; 或增强Treg的IL-10分泌，增加Treg的分化，增加Treg的数量或其组合。

    Anti-B7-H4 Antibodies and Their Uses
    4.
    发明申请
    Anti-B7-H4 Antibodies and Their Uses 有权
    抗B7-H4抗体及其用途

    公开(公告)号：US20140356364A1

    公开(公告)日：2014-12-04

    申请号：US14239117

    申请日：2012-08-15

    申请人： Solomon Langermann ,  Linda Liu ,  Shannon Marshall

    发明人： Solomon Langermann ,  Linda Liu ,  Shannon Marshall

    IPC分类号： C07K16/28 ,  C07K16/30

    CPC分类号： C07K16/2827 ,  C07K16/30 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/77

    摘要： The present invention relates to antibodies (including anti-B7-H4 antibodies) and their antigen-binding fragments and to other molecules (including fusion proteins that bind to the cognate antigen/receptor, etc.) that are capable of immunospecifically binding to B7-H4 and the uses of such molecules in the diagnosis and the treatment of cancer and other diseases. The invention particularly concerns the use of such molecules to retard or prevent tumor growth, inhibit tumor-mediated suppression, eliminate tumors and/or deplete or block the activity of tumor associated macrophages (“TAMs”) so as to alter their activity and/or decrease TAM—mediated immune suppression.

    摘要翻译： 本发明涉及抗体（包括抗B7-H4抗体）及其抗原结合片段以及能够免疫特异性结合B7-抗体的其它分子（包括与同源抗原/受体结合的融合蛋白等） H4和这些分子在诊断和治疗癌症等疾病中的应用。 本发明特别涉及使用这种分子来延缓或预防肿瘤生长，抑制肿瘤介导的抑制，消除肿瘤和/或消耗或阻断肿瘤相关巨噬细胞（“TAM”）的活性，从而改变其活性和/或 减少TAM介导的免疫抑制。

    B7-H4 FUSION PROTEINS AND METHODS OF USE THEREOF
    6.
    发明申请
    B7-H4 FUSION PROTEINS AND METHODS OF USE THEREOF 有权
    B7-H4融合蛋白及其使用方法

    公开(公告)号：US20120276095A1

    公开(公告)日：2012-11-01

    申请号：US13392811

    申请日：2010-08-31

    申请人： Solomon Langermann ,  Linda Liu ,  Joseph R. Podojil ,  Stephen D. Miller ,  Shannon Marshall

    发明人： Solomon Langermann ,  Linda Liu ,  Joseph R. Podojil ,  Stephen D. Miller ,  Shannon Marshall

    IPC分类号： A61K39/395 ,  A61P29/00 ,  C07K19/00

    CPC分类号： C07K14/70532 ,  A61K9/0019 ,  A61K38/00 ,  A61K38/1709 ,  A61K39/44 ,  C07K16/2827 ,  C07K2317/50 ,  C07K2317/56 ,  C07K2317/72 ,  C07K2319/30 ,  C07K2319/32 ,  G01N33/6863 ,  G01N33/6866 ,  G01N33/6869 ,  G01N2800/52

    摘要： Fusion proteins containing B7-H4 polypeptides are disclosed. The B7-H4 fusion proteins can include full-length B7-H4 polypeptides, or can contain a fragment of a full-length B7-H4 polypeptide, including some or all of the extracellular domain of the B7-H4 polypeptide. Methods for using the fusion proteins to downregulate T cell activation and for the treatment of inflammatory and autoimmune diseases and disorders are also disclosed. The B7-H4 fusion proteins are useful for treating inflammation by inhibiting or reducing differentiation, proliferation, activity, and/or cytokine production and/or secretion by ThI, ThI 7, Th22, and/or other cells that secrete, or cause other cells to secrete, inflammatory molecules, including, but not limited to, IL-1β, TNF-α, TGF-beta, IFN-γ, IL-17, IL-6, IL-23, IL-22, IL-21, and MMPs; or enhancing IL-IO secretion by Tregs, increasing the differentiation of Tregs, increasing the number of Tregs, or combinations thereof.

    摘要翻译： 公开了含有B7-H4多肽的融合蛋白。 B7-H4融合蛋白可以包括全长B7-H4多肽，或者可以含有全长B7-H4多肽的片段，包括B7-H4多肽的一些或全部细胞外结构域。 还公开了使用融合蛋白来下调T细胞活化和治疗炎性和自身免疫性疾病和病症的方法。 B7-H4融合蛋白可用于通过抑制或减少Th1，Th17，Th22和/或分泌或引起其他细胞的其他细胞的分化，增殖，活性和/或细胞因子产生和/或分泌来治疗炎症 包括但不限于IL-1和bgr; TNF-α，TGF-β，IFN-γ，IL-17，IL-6，IL-23，IL-22，IL-21， 和MMPs; 或增强Treg的IL-10分泌，增加Treg的分化，增加Treg的数量或其组合。

    METHODS AND COMPOSITIONS FOR THE INHIBITION OF TRANSPLANT REJECTION
    10.
    发明申请
    METHODS AND COMPOSITIONS FOR THE INHIBITION OF TRANSPLANT REJECTION 有权
    抑制运输阻止剂的方法和组合物

    公开(公告)号：US20120177645A1

    公开(公告)日：2012-07-12

    申请号：US13392399

    申请日：2010-08-31

    申请人： Solomon Langermann ,  Linda Liu

    发明人： Solomon Langermann ,  Linda Liu

    IPC分类号： A61K39/395 ,  A61P41/00 ,  C07K16/00

    CPC分类号： C07K14/70532 ,  A61K9/0019 ,  A61K38/00 ,  A61K38/1709 ,  A61K39/44 ,  C07K16/2827 ,  C07K2317/50 ,  C07K2317/56 ,  C07K2317/72 ,  C07K2319/30 ,  C07K2319/32 ,  G01N33/6863 ,  G01N33/6866 ,  G01N33/6869 ,  G01N2800/52

    摘要： Methods for modulating immune responses in a subject are provided. A preferred embodiment provides methods and compositions for reducing or inhibiting transplant rejection in a subject, preferably a human subject. Transplant rejection can be inhibited or reduced in a subject by administering an effective amount of B7-H4 polypeptide, fragments or fusions thereof to inhibit or reduce the biological activity of an immune cell or to reduce the amounts of proinflammatory molecules at a site of transplant. Th1, Th17 and Th22 cells are exemplary T cells that can be targeted for inhibition by B7-H4 polypeptides, fusion proteins or fragments thereof to inhibit or reduce inflammation.

    摘要翻译： 提供了调节受试者中免疫应答的方法。 优选的实施方案提供用于减少或抑制受试者，优选人受试者的移植排斥的方法和组合物。 通过施用有效量的B7-H4多肽，其片段或融合物来抑制或降低免疫细胞的生物活性或减少移植部位的促炎症分子的量，可以抑制或减少受试者的移植排斥反应。 Th1，Th17和Th22细胞是可被B7-H4多肽，融合蛋白或其片段抑制或减少炎症的靶向的示例性T细胞。