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    Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4)
    1.
    发明授权
    Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4) 有权
    对细胞毒性T淋巴细胞相关抗原（CTLA-4）具有亲和力的化合物

    公开(公告)号：US07892827B2

    公开(公告)日：2011-02-22

    申请号：US11720234

    申请日：2005-11-25

    申请人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Steffen Schlehuber ,  Martin Pöhlchen ,  Arne Skerra

    发明人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Steffen Schlehuber ,  Martin Pöhlchen ,  Arne Skerra

    IPC分类号： C12N5/00 ,  C07K14/00

    CPC分类号： C07K14/47

    摘要： The present invention relates to a compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4), wherein the compound exhibits a synergistic mode of action in that the compound: (a) increases T cell priming or T cell expansion or the generation of memory T cells by blocking of CTLA-4, and (b) enhances effector T cell activity in tumor tissue or lymphoid tissue by blocking of CTLA-4. The compound of the invention can be a protein, a small organic molecule, a peptide, or a nucleic acid. The invention also relates to a mutein derived from a protein selected from the group consisting of human neutrophil gelatinase-associated lipocalin (hNGAL), rat α2-microglobulin-related protein (A2m) and mouse 24p3/uterocalin (24p3), said mutein having binding specificity for the cytotoxic T lymphocyte-associated antigen (CTLA-4), wherein said mutein: (a) comprises amino acid replacements at least one of the sequence position corresponding to sequence positions 33 to 54, 66 to 83, 94 to 106, and 123 to 136 of hNGAL, and (b) binds human CTLA-4 with a KD of 50 nM or less. The invention also relates to a pharmaceutical composition comprising such a compound or mutein as well as to various pharmaceutical uses of such a compound or mutein, for example, for the prevention and/or treatment of cancer, an auto-immune disease or an infectious disease.

    摘要翻译： 本发明涉及对细胞毒性T淋巴细胞相关抗原（CTLA-4）具有亲和性的化合物，其中所述化合物表现出协同作用模式，因为化合物：（a）增加T细胞引发或T细胞扩增或 通过阻断CTLA-4产生记忆T细胞，和（b）通过阻断CTLA-4增强肿瘤组织或淋巴组织中的效应T细胞活性。 本发明的化合物可以是蛋白质，小有机分子，肽或核酸。 本发明还涉及衍生自选自人嗜中性粒细胞明胶酶相关脂质运载蛋白（hNGAL），大鼠α2-微球蛋白相关蛋白（A2m）和小鼠24p3 /子宫肌素（24p3）的蛋白质的突变蛋白，所述突变蛋白具有结合 细胞毒性T淋巴细胞相关抗原（CTLA-4）的特异性，其中所述突变蛋白：（a）包含氨基酸替换对应于序列位置33至54,66至83,94至106的序列位置中的至少一个，以及 123和136的hNGAL，和（b）以50nM或更低的KD结合人CTLA-4。 本发明还涉及包含这种化合物或突变蛋白的药物组合物以及这种化合物或突变蛋白的各种药物用途，例如用于预防和/或治疗癌症，自身免疫疾病或感染性疾病 。

    MUTEINS OF HUMAN LIPOCALIN 2 WITH AFFINITY FOR CTLA-4
    3.
    发明申请
    MUTEINS OF HUMAN LIPOCALIN 2 WITH AFFINITY FOR CTLA-4 有权
    人类LIPOCALIN 2与CTLA-4具有亲和力

    公开(公告)号：US20140051645A1

    公开(公告)日：2014-02-20

    申请号：US13991226

    申请日：2011-12-02

    申请人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Arne Skerra

    发明人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Arne Skerra

    IPC分类号： C07K14/435

    CPC分类号： C07K14/435 ,  C07K14/47 ,  C07K14/705 ,  C12N5/10 ,  G01N33/57407 ,  G01N33/57492 ,  G01N2333/70521

    摘要： The present invention relates to novel, specific-binding therapeutic and/or diagnostic proteins directed against Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) also known as CD152, which proteins preferably are muteins of a lipocalin protein, more preferably of lipocalin 2 (Lcn2 or NGAL). The invention also relates to nucleic acid molecules encoding such proteins and to methods for generation and use of such proteins and nucleic acid molecules. Accordingly, the invention also is directed to pharmaceutical and/or diagnostic compositions comprising such lipocalin proteins, including uses of these proteins.

    摘要翻译： 本发明涉及针对细胞毒性T淋巴细胞抗原4（CTLA-4）也被称为CD152的新型特异性结合的治疗和/或诊断蛋白质，该蛋白质优选是脂质运载蛋白的突变蛋白，更优选脂质运载蛋白2（ Lcn2或NGAL）。 本发明还涉及编码这种蛋白质的核酸分子以及用于产生和使用这些蛋白质和核酸分子的方法。 因此，本发明还涉及包含这种脂质运载蛋白的药物和/或诊断组合物，包括这些蛋白质的用途。

    Muteins of human lipocalin 2 with affinity for CTLA-4
    4.
    发明授权
    Muteins of human lipocalin 2 with affinity for CTLA-4 有权
    人脂多蛋白2的突变蛋白与CTLA-4具有亲和力

    公开(公告)号：US09221885B2

    公开(公告)日：2015-12-29

    申请号：US13991226

    申请日：2011-12-02

    申请人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Arne Skerra

    发明人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Arne Skerra

    IPC分类号： C07K14/435 ,  C07K14/705 ,  G01N33/53 ,  C07K14/47 ,  C12N5/10 ,  G01N33/574

    CPC分类号： C07K14/435 ,  C07K14/47 ,  C07K14/705 ,  C12N5/10 ,  G01N33/57407 ,  G01N33/57492 ,  G01N2333/70521

    摘要： The present invention relates to novel, specific-binding therapeutic and/or diagnostic proteins directed against Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) also known as CD152, which proteins preferably are muteins of a lipocalin protein, more preferably of lipocalin 2 (Lcn2 or NGAL). The invention also relates to nucleic acid molecules encoding such proteins and to methods for generation and use of such proteins and nucleic acid molecules. Accordingly, the invention also is directed to pharmaceutical and/or diagnostic compositions comprising such lipocalin proteins, including uses of these proteins.

    摘要翻译： 本发明涉及针对细胞毒性T淋巴细胞抗原4（CTLA-4）也被称为CD152的新型特异性结合的治疗和/或诊断蛋白质，该蛋白质优选是脂质运载蛋白的突变蛋白，更优选脂质运载蛋白2（ Lcn2或NGAL）。 本发明还涉及编码这种蛋白质的核酸分子以及用于产生和使用这些蛋白质和核酸分子的方法。 因此，本发明还涉及包含这种脂质运载蛋白的药物和/或诊断组合物，包括这些蛋白质的用途。

    Compound with Affinity for the Cytotoxic T Lymphocyte-Associated Antigen (Ctla-4)
    6.
    发明申请
    Compound with Affinity for the Cytotoxic T Lymphocyte-Associated Antigen (Ctla-4) 有权
    具有细胞毒性T淋巴细胞相关抗原亲和力的化合物（Ctla-4）

    公开(公告)号：US20090042785A1

    公开(公告)日：2009-02-12

    申请号：US11720234

    申请日：2005-11-25

    申请人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Steffen Schlehuber ,  Martin Pohlchen ,  Arne Skerra

    发明人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Steffen Schlehuber ,  Martin Pohlchen ,  Arne Skerra

    IPC分类号： A61K38/16 ,  C07K14/00 ,  C07K16/00 ,  A61P37/06 ,  A61P31/00 ,  A61P35/00 ,  C07H21/00 ,  C12N5/00

    CPC分类号： C07K14/47

    摘要： The present invention relates to a compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4), wherein the compound exhibits a synergistic mode of action in that the compound: (a) increases T cell priming or T cell expansion or the generation of memory T cells by blocking of CTLA-4, and (b) enhances effector T cell activity in tumor tissue or lymphoid tissue by blocking of CTLA-4. The compound of the invention can be a protein, a small organic molecule, a peptide, or a nucleic acid. The invention also relates to a mutein derived from a protein selected from the group consisting of human neutrophil gelatinase-associated lipocalin (hNGAL), rat α2-microglobulin-related protein (A2m) and mouse 24p3/uterocalin (24p3), said mutein having binding specificity for the cytotoxic T lymphocyte-associated antigen (CTLA-4), wherein said mutein: (a) comprises amino acid replacements at least one of the sequence position corresponding to sequence positions 33 to 54, 66 to 83, 94 to 106, and 123 to 136 of hNGAL, and (b) binds human CTLA-4 with a KD of 50 nM or less. The invention also relates to a pharmaceutical composition comprising such a compound or mutein as well as to various pharmaceutical uses of such a compound or mutein, for example, for the prevention and/or treatment of cancer, an auto-immune disease or an infectious disease.

    摘要翻译： 本发明涉及对细胞毒性T淋巴细胞相关抗原（CTLA-4）具有亲和性的化合物，其中所述化合物表现出协同作用模式，因为化合物：（a）增加T细胞引发或T细胞扩增或 通过阻断CTLA-4产生记忆T细胞，和（b）通过阻断CTLA-4增强肿瘤组织或淋巴组织中的效应T细胞活性。 本发明的化合物可以是蛋白质，小有机分子，肽或核酸。 本发明还涉及衍生自选自人嗜中性粒细胞明胶酶相关脂质运载蛋白（hNGAL），大鼠α2-微球蛋白相关蛋白（A2m）和小鼠24p3 /子宫肌素（24p3）的蛋白质的突变蛋白，所述突变蛋白具有结合 细胞毒性T淋巴细胞相关抗原（CTLA-4）的特异性，其中所述突变蛋白：（a）包含氨基酸替换对应于序列位置33至54,66至83,94至106的序列位置中的至少一个，以及 123和136的hNGAL，和（b）以50nM或更低的KD结合人CTLA-4。 本发明还涉及包含这种化合物或突变蛋白的药物组合物以及这种化合物或突变蛋白的各种药物用途，例如用于预防和/或治疗癌症，自身免疫疾病或感染性疾病 。

    Tear lipocalin in muteins binding IL-4 R alpha
    7.
    发明授权
    Tear lipocalin in muteins binding IL-4 R alpha 有权
    突变蛋白中的泪液脂质运载蛋白结合IL-4Rα

    公开(公告)号：US08986951B2

    公开(公告)日：2015-03-24

    申请号：US13702792

    申请日：2011-06-08

    申请人： Andreas Hohlbaum ,  Alexandra Baehre ,  Gabriele Matschiner ,  Stefan Trentmann ,  Klaus Kirchfeld ,  Hans-Juergen Christian

    发明人： Andreas Hohlbaum ,  Alexandra Baehre ,  Gabriele Matschiner ,  Stefan Trentmann ,  Klaus Kirchfeld ,  Hans-Juergen Christian

    IPC分类号： C12P21/06 ,  C07K14/435 ,  C07K14/47 ,  C12N9/16 ,  A61K38/17 ,  C12N15/09 ,  C12P21/02

    CPC分类号： A61K38/1709 ,  C07K14/435 ,  C07K14/47 ,  C07K2319/00 ,  C12N9/16

    摘要： The present invention relates to novel muteins derived from human tear lipocalin, which bind to IL 4 receptor alpha. The sequences of the muteins comprise particular combinations of amino acids. In particular a mutated amino acid residue is present at any one or more of the sequence positions 27, 28, 30, 31, 33, 53, 57, 61, 64, 66, 80, 83, 104-106 and 108 of the linear polypeptide sequence of the mature human tear lipocalin. A mutated amino acid residue is also present at any 2 or more of the sequence positions 26, 32, 34, 55, 56, 58 and 63 of the linear polypeptide sequence of the mature human tear lipocalin. The invention also provides a corresponding nucleic acid molecule encoding such a mutein and a method for producing such a mutein and its encoding nucleic acid molecule.

    摘要翻译： 本发明涉及衍生自与人IL-4受体α结合的人泪脂蛋白的新型突变蛋白。 突变蛋白的序列包含氨基酸的特定组合。 特别地，突变的氨基酸残基存在于线性的任何一个或多个序列位置27,28,30,31,33,53,57,61,64,66,80,83,104-106和108中的任何一个或多个 成熟人类脂质运载蛋白的多肽序列。 突变的氨基酸残基也存在于成熟人类泪液脂质运载蛋白的线性多肽序列的任何2个或更多个序列位置26,32,34,55,56,58和63。 本发明还提供了编码这种突变蛋白的相应核酸分子及其制备这种突变蛋白及其编码核酸分子的方法。

    Muteins of human lipocalin 2 with affinity for glypican-3 (GPC-3)
    9.
    发明授权
    Muteins of human lipocalin 2 with affinity for glypican-3 (GPC-3) 有权
    具有亲和性的磷脂酰肌醇蛋白聚糖3（GPC-3）的人脂质运载蛋白2的突变蛋白

    公开(公告)号：US09260492B2

    公开(公告)日：2016-02-16

    申请号：US13885229

    申请日：2011-11-15

    申请人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Kristian Jensen

    发明人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Kristian Jensen

    IPC分类号： C07K14/435 ,  C12N9/96 ,  C07K16/44 ,  A61K38/00 ,  C07K14/47 ,  C07K16/00 ,  C12P21/08

    CPC分类号： C07K14/435 ,  A61K38/00 ,  C07K14/47 ,  C07K14/4725 ,  C07K16/44 ,  C12N9/96

    摘要： Described are specific-binding therapeutic and/or diagnostic proteins directed against Glypican-3 (GPC3), which proteins include muteins of a lipocalin protein, such as lipocalin 2 (Lcn2 or NGAL). The invention also relates to nucleic acid molecules encoding such proteins and to methods for generation and use of such proteins and nucleic acid molecules. Accordingly, the invention also is directed to pharmaceutical and/or diagnostic compositions comprising such lipocalin proteins, including uses of these proteins.

    摘要翻译： 描述了针对磷酸甘油聚糖-3（GPC3）的特异性结合的治疗和/或诊断蛋白，其中蛋白质包括脂质运载蛋白的突变蛋白，例如脂笼蛋白2（Lcn2或NGAL）。 本发明还涉及编码这种蛋白质的核酸分子以及用于产生和使用这些蛋白质和核酸分子的方法。 因此，本发明还涉及包含这种脂质运载蛋白的药物和/或诊断组合物，包括这些蛋白质的用途。

    MUTEINS OF HUMAN LIPOCALIN 2 WITH AFFINITY FOR GLYPICAN-3 (GPC-3)
    10.
    发明申请
    MUTEINS OF HUMAN LIPOCALIN 2 WITH AFFINITY FOR GLYPICAN-3 (GPC-3) 有权
    人类脂蛋白2与甘油三酯（GPC-3）的亲和力

    公开(公告)号：US20130296258A1

    公开(公告)日：2013-11-07

    申请号：US13885229

    申请日：2011-11-15

    申请人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Kristian Jensen

    发明人： Gabriele Matschiner ,  Andreas Hohlbaum ,  Kristian Jensen

    IPC分类号： C07K14/435

    CPC分类号： C07K14/435 ,  A61K38/00 ,  C07K14/47 ,  C07K14/4725 ,  C07K16/44 ,  C12N9/96

    摘要： Described are specific-binding therapeutic and/or diagnostic proteins directed against Glypican-3 (GPC3), which proteins include muteins of a lipocalin protein, such as lipocalin 2 (Lcn2 or NGAL). The invention also relates to nucleic acid molecules encoding such proteins and to methods for generation and use of such proteins and nucleic acid molecules. Accordingly, the invention also is directed to pharmaceutical and/or diagnostic compositions comprising such lipocalin proteins, including uses of these proteins.

    摘要翻译： 描述了针对磷酸甘油聚糖-3（GPC3）的特异性结合的治疗和/或诊断蛋白，其中蛋白质包括脂质运载蛋白的突变蛋白，例如脂笼蛋白2（Lcn2或NGAL）。 本发明还涉及编码这种蛋白质的核酸分子以及用于产生和使用这些蛋白质和核酸分子的方法。 因此，本发明还涉及包含这种脂质运载蛋白的药物和/或诊断组合物，包括这些蛋白质的用途。