公开(公告)号：US20130079286A1

公开(公告)日：2013-03-28

申请号：US13514133

申请日：2010-12-07

申请人： Arne Skerra ,  Michaela Gebauer ,  Dominik Hinz ,  Sabine Rauth ,  Gabriele Matschiner ,  Martin Huelsmeyer

发明人： Arne Skerra ,  Michaela Gebauer ,  Dominik Hinz ,  Sabine Rauth ,  Gabriele Matschiner ,  Martin Huelsmeyer

IPC分类号： A61K38/17 ,  C07K14/47

CPC分类号： C07K14/47 ,  A61K38/00 ,  A61K38/1709 ,  A61K47/60 ,  C07K14/775 ,  C07K2319/30 ,  G01N33/566

摘要： The present invention relates to a novel library for the generation of muteins and to novel muteins derived from human lipocalin 2 (Lcn2, hNGAL) and related proteins that bind a given target with detectable affinity. The invention also relates to corresponding nucleic acid molecules encoding such a mutein and to a method for their generation. The invention further relates to a method for producing such a mutein. For example, such muteins may serve to bind and deplete pathological forms of natural biomolecules such as the amyloid beta peptide in Alzheimer's disease or may target the fibronectin extra-domain B, which is associated with tumor neovasculature.

摘要翻译： 本发明涉及用于产生突变蛋白的新文库和衍生自人脂质运载蛋白2（Lcn2，hNGAL）的新型突变蛋白以及以可检测的亲和力结合给定靶的相关蛋白。 本发明还涉及编码这种突变蛋白的相应核酸分子及其产生方法。 本发明还涉及一种生产这种突变蛋白的方法。 例如，这种突变蛋白可用于结合和消耗天然生物分子的病理形式，例如阿尔茨海默病中的淀粉状蛋白β肽，或可靶向与肿瘤新血管生成相关的纤连蛋白结构域外结构域B.

公开(公告)号：US09549968B2

公开(公告)日：2017-01-24

申请号：US13514133

申请日：2010-12-07

申请人： Arne Skerra ,  Michaela Gebauer ,  Dominik Hinz ,  Sabine Rauth ,  Gabriele Matschiner ,  Martin Huelsmeyer

发明人： Arne Skerra ,  Michaela Gebauer ,  Dominik Hinz ,  Sabine Rauth ,  Gabriele Matschiner ,  Martin Huelsmeyer

IPC分类号： A61K38/17 ,  C07K14/775 ,  G01N33/566 ,  C07K14/47 ,  A61K38/00

CPC分类号： C07K14/47 ,  A61K38/00 ,  A61K38/1709 ,  A61K47/60 ,  C07K14/775 ,  C07K2319/30 ,  G01N33/566

摘要： The present invention relates to a novel library for the generation of muteins and to novel muteins derived from human lipocalin 2 (Lcn2, hNGAL) and related proteins that bind a given target with detectable affinity. The invention also relates to corresponding nucleic acid molecules encoding such a mutein and to a method for their generation. The invention further relates to a method for producing such a mutein. For example, such muteins may serve to bind and deplete pathological forms of natural biomolecules such as the amyloid beta peptide in Alzheimer's disease or may target the fibronectin extra-domain B, which is associated with tumor neovasculature.

摘要翻译： 本发明涉及用于产生突变蛋白的新文库和衍生自人脂质运载蛋白2（Lcn2，hNGAL）的新型突变蛋白以及以可检测的亲和力结合给定靶的相关蛋白。 本发明还涉及编码这种突变蛋白的相应核酸分子及其产生方法。 本发明还涉及一种生产这种突变蛋白的方法。 例如，这种突变蛋白可用于结合和消耗天然生物分子的病理形式，例如阿尔茨海默病中的淀粉状蛋白β肽，或可靶向与肿瘤新血管生成相关的纤连蛋白结构域外结构域B.

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。

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。

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 。