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    scFv antibodies which pass epithelial and/or endothelial layers
    1.
    发明授权
    scFv antibodies which pass epithelial and/or endothelial layers 有权
    通过上皮和/或内皮层的scFv抗体

    公开(公告)号：US08936785B2

    公开(公告)日：2015-01-20

    申请号：US12307875

    申请日：2007-07-10

    申请人： Adrian Auf Der Maur ,  Alcide Barberis ,  David M. Urech ,  Peter Lichtlen

    发明人： Adrian Auf Der Maur ,  Alcide Barberis ,  David M. Urech ,  Peter Lichtlen

    IPC分类号： A61K39/395 ,  C07K16/18 ,  C07K16/22 ,  C07K16/24 ,  A61K39/00

    CPC分类号： C07K16/18 ,  A61K39/39591 ,  A61K2039/505 ,  A61K2039/54 ,  C07K16/22 ,  C07K16/241 ,  C07K2317/24 ,  C07K2317/622

    摘要： scFv antibodies which specifically bind selected antigens and are obtainable by a method comprising (i) selecting from a pool of soluble and stable antibody frameworks a soluble and stable framework matching best the framework of a non-human antibody against the antigen with a certain binding specificity, (ii) either providing said soluble and stable framework with CDRs that bind specifically to said antigen, or mutating the framework of said non-human antibody towards the sequence of said soluble and stable framework, to generate scFv antibodies, (iii) testing the generated antibody for solubility and stability, and testing the generated antibody for antigen binding, and (iv) selecting an scFV that is soluble, stable and binds to the antigen specifically. Also provided are pharmaceutical compositions comprising said scFv antibody, methods of treatment and diagnosis for diseases related to over expression of antigens that are specifically bound by said antibody.

    摘要翻译： scFv抗体，其特异性结合所选择的抗原，并且可通过以下方法获得：（i）从可溶性和稳定的抗体框架库中选择可溶性和稳定的框架，以最佳匹配抗人抗体的框架与一定的结合特异性 提供与所述抗原特异性结合的CDR提供所述可溶性和稳定的框架，或者将所述非人抗体的框架朝向所述可溶性和稳定框架的序列突变以产生scFv抗体，（iii）测试 产生抗体的溶解度和稳定性，并测试所产生的抗体的抗原结合，和（iv）选择可溶性，稳定并特异性结合抗原的scFV。 还提供了包含所述scFv抗体的药物组合物，与由所述抗体特异性结合的抗原过度表达相关疾病的治疗和诊断方法。

    Method for the identification and/or validation of receptor tyrosine kinase inhibitors
    3.
    发明授权
    Method for the identification and/or validation of receptor tyrosine kinase inhibitors 失效
    用于鉴定和/或验证受体酪氨酸激酶抑制剂的方法

    公开(公告)号：US07566528B2

    公开(公告)日：2009-07-28

    申请号：US11112344

    申请日：2005-04-22

    申请人： Tea Gunde ,  Catherine Berset ,  Alcide Barberis

    发明人： Tea Gunde ,  Catherine Berset ,  Alcide Barberis

    IPC分类号： C12Q1/02 ,  C12N1/19 ,  C12N1/38

    CPC分类号： C12Q1/485 ,  G01N2500/00

    摘要： An in vivo method for the identification and/or validation of receptor tyrosine kinase inhibitors is described. Said method is characterized by the following steps: providing host cells comprising a nucleic acid construct encoding a peptide which comprises a tyrosine kinase domain of a receptor tyrosine kinase wherein said peptide lacks a transmembrane domain or a functional fragment thereof and said tyrosine kinase activity in the cytoplasma leads to proliferation arrest, contacting said host cells with a candidate compound and identification of inhibitors of said tyrosine kinase activity by cultivation of said host cells under suitable conditions such that the modulation of the tyrosine kinase activity by the candidate compound leads to cell growth.

    摘要翻译： 描述了用于鉴定和/或验证受体酪氨酸激酶抑制剂的体内方法。 所述方法的特征在于以下步骤：提供宿主细胞，其包含编码包含受体酪氨酸激酶的酪氨酸激酶结构域的肽的核酸构建体，其中所述肽缺少跨膜结构域或其功能片段，并且所述酪氨酸激酶活性在 细胞质导致增殖停滞，通过在合适的条件下培养所述宿主细胞，使所述宿主细胞与候选化合物接触并鉴定所述酪氨酸激酶活性的抑制剂，使得由候选化合物调节酪氨酸激酶活性导致细胞生长。

    Protein kinase inhibitors
    4.
    发明申请
    Protein kinase inhibitors 审中-公开
    蛋白激酶抑制剂

    公开(公告)号：US20070149535A1

    公开(公告)日：2007-06-28

    申请号：US11635908

    申请日：2006-12-08

    申请人： Catherine Berset ,  Stephan Audetat ,  Alcide Barberis ,  Tea Gunde ,  Julia Tietz ,  Peter Traxler ,  Andreas Schumacher

    发明人： Catherine Berset ,  Stephan Audetat ,  Alcide Barberis ,  Tea Gunde ,  Julia Tietz ,  Peter Traxler ,  Andreas Schumacher

    IPC分类号： A61K31/498

    CPC分类号： A61K31/519 ,  A61K31/695

    摘要： The present invention relates to angiogenesis inhibitors, in particular receptor tyrosine kinase inhibitors, and their use for the treatment of hyperproliferative diseases, angiogenesis and disorders depending on angiogenesis such as tumour forming cancers. It also relates to a method of inhibiting angiogenesis or treating a vascular anomaly in a mammal comprising administering to the mammal an amount of an Eph receptor inhibitor which is effective for inhibiting angiogenesis or for treating the vascular anomaly in the mammal. Further, the present invention relates to the use of compounds for the treatment of angiogenesis related disorders involving a protein kinase, preferably a tyrosine kinase, and to some specific forms of said compounds as a medicament. Compounds useful in the practice of the invention have the general formula I wherein R1, R2, R3, R4 and R5 are as defined in the specification.

    摘要翻译： 本发明涉及血管生成抑制剂，特别是受体酪氨酸激酶抑制剂，以及它们用于治疗过度增殖性疾病，血管生成和取决于血管发生如肿瘤形成癌症的病症的用途。 它还涉及抑制哺乳动物血管生成或治疗血管异常的方法，其包括向哺乳动物施用一定量的有效抑制血管发生或治疗哺乳动物血管异常的Eph受体抑制剂。 此外，本发明涉及化合物用于治疗涉及蛋白激酶（优选酪氨酸激酶）的血管发生相关疾病以及作为药物的所述化合物的一些特定形式的用途。 可用于本发明实践的化合物具有通式I，其中R 1，R 2，R 3，R 4和R 5如说明书中所定义。

    Method for the identification and/or validation of receptor tyrosine kinase inhibitors
    9.
    发明申请
    Method for the identification and/or validation of receptor tyrosine kinase inhibitors 失效
    用于鉴定和/或验证受体酪氨酸激酶抑制剂的方法

    公开(公告)号：US20050239049A1

    公开(公告)日：2005-10-27

    申请号：US11112344

    申请日：2005-04-22

    申请人： Tea Gunde ,  Catherine Berset ,  Alcide Barberis

    发明人： Tea Gunde ,  Catherine Berset ,  Alcide Barberis

    IPC分类号： C12Q1/48 ,  C12Q1/00

    CPC分类号： C12Q1/485 ,  G01N2500/00

    摘要： An in vivo method for the identification and/or validation of receptor tyrosine kinase inhibitors is described. Said method is characterised by the following steps: providing host cells comprising a nucleic acid construct encoding a peptide which comprises a tyrosine kinase domain of a receptor tyrosine kinase wherein said peptide lacks a transmembrane domain or a functional fragment thereof and said tyrosine kinase activity in the cytoplasma leads to proliferation arrest, contacting said host cells with a candidate compound and identification of inhibitors of said tyrosine kinase activity by cultivation of said host cells under suitable conditions such that the modulation of the tyrosine kinase activity by the candidate compound leads to cell growth.

    摘要翻译： 描述了用于鉴定和/或验证受体酪氨酸激酶抑制剂的体内方法。 所述方法的特征在于以下步骤：提供宿主细胞，其包含编码包含受体酪氨酸激酶的酪氨酸激酶结构域的肽的核酸构建体，其中所述肽缺少跨膜结构域或其功能片段，并且所述酪氨酸激酶活性在 细胞质导致增殖停滞，通过在合适的条件下培养所述宿主细胞，使所述宿主细胞与候选化合物接触并鉴定所述酪氨酸激酶活性的抑制剂，使得由候选化合物调节酪氨酸激酶活性导致细胞生长。