Method for targeting transcriptionally active loci
    43.
    发明授权
    Method for targeting transcriptionally active loci 有权
    靶向转录活性位点的方法

    公开(公告)号:US07473557B2

    公开(公告)日:2009-01-06

    申请号:US10957760

    申请日:2004-10-04

    IPC分类号: C12N15/00 C12N15/87

    摘要: The present invention provides a method of achieving very high targeting efficiency by utilizing targeting vectors that utilize promoter-less selection cassettes and which are engineered to targeted into transcriptionally active loci. In particular, the invention provides a method for targeting promoter-less selection cassettes into transcriptionally active loci in stem cells or other eukaryotic cells with much greater efficiency than previously observed with other methods, thus reducing the number of drug-resistant clones to be screened or eliminating the need to screen for targeted cells altogether. The invention also encompasses the DNA targeting vectors, the targeted cells, as well as non-human organisms, especially mice, created from the targeted cells.

    摘要翻译: 本发明提供了一种通过利用利用无启动子选择盒并被设计成靶向转录活性位点的靶向载体来实现非常高的靶向效率的方法。 特别地,本发明提供了一种将无启动子选择盒定位在干细胞或其他真核细胞中的转录活性基因座的方法,其效率比先前用其它方法观察到的效率高得多,从而减少要筛选的耐药性克隆的数目 无需完全筛选靶细胞。 本发明还包括从靶细胞产生的DNA靶向载体,靶细胞以及非人生物,特别是小鼠。

    Angiopoietins and methods of use thereof
    45.
    发明授权
    Angiopoietins and methods of use thereof 有权
    促血管生成素及其使用方法

    公开(公告)号:US06455035B1

    公开(公告)日:2002-09-24

    申请号:US09286033

    申请日:1999-04-05

    IPC分类号: A61K3818

    CPC分类号: A61K38/1891 Y10S514/885

    摘要: The present invention provides for a method of decreasing or inhibiting vascular permeability and/or plasma leakage in a mammal comprising administering to the mammal a TIE-2 receptor activator. The invention also provides for a method of decreasing or inhibiting vascular permeability and/or plasma leakage in a mammal comprising administering to the mammal an Ang-2 inactivator such as an anti-Ang-2 neutralizing antibody.

    摘要翻译: 本发明提供了降低或抑制哺乳动物血管通透性和/或血浆渗漏的方法,包括向哺乳动物施用TIE-2受体激活剂。 本发明还提供减少或抑制哺乳动物血管渗透性和/或血浆渗漏的方法,包括向哺乳动物施用Ang-2灭活剂,例如抗Ang-2中和抗体。

    ERK3 MAP2 protein kinase
    46.
    发明授权
    ERK3 MAP2 protein kinase 失效
    ERK3 MAP2蛋白激酶

    公开(公告)号:US06303358B1

    公开(公告)日:2001-10-16

    申请号:US08888818

    申请日:1997-07-07

    IPC分类号: C12N912

    摘要: The present invention relates to a newly identified family of protein serine/threonine kinases which phosphorylate microtubule-associated protein 2 (MAP2). It is based, in part, on the cloning and characterization of novel MAP2 kinases designated extracellular signal-regulated kinase 1, 2, and 3 (ERK1, ERK2, ERK3) which are expressed in the central nervous system, and on the identification of another ERK family member, ERK4, with antisera. The present invention provides for recombinant nucleic acid molecules and proteins representing members of the MAP2 kinase family, and also for microorganisms, transgenic animals, and cell lines comprising recombinant MAP2 kinase molecules. In additional embodiments of the invention, the present invention provides for methods for assaying cellular factor activity, including, but not limited to, nerve growth factor activity, in which the activation of MAP2 kinase serves as an indicator of cellular factor activity. These methods may be extremely useful in screening compounds for the presence of a desired cellular factor activity. In specific embodiments, compounds which may be useful in the treatment of Alzheimer's disease, peripheral neuropathies, and diabetes may be identified using the methods of the invention.

    摘要翻译: 本发明涉及磷酸化微管相关蛋白2(MAP2)的新鉴定的蛋白丝氨酸/苏氨酸激酶家族。 它部分地基于在中枢神经系统中表达的称为细胞外信号调节激酶1,2和3(ERK1,ERK2,ERK3)的新型MAP2激酶的克隆和表征,以及鉴定另一种 ERK家族成员,ERK4,具有抗血清。 本发明提供了代表MAP2激酶家族成员的重组核酸分子和蛋白质,还提供了包含重组MAP2激酶分子的微生物,转基因动物和细胞系。 在本发明的另外的实施方案中,本发明提供了测定细胞因子活性的方法,包括但不限于神经生长因子活性,其中MAP2激酶的活化用作细胞因子活性的指标。 这些方法在筛选化合物中以期存在所需的细胞因子活性可能是非常有用的。 在具体实施方案中,可以使用本发明的方法鉴定可用于治疗阿尔茨海默氏病,周围神经病和糖尿病的化合物。

    ERK1 MAP2 protein kinase
    47.
    发明授权
    ERK1 MAP2 protein kinase 失效
    ERK1 MAP2蛋白激酶

    公开(公告)号:US06297035B1

    公开(公告)日:2001-10-02

    申请号:US08932012

    申请日:1997-09-17

    IPC分类号: C12N912

    摘要: The present invention relates to a newly identified family of protein serine/threonine kinases which phosphorylate microtubule-associated protein 2 (MAP2). It is based, in part, on the cloning and characterization of novel MAP2 kinases designated extracellular signal-regulated kinase 1, 2, and 3 (ERK1, ERK2, ERK3) which are expressed in the central nervous system, and on the identification of another ERK family member, ERK4, with antisera. The present invention provides for recombinant nucleic acid molecules and proteins representing members of the MAP2 kinase family, and also for microorganisms, transgenic animals, and cell lines comprising recombinant MAP2 kinase molecules. In additional embodiments of the invention, the present invention provides for methods for assaying cellular factor activity, including, but not limited to, nerve growth factor activity, in which the activation of MAP2 kinase serves as an indicator of cellular factor activity. These methods may be extremely useful in screening compounds for the presence of a desired cellular factor activity. In specific embodiments, compounds which may be useful in the treatment of Alzheimer's disease, peripheral neuropathies, and diabetes may be identified using the methods of the invention.

    摘要翻译: 本发明涉及磷酸化微管相关蛋白2(MAP2)的新鉴定的蛋白丝氨酸/苏氨酸激酶家族。 它部分地基于在中枢神经系统中表达的称为细胞外信号调节激酶1,2和3(ERK1,ERK2,ERK3)的新型MAP2激酶的克隆和表征,以及鉴定另一种 ERK家族成员,ERK4,具有抗血清。 本发明提供了代表MAP2激酶家族成员的重组核酸分子和蛋白质,还提供了包含重组MAP2激酶分子的微生物,转基因动物和细胞系。 在本发明的另外的实施方案中,本发明提供了测定细胞因子活性的方法,包括但不限于神经生长因子活性,其中MAP2激酶的活化用作细胞因子活性的指标。 这些方法在筛选化合物中以期存在所需的细胞因子活性可能是非常有用的。 在具体实施方案中,可以使用本发明的方法鉴定可用于治疗阿尔茨海默氏病,周围神经病和糖尿病的化合物。

    Antibodies directed toward extracellular signal-related kinases
    48.
    发明授权
    Antibodies directed toward extracellular signal-related kinases 失效
    针对细胞外信号相关激酶的抗体

    公开(公告)号:US06277963B1

    公开(公告)日:2001-08-21

    申请号:US08932787

    申请日:1997-09-18

    IPC分类号: C07K1640

    摘要: The present invention relates to a newly identified family of protein serine/threonine kinases which phosphorylate microtubule-associated protein 2 (MAP2). It is based, in part, on the cloning and characterization of novel MAP2 kinases designated extracellular signal-regulated kinase 1, 2, and 3 (ERK1, ERK2, ERK3) which are expressed in the central nervous system, and on the identification of another ERK family member, ERK4, with antisera. The present invention provides for recombinant nucleic acid molecules and proteins representing members of the MAP2 kinase family, and also for microorganisms, transgenic animals, and cell lines comprising recombinant MAP2 kinase molecules. In additional embodiments of the invention, the present invention provides for methods for assaying cellular factor activity, including, but not limited to, nerve growth factor activity, in which the activation of MAP2 kinase serves as an indicator of cellular factor activity. These methods may be extremely useful in screening compounds for the presence of a desired cellular factor activity. In specific embodiments, compounds which may be useful in the treatment of Alzheimer's disease, peripheral neuropathies, and diabetes may be identified using the methods of the invention.

    摘要翻译: 本发明涉及磷酸化微管相关蛋白2(MAP2)的新鉴定的蛋白丝氨酸/苏氨酸激酶家族。 它部分地基于在中枢神经系统中表达的称为细胞外信号调节激酶1,2和3(ERK1,ERK2,ERK3)的新型MAP2激酶的克隆和表征,以及鉴定另一种 ERK家族成员,ERK4,具有抗血清。 本发明提供了代表MAP2激酶家族成员的重组核酸分子和蛋白质,还提供了包含重组MAP2激酶分子的微生物,转基因动物和细胞系。 在本发明的另外的实施方案中,本发明提供了测定细胞因子活性的方法,包括但不限于神经生长因子活性,其中MAP2激酶的活化用作细胞因子活性的指标。 这些方法在筛选化合物中以期存在所需的细胞因子活性可能是非常有用的。 在具体实施方案中,可以使用本发明的方法鉴定可用于治疗阿尔茨海默氏病,周围神经病和糖尿病的化合物。