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    Method for producing biologically active human factor VIII in the milk of transgenic animals driven by mammary-specific expression cassettes
    3.
    发明申请
    Method for producing biologically active human factor VIII in the milk of transgenic animals driven by mammary-specific expression cassettes 有权
    在乳腺特异性表达盒驱动的转基因动物的乳中生产生物活性人因子VIII的方法

    公开(公告)号：US20050229261A1

    公开(公告)日：2005-10-13

    申请号：US10820777

    申请日：2004-04-09

    Applicant: Winston Cheng ,  Chuan-Mu Chen ,  Shwu-Wha Lin ,  Chih-Hong Wang ,  Chih-Jen Lin ,  Shinn-Chih Wu

    Inventor： Winston Cheng ,  Chuan-Mu Chen ,  Shwu-Wha Lin ,  Chih-Hong Wang ,  Chih-Jen Lin ,  Shinn-Chih Wu

    IPC: A01K67/027 ,  C07K14/755 ,  C12N15/85

    CPC classification number: C12N15/8509 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2267/01 ,  C07K14/755 ,  C12N2830/008

    Abstract: Hemophilia A is one of the major inherited bleeding disorders caused by a deficiency or abnormality in coagulation factor VIII (FVIII). Hemophiliacs have been treated with whole plasma or purified FVIII concentrates. The risk of transmitting blood-borne viruses and the cost of highly purified FVIII are the major factors that restrict prophylaxis in hemophilia therapy. One of the challenges created by the biotechnology revolution is the development of methods for the economical production of highly purified proteins in large scales. The present invention provides improved mammary expression cassettes useful for the expression of genes at high levels in the milk of transgenic animals. In particular, the present invention provides recombinant signal peptide sequences derived from a-lactalbumin and aS1-casein milk genes suitable for leading protein secretion in the mammary gland. These gene cassettes are capable of delivering different transgenic constructs which result in the production of full-length or B domain-deleted therapeutic levels of biologically active human FVIII in the transgenic animals in vivo. Within the scope of the invention are also method for producing the transgenic non-human mammal, such as mouse, rat, rabbit, goat, sheep, pig and bovine species, capable of expressing human FVIII, and methods of making milk and methods of identifying protein from the transgenic milk.

    Abstract translation: 血友病A是凝血因子VIII（FVIII）缺乏或异常引起的主要遗传性出血性疾病之一。 已经用全血浆或纯化的FVIII浓缩物治疗血友病患者。 传播血源性病毒的风险和高度纯化的FVIII的成本是限制血友病治疗预防的主要因素。 生物技术革命带来的挑战之一是开发大规模经济生产高纯度蛋白质的方法。 本发明提供了可用于在转基因动物的牛奶中高水平表达基因的改进的乳腺表达盒。 特别地，本发明提供了衍生自α-乳白蛋白的重组信号肽序列和适合于在乳腺中引导蛋白质分泌的α1酪蛋白乳基因。 这些基因盒能够递送不同的转基因构建体，其导致在转基因动物体内产生全长或B结构域缺失的生物活性人类FVIII的治疗水平。 在本发明的范围内，也是用于生产能够表达人FVIII的转基因非人哺乳动物如小鼠，大鼠，兔，山羊，绵羊，猪和牛物种的方法，以及制备牛奶的方法和鉴定方法 来自转基因乳的蛋白质。

    Method for manufacturing animal model for researching pulmonary tumor and use thereof
    4.
    发明授权
    Method for manufacturing animal model for researching pulmonary tumor and use thereof 有权
    制造肺肿瘤研究动物模型的方法及其应用

    公开(公告)号：US08247644B2

    公开(公告)日：2012-08-21

    申请号：US12828786

    申请日：2010-07-01

    Applicant: Chuan-Mu Chen

    Inventor： Chuan-Mu Chen

    IPC: A01K67/033 ,  A01K67/00 ,  C12N15/00

    CPC classification number: A01K67/0275 ,  A01K2217/052 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0325

    Abstract: The present invention is a method for manufacturing an animal model for researching a pulmonary tumor and a use thereof. A transgenic non-human animal of the present invention is prepared by embryonic gene microinjection and possesses a tissue-specific expression of vascular endothelial growth factor A165 (VEGF-A165) in lung. Through the expression of vascular endothelial growth factor A165, the lung cells in the transgenic non-human animal of the present invention have inflammatory, vascularogenesis and angiogenesis responses or induce lung tumors. Thus, the non-human animal of the present invention can serve as an animal model for analyzing the regulation and the anti-tumor drugs screening of pulmonary adenocarcinoma.

    Abstract translation: 本发明是一种用于制造用于研究肺肿瘤的动​​物模型及其用途的方法。 通过胚胎基因显微注射制备本发明的转基因非人动物，并且在肺中具有血管内皮生长因子A165（VEGF-A165）的组织特异性表达。 通过血管内皮生长因子A165的表达，本发明的转基因非人动物中的肺细胞具有炎性，血管发生和血管生成反应或诱导肺肿瘤。 因此，本发明的非人动物可以作为用于分析肺腺癌的调节和抗肿瘤药物筛选的动物模型。

    Method for Manufacturing Animal Model for Researching Pulmonary Tumor and Use Thereof
    8.
    发明申请
    Method for Manufacturing Animal Model for Researching Pulmonary Tumor and Use Thereof 有权
    制造用于研究肺肿瘤的动​​物模型及其使用方法

    公开(公告)号：US20110004950A1

    公开(公告)日：2011-01-06

    申请号：US12828786

    申请日：2010-07-01

    Applicant: Chuan-Mu CHEN

    Inventor： Chuan-Mu CHEN

    IPC: A01K67/027 ,  C12N15/63

    CPC classification number: A01K67/0275 ,  A01K2217/052 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0325

    Abstract: The present invention is a method for manufacturing an animal model for researching a pulmonary tumor and a use thereof. A transgenic non-human animal of the present invention is prepared by embryonic gene microinjection and possesses a tissue-specific expression of vascular endothelial growth factor A165 (VEGF-A165) in lung. Through the expression of vascular endothelial growth factor A165, the lung cells in the transgenic non-human animal of the present invention have inflammatory, vascularogenesis and angiogenesis responses or induce lung tumors. Thus, the non-human animal of the present invention can serve as an animal model for analyzing the regulation and the anti-tumor drugs screening of pulmonary adenocarcinoma.

    Abstract translation: 本发明是一种用于制造用于研究肺肿瘤的动​​物模型及其用途的方法。 通过胚胎基因显微注射制备本发明的转基因非人动物，并且在肺中具有血管内皮生长因子A165（VEGF-A165）的组织特异性表达。 通过血管内皮生长因子A165的表达，本发明的转基因非人动物中的肺细胞具有炎性，血管发生和血管生成反应或诱导肺肿瘤。 因此，本发明的非人动物可以作为用于分析肺腺癌的调节和抗肿瘤药物筛选的动物模型。

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