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1. 发明授权

US06689605B1 Controlling immune response to specific antigens 失效
标题翻译：控制对特定抗原的免疫应答
公开(公告)号：US06689605B1
公开(公告)日：2004-02-10
申请号：US09424281
申请日：2000-01-02
申请人： John D. Mountz , David T. Curiel , Huang-Ge Zhang
发明人： John D. Mountz , David T. Curiel , Huang-Ge Zhang
IPC分类号： C12N1563
CPC分类号： C07K14/70575 , A61K48/00 , A61K48/005 , A61K2039/5154 , C12N2799/022
摘要： One major problem with adenovirus gene therapy has been the T-cell mediated immune response elicited by inoculation of adenovirus, which leads to rapid clearance of the virus and loss of transgene expression. In the instant invention, the immune response to a virus is prevented by pre-treatment with adenovirus, adenoassociated virus or herpes virus infected antigen-presenting cell (APC) expressing Fas ligand with induced T-cell tolerance. Administration of AdCMVLacZ after tolerance resulted in prolonged expression of LacZ in tolerized animals compared to control treated animals. In control, but not tolerized animals, there was proliferation of CD3+ T-cell in the spleen in response to AdCMVLacZ treatment. Tolerance induction is also indicated by decreased production of interferon-&ggr; and IL-2 by peripheral T-cells isolated from treated animals after stimulation with the adenovirus infected APCs. T-cell tolerance is specific for the virus as the T-cell responses to an irrelative virus, mouse cytomegalovirus (MCMV) remained unimpaired. The instant invention utilizes virus specific T-cell tolerance, which is induced by APCs that co-express Fas ligand and virus antigens. The instant invention involves novel vectors and methods to induce tolerance to a viral vector gene therapy and prolong expression of a transgene in a viral host.
摘要翻译：腺病毒基因治疗的一个主要问题是通过接种腺病毒引起的T细胞介导的免疫应答，这导致病毒的快速清除和转基因表达的丧失。在本发明中，通过用表达具有诱导的T细胞耐受性的Fas配体的腺病毒，腺相关病毒或疱疹病毒感染的抗原呈递细胞（APC）预处理来防止对病毒的免疫应答。 ADMVLacZ的耐受性导致与对照处理的动物相比，耐受性动物中LacZ的表达延长。在控制但不能耐受的动物中，响应于AdCMVLacZ处理，脾脏中CD3 + T细胞增殖。通过用腺病毒感染的APC刺激后从处理的动物分离的外周T细胞的干扰素-γ和IL-2的产生减少也表示耐受性诱导。 T细胞耐受性对于病毒是特异性的，因为T细胞对不相关病毒的反应，小鼠巨细胞病毒（MCMV）保持不受损害。本发明利用由共表达Fas配体和病毒抗原的APC诱导的病毒特异性T细胞耐受性。本发明涉及诱导对病毒载体基因治疗的耐受并延长病毒宿主中转基因表达的新型载体和方法。

2. 发明授权

US06419919B2 Method for the augmentation of gene expression 失效
标题翻译：增加基因表达的方法
公开(公告)号：US06419919B2
公开(公告)日：2002-07-16
申请号：US09187952
申请日：1998-11-06
申请人： John D. Mountz , Huang-Ge Zhang , Tong Zhou , Carl K. Edwards, III
发明人： John D. Mountz , Huang-Ge Zhang , Tong Zhou , Carl K. Edwards, III
IPC分类号： A01N4304
CPC分类号： A61K48/00 , A61K38/191 , A61K39/39 , A61K2039/53 , A61K2039/55522
摘要： The present invention provides a method of increasing adenoviral gene expression in a tissue of an animal, comprising the step of administering to said animal a pharmacologically effective dose of tumor necrosis factor binding protein. Also provided is a various method of method of reducing an inflammatory response associated with adenoviral administration in a tissue of an animal, comprising the step of administering to said animal a pharmacologically effective dose of tumor necrosis factor binding protein.
摘要翻译：本发明提供了增加动物组织中腺病毒基因表达的方法，包括向所述动物施用药理学有效剂量的肿瘤坏死因子结合蛋白的步骤。还提供了减少与动物组织中腺病毒给药相关的炎症反应的各种方法的方法，其包括向所述动物施用药理学有效剂量的肿瘤坏死因子结合蛋白的步骤。

3. 发明授权

US06383794B1 Methods of producing high titer recombinant adeno-associated virus 失效
标题翻译：生产高滴度重组腺相关病毒的方法
公开(公告)号：US06383794B1
公开(公告)日：2002-05-07
申请号：US09379841
申请日：1999-08-24
申请人： John D. Mountz , Huang-Ge Zhang
发明人： John D. Mountz , Huang-Ge Zhang
IPC分类号： C12N701
CPC分类号： C12N15/86 , C12N2750/14143
摘要： The present invention discloses a method of producing large-scale recombinant adeno-associated virus stocks by infection of cells with at least one recombinant adenovirus vector(s). The vector(s) encode a therapeutic gene flanked by the terminal repeat ends of adeno-associated virus and the adeno-associated virus rep and cap genes. Transfection with two recombinant adenovirus vector(s) instead of two plasmids plus adenovirus results in the large scale, high titer production of recombinant adeno-associated virus with little to no contaminating adenovirus present.
摘要翻译：本发明公开了一种通过用至少一种重组腺病毒载体感染细胞来生产大规模重组腺相关病毒种群的方法。载体编码侧翼为腺相关病毒和腺相关病毒rep和cap基因的末端重复末端的治疗基因。用两种重组腺病毒载体代替两种质粒加上腺病毒的转染导致重组腺相关病毒的大规模，高滴度产生，几乎不发生污染性腺病毒。

4. 发明授权

US5888764A Human fas gene promoter region 失效
标题翻译：人类fas基因启动子区
公开(公告)号：US5888764A
公开(公告)日：1999-03-30
申请号：US377522
申请日：1995-01-20
申请人： John D. Mountz , Changdan Liu , Jianhua Cheng , William J. Koopman , Tong Zhou
发明人： John D. Mountz , Changdan Liu , Jianhua Cheng , William J. Koopman , Tong Zhou
IPC分类号： A01K67/027 , A61K38/00 , C07K14/715 , C12N1/21 , C12N15/12 , C12N15/67 , C12Q1/68 , C12N5/10 , C12N15/11 , C12P21/00
CPC分类号： A01K67/0275 , C07K14/715 , C12N15/67 , A01K2217/05 , A61K38/00 , C12N2799/022 , C12N2799/027
摘要： Disclosed is a 5' flanking sequence of the human fas gene containing a promoter region. This sequence also contains at least three transcription initiation sites, as well as consensus sequences for AP-1, GF-1, NY-Y, CP-2, EB20, and c-myb. Also disclosed are methods of altering senescence of the immune system by modifying Fas activity in cells to increase or decrease apoptosis. Fas expression and function on T cells from old (22-26-month-old) mice is also compared to young (2-month-old) mice and old CD2-fas transgenic mice. Fas expression and ligand-induced apoptosis was decreased on T cells from old mice compared to young mice. In 26-month-old CD2-fas transgenic mice, Fas and CD44 expression, Fas-induced apoptosis, T cell proliferation and cytokine production were comparable to that of the young mice. These results suggest that T cell senescence with age is associated with defective apoptosis and that the CD2-fas transgene allows the maintenance of Fas apoptosis function and T cell function in aged mice comparable to that of young mice.
摘要翻译：披露了含有启动子区的人fas基因的5'侧翼序列。该序列还含有至少三个转录起始位点，以及AP-1，GF-1，NY-Y，CP-2，EB20和c-myb的共有序列。还公开了通过改变细胞中的Fas活性来增加或减少凋亡来改变免疫系统衰老的方法。将老年（22-26个月大）小鼠的T细胞的Fas表达和功能与年轻（2月龄）的小鼠和老的CD2-fas转基因小鼠进行比较。与老年小鼠相比，来自老鼠的T细胞的Fas表达和配体诱导的凋亡降低。在26个月大的CD2-fas转基因小鼠中，Fas和CD44表达，Fas诱导的凋亡，T细胞增殖和细胞因子产生与年轻小鼠相当。这些结果表明，随着年龄的增长，T细胞衰老与细胞凋亡有关，CD2-fas转基因能够维持老年小鼠Fas细胞凋亡功能和T细胞功能，与年轻小鼠相当。

5. 发明授权

US5981829A .DELTA.Nur77 transgenic mouse 失效
标题翻译： DELTA Nur77转基因小鼠
公开(公告)号：US5981829A
公开(公告)日：1999-11-09
申请号：US852173
申请日：1997-05-06
申请人： John D. Mountz , Tong Zhou , Jianhua Cheng
发明人： John D. Mountz , Tong Zhou , Jianhua Cheng
IPC分类号： A01K67/027 , C07K14/47 , C07K14/725 , C12N15/85 , C12N5/00 , C12N15/00 , C12N15/09 , C12N15/63
CPC分类号： C12N15/8509 , A01K67/0275 , C07K14/47 , C07K14/7051 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2267/03
摘要： The present invention provides a transgenic mouse containing a transgene, said transgene comprising a truncated Nur77 (.DELTA.Nur77) gene. Also provided is a double transgenic mouse, wherein said double transgenic mouse comprises the .DELTA.Nur77 transgenic mouse backcrossed with the D.sup.b /HY T cell receptor transgenic mouse.
摘要翻译：本发明提供含有转基因的转基因小鼠，所述转基因包含截短的Nur77（DELTA Nur77）基因。还提供了双转基因小鼠，其中所述双转基因小鼠包含与Db / HY T细胞受体转基因小鼠回交的DELTA Nur77转基因小鼠。

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