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1. 发明申请

WO2012159120A3 GENE THERAPY BASED STRATEGY FOR TREATING HIV 审中-公开
标题翻译：基于治疗艾滋病的基因治疗策略
公开(公告)号：WO2012159120A3
公开(公告)日：2013-03-28
申请号：PCT/US2012038901
申请日：2012-05-21
申请人： UNIV FLORIDA , CHANG LUNG-JI
发明人： CHANG LUNG-JI
IPC分类号： A61K48/00 , A61K31/7088 , A61K31/7105 , A61K39/395 , A61P31/12 , A61P31/18
CPC分类号： A61K48/005 , C07K14/7158 , C12N15/1132 , C12N15/1138 , C12N2310/14 , C12N2310/141 , C12N2320/31
摘要： Disclosed herein are methods and compositions for treating or increasing resistance HIV infection. Vectors carrying a codon-optimized CCR5delta32 gene, Hl-promoter driven CCR5shRNA and/or a triple miRNA (microRNA) intronic cassette (miR155, 19a, 30a) against HIV-1 pol, int and vpu may be packaged into virus particles. In a specific embodiment, vectors carrying the CCR5shRNA and the triple miRNA against HIV-1, pol, int and vpu without the CCR5delta32 gene are provided. Significant resistance to HIV-1 infection and envelope mediated fusion was observed in the vector-modified HOS-R5 cells that endogenously express CD4, CCR5 and CXCR4. Expression of endogenous CCR5 was inhibited more than 90% after vector CCR5shRNA gene transfer as demonstrated by flow cytometry.
摘要翻译：本文公开了用于治疗或增加抗性HIV感染的方法和组合物。携带密码子优化的CCR5delta32基因，启动子驱动的CCR5shRNA和/或针对HIV-1 pol，int和vpu的三重miRNA（microRNA）内含子盒（miR155,19a，30a）的载体可以包装到病毒颗粒中。在具体实施方案中，提供携带CCR5shRNA和针对HIV-1，pol，int和vpu而没有CCR5delta32基因的三重miRNA的载体。在内源表达CD4，CCR5和CXCR4的载体修饰的HOS-R5细胞中观察到HIV-1感染和包膜介导融合的显着抗性。通过流式细胞术证明，载体CCR5shRNA基因转移后，内源性CCR5的表达被抑制超过90％。

2. 发明申请

WO2012065156A3 EX VIVO DEVELOPMENT, EXPANSION AND IN VIVO ANALYSIS OF A NOVEL LINEAGE OF DENDRITIC CELLS 审中-公开
标题翻译：新生儿细胞的新发展，扩张和体检分析
公开(公告)号：WO2012065156A3
公开(公告)日：2012-08-02
申请号：PCT/US2011060560
申请日：2011-11-14
申请人： UNIV FLORIDA , CHANG LUNG-JI
发明人： CHANG LUNG-JI
IPC分类号： C12N5/0784 , A61K35/12 , A61P35/00 , C12N5/02 , C12N15/86
CPC分类号： C12N5/0639 , A61K35/15 , A61K39/0011 , A61K2039/5154 , A61K2039/5156 , C12N2501/052 , C12N2501/125 , C12N2501/145 , C12N2501/22 , C12N2501/2302 , C12N2501/2304 , C12N2501/2307 , C12N2501/2315 , C12N2501/25 , C12N2501/26 , C12N2510/00
摘要： Disclosed herein are new methods of producing a novel line of dendritic cells. The method comprises subjecting a sample of hematopoietic stem/precursor cells to a first feeder culture system that is supplemented with a first set of factors and a second feeder culture system supplemented with a second group of factors. The disclosure also pertains to new cell types that may be used as cancer immunotherapy.
摘要翻译：本文公开了生产新型树突状细胞系的新方法。该方法包括将造血干/前体细胞的样品经受补充有第一组因子的第一饲养培养系统和补充有第二组因子的第二饲养培养系统。本公开还涉及可用作癌症免疫治疗的新细胞类型。

3. 发明申请

WO2012159120A2 GENE THERAPY BASED STRATEGY FOR TREATING HIV 审中-公开
标题翻译：基于治疗艾滋病的基因治疗策略
公开(公告)号：WO2012159120A2
公开(公告)日：2012-11-22
申请号：PCT/US2012/038901
申请日：2012-05-21
申请人： UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INC. , CHANG, Lung-ji
发明人： CHANG, Lung-ji
CPC分类号： A61K48/005 , C07K14/7158 , C12N15/1132 , C12N15/1138 , C12N2310/14 , C12N2310/141 , C12N2320/31
摘要： Disclosed herein are methods and compositions for treating or increasing resistance HIV infection. Vectors carrying a codon-optimized CCR5delta32 gene, Hl-promoter driven CCR5shRNA and/or a triple miRNA (microRNA) intronic cassette (miR155, 19a, 30a) against HIV-1 pol, int and vpu may be packaged into virus particles. In a specific embodiment, vectors carrying the CCR5shRNA and the triple miRNA against HIV-1, pol, int and vpu without the CCR5delta32 gene are provided. Significant resistance to HIV-1 infection and envelope mediated fusion was observed in the vector-modified HOS-R5 cells that endogenously express CD4, CCR5 and CXCR4. Expression of endogenous CCR5 was inhibited more than 90% after vector CCR5shRNA gene transfer as demonstrated by flow cytometry.
摘要翻译：本文公开了用于治疗或增加抗性HIV感染的方法和组合物。载有密码子优化的CCR5delta32基因，启动子驱动的CCR5shRNA和/或针对HIV-1 pol，int和vpu的三重miRNA（microRNA）内含子盒（miR155,19a，30a）的载体可以包装到病毒颗粒中。在具体实施方案中，提供携带CCR5shRNA和针对HIV-1，pol，int和vpu而没有CCR5delta32基因的三重miRNA的载体。在内源表达CD4，CCR5和CXCR4的载体修饰的HOS-R5细胞中观察到对HIV-1感染和包膜介导融合的显着抗性。内源性CCR5的表达在载体CCR5shRNA基因转移后被抑制超过90％，如流式细胞术所证实的。

4. 发明申请

WO2010030947A1 SYSTEM AND METHOD FOR PRODUCING T CELLS 审中-公开
标题翻译：用于生产T细胞的系统和方法
公开(公告)号：WO2010030947A1
公开(公告)日：2010-03-18
申请号：PCT/US2009/056739
申请日：2009-09-11
申请人： UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INC. , CHANG, Lung-Ji , PATEL, Ekta, Samir
发明人： CHANG, Lung-Ji , PATEL, Ekta, Samir
IPC分类号： C12N5/071
CPC分类号： C12N5/0636 , C12N2501/23 , C12N2501/26 , C12N2501/51 , C12N2501/515 , C12N2502/1394 , C12N2502/99
摘要： Disclosed herein is a system and method for producing T cells from stem cell populations. Specifically exemplified herein is a culture system and method that produces CD4 cells and/or T cell subtypes from a CD4 lineage using a sample of hematopoietic stem cells. Adult hematopoietic precursor/stem cells (HPC) are progenitors to all lineages of immune cells. There has been limited success in generating functional CD4 T cells with this convenient culture system. Also disclosed herein is a novel stromal cell line expressing DLl, interleukin-7 (IL-7), and FMS-like tyrosine kinase 3 ligand (Flt3-L). This improved culture system can greatly facilitate the study of late T cell development and enables immunotherapeutic applications.
摘要翻译：本文公开了一种从干细胞群体产生T细胞的系统和方法。本文具体示例的是使用造血干细胞样品从CD4谱系产生CD4细胞和/或T细胞亚型的培养系统和方法。成人造血前体/干细胞（HPC）是免疫细胞所有谱系的祖细胞。使用这种方便的培养系统产生功能性CD4T细胞的成功有限。本文还公开了表达DL1，白细胞介素-7（IL-7）和FMS样酪氨酸激酶3配体（Flt3-L）的新型基质细胞系。这种改进的培养系统可以大大促进晚期T细胞发育的研究，并实现免疫治疗应用。

5. 发明申请

WO2004044147A2 MODIFIED DENDRITIC CELLS 审中-公开
标题翻译：改良的DENDRITIC细胞
公开(公告)号：WO2004044147A2
公开(公告)日：2004-05-27
申请号：PCT/US2003/035482
申请日：2003-11-07
申请人： CHANG, Lung-Ji , CHEN, Xiaochuan
发明人： CHANG, Lung-Ji , CHEN, Xiaochuan
IPC分类号： C12N
CPC分类号： C12N15/1136 , A61K2035/124 , C07K14/5418 , C07K14/5428 , C07K14/5434 , C12N5/0639 , C12N15/86 , C12N2310/111 , C12N2310/14 , C12N2501/23 , C12N2510/00 , C12N2740/13043 , C12N2740/15043 , C12N2830/50 , C12N2840/203 , C12N2840/206
摘要： Infection of a dendritic cell with a lentivirus impairs the dendritic cell's ability to act as an antigen presenting cell that polarizes a naïve T cell to develop along the Th1 pathway. This impairment is restored by infecting dendritic cells with lentiviruses containing vectors encoding IL-7, IL-12, and siRNA targeting IL-10 RNA.
摘要翻译：用慢病毒感染树突状细胞会损害树突状细胞作为抗原呈递细胞的能力，其使初始T细胞沿着Th1途径极化。通过用含有编码IL-7，IL-12和靶向IL-10RNA的siRNA的载体的慢病毒感染树突状细胞来恢复该损伤。

6. 发明申请

WO9844788A3 ANIMAL MODEL FOR EVALUATION OF VACCINES 审中-公开
标题翻译：用于评估疫苗的动物模型
公开(公告)号：WO9844788A3
公开(公告)日：1999-03-11
申请号：PCT/US9806944
申请日：1998-04-09
申请人： CHANG LUNG JI
发明人： CHANG LUNG-JI
IPC分类号： A01K67/027 , A61K39/00 , A61K39/008 , A61K48/00 , A61P35/00 , C07K14/16 , C12N7/04 , G01N33/48 , A61K39/21 , C12N1/10 , C12N1/36 , C12N7/01
CPC分类号： C07K14/005 , A01K67/0271 , A61K39/00 , C12N7/00 , C12N2740/16061 , C12N2740/16122
摘要： The present invention provides animals and methods for the evaluation of vaccines. In particular, the present invention provides humanized animal models for the evaluation of vaccines designed to confer immunity against human pathogens, including vaccines directed against the human immunodeficiency virus. The present invention further relates to HIV vaccines. In particular, the present invention provides attenuated replication-competent HIV vaccines and replication-defective HIV vaccines. In addition, the invention provides modified Leishmania cells expressing HIV proteins.

7. 发明申请

WO1996014332A1 RETROVIRAL VECTORS CONTAINING RECOMBINANT CMV-IE/HIV-TAR/MOLONEY MURINE LEUKEMIA VIRUS LONG TERMINAL REPEATS 审中-公开
标题翻译：包含重组型CMV-IE / HIV-TAR / MOLONEY MURINE LEUKEMIA病毒的尾部转录物长期终端重复
公开(公告)号：WO1996014332A1
公开(公告)日：1996-05-17
申请号：PCT/US1995014576
申请日：1995-11-08
申请人： CHANG, Lung-Ji
IPC分类号： C07H21/04
CPC分类号： C12N15/86 , A61K48/00 , C07K14/005 , C12N2740/13043 , C12N2740/16022 , C12N2740/16322
摘要： Novel retroviral vectors were constructed by modifying the Moloney murine leukemia virus (MoMLV) long terminal repeat (LTR). A portion of the U3 region of the MoMLV LTR was replaced with the human cytomegalovirus immediate-early enhancer/promoter (CMV-IE) together with the human immunodeficiency virus type 1 (HIV-1) transactivation response element (TAR). Transfection studies involving the hybrid CMV-IE/HIV-1-TAR MoMLV LTR enhancer/promoter demonstrated that this regulatory element increases basal transcriptional levels 10- to 50-fold. Expression from the recombinant MoMLV LTR was further increased by the addition of HIV-1 Tat. Additional vector modifications included the addition of an HIV-1 extended packaging signal and 3' splice acceptor site. Modified retroviral vectors containing the hybrid LTR should be useful for the production of high levels of retroviral and cellular expression products.
摘要翻译：通过修饰莫洛尼鼠白血病病毒（MoMLV）长末端重复（LTR）构建新的逆转录病毒载体。 MoMLV LTR的U3区域的一部分与人类巨细胞病毒立即早期增强子/启动子（CMV-IE）一起被替换为人类免疫缺陷病毒1型（HIV-1）反式激活应答元件（TAR）。涉及杂交CMV-IE / HIV-1-TAR MoMLV LTR增强子/启动子的转染研究表明，该调节元件将基础转录水平提高10至50倍。通过添加HIV-1 Tat，来自重组MoMLV LTR的表达进一步增加。额外的载体修饰包括添加HIV-1扩展包装信号和3'剪接受体位点。含有杂交LTR的修饰的逆转录病毒载体应用于生产高水平的逆转录病毒和细胞表达产物。

8. 发明申请

WO2008119024A1 MODIFIED ANTIGEN PRESENTING CELLS AND METHODS OF USE 审中-公开
标题翻译：改良的抗原呈递细胞和使用方法
公开(公告)号：WO2008119024A1
公开(公告)日：2008-10-02
申请号：PCT/US2008/058445
申请日：2008-03-27
申请人： UNIVERSITY OF FLORIDA RESEARCH FOUNDATION INC. , CHANG, Lung-Ji , WANG, Bei , HAN, Shuhong
发明人： CHANG, Lung-Ji , WANG, Bei , HAN, Shuhong
IPC分类号： C12N5/10 , C12N15/00
CPC分类号： C12N5/0639 , A61K2039/5154 , C12N2501/07 , C12N2501/998 , C12N2510/00
摘要： The invention provides compositions comprising and methods of using antigen presenting cells into which has been introduced at least a first nucleotide sequence that encodes calnexin, wherein expression of calnexin in the antigen presenting cell increases the antigen presenting cell's ability to activate a T cell response.
摘要翻译：本发明提供组合物和使用抗原呈递细胞的方法，其中至少引入了编码钙粘蛋白的第一核苷酸序列，其中抗原呈递细胞中钙粘蛋白的表达增加了抗原呈递细胞激活T细胞应答的能力。

9. 发明申请

WO2007133730A2 MATERIALS AND METHODS FOR CONTROL OF INFECTIONS 审中-公开
标题翻译：感染控制的材料和方法
公开(公告)号：WO2007133730A2
公开(公告)日：2007-11-22
申请号：PCT/US2007011519
申请日：2007-05-11
申请人： UNIV FLORIDA , CHEGINI NASSER , LUO XIAOPING , PAN QUN , CHANG LUNG-JI
发明人： CHEGINI NASSER , LUO XIAOPING , PAN QUN , CHANG LUNG-JI
IPC分类号： A61K48/00
CPC分类号： C12N15/86 , A61K35/13 , C12N2740/15043 , C12N2830/002
摘要： The subject invention provides materials and methods for providing immediate and long-term protection against pathogenic microorganisms. One aspect of the subject invention provides a vector, such as a lentiviral vector carrying a nucleic acid sequence encoding an antimicrobial peptide, such as dermcidin (DCD), as an efficient means of delivery of the peptide. Preferably, the vector has a tetracycline-dependent transcriptional regulatory system such that expression of the nucleic acid sequence encoding the antimicrobial peptide is effectively turned "off' in the absence of tetracycline or its derivatives. Another aspect of the invention provides host cells that have been genetically modified with a vector of the invention to produce an antimicrobial peptide. Another aspect of the invention provides compositions comprising the vectors or host cells of the invention and a pharmaceutically acceptable carrier. Another aspect of the subject invention provides a method for treating or inhibiting the growth of a pathogenic microorganism by administering a vector or host cell of the invention to a subject suffering from, or susceptible to, infection by the pathogenic microorganism. Another aspect of the subject invention provides a method for detecting the presence of an antimicrobial peptide, such as DCD, within a male or female subject's urogenital tract.
摘要翻译：本发明提供了用于为病原微生物提供立即和长期保护的材料和方法。本发明的一个方面提供载体，例如携带编码抗微生物肽的核酸序列的慢病毒载体，例如皮霉素（DCD），作为递送肽的有效手段。优选地，载体具有四环素依赖性转录调节系统，使得在不存在四环素或其衍生物的情况下，编码抗微生物肽的核酸序列的表达被有效地“关闭”。本发明的另一方面提供了已经用本发明的载体进行遗传修饰以产生抗微生物肽本发明的另一方面提供了包含本发明的载体或宿主细胞和药学上可接受的载体的组合物。本发明的另一方面提供了一种治疗或抑制通过将本发明的载体或宿主细胞施用于患有或易感染病原微生物的受试者的病原微生物的生长，本发明的另一方面提供了一种用于检测抗微生物肽的存在的方法，作为DCD，在男性或女性受试者的urogenita中 l道。

10. 发明申请

WO2004065549A3 SMALL INTERFERENCE RNA GENE THERAPY 审中-公开
标题翻译：小干扰RNA基因治疗
公开(公告)号：WO2004065549A3
公开(公告)日：2005-03-24
申请号：PCT/US2004001320
申请日：2004-01-15
申请人： UNIV FLORIDA , CHANG LUNG-JI , HE JIN
发明人： CHANG LUNG-JI , HE JIN
IPC分类号： A61K48/00 , C12N15/11 , C12N15/113 , C07H21/04 , C12N15/63
CPC分类号： C12N15/1135 , A61K48/00 , C12N15/111 , C12N15/1132 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2330/30 , C12N2799/027
摘要： Gene expression is inhibited in a cell by introducing into the cell a lentiviral vector encoding a siRNA specific for the gene. Lentiviral vectors encoding siRNA specific for a cancer-associated gene inhibited expression of the gene and caused cell death after being introduced into cancer cells. Viral replication in HIV-infected cells was inhibited after introducing a lentiviral vector encoding siRNA specific for HIV genes in into the cells.
摘要翻译：通过向细胞中导入编码针对该基因特异的siRNA的慢病毒载体，在细胞中抑制基因表达。编码针对癌症相关基因的siRNA的慢病毒载体抑制基因的表达，并在导入癌细胞后导致细胞死亡。在将HIV基因特异性siRNA的慢病毒载体导入细胞后，HIV感染细胞中的病毒复制被抑制。

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