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    아데노바이러스 생산 신규 세포주 및 그의 용도
    3.
    发明申请
    아데노바이러스 생산 신규 세포주 및 그의 용도 审中-公开
    ADENOVIRUS生产新型细胞系及其用途

    公开(公告)号：WO2013077645A1

    公开(公告)日：2013-05-30

    申请号：PCT/KR2012/009931

    申请日：2012-11-22

    申请人： 주식회사 바이로메드

    发明人： 유승진 ,  주창완 ,  채진아 ,  차연숙

    IPC分类号： C12N5/10 ,  C12N15/861 ,  C12P21/00 ,  C12N5/09

    CPC分类号： C12N7/00 ,  C12N15/86 ,  C12N2710/10351 ,  C12P21/00

    摘要： 본 발명은 (a) 동물세포에서 작동가능한 프로모터 및 (b) 상기 프로모터에 작동적으로 결합된(operatively linked to) 서열목록 제1서열의 E1 코딩 변형 유전자 서열을 포함하는 발현 컨스트럭트가 지놈 DNA에 도입된 세포주에 관한 것이다. 본 발명에 따르면, 본 발명의 세포주는 복제 가능 아데노바이러스(RCA)의 생산 가능성이 낮은, 신규한 아데노바이러스 생산 세포주이다. 본 발명의 아데노바이러스 생산 세포주는 종래 아데노바이러스 생산 세포주와 비교하여 상동재조합(homologous recombination)으로 인한 RCA의 생성 가능성이 낮으며, 이로 인해, 아데노바이러스를 이용한 유전자치료 시 필요한 바이러스의 양을 조절할 수 있고, 아데노바이러스의 과잉생산으로 인한 조직손상 및 독성작용을 저지할 수 있다. 또한, 종래 아데노바이러스 생산 세포주인 HEK293 세포와 비교하여 우수한 아데노바이러스 생산능을 나타내어, 시간- 및 비용- 경제적인 복제 불능 아데노바이러스를 생산할 수 있다. 따라서 본 발명의 세포주는 복제 불능 아데노바이러스를 효율적으로 생산하고 유전자 치료시 안전한 유효량의 아데노바이러스를 제공할 수 있다.

    摘要翻译： 本发明涉及（a）动物细胞中的可操作的启动子和（b）将含有与启动子有效连接的SEQ ID NO：1的经修饰的E1编码基因序列的表达构建体导入基因组的细胞系 脱氧核糖核酸。 根据本发明，本发明的细胞系是不太可能产生复制型腺病毒（RCA）的新型细胞系。 与常规细胞系相比，本发明的腺病毒产生细胞系与同源重组产生RCA的可能性低。 因此，这可以在使用腺病毒的基因治疗期间调节所需量的病毒，并防止由腺病毒过量产生引起的组织损伤和毒性作用。 此外，与作为常规腺病毒产生细胞系之一的HEK293细胞相比，本发明的细胞系显示出优异的腺病毒产生能力。 因此，可以产生时间和成本节省的复制无能力的腺病毒。 因此，本发明的细胞系有效地产生复制无能的腺病毒，并且在基因治疗期间提供安全有效的腺病毒剂量。

    VIRAL VECTOR DRIVEN MUTANT BACTERIAL CYTOSINE DEAMINASE GENE AND USES THEREOF
    8.
    发明申请
    VIRAL VECTOR DRIVEN MUTANT BACTERIAL CYTOSINE DEAMINASE GENE AND USES THEREOF 审中-公开
    病毒载体驱动细菌细胞因子脱氧核糖核酸酶基因及其用途

    公开(公告)号：WO2008134044A2

    公开(公告)日：2008-11-06

    申请号：PCT/US2008005446

    申请日：2008-04-28

    申请人： BUCHSBAUM DONALD J ,  MARKERT JAMES M ,  KALIBEROV SERGEY A ,  GILLESPIE G YANCEY

    发明人： BUCHSBAUM DONALD J ,  MARKERT JAMES M ,  KALIBEROV SERGEY A ,  GILLESPIE G YANCEY

    IPC分类号： C12N15/86 ,  C12N15/09

    CPC分类号： C12N15/86 ,  A61K38/50 ,  A61K48/00 ,  C12N9/78 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2710/10351 ,  C12N2710/16643 ,  C12N2830/008 ,  C12Y305/04001

    摘要： The instant invention has developed viral vectors encoding a mutant bacterial cytosine deaminase (bCD) gene, which have a higher affinity for cytosine than wild type bCD (bCDwt) The purpose of the present invention was to evaluate cytotoxicity in vitro and therapeutic efficacy in vivo of these vectors in combination with the prodrug 5-FC and ionizing radiation against human glioma The present study demonstrates that infection with the viral vector expressing the mutant cytosine deaminase gene resulted in increased 5-FC-med?ated cell killing, compared with vectors expressing the wild-type gene Furthermore, a significant increase in cytotoxicity following infection with viral vector expressing the mutant cytosine deaminase gene and radiation treatment of glioma cells in vitro was demonstrated as compared to infection with viral vector expressing the wild-type gene Animal studies showed significant inhibition of subcutaneous or intracranial tumor growth of D54MG glioma xenografts by the combination of AdbCD-D314A/5-FC with ionizing radiation as compared with either agent alone, and with AdbCDwt/5-FC plus radiation

    摘要翻译： 本发明开发了编码与野生型bCD（bCDwt）相比对胞嘧啶具有更高亲和力的突变型细胞胞嘧啶脱氨酶（bCD）基因的病毒载体。本发明的目的是评估体外细胞毒性和体内治疗功效 这些载体与前体药物5-FC和针对人神经胶质瘤的电离辐射组合。本研究表明，与表达该胶质瘤的载体相比，表达突变胞嘧啶脱氨酶基因的病毒载体的感染导致5-FC-细胞杀伤增加 野生型基因此外，与表达野生型基因的病毒载体的感染相比，证明了表达突变胞嘧啶脱氨酶基因的病毒载体感染后的细胞毒性显着增加和体外胶质瘤细胞的放射治疗。动物研究显示显着的抑制 皮下或颅内肿瘤生长的D54MG胶质瘤异种移植物由c 与单独的任一种药物相比，AdbCD-D314A / 5-FC与电离辐射相比较，与AdbCDwt / 5-FC加辐射

    METHODS OF GENERATING CHIMERIC ADENOVIRUSES AND USES FOR SUCH CHIMERIC ADENOVIRUSES
    9.
    发明申请
    METHODS OF GENERATING CHIMERIC ADENOVIRUSES AND USES FOR SUCH CHIMERIC ADENOVIRUSES 审中-公开
    产生阴性腺瘤病毒的方法和用于这些重型腺病毒的方法

    公开(公告)号：WO2005001103A3

    公开(公告)日：2005-06-09

    申请号：PCT/US2004016614

    申请日：2004-06-15

    申请人： UNIV PENNSYLVANIA ,  ROY SOUMITRA ,  WILSON JAMES M

    发明人： ROY SOUMITRA ,  WILSON JAMES M

    IPC分类号： A61K39/00 ,  A61K39/12 ,  A61K39/235 ,  A61K48/00 ,  C07K14/075 ,  C12N5/10 ,  C12N7/01 ,  C12N15/34 ,  C12N15/86 ,  C12N15/861

    CPC分类号： C07K14/005 ,  A61K39/00 ,  A61K39/12 ,  A61K48/00 ,  A61K2039/5256 ,  C12N15/86 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10344 ,  C12N2710/10351 ,  C12N2760/14134 ,  C12N2810/6018

    摘要： A method for providing an adenovirus from a serotype which does not grow efficiently in a desired cell line with the ability to grow in that cell line is described. The method involves replacing the left and right termini of the adenovirus with the corresponding termini from an adenovirus which grow efficiently in the desired cell line. At a minimum, the left terminus spans the (5') inverted terminal repeat, the left terminus spans the E4 region and the (3') inverted terminal repeat. The resulting chimeric adenovirus contains the internal regions spanning the genes encoding the penton, hexon and fiber from the serotype which does not grow efficiently in the desired cell. Also provided are vectors constructed from novel simian adenovirus sequences and proteins, host cells containing same, and uses thereof.

    摘要翻译： 描述了从在该细胞系中具有生长能力的所需细胞系中不能有效生长的血清型提供腺病毒的方法。 该方法包括用在期望的细胞系中有效生长的腺病毒的相应末端替换腺病毒的左侧和右侧末端。 至少，左终点跨越（5'）反向末端重复，左终点跨越E4区域，（3'）反向末端重复。 所得到的嵌合腺病毒包含跨越编码来自血清型的五邻体，六邻体和纤维的基因的内部区域，其不能在期望的细胞中有效生长。 还提供了由新型猿猴腺病毒序列和蛋白构成的载体，含有其的宿主细胞及其用途。

    METHODS AND COMPOSITIONS FOR THE PRODUCTION OF ADENOVIRAL VECTORS
    10.
    发明申请
    METHODS AND COMPOSITIONS FOR THE PRODUCTION OF ADENOVIRAL VECTORS 审中-公开
    用于生产腺病毒载体的方法和组合物

    公开(公告)号：WO2004104190A2

    公开(公告)日：2004-12-02

    申请号：PCT/US2004/015009

    申请日：2004-05-14

    申请人： INTROGEN THERAPEUTICS, INC. ,  ZHANG, Shuyuan ,  PHAM, Hai

    发明人： ZHANG, Shuyuan ,  PHAM, Hai

    IPC分类号： C12N7/02

    CPC分类号： C12N7/00 ,  C12N15/86 ,  C12N2710/10343 ,  C12N2710/10351

    摘要： The present invention addresses the need to improve the yield of adenovirus when grown in cell culture systems. In particular, it has been demonstrated that for adenovirus, the use of infection temperatures lower than 37°C in a cell culture system results in improved yields of adenovirus. In addition, it has been demonstrated that when host cells are grow in a bioreactor, initiating adenovirus infection by diluting the host cells with fresh media and adenovirus results in improved yield of adenovirus. Methods of adenoviral production and purification using infection temperatures less than 37°C are disclosed. Methods of adenoviral production and purification wherein the host cells are grown in a bioreactor and adenovirus infection is initiated by diluting the host cells with fresh media and adenovirus are also disclosed.

    摘要翻译： 本发明解决了在细胞培养系统中生长时提高腺病毒产量的需要。 特别地，已经证明对于腺病毒，在细胞培养系统中使用低于37℃的感染温度导致腺病毒的产量提高。 此外，已经证明当宿主细胞在生物反应器中生长时，通过用新鲜培养基和腺病毒稀释宿主细胞来引发腺病毒感染导致腺病毒的产量提高。 公开了使用感染温度低于37℃的腺病毒产生和纯化方法。 还公开了通过用新鲜培养基和腺病毒稀释宿主细胞来引发宿主细胞在生物反应器中生长和腺病毒感染的腺病毒产生和纯化的方法。