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    Method of determining susceptibility of a tumor cell to a chemotherapeutic agent: novel use of herpes simplex virus
    1.
    发明授权
    Method of determining susceptibility of a tumor cell to a chemotherapeutic agent: novel use of herpes simplex virus 有权
    确定肿瘤细胞对化学治疗剂敏感性的方法：单纯疱疹病毒的新用途

    公开(公告)号：US08778331B2

    公开(公告)日：2014-07-15

    申请号：US12459332

    申请日：2009-06-30

    申请人： John Blaho

    发明人： John Blaho

    IPC分类号： A61K39/245 ,  C12N15/38

    CPC分类号： C12Q1/6897 ,  C12N2710/16631 ,  G01N33/5011 ,  G01N33/5026 ,  G01N2333/035

    摘要： The present invention provides a method of determining if a tumor cell is susceptible to killing by a chemotherapeutic agent, comprising: (a) providing a tumor cell; (b) infecting said tumor cell with a herpes simplex virus or a herpes simplex virus defective in an immediate early gene selected from the group consisting of ICP27, ICP4, and ICP22; and (c) determining the presence of apoptotic killing of said tumor cell, wherein the presence of apoptotic killing is indicative of susceptibility to said chemotherapeutic agent. Chemotherapeutic agent may include doxorubicin, etoposide, paclitaxel, cisplatin, or 5-fluorouracil. The present invention also provides a herpes simplex virus promoter construct having a lacZ gene to assess tumor resistance to chemotherapeutic agents.

    摘要翻译： 本发明提供了确定肿瘤细胞是否易受化学治疗剂杀伤的方法，其包括：（a）提供肿瘤细胞; （b）用选自ICP27，ICP4和ICP22的立即早期基因中的单纯疱疹病毒或单纯疱疹病毒感染所述肿瘤细胞; 和（c）确定所述肿瘤细胞的凋亡杀伤的存在，其中凋亡杀伤的存在指示对所述化学治疗剂的易感性。 化疗剂可包括多柔比星，依托泊苷，紫杉醇，顺铂或5-氟尿嘧啶。 本发明还提供了具有lacZ基因以评估对化学治疗剂的肿瘤抗性的单纯疱疹病毒启动子构建体。

    Genetically stable recombinant modified vaccinia ankara (rMVA) vaccines and methods of preparation thereof
    3.
    发明授权
    Genetically stable recombinant modified vaccinia ankara (rMVA) vaccines and methods of preparation thereof 有权
    基因稳定的重组修饰牛痘安卡拉（rMVA）疫苗及其制备方法

    公开(公告)号：US08580276B2

    公开(公告)日：2013-11-12

    申请号：US12795621

    申请日：2010-06-07

    申请人： Don Diamond ,  Zhongde Wang

    发明人： Don Diamond ,  Zhongde Wang

    IPC分类号： A61K39/285 ,  A61K39/245 ,  C12N7/01 ,  C12N15/38 ,  C12N15/863

    CPC分类号： A61K39/285 ,  A61K39/12 ,  A61K39/245 ,  A61K2039/5256 ,  C07K14/005 ,  C07K2319/40 ,  C12N7/00 ,  C12N15/86 ,  C12N2710/16134 ,  C12N2710/16151 ,  C12N2710/24143 ,  C12N2830/60

    摘要： A vaccine comprising an immunologically effective amount of recombinant modified vaccinia Ankara (rMVA) virus which is genetically stable after serial passage and produced by a) constructing a transfer plasmid vector comprising a modified H5 (mH5) promoter operably linked to a DNA sequence encoding a heterologous foreign protein antigen, wherein the expression of said DNA sequence is under the control of the mH5 promoter; b) generating rMVA virus by transfecting one or more plasmid vectors obtained from step a) into wild type MVA virus; c) identifying rMVA virus expressing one or more heterologous foreign protein antigens using one or more selection methods for serial passage; d) conducting serial passage; e) expanding an rMVA virus strain identified by step d); and f) purifying the rMVA viruses from step e) to form the vaccine. One embodiment is directed to a fusion cytomegalovirus (CMV) protein antigen comprising a nucleotide sequence encoding two or more antigenic portions of Immediate-Early Gene-1 or Immediate-Early Gene-2 (IEfusion), wherein the antigenic portions elicit an immune response when expressed by a vaccine.

    摘要翻译： 一种疫苗，其包含免疫有效量的重组修饰的痘苗安卡拉（rMVA）病毒，其在连续传代后基因稳定并通过以下方式产生：a）构建包含与编码异源的DNA序列可操作地连接的修饰的H5（mH5）启动子的转移质粒载体 外源蛋白抗原，其中所述DNA序列的表达在mH5启动子的控制下; b）通过将从步骤a）获得的一种或多种质粒载体转染入野生型MVA病毒来产生rMVA病毒; c）使用一种或多种连续通过的选择方法鉴定表达一种或多种异源外源蛋白抗原的rMVA病毒; d）连续通过; e）扩展由步骤d）鉴定的rMVA病毒株; 和f）从步骤e）纯化rMVA病毒以形成疫苗。 一个实施方案涉及包含编码立即早期基因-1或立即早期基因-2（IEfusion）的两个或多个抗原部分的核苷酸序列的融合巨细胞病毒（CMV）蛋白抗原，其中抗原部分引起免疫应答 用疫苗表达

    Immunological herpes simplex virus antigens and methods for use thereof
    4.
    发明授权
    Immunological herpes simplex virus antigens and methods for use thereof 有权
    免疫性单纯疱疹病毒抗原及其使用方法

    公开(公告)号：US08067010B2

    公开(公告)日：2011-11-29

    申请号：US12777156

    申请日：2010-05-10

    申请人： David M. Koelle ,  Lawrence Corey

    发明人： David M. Koelle ,  Lawrence Corey

    IPC分类号： A61K39/245 ,  A61K39/295 ,  A61K38/16 ,  A61K48/00 ,  C12N15/38 ,  C12N15/861 ,  C12N15/863 ,  C12N15/867 ,  C12N15/869 ,  C12N7/01 ,  C12N5/10

    CPC分类号： C07K14/005 ,  A61K39/00 ,  A61K2039/55572 ,  A61K2039/57 ,  C07K2319/00 ,  C12N2710/16622 ,  C12N2710/16634

    摘要： The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection. Disclosed herein are antigens and/or their constituent epitopes confirmed to be recognized by T-cells derived from herpetic lesions or from uterine cervix. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

    摘要翻译： 本发明提供可用于预防和治疗HSV感染的HSV抗原。 本文公开了抗原和/或其组成表位，其被证实被来自疱疹病变或子宫颈的T细胞识别。 对本发明的抗原具有特异性的T细胞已经证明了对负载有病毒编码的肽表位的细胞的细胞毒性活性，并且在许多情况下，针对感染HSV的细胞。 鉴定负责T细胞特异性的免疫原性抗原提供了改进的抗病毒治疗和预防策略。 含有编码本发明抗原的抗原或多核苷酸的组合物提供有效靶向的疫苗，用于预防和治疗HSV感染。

    Methods and compositions for cancer therapy using a novel adenovirus
    5.
    发明授权
    Methods and compositions for cancer therapy using a novel adenovirus 有权
    使用新型腺病毒的癌症治疗方法和组合物

    公开(公告)号：US07815902B2

    公开(公告)日：2010-10-19

    申请号：US11342719

    申请日：2006-01-30

    申请人： Svend O. Freytag ,  Jae Ho Kim ,  Ken Barton ,  Dell Paielli

    发明人： Svend O. Freytag ,  Jae Ho Kim ,  Ken Barton ,  Dell Paielli

    IPC分类号： A61K38/43 ,  C07H21/04 ,  C12N7/00 ,  C12N9/12 ,  C12N15/38

    CPC分类号： C12N9/78 ,  A61K35/13 ,  C12N9/1211 ,  C12N15/62 ,  C12N2799/022

    摘要： The invention comprises a novel virus that can kill mammalian cancer cells efficiently. The virus produces a novel protein that converts two non-toxic prodrugs into potent chemotherapeutic agents. These chemotherapeutic agents are produced locally and help the virus kill the cancer cells as well as sensitize them to radiation. In preclinical studies, the virus has proven effective at killing a variety of mammalian cancer cells either alone or when combined with prodrug therapy and/or radiation therapy. The invention may provide a safe and effective treatment for human cancer.

    摘要翻译： 本发明包括能有效杀死哺乳动物癌细胞的新型病毒。 该病毒产生一种将两种无毒前药转化为有效的化学治疗剂的新型蛋白质。 这些化学治疗剂是局部生产的，有助于病毒杀死癌细胞，并使其对辐射敏感。 在临床前研究中，已经证明该病毒可以单独或当与前药治疗和/或放射治疗组合时杀死多种哺乳动物癌细胞。 本发明可以为人类癌症提供安全有效的治疗。

    Multigene vectors
    8.
    发明授权
    Multigene vectors 失效
    多基因载体

    公开(公告)号：US5998174A

    公开(公告)日：1999-12-07

    申请号：US854601

    申请日：1997-05-12

    申请人： Joseph C. Glorioso ,  David Krisky

    发明人： Joseph C. Glorioso ,  David Krisky

    IPC分类号： C12N15/38 ,  C12N15/869 ,  C12N15/64 ,  C12N15/31 ,  C12N15/63

    CPC分类号： C12N15/86 ,  C12N2710/16643

    摘要： The present invention provides a method for preparing HSV vectors. The method comprises co-transfecting a source vector and a mutating cassette together into a population of appropriate host cells, such that homologous recombination occurs between the mutating cassette and the source vector whereby the mutating cassette replaces a region of the HSV genome. The mutating cassette has a unique restriction site not present in the sequence of the vector. The method further comprises plaquing the co-transfected host cells, selecting plaques in which recombination has occurred between the source vector and the mutating cassette, and isolating the viral DNA from the plaques. The isolated viral DNA is digested with a restriction endonuclease appropriate for cleaving the viral DNA at the unique restriction site within the mutating cassette to produce two viral polynucleotides. Following purification, the two viral polynucleotides can be ligated to form an HSV vector comprising the two viral polynucleotides. Alternatively, the two isolated viral polynucleotides can be recombined with an insertion cassette to form an HSV vector comprising the insertion cassette at the former locus of the unique restriction site. The present invention further provides a mutant vector, particularly an HSV vector constructed in accordance with the method for the present invention. The present invention further provides a multigene HSV vector, particularly a multigene HSV vector for cancer therapy.

    摘要翻译： 本发明提供一种HSV载体的制备方法。 该方法包括将源载体和突变盒共同转染到合适的宿主细胞群体中，使得在突变盒和源载体之间发生同源重组，由此突变盒替代HSV基因组的区域。 突变盒具有不存在于载体序列中的唯一限制性位点。 该方法还包括将共转染的宿主细胞进行筛选，选择在源载体和突变盒之间已经发生重组的斑块，并从噬斑中分离病毒DNA。 分离的病毒DNA用限制性内切核酸酶消化，其适用于在突变盒内的独特的限制性位点切割病毒DNA，以产生两个病毒多核苷酸。 纯化后，可以连接两种病毒多核苷酸以形成包含两种病毒多核苷酸的HSV载体。 或者，两个分离的病毒多核苷酸可以与插入盒重组以形成包含在唯一限制性位点前一位点的插入盒的HSV载体。 本发明还提供了突变载体，特别是根据本发明的方法构建的HSV载体。 本发明还提供了多基因HSV载体，特别是用于癌症治疗的多基因HSV载体。

    Human cytomegalovirus containing a .beta.-glucuronidase marker gene
    10.
    发明授权
    Human cytomegalovirus containing a .beta.-glucuronidase marker gene 失效
    含有β-葡糖苷酸酶标记基因的人巨细胞病毒

    公开(公告)号：US5877004A

    公开(公告)日：1999-03-02

    申请号：US462334

    申请日：1995-06-05

    申请人： Thomas R. Jones ,  Viera P. Muzithras ,  Yakov Gluzman

    发明人： Thomas R. Jones ,  Viera P. Muzithras ,  Yakov Gluzman

    IPC分类号： C07K14/045 ,  C12N7/01 ,  C12N9/24 ,  C12Q1/34 ,  C12Q1/68 ,  C12N15/38

    CPC分类号： C07K14/005 ,  C12N9/2402 ,  C12N9/2434 ,  C12Q1/34 ,  C12Q1/68 ,  C12Q1/6897 ,  C12Y302/01031 ,  C12N2710/16122 ,  G01N2333/045

    摘要： This invention relates to a method for identifying non-essential genes of the human cytomegalovirus (HCMV) genome through the insertion of a .beta.-glucuronidase marker gene into a specified HCMV gene, such that, if the product of the HCMV gene is not expressed, the gene is identified as non-essential for replication of HCMV. This invention also relates to a method of screening for compounds which inhibit HCMV by the insertion of the .beta.-glucuronidase marker gene into a HCMV gene, such that the enzyme marker is expressed and cleaves a conjugate chemical substrate in an assay system to yield a detectable fluorescing product or to result in a color change. This invention further provides the gene responsible in HCMV early cytopathic effect.

    摘要翻译： 本发明涉及通过将β-葡糖醛酸糖苷酶标记基因插入特定HCMV基因中鉴定人巨细胞病毒（HCMV）基因组的非必需基因的方法，使得如果HCMV基因的产物未被表达， 该基因被鉴定为对于HCMV的复制非必需的。 本发明还涉及通过将β-葡糖醛酸糖苷酶标记基因插入到HCMV基因中筛选抑制HCMV的化合物的方法，使得酶标记物在测定系统中表达并切割缀合物化学底物以产生可检测的 荧光产品或导致颜色变化。 本发明还提供了负责HCMV早期致细胞病变作用的基因。