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    Vector constructs for the selection and identification of open reading frames
    1.
    发明授权
    Vector constructs for the selection and identification of open reading frames 失效
    用于选择和识别开放阅读框架的向量结构

    公开(公告)号：US5981182A

    公开(公告)日：1999-11-09

    申请号：US816721

    申请日：1997-03-13

    申请人： William R. Jacobs, Jr. ,  Sabine Daugelat

    发明人： William R. Jacobs, Jr. ,  Sabine Daugelat

    IPC分类号： C12N1/11 ,  C12N15/10 ,  C12Q1/68 ,  C07H21/04 ,  C12N15/63 ,  C12P21/02

    CPC分类号： C12N15/1051 ,  C12N15/1034 ,  C12Q1/6897

    摘要： The present invention provides for novel vector constructs comprising an origin of replication; a nucleotide sequence encoding an intein, the nucleotide sequence having a unique restriction enzyme site, critical amino acid residues located at the splice junctions of the intein, the intein inserted into a nucleotide sequence encoding a selectable marker; and a nucleotide sequence encoding suitable regulatory elements so as to effect expression of the vector construct in a suitable host cell. The vector constructs of the present invention may contain a DNA of interest cloned into a unique restriction site of the intein, and may be used as a vaccine alone or transformed into a vaccine vector. The vector constructs of this invention may further be used in methods of selecting translated open reading frames or genes, leading to the identification of potentially protective antigens of pathogenic organisms.

    摘要翻译： 本发明提供了包含复制起点的新载体构建体; 编码内含肽的核苷酸序列，具有独特的限制酶位点的核苷酸序列，位于内含肽剪接点的关键氨基酸残基，插入编码可选择标记的核苷酸序列的内含肽; 以及编码合适的调控元件的核苷酸序列，以便在合适的宿主细胞中影响载体构建体的表达。 本发明的载体构建体可以含有克隆到内含肽的独特的限制性位点的目标DNA，并且可以单独使用或转化成疫苗载体。 本发明的载体构建体还可用于选择翻译的开放阅读框或基因的方法，导致鉴定病原体的潜在保护性抗原。

    Mycobacterial isocitrate lyase gene and uses thereof
    2.
    发明授权
    Mycobacterial isocitrate lyase gene and uses thereof 失效
    分枝杆菌异柠檬酸裂解酶基因及其用途

    公开(公告)号：US06733761B2

    公开(公告)日：2004-05-11

    申请号：US10029715

    申请日：2001-12-20

    申请人： John D. McKinney ,  William R. Jacobs, Jr.

    发明人： John D. McKinney ,  William R. Jacobs, Jr.

    IPC分类号： A61K3904

    CPC分类号： C12N9/88

    摘要： The present invention provides a purified and isolated nucleic acid encoding mycobacterial isocitrate lyase, as well as mutated forms of the nucleic acid. Further provided are purified and isolated isocitrate lyase proteins and mutated isocitrate lyase proteins. Additionally, the present invention provides vectors which comprises nucleic acid sequences encoding mycobacterial isocitrate lyase and mutated forms of this nucleic acid, as well as host cells containing these vectors. Also provided is a mycobacterium containing one or more mutations in its isocitrate lyase gene. Further provided by the present invention are agents that inhibit the activity or expression of a mycobacterial lyase protein, a method of identifying these, and a method of producing them. Finally, the present invention also provides a method of identifying genes required for persistence of mycobacteria.

    摘要翻译： 本发明提供了编码分枝杆菌异柠檬酸裂解酶的纯化和分离的核酸，以及核酸的突变形式。 还提供纯化和分离的异柠檬酸裂合酶蛋白和突变的异柠檬酸裂合酶蛋白。 另外，本发明提供了包含编码分枝杆菌异柠檬酸裂合酶和突变形式的核酸的核酸序列以及含有这些载体的宿主细胞的载体。 还提供了在其异柠檬酸裂合酶基因中含有一个或多个突变的分枝杆菌。 本发明进一步提供的是抑制分枝杆菌裂解酶蛋白的活性或表达的试剂，鉴定这些的方法及其制备方法。 最后，本发明还提供了鉴定分枝杆菌持久性所需的基因的方法。

    Recombinant mycobacteria
    3.
    发明授权
    Recombinant mycobacteria 失效
    重组分枝杆菌

    公开(公告)号：US06372478B1

    公开(公告)日：2002-04-16

    申请号：US09314207

    申请日：1999-05-19

    申请人： Barry R. Bloom ,  Ronald W. Davis ,  William R. Jacobs, Jr. ,  Richard A. Young ,  Robert N. Husson

    发明人： Barry R. Bloom ,  Ronald W. Davis ,  William R. Jacobs, Jr. ,  Richard A. Young ,  Robert N. Husson

    IPC分类号： C12N120

    CPC分类号： A61K39/04 ,  A61K39/00 ,  C07K14/005 ,  C07K14/35 ,  C12N15/74 ,  C12N15/87 ,  C12N2795/10022 ,  C12R1/32 ,  Y02A50/412 ,  Y02A50/476

    摘要： Recombinant mycobacterial vaccine vehicles capable of expressing DNA of interest which encodes at least one protein antigen for at least one pathogen against which an immune response is desired and which can be incorporated into the mycobacteria or stably integrated into the mycobacterial genome. The vaccine vehicles are useful for administration to mammalian hosts for purposes of immunization. A recombinant vector which replicates in E. coli but not in mycobacteria is also disclosed. The recombinant vector includes 1) a mycobacterial gene or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance). The present invention also relates to two types of recombinant vectors useful in introducing DNA of interest into mycobacteria, where it is expressed. One type of vector is a recombinant phasmid capable of replicating as a plasmid in E. coli and of lysogenizing a mycobacterial host. The other type of vector is a recombinant plasmid which can be introduced into mycobacteria, where it is stably maintained extrachromosomally.

    摘要翻译： 能够表达目的的DNA的重组分枝杆菌疫苗载体，其编码针对至少一种需要免疫应答的至少一种病原体的至少一种蛋白质抗原并且可以并入分枝杆菌中或稳定整合到分枝杆菌基因组中。 疫苗载体用于哺乳动物宿主用于免疫的目的。 还公开了在大肠杆菌中但不在分枝杆菌中复制的重组载体。 重组载体包括1）与用重组质粒转化的分枝杆菌基因组中与同源序列重组所必需的分枝杆菌基因或其部分; 2）编码在用重组质粒转化的分枝杆菌中表达所需的多肽或蛋白质的基因的全部或部分; 3）在大肠杆菌中复制和选择所需的DNA序列; 和4）在分枝杆菌中选择所需的DNA序列（例如耐药性）。 本发明还涉及可用于将感兴趣的DNA引入分枝杆菌的两种类型的重组载体，其中它被表达。 一种载体是能够在大肠杆菌中作为质粒复制并使分枝杆菌宿主溶解的重组噬菌粒。 另一种载体是可以引入分枝杆菌的重组质粒，其在染色体外稳定地保持。

    Mycobacteriophages and uses thereof
    4.
    发明授权
    Mycobacteriophages and uses thereof 失效
    分枝杆菌噬菌体及其用途

    公开(公告)号：US5968733A

    公开(公告)日：1999-10-19

    申请号：US14560

    申请日：1998-01-28

    申请人： Barry R. Bloom ,  Ronald W. Davis ,  William R. Jacobs, Jr. ,  Richard A. Young ,  Robert N. Husson

    发明人： Barry R. Bloom ,  Ronald W. Davis ,  William R. Jacobs, Jr. ,  Richard A. Young ,  Robert N. Husson

    IPC分类号： G01N33/53 ,  A61K39/00 ,  A61K39/04 ,  A61K39/39 ,  A61P31/04 ,  A61P31/06 ,  A61P31/08 ,  A61P31/12 ,  A61P31/16 ,  A61P31/18 ,  A61P31/22 ,  A61P37/04 ,  A61P39/02 ,  C07K14/01 ,  C07K14/35 ,  C12N1/21 ,  C12N15/09 ,  C12N15/74 ,  C12N15/87 ,  C12P21/02 ,  C12R1/19 ,  C12R1/32 ,  C12R1/325 ,  C12R1/33 ,  C12R1/34 ,  G01N33/50 ,  C12Q1/70 ,  C07H21/04

    CPC分类号： A61K39/04 ,  C07K14/005 ,  C07K14/35 ,  C12N15/74 ,  C12N15/87 ,  C12R1/32 ,  A61K39/00 ,  C12N2795/10022

    摘要： Recombinant mycobacterial vaccine vehicles capable of expressing DNA of interest which encodes at least one protein antigen for at least one pathogen against which an immune response is desired and which can be incorporated into the mycobacteria or stably integrated into the mycobacterial genome. The vaccine vehicles are useful for administration to mammalian hosts for purposes of immunization. A recombinant vector which replicates in E. coli but not in mycobacteria is also disclosed. The recombinant vector includes 1) a mycobacterial gene or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E. coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance). The present invention also relates to two types of recombinant vectors useful in introducing DNA of interest into mycobacteria, where it is expressed. One type of vector is a recombinant phasmid capable of replicating as a plasmid in E. coli and of lysogenizing a mycobacterial host. The other type of vector is a recombinant plasmid which can be introduced into mycobacteria, where it is stably maintained extrachromosomally.

    摘要翻译： 能够表达目的的DNA的重组分枝杆菌疫苗载体，其编码针对至少一种需要免疫应答的至少一种病原体的至少一种蛋白质抗原并且可以并入分枝杆菌中或稳定整合到分枝杆菌基因组中。 疫苗载体用于哺乳动物宿主用于免疫的目的。 还公开了在大肠杆菌中但不在分枝杆菌中复制的重组载体。 重组载体包括1）与用重组质粒转化的分枝杆菌基因组中与同源序列重组所必需的分枝杆菌基因或其部分; 2）编码在用重组质粒转化的分枝杆菌中表达所需的多肽或蛋白质的基因的全部或部分; 3）在大肠杆菌中复制和选择所需的DNA序列; 和4）在分枝杆菌中选择所需的DNA序列（例如耐药性）。 本发明还涉及可用于将感兴趣的DNA引入分枝杆菌的两种类型的重组载体，其中它被表达。 一种载体是能够在大肠杆菌中作为质粒复制并使分枝杆菌宿主溶解的重组噬菌粒。 另一种载体是可以引入分枝杆菌的重组质粒，其在染色体外稳定地保持。

    Dim mutants of mycobacteria and use thereof
    6.
    发明授权
    Dim mutants of mycobacteria and use thereof 有权
    分枝杆菌的突变体及其用途

    公开(公告)号：US06290966B1

    公开(公告)日：2001-09-18

    申请号：US09350326

    申请日：1999-07-09

    申请人： Jeffery S. Cox ,  William R. Jacobs, Jr.

    发明人： Jeffery S. Cox ,  William R. Jacobs, Jr.

    IPC分类号： A61K3902

    CPC分类号： C12R1/32 ,  A61K2039/52 ,  C07K14/35

    摘要： Disclosed are novel recombinant mutant strains of mycobacteria that are deficient for the synthesis or transport of dimycoserosalphthiocerol (“DIM”). The present invention also provides a method of producing a recombinant mutant mycobacterium that is deficient for the synthesis or transport of DIM, comprising mutating a nucleic acid responsible for the synthesis or transport of dimycoserosalphthiocerol, including a nucleic acid comprising the promoter for the pps operon, fadD28 or mmpL7. The present invention also provides a vaccine comprising a DIM mutant mycobacterium of the present invention, as well as a method for the treatment or prevention of tuberculosis in a subject using the vaccine.

    摘要翻译： 公开了分子细菌的新型重组突变菌株，其用于合成或转运二环神经节硫辛（“DIM”）。 本发明还提供了一种制备DIM的合成或转运缺陷的重组突变型分枝杆菌的方法，包括突变负责合成或转运二环神经节硫蛋白的核酸，包括包含用于pps操纵子的启动子的核酸， fadD28或mmpL7。 本发明还提供了包含本发明的DIM突变型分枝杆菌的疫苗，以及使用疫苗治疗或预防受试者的结核病的方法。

    Mycobacterial mutants inducing IL-12
    9.
    发明授权
    Mycobacterial mutants inducing IL-12 有权
    分枝杆菌突变体诱导IL-12

    公开(公告)号：US08591918B2

    公开(公告)日：2013-11-26

    申请号：US12450193

    申请日：2008-03-10

    申请人： William R. Jacobs, Jr. ,  Kari Sweeney ,  Dee Dao ,  Steven A. Porcelli ,  John Chan ,  Tsungda Hsu

    发明人： William R. Jacobs, Jr. ,  Kari Sweeney ,  Dee Dao ,  Steven A. Porcelli ,  John Chan ,  Tsungda Hsu

    IPC分类号： A61K39/04 ,  A61K49/00 ,  A01N63/00

    CPC分类号： C07K14/35

    摘要： Provided are mycobacteria deleted in at least a portion of a region 3 ESAT-6-like gene cluster. Also provided are mycobacteria comprising a mutation in an roc-1 gene. Additionally, vaccines comprising these mycobacteria are provided. Further provided are methods of making a recombinant mycobacterium, methods of inducing an immune response in a mammal, methods of inhibiting IL-12 production in a mammal, and methods of stimulating IL-12 production in a mammal. Vaccine adjuvants are also provided, as are methods of inducing immunity to a target antigen in a mammal.

    摘要翻译： 提供在区域3 ESAT-6样基因簇的至少一部分中缺失分枝杆菌。 还提供了包含roc-1基因突变的分枝杆菌。 另外，提供了包含这些分枝杆菌的疫苗。 进一步提供了制备重组分枝杆菌的方法，在哺乳动物中诱导免疫应答的方法，抑制哺乳动物中IL-12产生的抑制方法，以及刺激哺乳动物中IL-12产生的方法。 还提供疫苗佐剂，以及在哺乳动物中诱导免疫目标抗原的方法。

    Mycobacterial mutants affecting host apoptosis
    10.
    发明授权
    Mycobacterial mutants affecting host apoptosis 有权
    分枝杆菌突变体影响宿主细胞凋亡

    公开(公告)号：US08394388B2

    公开(公告)日：2013-03-12

    申请号：US11794506

    申请日：2006-01-12

    申请人： William R. Jacobs, Jr. ,  Steven A. Porcelli ,  Volker Briken ,  Miriam Braunstein

    发明人： William R. Jacobs, Jr. ,  Steven A. Porcelli ,  Volker Briken ,  Miriam Braunstein

    IPC分类号： A61K39/04 ,  C12N1/20

    CPC分类号： C07K14/35 ,  A61K48/00 ,  A61K2039/522

    摘要： Provided are recombinant mycobacteria having a mutation in an nlaA gene or in a nuoG gene. Also provided are isolated and purified nlaA proteins and nuoG proteins from a mycobacterium. Additionally provided are isolated and purified nucleic acids comprising a recombinant nlaA gene or a recombinant nuoG gene. Further provided are methods of inducing an immune response in a mammal and methods of making a recombinant mycobacterium using the nlaA gene or the nuoG gene.

    摘要翻译： 提供了在nlaA基因或nuoG基因中具有突变的重组分枝杆菌。 还提供了分离和纯化的来自分枝杆菌的nlaA蛋白和nuoG蛋白。 另外提供了分离和纯化的包含重组nlaA基因或重组nuoG基因的核酸。 还提供了在哺乳动物中诱导免疫应答的方法和使用nlaA基因或nuoG基因制备重组分枝杆菌的方法。