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    Plasmids for expression of human superoxide dismutase (SOD) analogs containing lambda PL promoter with engineered restriction site for substituting ribosomal binding sites and methods of use thereof
    1.
    发明授权
    Plasmids for expression of human superoxide dismutase (SOD) analogs containing lambda PL promoter with engineered restriction site for substituting ribosomal binding sites and methods of use thereof 失效
    用于表达含有λPL启动子的人超氧化物歧化酶（SOD）类似物用于代替核糖体结合位点的工程化限制性位点的质粒及其使用方法

    公开(公告)号：US5162217A

    公开(公告)日：1992-11-10

    申请号：US449125

    申请日：1989-12-08

    申请人： Jacob R. Hartman ,  Amos B. Oppenheim ,  Marian Gorecki ,  Haim Aviv ,  Rachel Oren

    发明人： Jacob R. Hartman ,  Amos B. Oppenheim ,  Marian Gorecki ,  Haim Aviv ,  Rachel Oren

    IPC分类号： A23K1/165 ,  A61K38/44 ,  C07K14/61 ,  C07K14/775 ,  C12N9/02 ,  C12N15/53 ,  C12N15/69 ,  C12N15/73

    CPC分类号： C12N9/0089 ,  A23K20/168 ,  A61K38/446 ,  C07K14/61 ,  C07K14/775 ,  C12N15/69 ,  C12N15/73 ,  Y10S514/886

    摘要： An improved plasmid for the production of superoxide dismutase which upon introduction into a host containing the thermolabile repressor C.sub.I renders the host capable of effecting expression of a gene encoding superoxide dismutase. The plasmid which includes in 5' to 3' order the following: the promoter and operator P.sub.L O.sub.L from lambda bacteriophage; the N utilization site; a first restriction enzyme site permitting replacement of the ribosomal binding site which follows thereafter; a ribosomal binding site; an ATG initiation codon; a second restriction enzyme site; a gene encoding superoxide dismutase; an origin of replication and a gene associated with a selectable or identifiable phenotypic trait manifested when the plasmid is present in the host. The distance between the 3' end of P.sub.L O.sub.L and the 5' end of the N utilization site is less than about 80 base pairs. The distance between the 3' end of the N utilization site and the 5' end of the ribosomal binding site is less than about 300 base pairs.Host vector systems have been constructed from these plasmids and used to produce human superoxide dismutase and analogs thereof. Such SOD or analogs may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs and reduce spinal cord injury.

    摘要翻译： 用于生产超氧化物歧化酶的改良质粒，其在引入含有不耐热阻遏物CI的宿主中时，使宿主能够实现编码超氧化物歧化酶的基因的表达。 包含5'至3'的质粒命名如下：来自λ噬菌体的启动子和操纵子PLOL; N利用场所; 第一限制性内切酶位点，其允许置换随后的核糖体结合位点; 核糖体结合位点; ATG起始密码子; 第二限制酶位点; 编码超氧化物歧化酶的基因; 复制起点和当质粒存在于宿主中时显示的与可选择或可鉴定的表型性状相关的基因。 PLOL的3'端与N利用位点的5'端之间的距离小于约80个碱基对。 N利用位点的3'末端与核糖体结合位点的5'末端之间的距离小于约300个碱基对。 宿主载体系统已经由这些质粒构建并用于产生人超氧化物歧化酶及其类似物。 这种SOD或类似物可用于催化超氧自由基的减少，减少再灌注损伤，延长分离器官的存活时间并减少脊髓损伤。

    Therapeutic compositions comprising a mixture of human CuZn superoxide dismutase analogs
    2.
    发明授权
    Therapeutic compositions comprising a mixture of human CuZn superoxide dismutase analogs 失效
    包含人CuZn超氧化物歧化酶类似物的混合物的治疗组合物

    公开(公告)号：US5455029A

    公开(公告)日：1995-10-03

    申请号：US933500

    申请日：1992-08-21

    申请人： Jacob R. Hartman ,  Amos B. Oppenheim ,  Marian Gorecki ,  Haim Aviv ,  Rachel Oren

    发明人： Jacob R. Hartman ,  Amos B. Oppenheim ,  Marian Gorecki ,  Haim Aviv ,  Rachel Oren

    IPC分类号： A23K1/165 ,  A61K38/44 ,  C07K14/61 ,  C07K14/775 ,  C12N9/02 ,  C12N15/53 ,  C12N15/69 ,  C12N15/73

    CPC分类号： C12N9/0089 ,  A23K20/168 ,  A61K38/446 ,  C07K14/61 ,  C07K14/775 ,  C12N15/69 ,  C12N15/73 ,  Y10S514/886

    摘要： An improved plasmid for the production of superoxide dismutase on an analog thereof which upon introduction into a suitable host containing the thermolabile repressor C.sub.I renders the host capable of effecting expression of a gene encoding superoxide dismutase or the analog. The plasmid is a double-stranded DNA molecule which includes in 5' to 3' order the following: the promoter and operator P.sub.L O.sub.L from lambda bacteriophage; the N utilization site; a first restriction enzyme site permitting replacement of the ribosomal binding site which follows thereafter; a ribosomal binding site; an ATG initiation codon; a second restriction enzyme site; a gene encoding superoxide dismutase or the analog; an origin of replication and a gene associated with a selectable or identifiable phenotypic trait manifested when the plasmid is present in the host. The distance between the 3' end of P.sub.L O.sub.L and the 5' end of the N utilization site is less than about 80 base pairs. The distance between the 3' end of the N utilization site and the 5' end of the ribosomal binding site is less than about 300 base pairs.Host vector systems have been constructed from these plasmids and used to produce human superoxide dismutase and analogs thereof. Such SOD or analogs may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs and reduce spinal cord injury.

    摘要翻译： 用于在其类似物上产生超氧化物歧化酶的改进的质粒，其在引入含有不耐热阻遏物CI的合适宿主中时，使宿主能够实现编码超氧化物歧化酶或类似物的基因的表达。 该质粒是双链DNA分子，其以5'至3'的顺序包括以下：来自λ噬菌体的启动子和操纵子PLOL; N利用场所; 第一限制性内切酶位点，其允许置换随后的核糖体结合位点; 核糖体结合位点; ATG起始密码子; 第二限制酶位点; 编码超氧化物歧化酶或类似物的基因; 复制起点和当质粒存在于宿主中时显示的与可选择或可鉴定的表型性状相关的基因。 PLOL的3'端与N利用位点的5'端之间的距离小于约80个碱基对。 N利用位点的3'末端与核糖体结合位点的5'末端之间的距离小于约300个碱基对。 宿主载体系统已经由这些质粒构建并用于产生人超氧化物歧化酶及其类似物。 这种SOD或类似物可用于催化超氧自由基的减少，减少再灌注损伤，延长分离器官的存活时间并减少脊髓损伤。

    Plasmids for expression of human superoxide dismutase (SOD) analogs containing lambda pl promoter with engineered restriction site for substituting ribosomal binding sites and methods of use thereof
    4.
    发明授权
    Plasmids for expression of human superoxide dismutase (SOD) analogs containing lambda pl promoter with engineered restriction site for substituting ribosomal binding sites and methods of use thereof 失效
    用于表达含有用于取代核糖体结合位点的工程化限制性位点的含有λPL启动子的人超氧化物歧化酶（SOD）类似物的质粒及其使用方法

    公开(公告)号：US5143836A

    公开(公告)日：1992-09-01

    申请号：US194424

    申请日：1988-05-13

    申请人： Jacob R. Hartman ,  Amos B. Oppenheim ,  Marian Gorecki ,  Haim Aviv

    发明人： Jacob R. Hartman ,  Amos B. Oppenheim ,  Marian Gorecki ,  Haim Aviv

    IPC分类号： A23K1/165 ,  A61K38/44 ,  C07K14/61 ,  C07K14/775 ,  C12N9/02 ,  C12N15/69 ,  C12N15/73

    CPC分类号： C12N9/0089 ,  A23K20/168 ,  A61K38/446 ,  C07K14/61 ,  C07K14/775 ,  C12N15/69 ,  C12N15/73

    摘要： An improved plasmid for the production of superoxide dismutase which upon introduction into a host containing the thermolabile repressor C.sub.I renders the host capable of effecting expression of a gene encoding superoxide dismutase. The plasmid includes in 5' to 3' order the following: the promoter and operator P.sub.L O.sub.L from lambda bacteriophage; the N utilization site; a first restriction enzyme site permitting replacement of the ribosomal binding site which follows thereafter; a ribosomal binding site; an ATG initiation codon; a second restriction enzyme site; a gene encoding superoxide dismutase; an origin of replication and a gene associated with a selectable or identifiable phenotypic trait manifested when the plasmid is present in the host. The distance between the 3' end of P.sub.L O.sub.L and the 5' end of the N utilization site is less than about 80 base pairs. The distance between the 3' end of the N utilization site and the 5' end of the ribosomal binding site is less than about 300 base pairs.Host vector systems have been constructed from these plasmids and used to produce human superoxide dismutase and analogs thereof. Such SOD or analogs may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs and reduce spinal cord injury.

    摘要翻译： 用于生产超氧化物歧化酶的改良质粒，其在引入含有不耐热阻遏物CI的宿主中时，使宿主能够实现编码超氧化物歧化酶的基因的表达。 该质粒以5'至3'的顺序包括以下：来自λ噬菌体的启动子和操纵子PLOL; N利用场所; 第一限制性内切酶位点，其允许置换随后的核糖体结合位点; 核糖体结合位点; ATG起始密码子; 第二限制酶位点; 编码超氧化物歧化酶的基因; 复制起点和当质粒存在于宿主中时显示的与可选择或可鉴定的表型性状相关的基因。 PLOL的3'端与N利用位点的5'端之间的距离小于约80个碱基对。 N利用位点的3'末端与核糖体结合位点的5'末端之间的距离小于约300个碱基对。 宿主载体系统已经由这些质粒构建并用于产生人超氧化物歧化酶及其类似物。 这种SOD或类似物可用于催化超氧自由基的还原，减少再灌注损伤，延长分离器官的存活时间并减少脊髓损伤。

    Gene encoding human manganese superoxide dismutase and recombinant polypeptide encoded thereby
    6.
    发明授权
    Gene encoding human manganese superoxide dismutase and recombinant polypeptide encoded thereby 失效
    编码人类锰超氧化物歧化酶的基因和由此编码的重组多肽

    公开(公告)号：US06610520B1

    公开(公告)日：2003-08-26

    申请号：US08299047

    申请日：1994-08-31

    申请人： Jacob R. Hartman ,  Yaffa Beck

    发明人： Jacob R. Hartman ,  Yaffa Beck

    IPC分类号： C12N902

    CPC分类号： A61K38/446 ,  C12N9/0089 ,  Y02A50/473

    摘要： A double-stranded cDNA molecule which includes DNA encoding human manganese superoxide dismutase has been created. The sequence of one strand of a double-stranded DNA molecule which encodes human manganese superoxide dismutase has been discovered. Such molecules may be introduced in procaryotic, e.g., bacterial, or eukaryotic, e.g., yeast or mammalian, cells and the resulting cells cultured or grown under suitable conditions so as to produce human manganese superoxide dismutase or analogs thereof which may then be recovered. By this invention, human MnSOD gene fragments from various plasmids may be ligated to yield a complete genomic human MnSOD gene fragment. Human MnSOD or analogs thereof may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs, or treat inflammations. The invention also concerns a method of producing enzymatically active human manganese superoxide dismutase or an analog thereof in a bacterial cell which contains and is capable of expressing a DNA sequence encoding the superoxide dismutase by maintaining the bacterial cell under suitable conditions and in a suitable production medium. The production medium is supplemented with an amount of Mn++ so that the concentration of Mn++ in the medium is greater than about 2 ppm. Genomic MnSOD DNA should also be capable of expression in eucaryotic cells under suitable conditions. This invention also concerns a method of recovering purified enzymatically active manganese superoxide dismutase from bacterial cells. It should also be possible to recover manganese SOD from genomic MnSOD DNA expressed in eucaryotic cells using similar methods.

    摘要翻译： 已经产生了包含编码人锰超氧化物歧化酶的DNA的双链cDNA分子。 已经发现编码人锰超氧化物歧化酶的双链DNA分子的一条链的序列。 这样的分子可以在原核细胞中，例如细菌的，或真核的，例如酵母或哺乳动物细胞中引入，所得细胞在合适的条件下培养或生长，以产生可以被回收的人锰超氧化物歧化酶或其类似物。 通过本发明，可以连接各种质粒的人类MnSOD基因片段以产生完整的基因组人类MnSOD基因片段。 人类MnSOD或其类似物可用于催化超氧自由基的还原，减少再灌注损伤，延长分离的器官的存活时间或治疗炎症。本发明还涉及生产酶活性人锰超氧化物歧化酶或其类似物的方法 在细菌细胞中，其含有并且能够通过将细菌细胞维持在合适的条件下并在合适的生产培养基中表达编码超氧化物歧化酶的DNA序列。 生产培养基补充一定量的Mn ++，使得培养基中Mn ++的浓度大于约2ppm。 基因组MnSOD DNA也应该能够在合适条件下在真核细胞中表达。本发明还涉及从细菌细胞中回收纯化的酶活性锰超氧化物歧化酶的方法。 也可以使用类似的方法从真核细胞中表达的基因组MnSOD DNA中回收锰SOD。

    Methods of use of human manganese superoxide dismutase
    7.
    发明授权
    Methods of use of human manganese superoxide dismutase 失效
    人锰超氧化物歧化酶的使用方法

    公开(公告)号：US5540911A

    公开(公告)日：1996-07-30

    申请号：US370461

    申请日：1995-01-09

    申请人： Jacob R. Hartman ,  Yaffa Beck

    发明人： Jacob R. Hartman ,  Yaffa Beck

    IPC分类号： A61K38/00 ,  A61K38/44 ,  C12N9/02 ,  C12N15/53 ,  A61K37/50

    CPC分类号： A61K38/446 ,  C12N9/0089

    摘要： This invention provides plasmids for expression of human superoxide dismutase of analogs thereof. The invention further provides a method of producing enzymatically active human MnSOD or an analog thereof by introducing plasmids for expression of human MnSOD into procaryotic or eucaryotic cells and growing the resulting cells under suitable conditions, including conditions wherein the production medium is supplemented with Mn.sup.++. The invention additionally provides a method of recovering purified enzymatically active MnSOD from procaryotic and eucaryotic cells. Human MnSOD or analogs thereof may be used to reduce reperfusion injury, prolong the survival time of isolated organs or treat inflammations or bronchial pulmonary dysplasia.

    摘要翻译： 本发明提供了用于表达其类似物的人超氧化物歧化酶的质粒。 本发明还提供了通过将质粒用于表达人类MnSOD的原料或真核细胞，并在合适的条件下生长所得细胞，包括其中生产培养基中补充有Mn ++的条件，生产酶活性人类MnSOD或其类似物的方法。 本发明另外提供从原核和真核细胞中回收纯化的酶活性MnSOD的方法。 人类MnSOD或其类似物可用于减少再灌注损伤，延长分离的器官的存活时间或治疗炎症或支气管肺发育不良。

    Polypeptide analogs of human manganese superoxide dismutase and compositions and complexes thereof
    8.
    发明授权
    Polypeptide analogs of human manganese superoxide dismutase and compositions and complexes thereof 失效
    人锰超氧化物歧化酶的多肽类似物及其组合物及其复合物

    公开(公告)号：US5246847A

    公开(公告)日：1993-09-21

    申请号：US842740

    申请日：1992-02-27

    申请人： Jacob R. Hartman ,  Yaffa Beck

    发明人： Jacob R. Hartman ,  Yaffa Beck

    IPC分类号： A61K38/44 ,  C12N9/02

    CPC分类号： C12N9/0089 ,  A61K38/446

    摘要： A double-stranded cDNA molecule which includes DNA encoding human manganese superoxide dismutase has been created. The sequence of one strand of a double-stranded DNA molecule which encodes human maganese superoxide dismutase has been discovered. Such molecules may be introduced in procaryotic, e.g., bacterial, or eukaryotic, e.g., yeast or mammalian, cells and the resulting cells cultured or grown under suitable conditions so as to produce human manganese superoxide dismutase or analogs thereof which may then be recovered. Human MnSOD or analogs thereof may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs, or treat inflammations.The invention also concerns a method of producing enzymatically active human manganese superoxide dismutase or an analog thereof in a bacterial cell which contains and is capable of expressing a DNA sequence encoding the superoxide dismutase by maintaining the bacterial cell under suitable conditions and in a suitable production medium. The production medium is supplemented with an amount of Mn.sup.++ so that the concentration of Mn.sup.++ in the medium is greater than about 2 ppm.This invention also concerns a method of recovering purified enzymatically active manganese superoxide dismutase from bacterial cells.

    摘要翻译： 已经产生了包含编码人锰超氧化物歧化酶的DNA的双链cDNA分子。 已经发现了编码人类超氧化物歧化酶的双链DNA分子的一条链的序列。 这样的分子可以在原核细胞中，例如细菌的，或真核的，例如酵母或哺乳动物细胞中引入，所得细胞在合适的条件下培养或生长，以产生可以被回收的人锰超氧化物歧化酶或其类似物。 人类MnSOD或其类似物可用于催化超氧自由基的还原，减少再灌注损伤，延长分离的器官的存活时间或治疗炎症。 本发明还涉及在细菌细胞中生产酶促活性人锰超氧化物歧化酶或其类似物的方法，其含有并且能够通过将细菌细胞维持在合适的条件下并在合适的生产培养基中表达编码超氧化物歧化酶的DNA序列 。 生产培养基补充一定量的Mn ++，使得培养基中Mn ++的浓度大于约2ppm。 本发明还涉及从细菌细胞中回收纯化的酶活性锰超氧化物歧化酶的方法。

    Human manganese superoxide dismutase DNA, its expression and method of recovering human manganese superoxide dismutase
    9.
    发明授权
    Human manganese superoxide dismutase DNA, its expression and method of recovering human manganese superoxide dismutase 失效
    人锰超氧化物歧化酶DNA，其表达及回收人锰超氧化物歧化酶的方法

    公开(公告)号：US06361772B1

    公开(公告)日：2002-03-26

    申请号：US08686466

    申请日：1996-07-25

    申请人： Jacob R. Hartman ,  Yaffa Beck

    发明人： Jacob R. Hartman ,  Yaffa Beck

    IPC分类号： A61K3844

    CPC分类号： A61K38/446 ,  C12N9/0089 ,  Y02A50/473

    摘要： A double-stranded cDNA molecule which includes DNA encoding human manganese superoxide dismutase has been created. The sequence of one strand of a double-stranded DNA molecule which encodes human manganese superoxide dismutase has been discovered. Such molecules may be introduced in procaryotic, e.g., bacterial, or eukaryotic, e.g., yeast or mammalian, cells and the resulting cells cultured or grown under suitable conditions so as to produce human manganese superoxide dismutase or analogs thereof which may then be recovered. By this invention, human MnSOD gene fragments from various plasmids may be ligated to yield a complete genomic human MnSOD gene fragment. Human MnSOD or analogs thereof may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs, or treat inflammations. The invention also concerns a method of producing enzymatically active human manganese superoxide dismutase or an analog thereof in a bacterial cell which contains and is capable of expressing a DNA sequence encoding the superoxide dismutase by maintaining the bacterial cell under suitable conditions and in a suitable production medium. The production medium is supplemented with an amount of Mn++ so that the concentration of Mn++ in the medium is greater than about 2 ppm. Genomic MnSOD DNA should also be capable of expression in eucaryotic cells under suitable conditions. This invention also concerns a method of recovering purified enzymatically active manganese superoxide dismutase from bacterial cells. It should also be possible to recover manganese SOD from genomic MnSOD DNA expressed in eucaryotic cells using similar methods.

    摘要翻译： 已经产生了包含编码人锰超氧化物歧化酶的DNA的双链cDNA分子。 已经发现编码人锰超氧化物歧化酶的双链DNA分子的一条链的序列。 这样的分子可以在原核细胞中，例如细菌的，或真核的，例如酵母或哺乳动物细胞中引入，所得细胞在合适的条件下培养或生长，以产生可以被回收的人锰超氧化物歧化酶或其类似物。 通过本发明，可以连接各种质粒的人类MnSOD基因片段以产生完整的基因组人类MnSOD基因片段。 人类MnSOD或其类似物可用于催化超氧自由基的还原，减少再灌注损伤，延长分离的器官的存活时间或治疗炎症。本发明还涉及生产酶活性人锰超氧化物歧化酶或其类似物的方法 在细菌细胞中，其含有并且能够通过将细菌细胞维持在合适的条件下并在合适的生产培养基中表达编码超氧化物歧化酶的DNA序列。 生产培养基补充一定量的Mn ++，使得培养基中Mn ++的浓度大于约2ppm。 基因组MnSOD DNA也应该能够在合适条件下在真核细胞中表达。本发明还涉及从细菌细胞中回收纯化的酶活性锰超氧化物歧化酶的方法。 也可以使用类似的方法从真核细胞中表达的基因组MnSOD DNA中回收锰SOD。

    Plasmids for expression and method of producing a human manganese superoxide dimutase analog
    10.
    发明授权
    Plasmids for expression and method of producing a human manganese superoxide dimutase analog 失效
    用于表达的质粒和生产人锰超氧化物二脱水酶类似物的方法

    公开(公告)号：US5270195A

    公开(公告)日：1993-12-14

    申请号：US912213

    申请日：1992-07-10

    申请人： Jacob R. Hartman ,  Yaffa Beck

    发明人： Jacob R. Hartman ,  Yaffa Beck

    IPC分类号： C12N1/21 ,  C12N9/02 ,  C12N15/53

    CPC分类号： C12N9/0089

    摘要： An expression plasmid has been constructed which includes DNA encoding human manganese superoxide dismutase. Such plasmids may be introduced into host cells and the resulting cells cultured or grown under suitable conditions so as to produce enzymatically active human manganese superoxide dismutase or analogs thereof which may then be recovered. A method of producing an enzymatically active analog of human manganese superoxide dismutase by supplementing the culture media with Mn.sup.++ has been developed.

    摘要翻译： 已经构建了包含编码人锰超氧化物歧化酶的DNA的表达质粒。 可以将这样的质粒引入宿主细胞，并将所得细胞在合适的条件下培养或生长，以便产生酶活性的人锰超氧化物歧化酶或其类似物，然后可以回收它们。 已经开发了通过用Mn ++补充培养基来生产人锰超氧化物歧化酶的酶活性类似物的方法。