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    Fibrin binding domain polypeptides and uses and methods of producing same
    1.
    发明授权
    Fibrin binding domain polypeptides and uses and methods of producing same 失效

    公开(公告)号：US07087722B1

    公开(公告)日：2006-08-08

    申请号：US09492971

    申请日：2000-01-27

    申请人： Tikva Vogel ,  Avigdor Levanon ,  Moshe Werber ,  Rachel Guy ,  Amos Panet

    发明人： Tikva Vogel ,  Avigdor Levanon ,  Moshe Werber ,  Rachel Guy ,  Amos Panet

    IPC分类号： A61K35/14 ,  A61K51/00 ,  A61K49/00 ,  C07K1/00 ,  C12Q1/56

    CPC分类号： A61K51/088 ,  C07K5/1021 ,  C07K7/06 ,  G01N33/60 ,  G01N2800/226

    摘要： This invention provides an imaging agent which comprises a polypeptide labeled with an imageable marker, such polypeptide having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin. The invention further provides a method wherein the imaging agent is used for imaging a fibrin-containing substance, i.e., a thrombus or atherosclerotic plaque. Further provided are plasmids for expression of polypeptides having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin, hosts containing these plasmids, methods of producing the polypeptides, methods of treatment using the polypeptides, and methods of recovering, refolding and reoxidizing the polypeptides. The invention also provides for purified polypeptides substantially free of other substances of human origin which have an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and which are capable of binding to fibrin.

    Plasmids for production of human growth hormone or polypeptide analog thereof, hosts containing the plasmids, products manufactured thereby, and related methods
    4.
    发明授权
    Plasmids for production of human growth hormone or polypeptide analog thereof, hosts containing the plasmids, products manufactured thereby, and related methods 失效
    用于生产人生长激素或其多肽类似物的质粒，含有质粒的宿主，由此制备的产品及相关方法

    公开(公告)号：US5637495A

    公开(公告)日：1997-06-10

    申请号：US340045

    申请日：1994-11-14

    申请人： Marian Gorecki ,  Avigdor Levanon ,  Amos Oppenheim ,  Tikva Vogel

    发明人： Marian Gorecki ,  Avigdor Levanon ,  Amos Oppenheim ,  Tikva Vogel

    IPC分类号： A61K38/00 ,  C07K14/61 ,  C12N9/02 ,  C12N15/73 ,  C12N15/00 ,  C12N15/70

    CPC分类号： C12N9/0089 ,  C07K14/61 ,  C12N15/73 ,  A61K38/00

    摘要： An improved vector upon introduction into a suitable bacterial host containing the thermolabile repressor C.sub.I renders the host cell capable, upon increasing the temperature of the host cell to a temperature at which the repressor is destroyed, of effecting expression of a desired gene inserted into the vector and production of polypeptide encoded by the gene. The vector is a double-stranded DNA molecule which includes in 5' to 3' order the following: a DNA sequence which contains the promoter and operator P.sub.L O.sub.L from lambda bacteriophage; the N utilization site for binding antiterminator N protein produced by the host cell; a DNA sequence which contains a ribosomal binding site for rendering the mRNA of the desired gene capable of binding to ribosomes within the host cell; an ATG initiation codon or a DNA sequence which is converted into an ATG initiation codon upon insertion of the desired gene into the vector; a restriction enzyme site for inserting the desired gene into the vector in phase with the ATG initiation codon; and additionally a DNA sequence which contains an origin of replication from a bacterial plasmid capable of autonomous replication in the host cell and a DNA sequence which contains a gene associated with a selectable or identifiable trait which is manifested when the vector is present in the host cell.

    摘要翻译： 在引入含有不耐热阻遏物CI的合适的细菌宿主中时，改进的载体使宿主细胞在将宿主细胞的温度升高至阻遏物被破坏的温度时能够实现插入到载体中的所需基因的表达 并产生由该基因编码的多肽。 载体是双链DNA分子，其以5'至3'的顺序包括以下：含有来自λ噬菌体的启动子和操纵子PLOL的DNA序列; 用于结合由宿主细胞产生的抗终止子N蛋白的N利用位点; 一个DNA序列，其含有一个核糖体结合位点，用于使所需基因的mRNA能够结合宿主细胞内的核糖体; ATG起始密码子或将所需基因插入载体后转化为ATG起始密码子的DNA序列; 用于将所需基因插入与ATG起始密码子同相载体的限制酶位点; 另外还包含含有能够在宿主细胞中自主复制的细菌质粒的复制起点的DNA序列和含有与可选择或可识别的性状相关的基因的DNA序列，所述基因在载体存在于宿主细胞中时显示 。

    Expressions vectors containing Lambda P.sub.L promoter and T.sub.1 T.sub.2 RNA termination sequence, plasmids containing the vectors, hosts containing the plasmids and relatedmethods
    5.
    发明授权
    Expressions vectors containing Lambda P.sub.L promoter and T.sub.1 T.sub.2 RNA termination sequence, plasmids containing the vectors, hosts containing the plasmids and relatedmethods 失效
    含有λPL启动子和T1 T2 rRNA终止序列的表达载体，含有载体的质粒，含有质粒的宿主及相关方法

    公开(公告)号：US5126252A

    公开(公告)日：1992-06-30

    申请号：US317434

    申请日：1989-03-01

    申请人： Amos B. Oppenheim ,  Avigdor Levanon ,  Hilla Locker-Galadi ,  Marian Gorecki

    发明人： Amos B. Oppenheim ,  Avigdor Levanon ,  Hilla Locker-Galadi ,  Marian Gorecki

    IPC分类号： A23K1/165 ,  A61K38/44 ,  C07K14/61 ,  C07K14/775 ,  C12N1/21 ,  C12N9/02 ,  C12N15/18 ,  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 vector upon introduction into a suitable host containing the thermolabile repressor C.sub.I renders the host capable of effecting expression of a desired gene. The vector 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 or DNA which is converted into an ATG initiation codon upon insertion of the desired gene into the vector; a second restriction enzyme site for inserting the gene in phase with the ATG codon; a T.sub.1 T.sub.2 rRNA transcription termination sequence; an origin of replication and a gene associated with a selectable or identificable phenotypic trait manifested when the vector is present in the host. The distance between the 3' end of the P.sub.L O.sub.L promoter and operator sequence and the 5' end of the N utilization site is less than about 80 base pairs and 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.Plasmids have been constructed from the vectors and used to produce bovine, chicken and porcine growth hormones, human apolipoprotein E and human superoxide dismutase.

    摘要翻译： 在引入含有热不稳定阻遏物CI的合适宿主中时的改良载体使宿主能够实现所需基因的表达。 载体是双链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起始密码子或DNA，将所需基因插入载体后转化为ATG起始密码子; 用于将基因插入与ATG密码子同相的第二限制酶切位点; T1T2 rRNA转录终止序列; 当载体存在于宿主中时，复制起点和与可选择或可鉴定的表型性状相关的基因表现出来。 PLOL启动子的3'末端与N序列的5'末端之间的距离小于约80个碱基对，并且N个利用位点的3'末端与5'末端之间的距离 核糖体结合位点小于约300个碱基对。 质粒由载体构建，用于生产牛，鸡和猪生长激素，人载脂蛋白E和人超氧化物歧化酶。

    Plasmids for the production of human Cu-Zn superoxide dismutase, bacterial hosts containing the plasmids and methods for production and recovery of such superoxide dismutase
    6.
    发明授权
    Plasmids for the production of human Cu-Zn superoxide dismutase, bacterial hosts containing the plasmids and methods for production and recovery of such superoxide dismutase 失效
    用于生产人类Cu-Zn超氧化物歧化酶的质粒，含有质粒的细菌宿主和生产和回收这种超氧化物歧化酶的方法

    公开(公告)号：US5112744A

    公开(公告)日：1992-05-12

    申请号：US539367

    申请日：1990-06-15

    申请人： Amos B. Oppenheim ,  Avigdor Levanon ,  Hilla Locker-Galadi ,  Marian Gorecki

    发明人： Amos B. Oppenheim ,  Avigdor Levanon ,  Hilla Locker-Galadi ,  Marian Gorecki

    IPC分类号： A23K1/165 ,  A61K38/44 ,  C07K14/61 ,  C07K14/775 ,  C12N1/21 ,  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

    摘要： An improved vector upon introduction into a suitable host containing the thermolabile repressor C.sub.I renders the host capable of effecting expression of a desired gene. The vector 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; and ATG initiation codon or DNA which is converted into and ATG initiation codon upon insertion of the desired gene into the vector; a second restriction enzyme site for inserting the gene in phase with the ATG codon; a T.sub.1 T.sub.2 rRNA transcription termination sequence; and origin of replication and a gene associated with a selectable or identifiable phenotypic trait manifested when the vector is present in the host. The distance between the 3' end of the P.sub.L O.sub.L promotor and operator sequence and the 5' end of the N utilization site is less than about 80 base pairs and 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.Plasmids have been constructed from the vectors and used to produce bovine, chicken and porcine growth hormones, human apolipoprotein E and human superoxide dismutase.

    摘要翻译： 在引入含有热不稳定阻遏物CI的合适宿主中时的改良载体使宿主能够实现所需基因的表达。 载体是双链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; 和ATG起始密码子或DNA，将所需基因插入载体后转化成ATG起始密码子; 用于将基因插入与ATG密码子同相的第二限制酶切位点; T1T2 rRNA转录终止序列; 和复制起点和与载体存在于宿主中时表现的可选择或可鉴定的表型性状相关的基因。 PLOL启动子的3'末端与N序列的5'末端之间的距离小于约80个碱基对，N个利用位点的3'末端与5'末端之间的距离 核糖体结合位点小于约300个碱基对。 质粒由载体构建，用于生产牛，鸡和猪生长激素，人载脂蛋白E和人超氧化物歧化酶。

    Method for recovering a purified animal growth hormone or polypeptide analog thereof from a bacterial cell
    7.
    发明授权
    Method for recovering a purified animal growth hormone or polypeptide analog thereof from a bacterial cell 失效
    从细菌细胞中回收纯化的动物生长激素或其多肽类似物的方法

    公开(公告)号：US4997916A

    公开(公告)日：1991-03-05

    申请号：US320320

    申请日：1989-03-07

    申请人： Haim Aviv ,  Marian Gorecki ,  Avigdor Levanon ,  Amos Oppenheim ,  Tikva Vogel ,  Elisha Zeelon ,  Menachem Zeevi

    发明人： Haim Aviv ,  Marian Gorecki ,  Avigdor Levanon ,  Amos Oppenheim ,  Tikva Vogel ,  Elisha Zeelon ,  Menachem Zeevi

    IPC分类号： A61K38/00 ,  C07K14/61 ,  C12N15/73

    CPC分类号： C07K14/61 ,  C12N15/73 ,  A61K38/00 ,  Y10S530/82 ,  Y10S530/825

    摘要： A method is provided for recovering a purified animal growth hormone or a polypeptide analog thereof having substantially the same amino acid sequence as, and the biological activity of, the corresponding naturally-occurring animal growth hormone from a bacterial cell in which the animal growth hormone or polypeptide analog has been produced by means of expression of a plasmid encoding the hormone or polypeptide analog which comprises: (a) disrupting the cell wall of the bacterial cell in a buffered neutral pH solution so as to produce a lysate containing precipitated hormone or polypeptide analog; (b) recovering the resulting precipitated hormone or polypeptide analog; (c) suspending the precipitated hormone or polypeptide analog so recovered in distilled water; (d) treating the resulting precipitate-containing suspension with a sodium hydroxide solution having an alkaline pH of about 11.8 so as to solubilize the precipitate and thus the hormone or polypeptide analog contained therein; (e) separating the solubilized hormone or polypeptide analog from other soluble components by gel filtration chromatography; and (f) subjecting the hormone or polypeptide analog thus separated to ion exchange chromatography to purify the hormone or analog and thereby recover purified hormone or polypeptide analog.

    摘要翻译： 提供了一种用于从动物生长激素或细菌细胞的细菌细胞中回收纯化的动物生长激素或其多肽类似物，其具有与相应天然存在的动物生长激素基本上相同的氨基酸序列和生物学活性， 已经通过表达编码激素或多肽类似物的质粒产生多肽类似物，其包括：（a）在缓冲的中性pH溶液中破坏细菌细胞的细胞壁，以产生含有沉淀激素或多肽类似物的裂解物 ; （b）回收所得沉淀的激素或多肽类似物; （c）将沉淀的激素或多肽类似物悬浮于蒸馏水中; （d）用碱性pH为约11.8的氢氧化钠溶液处理所得沉淀物的悬浮液，以溶解沉淀物，从而溶解其中所含的激素或多肽类似物; （e）通过凝胶过滤色谱法将溶解的激素或多肽类似物与其他可溶组分分离; 和（f）使由此分离的激素或多肽类似物经离子交换色谱纯化激素或类似物，从而回收纯化的激素或多肽类似物。

    Polypeptide having factor Xa inhibitory activity
    9.
    发明授权
    Polypeptide having factor Xa inhibitory activity 失效
    具有因子Xa抑制活性的多肽

    公开(公告)号：US06211341B1

    公开(公告)日：2001-04-03

    申请号：US09228152

    申请日：1999-01-11

    申请人： Elisha P. Zeelon ,  Moshe M. Werber ,  Avigdor Levanon

    发明人： Elisha P. Zeelon ,  Moshe M. Werber ,  Avigdor Levanon

    IPC分类号： C07K1600

    CPC分类号： A61K38/58 ,  C07K14/81 ,  Y02A50/473 ,  Y10S514/888 ,  Y10S530/858

    摘要： The present invention provides an antibody which specifically reacts with an epitope of a polypeptide comprising the amino acid sequence X-Y-CYS GLN GLU GLU GLU CYS PRO ASP PRO TYR LEU CYS SER PRO VAL THR ASN ARG CYS GLU CYS THR PRO VAL LEU CYS ARG MET TYR CYS LYS PHE TRP ALA LYS ASP GLU LYS GLY CYS GLU ILE CYS LYS CYS GLU GLU LEU CYS GLN ASN GLN ASN CYS THR LYS ASP MET LEU CYS SER SER VAL THR ASN ARG CYS ASP CYS GLN ASP PHE LYS CYS PRO GLN SER TYR CYS-Z (SEQ. ID NO. 1) wherein X is MET or absent; Y is 0-28 amino acids of the sequence LYS MET CYS TRP ASN LYS GLY CYS PRO CYS GLY GLN ARG CYS ASN LEU HIS ARG ASN GLU CYS GLU VAL ILE ALA GLU ASN ILE GLU, (SEQ. ID NO. 2) with the proviso that if part of the sequence is present, it is a carboxy-terminal part of the sequence including the carboxy-terminal GLU and wherein Val may be preceded by Gly; and Z is absent or all or a part of the sequence Pro110-Lys156 shown in FIG. 7 (SEQ. ID NO. 24), with the proviso that if part of the sequence is present, it is the amino part of the sequence. The present invention also provides a monoclonal antibody as described above.

    摘要翻译： 本发明提供了与包含氨基酸序列的多肽的表位特异性反应的抗体XY-CYS GLN GLU GLU GLU CYS PRO ASP PRO TYR LEU CYS SER PRO VAL THR ASN ARG CYS GLU CYS THR PRO VAL LEU CYS ARG MET TYR CYS LYS PHE TRP ALA LYS ASP GLU LYS GLY CYS GLU ILE CYS LYS CYS GLU GLU LEU CYS GLN ASN GLN ASN CYS THR LYS ASP MET LEU CYS SER SER VAL THR ASN ARG CYS ASP CYS GLN ASP PHE LYS CYS PRO GLN SER TYR CYS-Z（SEQ ID NO：1）其中X是MET或不存在; Y是序列的0-28个氨基酸LYS MET CYS TRP ASN LYS GLY CYS PRO CYS GLY GLN ARG CYS ASN LEU HIS ARG ASN GLU CYS GLU VAL ILE ALA GLU ASN ILE GLU（SEQ.ID NO。2）与 条件是如果存在序列的一部分，则其是包含羧基末端GLU的序列的羧基末端部分，并且其中Val可以在之前是Gly; Z不存在，或全部或部分序列Pro110-Lys156如图1所示。 7（SEQ ID NO.24），条件是如果存在部分序列，则是序列的氨基部分。 本发明还提供如上所述的单克隆抗体。

    Expression vectors for enhanced production of polypeptides, plasmids containing the vectors, hosts containing the plasmids, products manufactured thereby and related methods
    10.
    发明授权
    Expression vectors for enhanced production of polypeptides, plasmids containing the vectors, hosts containing the plasmids, products manufactured thereby and related methods 失效
    用于增强多肽生产的表达载体，含有载体的质粒，含有质粒的宿主，由此制备的产品及相关方法

    公开(公告)号：US6054291A

    公开(公告)日：2000-04-25

    申请号：US871302

    申请日：1997-06-09

    申请人： Marian Gorecki ,  Avigdor Levanon ,  Amos Oppenheim ,  Tikva Vogel

    发明人： Marian Gorecki ,  Avigdor Levanon ,  Amos Oppenheim ,  Tikva Vogel

    IPC分类号： A61K38/00 ,  C07K14/61 ,  C12N9/02 ,  C12N15/73 ,  C12P21/02

    CPC分类号： C12N9/0089 ,  C07K14/61 ,  C12N15/73 ,  A61K38/00

    摘要： An improved vector upon introduction into a suitable bacterial host containing the thermolabile repressor C.sub.I renders the host cell capable, upon increasing the temperature of the host cell to a temperature at which the repressor is destroyed, of effecting expression of a desired gene inserted into the vector and production of polypeptide encoded by the gene. The vector is a double-stranded DNA molecule which includes in 5' to 3' order the following: a DNA sequence which contains the promoter and operator P.sub.L O.sub.L from lambda bacteriophage; the N utilization site for binding antiterminator N protein produced by the host cell; a DNA sequence which contains a ribosomal binding site for rendering the mRNA of the desired gene capable of binding to ribosomes within the host cell; an ATG initiation codon or a DNA sequence which is converted into an ATG initiation codon upon insertion of the desired gene into the vector; a restriction enzyme site for inserting the desired gene into the vector in phase with the ATG initiation codon; and additionally a DNA sequence which contains an origin of replication from a bacterial plasmid capable of autonomous replication in the host cell and a DNA sequence which contains a gene associated with a selectable or identifiable trait which is manifested when the vector is present in the host cell.

    摘要翻译： 在引入含有不耐热阻遏物CI的合适的细菌宿主中时，改进的载体使宿主细胞在将宿主细胞的温度升高至阻遏物被破坏的温度时能够实现插入到载体中的所需基因的表达 并产生由该基因编码的多肽。 载体是双链DNA分子，其以5'至3'的顺序包括以下：含有来自λ噬菌体的启动子和操纵子PLOL的DNA序列; 用于结合由宿主细胞产生的抗终止子N蛋白的N利用位点; 一个DNA序列，其含有一个核糖体结合位点，用于使所需基因的mRNA能够结合宿主细胞内的核糖体; ATG起始密码子或将所需基因插入载体后转化为ATG起始密码子的DNA序列; 用于将所需基因插入与ATG起始密码子同相载体的限制酶位点; 另外还包含含有能够在宿主细胞中自主复制的细菌质粒的复制起点的DNA序列和含有与可选择或可识别的性状相关的基因的DNA序列，所述基因在载体存在于宿主细胞中时显示 。