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    I Sce I-induced gene replacement and gene conversion in embryonic stem cells
    2.
    发明授权
    I Sce I-induced gene replacement and gene conversion in embryonic stem cells 失效
    I Sce I诱导的胚胎干细胞中的基因替换和基因转化

    公开(公告)号：US5830729A

    公开(公告)日：1998-11-03

    申请号：US693948

    申请日：1996-08-07

    申请人： Frederic Jaisser ,  Michel Cohen-Tannoudji ,  Sylvie Robine ,  Andre Choulika ,  Daniel Louvard ,  Charles Babinet

    发明人： Frederic Jaisser ,  Michel Cohen-Tannoudji ,  Sylvie Robine ,  Andre Choulika ,  Daniel Louvard ,  Charles Babinet

    IPC分类号： C07K14/47 ,  C12N15/36 ,  C12N15/00

    CPC分类号： C07K14/4735

    摘要： This invention relates to a method of constructing a villin gene hybrid by inserting an I-Sce I restriction site next to or within a gene or cDNA encoding a villin protein. The insertion site of the I-Sce I restriction site is chosen as to provide a first downstream part and a second upstream part from the site, containing at least twelve nucleotides of the gene or cDNA encoding the villin protein. Furthermore, the insertion of the restriction permits a high frequency of homologous recombination events. The villin gene hybrid may be used to transfect eukaryotic cells, and particularly, embryonic stem cells.

    摘要翻译： 本发明涉及一种通过在编码绒毛蛋白的基因或cDNA之前或之内插入I-Sce I限制性位点来构建绒毛蛋白基因杂交体的方法。 选择I-Sce I限制性位点的插入位点，从该位点提供第一个下游部分和第二个上游部分，其中含有至少12个核苷酸的基因或编码绒毛蛋白的cDNA。 此外，插入限制允许高频率的同源重组事件。 绒毛蛋白基因杂交体可用于转染真核细胞，特别是胚胎干细胞。

    Shiga toxin B-subunit as a vector for tumor diagnosis and drug delivery to GB3 expressing tumors
    3.
    发明授权
    Shiga toxin B-subunit as a vector for tumor diagnosis and drug delivery to GB3 expressing tumors 有权
    志贺毒素B亚基作为肿瘤诊断和药物递送到GB3表达肿瘤的载体

    公开(公告)号：US08313731B2

    公开(公告)日：2012-11-20

    申请号：US13159124

    申请日：2011-06-13

    申请人： Ludger Johannes ,  David Grierson ,  Sylvie Robine ,  Jean-Claude Florent ,  Philipe Maillard ,  Jacky Roger

    发明人： Ludger Johannes ,  David Grierson ,  Sylvie Robine ,  Jean-Claude Florent ,  Philipe Maillard ,  Jacky Roger

    IPC分类号： A61K49/00 ,  C07K14/00

    CPC分类号： A61K49/085 ,  A61K38/00 ,  A61K41/0071 ,  A61K47/6415 ,  A61K47/67 ,  A61K49/0008 ,  A61K49/14 ,  B82Y5/00 ,  C07K14/25 ,  C07K14/36

    摘要： The invention relates to new compounds for cancer therapy or diagnosis and more specifically to the use of a non-toxic B subunit of Shiga toxin mutant as a vector for diagnostic products or drugs in over-expressing Gb3 receptor cells, such compounds having the following formula: STxB-Z(n)-Cys-Y(m)-T wherein STxB is the Shiga Toxin B subunit or a functional equivalent thereof, Z(n) wherein n is 0 or 1 and when n is 1, Z is an amino-acid residue devoid of sulfydryl group, or is a polypeptide, Cys is the amino-acid residue for Cysteine, T is a molecule linked by a covalent bound to the S part of Cys, selected in a group comprising: agents for in vivo diagnosis, cytotoxic agents, prodrugs, or enzymes for the conversion of a prodrug to a drug, Y(m) wherein m is 0 or 1 and when m is 1, Y is a linker between T and Cys, said linker being either cleavable or not cleavable for the release of T after the internalization of the hybrid compound into said cells.

    摘要翻译： 本发明涉及用于癌症治疗或诊断的新化合物，更具体地涉及使用志贺毒素突变体的无毒性B亚基作为过表达Gb3受体细胞的诊断产物或药物的载体，具有下式 ：STxB-Z（n）-Cys-Y（m）-T其中STxB是滋贺毒素B亚基或其功能等同物，Z（n）其中n为0或1，当n为1时，Z为氨基 - 不含巯基的酸性残基，或是多肽，Cys是半胱氨酸的氨基酸残基，T是通过与Sys的S部分共价结合连接的分子，选自以下组中：包括用于体内诊断的试剂 ，前药或前药转化为药物的Y（m），其中m为0或1，当m为1时，Y为T和Cys之间的接头，所述接头可切割或不切割 在将杂化化合物内化至所述细胞后，可以切割T释放T。

    Shiga toxin B-subunit as a vector for tumor diagnosis and drug delivery to Gb3 expressing tumors
    4.
    发明授权
    Shiga toxin B-subunit as a vector for tumor diagnosis and drug delivery to Gb3 expressing tumors 有权
    志贺毒素B亚基作为肿瘤诊断和药物递送至Gb3表达肿瘤的载体

    公开(公告)号：US07718601B2

    公开(公告)日：2010-05-18

    申请号：US11046786

    申请日：2005-02-01

    申请人： Ludger Johannes ,  David Grierson ,  Sylvie Robine ,  Jean-Claude Florent ,  Philipe Maillard ,  Jacky Roger

    发明人： Ludger Johannes ,  David Grierson ,  Sylvie Robine ,  Jean-Claude Florent ,  Philipe Maillard ,  Jacky Roger

    IPC分类号： C07K14/00 ,  A61K38/00

    CPC分类号： A61K49/085 ,  A61K38/00 ,  A61K41/0071 ,  A61K47/6415 ,  A61K47/67 ,  A61K49/0008 ,  A61K49/14 ,  B82Y5/00 ,  C07K14/25 ,  C07K14/36

    摘要： The invention relates to new compounds for cancer therapy or diagnosis and to the use of a non-toxic B subunit of Shiga toxin mutant as a vector for diagnostic products or drugs in over-expressing Gb3 receptor cells, such compounds having the following formula: STxB-Z(n)-Cys-Y(m)-T wherein-STxB is the Shiga Toxin B subunit or a functional equivalent thereof, -Z(n) wherein n is 0 or 1, Z is an amino-acid residue devoid of sulfydryl groups, or is a polypeptide, -T is a molecule linked by a covalent bound to the S part of Cys, selected from: agents for in vivo diagnosis, cytotoxic agents, prodrugs, or enzymes for the conversion of a prodrug to a drug, - Y(m) wherein m is 0 or 1, Y is a linker between T and Cys, which is either cleavable or not cleavable for the release of T after the internalization of the hybrid compound into cells.

    摘要翻译： 本发明涉及用于癌症治疗或诊断的新化合物，以及使用志贺毒素突变体的无毒性B亚基作为过表达Gb3受体细胞的诊断产品或药物的载体，具有下式：STxB -Z（n）-Cys-Y（m）-T其中-STxB是志贺毒素B亚基或其功能等同物，-Z（n）其中n为0或1，Z为不含 或者是多肽，-T是通过与Sys的S部分的共价结合连接的分子，其选自：用于体内诊断的试剂，细胞毒性剂，前药或用于将前药转化成药物的酶 ， - Y（m）其中m是0或1，Y是T和Cys之间的连接体，在混合化合物内化到细胞中之后，它们是可切割的或不可裂解的用于释放T。

    Shiga toxin B-subunit as a vector for tumor diagnosis and drug delivery to Gb3 expressing tumors
    7.
    发明申请
    Shiga toxin B-subunit as a vector for tumor diagnosis and drug delivery to Gb3 expressing tumors 有权
    志贺毒素B亚基作为肿瘤诊断和药物递送至Gb3表达肿瘤的载体

    公开(公告)号：US20060008475A1

    公开(公告)日：2006-01-12

    申请号：US11046786

    申请日：2005-02-01

    申请人： Ludger Johannes ,  David Grierson ,  Sylvie Robine ,  Jean-Claude Florent ,  Philipe Maillard ,  Jacky Roger

    发明人： Ludger Johannes ,  David Grierson ,  Sylvie Robine ,  Jean-Claude Florent ,  Philipe Maillard ,  Jacky Roger

    IPC分类号： A61K39/095

    CPC分类号： A61K49/085 ,  A61K38/00 ,  A61K41/0071 ,  A61K47/6415 ,  A61K47/67 ,  A61K49/0008 ,  A61K49/14 ,  B82Y5/00 ,  C07K14/25 ,  C07K14/36

    摘要： The invention relates to new compounds for cancer therapy or diagnosis and to the use of a non-toxic B subunit of Shiga toxin mutant as a vector for diagnostic products or drugs in over-expressing Gb3 receptor cells, such compounds having the following formula: STxB-Z(n)-Cys-Y(m)-T wherein—STxB is the Shiga Toxin B subunit or a functional equivalent thereof, —Z(n) wherein n is 0 or 1, Z is an amino-acid residue devoid of sulfydryl groups, or is a polypeptide, —T is a molecule linked by a covalent bound to the S part of Cys, selected from: agents for in vivo diagnosis, cytotoxic agents, prodrugs, or enzymes for the conversion of a prodrug to a drug, —Y(m) wherein m is 0 or 1, Y is a linker between T and Cys, which is either cleavable or not cleavable for the release of T after the internalization of the hybrid compound into cells.

    摘要翻译： 本发明涉及用于癌症治疗或诊断的新化合物，以及使用志贺毒素突变体的无毒性B亚基作为过表达Gb3受体细胞的诊断产品或药物的载体，具有下式：STxB -Z（n）-Cys-Y（m）-T其中-STxB是志贺毒素B亚基或其功能等同物，-Z（n）其中n为0或1，Z为不含 或者是多肽，-T是通过与Sys的S部分的共价结合连接的分子，其选自：用于体内诊断的试剂，细胞毒性剂，前药或用于将前药转化为药物的酶 -Y（m）其中m是0或1，Y是T和Cys之间的连接体，其在将杂化化合物内化为细胞后可以切割或不可切割以释放T。

    Multi-photon imaging installation
    8.
    发明授权
    Multi-photon imaging installation 失效
    多光子成像安装

    公开(公告)号：US06879394B2

    公开(公告)日：2005-04-12

    申请号：US10441027

    申请日：2003-05-20

    申请人： François Amblard ,  Xavier Sastre-Garau ,  Sylvie Robine

    发明人： François Amblard ,  Xavier Sastre-Garau ,  Sylvie Robine

    IPC分类号： A61B1/00 ,  A61B3/10 ,  A61B3/12 ,  A61N5/06 ,  G01N21/64 ,  G01N21/65 ,  G02B21/00 ,  G02B23/24

    CPC分类号： G01N21/6486 ,  G01N21/6458 ,  G02B21/0024 ,  G02B21/0076 ,  G02B21/0084

    摘要： An installation is provided for multi-dimensional non-linear imaging of a material comprising intrinsic chromophores, using laser scanning. This installation comprises i) at least one source (115) of time stamp pulses of synchronized photons, ii) means (12-14) for locally focusing the pulses on a material to cause its intrinsic chromophores to absorb groups of at least two synchronized photons to produce response photons, iii) means (22, 40, 53) for directing the response photons to at leat one collecting zone, iv) means (30-34) for collecting the response photons in the collecting zone(s) whatever their energy, v) processing means for converting the collected photons into data at least representative of their number and storing them in correspondence with at least the time stamp pulses that cause the material to produce the response photons, vi) means for scanning (11, 20) the pulses through a chosen area of the material, and vii) means for delivering from said data stored an image representative of said material chosen area, with a sub-millimeter resolution, and in function of the respective time stamp pulses of data.

    摘要翻译： 提供了一种用于使用激光扫描对包括内在发色团的材料进行多维非线性成像的装置。 该装置包括i）同步光子的时间戳脉冲的至少一个源（115），ii）用于将材料上的脉冲局部聚焦以使其内在发色团吸收至少两个同步光子的组的装置（12-14） 以产生响应光子，iii）用于将响应光子引导到一个收集区的装置（22,40,53），iv）用于收集收集区中的响应光子的装置（30-34），无论其能量如何 v）处理装置，用于将所收集的光子转换成至少代表其数量的数据，并且至少存储它们与至少引起材料产生响应光子的时间戳脉冲相对应; vi）扫描装置（11,20） 脉冲通过材料的选定区域，以及vii）用于从所述数据传送的装置，用于存储表示所述材料选择区域的图像，具有亚毫米分辨率，并且具有数据的相应时间戳脉冲的功能。

    I-Sce I induced gene replacement and gene conversion in embryonic stem cells
    9.
    发明授权
    I-Sce I induced gene replacement and gene conversion in embryonic stem cells 失效
    I-Sce I诱导胚胎干细胞中的基因替换和基因转化

    公开(公告)号：US06566579B1

    公开(公告)日：2003-05-20

    申请号：US09116834

    申请日：1998-07-17

    申请人： Frederic Jaisser ,  Michel Cohen-Tannoudji ,  Sylvie Robine ,  Andre Choulika ,  Daniel Louvard ,  Charles Babinet

    发明人： Frederic Jaisser ,  Michel Cohen-Tannoudji ,  Sylvie Robine ,  Andre Choulika ,  Daniel Louvard ,  Charles Babinet

    IPC分类号： G01N3300

    CPC分类号： C07K14/4735

    摘要： The invention relates to methods of introducing a heterologous DNA sequence into a mouse embryonic stem cell wherein the DNA sequence is inserted by homologous recombination into a villin gene/I-SceI hybrid by creating a double strand break with I-SceI meganuclease. Subsequently, the mouse embryonic stem cells can be used to generate a transgenic mouse comprising the heterologous DNA sequence. Additionally, the methods can be used for gene replacement in ovo where a mouse oocyte containing a villin gene/I-SceI hybrid within its genome exists or is first generated. More generally, the methods can be used for the targeted insertion of a heterologous DNA sequence into any cell containing a villin gene/I-SceI hybrid sequence within its genome.

    摘要翻译： 本发明涉及将异源DNA序列引入小鼠胚胎干细胞的方法，其中通过与I-SceI大范围核酸酶产生双链断裂，将DNA序列通过同源重组插入到绒毛蛋白基因/ I-SceI杂交体中。 随后，小鼠胚胎干细胞可用于产生包含异源DNA序列的转基因小鼠。 此外，该方法可用于卵巢中的基因替换，其中在其基因组内含有绒毛蛋白基因/ I-SceI杂交体的小鼠卵母细胞存在或首先产生。 更一般地，该方法可用于将异源DNA序列靶向插入到其基因组内含有绒毛蛋白基因/ I-SceI杂交序列的任何细胞中。