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61. 发明授权

US09315788B2 Method for the generation of compact TALE-nucleases and uses thereof 有权
标题翻译：用于产生紧密TALE-核酸酶的方法及其用途
公开(公告)号：US09315788B2
公开(公告)日：2016-04-19
申请号：US13440940
申请日：2012-04-05
申请人： Philippe Duchateau , Julien Valton , Claudia Bertonati , Jean-Charles Epinat , George H. Silva , Alexandre Juillerat , Marine Beurdeley
发明人： Philippe Duchateau , Julien Valton , Claudia Bertonati , Jean-Charles Epinat , George H. Silva , Alexandre Juillerat , Marine Beurdeley
IPC分类号： C12N9/22 , C07K14/47 , C12N9/16
CPC分类号： C12N9/22 , A61K38/00 , C07K14/4703 , C07K2319/00 , C07K2319/80 , C12N9/16 , C12P19/34
摘要： The present invention relates to a method for the generation of compact Transcription Activator-Like Effector Nucleases (TALENs) that can efficiently target and process double-stranded DNA. More specifically, the present invention concerns a method for the creation of TALENs that consist of a single TALE DNA binding domain fused to at least one catalytic domain such that the active entity is composed of a single polypeptide chain for simple and efficient vectorization and does not require dimerization to target a specific single double-stranded DNA target sequence of interest and process DNA nearby said DNA target sequence. The present invention also relates to compact TALENs, vectors, compositions and kits used to implement the method.
摘要翻译：本发明涉及能够有效靶向和加工双链DNA的致密转录激活子样效应核酸酶（TALEN）的生成方法。更具体地，本发明涉及一种用于产生TALEN的方法，其由与至少一个催化结构域融合的单个TALE DNA结合结构域组成，使得活性实体由单个多肽链组成，用于简单和有效的载体化，并且不需要二聚化来靶向特定的单个双链DNA靶序列，并在DNA靶序列附近处理DNA。本发明还涉及用于实施该方法的紧凑型TALEN，载体，组合物和试剂盒。

62. 发明授权

US09273296B2 Meganuclease variants cleaving a DNA target sequence from a glutamine synthetase gene and uses thereof 有权
标题翻译：从谷氨酰胺合成酶基因切割DNA靶序列的大范围核酸酶变体及其用途
公开(公告)号：US09273296B2
公开(公告)日：2016-03-01
申请号：US13062795
申请日：2008-09-08
申请人： Julianne Smith
发明人： Julianne Smith
IPC分类号： C12N9/22
CPC分类号： C12N9/22
摘要： An I-CreI variant, wherein one of the two I-CreI monomers has at least two substitutions, one in each of the two functional subdomains of the LAGLIDADG core domain situated respectively from positions 28 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from the glutamine synthetase gene. Use of said variant and derived products for improving expression system for the production of recombinant protein.
摘要翻译： I-CreI变体，其中两个I-CreI单体中的一个具有至少两个取代，LAGLIDADG核心结构域的两个功能亚结构域中的每一个分别位于I-CreI的位置28至40和44至77之间，所述变体能够从谷氨酰胺合成酶基因切割DNA靶序列。使用所述变体和衍生产物来改进重组蛋白质生产的表达系统。

63. 发明授权

US08927247B2 I-CreI derived single-chain meganuclease and uses thereof 有权
标题翻译： I-CreI衍生的单链大范围核酸酶及其用途
公开(公告)号：US08927247B2
公开(公告)日：2015-01-06
申请号：US12864998
申请日：2009-02-02
申请人： Sylvestre Grizot
发明人： Sylvestre Grizot
IPC分类号： C12N9/16 , C07K14/00 , C12N9/22
CPC分类号： C12N9/22 , C07K2319/00
摘要： A new I-CreI derived single-chain meganuclease comprising two domains, each domain comprising a portion of a parent I-CreI monomer which extends at least from the beginning of the first alpha helix to the end of the C-terminal loop and said two domains being joined by a peptidic linker which allows them to fold as a I-CreI dimer that is able to bind and cleave a chimeric DNA target comprising one different half of each parent homodimeric I-CreI meganuclease target sequence. Use of said I-CreI derived single-chain meganuclease for genetic engineering, genome therapy and antiviral therapy.
摘要翻译：一种新的I-CreI衍生的单链大范围核酸酶包含两个结构域，每个结构域包含一部分母本I-CreI单体，其至少从第一个α螺旋的开始延伸到C末端环的末端，结构域通过肽接头连接，其允许它们作为I-CreI二聚体折叠，其能够结合和切割包含每个亲代二聚体I-CreI大范围核酸酶靶序列的一个不同一半的嵌合DNA靶标。使用所述I-CreI衍生的单链大范围核酸酶进行遗传工程，基因组治疗和抗病毒治疗。

64. 发明申请

US20140370558A1 MODIFYING SOYBEAN OIL COMPOSITION THROUGH TARGETED KNOCKOUT OF THE FAD2-1A/1B GENES 审中-公开
标题翻译：通过FAD2-1A / 1B基因的特异性敲除来修饰大豆油组成
公开(公告)号：US20140370558A1
公开(公告)日：2014-12-18
申请号：US14208027
申请日：2014-03-13
申请人： CELLECTIS
发明人： Luc Mathis , Daniel F. Voytas , Feng Zhang , William Haun
IPC分类号： C12N15/01 , C12P7/64
CPC分类号： C12N15/01 , C12N9/0071 , C12N15/8247 , C12P7/6445 , C12Y114/19006
摘要： Materials and methods are provided for making soybean varieties that have altered oil composition as a result of mutations in the FAD2-1A and FAD2-1B genes.
摘要翻译：提供材料和方法用于制造由于FAD2-1A和FAD2-1B基因突变而导致油组成变化的大豆品种。

65. 发明申请

US20140309145A1 HIGH THROUGHPUT METHOD FOR ASSEMBLY AND CLONING POLYNUCLEOTIDES COMPRISING HIGHLY SIMILAR POLYNUCLEOTIDIC MODULES 审中-公开
标题翻译：用于组装和克隆包含高类似多核模块的多核苷酸的高通量方法
公开(公告)号：US20140309145A1
公开(公告)日：2014-10-16
申请号：US14235759
申请日：2012-07-20
申请人： Julien Valton , Alexandre Juillerat , Philippe Duchateau
发明人： Julien Valton , Alexandre Juillerat , Philippe Duchateau
IPC分类号： C12N15/10
CPC分类号： C12N15/1093 , C07K14/195 , C12N15/66 , C12P19/34 , G01N33/6845
摘要： The present invention relates to a method for the assembly and cloning of polynucleotides comprising highly similar polynucleotidic modules, that is highly versatile, does not require intermediate amplification step and can be easily automated for high throughput production of customized polynucleotidic modules.
摘要翻译：本发明涉及用于组装和克隆多核苷酸的方法，所述多核苷酸包含高度相似的多核苷酸模块，其是高通用性的，不需要中间扩增步骤，并且可以容易地自动化以用于定制多核苷酸模块的高通量生产。

66. 发明授权

US08802431B2 Population of multipotent cardiac precursor cells derived from human blastocysts derived stem cells 有权
标题翻译：源自人囊胚来源的干细胞的多能心脏前体细胞群体
公开(公告)号：US08802431B2
公开(公告)日：2014-08-12
申请号：US12308767
申请日：2007-07-13
申请人： Peter Sartipy , Karolina Åkesson , Caroline Améen
发明人： Peter Sartipy , Karolina Åkesson , Caroline Améen
IPC分类号： C12N5/071 , C12N5/00 , C12N5/02
CPC分类号： C12N5/0657 , C12N2500/44 , C12N2506/02 , C12N2533/54
摘要： A novel population of multipotent cardiac precursor (MCP) cells derived from human blastocysts derived stem cells is disclosed, methods for the preparation thereof and use of the cells for in vitro testing. Basement cells derived from hBS cells are also disclosed and method for the preparation of MCP cells from basement cells. The MCP cells have the following characteristics i) at least 1% of the cells exhibit no antigen expression of one or more markers for undifferentiated cell, the marker being selected from the group consisting of SSEA-3, SSEA-4, TRA-1-60, TRA-1-81 and Oct-4, ii) at least 1% of the cells exhibit no protein expression of one or more of a neural marker including nestin or GFAP iii) at least 1% of the cells exhibit protein and/or gene expression of one or more of a mesodermal marker including brachyury, vimentin or desmin iv) at least 1% of the cells exhibit protein and/or gene expression of Flk-1 (KDR). Furthermore, the MCP cells have a characteristic morphology. They grow as clusters of small, round and phase-bright cells; individual cells are 5-20 μm in diameter and each cluster is composed of 2-500 cells. They form clusters of round or elongated shape, that appear as loosely adherent cell clumps that as illustrated in FIG. 2 panel a, b and c. Furthermore, they have a relatively high nucleus-to-cytoplasma ratio, e.g. 1:2-1:64 of the total volume of the cell and/or appear as balloons on a string, as illustrated in FIG. 18, schematic sketch. Moreover, the MCP cells are non-contracting.
摘要翻译：公开了衍生自人囊胚来源的干细胞的多能心脏前体（MCP）细胞的新型群体，其制备方法和细胞用于体外测试。还公开了源自hBS细胞的基底细胞以及从基底细胞制备MCP细胞的方法。 MCP细胞具有以下特征：i）至少1％的细胞对未分化细胞表现出一种或多种标志物的抗原表达，所述标记选自SSEA-3，SSEA-4，TRA-1- 60，TRA-1-81和Oct-4，ii）至少1％的细胞不显示包括巢蛋白或GFAP的神经标记中的一种或多种的蛋白质表达（iii）至少1％的细胞表现出蛋白质和/ 或一个或多个中胚层标志物的基因表达，包括brachyury，波形蛋白或结蛋白iv）至少1％的细胞表现出Flk-1（KDR）的蛋白质和/或基因表达。此外，MCP电池具有特征形态。它们生长成小，圆和相亮细胞的簇; 单个细胞的直径为5-20μm，每个簇由2-500个细胞组成。它们形成圆形或细长形状的簇，其呈现为松散贴附的细胞团，如图1所示。 2面板a，b和c。此外，它们具有相对较高的细胞核 - 细胞质比例，例如 1：2-1：64和/或在气球上显示为气球，如图1所示。 18，原理图草图。此外，MCP细胞是非收缩的。

67. 发明授权

US08715992B2 I-CreI meganuclease variants with modified specificity, method of preparation and uses thereof 有权
标题翻译：具有修饰特异性的I-CreI大范围核酸酶变体，其制备方法及其应用
公开(公告)号：US08715992B2
公开(公告)日：2014-05-06
申请号：US13422902
申请日：2012-03-16
申请人： Philippe Duchateau , Frederic Paques
发明人： Philippe Duchateau , Frederic Paques
IPC分类号： C12N9/00 , C12N9/22 , C12N1/20 , C12N15/00 , C07H21/04
CPC分类号： C12N9/22 , A61K38/00 , A61K48/00
摘要： Method of preparing I-CreI meganuclease variants having a modified cleavage specificity, variants obtainable by said method and their applications either for cleaving new DNA target or for genetic engineering and genome engineering for non-therapeutic purposes. Nucleic acids encoding said variants, expression cassettes comprising said nucleic acids, vectors comprising said expression cassettes, cells or organisms, plants or animals except humans, transformed by said vectors.
摘要翻译：制备具有修饰的切割特异性的I-CreI大范围核酸酶变体的方法，通过所述方法获得的变体及其用于切割新的DNA靶或用于非治疗目的的基因工程和基因工程的应用。编码所述变体的核酸，包含所述核酸的表达盒，包含所述表达盒的载体，细胞或生物，除人以外的植物或动物，由所述载体转化。

68. 发明申请

US20140121115A1 CUSTOM-MADE MEGANUCLEASE AND USE THEREOF 审中-公开
标题翻译：自定义MEGANUCLEASE及其使用
公开(公告)号：US20140121115A1
公开(公告)日：2014-05-01
申请号：US13725798
申请日：2012-12-21
申请人： Sylvain Arnould , Sylvia Bruneau , Jean-Pierre Cabaniols , Patrick Chames , Andre Choulika , Phillipe Duchateau , Jean-Charles Epinat , Agnes Gouble , Emmanuel Lacroix , Frederic Paques , Christophe Perez-Michaut , Julianne Smith , Davie Sourdive
发明人： Sylvain Arnould , Sylvia Bruneau , Jean-Pierre Cabaniols , Patrick Chames , Andre Choulika , Phillipe Duchateau , Jean-Charles Epinat , Agnes Gouble , Emmanuel Lacroix , Frederic Paques , Christophe Perez-Michaut , Julianne Smith , Davie Sourdive
IPC分类号： C12N15/10
CPC分类号： C12N15/907 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/03 , A01K2267/0337 , A61K38/00 , A61K38/1709 , A61K38/465 , A61K48/00 , A61K48/0058 , C07K14/435 , C07K2319/81 , C12N7/00 , C12N9/22 , C12N15/1058 , C12N15/8509 , C12N15/86 , C12N15/90 , C12N2730/10143 , C12N2799/022 , C12N2800/80 , C12N2830/002 , C12N2830/55 , C12N2840/20 , C12N2840/44 , C12Y301/00 , C12Y301/21004
摘要： New rare-cutting endonucleases, also called custom-made meganucleases, which recognize and cleave a specific nucleotide sequence, derived polynucleotide sequences, recombinant vector cell, animal, or plant comprising said polynucleotide sequences, process for producing said rare-cutting endonucleases and any use thereof, more particularly, for genetic engineering, antiviral therapy and gene therapy.
摘要翻译：新的稀释内切核酸酶，也称为定制的大范围核酸酶，其识别和切割特定的核苷酸序列，衍生的多核苷酸序列，包含所述多核苷酸序列的重组载体细胞，动物或植物，用于产生所述稀少内切核酸酶的方法和任何用途更具体地，涉及基因工程，抗病毒治疗和基因治疗。

69. 发明申请

US20130236946A1 MEGANUCLEASE VARIANTS CLEAVING A DNA TARGET SEQUENCE FROM THE MOUSE ROSA26 LOCUS AND USES THEREOF 审中-公开
标题翻译： MEGANUCLEASE变种清除鼠标ROSA26位置的DNA目标序列及其用途
公开(公告)号：US20130236946A1
公开(公告)日：2013-09-12
申请号：US13857411
申请日：2013-04-05
申请人： CELLECTIS
发明人： Agnes GOUBLE
IPC分类号： C12N9/16
CPC分类号： C12N9/16 , A01K2227/105 , C12N9/22 , C12N15/8509 , C12N15/902
摘要： An I-CreI variant, wherein one of the two I-CreI monomers has at least two substitutions, one in each of the two functional subdomains of the LAGLIDADG core domain situated respectively from positions 26 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from the mouse ROSA26 locus. Use of said variant and derived products for the engineering of transgenic mice and recombinant mouse cell lines expressing an heterologous protein of interest.
摘要翻译： I-CreI变体，其中两个I-CreI单体之一具有至少两个取代，LAGLIDADG核心结构域的两个功能亚结构域中的每一个分别位于I-CreI的位置26至40和44至77之间，所述变体能够从小鼠ROSA26基因座切割DNA靶序列。所述变体和衍生产物用于工程化转基因小鼠和表达感兴趣的异源蛋白质的重组小鼠细胞系的用途。

70. 发明申请

US20130059387A1 MEGANUCLEASE VARIANTS CLEAVING A DNA TARGET SEQUENCE FROM THE HPRT GENE AND USES THEREOF 审中-公开
标题翻译：从HPRT基因中清除DNA靶目标序列的MEGANUCLEASE变体及其用途
公开(公告)号：US20130059387A1
公开(公告)日：2013-03-07
申请号：US13553221
申请日：2012-07-19
申请人： Julianne Smith , Sylvestre Grizot , Agnès Gouble
发明人： Julianne Smith , Sylvestre Grizot , Agnès Gouble
IPC分类号： C12N15/90
CPC分类号： C12N9/22
摘要： A method for inducing a site-specific modification in the HPRT gene, for a non-therapeutic purpose, by contacting a DNA target sequence selected from the group consisting of the sequences SEQ ID NO: 1 to 14 thereby cleaving the DNA target with an I-CreI variant or single-chain derivative having at least one substitution in one of the two functional subdomains of the LAGLIDADG (SEQ ID NO: 153) core domain situated from positions 26 to 40 and 44 to 77 of I-CreI.
摘要翻译：通过使选自SEQ ID NO：1至14的序列的DNA靶序列接触，将DNA靶标与I切割，从而在非治疗目的下诱导HPRT基因中的位点特异性修饰的方法 -CreI变体或单链衍生物，其在I-CreI的位置26至40和44至77的LAGLIDADG（SEQ ID NO：153）核心结构域的两个功能亚结构域之一中具有至少一个取代。

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