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1. 发明申请

WO2022003158A1 METHOD FOR DETERMINING POTENCY OF CHIMERIC ANTIGEN RECEPTOR EXPRESSING IMMUNE CELLS 审中-公开
公开(公告)号：WO2022003158A1
公开(公告)日：2022-01-06
申请号：PCT/EP2021/068335
申请日：2021-07-02
申请人： CELLECTIS S.A.
发明人： NAJ, Xenia , PETIT, Anne-Sophie , GALETTO, Roman , CABANIOLS, Jean-Pierre
IPC分类号： G01N33/50 , C07K16/30 , A61K2039/5156 , C07K14/7051 , C07K16/2803 , C07K16/2851 , C07K16/2866 , C07K16/40 , C07K2317/622 , C07K2319/03 , G01N33/505
摘要： The invention relates to a new potency assay for characterizing the quality and activity of an immune cell expressing a chimeric antigen receptor, the kit to carry out this assay and uses thereof.

2. 发明申请

WO2015136001A1 METHOD FOR GENERATING T-CELLS COMPATIBLE FOR ALLOGENIC TRANSPLANTATION 审中-公开
标题翻译：用于产生用于同种异体移植的T细胞的方法
公开(公告)号：WO2015136001A1
公开(公告)日：2015-09-17
申请号：PCT/EP2015/055097
申请日：2015-03-11
申请人： CELLECTIS
发明人： POIROT, Laurent , SOURDIVE, David , DUCHATEAU, Philippe , CABANIOLS, Jean-Pierre
IPC分类号： C07K14/74 , C12N5/0783
CPC分类号： C12N15/85 , C07K14/70503 , C07K14/70539 , C07K2317/24 , C07K2317/622 , C12N5/0636 , C12N15/1138 , C12N15/907
摘要： The present invention pertains to engineered T-cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered T-cells of the invention are characterized in that the expression of beta 2-microglobulin (B2M) and/or class I I major histocompatibility complex transactivator (CIITA) is inhibited, e.g., by using rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding B2M and/or CIITA, or by using nucleic acid molecules which inhibit the expression of B2M and/or CIITA. In order to further render the T-cell non-alloreactive, at least one gene encoding a component of the T-cell receptor is inactivated, e.g., by using a rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding said TCR component. In addition, expression of immunosuppressive polypeptide can be performed on those modified T-cells in order to prolong the survival of these modified T cells in host organism. Such modified T-cell is particularly suitable for allogeneic transplantations, especially because it reduces both the risk of rejection by the host's immune system and the risk of developing graft versus host disease. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer, infections and auto-immune diseases.
摘要翻译：本发明涉及工程化T细胞，其制备方法及其作为药物的用途，特别是用于免疫治疗。本发明的工程化T细胞的特征在于，β2微球蛋白（B2M）和/或II类主要组织相容性复合物反式激活因子（CIITA）的表达受到抑制，例如通过使用能够选择性失活的稀有内切核酸酶 DNA切割编码B2M和/或CIITA的基因，或通过使用抑制B2M和/或CIITA表达的核酸分子。为了进一步使T细胞非同种异体反应，至少一种编码T细胞受体成分的基因被灭活，例如通过使用能够通过DNA切割选择性失活的稀有切割内切核酸酶，编码所述TCR的基因零件。此外，可以对这些修饰的T细胞进行免疫抑制多肽的表达，以延长宿主生物体中这些修饰的T细胞的存活。这种修饰的T细胞特别适用于同种异体移植，特别是因为它降低宿主免疫系统的排斥风险和发生移植物抗宿主病的风险。本发明开启了使用T细胞治疗癌症，感染和自身免疫疾病的标准和负担得起的过继免疫治疗策略的方法。

3. 发明申请

WO2011101811A2 IMPROVED MEGANUCLEASE RECOMBINATION SYSTEM 审中-公开
标题翻译：改进的大分子核酸酶重组系统
公开(公告)号：WO2011101811A2
公开(公告)日：2011-08-25
申请号：PCT/IB2011/050682
申请日：2011-02-18
申请人： CELLECTIS , DELENDA, Christophe , CABANIOLS, Jean-Pierre
发明人： DELENDA, Christophe , CABANIOLS, Jean-Pierre
IPC分类号： C12N9/22 , C12N15/90
CPC分类号： C12N9/22 , C12N15/907
摘要： The invention relates to a set of genetic constructs which comprises at least a first recombinogenic construct (i) with at least two portions homologous to the genomic regions preceding and following the DNA target site of a site specific endonuclease and also comprising both a negative selection and positive selection mark interposed with the homologous portions as well as a region into which a sequence of interest can be cloned adjacent to the positive selection marker; and a second construct (ii, iii or iv) comprising the meganuclease. The present invention also relates to a kit comprising these constructs and methods to use this set of constructs to introduce into the genome of a target cell, tissue or organism a sequence of interest.
摘要翻译：本发明涉及一组遗传构建体，其包含至少第一种重组基因构建体（i）和至少两个与位点特异性内切核酸酶的DNA靶位点之前和之后的基因组区域同源的部分并且还包括插入同源部分的负选择和正选择标记以及与正选择标记相邻的可以克隆感兴趣序列的区域; 和包含大范围核酸酶的第二构建体（ii，iii或iv）。本发明还涉及包含这些构建体的试剂盒以及使用该组构建体将靶序列引入靶细胞，组织或生物的基因组的方法。

4. 发明申请

WO2011021166A1 MEGANUCLEASE VARIANTS CLEAVING A DNA TARGET SEQUENCE FROM THE HUMAN LYSOSOMAL ACID ALPHA-GLUCOSIDASE GENE AND USES THEREOF 审中-公开
标题翻译：从人类LYSOSOMAL ACID ALPHA-GLUCOSIDASE基因中清除DNA靶标序列的MEGANUCLEASE变体及其用途
公开(公告)号：WO2011021166A1
公开(公告)日：2011-02-24
申请号：PCT/IB2010/053751
申请日：2010-08-19
申请人： CELLECTIS , CABANIOLS, Jean-Pierre
发明人： CABANIOLS, Jean-Pierre
IPC分类号： A61K38/46 , C12N9/22 , C12N15/90
CPC分类号： C12N9/22 , A61K38/00 , A61K48/00 , C07K2319/09 , C07K2319/20 , C12N15/90
摘要： An l- Cre l variant, wherein one of the two l- Cre l 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 l- Cre l, said variant being able to cleave a DNA target sequence from the human lysosomal acid α-glucosidase gene. Use of said variant and derived products for the prevention and the treatment of pathological conditions caused by a mutation in the human lysosomal acid α-glucosidase gene (Pompe's disease).
摘要翻译： 1-CreI变体，其中两个I-Cre1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-Cre1的位置26至40和44至77之间，所述变体能够从人溶酶体酸α-葡糖苷酶基因切割DNA靶序列。所述变体和衍生产物用于预防和治疗由人溶酶体酸α-葡糖苷酶基因（庞培氏病）突变引起的病理状况。

5. 发明申请

WO2011021062A1 MEGANUCLEASE VARIANTS CLEAVING A DNA TARGET SEQUENCE FROM THE HUMAN LYSOSOMAL ACID ALPHA-GLUCOSIDASE GENE AND USES THEREOF 审中-公开
标题翻译：从人类LYSOSOMAL ACID ALPHA-GLUCOSIDASE基因中清除DNA靶标序列的MEGANUCLEASE变体及其用途
公开(公告)号：WO2011021062A1
公开(公告)日：2011-02-24
申请号：PCT/IB2009/006832
申请日：2009-08-21
申请人： CELLECTIS , CABANIOLS, Jean-Pierre
发明人： CABANIOLS, Jean-Pierre
IPC分类号： A61K38/46 , C12N9/22 , C12N15/90
CPC分类号： C12N9/22 , A61K38/00 , A61K48/00 , C07K2319/09 , C07K2319/20 , C12N15/90
摘要： An I-Crel 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 l-Crel, said variant being able to cleave a DNA target sequence from the human lysosomal acid α-glucosidase gene. Use of said variant and derived products for the prevention and the treatment of pathological conditions caused by a mutation in the human lysosomal acid α-glucosidase gene (Pompe's disease).
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，所述变体能够从人溶酶体酸α-葡糖苷酶基因切割DNA靶序列。所述变体和衍生产物用于预防和治疗由人溶酶体酸α-葡糖苷酶基因（庞培氏病）突变引起的病理状况。

6. 发明申请

WO2018007263A1 SEQUENTIAL GENE EDITING IN PRIMARY IMMUNE CELLS 审中-公开
标题翻译：一级免疫细胞的序列基因编辑
公开(公告)号：WO2018007263A1
公开(公告)日：2018-01-11
申请号：PCT/EP2017/066355
申请日：2017-06-30
申请人： CELLECTIS
发明人： CABANIOLS, Jean-Pierre , EPINAT, Jean-Charles , DUCHATEAU, Philippe
IPC分类号： C07K14/725 , C12N5/0783 , C12N9/22 , C12N15/63
摘要： The invention pertains to the field of adaptive cell immunotherapy. It aims at reducing the occurrence of translocations and cell deaths when several specific endonuclease reagents are used altogether to genetically modify primary immune cells at different genetic loci. The method of the invention allows to yield safer immune primary cells harboring several genetic modifications, such as triple or quadruple gene inactivated cells, from populations or sub-populations of cells originating from a single donor or patient,for their subsequent use in therapeutic treatments.
摘要翻译：本发明涉及适应性细胞免疫疗法领域。它旨在减少易位和细胞死亡的发生，当几种特定的内切核酸酶试剂一起用于遗传修饰不同遗传基因座上的原代免疫细胞时。本发明的方法允许从源自单个供体或患者的细胞群体或亚群体产生带有几种遗传修饰的更安全的免疫原代细胞，例如三重或四重基因失活细胞，用于随后用于治疗性处理。

7. 发明申请

WO2016142532A1 METHODS FOR ENGINEERING ALLOGENEIC T CELL TO INCREASE THEIR PERSISTENCE AND/OR ENGRAFTMENT INTO PATIENTS 审中-公开
标题翻译：用于工程化全细胞培养方法以将其持续和/或成熟进入患者
公开(公告)号：WO2016142532A1
公开(公告)日：2016-09-15
申请号：PCT/EP2016/055332
申请日：2016-03-11
申请人： CELLECTIS
发明人： DUCHATEAU, Philippe , CABANIOLS, Jean-Pierre , VALTON, Julien , POIROT, Laurent
IPC分类号： C07K14/74 , C12N5/0783 , C12N15/85
CPC分类号： C12N5/0006 , A01K2207/12 , A61K35/17 , A61K2039/5156 , A61K2039/5158 , C12N5/0638 , C12N2501/48 , C12N2501/51 , C12N2501/599 , C12N2510/00
摘要： The present invention relates to methods for developing engineered immune cells such as T-cells for immunotherapy that have a higher potential of persistence and/or engraftment in host organism. IN particular, this method involves an inactivation of at least one gene involved in self/non self recognition, combined with a step of contact with at least one non-endogenous immunosuppressive polypeptide. The invention allows the possibility for a standard and affordable adoptive immunotherapy, whereby the risk of GvH is reduced.
摘要翻译：本发明涉及用于开发工程化免疫细胞的方法，例如用于免疫治疗的T细胞，其在宿主生物体中具有更高的持久性和/或移植潜力。特别地，该方法包括与自身/非自我认知相关的至少一种基因的失活，以及与至少一种非内源免疫抑制性多肽接触的步骤。本发明允许标准和负担得起的过继免疫治疗的可能性，从而降低GvH的风险。

8. 发明申请

WO2004067736A2 CUSTOM-MADE MEGANUCLEASE AND USE THEREOF 审中-公开
标题翻译：定制的大核糖核酸酶及其用途
公开(公告)号：WO2004067736A2
公开(公告)日：2004-08-12
申请号：PCT/IB2004/000827
申请日：2004-01-28
申请人： CELLECTIS , ARNOULD, Sylvain , BRUNEAU, Sylvia , CABANIOLS, Jean-Pierre , CHAMES, Patrick , CHOULIKA, André , DUCHATEAU, Philippe , EPINAT, Jean-Charles , GOUBLE, Agnès , LACROIX, Emmanuel , PAQUES, Frédéric , PEREZ-MICHAUT, Christophe , SMITH, Julianne , SOURDIVE, David
发明人： ARNOULD, Sylvain , BRUNEAU, Sylvia , CABANIOLS, Jean-Pierre , CHAMES, Patrick , CHOULIKA, André , DUCHATEAU, Philippe , EPINAT, Jean-Charles , GOUBLE, Agnès , LACROIX, Emmanuel , PAQUES, Frédéric , PEREZ-MICHAUT, Christophe , SMITH, Julianne , SOURDIVE, David
IPC分类号： C12N9/22
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：新的罕见切割核酸内切酶，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，重组载体细胞，动物或包含所述多核苷酸序列的植物，产生所述稀有切割内切核酸酶及其任何用途，更具体地，用于基因工程，抗病毒疗法和基因疗法。

9. 发明申请

WO2011101696A1 IMPROVED MEGANUCLEASE RECOMBINATION SYSTEM 审中-公开
标题翻译：改进的MEGANUCLEASE重组系统
公开(公告)号：WO2011101696A1
公开(公告)日：2011-08-25
申请号：PCT/IB2010/000546
申请日：2010-02-18
申请人： CELLECTIS , DELENDA, Christophe , CABANIOLS, Jean-Pierre
发明人： DELENDA, Christophe , CABANIOLS, Jean-Pierre
IPC分类号： C12N9/22 , C12N15/90
CPC分类号： C12N9/22 , C12N15/907
摘要： The invention relates to a set of genetic constructs which comprises at least a first recombinogenic construct (i) with at least two portions homologous to the genomic regions preceding and following the DNA target site of a meganuclease and also comprising both a negative selection and positive selection mark interposed with the homologous portions as well as a region into which a sequence of interest can be cloned adjacent to the positive selection marker; and a second construct (ii, iii or iv) comprising the meganuclease. The present invention also relates to a kit comprising these constructs and methods to use this set of constructs to introduce into the genome of a target cell, tissue or organism a sequence of interest.
摘要翻译：本发明涉及一组基因构建体，其包含至少第一重组构建体（i），其具有与大范围核酸酶的DNA靶位点之前和之后的基因组区域同源的至少两个部分，并且还包括阴性选择和阳性选择标记有同源部分以及可以克隆与阳性选择标记相邻的感兴趣序列的区域; 和包含大范围核酸酶的第二构建体（ii，iii或iv）。本发明还涉及一种试剂盒，其包含这些构建体和使用该组构建体将靶细胞，组织或生物体的基因组引入目的序列的方法。

10. 发明申请

WO2010046786A1 MEGANUCLEASE RECOMBINATION SYSTEM 审中-公开
标题翻译： MEGANUCLEASE重组系统
公开(公告)号：WO2010046786A1
公开(公告)日：2010-04-29
申请号：PCT/IB2009/007526
申请日：2009-10-23
申请人： CELLECTIS , CABANIOLS, Jean-Pierre , CHOULIKA, André , DELENDA, Christophe
发明人： CABANIOLS, Jean-Pierre , CHOULIKA, André , DELENDA, Christophe
IPC分类号： C12N15/85 , C12N15/90
CPC分类号： C12N15/85 , C12N15/902
摘要： The invention relates to a set of genetic constructs which allow the efficient and reproducible introduction of a specific nucleotide sequence at a fixed position in the genome by generating a double strand break at a specific position in the genome using a meganuclease and so stimulating a homologous recombination event at this locus between the genomic site and a transfected donor sequence. The present invention also relates to methods using these constructs and to these materials in the form of a kit.
摘要翻译：本发明涉及一组基因构建体，其允许通过使用大范围核酸酶在基因组中的特定位置处产生双链断裂并且因此刺激同源重组而在基因组中的固定位置有效且可重复地引入特定核苷酸序列在该基因座位点和转染供体序列之间的事件。本发明还涉及以试剂盒形式使用这些构建体和这些材料的方法。

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