公开(公告)号：US20170296623A1

公开(公告)日：2017-10-19

申请号：US15532430

申请日：2015-12-17

Applicant: CELLECTIS

Inventor： Alexandre JUILLERAT ,  Philippe DUCHATEAU ,  Laurent POIROT

IPC: A61K38/17 ,  C07K14/47 ,  C07K14/705 ,  C07K14/525 ,  A61K38/00 ,  C07K14/00

CPC classification number: A61K38/17 ,  A61K35/17 ,  A61K38/00 ,  A61K39/395 ,  A61K2039/505 ,  A61K2039/507 ,  C07K14/00 ,  C07K14/4748 ,  C07K14/525 ,  C07K14/70596 ,  C07K16/2878 ,  C07K16/2887 ,  C07K16/3069 ,  C07K2319/00

Abstract: The invention relates to negative T-cell signal inducing chimeric antigen receptor (N-CAR or i-CAR) and to T-cells comprising such N-CAR as well as a positive T-cell signal inducing CAR (P-CAR) as well as their use in therapy.

公开(公告)号：US20170292118A1

公开(公告)日：2017-10-12

申请号：US15517708

申请日：2015-10-07

Applicant: CELLECTIS

Inventor： Philippe DUCHATEAU ,  Alexandre JUILLERAT ,  Laurent POIROT

IPC: C12N5/16 ,  C12N5/078 ,  C12N15/87 ,  C07K14/725 ,  C12N15/02 ,  C12N5/07 ,  C07K14/705

CPC classification number: C12N5/163 ,  C07K14/705 ,  C07K14/7051 ,  C07K2317/622 ,  C07K2319/01 ,  C07K2319/03 ,  C07K2319/70 ,  C07K2319/74 ,  C12N5/06 ,  C12N5/0634 ,  C12N5/0636 ,  C12N5/10 ,  C12N15/02 ,  C12N15/87

Abstract: The present invention relates to a method to modulate the level of activation of an engineered immune cell (such as a Chimeric Antigen Receptor T-cell) for immunotherapy. The present invention also relates to cells obtained by the present method, preferably comprising said modulable/tunable chimeric antigen receptors for use in therapeutic or prophylactic treatment.

公开(公告)号：US20170016025A1

公开(公告)日：2017-01-19

申请号：US15123974

申请日：2015-03-11

Applicant: CELLECTIS

Inventor： Laurent POIROT ,  David SOURDIVE ,  Philippe DUCHATEAU ,  Jean-Pierre CABANIOLS

IPC: C12N15/85 ,  C07K14/74 ,  C07K14/705 ,  C12N15/90 ,  C12N15/113

CPC classification number: C12N15/85 ,  C07K14/70503 ,  C07K14/70539 ,  C07K2317/24 ,  C07K2317/622 ,  C12N5/0636 ,  C12N15/1138 ,  C12N15/907

Abstract: 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 II 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.

Abstract translation: 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来编码所述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。

公开(公告)号：US20160361359A1

公开(公告)日：2016-12-15

申请号：US15037988

申请日：2014-11-21

Applicant: CELLECTIS

Inventor： Julien VALTON ,  Philippe DUCHATEAU ,  David SOURDIVE

IPC: A61K35/17 ,  C12N5/0783 ,  A61K31/7076

Abstract: The present invention relates to the use of “off-the-shelf” allogeneic therapeutic cells for immunotherapy in conjunction with chemotherapy to treat patients with cancer. In particular, the inventors develop a method of engineering allogeneic T-cell resistant to chemotherapeutic agents. The therapeutic benefits afforded by this strategy should be enhanced by the synergistic effects between chemotherapy and immunotherapy. In particular, the present invention relates to a method for modifying T-cells by inactivating at least one gene encoding T-cell receptor component and by modifying said T-cells to confer drug resistance. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer.

Abstract translation: 本发明涉及“现成”同种异体治疗性细胞用于免疫治疗与化疗联合治疗癌症患者的用途。 特别地，本发明人开发了一种对化疗药物耐药的同种异体T细胞的方法。 通过化学疗法和免疫治疗之间的协同效应，可以提高该策略提供的治疗效果。 特别地，本发明涉及通过使至少一种编码T细胞受体成分的基因失活并通过修饰所述T细胞以赋予耐药性来修饰T细胞的方法。 本发明开启了治疗癌症的标准和负担得起的过继免疫治疗策略的方法。

公开(公告)号：US20160355875A1

公开(公告)日：2016-12-08

申请号：US15028644

申请日：2014-10-10

Applicant: CELLECTIS

Inventor： Julien VALTON ,  Alexandre JUILLERAT ,  Fayza DABOUSSI ,  Marine BEURDELEY ,  Claudia BERTONATI ,  Philippe DUCHATEAU

IPC: C12Q1/68 ,  G01N33/53

CPC classification number: C12Q1/6816 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/6841 ,  G01N33/5308 ,  C12Q2522/101 ,  C12Q2565/531

Abstract: The present invention relates to a method for the detection of a specific nucleic acid. Specifically, the invention provides a method and kits for detecting the presence of a specific nucleic acid using engineered DNA-binding domains such as Transcription Activator Like-Effector (TALE) domain or modular base-per-base binding domains (MBBBD). The method of the invention is particularly useful for in vitro diagnostic application.

Abstract translation: 本发明涉及用于检测特定核酸的方法。 具体地，本发明提供了使用工程化的DNA结合结构域如转录激活子效应（TALE）结构域或模块化碱基结合结构域（MBBBD）来检测特异性核酸的存在的方法和试剂盒。 本发明的方法对于体外诊断应用特别有用。

公开(公告)号：US20160138047A1

公开(公告)日：2016-05-19

申请号：US14898148

申请日：2014-06-13

Applicant: CELLECTIS

Inventor： Philippe DUCHATEAU ,  Sylvain ARNOULD ,  Julianne SMITH

IPC: C12N15/90 ,  C12N15/86 ,  C12N7/00 ,  C12N9/22 ,  C07K14/00

CPC classification number: C12N15/86 ,  C07K14/00 ,  C07K2319/80 ,  C12N7/00 ,  C12N9/22 ,  C12N2740/15043 ,  C12Y301/21004

Abstract: The present invention is in the field of the gene editing molecular tools. The present invention relates to rewritten nucleic acid sequences encoding repeated DNA recognition motifs of TALE (Transcription Activator-Like Effector) proteins. These nucleic acid sequences allow assembly and cloning of TALE repeats in any type of vectors, especially viral vectors. The invention thereby contributes to improving gene targeting in cells using TALE derived proteins, in particular for genetic regulation or modification. The present invention is particularly drawn to virus mediated transformation methods, by providing vectors, compositions and kits including said new nucleic acid sequences.

Abstract translation: 本发明是在基因编辑领域的分子工具。 本发明涉及编码TALE（转录激活子样效应物）蛋白的重复DNA识别基序的重写核酸序列。 这些核酸序列允许在任何类型的载体，特别是病毒载体中组装和克隆TALE重复。 因此，本发明有助于使用TALE衍生的蛋白质改善细胞中的基因靶向，特别是用于遗传调控或修饰。 通过提供载体，组合物和试剂盒，包括所述新的核酸序列，本发明特别地涉及病毒介导的转化方法。

公开(公告)号：US20160122774A1

公开(公告)日：2016-05-05

申请号：US14892743

申请日：2014-05-28

Applicant: CELLECTIS

Inventor： Philippe DUCHATEAU ,  Claudia BERTONATI

IPC: C12N15/82 ,  C12N15/90

CPC classification number: C12N15/8213 ,  C12N15/10 ,  C12N15/907 ,  C12Q1/683 ,  C12Q2521/307

Abstract: The present invention is in the field of a method for genome engineering based on the type II CRISPR system, particularly a method for improving specificity and reducing potential off-site. The method is based on the use of nickase architectures of Cas9 and single or multiple crRNA(s) harboring two different targets lowering the risk of producing off-site cleavage. The present invention also relates to polypeptides, polynucleotides, vectors, compositions, therapeutic applications related to the method described here.

Abstract translation: 本发明在基于II型CRISPR系统的基因组工程方法的领域中，特别是一种提高特异性并降低非局部潜在能力的方法。 该方法基于使用Cas9的切口结构和含有两个不同靶标的单个或多个crRNA，其降低产生场外切割的风险。 本发明还涉及与这里描述的方法相关的多肽，多核苷酸，载体，组合物，治疗应用。