公开(公告)号：US20180044399A1

公开(公告)日：2018-02-15

申请号：US15525906

申请日：2015-11-09

Applicant: RINAT NEUROSCIENCE CORP. ,  CELLECTIS

Inventor： Arvind RAJPAL ,  Shobha Chowdary POTLURI ,  Laurent POIROT ,  Alexandre JUILLERAT ,  Thomas Charles PERTEL ,  Donna Marie STONE ,  Barbra Johnson SASU

IPC: C07K14/705 ,  C07K14/725 ,  A61K35/17 ,  C07K16/28 ,  C12N5/0783

CPC classification number: C07K14/70503 ,  A61K35/17 ,  A61K2039/5156 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70521 ,  C07K14/70578 ,  C07K16/2803 ,  C07K16/3069 ,  C07K2317/622 ,  C07K2317/76 ,  C07K2319/03 ,  C07K2319/70 ,  C07K2319/74 ,  C12N5/0636 ,  C12N2510/00

Abstract: The invention relates to an inhibitory chimeric antigen receptor (N-CAR) comprising an extracellular domain comprising an antigen binding domain, a transmembrane domain, and, an intracellular domain wherein the intracellular domain comprises an Immunoreceptor Tyrosine-based Switch Motif ITSM, wherein said ITSM is a sequence of amino acid TX1YX2X3X4, wherein X1 is an amino acid X2 is an amino acid X3 is an amino acid and X4 is V or

公开(公告)号：US20240318154A1

公开(公告)日：2024-09-26

申请号：US18561938

申请日：2022-05-20

Applicant: CELLECTIS ,  Albert-Ludwigs-Universitat Freiburg

Inventor： Toni CATHOMEN ,  Tatjana CORNU ,  Julia KLERMUND ,  Manuel RHIEL ,  Julia ROSITZKA ,  Philippe DUCHATEAU ,  Alexandre JUILLERAT

IPC: C12N9/22 ,  A61K35/28 ,  C07K14/47 ,  C12N5/0789 ,  C12N15/90

CPC classification number: C12N9/22 ,  A61K35/28 ,  C07K14/4705 ,  C12N5/0647 ,  C12N15/907 ,  C12N2510/00

Abstract: The present invention generally relates to the field of genome engineering (gene editing), and more specifically to gene therapy for the treatment of Severe Combined Immunodeficiency (SCID) related to RAG1. Particularly, the present invention pertains to the treatment of RAG1 deficiency in long-term repopulating hematopoietic stem cells (HSCs). The present invention provides means and methods for genetically modifying HSCs involving gene editing reagents, such as TALE-nucleases, that specifically target a non-functional endogenous RAG1 gene, comprising at least one mutation causing Severe Combined Immunodeficiency (SCID), thereby allowing the restoration of the normal cellular phenotype. The present invention also provides engineered RAG1-edited HSCs comprising an exogenous sequence comprising a nucleic acid sequence encoding a functional RAG1 protein which is integrated in said HSCs' genome into a non-functional RAG1 endogenous locus, resulting in the expression of a functional RAG1 polypeptide. The present invention further provides populations of cells comprising said engineered HSCs, pharmaceutical compositions comprising said engineered HSCs or populations of cells, as well as their use in gene therapy for the treatment of Severe Combined Immunodeficiency (SCID) related to RAG1.

公开(公告)号：US20200237823A1

公开(公告)日：2020-07-30

申请号：US16755082

申请日：2018-03-09

Applicant: CELLECTIS

Inventor： Brian BUSSER ,  Philippe DUCHATEAU ,  Alexandre JUILLERAT ,  Laurent POIROT ,  Julien VALTON

IPC: A61K35/17 ,  C07K16/28 ,  C07K16/30

Abstract: The invention pertains to the field of adaptive cell immunotherapy. It provides with the genetic insertion of exogenous coding sequence(s) that help the immune cells to direct their immune response against infected or malignant cells. These exogenous coding sequences are more particularly inserted under the transcriptional control of endogenous gene promoters that are sensitive to immune cells activation. Such method allows the production of safer immune primary cells of higher therapeutic potential.

公开(公告)号：US20190338015A1

公开(公告)日：2019-11-07

申请号：US16342139

申请日：2017-10-19

Applicant: CELLECTIS

Inventor： Alexandre JUILLERAT ,  Philippe DUCHATEAU ,  Laurent POIROT ,  Murielle DERRIEN ,  Donna Marie STONE ,  Javier Fernando CHAPARRO RIGGERS

IPC: C07K14/705 ,  C12N5/0783 ,  A61K35/17 ,  C07K14/725 ,  C07K16/28

Abstract: The invention relates to cell death inducing chimeric antigen receptors (D-CAR). In particular, the present invention relates to cell death inducing chimeric antigen receptors which comprise at least one death domain in their endodomain, including cell death inducing chimeric antigen receptors comprising within their death domains modifications which attenuate the self-association and/or binding to pro-apoptotic or pro-necrotic adaptor proteins, such as FADD or TRADD. Moreover, the present invention relates to an engineered immune cell expressing at its surface a cell death inducing CAR of the present invention and, optionally, an activating chimeric antigen receptor, wherein the extracellular ligand-binding domains of the cell death inducing CAR and the activating CAR bind to different antigens. The engineered immune cell may furthermore comprise at least one edited (e.g., inactivated) gene selected from TCR genes, immune check point genes, genes involved in drug resistance, and combinations thereof.

公开(公告)号：US20180000914A1

公开(公告)日：2018-01-04

申请号：US15546604

申请日：2016-01-25

Applicant: Cellectis

Inventor： Julien VALTON ,  Philippe DUCHATEAU ,  Alexandre JUILLERAT ,  Arvind RAJPAL ,  Barbra Johnson SASU ,  Julianne SMITH

IPC: A61K39/00 ,  C07K14/725 ,  C12N5/0783 ,  C07K14/735 ,  A61K39/395 ,  C07K16/28 ,  C07K14/705

CPC classification number: C07K16/2866 ,  A61K35/17 ,  A61K39/0011 ,  A61K39/39558 ,  A61K2039/505 ,  A61K2039/5156 ,  A61K2039/5158 ,  A61K2039/6056 ,  A61K2039/64 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70535 ,  C07K14/70578 ,  C07K16/2803 ,  C07K16/2887 ,  C07K16/3061 ,  C07K2317/24 ,  C07K2317/53 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/03 ,  C12N5/0093 ,  C12N5/0636 ,  C12N5/0638 ,  C12N2510/00 ,  G01N15/1031 ,  G01N15/14 ,  G01N2015/008 ,  G01N2015/1006 ,  G01N2015/1081 ,  G01N2015/149

Abstract: The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from an anti-HSP70 monoclonal antibody, conferring specific immunity against HSP70 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating in particular leukemia.

公开(公告)号：US20230212613A1

公开(公告)日：2023-07-06

申请号：US17996733

申请日：2021-05-06

Applicant: CELLECTIS S.A.

Inventor： Ming YANG ,  Alexandre JUILLERAT ,  Philippe DUCHATEAU ,  Patrick HONG

IPC: C12N15/90 ,  C07K14/725 ,  C12N9/22 ,  C12N5/0783

CPC classification number: C12N15/907 ,  C07K14/7051 ,  C12N9/22 ,  C12N5/0636 ,  C12N2310/20

Abstract: The present disclosure provides methods for targeted insertion of an exogenous sequence at a genomic locus in a cell, wherein said insertion is induced by a sequence-specific endonuclease that has cleavage activity at said locus, at least 5 hours before the introduction into said cell of a DNA template comprising said exogenous sequence.

公开(公告)号：US20180002435A1

公开(公告)日：2018-01-04

申请号：US15546630

申请日：2016-01-25

Applicant: Cellectis ,  RINAT NEUROSCIENCE CORPORATION

Inventor： Barbara Johnson SASU ,  Arvind RAJPAL ,  Philippe DUCHATEAU ,  Alexandre JUILLERAT ,  Julien VALTON

IPC: C07K16/28 ,  C07K14/705 ,  G01N15/10 ,  G01N15/14 ,  C12N5/0783 ,  C07K14/725 ,  G01N15/00

CPC classification number: C07K16/2866 ,  A61K35/17 ,  A61K39/0011 ,  A61K39/39558 ,  A61K2039/505 ,  A61K2039/5156 ,  A61K2039/5158 ,  A61K2039/6056 ,  A61K2039/64 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70535 ,  C07K14/70578 ,  C07K16/2803 ,  C07K16/2887 ,  C07K16/3061 ,  C07K2317/24 ,  C07K2317/53 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/03 ,  C12N5/0093 ,  C12N5/0636 ,  C12N5/0638 ,  C12N2510/00 ,  G01N15/1031 ,  G01N15/14 ,  G01N2015/008 ,  G01N2015/1006 ,  G01N2015/1081 ,  G01N2015/149

Abstract: A polypeptide encoding a chimeric antigen receptor (CAR) comprising at least one extracellular binding domain that comprises a scFv formed by at least a VH chain and a VL chain specific to an antigen, wherein said extracellular binding domain comprises at least one mAb-specific epitope.

公开(公告)号：US20180002427A1

公开(公告)日：2018-01-04

申请号：US15546619

申请日：2016-01-25

Applicant: CELLECTIS

Inventor： Julianne SMITH ,  Julien VALTON ,  Philippe DUCHATEAU ,  Alexandre JUILLERAT ,  Arvind RAJPAL ,  Barbra Johnson SASU

IPC: C07K16/28 ,  C12N5/00 ,  C07K16/30 ,  A61K39/00 ,  A61K35/17 ,  C12N5/0783 ,  C07K14/725

CPC classification number: C07K16/2866 ,  A61K35/17 ,  A61K39/0011 ,  A61K39/39558 ,  A61K2039/505 ,  A61K2039/5156 ,  A61K2039/5158 ,  A61K2039/6056 ,  A61K2039/64 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70535 ,  C07K14/70578 ,  C07K16/2803 ,  C07K16/2887 ,  C07K16/3061 ,  C07K2317/24 ,  C07K2317/53 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/03 ,  C12N5/0093 ,  C12N5/0636 ,  C12N5/0638 ,  C12N2510/00 ,  G01N15/1031 ,  G01N15/14 ,  G01N2015/008 ,  G01N2015/1006 ,  G01N2015/1081 ,  G01N2015/149

Abstract: The present invention relates to a new generation of chimeric antigen receptors (CAR) referred to as multi-chain CARs, which are made specific to the antigen CLL1. Such CARs aim to redirect immune cell specificity and reactivity toward malignant cells expressing the tumor antigen CLL1. The alpha, beta and gamma polypeptides composing these CARs are designed to assemble in juxtamembrane position, which forms flexible architecture closer to natural receptors, that confers optimal signal transduction. The invention encompasses the polynucleotides, vectors encoding said multi-chain CAR and the isolated cells expressing them at their surface, in particularly for their use in immunotherapy. The invention opens the way to efficient adoptive immunotherapy strategies for treating cancer, especially leukemia.

公开(公告)号：US20160304893A1

公开(公告)日：2016-10-20

申请号：US15103773

申请日：2014-12-12

Applicant: CELLECTIS

Inventor： Fayza DABOUSSI ,  Marine BEURDELEY ,  Alexandre JUILLERAT

IPC: C12N15/82 ,  C12N9/22

CPC classification number: C12N15/8213 ,  C12N9/22

Abstract: The present invention relates to a method of genome engineering in microalgae using the Cas9/CRISPR system. In particular, the present invention relates to methods of delivering RNA guides via cell penetrating peptides in microalgae, preferably in stable integrated Cas9 microalgae. The present invention also relates to kits and isolated cells comprising Cas9, split Cas9 or guide RNA and Cas9-fused cell-penetrating peptides. The present invention also relates to isolated cells obtained by the methods of the invention.

Abstract translation: 本发明涉及使用Cas9 / CRISPR系统的微藻中的基因组工程方法。 特别地，本发明涉及通过微藻中的细胞穿透肽递送RNA引导物的方法，优选在稳定的综合Cas9微藻中。 本发明还涉及包含Cas9，裂解Cas9或引导RNA和Cas9融合的细胞穿透肽的试剂盒和分离的细胞。 本发明还涉及通过本发明的方法获得的分离的细胞。

公开(公告)号：US20160273002A1

公开(公告)日：2016-09-22

申请号：US15031996

申请日：2014-10-24

Applicant: CELLECTIS

Inventor： Philippe DUCHATEAU ,  Alexandre JUILLERAT

IPC: C12N15/90 ,  C07K14/195 ,  C12N9/22

CPC classification number: C12N15/907 ,  A61K38/00 ,  A61K48/00 ,  A61K48/005 ,  C07K14/195 ,  C07K2319/80 ,  C12N9/22 ,  C12Y301/00 ,  C12Y301/21004

Abstract: The present invention is in the field of genetic editing tools and methods of genetic engineering. It relates to the engineering of rare-cutting endonucleases designed to contract highly repetitive motives in chromosomes, which are at the origin of certain genetic diseases, in particular the so-called “triplet repeat diseases”, such as the Huntington disease. The invention encompasses the method for contracting the repetitive motives, the rare-cutting endonucleases for use to contract repetitive motives in a gene subjected to repeat disorder, the polynucleotides and vectors encoding thereof as well as the resulting pharmaceutical compositions.

Abstract translation: 本发明在遗传编辑工具和基因工程方法领域。 它涉及设计用于在染色体中收缩高度重复动机的稀有内切核酸酶的工程，这些动机是某些遗传疾病的起源，特别是所谓的“三重重复疾病”，如亨廷顿疾病。 本发明包括用于收缩重复动机的方法，用于在重复病症的基因中重复动作的稀有内切核酸酶，编码它们的多核苷酸和载体以及所得药物组合物。