公开(公告)号：US20240042030A1

公开(公告)日：2024-02-08

申请号：US18361056

申请日：2023-07-28

Applicant: Allogene Therapeutics, Inc.

Inventor： Cesar Adolfo SOMMER ,  Hsin-Yuan CHENG ,  Barbra Johnson SASU

IPC: A61K39/00 ,  C12N15/113 ,  C12N5/0783 ,  A61P35/00

CPC classification number: A61K39/4631 ,  C12N15/113 ,  A61K39/4613 ,  C12N5/0646 ,  A61P35/00 ,  C12N2510/00

Abstract: Provided herein are engineered immune cells and populations thereof for administration to subjects to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of CD48, CD58, ICAM-1, RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) and/or a CD70 binding protein to target tumor cells or other damaged cells in the subject and/or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

公开(公告)号：US20240003056A1

公开(公告)日：2024-01-04

申请号：US18354037

申请日：2023-07-18

Applicant: ALLOGENE THERAPEUTICS, INC.

Inventor： Thomas Charles PERTEL ,  Barbra Johnson SASU

IPC: C40B40/10 ,  C07K16/40 ,  C12N15/63

CPC classification number: C40B40/10 ,  C07K16/40 ,  C12N15/63 ,  C07K2317/565

Abstract: The present disclosure provides, among other things, antibodies for detecting TALENs and/or FokI nucleases in a sample and methods of using the same.

公开(公告)号：US11781248B2

公开(公告)日：2023-10-10

申请号：US16900602

申请日：2020-06-12

Applicant: ALLOGENE THERAPEUTICS, INC.

Inventor： Thomas Charles Pertel ,  Barbra Johnson Sasu

IPC: C40B40/10 ,  C07K16/40 ,  C12N15/63

CPC classification number: C40B40/10 ,  C07K16/40 ,  C12N15/63 ,  C07K2317/565

Abstract: The present disclosure provides, among other things, antibodies for detecting TALENs and/or FokI nucleases in a sample and methods of using the same.

公开(公告)号：US20220281950A1

公开(公告)日：2022-09-08

申请号：US17687193

申请日：2022-03-04

Applicant: Allogene Therapeutics, Inc.

Inventor： Michael Thomas BETHUNE ,  Eric Hans GSCHWENG ,  Thomas John VAN BLARCOM ,  Cesar Adolfo SOMMER

IPC: C07K14/705 ,  C12N15/86 ,  C12N5/0783 ,  A61K35/17 ,  C12N15/11 ,  C12N9/22 ,  C12N15/90 ,  A61P37/06

Abstract: Compositions, methods, expression vectors and engineered immune cells for improving therapies that entail the administration of allogeneic cells to a patient. An immune cell, e.g., a T cell, modified to comprise and/or express FasL protein or a FasL protein derivative from, for example, an expression vector comprising a polynucleotide that encodes FasL protein or a FasL protein derivative, and to express FasR at a reduced level, and further modified to comprise and/or express an antigen binding protein e.g., a chimeric antigen receptor (CAR). An improved method of CAR T-cell therapy that comprises administering the improved immune cells, and compositions that comprise the improved immune cells. Methods of improving persistence of administered cells and reducing activation-induced cell death comprising administering the improved cells.

公开(公告)号：US20220249556A1

公开(公告)日：2022-08-11

申请号：US17587138

申请日：2022-01-28

Applicant: Allogene Therapeutics, Inc.

Inventor： Todd LUMAN ,  Josergio ZARAGOZA ,  Abraham GERMANSDERFER ,  Suma RAO ,  Yajin NI ,  Chupei ZHANG ,  Tom Tao HUANG

IPC: A61K35/17 ,  C12N5/0783 ,  C12N15/86

Abstract: Provided herein are improved methods for transducing immune cells, such as T cells, with retroviral vectors to express exogenous gene products, such as chimeric antigen receptors (CARs). Provided herein are methods that increase transduction efficiency thereby increasing the percentage of immune cells in a population expressing the exogenous gene product. Associated cells, cell populations, compositions and methods of use are also provided.

公开(公告)号：US20220235346A1

公开(公告)日：2022-07-28

申请号：US17716253

申请日：2022-04-08

Applicant: Allogene Therapeutics, Inc.

Inventor： Meritxell GALINDO CASAS ,  Thomas John VAN BLARCOM

IPC: C12N9/64 ,  C12N9/90 ,  A61K38/48 ,  A61K38/52 ,  A61K35/17 ,  C12N5/0783 ,  C12N11/18 ,  A61K31/7088

Abstract: Provided herein are modified caspase-9 polypeptides, and chimeric caspase-9 proteins containing the modified caspase-9 polypeptides. The disclosure further provides polynucleotides encoding these proteins, engineered host cells containing these polynucleotides and proteins, including host cells that co-express a chimeric antigen receptor, and methods of making and using the same.

公开(公告)号：US20220227832A1

公开(公告)日：2022-07-21

申请号：US17557654

申请日：2021-12-21

Applicant: ALLOGENE THERAPEUTICS, INC. ,  PFIZER INC.

Inventor： Shanshan LANG ,  Thomas John VAN BLARCOM ,  Michael Thomas BETHUNE ,  Siler PANOWSKI ,  Nguyen TAN ,  Yi ZHANG ,  Barbra Johnson SASU ,  Zhe LI

IPC: C07K14/725 ,  C07K14/705 ,  C12N15/79 ,  C07K19/00

Abstract: A reversibly gated effector polypeptide e.g. a chimeric antigen receptor (protease-activating CD45-gate CAR) comprising an extracellular CD45 recruiting domain, a protease-cleavable linker, and a polypeptide comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Nucleic acids including vectors and expression vectors that encode the protease-activating CD45-gate CAR and cells including immune cells such as T cells that comprise and express the nucleic acids. Methods of treatment of various conditions including various forms of cancer comprising administering the cells including CAR T cell therapy. In some embodiments, the CD45 gate at least partially inhibits activation of the protease-activating CD45-gate CAR when the protease-activating CD45-gate CAR binds antigen. The inhibition is at least partially diminished, relieved and/or eliminated when the protease-activating CD45-gate CAR is exposed to a protease that can cleave the linker.

公开(公告)号：US20210260118A1

公开(公告)日：2021-08-26

申请号：US17183689

申请日：2021-02-24

Applicant: Allogene Therapeutics, Inc.

Inventor： Regina Junhui LIN ,  Siler PANOWSKI ,  Cesar Adolfo SOMMER ,  Thomas John VAN BLARCOM ,  Barbra Johnson SASU ,  Arun BALAKUMARAN

IPC: A61K35/17 ,  C07K14/715 ,  C07K16/28 ,  C12N15/86 ,  A61P35/00

Abstract: Provided here are engineered immune cells that comprise a constitutively active chimeric cytokine receptor (CACCR) and a B-cell maturation antigen (BCMA) specific chimeric antigen receptor (CAR). Also provided herein are engineered immune cells that comprise one or more nucleic acids e.g. a bicistronic vector such as a viral vector that encode the CACCRs and BCMA CARs and engineered immune cells e.g. engineered autologous or allogeneic T cells that express both CACCRs and BCMA CARs from the nucleic acids. When present on chimeric antigen receptor (CAR)-bearing engineered immune cells, the CACCRs allow for increased immune cell activation, proliferation, persistence, and/or potency. Further provided herein are methods of making and using the engineered immune cells described herein, such as methods of treating a disease or condition by administering at least one appropriate dose of the cells to a patient suffering from the condition.

公开(公告)号：US20210061881A1

公开(公告)日：2021-03-04

申请号：US17005757

申请日：2020-08-28

Applicant: Allogene Therapeutics, Inc.

Inventor： Regina Junhui LIN ,  Siler PANOWSKI ,  Thomas John VAN BLARCOM ,  Shanshan LANG ,  Barbra Johnson SASU

IPC: C07K14/71 ,  C12N15/86 ,  C12N5/0783 ,  A61K35/17

Abstract: Provided herein are chimeric cytokine receptors bearing a binding domain capable of binding a TGF-β ligand or a TGF-β receptor antibody. When present on chimeric antigen receptor (CAR)-bearing immune cells (CAR-T-cells), such receptors allow for increased CAR-T cell expansion, activity and persistence, constitutively and/or through engagement of a TGF-β ligand or a TGF-β receptor antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.

公开(公告)号：US20200317780A1

公开(公告)日：2020-10-08

申请号：US16826102

申请日：2020-03-20

Applicant: Allogene Therapeutics, Inc.

Inventor： Yajin NI ,  Hongxiu NING ,  Janet M. LEE ,  Mark W. LEONARD

IPC: C07K16/28 ,  C12N5/078 ,  C12N15/113

Abstract: Provided herein are improved methods for robust TCR+ cell depletion and production of populations of TCR− cells, which can be beneficial to minimize the GvHD risk in patients receiving allogeneic CAR T cell therapy. Provided herein are methods that increase the efficiency of depleting TCR+ cells from a population of cells in order to significantly reduce any residual levels of TCR+ cells present in cell populations in which expression of endogenous TCR has been reduced or eliminated. Associated kits and cell populations are also provided.