公开(公告)号：US20230348862A1

公开(公告)日：2023-11-02

申请号：US18127936

申请日：2023-03-29

Applicant: The Regents of the University of California

Inventor： Sonja Schrepfer ,  Tobias Deuse

IPC: C12N15/113 ,  C12N15/52 ,  C12N15/85 ,  C12N5/074

CPC classification number: C12N5/0696 ,  C12N15/1138 ,  C12N15/52 ,  C12N15/85 ,  C12N2310/20 ,  C12N2501/599 ,  C12N2840/005 ,  C12N2840/007 ,  C12Y207/01021 ,  C12Y305/04001

Abstract: The invention provides pluripotent cells that are used therapeutically for regenerating tissues but avoid rejection by subjects that receive them. In particular, the invention provides hypo-immunogenic pluripotent cells that avoid host immune rejection. The cells lack major immune antigens that trigger immune responses and are engineered to avoid phagocytic endocytosis. The invention further provides universally acceptable “off-the-shelf” pluripotent cells and derivatives thereof for generating or regenerating specific tissues and organs.

公开(公告)号：US20220213434A1

公开(公告)日：2022-07-07

申请号：US17607841

申请日：2020-05-09

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Sonja Schrepfer ,  Tobias Deuse

IPC: C12N5/0735 ,  C12N15/113 ,  C12N5/074

Abstract: The invention discloses for the first time pluripotent cells, including induced pluripotent stem cells, embryonic stem cells, and hypo-immune pluripotent cells that are ABO blood type O Rhesus Factor negative and evade rejection resulting from blood type antigen mismatch. The invention further provides universally acceptable “off-the-shelf” pluripotent cells and derivatives thereof for generating or regenerating specific tissues and organs.

公开(公告)号：US20250032544A1

公开(公告)日：2025-01-30

申请号：US18716906

申请日：2022-12-07

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Tobias Deuse

IPC: A61K35/17 ,  A61K39/00 ,  A61P35/02 ,  C07K14/705

Abstract: The invention provides recombinant CD47 engager receptor proteins comprising an intracellular domain that enhances an immune response in a cell when the CD47 engager receptor protein binds to CD47 on a target cell. The invention also provides cells comprising the CD47 engager receptor proteins. The CD47 engager receptor protein may be a switched Signal Regulatory Protein Alpha (SIRPα) receptor (SIRPα switch receptors) and cells that comprise them (SIRPα switch cells). SIRPα switch receptors recognize CD47 on target tumor cells and transmit an intracellular signal within the SIRPα switch cells that upregulates natural killer cell (NK), T cell, and macrophage activity. The result is increased tumor cell killing.

公开(公告)号：US20240325536A1

公开(公告)日：2024-10-03

申请号：US18281532

申请日：2022-03-29

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Tobias Deuse

IPC: A61K39/00 ,  A61K35/36 ,  A61K35/39 ,  C07K14/725 ,  C07K14/735 ,  C07K16/28

CPC classification number: A61K39/464412 ,  A61K35/36 ,  A61K35/39 ,  A61K39/4611 ,  A61K39/4621 ,  A61K39/4631 ,  C07K14/7051 ,  C07K14/70535 ,  C07K16/2803 ,  A61K2239/26 ,  C07K2317/622

Abstract: The invention provides, for the first time, cells that express truncated or modified Fc Receptor proteins (e.g. CD16t, CD32t, or CD64t) to evade antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). The cells may be pluripotent cells, including hypoimmune pluripotent cells (HIP) or ABO blood type O Rhesus Factor negative HIP cells (HIPO−), that express a truncated or modified Fc Receptor. The invention encompasses cells derived from the pluripotent cells as well as primary cells. The cells may also be differentiated cells, including chimeric antigen receptor (CAR) cells, T cells, natural killer (NK) cells, endothelial cells, dopaminergic neurons, neuroglial cells, pancreatic islet cells, pancreatic beta cells, thyroid cells, fibroblasts, hepatocytes, cardiomyocytes, or retinal pigment endothelium cells.

公开(公告)号：US20220347215A1

公开(公告)日：2022-11-03

申请号：US17621689

申请日：2020-06-24

Applicant: The Regents of the University of California

Inventor： Tobias Deuse

IPC: A61K35/17 ,  C12N5/0783 ,  C12N9/22 ,  C12N15/11 ,  C12N15/86 ,  C07K14/705 ,  A61P35/02

Abstract: The invention provides Natural Killer (NK) cells that have a reduced or ablated Signal Regulatory Protein Alpha (SIRPα-) function when compared to a NK cell having an unmodified SIRPα-function that effectively kills a population of cancer cells that express CD47.

公开(公告)号：US12221622B2

公开(公告)日：2025-02-11

申请号：US16870960

申请日：2020-05-09

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Sonja Schrepfer ,  Tobias Deuse

IPC: C12N5/0735 ,  A61K35/34 ,  A61K35/545 ,  C12N5/074 ,  C12N9/22 ,  C12N15/113

Abstract: The invention discloses for the first time pluripotent cells, including induced pluripotent stem cells, embryonic stem cells, hypo-immune pluripotent cells, cells that have been derived therefrom, and cells that have been biologically differentiated therefrom into particular tissue lineages that are ABO blood type O Rhesus Factor negative or otherwise evade rejection resulting from blood type antigen mismatch. The invention further provides universally acceptable “off-the-shelf” pluripotent cells and derivatives thereof for generating or regenerating specific tissues and organs.

公开(公告)号：US20210292715A1

公开(公告)日：2021-09-23

申请号：US17260224

申请日：2019-07-17

Applicant: The Regents of the University of California

Inventor： Sonja Schrepfer ,  Tobias Deuse

IPC: C12N5/074 ,  C12N5/077

Abstract: The invention provides universally acceptable “off-the-shelf” hypoimmunogenic pluripotent cells and differentiated cardiac, endothelial, neuronal, islet, or retinal pigment cells thereof. Such hypoimmune cells are used to treat patients in need thereof. The cells lack major immune antigens that trigger immune responses and are engineered to avoid phagocytic endocytosis.

公开(公告)号：US11162079B2

公开(公告)日：2021-11-02

申请号：US16870959

申请日：2020-05-09

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Sonja Schrepfer ,  Tobias Deuse

IPC: A61K9/127 ,  C12N5/074 ,  C12N5/0735 ,  C12N5/077

Abstract: The invention discloses for the first time pluripotent cells, including hypoimmune pluripotent ABO blood type O Rhesus Factor negative (HIPO−) cells, that evade rejection by the host allogeneic immune system and avoid blood antigen type rejection. The HIPO− cells comprise reduced HLA-I and HLA-II expression, increased CD47 expression, and a universal blood group O Rh− (“O−”) blood type. The universal blood type is achieved by eliminating ABO blood group A and B antigents as well as eliminating Rh factor expression, or by starting with an O− parent cell line. These new, novel HIPO− cells evade host immune rejection because they have an impaired antigen presentation capacity, protection from innate immune clearance, and lack blood group rejection. The cells of the invention also include O− pluripotent stem cells (iPSCO−) and O− embryonic stem cells (ESCO−). The invention further provides universally acceptable “off”-the-shelf pluripotent cells and derivatives thereof for generating or regenerating specific tissues and organs.

公开(公告)号：US20240139341A1

公开(公告)日：2024-05-02

申请号：US18279199

申请日：2022-03-07

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Tobias Deuse

IPC: A61K48/00 ,  C12N15/86

CPC classification number: A61K48/0041 ,  C12N15/86 ,  C12N2740/15043 ,  C12N2740/15052

Abstract: The invention relates to gene therapies using viral vectors. The invention provides, for the first time, packaging cells that comprise enhanced Fc receptor expression (e.g. CD16, CD32, or CD64) to generate gene therapy viruses that evade antibody-dependent inactivation (ADI) or complement-dependent inactivation (CDI). The invention also provides gene therapy viruses with the enhanced Fc receptors displayed on their viral envelope.

公开(公告)号：US20240091274A1

公开(公告)日：2024-03-21

申请号：US17768217

申请日：2020-10-09

Applicant: The Regents of the University of California

Inventor： Tobias Deuse

IPC: A61K35/545 ,  A61K39/00 ,  C12N5/074

CPC classification number: A61K35/545 ,  A61K39/4631 ,  C12N5/0696 ,  C12N2501/50 ,  C12N2506/02 ,  C12N2506/11 ,  C12N2506/45 ,  C12N2510/00

Abstract: The invention provides, for the first time, cells that comprise enhanced CD16, CD32, or CD64 expression to evade antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). The cells may be pluripotent cells, including hypoimmune pluripotent cells (HIP) or ABO blood type O Rhesus Factor negative HIP cells (HIPO−), that further comprise the enhanced CD16, CD32, or CD64 expression. The invention encompasses cells derived from the pluripotent cells.