SELECTIVE CONTROL AND TUNING of CHIMERIC AGONIST RECEPTORS (CARs) ACTIVITY for CELL-BASED IMMUNOTHERAPY

Tech ID: 24753 / UC Case 2013-025-0

Invention Novelty

An On-switch engineering method to increase safety and efficacy of cell-based therapies by allowing ongoing in vivo control of CARs activity in patients

Value Proposition

A major class of targeted cell-based immunotherapy for cancer and autoimmune diseases involves the use of genetically modified human T cells expressing Chimeric Antigen Receptors (CARs). CAR-modified immune cells can have toxic effects, either through reaction with normal cells that also express the target antigen or though systemic hyperimmune stimulation. Thus there is a major need to pharmacologically control the response of CAR-modified cells after administration to the patient.

 The current invention provides the additional advantages:

  • Specific tuning of the CARs activity by varying dose of the small-molecule drug
  • Specific temporal control of CAR activity by varying time course of drug administration
  • Specific targeting of CAR activity by varying distribution of drug
  • Reduce on-target toxicities and hyperimmune response toxicities; improve treatment efficacy
  • Compatible with a wide range of CARs and activation agents
  • Improved safety, tunability and efficiency compared to apoptosis-based safety switches for eliminating CAR T cells (adoptive cell transfer therapy can be tuned instead of aborted; mutation of switch will not lead to constitutively active T cells)

Technology Description

Scientists at the University of California San Francisco developed a method to design split Chimeric Antigen Receptors (CARs) including an extracellular antigen recognition, a transmembrane, and an intracellular signaling domain for pharmacologically conditional switch-on via a small-molecule drug. In other words, the on-switch CAR expressing immune cells as delivered to patients are rendered inactive until the small-molecule is present. Then, the customized antibody portion of CARs binds to an antigen of interest on a target tumor cell surface. Upon antigen engagement, the intracellular signaling domain will activate the immune cell resulting in the release of cytolytic molecules to induce tumor cell death.

Application

Development of therapeutics requiring conditional activation of synthetic receptors

Looking for Partners

To develop and commercialize this technology for a tunable cell-based immunotherapy 

Stage of Development

Preclinical

Related Materials

  • Manuscript available under CDA/NDA

Data Availability

 In vitro data

Patent Status

Country Type Number Dated Case
Rep Of Korea Issued Patent 10-2813881 05/23/2025 2013-025
Japan Issued Patent 7676476 05/02/2025 2013-025
United States Of America Issued Patent 12,161,672 12/10/2024 2013-025
Brazil Issued Patent BR112015019640-3 04/09/2024 2013-025
Hong Kong Issued Patent HK40013763 01/12/2024 2013-025
Macau Issued Patent J/007637 01/10/2024 2013-025
Israel Issued Patent 272279 01/02/2024 2013-025
Hong Kong Issued Patent HK40050006 12/29/2023 2013-025
Austria Issued Patent 3881868 09/27/2023 2013-025
Belgium Issued Patent 3881868 09/27/2023 2013-025
Bulgaria Issued Patent 3881868 09/27/2023 2013-025
Germany Issued Patent 3881868 09/27/2023 2013-025
Denmark Issued Patent 3881868 09/27/2023 2013-025
Estonia Issued Patent 3881868 09/27/2023 2013-025
Finland Issued Patent 3881868 09/27/2023 2013-025
France Issued Patent 3881868 09/27/2023 2013-025
United Kingdom Issued Patent 3881868 09/27/2023 2013-025
Italy Issued Patent 3881868 09/27/2023 2013-025
Lithuania Issued Patent 3881868 09/27/2023 2013-025
Luxembourg Issued Patent 3881868 09/27/2023 2013-025
Latvia Issued Patent 3881868 09/27/2023 2013-025
Malta Issued Patent 3881868 09/27/2023 2013-025
Netherlands (Holland) Issued Patent 3881868 09/27/2023 2013-025
Portugal Issued Patent 3881868 09/27/2023 2013-025
Sweden Issued Patent 3881868 09/27/2023 2013-025
Slovenia Issued Patent 3881868 09/27/2023 2013-025
Unitary Patent Issued Patent 3881868 09/27/2023 2013-025
China Issued Patent ZL 201910722248.1 09/08/2023 2013-025
Australia Issued Patent 2021204054 08/03/2023 2013-025
Japan Issued Patent 7317159 07/20/2023 2013-025
United States Of America Issued Patent 11,478,510 10/25/2022 2013-025
India Issued Patent 401400 07/15/2022 2013-025
Japan Issued Patent 7014843 01/24/2022 2013-025
Hong Kong Issued Patent 40020273 01/07/2022 2013-025
Rep Of Korea Issued Patent 10-2332790 10/25/2021 2013-025
Australia Issued Patent 2019246785 07/22/2021 2013-025
New Zealand Issued Patent 710925 06/29/2021 2013-025
New Zealand Issued Patent 750521 06/29/2021 2013-025
Austria Issued Patent 3613439 04/07/2021 2013-025
Belgium Issued Patent 3613439 04/07/2021 2013-025
Switzerland Issued Patent 3613439 04/07/2021 2013-025
Czech Republic Issued Patent 3613439 04/07/2021 2013-025
Germany Issued Patent 3613439 04/07/2021 2013-025
Spain Issued Patent 3613439 04/07/2021 2013-025
France Issued Patent 3613439 04/07/2021 2013-025
United Kingdom Issued Patent 3613439 04/07/2021 2013-025
Greece Issued Patent 3613439 04/07/2021 2013-025
Ireland Issued Patent 3613439 04/07/2021 2013-025
Italy Issued Patent 3613439 04/07/2021 2013-025
Netherlands (Holland) Issued Patent 3613439 04/07/2021 2013-025
Norway Issued Patent 3613439 04/07/2021 2013-025
Poland Issued Patent 3613439 04/07/2021 2013-025
Portugal Issued Patent 3613439 04/07/2021 2013-025
Sweden Issued Patent 3613439 04/07/2021 2013-025
Slovenia Issued Patent 3613439 04/07/2021 2013-025
Slovak Republic Issued Patent 3613439 04/07/2021 2013-025
Turkey Issued Patent 3613439 04/07/2021 2013-025
United States Of America Issued Patent 10,888,581 01/12/2021 2013-025
Hong Kong Issued Patent HK1253407 10/23/2020 2013-025
Hong Kong Issued Patent HK1218625 10/09/2020 2013-025
Macau Issued Patent J/003907 08/26/2020 2013-025
Rep Of Korea Issued Patent 10-2132246 07/03/2020 2013-025
Israel Issued Patent 240472 05/28/2020 2013-025
Japan Issued Patent 6687712 04/28/2020 2013-025
United States Of America Issued Patent 10,632,152 04/28/2020 2013-025
Rep Of Korea Issued Patent 2064230 01/03/2020 2013-025
Mexico Issued Patent 369545 11/12/2019 2013-025
Austria Issued Patent 3300745 09/11/2019 2013-025
Belgium Issued Patent 3300745 09/11/2019 2013-025
Switzerland Issued Patent 3300745 09/11/2019 2013-025
Cyprus Issued Patent CY20191101245 09/11/2019 2013-025
Czech Republic Issued Patent 3300745 09/11/2019 2013-025
Germany Issued Patent 3300745 09/11/2019 2013-025
Denmark Issued Patent 3300745 09/11/2019 2013-025
Estonia Issued Patent 3300745 09/11/2019 2013-025
Spain Issued Patent 2758227 09/11/2019 2013-025
Finland Issued Patent 3300745 09/11/2019 2013-025
France Issued Patent 3300745 09/11/2019 2013-025
United Kingdom Issued Patent 3300745 09/11/2019 2013-025
Greece Issued Patent 3300745 09/11/2019 2013-025
Croatia Issued Patent 3300745 09/11/2019 2013-025
Hungary Issued Patent 3300745 09/11/2019 2013-025
Ireland Issued Patent 3300745 09/11/2019 2013-025
Iceland Issued Patent 3300745 09/11/2019 2013-025
Italy Issued Patent 3300745 09/11/2019 2013-025
Liechtenstein Issued Patent 3300745 09/11/2019 2013-025
Lithuania Issued Patent 3300745 09/11/2019 2013-025
Luxembourg Issued Patent 3300745 09/11/2019 2013-025
Latvia Issued Patent 3300745 09/11/2019 2013-025
Monaco Issued Patent 3300745 09/11/2019 2013-025
Netherlands (Holland) Issued Patent 3300745 09/11/2019 2013-025
Norway Issued Patent 3300745 09/11/2019 2013-025
Poland Issued Patent 3300745 09/11/2019 2013-025
Portugal Issued Patent 3300745 09/11/2019 2013-025
Romania Issued Patent 3300745 09/11/2019 2013-025
Sweden Issued Patent 3300745 09/11/2019 2013-025
Slovenia Issued Patent 3300745 09/11/2019 2013-025
Slovak Republic Issued Patent 3300745 09/11/2019 2013-025
Turkey Issued Patent 3300745 09/11/2019 2013-025
China Issued Patent ZL201480016737.0 08/30/2019 2013-025
Japan Issued Patent 6450690 01/09/2019 2013-025
United States Of America Issued Patent 10,105,391 10/23/2018 2013-025
Australia Issued Patent 2014216130 03/01/2018 2013-025
United States Of America Issued Patent 9,821,012 11/21/2017 2013-025
Austria Issued Patent 2956175 10/04/2017 2013-025
Belgium Issued Patent 2956175 10/04/2017 2013-025
Switzerland Issued Patent 2956175 10/04/2017 2013-025
Czech Republic Issued Patent 2956175 10/04/2017 2013-025
Germany Issued Patent 2956175 10/04/2017 2013-025
Denmark Issued Patent 2956175 10/04/2017 2013-025
Spain Issued Patent 2956175 10/04/2017 2013-025
Finland Issued Patent 2956175 10/04/2017 2013-025
France Issued Patent 2956175 10/04/2017 2013-025
United Kingdom Issued Patent 2956175 10/04/2017 2013-025
Greece Issued Patent 2956175 10/04/2017 2013-025
Hungary Issued Patent 2956175 10/04/2017 2013-025
Ireland Issued Patent 2956175 10/04/2017 2013-025
Iceland Issued Patent 2956175 10/04/2017 2013-025
Italy Issued Patent 2956175 10/04/2017 2013-025
Lithuania Issued Patent 2956175 10/04/2017 2013-025
Luxembourg Issued Patent 2956175 10/04/2017 2013-025
Monaco Issued Patent 2956175 10/04/2017 2013-025
Netherlands (Holland) Issued Patent 2956175 10/04/2017 2013-025
Norway Issued Patent 2956175 10/04/2017 2013-025
Poland Issued Patent 2956175 10/04/2017 2013-025
Portugal Issued Patent 2956175 10/04/2017 2013-025
Sweden Issued Patent 2956175 10/04/2017 2013-025
Turkey Issued Patent 2956175 10/04/2017 2013-025
United States Of America Issued Patent 9,587,020 03/07/2017 2013-025
European Patent Office Published Application 4303232 01/10/2024 2013-025
United States Of America Published Application 20210196757 07/01/2021 2013-025
Canada Published Application 2013-025
 

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Inventors

  • Lim, Wendell A.
  • Onuffer, James J.
  • Wu, Chia Yung

Other Information

Keywords

Chimeric antigen receptors, CARs, Cell-based therapy, Cancer, Modulation, T-cells

Categorized As

Related cases

2013-025-0

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