Patents by Inventor Wendell A. Lim

Wendell A. Lim has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Publication number: 20240344025
    Abstract: Provided herein is a synthetic immuno-suppressive cell that contains comprises a molecular circuit comprising the following components: (a) a binding-triggered transcriptional switch (BTTS); and one or both of: (b) a nucleic acid encoding a pro-inflammatory cytokine sink, (c) a nucleic acid encoding an anti-inflammatory cytokine, (d) a nucleic acid encoding an immune inhibitory receptor, or ligand thereof, and (c) a nucleic acid encoding an ectonucleotidase. In this circuit, binding of the BTTS to a marker on the surface of a target cell activates expression of one or any combination of (b)-(c) by the synthetic immuno-suppressive cell.
    Type: Application
    Filed: September 21, 2022
    Publication date: October 17, 2024
    Inventors: Wendell A. LIM, Nishith REDDY, Milos SIMIC
  • Publication number: 20240342281
    Abstract: Provided herein is a cytotoxic immune cell that is primed by and/or whose cytotoxicity within the tumor microenvironment is enhanced by binding to a stromal marker, e.g., Fibroblast Activation Protein Alpha (FAP). In some embodiments, the cells may contain a protein circuit that contains at least two components, wherein one of the components binding-triggered transcriptional switch that is activated by binding to the stromal marker. The second component may be a nucleic acid encoding an immune receptor (e.g., a chimeric antigen receptor or TCR) that is activated by binding to a cancer-specific antigen and/or a pro-inflammatory cytokine.
    Type: Application
    Filed: August 3, 2022
    Publication date: October 17, 2024
    Inventors: Wendell A. LIM, Gregory ALLEN
  • Publication number: 20240325449
    Abstract: Methods are provided for treating a subject for glioblastoma, including e.g., an EGFRvIII negative glioblastoma. The methods of the present disclosure involve administering to a subject a molecular circuit that includes a binding triggered transcriptional switch (BT'S) that binds to a priming antigen expressed by the subjects glioblastoma multiforme (GBM) that, when bound to the priming antigen, induces one or more encoded therapeutics specific for one or more antigens expressed by the GBM. Nucleic acids containing sequences encoding all or portions of such circuits are also provided, as well as cells, expression cassettes and vectors that contain such nucleic acids. Also provided are kits for practicing the described methods.
    Type: Application
    Filed: June 7, 2024
    Publication date: October 3, 2024
    Inventors: Wendell A. Lim, Hideho Okada, Kole T. Roybal, Joseph H. Choe, Payal B. Watchmaker
  • Publication number: 20240327513
    Abstract: Provided herein is cleavable fusion protein comprising: an extracellular binding domain comprising a first protein binding domain that specifically binds to a cell surface protein, a transmembrane domain, one or more force-dependent cleavage sites and an intracellular domain comprising: i. a second protein binding domain that specifically binds to a target protein; and ii. a degradation domain. When the fusion protein is expressed in a mammalian cell, binding of the first binding domain to the cell surface protein induces proteolytic cleavage of the one or more force-dependent cleavage site to release the intracellular domain. Protein circuits, cells and methods that make use of the fusion protein are also provided.
    Type: Application
    Filed: March 14, 2022
    Publication date: October 3, 2024
    Inventors: Andrew H. NG, Matthew KIM, Wendell A. LIM, Hana EL-SAMAD
  • Patent number: 12090170
    Abstract: Methods are provided for treating a subject for glioblastoma, including e.g., an EGFRvIII negative glioblastoma. The methods of the present disclosure involve administering to a subject a molecular circuit that includes a binding triggered transcriptional switch (BTTS) that binds to a priming antigen expressed by the subjects glioblastoma multiforme (GBM) that, when bound to the priming antigen, induces one or more encoded therapeutics specific for one or more antigens expressed by the GBM. Nucleic acids containing sequences encoding all or portions of such circuits are also provided, as well as cells, expression cassettes and vectors that contain such nucleic acids. Also provided are kits for practicing the described methods.
    Type: Grant
    Filed: April 4, 2019
    Date of Patent: September 17, 2024
    Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
    Inventors: Wendell A. Lim, Hideho Okada, Kole T. Roybal, Joseph H. Choe, Payal B. Watchmaker
  • Publication number: 20240299545
    Abstract: The present disclosure relates generally to the field of immunology, and particularly relates to hybrid chimeric antigen receptors designed to combine fast time-scale intracellular signal transduction and long time-scale transcription regulation. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions or diseases, such as cancers.
    Type: Application
    Filed: March 23, 2022
    Publication date: September 12, 2024
    Inventors: Kole T. ROYBAL, Wendell A. LIM, Joseph H. CHOE
  • Patent number: 12065479
    Abstract: Provided are chimeric polypeptides which modulate various cellular processes following cleavage of a force sensor cleavage domain, including non-Notch force sensor cleavage domains, induced upon binding of a specific binding member of the chimeric polypeptide with its binding partner. Methods of using force sensor cleavage domain-containing chimeric polypeptides to modulate cellular functions, including e.g., modulation (including induction or repression) of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of monitoring cell-cell signaling and method of treating a subject using the described components, as well as kits for practicing the subject methods.
    Type: Grant
    Filed: November 15, 2018
    Date of Patent: August 20, 2024
    Assignees: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
    Inventors: Joseph H. Choe, Paul Langridge, Wendell A. Lim, Kole T. Roybal, Gary Struhl
  • Publication number: 20240115608
    Abstract: An engineered immune receptor (e.g., a chimeric antigen receptor (CAR) or chimeric costimulatory receptor (CCR)) that contains one or more short linear motifs that bind to other intracellular signaling proteins are provided, as well as nucleic acids encoding the same, cells that contain the same and methods of use. Examples of such motifs include a PLC?1-binding motifs and TRAF binding motifs, but other motifs may be used. These motifs are thought to recruit other proteins to the engineered immune receptor, thereby altering cellular responses.
    Type: Application
    Filed: February 7, 2022
    Publication date: April 11, 2024
    Inventors: Wendell A. LIM, Kyle DANIELS
  • Publication number: 20230405120
    Abstract: Described herein is an engineered cell adhesion molecule. The engineered cell adhesion molecule is a fusion protein comprising: an extracellular binding domain comprising a first binding moiety, a transmembrane domain and an intracellular domain that is capable of signaling to and reorganize the cytoskeleton of the cell upon specific binding of the first binding moiety to a second binding moiety. Various compositions, cells and methods that employ the cells are also described.
    Type: Application
    Filed: November 1, 2021
    Publication date: December 21, 2023
    Inventors: Wendell A. LIM, Adam J. STEVENS
  • Publication number: 20230330142
    Abstract: The present disclosure provides immune cells genetically modified to produce two antigen-triggered polypeptides, each recognizing a different cell surface antigen, wherein the two different cell surface antigens employed are selected from those pairs described herein. The present disclosure further provides systems comprising two antigen-triggered polypeptides (or nucleic acids encoding same), each recognizing a different cell surface antigen, wherein the two different cell surface antigens employed are selected from those pairs described herein. Also provided are method of killing a target cancer cell, using the described genetically modified immune cells and/or systems. The present disclosure also provides polyspecific-immune inducing polypeptides including first and second antigen binding domains specific for first and second antigens, respectively, present on the surface of a target cancer cell.
    Type: Application
    Filed: August 12, 2021
    Publication date: October 19, 2023
    Inventors: Ruth DANNENFELSER, Gregory ALLEN, Olga G. TROYANSKAYA, Wendell A. LIM
  • Publication number: 20230212557
    Abstract: The present disclosure provides synthetic modular polypeptide libraries and nucleic acids encoding such synthetic modular polypeptide libraries. Also provided are methods of making synthetic modular polypeptide libraries and nucleic acids encoding synthetic modular polypeptide libraries. Methods of screening a synthetic modular polypeptide library to identify a selected phenotype associated with a member of a synthetic modular polypeptide library are also provided where such methods fmd use in both in vitro and in vivo assays.
    Type: Application
    Filed: December 19, 2022
    Publication date: July 6, 2023
    Inventors: Wendell A. Lim, Scott M. Coyle, Russell M. Gordley, Kole T. Roybal
  • Publication number: 20230078007
    Abstract: Provided herein is an in-series synthetic receptor circuit for dual-antigen AND-gate control over expression of a therapeutic payload by engineered cells. In some embodiments, the circuit may be composed of a first binding-triggered transcriptional switch, a second binding-triggered transcriptional switch and a therapeutic payload (e.g., a chimeric antigen receptor), where binding of the first binding-triggered transcriptional switch to a first antigen activates expression of the second binding-triggered transcriptional switch, and binding of the second binding-triggered transcriptional switch to a second antigen activates expression of the therapeutic payload. If the cell is an immune cell and the therapeutic payload is a chimeric antigen receptor, then the immune cell may be activated by binding of the chimeric antigen receptor to a third antigen. Methods of treatment using the cell also provided.
    Type: Application
    Filed: February 19, 2021
    Publication date: March 16, 2023
    Inventors: Jasper Z. WILLIAMS, Devan SHAH, Wendell A. LIM
  • Publication number: 20230055337
    Abstract: Provided herein is a cell comprising a recombinant nucleic acid encoding a transmembrane protein that has an extracellular binding domain that specifically binds to a brain-selective extracellular antigen, e.g., MOG, CDH10, PTPRZ1 or NRCAM, wherein the cell does not comprise a nucleic acid encoding an antigen-specific therapeutic that binds to a killing antigen expressed by a glioblastoma.
    Type: Application
    Filed: November 6, 2020
    Publication date: February 23, 2023
    Inventors: Wendell A. Lim, Milos Simic, Hideho Okada, Joseph H. Choe, Payal B. Watchmaker
  • Publication number: 20230051989
    Abstract: The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.
    Type: Application
    Filed: September 14, 2022
    Publication date: February 16, 2023
    Inventors: Chia-Yung Wu, James Onuffer, Wendell A. Lim
  • Patent number: 11560561
    Abstract: The present disclosure provides synthetic modular polypeptide libraries and nucleic acids encoding such synthetic modular polypeptide libraries. Also provided are methods of making synthetic modular polypeptide libraries and nucleic acids encoding synthetic modular polypeptide libraries. Methods of screening a synthetic modular polypeptide library to identify a selected phenotype associated with a member of a synthetic modular polypeptide library are also provided where such methods find use in both in vitro and in vivo assays.
    Type: Grant
    Filed: August 31, 2016
    Date of Patent: January 24, 2023
    Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
    Inventors: Wendell A. Lim, Scott M. Coyle, Russell M. Gordley, Kole T. Roybal
  • Publication number: 20220409666
    Abstract: The present disclosure provides an immune cell genetically modified to produce two antigen triggered polypeptides, each recognizing a different cell surface antigen. The present disclosure provides a system two antigen-triggered polypeptides, each recognizing a different cell surface antigen. The present disclosure provides a method of killing a target cancer cell, using a genetically modified immune cell or a system of the present disclosure. The present disclosure provides a computational method to identify target N antigen pairs on a cancer cell.
    Type: Application
    Filed: June 23, 2022
    Publication date: December 29, 2022
    Inventors: Wendell A. Lim, Olga G. Troyanskaya, Benjamin VanderSluis, Ruth Dannenfelser
  • Publication number: 20220378832
    Abstract: A method for treating a subject for glioblastoma is provided. In some embodiments, the method may comprise administering to a subject a molecular circuit that includes a binding triggered transcriptional switch (BTTS) that, when bound to MOG, induces one or more encoded therapeutics specific for one or more antigens expressed by the GBM. Nucleic acids containing sequences encoding all or portions of such circuits are also provided, as well as cells, expression cassettes and vectors that contain such nucleic acids. Also provided are kits for practicing the described methods.
    Type: Application
    Filed: November 6, 2020
    Publication date: December 1, 2022
    Inventors: Wendell A. Lim, Milos Simic, Hideho Okada, Kole T. Roybal, Joseph H. Choe, Payal B. Watchmaker
  • Patent number: 11478510
    Abstract: The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.
    Type: Grant
    Filed: March 19, 2020
    Date of Patent: October 25, 2022
    Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
    Inventors: Chia-Yung Wu, James Onuffer, Wendell A. Lim
  • Publication number: 20220324982
    Abstract: The instant disclosure provides chimeric polypeptides which modulate various cellular processes following a cleavage event induced upon binding of a specific binding member of the polypeptide with its binding partner. Methods of using chimeric polypeptides to modulate cellular functions, including e.g., induction of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of treating a subject using the described components and methods as well as kits for practicing the subject methods.
    Type: Application
    Filed: June 15, 2022
    Publication date: October 13, 2022
    Inventors: Wendell A. Lim, Kole T. Roybal, Jasper Z. Williams
  • Publication number: 20220265854
    Abstract: The present disclosure provides a genetically modified, in vitro immune cell. The immune cell is genetically modified with one or more nucleic acids comprising nucleotide sequences encoding: a) a chimeric polypeptide comprising: i) an antibody specific for a target antigen; and ii) a binding triggered transcriptional activator; and b) a cytokine or proliferation-inducing polypeptide that increases proliferation and/or activity of an effector immune cell, where the nucleotide sequence encoding the cytokine or proliferation-inducing polypeptide is operably linked to a transcriptional control element responsive to the transcriptional activator. The present disclosure provides compositions comprising the genetically modified, in vitro immune cell; and treatment methods comprising administration of the genetically modified, in vitro immune cell.
    Type: Application
    Filed: September 15, 2020
    Publication date: August 25, 2022
    Inventors: Wendell A. Lim, Nicholas W. Frankel