Patents by Inventor Gerald R. Crabtree

Gerald R. Crabtree 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).

  • Patent number: 11267809
    Abstract: The invention provided here creates a new paradigm for the treatment of a variety of conditions where modulation of a BAF complex is desired. The disclosure that follows outlines a strategy for modulating a BAF complex in a cell, and provides effective compounds, pharmaceutical compositions, development strategies, and treatment protocols, and describes many of the ensuing benefits. A new family of BAF complex modulating compounds has been developed based on a new chemical scaffold including a 12-membered macrolactam core structures. Contacting target cells in vitro or in vivo with the compounds and compositions of this invention can selectively inhibit the activity of BAF complexes in such cells. Some of the BAF complex modulating compounds in this family are particularly effective agents for treating cancer in conjunction with a ATR inhibitor.
    Type: Grant
    Filed: September 13, 2018
    Date of Patent: March 8, 2022
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Emma J. Chory, Gerald R. Crabtree, Emily C. Dykhuizen
  • Publication number: 20210315876
    Abstract: This disclosure provides methods of using BAF complex modulating compounds as inhibitors of BAF-mediated transcription in target cells. The BAF complex modulating compounds include 12-membered macrolactam compounds that can target a BAF-specific subunit (e.g., ARID1A) to prevent nucleosomal positioning, relieving transcriptional repression of HIV-1. The subject methods can provide for reversal of latency of HIV-1 in cells in vitro or in vivo. Use of the macrolactam BAF complex modulating compounds represent a method of HIV latency reversal with a unique mechanism of action, which can be optionally combined with other Latency Reversal Agents to improve reservoir targeting. The subject methods can be utilized in conjunction with any convenient methods of treating HIV or HIV latency, including methods related to immune system activation, antiretroviral therapies and/or anti-HIV agents.
    Type: Application
    Filed: July 11, 2019
    Publication date: October 14, 2021
    Inventors: Emily C. Dykhuizen, Gerald R. Crabtree, Tokameh Mahmoudi
  • Patent number: 10976320
    Abstract: Methods for identifying and treating cancer patients likely to respond to topoisomerase inhibitors or likely to fail to respond to topoisomerase inhibitors are provided. The methods take advantage of the newly discovered role of BAF complexes in decatenation of DNA by topoisomerase IIa. Cancer cells are frequently at least partly defective in BAF complex activity. Such cells are targeted for therapy using certain topoisomerase IIa inhibitors according to the disclosed methods of treatment. Therapy of such cells using other topoisomerase inhibitors should be avoided.
    Type: Grant
    Filed: May 21, 2014
    Date of Patent: April 13, 2021
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Emily Carla Dykhuizen, Diana Clare Hargreaves, Cigall Kadoch, Gerald R. Crabtree
  • Publication number: 20200255416
    Abstract: The invention provided here creates a new paradigm for the treatment of a variety of conditions where modulation of a BAF complex is desired. The disclosure that follows outlines a strategy for modulating a BAF complex in a cell, and provides effective compounds, pharmaceutical compositions, development strategies, and treatment protocols, and describes many of the ensuing benefits. A new family of BAF complex modulating compounds has been developed based on a new chemical scaffold including a 12-membered macrolactam core structures. Contacting target cells in vitro or in vivo with the compounds and compositions of this invention can selectively inhibit the activity of BAF complexes in such cells. Some of the BAF complex modulating compounds in this family are particularly effective agents for treating cancer in conjunction with a ATR inhibitor.
    Type: Application
    Filed: September 13, 2018
    Publication date: August 13, 2020
    Inventors: Emma J. CHORY, Gerald R. CRABTREE, Emily C. DYKHUIZEN
  • Publication number: 20190269761
    Abstract: Methods and compositions are provided for treating human synovial sarcoma (SS). Also provided are screens to identify therapeutics for the treatment of synovial sarcoma. These methods, compositions, and screens are based on the discovery that promoting the assembly of wild type BAF (also called mSWI/SNF) complexes in SS cells by increasing levels of wild type SS18 and/or decreasing levels of SS18-SSX fusion protein leads to the cessation of proliferation of malignant cells in synovial sarcoma.
    Type: Application
    Filed: August 28, 2018
    Publication date: September 5, 2019
    Inventors: Cigall Kadoch, Gerald R. Crabtree
  • Publication number: 20180305424
    Abstract: Methods of inducibly targeting a chromatin effector to a genomic locus are provided. Aspects of the methods include employing a chemical inducer of proximity (CIP) system. Aspects of the invention further include methods of screening candidate agents that modulate chromatin-mediated transcription control and methods of inducibly modulating expression of a coding sequence from genomic locus. Also provided are compositions, e.g., cells, reagents and kits, etc., that find use in methods of the invention.
    Type: Application
    Filed: October 25, 2016
    Publication date: October 25, 2018
    Inventors: GERALD R. CRABTREE, Somon M.G. Braun, Joseph Paul Calarco, Cigall Kadoch
  • Publication number: 20180303802
    Abstract: Methods useful in the treatment of synovial sarcoma are provided. The methods comprise administering to a subject suffering from synovial sarcoma a compound as disclosed herein. Also provided are novel compounds having therapeutic effects on subjects suffering from synovial sarcoma and pharmaceutical compositions comprising the compounds. The compounds were identified by screening for agents that promote the assembly of wild-type BAF (also called mSWI/SNF) complexes in modified SS cells.
    Type: Application
    Filed: October 5, 2016
    Publication date: October 25, 2018
    Inventors: Cigall KADOCH, Gerald R. CRABTREE
  • Patent number: 10105420
    Abstract: Methods and compositions are provided for treating human synovial sarcoma (SS). Also provided are screens to identify therapeutics for the treatment of synovial sarcoma. These methods, compositions, and screens are based on the discovery that promoting the assembly of wild type BAF (also called mSWI/SNF) complexes in SS cells by increasing levels of wild type SS18 and/or decreasing levels of SS18-SSX fusion protein leads to the cessation of proliferation of malignant cells in synovial sarcoma.
    Type: Grant
    Filed: July 20, 2016
    Date of Patent: October 23, 2018
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Cigall Kadoch, Gerald R. Crabtree
  • Publication number: 20170014491
    Abstract: Methods and compositions are provided for treating human synovial sarcoma (SS). Also provided are screens to identify therapeutics for the treatment of synovial sarcoma. These methods, compositions, and screens are based on the discovery that promoting the assembly of wild type BAF (also called mSWI/SNF) complexes in SS cells by increasing levels of wild type SS18 and/or decreasing levels of SS18-SSX fusion protein leads to the cessation of proliferation of malignant cells in synovial sarcoma.
    Type: Application
    Filed: July 20, 2016
    Publication date: January 19, 2017
    Inventors: Cigall Kadoch, Gerald R. Crabtree
  • Patent number: 9410943
    Abstract: Methods and compositions are provided for treating human synovial sarcoma (SS). Also provided are screens to identify therapeutics for the treatment of synovial sarcoma. These methods, compositions, and screens are based on the discovery that promoting the assembly of wild type BAF (also called mSWI/SNF) complexes in SS cells by increasing levels of wild type SS18 and/or decreasing levels of SS18-SSX fusion protein leads to the cessation of proliferation of malignant cells in synovial sarcoma.
    Type: Grant
    Filed: March 13, 2014
    Date of Patent: August 9, 2016
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Cigall Kadoch, Gerald R. Crabtree
  • Publication number: 20150185221
    Abstract: Methods for identifying and treating cancer patients likely to respond to topoisomerase inhibitors or likely to fail to respond to topoisomerase inhibitors are provided. The methods take advantage of the newly discovered role of BAF complexes in decatenation of DNA by topoisomerase IIa. Cancer cells are frequently at least partly defective in BAF complex activity. Such cells are targeted for therapy using certain topoisomerase IIa inhibitors according to the disclosed methods of treatment. Therapy of such cells using other topoisomerase inhibitors should be avoided.
    Type: Application
    Filed: May 21, 2014
    Publication date: July 2, 2015
    Inventors: Emily Carla Dykhuizen, Diana Clare Hargreaves, Cigall Kadoch, Gerald R. Crabtree
  • Publication number: 20140288162
    Abstract: Methods and compositions are provided for treating human synovial sarcoma (SS). Also provided are screens to identify therapeutics for the treatment of synovial sarcoma. These methods, compositions, and screens are based on the discovery that promoting the assembly of wild type BAF (also called mSWI/SNF) complexes in SS cells by increasing levels of wild type SS18 and/or decreasing levels of SS18-SSX fusion protein leads to the cessation of proliferation of malignant cells in synovial sarcoma.
    Type: Application
    Filed: March 13, 2014
    Publication date: September 25, 2014
    Inventors: Cigall Kadoch, Gerald R. Crabtree
  • Publication number: 20140030234
    Abstract: Methods and compositions are provided for modulating pancreatic islet ?-cell development. Aspects of the methods include promoting ?-cell development by providing agents that promote calcineurin/N FAT signaling, and inhibiting ?-cell development by providing agents that inhibit calcineurin/NFAT signaling. These methods find a number of uses, including, for example, in the treatment of diabetes and human islet diseases. In addition, reagents, devices and kits thereof that find use in practicing the subject methods are provided.
    Type: Application
    Filed: July 11, 2013
    Publication date: January 30, 2014
    Inventors: Seung K. Kim, William Goodyer, Gerald R. Crabtree, Pei Wang
  • Publication number: 20130158098
    Abstract: Methods of inducing proximity of chimeric molecules in a cell are provided. Aspects of the methods include contacting a cell with an amount of alkenyl substituted cycloaliphatic (ASC) inducer compound, e.g., abscisic acid, effective to induce proximity of first and second chimeric molecules. Also provided are compositions and kits for practicing various embodiments of the methods. Methods of the invention find use in a variety of different applications, including transcription induction applications.
    Type: Application
    Filed: June 15, 2011
    Publication date: June 20, 2013
    Applicant: The Board of Trustees of the Leland Standford Junior University
    Inventors: Fu-Sen Liang, Gerald R. Crabtree
  • Publication number: 20120277111
    Abstract: Methods of converting non-neuronal somatic cells into induced neuronal cells are provided. Aspects of the methods include contacting a non-neuronal somatic cell with a microRNA mediated neuronal cell induction agent. Aspects of the invention further include compositions produced by methods of the invention as well as compositions that find use in practicing embodiments of methods of invention. The methods and compositions find use in a variety of different applications.
    Type: Application
    Filed: April 6, 2012
    Publication date: November 1, 2012
    Inventors: Gerald R. Crabtree, Andrew Yoo
  • Patent number: 8084596
    Abstract: We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins and disclose methods and materials for using that procedure to regulatably initiate cell-specific apoptosis (programmed cell death) in genetically engineered cells.
    Type: Grant
    Filed: January 7, 2010
    Date of Patent: December 27, 2011
    Assignees: The Board of Trustees of the Leland Stanford Junior University, President and Fellows of Harvard College
    Inventors: Gerald R. Crabtree, Peter Belshaw, Stuart L. Schreiber, David M. Spencer, Thomas J. Wandless
  • Patent number: 8044099
    Abstract: Bifunctional molecules and methods for their use are provided. The subject bifunctional molecules are conjugates of a drug moiety and a pharmacokinetic modulating moiety, where these two moieties are optionally joined by a linking group. The bifunctional molecules are further characterized in that they exhibit at least one modulated pharmacokinetic property upon administration to a host as compared to a free drug control. The subject bifunctional molecules find use in a variety of therapeutic applications.
    Type: Grant
    Filed: December 13, 2004
    Date of Patent: October 25, 2011
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Roger Briesewitz, Gerald R. Crabtree, Thomas J. Wandless
  • Publication number: 20110160246
    Abstract: Methods and compositions are provided for reducing aggregation of neurodegenerative proteins associated with neurotoxicity or other proteins. The compounds comprise a first domain or targeting element for binding to the target proteins linked to a second domain or recruiting element that binds to an aggregation inhibiting protein, e.g. a prolyl isomerase. By associating the aggregating forming proteins or neuronal cells under conditions where aggregating proteins are produced with the compound and the aggregation inhibiting protein, aggregation is reduced. The subject agents can be used in assays, investigating the etiology of the neuronal diseases and for prophylaxis and therapy.
    Type: Application
    Filed: November 11, 2010
    Publication date: June 30, 2011
    Inventors: Isabella A. Graef, Gerald R. Crabtree, Jason E. Gestwicki
  • Patent number: 7923230
    Abstract: Methods and compositions are provided for reducing aggregation of neurodegenerative proteins associated with neurotoxicity or other proteins. The compounds comprise a first domain or targeting element for binding to the target proteins linked to a second domain or recruiting element that binds to an aggregation inhibiting protein, e.g. a prolyl isomerase. By associating the aggregating forming proteins or neuronal cells under conditions where aggregating proteins are produced with the compound and the aggregation inhibiting protein, aggregation is reduced. The subject agents can be used in assays, investigating the etiology of the neuronal diseases and for prophylaxis and therapy.
    Type: Grant
    Filed: March 17, 2008
    Date of Patent: April 12, 2011
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Isabella A. Graef, Gerald R. Crabtree, Jason E. Gestwicki
  • Publication number: 20110003385
    Abstract: Dimerization and oligomerization of proteins are general biological control mechanisms that contribute to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins. In principle, any two target proteins can be induced to associate by treating the cells or organisms that harbor them with cell permeable, synthetic ligands.
    Type: Application
    Filed: January 8, 2010
    Publication date: January 6, 2011
    Inventors: Gerald R. Crabtree, Stuart L. Schreiber, David M. Spencer, Thomas J. Wandless, Steffan N. Ho, Peter Belshaw