Abstract: The present disclosure provides a method of increasing the functionality of a GABAergic interneuron in the hilus of the hippocampus of an individual having at least one apolipoprotein E4 (apoE4) allele. The method generally involves reducing tau levels in the interneuron.
Type:
Grant
Filed:
December 22, 2017
Date of Patent:
April 16, 2024
Assignee:
The J. David Gladstone Institutes, a testamentary trust established under the of Will of J. David Gladstone
Abstract: The invention relates to devices, methods, kits, and compositions for in vitro generation of three-dimensional micro-tissues that are accurate models of heart, skeletal muscle, neuronal, and other tissues.
Type:
Grant
Filed:
October 26, 2020
Date of Patent:
February 13, 2024
Assignees:
The J. David Gladstone Institutes, a testamentary trust established under the Will of J. David Gladstone, The Regents of the University of California
Inventors:
Nathaniel Huebsch, Bruce Conklin, Kevin E. Healy, Peter Loskill
Abstract: The present disclosure provides compositions and methods for reactivating latent immunodeficiency virus and/or reducing transcription of HIV integrated into the genome of an HIV-infected cell. The present disclosure provides compositions and methods for treating an immunodeficiency virus infection.
Abstract: In various embodiments a compound comprising the enantiomerically enriched S-isomer S-BHB-S-1,3-butanediol is provided along with methods of use thereof.
Type:
Grant
Filed:
July 19, 2018
Date of Patent:
October 3, 2023
Assignees:
Buck Institute for Research on Aging, The Regents of The University Of California, The J. David Gladstone Institutes
Abstract: Methods of generating spinal cord glutamatergic interneurons (V2a interneurons) from human pluripotent stem cells (hPSCs) are provided. A method of the present disclosure may include culturing a first population of hPSCs in vitro in a neural induction medium that includes: a retinoic acid signaling pathway activator; a sonic hedgehog (Shh) signaling pathway activator; and a Notch signaling pathway inhibitor, wherein the culturing results in generation of a second population of cultured cells containing CHX10+ V2a interneurons. Also provided are non-human animal models that include the hPSC-derived spinal cord glutamatergic interneurons, and methods of producing the non-human animal models.
Type:
Grant
Filed:
May 26, 2017
Date of Patent:
July 18, 2023
Assignees:
The J. David Gladstone Institutes, a testamentary trust established under the Will of J. David Gladstone, The Regents of the University of California, Georgia Tech Research Corporation
Abstract: Aspects of the present disclosure include fatty acid ?-hydroxyester compounds (e.g., fatty acid esters of ?-hydroxybutyrate), fatty acid esters of butanediol, and pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions having one or more fatty acid ?-hydroxyester compounds and/or one or more fatty acid esters of butanediol. Methods for treating a subject by administering one or more esters to the subject are also provided. Kits containing one or more of the subject esters are also described.
Type:
Grant
Filed:
December 2, 2020
Date of Patent:
March 21, 2023
Assignees:
The J. David Gladstone Institutes, The Regents of The University Of California, Ithaca College
Inventors:
Eric Verdin, Scott Michael Ulrich, John C. Newman
Abstract: The present disclosure provides compositions and methods for reactivating latent immunodeficiency virus using a glycogen synthase kinase 3? inhibitor, such as a glycogen synthase kinase 3? (GSK-3?) or a glycogen synthase kinase 3? (GSK-3?) inhibitor. In some embodiments, the glycogen synthase kinase 3 inhibitor is a glycogen synthase kinase antagonist, e.g., Tideglusib (4-benzyl-2-(naphthalen-1-yl)-1,2,4-thiadiazolidine-3,5-dione), or a pharmaceutically acceptable salt or derivative thereof. In other embodiments, the glycogen synthase kinase 3 inhibitor is a maleimide-based glycogen synthase kinase 3 inhibitor, e.g., SB-216763 (3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione) or a pharmaceutically acceptable salt or derivative thereof.
Type:
Grant
Filed:
June 5, 2018
Date of Patent:
February 28, 2023
Assignee:
The J. David Gladstone Institutes, a testamentary trust established under the Will of J. David Gladstone
Abstract: Provided are methods and compositions for generating a deletion library, and methods and compositions for generating and identifying a defective interfering particle (DIP). Also provided are transposon cassettes. A subject method can include: inserting a transposon cassette comprising a target sequence for a sequence specific DNA endonuclease into a population of circular target DNAs to generate a population of transposon-inserted circular target DNAs; contacting the population of transposon-inserted circular target DNAs with the sequence specific DNA endonuclease to generate a population of cleaved linear target DNAs; contacting the population of cleaved linear target DNAs with one or more exonucleases to generate a population of deletion DNAs; and circularizing the deletion DNAs to generate a library of circularized deletion DNAs. The population of circular target DNAs can include viral genomic DNA. Also provided are human immunodeficiency virus (HIV) deletion mutants, e.g.
Type:
Grant
Filed:
December 14, 2017
Date of Patent:
February 21, 2023
Assignees:
The J. David Gladstone Institutes, The Regents of the University of California
Abstract: The present invention provides compositions exhibiting in vivo activity of fibrin in an in vitro setting, in vitro assays comprising such compositions, methods of producing such compositions, and methods of using such compositions and assays. The compositions of the invention include molecules with the biochemical properties of 1) high affinity binding to fibrin receptors and 2) activation of cell-signaling systems comparable to that observed in vivo by fibrin. The fibrin compositions of the invention are compatible both in biochemical assays and cell-based assays, and thus useful for in vitro assays for screening of test agents that modulate cell activation and/or signaling pathways mediated by fibrin or associated with fibrin activity.
Type:
Grant
Filed:
September 16, 2019
Date of Patent:
February 7, 2023
Assignee:
The J. David Gladstone Institutes, a testamentary trust established under the Will of J. David Gladstone
Inventors:
Katerina Akassoglou, Jae Kyu Ryu, Anke Meyer-Franke
Abstract: The present disclosure provides methods for inducing cell cycle reentry of postmitotic cell. The present disclosure further provides cells and compositions for treating diseases, such as cardiovascular diseases, neural disorders, hearing loss, and diabetes.
Type:
Grant
Filed:
February 3, 2020
Date of Patent:
January 3, 2023
Assignee:
The J. David Gladstone Institutes, a testamentary trust established under the Will of J. David Gladstone
Abstract: This application relates generally to the production of modified, non-natural ?1-?2 domains of NKG2D ligands with attached polypeptides having specific target-binding properties, for example, antibodies or variable fragments of antibodies, that are selectively delivered to Chimeric Antigen Receptors (CARs) comprised of modified, non-natural NKG2D receptors on engineered mammalian cells. The targeting of surface-expressed molecules includes those of virus-infected cells that can then be attacked and ablated by engineered cells of the immunity system expressing CARs cognate to the modified, non-natural ?1-?2 domains of NKG2D ligands with attached polypeptides.
Type:
Grant
Filed:
January 28, 2020
Date of Patent:
September 13, 2022
Assignees:
Xyphos Biosciences Inc., THE J. DAVID GLADSTONE INSTITUTES
Inventors:
Kaman Kim, Nigel Killeen, Eytan Herzig, Warner Greene
Abstract: Provided are methods and compositions for identifying candidate agents for treatment of obesity, liver disease, and/or diabetes. Such methods include, e.g., contacting a mammalian cell or cell population with a test agent, and measuring an expression level and/or activity level of ClpP in the mammalian cell or in cells of the cell population. Also provided are methods and compositions for treating an individual (e.g., one who is obese and/or has diabetes). Treatment methods include administering an inhibitor of ClpP to the individual (e.g., to prevent or reduce weight gain, to increase insulin sensitivity, and/or to increase glucose tolerance).
Abstract: The present disclosure provides automated robotic microscopy systems that facilitate high throughput and high content analysis of biological samples, such as living cells and/or tissues. In certain aspects, the systems are configured to reduce user intervention relative to existing technologies, and allow for precise return to and re-imaging of the same field (e.g., the same cell) that has been previously imaged. This capability enables experiments and testing of hypotheses that deal with causality over time with greater precision and throughput than conventional microscopy methods.
Type:
Grant
Filed:
September 26, 2019
Date of Patent:
June 14, 2022
Assignee:
The J. David Gladstone Institutes
Inventors:
Steven M. Finkbeiner, Dale Michael Ando, Aaron C. Daub
Abstract: Compositions and methods of producing mammalian cell populations that include a high proportion of pancreatic beta cells are described herein. Such cell populations are useful for treatment of diabetes. Also provided are materials and methods for the direct differentiation of stem cells, such as embryonic stem cells, into functional pancreatic beta cells. The disclosure provides the benefit of direct differentiation, which results in the production of functional pancreatic beta cells efficiently and at low cost.
Type:
Grant
Filed:
July 26, 2016
Date of Patent:
May 17, 2022
Assignees:
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, The J. David Gladstone Institutes, a testamentary trust established under the Will of J. David Gladstone
Inventors:
Matthias Hebrok, Holger Andreas Russ, Sheng Ding, Saiyong Zhu
Abstract: Provided herein are methods for treating an individual for a disease (e.g., an autoimmune disease or a cancer) using an active agent which affects metabolism of ?-ketoglutarate (?-KG) and/or 2-hydroxyglutarate (2-HG) in differentiating T cells. In some embodiments, a Got1 inhibitor is used to generate a population of T cells enriched in peripheral regulatory T (iTreg) cells, which population enriched in iTreg cells may find use in treating an autoimmune disease. In some embodiments, a TCA cycle-associated metabolite, or a derivative thereof, is used to generate a population of T cells in enriched in IL-17- and IL-17F-producing CD4 T (TH17) cells, which population enriched in TH17 cells may find use in treating a cancer.
Type:
Grant
Filed:
January 12, 2017
Date of Patent:
February 8, 2022
Assignee:
The J. David Gladstone Institutes, a testamentary trust established under the Will of J. David Gladstone
Abstract: This invention provides methods for promoting and/or restoring neurite outgrowth and neuronal regeneration by contacting an injured neuron with an inhibitor of low density lipoprotein receptor-related protein-1 (LRP-1).
Type:
Application
Filed:
November 5, 2020
Publication date:
September 16, 2021
Applicant:
The J. David Gladstone Institutes
Inventors:
Steven L. Gonias, Travis Stiles, Alban Gaultier, Wendy M. Campana, Katerina Akassoglou
Abstract: The present disclosure provides compositions and methods for reactivating latent immunodeficiency virus and/or reducing transcription of HIV integrated into the genome of an HIV-infected cell. The present disclosure provides compositions and methods for treating an immunodeficiency virus infection.
Type:
Grant
Filed:
May 24, 2019
Date of Patent:
August 24, 2021
Assignee:
The J. David Gladstone Institutes, a testamentary trust established under the Will of J. David Gladstone
Abstract: The present invention provides assays and compositions to identify the risk of toxicity in a patient population with genotypic variations in specific proteins and/or protein complexes within the patient population.
Type:
Grant
Filed:
August 8, 2016
Date of Patent:
June 1, 2021
Assignees:
The J. David Gladstone Institutes, The Regents of the University of California
Abstract: Aspects of the present disclosure include fatty acid ?-hydroxyester compounds (e.g., fatty acid esters of ?-hydroxybutyrate), fatty acid esters of butanediol, and pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions having one or more fatty acid ?-hydroxyester compounds and/or one or more fatty acid esters of butanediol. Methods for treating a subject by administering one or more esters to the subject are also provided. Kits containing one or more of the subject esters are also described.
Type:
Grant
Filed:
June 2, 2017
Date of Patent:
January 12, 2021
Assignees:
The J. David Gladstone Institutes, The Regents of The University Of California, Ithaca College
Inventors:
Eric Verdin, Scott Michael Ulrich, John C. Newman