Patents Assigned to BUCK INSTITUTE FOR RESEARCH ON AGING
  • Publication number: 20220000873
    Abstract: In various embodiments methods for the treatment or prophylaxis of an age-related and/or pathology-associated increase in intestinal barrier permeability are provided. In certain embodiments the methods comprise administering to a mammal in need thereof an effective amount of one or more agent(s) that inhibit superoxide or hydrogen peroxide production from the outer ubiquinone-binding site of complex III of the mitochondrial electron transport chain (site IIIQo).
    Type: Application
    Filed: December 9, 2019
    Publication date: January 6, 2022
    Applicant: Buck Institute for Research on Aging
    Inventors: Mark A. Watson, Martin D. Brand, Pankaj Kapahi
  • Patent number: 11091444
    Abstract: In certain embodiments hydantoin compounds are provided herein that are effective to inhibit BACE activity against APP. Without being bound to a particular theory, it is believed the activity of the hydantoins identified herein appears to be associated with binding to BACE and/or to APP particularly when these moieties form a BACE/APP complex. Accordingly, it is believed the compounds described herein represent a new class of compounds designated herein as APP-Binding-BACE Inhibitors (ABBIs) and provide a new mechanism to modulate APP processing. The hydantoins described herein appear to show improved brain permeability and functional BACE inhibition.
    Type: Grant
    Filed: January 10, 2020
    Date of Patent: August 17, 2021
    Assignee: BUCK INSTITUTE FOR RESEARCH ON AGING
    Inventors: Varghese John, Dale E. Bredesen
  • Patent number: 11066448
    Abstract: In various embodiments constructs are provided for the delivery of an effector molecule into a cell. In certain embodiments the construct comprises a cell penetrating peptide (CPP) attached to an effector that is to be delivered into a cell, where the cell penetrating peptide comprises a Zika cell penetrating peptide (Zika CPP), and the effector is selected from the group consisting of a protein, a nucleic acid, an organic compound, a nanoparticle, a viral particle, and the like.
    Type: Grant
    Filed: May 7, 2019
    Date of Patent: July 20, 2021
    Assignee: Buck Institute for Research on Aging
    Inventors: Barbara J. Bailus, Lisa M. Ellerby
  • Patent number: 10844071
    Abstract: In certain embodiments compounds corresponding in structure to the formula: are provided that are effective to lower p-tau and/or to prevent or reduce elevation of p-tau, particularly in response to stress (e.g., elevated cortisol levels). The compounds are useful in the treatment or prophylaxis of pathologies characterized by abnormal amyloid plaque and or tangle formation and/or deposition.
    Type: Grant
    Filed: February 21, 2020
    Date of Patent: November 24, 2020
    Assignee: BUCK INSTITUTE FOR RESEARCH ON AGING
    Inventors: Varghese John, Dale E. Bredesen
  • Patent number: 10835546
    Abstract: In certain embodiments APP-specific BACE inhibitors (ASBIs) are provided as well as uses thereof. In certain embodiments methods of preventing delaying the onset of a pre-Alzheimer's condition and/or cognitive dysfunction, and/or ameliorating one or more symptoms of a pre-Alzheimer's condition and/or cognitive dysfunction, or preventing or delaying the progression of a pre-Alzheimer's condition or cognitive dysfunction to Alzheimer's disease are provided where the method involves administering to a subject in need thereof an APP specific BACE inhibitor (ASBI) in an amount sufficient to prevent or delay the onset of a pre-Alzheimer's cognitive dysfunction, and/or to ameliorate one or more symptoms of a pre-Alzheimer's cognitive dysfunction, and/or to prevent or delay the progression of a pre-Alzheimer's cognitive dysfunction to Alzheimer's disease. In certain embodiments the ASBI is a flavonoid (e.g. galangin) or flavonoid progrug (e.g., galangin prodrug).
    Type: Grant
    Filed: June 6, 2019
    Date of Patent: November 17, 2020
    Assignee: BUCK INSTITUTE FOR RESEARCH ON AGING
    Inventors: Varghese John, Dale E. Bredesen
  • Patent number: 10766867
    Abstract: In certain embodiments hydantoin compounds are provided herein that are effective to inhibit BACE activity against APP. Without being bound to a particular theory, it is believed the activity of the hydantoins identified herein appears to be associated with binding to BACE and/or to APP particularly when these moieties form a BACE/APP complex. Accordingly, it is believed the compounds described herein represent a new class of compounds designated herein as APP-Binding-BACE Inhibitors (ABBIs) and provide a new mechanism to modulate APP processing. The hydantoins described herein appear to show improved brain permeability and functional BACE inhibition.
    Type: Grant
    Filed: December 6, 2017
    Date of Patent: September 8, 2020
    Assignee: BUCK INSTITUTE FOR RESEARCH ON AGING
    Inventors: Varghese John, Dale E. Bredesen
  • Patent number: 10655144
    Abstract: This disclosure provides non-human animal models for age-related disorders and age-sensitive traits, particularly those caused by senescence-inducing stimuli, wherein the models comprise transgenes selectively expressed by senescent cells. The disclosure further provides methods for identifying therapeutic agents effective for treating or preventing age-related disorders and age-sensitive traits using the animal models, therapeutic agents identified using such methods, pharmaceutical compositions comprising the identified therapeutic agents, and methods of treating or preventing age-related disorders and age-sensitive traits.
    Type: Grant
    Filed: January 12, 2018
    Date of Patent: May 19, 2020
    Assignee: Buck Institute for Research on Aging
    Inventors: Marco Demaria, Francis Rodier, Remi-Martin Laberge, Judith Campisi
  • Patent number: 10618899
    Abstract: Various [1,2,3]triazolo[4,5-d]pyrimidines are provided that are effective to lower p-tau and/or to prevent or reduce elevation of p-tau, particularly in response to stress (e.g., elevated cortisol levels). The compounds are useful in the treatment or prophylaxis of pathologies characterized by abnormal amyloid plaque and or tangle formation and/or deposition.
    Type: Grant
    Filed: February 17, 2016
    Date of Patent: April 14, 2020
    Assignee: Buck Institute for Research on Aging
    Inventors: Varghese John, Dale E. Bredesen
  • Patent number: 10517866
    Abstract: Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
    Type: Grant
    Filed: May 16, 2018
    Date of Patent: December 31, 2019
    Assignees: Unity Biotechnology, Inc., Buck Institute for Research on Aging, Mayo Foundation for Medical Education and Research
    Inventors: Remi-Martin Laberge, James L. Kirkland, Tamar Tchkonia, Yi Zhu, Nathaniel David, Alain Philippe Vasserot, Darren J. Baker, Bennett G. Childs, Jan M. A. van Deursen
  • Patent number: 10517844
    Abstract: In various embodiments a cancer treatment method is provided based on inhibition of proline catabolism. When combined with p53 restoration therapy and/or inhibition of glutaminase, the inhibition of proline catabolism results in a “synthetic lethal” and synergistic anticancer response. Novel suicide inhibitors that induce the degradation of proline dehydrogenase (PRODH) are also provided. Also provided is a method of assaying PRODH to identify responders/non-responders to inhibition of proline catabolism and/or glutaminase.
    Type: Grant
    Filed: November 12, 2015
    Date of Patent: December 31, 2019
    Assignee: Buck Institute for Research on Aging
    Inventors: Gary K. Scott, Christopher C. Benz
  • Patent number: 10478433
    Abstract: Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
    Type: Grant
    Filed: June 13, 2018
    Date of Patent: November 19, 2019
    Assignees: Unity Biotechnology, Inc., Buck Institute for Research on Aging, Mayo Foundation for Medical Education and Research
    Inventors: Remi-Martin Laberge, Judith Campisi, Marco Demaria, Nathaniel David, Darren J. Baker, James L. Kirkland, Tamar Tchkonia, Yi Zhu, Jan M. A. van Deursen, Alain Philippe Vasserot, Bennett G. Childs
  • Patent number: 10478432
    Abstract: Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
    Type: Grant
    Filed: April 18, 2018
    Date of Patent: November 19, 2019
    Assignees: Unity Biotechnology, Inc., Buck Institute for Research on Aging, Mayo Foundation for Medical Education and Research
    Inventors: Remi-Martin Laberge, Judith Campisi, Marco Demaria, Nathaniel David, Alain Philippe Vasserot, James L. Kirkland, Tamar Tchkonia, Yi Zhu, Darren J. Baker, Bennett G. Childs, Jan M. A. van Deursen
  • Patent number: 10449177
    Abstract: The invention provides compositions and methods for the treatment of mild cognitive impairment (MCI), and for inhibiting, reducing, delaying and/or preventing the progression of MCI to Alzheimer's disease. The methods entail administering an effective amount of one or more compounds selected from the group consisting of tropisetron, disulfuram, honokiol and nimetazepam. The methods also are useful for prophylactic and therapeutic treatment of amyloidogenic diseases, including Alzheimer's disease.
    Type: Grant
    Filed: August 19, 2011
    Date of Patent: October 22, 2019
    Assignee: Buck Institute for Research on Aging
    Inventors: Varghese John, Dale E. Bredesen
  • Patent number: 10413542
    Abstract: Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
    Type: Grant
    Filed: April 11, 2018
    Date of Patent: September 17, 2019
    Assignees: Buck Institute for Research on Aging, Unity Biotechnology, Inc., Mayo Foundation for Medical Education and Research
    Inventors: Remi-Martin Laberge, Nathaniel David, Alain Philippe Vasserot, Darren J. Baker, Bennett G. Childs, James L. Kirkland, Tamar Tchkonia, Jan M. A. van Deursen, Yi Zhu
  • Patent number: 10357508
    Abstract: In certain embodiments APP-specific BACE inhibitors (ASBIs) are provided as well as uses thereof. In certain embodiments methods of preventing or delaying the onset of a pre-Alzheimer's condition and/or cognitive dysfunction, and/or ameliorating one or more symptoms of a pre-Alzheimer's condition and/or cognitive dysfunction, or preventing or delaying the progression of a pre-Alzheimer's condition or cognitive dysfunction to Alzheimer's disease are provided where the method involves administering to a subject in need thereof an APP specific BACE inhibitor (ASBI) in an amount sufficient to prevent or delay the onset of a pre-Alzheimer's cognitive dysfunction, and/or to ameliorate one or more symptoms of a pre-Alzheimer's cognitive dysfunction, and/or to prevent or delay the progression of a pre-Alzheimer's cognitive dysfunction to Alzheimer's disease. In certain embodiments the ASBI is a flavonoid (e.g. galangin) or flavonoid prodrug (e.g., galangin prodrug).
    Type: Grant
    Filed: March 15, 2013
    Date of Patent: July 23, 2019
    Assignee: BUCK INSTITUTE FOR RESEARCH ON AGING
    Inventors: Varghese John, Dale E. Bredesen
  • Patent number: 10328073
    Abstract: Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
    Type: Grant
    Filed: August 3, 2018
    Date of Patent: June 25, 2019
    Assignees: Unity Biotechnology, Inc., Buck Institute for Research on Aging, Mayo Foundation for Medical Education and Research
    Inventors: Remi-Martin Laberge, Judith Campisi, Marco Demaria, Nathaniel David, Alain Philippe Vasserot, James L. Kirkland, Tamar Tchkonia, Yi Zhu, Darren J. Baker, Bennett G. Childs, Jan M. A. van Deursen
  • Patent number: 10328058
    Abstract: Foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines. In advanced lesions, senescent cells promote features of plaque instability, including elastic fiber degradation and fibrous cap thinning, by heightening metalloprotease production. This invention provides methods and materials for treating arthritis by removing senescent cells in or around atherosclerotic plaques, thereby stabilizing the plaques, inhibiting rupture of the plaques and pathological sequelae that manifest as coronary artery disease.
    Type: Grant
    Filed: October 24, 2017
    Date of Patent: June 25, 2019
    Assignees: Mayo Foundation for Medical Education and Research, Unity Biotechnology, Inc., Buck Institute for Research on Aging
    Inventors: Darren J. Baker, Marco Demaria, Albert Davalos, Bennett G. Childs, Jan M. A. van Deursen, James L. Kirkland, Tamar Tchkonia, Yi Zhu, Nathaniel David, Remi-Martin Laberge, Judith Campisi
  • Patent number: 10279018
    Abstract: Provided herein are immunogenic compositions (vaccines) and methods for immunizing a subject with the immunogenic compositions for inducing an adaptive immune response directed specifically against senescent cells for treatment and prophylaxis of age-related diseases and disorders, and other diseases and disorders associated with or exacerbated by the presence of senescent cells. The immunogenic compositions provided herein comprise at least one or more senescent cell-associated antigens, polynucleotides encoding senescent cell-associated antigens, and recombinant expression vectors comprising the polynucleotides for use in administering to a subject in need thereof.
    Type: Grant
    Filed: December 3, 2013
    Date of Patent: May 7, 2019
    Assignees: UNITY BIOTECHNOLOGY, INC., BUCK INSTITUTE FOR RESEARCH ON AGING, KYTHERA BIOPHARMACEUTICALS, INC.
    Inventors: Alain Philippe Vasserot, Serge Lichtsteiner, Judith Campisi
  • Patent number: 10258618
    Abstract: Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
    Type: Grant
    Filed: April 17, 2018
    Date of Patent: April 16, 2019
    Assignees: UNITY BIOTECHNOLOGY, INC., BUCK INSTITUTE FOR RESEARCH AGING, MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH
    Inventors: Remi-Martin Laberge, Judith Campisi, Marco Demaria, Nathaniel David, Darren J. Baker, James L. Kirkland, Tamar Tchkonia, Yi Zhu, Jan M. A. van Deursen
  • Patent number: 10202355
    Abstract: In certain embodiments hydantoin compounds are provided herein that are effective to inhibit BACE activity against APP. Without being bound to a particular theory, it is believed the activity of the hydantoins identified herein appears to be associated with binding to BACE and/or to APP particularly when these moieties form a BACE/APP complex. Accordingly, it is believed the compounds described herein represent a new class of compounds designated herein as APP-Binding-BACE Inhibitors (ABBIs) and provide a new mechanism to modulate APP processing. The hydantoins described herein appear to show improved brain permeability and functional BACE inhibition.
    Type: Grant
    Filed: February 12, 2014
    Date of Patent: February 12, 2019
    Assignee: BUCK INSTITUTE FOR RESEARCH ON AGING
    Inventors: Varghese John, Dale E. Bredesen