Patents by Inventor Jason E. Gestwicki
Jason E. Gestwicki 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).
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Publication number: 20200140500Abstract: The invention provides high throughput methods, protein inhibitors, and uses thereof. The invention provides high throughput methods of screening compounds for modulation of protein thermal stability, the method comprising contacting a protein with each of a plurality of test compounds; and (b) measuring the melting transition (Tm) of the protein in the presence of each of the plurality of test compounds, wherein a compound that decreases or increases the apparent Tm by at least 2 standard deviations is identified as a pharmacological protein chaperone.Type: ApplicationFiled: September 27, 2019Publication date: May 7, 2020Inventors: Kathryn McMenimen, Jason E. Gestwicki, Brian DeVree, Leah Makley
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Publication number: 20200138832Abstract: The invention provides inhibitors of ?-crystallin aggregation, including prodrugs of a steroid and/or sterol, and methods of using said ?-crystallin aggregation inhibitors to, e.g., treat or prevent cataracts in a subject having or at risk of developing cataracts.Type: ApplicationFiled: September 30, 2019Publication date: May 7, 2020Inventors: Jason E. Gestwicki, Kathryn McMenimen, Brian DeVree, Leah Makley
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Patent number: 10221171Abstract: Provided herein are compounds of formula (I) which are, inter alia, useful allosteric inhibitors of Hsp70. The compounds and methods provided are useful for the treatment of cancer, infectious and neurodegenerative diseases.Type: GrantFiled: January 11, 2016Date of Patent: March 5, 2019Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIAInventors: Jason E. Gestwicki, Xiaokai Li
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Publication number: 20180318321Abstract: The invention provides inhibitors of ?-crystallin aggregation and methods of using ?-crystallin aggregation inhibitors to, e.g., treat or prevent cataracts in a subject having or at risk of developing cataracts. The invention further provides high throughput methods of screening compounds for modulation of protein thermal stability, the method comprising contacting a protein with each of a plurality of test compounds; and (b) measuring the melting transition (Tm) of the protein in the presence of each of the plurality of test compounds, wherein a compound that decreases or increases the apparent Tm by at least 2 standard deviations is identified as a pharmacological protein chaperone.Type: ApplicationFiled: July 16, 2018Publication date: November 8, 2018Inventors: Jason E. Gestwicki, Kathryn McMenimen, Brian DeVree, Leah Makley
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Publication number: 20180002325Abstract: Provided herein are compounds of formula (I) which are, inter alia, useful allosteric inhibitors of Hsp70. The compounds and methods provided are useful for the treatment of cancer, infectious and neurodegenerative diseases.Type: ApplicationFiled: January 11, 2016Publication date: January 4, 2018Inventors: Jason E. Gestwicki, Xiaokai Li
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Patent number: 9808448Abstract: Disclosed are compounds of formula (l)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.Type: GrantFiled: April 11, 2017Date of Patent: November 7, 2017Assignees: REGENTS OF THE UNIVERSITY OF MICHIGAN, UNIVERSITY OF SOUTH FLORIDAInventors: Jason E. Gestwicki, Chad Dickey
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Publication number: 20170273963Abstract: Disclosed are compounds of formula (I)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.Type: ApplicationFiled: April 11, 2017Publication date: September 28, 2017Inventors: Jason E. Gestwicki, Chad Dickey
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Patent number: 9675623Abstract: The invention provides inhibitors of ?-crystallin aggregation and methods of using ?-crystallin aggregation inhibitors to, e.g., treat or prevent cataracts in a subject having or at risk of developing cataracts. The invention further provides high throughput methods of screening compounds for modulation of protein thermal stability, the method comprising contacting a protein with each of a plurality of test compounds; and (b) measuring the melting transition (Tm) of the protein in the presence of each of the plurality of test compounds, wherein a compound that decreases or increases the apparent Tm by at least 2 standard deviations is identified as a pharmacological protein chaperone.Type: GrantFiled: July 17, 2013Date of Patent: June 13, 2017Assignee: THE REGENTS OF THE UNIVERSITY OF MICHIGANInventors: Jason E. Gestwicki, Kathryn McMenimen, Leah Makley
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Patent number: 9642843Abstract: Disclosed are compounds of formula (1)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.Type: GrantFiled: February 27, 2014Date of Patent: May 9, 2017Assignee: THE REGENTS OF THE UNIVERSITY OF MICHIGANInventor: Jason E. Gestwicki
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Publication number: 20170020895Abstract: The invention provides inhibitors of ?-crystallin aggregation and methods of using ?-crystallin aggregation inhibitors to, e.g., treat or prevent cataracts in a subject having or at risk of developing cataracts. The invention further provides high throughput methods of screening compounds for modulation of protein thermal stability, the method comprising contacting a protein with each of a plurality of test compounds; and (b) measuring the melting transition (Tm) of the protein in the presence of each of the plurality of test compounds, wherein a compound that decreases or increases the apparent Tm by at least 2 standard deviations is identified as a pharmacological protein chaperone.Type: ApplicationFiled: October 6, 2016Publication date: January 26, 2017Inventor: Jason E. Gestwicki
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Publication number: 20160000770Abstract: Disclosed are compounds of formula (1)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.Type: ApplicationFiled: February 27, 2014Publication date: January 7, 2016Inventors: Jason E. Gestwicki, Chad Dickey
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Publication number: 20140275169Abstract: Disclosed herein are combination therapies for enhancing protein degradation. One component is an inhibitor of USP14, while the second component is an inhibitor of Hsp70. In certain embodiments, the invention relates to methods of treating or preventing a tauopathy, such as Alzheimer's disease.Type: ApplicationFiled: March 13, 2014Publication date: September 18, 2014Applicants: The Regents of the University of Michigan, President and Fellows of Harvard CollegeInventors: Daniel J. Finley, Jessica Robert, Monica Boselli, Jason E. Gestwicki, Xiaokai Li
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Publication number: 20140031327Abstract: The invention provides inhibitors of ?-crystallin aggregation and methods of using ?-crystallin aggregation inhibitors to, e.g., treat or prevent cataracts in a subject having or at risk of developing cataracts. The invention further provides high throughput methods of screening compounds for modulation of protein thermal stability, the method comprising contacting a protein with each of a plurality of test compounds; and (b) measuring the melting transition (Tm) of the protein in the presence of each of the plurality of test compounds, wherein a compound that decreases or increases the apparent Tm by at least 2 standard deviations is identified as a pharmacological protein chaperone.Type: ApplicationFiled: July 17, 2013Publication date: January 30, 2014Applicant: REGENTS OF THE UNIVERSITY OF MICHIGANInventor: Jason E. Gestwicki
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Patent number: 8497992Abstract: A system for determining whether interaction occurs between a trial substance and a target substance. The system includes a photonic crystal sensor having a photonic crystal structure and a defect member disposed adjacent the photonic crystal structure. The defect member defines an operative surface able to receive the target substance and the trial substance. The system further includes a light source that inputs a light signal to the photonic crystal structure and the defect member. The light signal is internally reflected, and a resultant output signal is outputted. The output signal relates to whether the trial substance interacts with the target substance at the operative surface. Furthermore, the system includes an identity detector that identifies the trial substance that interacts with the target substance.Type: GrantFiled: November 11, 2009Date of Patent: July 30, 2013Assignee: The Regents of The University of MichiganInventors: Jingyong Ye, Jason E. Gestwicki, Theodore B. Norris, James R. Baker, Jr., Tommaso F. Bersano-Begey
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Publication number: 20110160246Abstract: 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: ApplicationFiled: November 11, 2010Publication date: June 30, 2011Inventors: Isabella A. Graef, Gerald R. Crabtree, Jason E. Gestwicki
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Patent number: 7923230Abstract: 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: GrantFiled: March 17, 2008Date of Patent: April 12, 2011Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Isabella A. Graef, Gerald R. Crabtree, Jason E. Gestwicki
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Publication number: 20100104585Abstract: Multivalent ligands which carry or display at least one recognition element (RE), and preferably a plurality of recognition elements, for binding directly or indirectly to cells or other biological particles or more generally by binding to any biological molecule. The multivalent ligands provided can function for binding or targeting to any biological particle or molecule and particularly to targeting of cells or cell types or viruses, for cell aggregation and for macromolecular assembly of biological macromolecules. The multivalent ligands of this invention are applicable for creating scaffolds (assemblies) of chemical or biological species, including without limitation, antigens, epitopes, ligand binding groups, ligands for cell receptors and various macromolecules. In these scaffolds, the number, spacing, relative positioning and relative orientation of recognition elements can be controlled.Type: ApplicationFiled: October 1, 2009Publication date: April 29, 2010Inventors: Laura L. Kiessling, Byron R. Griffith, Jason E. Gestwicki, Laura Strong
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Publication number: 20100065732Abstract: A system for determining whether interaction occurs between a trial substance and a target substance. The system includes a photonic crystal sensor having a photonic crystal structure and a defect member disposed adjacent the photonic crystal structure. The defect member defines an operative surface able to receive the target substance and the trial substance. The system further includes a light source that inputs a light signal to the photonic crystal structure and the defect member. The light signal is internally reflected, and a resultant output signal is outputted. The output signal relates to whether the trial substance interacts with the target substance at the operative surface. Furthermore, the system includes an identity detector that identifies the trial substance that interacts with the target substance.Type: ApplicationFiled: November 11, 2009Publication date: March 18, 2010Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGANInventors: Jingyong Ye, Jason E. Gestwicki, Theodore B. Norris, James R. Baker, JR., Tommaso F. Bersano-Begey
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Publication number: 20090054334Abstract: A method is provided for improving at least one pharmacokinetic property and maintaining or improving affinity of a therapeutic upon administration to a host. In the method, one administers to the host an effective amount of a bifunctional compound of less than about 5000 Daltons comprising the therapeutic or an active derivative, fragment or analog thereof and a recruiter ligand moiety. The recruiter ligand moiety binds to at least one biomoiety. The bifunctional compound has at least one modulated pharmacokinetic property upon administration to the host and equivalent or greater affinity for a target of the therapeutic as compared to a free drug control that comprises the therapeutic. In addition, the overall drug efficacy is improved by the steric bulk of the bifunctional complexed with the recruited biomoiety.Type: ApplicationFiled: May 23, 2008Publication date: February 26, 2009Inventors: Mitchell W. Mutz, Jason E. Gestwicki
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Patent number: 7485706Abstract: 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: GrantFiled: July 28, 2004Date of Patent: February 3, 2009Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Isabella A. Graef, Gerald R. Crabtree, Jason E. Gestwicki