Patents by Inventor Gokhan S. Hotamisligil
Gokhan S. Hotamisligil 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: 20230203142Abstract: The present invention provides a method to identify compounds useful in inhibiting the adverse effects of excessive FABP4 on the modulation of NDPK-ADK agonism of G protein-coupled receptors (GPCR) and channels in FABP4-mediated disorders. It has been surprisingly discovered that the fatty acid binding protein 4 (FABP4) inhibits the ability of the nucleoside diphosphate kinase (NDPK) and adenosine kinase (ADK) complex to agonize GPCRs on target cells by forming an NDPK-ADK/FABP4 complex, resulting in, amongst other things, impaired or reduced insulin secretion in islet ?-cells and an increase in glucose levels in the bloodstream. By inhibiting the formation of the NDPK-ADK/FABP4 complex, or inhibiting FABP4 downregulation of NDPK-ADK complex modulation of GPCRs, it has been discovered that FABP4-medited effects can be blunted, including the modulation of islet ?-cell insulin secretion, providing for a reduction in glucose levels and the attenuation of metabolic dysfunction.Type: ApplicationFiled: November 8, 2022Publication date: June 29, 2023Inventors: Gökhan S. Hotamisligil, Ediz Calay, Kacey Prentice, Jani Pertti Kristian Saksi
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Patent number: 11685774Abstract: A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of secreted aP2, secretion of aP2, or a serum aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Exemplary compositions inhibit cellular secretion of aP2 or bind to circulating aP2, thereby reducing the level or activity of aP2 in blood or serum.Type: GrantFiled: November 23, 2020Date of Patent: June 27, 2023Assignee: President And Fellows of Harvard CollegeInventors: Gokhan S. Hotamisligil, Haiming Cao
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Publication number: 20220411490Abstract: Provided herein are compounds, compositions, and methods of identifying compounds that neutralize the ability of the cannabinoid receptor type-1 (CB1) agonist 2-arachidonylglycerol (2-AG) in complex with its obligate binding partner adipocyte lipid binding protein (aP2) from agonizing CB1 signaling in peripheral tissues. Further provided herein are methods of treating a disorder associated with dysregulated or abnormal hepatic de novo lipogenesis and/or hepatic selective insulin resistance by inhibiting cannabinoid receptor type-1 (CB1) agonist 2-arachidonylglycerol (2-AG) in complex with its obligate binding partner adipocyte lipid binding protein (aP2) from binding and agonizing CB1.Type: ApplicationFiled: May 26, 2022Publication date: December 29, 2022Inventors: Gokhan S. Hotamisligil, Kosei Eguchi
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Patent number: 11345748Abstract: Provided herein are compounds, compositions, and methods of identifying compounds that neutralize the ability of the cannabinoid receptor type-1 (CB1) agonist 2-arachidonylglycerol (2-AG) in complex with its obligate binding partner adipocyte lipid binding protein (aP2) from agonizing CB1 signaling in peripheral tissues. Further provided herein are methods of treating a disorder associated with dysregulated or abnormal hepatic de novo lipogenesis and/or hepatic selective insulin resistance by inhibiting cannabinoid receptor type-1 (CB1) agonist 2-arachidonylglycerol (2-AG) in complex with its obligate binding partner adipocyte lipid binding protein (aP2) from binding and agonizing CB1.Type: GrantFiled: December 9, 2019Date of Patent: May 31, 2022Assignee: President and Fellows of Harvard CollegeInventors: Gökhan S. Hotamisligil, Kosei Eguchi
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Publication number: 20220089705Abstract: This invention is in the area of improved anti-aP2 antibodies and antigen binding agents, and compositions thereof, which target the lipid chaperone aP2/FABP4 (referred to as “aP2”) for use in treating disorders such as diabetes, obesity, cardiovascular disease, fatty liver disease, and/or cancer, among others. In one aspect, improved treatments for aP2 mediated disorders are disclosed in which serum aP2 is targeted and the biological activity of aP2 is neutralized or modulated using low-binding affinity aP2 monoclonal antibodies, providing lower fasting blood glucose levels, improved systemic glucose metabolism, increased systemic insulin sensitivity, reduced fat mass, reduced liver steatosis, reduced cardiovascular disease and/or a reduced risk of developing cardiovascular disease.Type: ApplicationFiled: May 21, 2021Publication date: March 24, 2022Applicant: President and Fellows of Harvard CollegeInventors: Gökhan S. Hotamisligil, Mehmet F. Burak, Feyza Engin, Scott B. Widenmaier, Karen Inouye, Elisabeth Helen Roberts, Adrian Richard Moore, Carl Brendan Doyle, Ralph Adams, Karine Jeannine Madeleine Hervé, Shauna Mhairi Wales, Kerry Louise Tyson
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Publication number: 20210171599Abstract: The present invention provides a method to identify and use compounds for the inhibition of abnormal or dysregulated hepatic glucose production that results in elevated blood glucose levels and associated metabolic disorders. The invention is based on the surprising discovery that the glucagon forms an obligate binding complex with aP2, which is necessary for activation of the glucagon G-coupled protein receptor.Type: ApplicationFiled: July 23, 2020Publication date: June 10, 2021Applicants: President and Fellows of Harvard College, The Brigham and Women's Hospital, Inc.Inventors: Gokhan S. Hotamisligil, Ediz Calay, Amir Tirosh, Gurol Tuncman, Motohiro Sekiya
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Patent number: 11014979Abstract: This invention is in the area of improved anti-aP2 antibodies and antigen binding agents, and compositions thereof, which target the lipid chaperone aP2/FABP4 (referred to as “aP2”) for use in treating disorders such as diabetes, obesity, cardiovascular disease, fatty liver disease, and/or cancer, among others. In one aspect, improved treatments for aP2 mediated disorders are disclosed in which serum aP2 is targeted and the biological activity of aP2 is neutralized or modulated using low-binding affinity aP2 monoclonal antibodies, providing lower fasting blood glucose levels, improved systemic glucose metabolism, increased systemic insulin sensitivity, reduced fat mass, reduced liver steatosis, reduced cardiovascular disease and/or a reduced risk of developing cardiovascular disease.Type: GrantFiled: November 20, 2018Date of Patent: May 25, 2021Assignee: President and Fellows of Harvard CollegeInventors: Gökhan S. Hotamisligil, Mehmet F. Burak, Feyza Engin, Scott B. Widenmaier, Elisabeth Helen Roberts, Adrian Richard Moore, Carl Brendan Doyle, Ralph Adams, Karine Jeannine Madeleine Hervé, Shauna Mhairi Wales, Kerry Louise Tyson, Karen Inouye
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Publication number: 20210147527Abstract: A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of secreted aP2, secretion of aP2, or a serum aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Exemplary compositions inhibit cellular secretion of aP2 or bind to circulating aP2, thereby reducing the level or activity of aP2 in blood or serum.Type: ApplicationFiled: November 23, 2020Publication date: May 20, 2021Applicant: President and Fellows of Harvard CollegeInventors: Gokhan S. Hotamisligil, Haiming Cao
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Patent number: 10882901Abstract: A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of secreted aP2, secretion of aP2, or a serum aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Exemplary compositions inhibit cellular secretion of aP2 or bind to circulating aP2, thereby reducing the level or activity of aP2 in blood or serum.Type: GrantFiled: December 21, 2017Date of Patent: January 5, 2021Assignee: President and Fellows of Harvard CollegeInventors: Gokhan S. Hotamisligil, Haiming Cao
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Publication number: 20200102380Abstract: Provided herein are compounds, compositions, and methods of identifying compounds that neutralize the ability of the cannabinoid receptor type-1 (CB1) agonist 2-arachidonylglycerol (2-AG) in complex with its obligate binding partner adipocyte lipid binding protein (aP2) from agonizing CB1 signaling in peripheral tissues. Further provided herein are methods of treating a disorder associated with dysregulated or abnormal hepatic de novo lipogenesis and/or hepatic selective insulin resistance by inhibiting cannabinoid receptor type-1 (CB1) agonist 2-arachidonylglycerol (2-AG) in complex with its obligate binding partner adipocyte lipid binding protein (aP2) from binding and agonizing CB1.Type: ApplicationFiled: December 9, 2019Publication date: April 2, 2020Applicant: President and Fellows of Harvard CollegeInventors: Gökhan S. Hotamisligil, Kosei Eguchi
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Publication number: 20190161536Abstract: This invention is in the area of improved anti-aP2 antibodies and antigen binding agents, and compositions thereof, which target the lipid chaperone aP2/FABP4 (referred to as “aP2”) for use in treating disorders such as diabetes, obesity, cardiovascular disease, fatty liver disease, and/or cancer, among others. In one aspect, improved treatments for aP2 mediated disorders are disclosed in which serum aP2 is targeted and the biological activity of aP2 is neutralized or modulated using low-binding affinity aP2 monoclonal antibodies, providing lower fasting blood glucose levels, improved systemic glucose metabolism, increased systemic insulin sensitivity, reduced fat mass, reduced liver steatosis, reduced cardiovascular disease and/or a reduced risk of developing cardiovascular disease.Type: ApplicationFiled: November 20, 2018Publication date: May 30, 2019Applicants: President and Fellows of Harvard College, UCB Biopharma SPRLInventors: Gökhan S. Hotamisligil, Mehmet F. Burak, Feyza Engin, Scott B. Widenmaier, Elisabeth Helen Roberts, Adrian Richard Moore, Carl Brendan Doyle, Ralph Adams, Karine Jeannine Madeleine Hervé, Shauna Mhairi Wales, Kerry Louise Tyson
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Publication number: 20190135888Abstract: The present invention provides a method to identify and use compounds for the inhibition of abnormal or dysregulated hepatic glucose production that results in elevated blood glucose levels and associated metabolic disorders. The invention is based on the surprising discovery that the glucagon forms an obligate binding complex with aP2, which is necessary for activation of the glucagon G-coupled protein receptor.Type: ApplicationFiled: December 20, 2018Publication date: May 9, 2019Applicant: President and Fellows of Harvard CollegeInventors: Gokhan S. Hotamisligil, Ediz Calay, Amir Tirosh, Gurol Tuncman, Motohiro Sekiya
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Patent number: 10160798Abstract: This invention is in the area of improved anti-aP2 antibodies and antigen binding agents, and compositions thereof, which target the lipid chaperone aP2/FABP4 (referred to as “aP2”) for use in treating disorders such as diabetes, obesity, cardiovascular disease, fatty liver disease, and/or cancer, among others. In one aspect, improved treatments for aP2 mediated disorders are disclosed in which serum aP2 is targeted and the biological activity of aP2 is neutralized or modulated using low-binding affinity aP2 monoclonal antibodies, providing lower fasting blood glucose levels, improved systemic glucose metabolism, increased systemic insulin sensitivity, reduced fat mass, reduced liver steatosis, reduced cardiovascular disease and/or a reduced risk of developing cardiovascular disease.Type: GrantFiled: April 29, 2016Date of Patent: December 25, 2018Assignees: President and Fellows of Harvard College, UCB Biopharma SPRLInventors: Gökhan S. Hotamisligil, Mehmet F. Burak, Feyza Engin, Scott B. Widenmaier, Elisabeth Helen Roberts, Adrian Richard Moore, Carl Brendan Doyle, Ralph Adams, Karine Jeannine Madeleine Hervé, Shauna Mhairi Wales, Kerry Louise Tyson
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Patent number: 9987243Abstract: The present invention provides for a novel lipokine, trans-C16:1n7-palmitoleate, which also serves as a biomarker for metabolic status. More specifically, low concentrations of trans-C16:1n7-palmitoleate the serum indicates a risk of metabolic disease. Additionally, administering trans C16:1n7-palmitoleate to a subject (via pharmaceutical, nutraceutical, or other means), positively impacts glucose metabolism.Type: GrantFiled: August 26, 2016Date of Patent: June 5, 2018Assignee: Trustees of Tufts CollegeInventors: Dariush Mozaffarian, Haiming Cao, Gokhan S. Hotamisligil
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Publication number: 20180105586Abstract: A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of secreted aP2, secretion of aP2, or a serum aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Exemplary compositions inhibit cellular secretion of aP2 or bind to circulating aP2, thereby reducing the level or activity of aP2 in blood or serum.Type: ApplicationFiled: December 21, 2017Publication date: April 19, 2018Applicant: President and Fellows of Harvard CollegeInventors: Gokhan S. Hotamisligil, Haiming Cao
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Patent number: 9879078Abstract: A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of secreted aP2, secretion of aP2, or a serum aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Exemplary compositions inhibit cellular secretion of aP2 or bind to circulating aP2, thereby reducing the level or activity of aP2 in blood or serum.Type: GrantFiled: April 7, 2016Date of Patent: January 30, 2018Assignee: President and Fellows of Harvard CollegeInventors: Gokhan S. Hotamisligil, Haiming Cao
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Publication number: 20160361284Abstract: The present invention provides for a novel lipokine, trans-C16:1n7-palmitoleate, which also serves as a biomarker for metabolic status. More specifically, low concentrations of trans-C16:1n7-palmitoleate the serum indicates a risk of metabolic disease. Additionally, administering trans C16:1n7-palmitoleate to a subject (via pharmaceutical, nutraceutical, or other means), positively impacts glucose metabolism.Type: ApplicationFiled: August 26, 2016Publication date: December 15, 2016Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Dariush Mozaffarian, Haiming Cao, Gokhan S. Hotamisligil
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Publication number: 20160319003Abstract: This invention is in the area of improved anti-aP2 antibodies and antigen binding agents, and compositions thereof, which target the lipid chaperone aP2/FABP4 (referred to as “aP2”) for use in treating disorders such as diabetes, obesity, cardiovascular disease, fatty liver disease, and/or cancer, among others. In one aspect, improved treatments for aP2 mediated disorders are disclosed in which serum aP2 is targeted and the biological activity of aP2 is neutralized or modulated using low-binding affinity aP2 monoclonal antibodies, providing lower fasting blood glucose levels, improved systemic glucose metabolism, increased systemic insulin sensitivity, reduced fat mass, reduced liver steatosis, reduced cardiovascular disease and/or a reduced risk of developing cardiovascular disease.Type: ApplicationFiled: April 29, 2016Publication date: November 3, 2016Inventors: Gökhan S. Hotamisligil, Mehmet F. Burak, Feyza Engin, Scott B. Widenmaier, Elisabeth Helen Roberts, Adrian Richard Moore, Carl Brendan Doyle, Ralph Adams, Karine Jeannine Madeleine Hervé, Shauna Mhairi Wales, Kerry Louise Tyson
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Publication number: 20160297874Abstract: A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of secreted aP2, secretion of aP2, or a serum aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Exemplary compositions inhibit cellular secretion of aP2 or bind to circulating aP2, thereby reducing the level or activity of aP2 in blood or serum.Type: ApplicationFiled: April 7, 2016Publication date: October 13, 2016Inventors: Gokhan S. Hotamisligil, Haiming Cao
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Patent number: 9239334Abstract: The present invention provides for a novel lipokine, C16:1n7-palmitoleate, which also serves as a biomarker for metabolic status. More specifically, a low concentration of C16:1n7-palmitoleate in the free fatty acid component of the serum indicates a risk of metabolic disease, and that de novo lipogenesis should be stimulated. Additionally, administering C16:1n7-palmitoleate to a subject (via nutraceutical or other means), positively impacts lipid metabolism.Type: GrantFiled: September 8, 2009Date of Patent: January 19, 2016Assignee: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Haiming Cao, Gokhan S. Hotamisligil