Patents by Inventor Matthew D. Shair

Matthew D. Shair 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: 10508121
    Abstract: Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the ?-catenin pathway, methods of modulating STAT 1 activity, methods of modulating the TGF?/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.
    Type: Grant
    Filed: March 5, 2019
    Date of Patent: December 17, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Juergen Ramharter, Henry Efrem Pelish, Brian Bor-Jen Liau, Jae Young Ahn
  • Publication number: 20190185484
    Abstract: Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the ?-catenin pathway, methods of modulating STAT 1 activity, methods of modulating the TGF?/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.
    Type: Application
    Filed: March 5, 2019
    Publication date: June 20, 2019
    Applicant: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Juergen Ramharter, Henry Efrem Pelish, Brian Bor-Jen Liau, Jae Young Ahn
  • Patent number: 10273241
    Abstract: Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the -catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGF?/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.
    Type: Grant
    Filed: May 16, 2018
    Date of Patent: April 30, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Juergen Ramharter, Henry Efrem Pelish, Brian Bor-Jen Liau, Jae Young Ahn
  • Patent number: 10273264
    Abstract: Compounds of Formula (A?), (B?), (C?), (D?), (E?), (A?), (B?), (C?), (D?), (E?), (G1), and (G2) are useful as therapeutics for treating a wide variety of conditions in a host such as a human, e.g., including but not limited to, conditions associated with angiogenesis and/or which are mediated by CDK8 and/or CDK19 kinase activity. Also provided are methods of modulating the ?-catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGF?/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using an effective amount of a compound of Formula (A?), (B?), (C?), (D?), (E?), (A?), (B?), (C?), (D?), (E?), (G1), or (G2).
    Type: Grant
    Filed: December 22, 2017
    Date of Patent: April 30, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Henry Efrem Pelish
  • Patent number: 10273240
    Abstract: New cortistatin compounds and pharmaceutically acceptable salts and pharmaceutically acceptable compositions thereof are provided. These compounds can be used to treat a disorder mediated by CDK8 and/or CDK19 kinase or by the Mediator Complex generally. In particular, the compounds can be used, for example, to treat a disorder such as a tumor, cancer, or a disorder associated with angiogenesis.
    Type: Grant
    Filed: November 8, 2017
    Date of Patent: April 30, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Henry Efrem Pelish
  • Publication number: 20190062340
    Abstract: Specific cortistatin derivatives with advantageous properties for in vivo administration to a host, including a human, in need thereof are provided. These novel species have advantageous pharmacokinetics, low toxicity, low to moderate hERG activity, and/or other pharmacological properties which make them stand out among the class of cortistatins as superior candidates for human administration.
    Type: Application
    Filed: December 21, 2016
    Publication date: February 28, 2019
    Applicant: President and Fellows of Harward College
    Inventors: Matthew D. SHAIR, Henry Efrem PELISH, Jae Young AHN
  • Patent number: 10202400
    Abstract: The present invention relates to analogs of cortistatin A, J, K, and L, having the general formula: and salts thereof, wherein R1, R2, R3, R4, n, and m are as defined herein; processes for preparing such compounds and intermediates thereto; pharmaceutical compositions comprising such compounds; methods for treating a proliferative disease; methods for treating a disease associated with aberrant angiogenesis; methods for inhibiting angiogenesis; and processes for preparing cortistatin A, J, K, and L, and analogs thereof.
    Type: Grant
    Filed: July 24, 2017
    Date of Patent: February 12, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Alec Nathanson Flyer, Hong Myung Lee, Andrew G. Myers, Cristina Montserrat Nieto-Oberhuber, Matthew D. Shair, Chong Si
  • Publication number: 20180369230
    Abstract: The invention relates to methods to to treat patients with specific Cortistatin analogs.
    Type: Application
    Filed: June 22, 2018
    Publication date: December 27, 2018
    Applicant: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Henry Efrem Pelish, Ioana Ilinca Nitulescu, Jae Young Ahn
  • Publication number: 20180319814
    Abstract: Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the -catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGF?/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.
    Type: Application
    Filed: May 16, 2018
    Publication date: November 8, 2018
    Applicant: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Juergen Ramharter, Henry Efrem Pelish, Brian Bor-Jen Liau, Jae Young Ahn
  • Publication number: 20180298024
    Abstract: Specific Cortistatin derivatives with advantageous properties for in vivo administration to a host, including a human, in need thereof are provided. These novel species have advantageous pharmacokinetics, low toxicity, low to moderate hERG activity, and/or other pharmacological properties which make them stand out among the class of Cortistatins as superior candidates for human administration.
    Type: Application
    Filed: June 22, 2018
    Publication date: October 18, 2018
    Applicant: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Henry Efrem Pelish
  • Patent number: 9994582
    Abstract: Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the ?-catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGF?/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.
    Type: Grant
    Filed: June 24, 2016
    Date of Patent: June 12, 2018
    Assignee: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Juergen Ramharter, Henry Efrem Pelish, Brian Bor-Jen Liau, Jae Young Ahn
  • Publication number: 20180134725
    Abstract: New cortistatin compounds and pharmaceutically acceptable salts and pharmaceutically acceptable compositions thereof are provided. These compounds can be used to treat a disorder mediated by CDK8 and/or CDK19 kinase or by the Mediator Complex generally. In particular, the compounds can be used, for example, to treat a disorder such as a tumor, cancer, or a disorder associated with angiogenesis.
    Type: Application
    Filed: November 8, 2017
    Publication date: May 17, 2018
    Applicant: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Henry Efrem Pelish
  • Publication number: 20180135134
    Abstract: A method for the targeted selection and treatment of patients with a tumor or cancer, comprising (i) determining whether the patient has a RUNX1 pathway impairment; and if so (ii) administering an effective amount of a cortistatin or its pharmaceutically acceptable salt or oxide, optionally in a pharmaceutically acceptable composition.
    Type: Application
    Filed: November 8, 2017
    Publication date: May 17, 2018
    Applicant: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Henry Efrem Pelish, Ioana IIinca Nitulescu
  • Publication number: 20180118778
    Abstract: Compounds of Formula (A?), (B?), (C?), (D?), (E?), (A?), (B?), (C?), (D?), (E?), (G1), and (G2) are useful as therapeutics for treating a wide variety of conditions in a host such as a human, e.g., including but not limited to, conditions associated with angiogenesis and/or which are mediated by CDK8 and/or CDK19 kinase activity. Also provided are methods of modulating the ?-catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGF?/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using an effective amount of a compound of Formula (A?), (B?), (C?), (D?), (E?), (A?), (B?), (C?), (D?), (E?), (G1), or (G2).
    Type: Application
    Filed: December 22, 2017
    Publication date: May 3, 2018
    Applicant: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Henry Efrem Pelish
  • Publication number: 20170320886
    Abstract: The present invention relates to analogs of cortistatin A, J, K, and L, having the general formula: and salts thereof, wherein R1, R2, R3, R4, n, and m are as defined herein; processes for preparing such compounds and intermediates thereto; pharmaceutical compositions comprising such compounds; methods for treating a proliferative disease; methods for treating a disease associated with aberrant angiogenesis; methods for inhibiting angiogenesis; and processes for preparing cortistatin A, J, K, and L, and analogs thereof.
    Type: Application
    Filed: July 24, 2017
    Publication date: November 9, 2017
    Applicant: President and Fellows of Harvard College
    Inventors: Alec Nathanson Flyer, Hong Myung Lee, Andrew G. Myers, Cristina Montserrat Nieto-Oberhuber, Matthew D. Shair, Chong Si Allston
  • Patent number: 9790253
    Abstract: Provided are a number of compounds structurally related to OSW-1, a natural compound that binds OSBPs. Also provided are pharmaceutical compositions comprising the OSW-1 analogs, as well as methods for use of these OSW-1 analogs, or pharmaceutically acceptable salts, enantiomers, or stereoisomers thereof in the treatment of atherosclerosis. Alzheimer's disease, and cancer, including p21-deficient cancer. Conjugates of OSW-1 analogs with monoclonal antibodies, including monoclonal antibodies targeted to cancer cells, are also provided. Also provided are pharmaceutical compositions comprising the conjugates, as well as methods for use of these conjugates, in the treatment of cancer, including p21-deficient cancer.
    Type: Grant
    Filed: May 18, 2012
    Date of Patent: October 17, 2017
    Assignee: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Anthony William George Burgett
  • Patent number: 9714255
    Abstract: The present invention relates to analogs of cortistatin A, J, K, and L, having the general formula: and salts thereof, wherein R1, R2, R3, R4, n, and m are as defined herein; processes for preparing such compounds and intermediates thereto; pharmaceutical compositions comprising such compounds; methods for treating a proliferative disease; methods for treating a disease associated with aberrant angiogenesis; methods for inhibiting angiogenesis; and processes for preparing cortistatin A, J, K, and L, and analogs thereof.
    Type: Grant
    Filed: September 8, 2015
    Date of Patent: July 25, 2017
    Assignee: President and Fellows of Harvard College
    Inventors: Alec Nathanson Flyer, Hong Myung Lee, Andrew G. Myers, Cristina Montserrat Nieto-Oberhuber, Matthew D. Shair, Chong Si
  • Publication number: 20170029435
    Abstract: Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the ?-catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGF?/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.
    Type: Application
    Filed: June 24, 2016
    Publication date: February 2, 2017
    Inventors: Matthew D. Shair, Juergen Ramharter, Henry Efrem Pelish, Brian Bor-Jen Liau, Jae Young Ahn
  • Patent number: 9321713
    Abstract: The present invention provides a novel 11-step enantioselective approach to the natural product hyperforin, which enables access to a wide variety of hyperforin analogs. The present invention also provides pharmaceutical compositions comprising inventive hyperforin analogs. Hyperforin analogs synthesized using the present synthetic method are envisioned useful in the treatment of various conditions, including, but not limited to, depression and conditions characterized by depression, inflammatory skin conditions, diabetes, asthma, chronic obstructive pulmonary disease (COPD), kidney disorders, and ischemic brain damage.
    Type: Grant
    Filed: June 1, 2012
    Date of Patent: April 26, 2016
    Assignee: President and Fellows of Harvard College
    Inventors: Matthew D. Shair, Brian A. Sparling, David Moebius
  • Publication number: 20150376201
    Abstract: The present invention relates to analogs of cortistatin A, J, K, and L, having the general formula: and salts thereof, wherein R1, R2, R3, R4, n, and m are as defined herein; processes for preparing such compounds and intermediates thereto; pharmaceutical compositions comprising such compounds; methods for treating a proliferative disease; methods for treating a disease associated with aberrant angiogenesis; methods for inhibiting angiogenesis; and processes for preparing cortistatin A, J, K, and L, and analogs thereof.
    Type: Application
    Filed: September 8, 2015
    Publication date: December 31, 2015
    Applicant: President and Fellows of Harvard College
    Inventors: Alec Nathanson Flyer, Hong Myung Lee, Andrew G. Myers, Cristina Montserrat Nieto-Oberhuber, Matthew D. Shair, Chong Si