Patents by Inventor John H. Bushweller
John H. Bushweller 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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Patent number: 11931352Abstract: This invention relates to methods and compositions for treatment of inv (16) leukemia and particularly to treatment of acute myeloid leukemia. Disclosed is a method of treating inv (16) leukemia comprising the step of administering to a subject in in need thereof a therapeutically effective combination of a) a compound of the formula (1) (1) and b) a BRD4 inhibitor selected from the group consisting of JQ1, CeMMECZ, 1-BET 151 (or GSK1210151A), 1-BET 762 (or GSK525762), PFI-1, bromosporine, OTX-015 (or MK-8628), TEN-010, CPI-203, CPI-0610, RVX-208, BI2536, TG101348, LY294002, ABBV-075 (or mivebresib), FT-1101, ZEN003694, pharmaceutically acceptable salts and mixtures thereof. The therapeutically effective combination synergistically inhibits proliferation of inv (16) leukemia cells. This invention also relates to pharmaceutical compositions comprising a therapeutically effective combination of the compound of formula (1) and the BRD4 inhibitor and a pharmaceutically acceptable excipient.Type: GrantFiled: May 24, 2019Date of Patent: March 19, 2024Assignees: UNIVERSITY OF VIRGINIA PATENT FOUNDATION, UNIVERSITY OF MASSACHUSETTSInventors: John H. Bushweller, Anuradha Illendula, Lucio Hernan Castilla, John Anto Pulikkan
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Patent number: 11241421Abstract: This invention relates to methods and compositions for treatment of inv(16) leukemia and particularly to treatment of acute myeloid leukemia. Disclosed is a method of treating inv(16) leukemia comprising the step of administering to a subject in need thereof a therapeutically effective combination of a) a compound of the formula (1) and b) a chemotherapeutic agent selected from the group consisting of pirarubicin, aclarubicin, mitoxantrone, doxorubicin, daunorubicin, idarubicin, epirubicin, cytarabine, pharmaceutically acceptable salts and mixtures thereof. The therapeutically effective combination synergistically inhibits proliferation of inv(16) leukemia cells. This invention also relates to pharmaceutical compositions comprising a therapeutically effective combination of the compound of formula (1) and the chemotherapeutic agent and a pharmaceutically acceptable excipient.Type: GrantFiled: July 27, 2017Date of Patent: February 8, 2022Assignee: UNIVERSITY OF VIRGINIA PATENT FOUNDATIONInventors: John H. Bushweller, Anuradha Illendula
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Publication number: 20210205280Abstract: This invention relates to methods and compositions for treatment of inv (16) leukemia and particularly to treatment of acute myeloid leukemia. Disclosed is a method of treating inv (16) leukemia comprising the step of administering to a subject in in need thereof a therapeutically effective combination of a) a compound of the formula (1) (1) and b) a BRD4 inhibitor selected from the group consisting of JQ1, CeMMECZ, 1-BET 151 (or GSK1210151A), 1-BET 762 (or GSK525762), PFI-1, bromosporine, OTX-015 (or MK-8628), TEN-010, CPI-203, CPI-0610, RVX-208, BI2536, TG101348, LY294002, ABBV-075 (or mivebresib), FT-1101, ZEN003694, pharmaceutically acceptable salts and mixtures thereof. The therapeutically effective combination synergistitally inhibits proliferation of inv (16) leukemia cells. This invention also relates to pharmaceutical compositions comprising a therapeutically effective combination of the compound of formula (1) and the BRD4 inhibitor and a pharmaceutically acceptable excipient.Type: ApplicationFiled: May 24, 2019Publication date: July 8, 2021Inventors: John H. BUSHWELLER, Anuradha ILLENDULA, Lucio Hernan CASTILLA, John Anto PULIKKAN
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Patent number: 10562890Abstract: This invention relates to compounds that bind to wild-type CBF? and inhibit CBF? binding to RUNX proteins. The potent compounds of the invention inhibit this protein-protein interaction at low micromolar concentrations, using allosteric mechanism to achieve inhibition, displace wild-type CBF? from RUNX1 in cells, change occupancy of RUNX1 on target genes, and alter gene expression of RUNX1 target genes. These inhibitors show clear biological effects consistent with on-target RUNX protein activity. Pharmaceutical compositions containing a compound of the invention and a pharmaceutically acceptable carrier represent a separate embodiment of the invention. Another embodiment of the invention are methods of treating a RUNX-signaling-dependent cancer that expresses wild-type CBF? in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.Type: GrantFiled: August 13, 2015Date of Patent: February 18, 2020Assignee: UNIVERSITY OF VIRGINIA PATENT FOUNDATIONInventors: John H. Bushweller, Anuradha Illendula
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Publication number: 20190343820Abstract: This invention relates to methods and compositions for treatment of inv(16) leukemia and particularly to treatment of acute myeloid leukemia. Disclosed is a method of treating inv(16) leukemia comprising the step of administering to a subject in need thereof a therapeutically effective combination of a) a compound of the formula (1) and b) a chemotherapeutic agent selected from the group consisting of pirarubicin, aclarubicin, mitoxantrone, doxorubicin, daunorubicin, idarubicin, epirubicin, cytarabine, pharmaceutically acceptable salts and mixtures thereof. The therapeutically effective combination synergistically inhibits proliferation of inv(16) leukemia cells. This invention also relates to pharmaceutical compositions comprising a therapeutically effective combination of the compound of formula (1) and the chemotherapeutic agent and a pharmaceutically acceptable excipient.Type: ApplicationFiled: July 27, 2017Publication date: November 14, 2019Inventors: John H. BUSHWELLER, Anuradha ILLENDULA
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Patent number: 9926290Abstract: This invention describes the development of targeted small molecule inhibitors of the inv(16) fusion, the causative agent in ˜12% of acute myeloid leukemia (AML). The inv(16) fusion results in expression of the CBF?-SMMHC fusion protein in the blood cells of afflicted patients. The present invention provides compounds which inhibit the function of both CBF? and the CBF?-SMMHC fusion. These compounds block the growth of an inv(16) leukemia cell line as well as increase its apoptosis, while showing minimal effects against non inv(16) cell lines. As a mechanism to develop inhibitors with selectivity for the CBF?-SMMHC fusion protein, the present invention further provides dimeric derivatives of these compounds which show both increased potency as well as selectivity for CBF?-SMMHC. These compounds show potent inhibition of an inv(16) leukemia cell line with minimal effects on non inv(16) cell lines.Type: GrantFiled: December 14, 2015Date of Patent: March 27, 2018Assignee: University of Virginia Patent FoundationInventors: John H. Bushweller, Jolanta Grembecka, Anuradha Illendula, Lauren Mishra
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Publication number: 20170233375Abstract: This invention relates to compounds that bind to wild-type CBF? and inhibit CBF? binding to RUNX proteins. The potent compounds of the invention inhibit this protein-protein interaction at low micromolar concentrations, using allosteric mechanism to achieve inhibition, displace wild-type CBF? from RUNX1 in cells, change occupancy of RUNX1 on target genes, and alter gene expression of RUNX1 target genes. These inhibitors show clear biological effects consistent with on-target RUNX protein activity. Pharmaceutical compositions containing a compound of the invention and a pharmaceutically acceptable carrier represent a separate embodiment of the invention. Another embodiment of the invention are methods of treating a RUNX-signaling-dependent cancer that expresses wild-type CBF? in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.Type: ApplicationFiled: August 13, 2015Publication date: August 17, 2017Applicant: UNIVERSITY OF VIRGINIA PATENT FOUNDATIONInventors: John H. BUSHWELLER, Anuradha ILLENDULA
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Publication number: 20160096820Abstract: This invention describes the development of targeted small molecule inhibitors of the inv(16) fusion, the causative agent in ˜12% of acute myeloid leukemia (AML). The inv(16) fusion results in expression of the CBF?-SMMHC fusion protein in the blood cells of afflicted patients. The present invention provides compounds which inhibit the function of both CBF? and the CBF?-SMMHC fusion. These compounds block the growth of an inv(16) leukemia cell line as well as increase its apoptosis, while showing minimal effects against non inv(16) cell lines. As a mechanism to develop inhibitors with selectivity for the CBF?-SMMHC fusion protein, the present invention further provides dimeric derivatives of these compounds which show both increased potency as well as selectivity for CBF?-SMMHC. These compounds show potent inhibition of an inv(16) leukemia cell line with minimal effects on non inv(16) cell lines.Type: ApplicationFiled: December 14, 2015Publication date: April 7, 2016Inventors: John H. Bushweller, Jolanta Grembecka, Anuradha Illendula, Lauren Dixon
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Patent number: 9221764Abstract: This invention describes the development of targeted small molecule inhibitors of the inv(16) fusion, the causative agent in ˜12% of acute myeloid leukemia (AML). The inv(16) fusion results in expression of the CBF?-SMMHC fusion protein in the blood cells of afflicted patients. The present invention provides compounds which inhibit the function of both CBF? and the CBF?-SMMHC fusion. These compounds block the growth of an inv(16) leukemia cell line as well as increase its apoptosis, while showing minimal effects against non inv(16) cell lines. As a mechanism to develop inhibitors with selectivity for the CBF?-SMMHC fusion protein, the present invention further provides dimeric derivatives of these compounds which show both increased potency as well as selectivity for CBF?-SMMHC. These compounds show potent inhibition of an inv(16) leukemia cell line with minimal effects on non inv(16) cell lines.Type: GrantFiled: May 7, 2014Date of Patent: December 29, 2015Assignee: University of Virginia Patent FoundationInventors: John H. Bushweller, Jolanta Grembecka, Anuradha Illendula, Lauren Dixon
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Publication number: 20140243331Abstract: This invention describes the development of targeted small molecule inhibitors of the inv(16) fusion, the causative agent in ˜12% of acute myeloid leukemia (AML). The inv(16) fusion results in expression of the CBF?-SMMHC fusion protein in the blood cells of afflicted patients. The present invention provides compounds which inhibit the function of both CBF? and the CBF?-SMMHC fusion. These compounds block the growth of an inv(16) leukemia cell line as well as increase its apoptosis, while showing minimal effects against non inv(16) cell lines. As a mechanism to develop inhibitors with selectivity for the CBF?-SMMHC fusion protein, the present invention further provides dimeric derivatives of these compounds which show both increased potency as well as selectivity for CBF?-SMMHC. These compounds show potent inhibition of an inv(16) leukemia cell line with minimal effects on non inv(16) cell lines.Type: ApplicationFiled: May 7, 2014Publication date: August 28, 2014Applicant: UNIVERSITY OF VIRGINIA PATENT FOUNDATIONInventors: John H. Bushweller, Jolanta Grembecka, Anuradha Illendula, Lauren Dixon
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Patent number: 8748618Abstract: This invention describes the development of targeted small molecule inhibitors of the inv(16) fusion, the causative agent in ˜12% of acute myeloid leukemia (AML). The inv(16) fusion results in expression of the CBF?-SMMHC fusion protein in the blood cells of afflicted patients. The present invention provides compounds which inhibit the function of both CBF? and the CBF?-SMMHC fusion. These compounds block the growth of an inv(16) leukemia cell line as well as increase its apoptosis, while showing minimal effects against non inv(16) cell lines. As a mechanism to develop inhibitors with selectivity for the CBF?-SMMHC fusion protein, the present invention further provides dimeric derivatives of these compounds which show both increased potency as well selectivity for CBF?-SMMHC. These compounds show potent inhibition of an inv(16) leukemia cell line with minimal effects on non inv(16) cell lines.Type: GrantFiled: May 13, 2010Date of Patent: June 10, 2014Assignee: University of Virginia Patent FoundationInventors: John H. Bushweller, Jolanta Grembecka, Anuradha Illendula, Lauren Dixon
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Publication number: 20120059003Abstract: This invention describes the development of targeted small molecule inhibitors of the inv(16) fusion, the causative agent in ˜12% of acute myeloid leukemia (AML). The inv(16) fusion results in expression of the CBF?-SMMHC fusion protein in the blood cells of afflicted patients. The present invention provides compounds which inhibit the function of both CBF? and the CBF?-SMMHC fusion. These compounds block the growth of an inv(16) leukemia cell line as well as increase its apoptosis, while showing minimal effects against non inv(16) cell lines. As a mechanism to develop inhibitors with selectivity for the CBF?-SMMHC fusion protein, the present invention further provides dimeric derivatives of these compounds which show both increased potency as well selectivity for CBF?-SMMHC. These compounds show potent inhibition of an inv(16) leukemia cell line with minimal effects on non inv(16) cell lines.Type: ApplicationFiled: May 13, 2010Publication date: March 8, 2012Applicant: UNIVERSITY OF VIRGINIA PATENT FOUNDATIONInventors: John H. Bushweller, Jolanta Grembecka, Anuradha Illendula, Lauren Dixon