Patents Assigned to Merck HDAC Research, LLC
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Patent number: 8227636Abstract: The present invention is directed to prodrugs of hydroxamic acid based histone deacetylase (HDAC) inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The prodrugs are acylated derivatives having increased aqueous solubility and cellular permeability as compared with the free hydroxamic acid, and are useful for inhibiting HDACs, and for selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the prodrugs of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The prodrugs of the invention are also useful in the prevention and treatment of thioredoxin (TRX)-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.Type: GrantFiled: April 5, 2005Date of Patent: July 24, 2012Assignee: Merck HDAC Research, LLCInventors: Thomas A. Miller, David J. Witter, Sandro Belvedere
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Patent number: 8101663Abstract: The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo. The present invention also provides a novel Form I polymorph of SAHA, characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well a unique crystalline structure.Type: GrantFiled: December 7, 2009Date of Patent: January 24, 2012Assignee: Merck HDAC Research, LLCInventors: Thomas A. Miller, Victoria M. Richon
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Patent number: 8067472Abstract: The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.Type: GrantFiled: April 23, 2010Date of Patent: November 29, 2011Assignees: Merck HDAC Research, LLC, Sloan-Kettering Institute for Cancer ResearchInventors: Victoria M. Richon, Judy H. Chiao, William Kevin Kelly, Thomas A. Miller
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Patent number: 7935724Abstract: The present invention relates to a novel class of hydroxamic acid derivatives having a benzothiophene or thiophene backbone. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also inhibit historic deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells.Type: GrantFiled: October 8, 2004Date of Patent: May 3, 2011Assignee: Merck HDAC Research, LLCInventors: Thomas A. Miller, David J. Witter, Sandro Belvedere
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Patent number: 7851509Abstract: The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo. The present invention also provides a novel Form I polymorph of SAHA, characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well a unique crystalline structure.Type: GrantFiled: March 18, 2008Date of Patent: December 14, 2010Assignee: Merck HDAC Research, LLCInventors: Thomas A. Miller, Victoria M. Richon
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Patent number: 7847122Abstract: The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo. The present invention also provides a novel Form I polymorph of SAHA, characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well a unique crystalline structure.Type: GrantFiled: March 18, 2008Date of Patent: December 7, 2010Assignee: Merck HDAC Research, LLCInventor: Thomas A. Miller
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Patent number: 7732490Abstract: The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.Type: GrantFiled: September 11, 2007Date of Patent: June 8, 2010Assignees: Merck HDAC Research, LLC, Sloan-Kettering Institute for Cancer ResearchInventors: Victoria M. Richon, Judy H. Chiao, William Kevin Kelly, Thomas A. Miller
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Patent number: 7652069Abstract: The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo. The present invention also provides a novel Form I polymorph of SAHA, characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well a unique crystalline structure.Type: GrantFiled: October 30, 2007Date of Patent: January 26, 2010Assignee: Merck HDAC Research, LLCInventors: Thomas A. Miller, Victoria M. Richon
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Patent number: 7456219Abstract: The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo. The present invention also provides a novel Form I polymorph of SAHA, characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well a unique crystalline structure.Type: GrantFiled: June 19, 2003Date of Patent: November 25, 2008Assignee: Merck HDAC Research, LLCInventors: Thomas A. Miller, Victoria M. Richon, Judy H. Chiao
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Patent number: 7399787Abstract: The present invention provides methods of treating cancers, chemoprevention, selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.Type: GrantFiled: July 9, 2003Date of Patent: July 15, 2008Assignee: Merck HDAC Research, LLCInventors: Judy H. Chiao, Nicholas G. Bacopoulos, Thomas A. Miller, Carolyn M. Paradise, Victoria M. Richon
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Patent number: 7375137Abstract: The present invention provides methods of treating cancers, chemoprevention, selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.Type: GrantFiled: March 28, 2006Date of Patent: May 20, 2008Assignee: Merck HDAC Research, LLCInventors: Nicholas G. Bacopoulos, Judy H. Chiao, Thomas A. Miller, Carolyn M. Paradise, Victoria M. Richon
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Patent number: 7148257Abstract: Methods for treating mesothelioma comprising administering the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) are disclosed.Type: GrantFiled: August 26, 2003Date of Patent: December 12, 2006Assignees: Merck HDAC Research, LLC, Sloan-Kettering Institute for Cancer ResearchInventors: Nicholas G. Bacopoulos, Judy H. Chiao, Thomas A. Miller, Carolyn M. Paradise, Victoria M. Richon