Patents by Inventor James Elliot Bradner
James Elliot Bradner 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: 20200121721Abstract: Described herein are methods for genetically modifying expanded hematopoietic cells comprising obtaining a quantity of hematopoietic cells, culturing the quantity of hematopoietic cells in the presence of at least one histone deacetylase inhibitor (HDACi) and at least one growth factor to expand the hematopoietic cells, and contacting the expanded hematopoietic cells with a nucleic acid sequence, wherein the nucleic acid sequence modifies the quantity of expanded hematopoietic cells. Further described herein are compositions comprising the genetically modified hematopoietic cells produced by these methods.Type: ApplicationFiled: September 11, 2019Publication date: April 23, 2020Applicants: THE BRIGHAM AND WOMEN'S HOSPITAL, INC., DANA-FARBER CANCER INSTITUTE, INC., NATIONAL UNIVERSITY OF SINGAPOREInventors: Alexander FEDERATION, Li CHAI, Hiro TATETSU, Daniel Geoffrey TENEN, James Elliot BRADNER
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Patent number: 10172821Abstract: In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.Type: GrantFiled: June 29, 2017Date of Patent: January 8, 2019Assignee: President & Fellows of Harvard College Dana-Farber Cancer Institute, Inc.Inventors: James Elliot Bradner, Ralph Mazitschek
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Publication number: 20170360740Abstract: In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.Type: ApplicationFiled: June 29, 2017Publication date: December 21, 2017Inventors: James Elliot Bradner, Ralph Mazitschek
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Patent number: 9724321Abstract: In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.Type: GrantFiled: September 23, 2015Date of Patent: August 8, 2017Assignees: President & Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.Inventors: James Elliot Bradner, Ralph Mazitschek
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Publication number: 20170173083Abstract: Described herein are methods and compositions which lead to the efficient ex vivo expansion of hematopoietic cells, such as hematopoietic stem cells (HSCs) and hematopoietic stem and progenitor cells HSPCs. Using combinations of small molecule drugs and cytokines/growth factors/grown factors targeting epigenetic status in cells, significant improvements in the expansion of cells was observed, including cells isolated from human cord blood or peripheral mobilized stem/progenitor cells. Multiple genes implicated in HSPC function were unperturbed, and efficiency of genomic editing using lentivirus was greatly enhanced following treatment. These novel approaches could be used therapeutically in a variety of hematopoietic transplantation settings, in addition to benefiting gene therapy techniques.Type: ApplicationFiled: March 25, 2015Publication date: June 22, 2017Applicants: THE BRIGHAM AND WOMEN'S HOSPITAL, INC., DANA-FARBER CANCER INSTITUTE, INC., NATIONAL UNIVERSITY OF SINGAPOREInventors: Alexander FEDERATION, Li CHAI, Hiro TATETSU, Daniel Geoffrey TENEN, James Elliot BRADNER
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Publication number: 20160143874Abstract: In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for exmaple. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.Type: ApplicationFiled: September 23, 2015Publication date: May 26, 2016Inventors: James Elliot Bradner, Ralph Mazitschek
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Patent number: 9199923Abstract: In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.Type: GrantFiled: March 6, 2014Date of Patent: December 1, 2015Assignees: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.Inventors: James Elliot Bradner, Ralph Mazitschek
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Publication number: 20150038581Abstract: In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.Type: ApplicationFiled: March 6, 2014Publication date: February 5, 2015Inventors: James Elliot Bradner, Ralph Mazitschek
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Publication number: 20140213620Abstract: In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.Type: ApplicationFiled: July 17, 2013Publication date: July 31, 2014Inventors: James Elliot Bradner, Ralph Mazitschek
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Patent number: 8754237Abstract: In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel bifunctional, trifunctional, or multifunctional compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.Type: GrantFiled: July 16, 2012Date of Patent: June 17, 2014Assignees: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.Inventors: James Elliot Bradner, Ralph Mazitschek, Weiping Tang, Stuart L. Schreiber
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Patent number: 8716344Abstract: The present invention relates to compounds of the following formula wherein R3 is a fluorescent tag. Another aspect of the invention provides an assay for determining the inhibitory effect of a test compound on an HDAC protein comprising: incubating the HDAC protein with a substrate of the above formula in the presence of a test compound; and determining the activity of the HDAC protein.Type: GrantFiled: August 11, 2010Date of Patent: May 6, 2014Assignees: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.Inventors: Ralph Mazitschek, James Elliot Bradner
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Publication number: 20130331455Abstract: The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds.Type: ApplicationFiled: April 12, 2013Publication date: December 12, 2013Applicants: Dana-Farber Cancer Institute, Inc., President and Fellows of Harvard CollegeInventors: Weiping Tang, James Elliot Bradner, Stuart L. Schreiber
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Publication number: 20130261023Abstract: The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support using isocyanate or isothiocyanate chemistry, wherein the density of the array of compounds is at least 1000 spots per cm2.Type: ApplicationFiled: October 10, 2012Publication date: October 3, 2013Applicants: Dana-Farber Cancer Institute, Inc., President and Fellows of Harvard CollegeInventors: David W. Barnes, Angela N. Koehler, James Elliot Bradner, Ralph Mazitschek, Stuart L. Schreiber
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Patent number: 8440716Abstract: The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds.Type: GrantFiled: July 22, 2009Date of Patent: May 14, 2013Assignees: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.Inventors: Weiping Tang, James Elliot Bradner, Stuart L. Schreiber
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Patent number: 8383855Abstract: In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.Type: GrantFiled: February 14, 2007Date of Patent: February 26, 2013Assignees: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.Inventors: James Elliot Bradner, Ralph Mazitschek
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Publication number: 20130040998Abstract: Fluorinated deacetylase inhibitors of the general formulae (I), (II), and (III): and pharmaceutically acceptable salts thereof, as described herein, are useful as inhibitors of histone deacetylases or other deacetylases, and thus are useful for the treatment of various diseases and disorders associated with acetylase activity as described herein (e.g., cancer, neurodegenerative diseases, inflammatory diseases).Type: ApplicationFiled: January 5, 2011Publication date: February 14, 2013Applicants: Dana-Farber Cancer Institute, Inc., President and Fellows of Harvard CollegeInventors: James Elliot Bradner, Ralph Mazitschek
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Publication number: 20130018103Abstract: In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel bifunctional, trifunctional, or multifunctional compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.Type: ApplicationFiled: July 16, 2012Publication date: January 17, 2013Applicants: Dana-Farber Cancer Institute, Inc., President and Fellows of Harvard CollegeInventors: James Elliot Bradner, Ralph Mazitschek, Weiping Tang, Stuart S. Schreiber
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Patent number: 8304451Abstract: In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel inhibitors of histone deacetylases, tubulin deacetylases, and/or aggresome inhibitors, and pharmaceutically acceptable salts and derivatives thereof. The inventive compounds fall into two classes—“isotubacin” class and “isoisotubacin” class—all of which include a 1,3-dioxane core. The present invention further provides methods for treating disorders regulated by histone deacetylase activity, tubulin deacetylase activity, and/or the aggresome (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, protein degradation disorders, protein deposition disorders, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.Type: GrantFiled: May 2, 2007Date of Patent: November 6, 2012Assignees: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.Inventors: Ralph Mazitschek, Nicholas Paul Kwiatkowski, James Elliot Bradner
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Publication number: 20120208889Abstract: HDAC inhibitors of the general formula (I) and (II) and pharmaceutically acceptable salts thereof, as described herein, are useful as inhibitors of histone deacetylases or other deacetylases, and thus are useful for the treatment of various diseases and disorders associated with acetylase/deacetylase activity as described herein (e.g., cancer). In certain embodiments, the compounds of the invention selectively target either a class or isoform of the HDAC family. Another aspect of the invention provides an assay for determining the inhibitory effect of a test compound on an HDAC protein comprising: incubating the HDAC protein with a substrate of general formula (IIIc) in the presence of a test compound; and determining the activity of the HDAC protein.Type: ApplicationFiled: August 11, 2010Publication date: August 16, 2012Applicants: Dana-Farber Cancer Institue, Inc., President and Fellows of Harvard CollegeInventors: Ralph Mazitschek, James Elliot Bradner
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Patent number: 8222423Abstract: In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel bifunctional, trifunctional, or multifunctional compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.Type: GrantFiled: February 14, 2007Date of Patent: July 17, 2012Assignees: Dana-Farber Cancer Institute, Inc., President and Fellows of Harvard College, Howard Hughes Medical InstituteInventors: James Elliot Bradner, Ralph Mazitschek, Tang Weiping, Stuart S. Schreiber