Patents by Inventor John M. Essigmann
John M. Essigmann 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: 20180362574Abstract: The present invention provides compounds of Formula (I) or (II), which are thought to be able to inhibit mTOR (mammalian target of rapamycin) signaling pathway, induce UPR (unfolded protein response), and/or perturb mitochondrial function of a cyst cell (e.g., a cyst cell causing polycystic kidney disease (PKD, e.g., autosomal dominant PKD (ADPKD) or autosomal recessive PKD (ARPKD)) or polycystic liver disease (PLD, e.g., autosomal dominant PLD (ADPLD) or autosomal recessive PLD (ARPLD)). The invention also provides pharmaceutical compositions, kits, and methods involving the compounds described herein for use in treating PKD or PLD, inhibiting the growth of a cyst cell, and/or killing a cyst cell.Type: ApplicationFiled: April 13, 2018Publication date: December 20, 2018Applicants: Massachusetts Institute of Technology, Yale UniversityInventors: Bogdan I. Fedeles, Sorin V. Fedeles, Robert G. Croy, Stefan Somlo, John M. Essigmann
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Patent number: 9982009Abstract: The present invention provides compounds of Formula (I) or (II), which are thought to be able to inhibit mTOR (mammalian target of rapamycin) signaling pathway, induce UPR (unfolded protein response), and/or perturb mitochondrial function of a cyst cell (e.g., a cyst cell causing polycystic kidney disease (PKD, e.g., autosomal dominant PKD (ADPKD) or autosomal recessive PKD (ARPKD)) or polycystic liver disease (PLD, e.g., autosomal dominant PLD (ADPLD) or autosomal recessive PLD (ARPLD)). The invention also provides pharmaceutical compositions, kits, and methods involving the compounds described herein for use in treating PKD or PLD, inhibiting the growth of a cyst cell, and/or killing a cyst cell.Type: GrantFiled: October 15, 2014Date of Patent: May 29, 2018Assignees: Massachusetts Institute of Technology, Yale UniversityInventors: Bogdan I. Fedeles, Sorin V. Fedeles, Robert G. Croy, Stefan Somlo, John M. Essigmann
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Publication number: 20170313736Abstract: The present disclosure provides nucleoside analogs of Formula (I) or (II). The nucleoside analogs are expected to show multiple tautomerism and may increase the mutation of an RNA and/or DNA (be mutagenic) of a virus or cancer cell. The multiple tautomerism and mutagenesis of the nucleoside analogs may be adjusted by substituting the nucleoside analogs with one or more electron-donating groups and/or electron-withdrawing groups to increase or decrease the pKa (e.g., to a pKa between 5.5 or 8.5). The present disclosure also provides pharmaceutical compositions and kits including the nucleoside analogs and methods of treating a viral infection (e.g., influenza, HIV infection, or hepatitis) or cancer using the nucleoside analogs, pharmaceutical compositions, or kits.Type: ApplicationFiled: July 6, 2017Publication date: November 2, 2017Applicant: Massachusetts Institute of TechnologyInventors: John M. Essigmann, Andrei Tokmakoff, Bogdan I. Fedeles, Vipender Singh, Chunte Peng
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Patent number: 9714265Abstract: The present disclosure provides nucleoside analogs of Formula (I) or (II). The nucleoside analogs are expected to show multiple tautomerism and may increase the mutation of an RNA and/or DNA (be mutagenic) of a virus or cancer cell. The multiple tautomerism and mutagenesis of the nucleoside analogs may be adjusted by substituting the nucleoside analogs with one or more electron-donating groups and/or electron-withdrawing groups to increase or decrease the pKa (e.g., to a pKa between 5.5 or 8.5). The present disclosure also provides pharmaceutical compositions and kits including the nucleoside analogs and methods of treating a viral infection (e.g., influenza, HIV infection, or hepatitis) or cancer using the nucleoside analogs, pharmaceutical compositions, or kits.Type: GrantFiled: January 28, 2016Date of Patent: July 25, 2017Assignee: Massachusetts Institute of TechnologyInventors: John M. Essigmann, Andrei Tokmakoff, Bogdan I. Fedeles, Vipender Singh, Chunte Peng
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Publication number: 20160222050Abstract: The present disclosure provides nucleoside analogs of Formula (I) or (II). The nucleoside analogs are expected to show multiple tautomerism and may increase the mutation of an RNA and/or DNA (be mutagenic) of a virus or cancer cell. The multiple tautomerism and mutagenesis of the nucleoside analogs may be adjusted by substituting the nucleoside analogs with one or more electron-donating groups and/or electron-withdrawing groups to increase or decrease the pKa (e.g., to a pKa between 5.5 or 8.5). The present disclosure also provides pharmaceutical compositions and kits including the nucleoside analogs and methods of treating a viral infection (e.g., influenza, HIV infection, or hepatitis) or cancer using the nucleoside analogs, pharmaceutical compositions, or kits.Type: ApplicationFiled: January 28, 2016Publication date: August 4, 2016Inventors: John M. Essigmann, Andrei Tokmakoff, Bogdan I. Fedeles, Vipender Singh, Chunte Peng
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Patent number: 9283242Abstract: The present invention provides pharmaceutical compositions comprising a dihydro base described herein (e.g., compound DHdC). The dihydro base may show multiple tautomerism and may increase mutation of an RNA and/or DNA of a virus or cancer cell. The dihydro base may be used to reduce DNA methylation (e.g., in a cancer cell). The present invention also provides kits including the inventive pharmaceutical compositions and methods of treating a viral infection (e.g., influenza, HIV infection, or hepatitis C) or cancer using the pharmaceutical compositions or kits.Type: GrantFiled: January 22, 2014Date of Patent: March 15, 2016Assignee: Massachusetts Institute of TechnologyInventors: John M. Essigmann, Deyu Li, Katherine J. Silvestre
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Publication number: 20150105361Abstract: The present invention provides compounds of Formula (I) or (II), which are thought to be able to inhibit mTOR (mammalian target of rapamycin) signaling pathway, induce UPR (unfolded protein response), and/or perturb mitochondrial function of a cyst cell (e.g., a cyst cell causing polycystic kidney disease (PKD, e.g., autosomal dominant PKD (ADPKD) or autosomal recessive PKD (ARPKD)) or polycystic liver disease (PLD, e.g., autosomal dominant PLD (ADPLD) or autosomal recessive PLD (ARPLD)). The invention also provides pharmaceutical compositions, kits, and methods involving the compounds described herein for use in treating PKD or PLD, inhibiting the growth of a cyst cell, and/or killing a cyst cell.Type: ApplicationFiled: October 15, 2014Publication date: April 16, 2015Applicants: Massachusetts Institute of Technology, Yale UniversityInventors: Bogdan I. Fedeles, Sorin V. Fedeles, Robert G. Croy, Stefan Somlo, John M. Essigmann
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Publication number: 20140206639Abstract: The present invention provides pharmaceutical compositions comprising a dihydro base described herein (e.g., compound DHdC). The dihydro base may show multiple tautomerism and may increase mutation of an RNA and/or DNA of a virus or cancer cell. The dihydro base may be used to reduce DNA methylation (e.g., in a cancer cell). The present invention also provides kits including the inventive pharmaceutical compositions and methods of treating a viral infection (e.g., influenza, HIV infection, or hepatitis C) or cancer using the pharmaceutical compositions or kits.Type: ApplicationFiled: January 22, 2014Publication date: July 24, 2014Applicant: Massachusetts Institute of TechnologyInventors: John M. Essigmann, Deyu Li, Katherine J. Silvestre
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Patent number: 7943600Abstract: This invention provides methods and pharmaceutical compositions for treating a subject having a condition associated with an antibiotic resistant bacterial infection. The invention includes administering to a subject a therapeutically effective combination of an antibiotic and a toxic compound (e.g., a nucleic acid damaging agent, an alkylating agent, or a heavy metal containing compound).Type: GrantFiled: December 20, 2005Date of Patent: May 17, 2011Assignees: Massachusetts Institute of Technology, University of MassachusettsInventors: Doriana Froim, John M. Essigmann, Martin G. Marinus
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Publication number: 20090062236Abstract: The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.Type: ApplicationFiled: January 29, 2007Publication date: March 5, 2009Applicant: Massachusetts Institute of TechnologyInventors: John M. Essigmann, Robert G. Croy, Kevin J. Yarema, Marshall Morningstar
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Patent number: 7169611Abstract: The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.Type: GrantFiled: November 18, 2002Date of Patent: January 30, 2007Assignee: Massachusetts Institute of TechnologyInventors: John M. Essigmann, Robert G. Croy, Kevin J. Yarema, Marshall Morningstar
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Publication number: 20030220311Abstract: The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.Type: ApplicationFiled: November 18, 2002Publication date: November 27, 2003Inventors: John M. Essigmann, Robert G. Croy, Kevin J. Yarema, Marshall Morningstar
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Patent number: 6500669Abstract: The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.Type: GrantFiled: June 23, 1998Date of Patent: December 31, 2002Assignee: Massachusetts Institute of TechnologyInventors: John M. Essigmann, Robert G. Croy, Kevin J. Yarema, Marshall Morningstar
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Patent number: 6475791Abstract: Methods disclosed herein capitalize on the ability of DNA Structure Specific Recognition Proteins (SSRPs) to bind to genomic lesions formed by chemotherapeutic agents, particularly cisplatin-type agents. Methods are provided for predicting whether an agent that damages DNA will also be cytotoxic, and for predicting whether particular eukaryotic cells will be susceptible to killing by a genotoxic drug. A screening method is provided for identifying new genotoxic drugs that produce SSRP-recognized lesions in DNA. Methods also are provided for sensitizing particular eukaryotic cells to killing by chemotherapeutic agents, particularly cisplatin-type drugs.Type: GrantFiled: June 2, 1997Date of Patent: November 5, 2002Assignee: Massachusetts Institute of TechnologyInventors: Stephen J. Lippard, John M. Essigmann, Brian A. Donahue, Jeffrey H. Toney, Suzanne L. Bruhn, Pieter M. Pil, Steven J. Brown, Patti J. Kellett
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Patent number: 6132776Abstract: Methods and compositions related to HIV are disclosed. Using the methods of the present invention, nucleoside analogs may be screened for the ability to be incorporated by reverse transcriptase of human immunodeficiency virus ("HIV RT") and cause incorrect base pairing. Progressive mutation of the virus by such nucleoside analogs renders it non-viable.Type: GrantFiled: June 16, 1997Date of Patent: October 17, 2000Assignee: University of WashingtonInventors: Lawrence A. Loeb, John M. Essigmann
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Patent number: 5882941Abstract: The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.Type: GrantFiled: May 4, 1994Date of Patent: March 16, 1999Assignee: Massachusette Institute of TechnologyInventors: John M. Essigmann, Robert G. Croy, Zhenghuan Chen
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Patent number: 5879917Abstract: The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.Type: GrantFiled: May 4, 1995Date of Patent: March 9, 1999Assignee: Massachusetts Institute of TechnologyInventors: John M. Essigmann, Robert G. Croy, Kevin J. Yarema, Marshall Morningstar
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Patent number: 5705334Abstract: Methods disclosed herein capitalize on the ability of DNA Structure Specific Recognition Proteins (SSRPs) to bind to genomic lesions formed by chemotherapeutic agents, particularly cisplatin-type agents. Methods are provided for predicting whether an agent that damages DNA will also be cytotoxic, and for predicting whether particular eukaryotic cells will be susceptible to killing by a genotoxic drug. A screening method is provided for identifying new genotoxic drugs that produce SSRP-recognized lesions in DNA. Methods also are provided for sensitizing particular eukaryotic cells to killing by chemotherapeutic agents, particularly cisplatin-type drugs.Type: GrantFiled: October 25, 1994Date of Patent: January 6, 1998Assignee: Massachusetts Institute of TechnologyInventors: Stephen J. Lippard, John M. Essigmann, Brian Donahue, Jeffrey H. Toney, Suzanne L. Bruhn, Pieter M. Pil, Steven J. Brown, Patti J. Kellett
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Patent number: 5670621Abstract: DNA structure specific recognition protein of eukaryotic origin and DNA encoding such a factor, as well as probes specific for DNA structure specific recognition protein or DNA encoding it and methods of detecting DNA structure specific recognition protein in eukaryotic cells. In particular, a mammalian cellular factor that selectively recognizes and binds DNA damaged or modified by a drug (the anticancer drug, cis-diamminedichloroplatinum (II) or cisplatin) has been identified.Type: GrantFiled: June 9, 1994Date of Patent: September 23, 1997Assignee: Massachusetts Institute of TechnologyInventors: Brian A. Donahue, Jeffrey H. Toney, John M. Essigmann, Stephen J. Lippard, Pieter M. Pil, Suzanne L. Bruhn, Steven J. Brown, Patti J. Kellett
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Patent number: 5512431Abstract: Methods and compositions related to HIV are disclosed. Using the methods of the present invention, nucleoside analogs may be screened for the ability to be incorporated by reverse transcriptase of human immunodeficiency virus ("HIV RT") and cause incorrect base pairing. Progressive mutation of the virus by such nucleoside analogs renders it non-viable.Type: GrantFiled: June 29, 1994Date of Patent: April 30, 1996Assignee: Darwin Molecular CorporationInventors: Lawrence A. Loeb, John M. Essigmann