Patents by Inventor Robert H. Mach
Robert H. Mach 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: 11542282Abstract: The present disclosure provides compounds of Formula (I) or (II), pharmaceutically acceptable salt, isotopic variant, stereoisomer, or a mixture thereof. Also provided are pharmaceutical compositions comprising a compound, methods of treating a poly(ADP-ribose)polymerase-1-mediated disease or disorder in a subject, methods of detecting a poly(ADP-ribose)polymerase-1-mediated neurodegenerative disease or disorder, or methods of monitoring cancer treatment in a subject. In some embodiments, the poly(ADP-ribose)polymerase-1-mediated disease or disorder is a neurodegenerative disease or cancer.Type: GrantFiled: February 28, 2019Date of Patent: January 3, 2023Assignee: The Trustees of the University of PennsylvaniaInventors: Robert H. Mach, Sean W. Reilly, Mehran Makvandi, Laura Puentes
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Patent number: 11161865Abstract: The present disclosure relates to compounds of Formula I and II, wherein R1-R20 and FL are defined herein. Also provided are methods of targeting alpha-radiation to poly(ADP-ribose)polymerase 1 (PARP-1) enzyme expression, reducing proliferation of cancer cells, reducing proliferation of cancer cells, detecting intact and enzymatically active poly(ADP-ribose)polymerase 1 (PARP-1) enzyme expression, detecting PARP-1 enzyme expression in a subjects tissue sample, monitoring cancer treatment in a subject, or detecting a PARP-1 receptive cancer in a subject.Type: GrantFiled: May 24, 2018Date of Patent: November 2, 2021Assignee: The Trustees of the University of PennsylvaniaInventors: Robert H. Mach, Sean Reilly, Mehran Makvandi, Kuiying Xu, Daniel A. Pryma, Roger A. Greenberg
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Publication number: 20210138093Abstract: The present invention provides radiolabeled trimethoprim which are useful in imaging tests such as PET scans. The compounds show robust bacterial uptake in vitro and identify infections from inflammation or tumor when administered to a subject. The compounds show rapid and sensitive detection of Ec DHFR containing tumors from control tumors and background tissue. In one aspect, a compound having the structure of formula (I) is provided or a pharmaceutically acceptable salt or prodrug thereof, wherein R is defined herein. Also provided are compositions containing these compounds, positron emission tomography reporter probe comprising these compounds, and methods of imaging a bacterial infection, tracking or monitoring bacteria, distinguishing a bacterial infection from inflammation or tumor, monitoring genetically fused protein expression, and monitoring genetically engineered cells in clinical scenarios such as immunotherapy for cancer treatment.Type: ApplicationFiled: November 16, 2020Publication date: May 13, 2021Inventors: Mark Sellmyer, Robert H. Mach, David A. Mankoff, Iljung Lee
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Publication number: 20200407374Abstract: The present disclosure provides compounds of Formula (I) or (II), pharmaceutically acceptable salt, isotopic variant, stereoisomer, or a mixture thereof. Also provided are pharmaceutical compositions comprising a compound, methods of treating a poly(ADP-ribose)polymerase-1-mediated disease or disorder in a subject, methods of detecting a poly(ADP-ribose)polymerase-1-mediated neurodegenerative disease or disorder, or methods of monitoring cancer treatment in a subject. In some embodiments, the poly(ADP-ribose)polymerase-1-mediated disease or disorder is a neurodegenerative disease or cancer.Type: ApplicationFiled: February 28, 2019Publication date: December 31, 2020Inventors: Robert H. MACH, Sean W. REILLY, Mehran MAKVANDI, Laura PUENTES
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Patent number: 10835625Abstract: The present invention provides radiolabeled trimethoprim which are useful in imaging tests such as PET scans. The compounds show robust bacterial uptake in vitro and identify infections from inflammation or tumor when administered to a subject. The compounds show rapid and sensitive detection of Ec DHFR containing tumors from control tumors and background tissue. In one aspect, a compound having the structure of formula (I) is provided or a pharmaceutically acceptable salt or prodrug thereof, wherein R is defined herein. Also provided are compositions containing these compounds, positron emission tomography reporter probe comprising these compounds, and methods of imaging a bacterial infection, tracking or monitoring bacteria, distinguishing a bacterial infection from inflammation or tumor, monitoring genetically fused protein expression, and monitoring genetically engineered cells in clinical scenarios such as immunotherapy for cancer treatment.Type: GrantFiled: July 15, 2019Date of Patent: November 17, 2020Assignee: The Trustees of the University of PennsylvaniaInventors: Mark Sellmyer, Robert H. Mach, David A. Mankoff, Iljung Lee
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Publication number: 20200109156Abstract: The present disclosure relates to compounds of Formula I and II, wherein R1-R20 and FL are defined herein. Also provided are methods of targeting alpha-radiation to poly(ADP-ribose)polymerase 1 (PARP-1) enzyme expression, reducing proliferation of cancer cells, reducing proliferation of cancer cells, detecting intact and enzymatically active poly(ADP-ribose)polymerase 1 (PARP-1) enzyme expression, detecting PARP-1 enzyme expression in a subjects tissue sample, monitoring cancer treatment in a subject, or detecting a PARP-1 receptive cancer in a subject.Type: ApplicationFiled: May 24, 2018Publication date: April 9, 2020Inventors: Robert H. MACH, Sean REILLY, Mehran MAKVANDI, Kuiying XU, Daniel A. PRYMA, Roger A. GREENBERG
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Publication number: 20190381197Abstract: The present invention provides radiolabeled trimethoprim which are useful in imaging tests such as PET scans. The compounds show robust bacterial uptake in vitro and identify infections from inflammation or tumor when administered to a subject. The compounds show rapid and sensitive detection of Ec DHFR containing tumors from control tumors and background tissue. In one aspect, a compound having the structure of formula (I) is provided or a pharmaceutically acceptable salt or prodrug thereof, wherein R is defined herein. Also provided are compositions containing these compounds, positron emission tomography reporter probe comprising these compounds, and methods of imaging a bacterial infection, tracking or monitoring bacteria, distinguishing a bacterial infection from inflammation or tumor, monitoring genetically fused protein expression, and monitoring genetically engineered cells in clinical scenarios such as immunotherapy for cancer treatment.Type: ApplicationFiled: July 15, 2019Publication date: December 19, 2019Inventors: Mark Sellmyer, Robert H. Mach, David A. Mankoff, Iljung Lee
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Patent number: 10457642Abstract: Described herein is an alpha-emitting radionuclide, 211At, which has been incorporated into a selective sigma-2 ligand moiety to provide cytotoxic capabilities to a chemical compound. As described herein, a compound of formula (I), wherein R1-R4, m, and n are defined herein, was prepared and utilized in in vitro and in vivo tumor targeting of alpha-emitting sigma-2 ligand in a breast cancer model. In one embodiment, the compound is 5-(211At)—N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2,3-dimethoxybenzamide.Type: GrantFiled: April 26, 2016Date of Patent: October 29, 2019Assignee: The Trustees of the University of PennsylvaniaInventors: Daniel A. Pryma, Brian P. Lieberman, Mehran Makvandi, Robert H. Mach
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Patent number: 10398790Abstract: The present invention provides radiolabeled trimethoprim which are useful in imaging tests such as PET scans. The compounds show robust bacterial uptake in vitro and identify infections from inflammation or tumor when administered to a subject. The compounds show rapid and sensitive detection of Ec DHFR containing tumors from control tumors and background tissue. In one aspect, a compound having the structure of formula (I) is provided or a pharmaceutically acceptable salt or prodrug thereof, wherein R is defined herein. Also provided are compositions containing these compounds, positron emission tomography reporter probe comprising these compounds, and methods of imaging a bacterial infection, tracking or monitoring bacteria, distinguishing a bacterial infection from inflammation or tumor, monitoring genetically fused protein expression, and monitoring genetically engineered cells in clinical scenarios such as immunotherapy for cancer treatment.Type: GrantFiled: May 10, 2016Date of Patent: September 3, 2019Assignee: The Trustees of the University of PennsylvaniaInventors: Mark Sellmyer, Robert H. Mach, David A. Mankoff, Iljung Lee
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Publication number: 20180162818Abstract: Described herein is an alpha-emitting radionuclide, 211At, which has been incorporated into a selective sigma-2 ligand moiety to provide cytotoxic capabilities to a chemical compound. As described herein, a compound of formula (I), wherein R1-R4, m, and n are defined herein, was prepared and utilized in in vitro and in vivo tumor targeting of alpha-emitting sigma-2 ligand in a breast cancer model. In one embodiment, the compound is 5-(211At)—N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2,3-dimethoxybenzamide.Type: ApplicationFiled: April 26, 2016Publication date: June 14, 2018Applicant: The Trustees of The University of PennsylvaniaInventors: Daniel A. PRYMA, Brian p. LIEBERMAN, Mehran MAKVANDI, Robert H. MACH
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Publication number: 20180104365Abstract: The present invention provides radiolabeled trimethoprim which are useful in imaging tests such as PET scans. The compounds show robust bacterial uptake in vitro and identify infections from inflammation or tumor when administered to a subject. The compounds show rapid and sensitive detection of Ec DHFR containing tumors from control tumors and background tissue. In one aspect, a compound having the structure of formula (I) is provided or a pharmaceutically acceptable salt or prodrug thereof, wherein R is defined herein. Also provided are compositions containing these compounds, positron emission tomography reporter probe comprising these compounds, and methods of imaging a bacterial infection, tracking or monitoring bacteria, distinguishing a bacterial infection from inflammation or tumor, monitoring genetically fused protein expression, and monitoring genetically engineered cells in clinical scenarios such as immunotherapy for cancer treatment.Type: ApplicationFiled: May 10, 2016Publication date: April 19, 2018Inventors: Mark SELLMYER, Robert H. MACH, David A. MANKGFF, lljung LEE
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Patent number: 9035057Abstract: Tracers for imaging distribution of reactive oxygen species (ROS) are disclosed. The tracers include radiolabeled dihydroethidine (DHE) analogues. Further disclosed are uses of the compounds, including methods of imaging tissue distribution of ROS in vivo by positron emission tomography (PET). Methods of synthesizing the compounds are also disclosed.Type: GrantFiled: December 16, 2010Date of Patent: May 19, 2015Assignee: Washington UniversityInventors: Robert H. Mach, Mark Mintun, Wenhua Chu, Laura Dugan
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Patent number: 8722014Abstract: Tracers for cationic amino acid transport systems and methods of synthesis are disclosed, including compounds comprising a 1H-[1,2,3]triazole moiety. Further disclosed are uses of the analogues, including in vivo imaging of tumors by Positron emission tomography (PET) or Single Photon Emission Computed Tomography (SPECT).Type: GrantFiled: May 3, 2010Date of Patent: May 13, 2014Assignee: Washington UniversityInventors: Robert H. Mach, Jonathan McConathy
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Patent number: 8658131Abstract: Bipiperidinyl compounds and salts thereof are disclosed. The compounds include high affinity ligands for ?1 receptors. Some compounds are also highly selective for ?1 receptor compared to ?2 receptor. Compounds can comprise radioisotopes, including 18F or 11C. Radiolabeled compounds can be used as probes for imaging distribution of ?1 receptor in a subject such as a human using positron emission tomography (PET) scanning.Type: GrantFiled: June 21, 2011Date of Patent: February 25, 2014Assignee: Washington UniversityInventors: Zhude Tu, Robert H. Mach, Wei Wang, Stanley M. Parsons
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Patent number: 8506927Abstract: Pegylated fluoroalkoxybenzamide compounds which selectively bind Sigma-2 receptors are disclosed. These compounds, when labeled with a positron-emitting radioisotope such as 18F, can be used as radiotracers for medical imaging such as imaging of tumors by positron emission tomography (PET). In addition, these compounds, when labeled with 123I, can be used as radiotracers for imaging of tumors by single photon emission computed tomography (SPECT). Methods for synthesis of these compounds are also disclosed.Type: GrantFiled: January 5, 2012Date of Patent: August 13, 2013Assignee: Washington UniversityInventors: Robert H. Mach, Zhude Tu
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Publication number: 20130079522Abstract: Tracers for imaging distribution of reactive oxygen species (ROS) are disclosed. The tracers include radiolabeled dihydroethidine (DHE) analogues. Further disclosed are uses of the compounds, including methods of imaging tissue distribution of ROS in vivo by positron emission tomography (PET). Methods of synthesizing the compounds are also disclosed.Type: ApplicationFiled: December 16, 2010Publication date: March 28, 2013Applicant: WASHINGTON UNIVERSITYInventors: Robert H. Mach, Mark Mintun, Wenhua Chu, Laura Dugan
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Patent number: 8329686Abstract: Novel isatin analogues, including isatin analogues comprising Michael Acceptors (IMAs) are disclosed. Further disclosed are methods of synthesis of the isatin analogues, and uses of the analogues, including inhibition of caspase-3 and caspase-7, and in vivo imaging of apoptosis by Positron emission tomography (PET) or Single Photon Emission Computed Tomography (SPECT).Type: GrantFiled: August 29, 2007Date of Patent: December 11, 2012Assignee: Washington UniversityInventors: Robert H. Mach, Michael Welch, Wenhua Chu, Justin Rothfuss
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Publication number: 20120171119Abstract: Pegylated fluoroalkoxybenzamide compounds which selectively bind Sigma-2 receptors are disclosed. These compounds, when labeled with a positron-emitting radioisotope such as 18F, can be used as radiotracers for medical imaging such as imaging of tumors by positron emission tomography (PET). In addition, these compounds, when labeled with 123I, can be used as radiotracers for imaging of tumors by single photon emission computed tomography (SPECT). Methods for synthesis of these compounds are also disclosed.Type: ApplicationFiled: January 5, 2012Publication date: July 5, 2012Applicant: Washington UniversityInventors: Robert H. Mach, Zhude Tu
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Patent number: 8193360Abstract: Fluoroalkoxybenzamide compounds which selectively bind Sigma-2 receptors are disclosed. These compounds, when labelled with 18F, can be used as radiotracers for imaging of tumors by positron emission tomography (PET). In addition, these compounds, when labelled with 123I, can be used as radiotracers for imaging of tumors by single photon emission computed tomography (SPECT). Methods for synthesis of these compounds are also disclosed.Type: GrantFiled: April 7, 2011Date of Patent: June 5, 2012Assignee: Washington UniversityInventors: Robert H. Mach, Zhude Tu
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Patent number: 8168650Abstract: A series of N-substituted 9-azabicyclo[3.3.1]nonan-3?-yl phenylcarbamate analogs are disclosed, as well as methods of their preparation. Their affinities for sigma (?1 and ?2) receptors are described. Two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3.3.1]nonan-3?-yl)-N?-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3.3.1]nonan-3?-yl)-N?-(2-methoxy-5-methylphenyl)carbamate, are shown to have a high affinity and selectivity for ?2 versus ?1 receptors. Among the disclosed compounds are biotinylated and fluorescent analogs. These compounds can serve as probes to the ?2 receptor. In addition, some disclosed compounds can induce apoptotic cell death by both caspase-dependent and caspase-independent mechanisms, and are effective for treatment of tumors. The compounds can be used as chemotherapeutics or chemosensitizers in the treatment of a wide variety of solid tumors.Type: GrantFiled: August 19, 2009Date of Patent: May 1, 2012Assignee: Washington UniversityInventors: Robert H. Mach, Richard Hotchkiss, William Hawkins, Rebecca Aft, Zhude Tu