Patents by Inventor Marvin J. Miller
Marvin J. Miller 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).
-
Patent number: 11820767Abstract: Described herein are compounds and compositions, and methods of making and their use as effective agents against mycobacterial infections.Type: GrantFiled: December 28, 2020Date of Patent: November 21, 2023Assignee: UNIVERSITY OF NOTRE DAME DU LACInventors: Marvin J. Miller, Garrett C. Moraski
-
Patent number: 11731947Abstract: Substituted nitrobenzothiazinones (BTZs) are potent antituberculosis prodrugs that are reductively activated to produce nitroso moieties that form covalent adducts with a cysteine residue of decaprenylphosphoryl-?-D-ribose-2?-oxi-dase (DprE1) of Mycobacterium tuberculosis (Mtb). The resulting cell wall synthesis inhibition is lethal to Mtb, leading to consideration of development of BTZs for clinical use. The hydride-induced reduction of the nitroaromatic proceeds by reversible formation of the corresponding Meisenheimer complex. Herein we demonstrate that chemical reduction of BTZ043 with NaBD4 followed by reoxidation incorporates deuterium into the core nitro aromatic warhead. Subsequent reduction of the deuterated species is not affected, but, as expected, reoxidation is slowed by the deuterium isotope effect, thus prolonging the lifetime of the active nitroso oxidation state.Type: GrantFiled: April 3, 2020Date of Patent: August 22, 2023Assignee: University of Notre Dame du LacInventors: Marvin J. Miller, Viktor Krchnak, Rui Liu
-
Publication number: 20220340566Abstract: A compound represented by formula (I): or its pharmaceutically acceptable salt, wherein a group represented by formula: is a group represented by formula: R1 is each independently halogen, hydroxy, cyano or the like; m is 0, 1, 2, 3 or 4; R2 is a hydrogen atom, halogen, cyano, substituted or unsubstituted alkyl or the like; R3a, R3b, R3c and R3d are each independently hydrogen atom, halogen or the like, with the proviso that R3a, R3b, R3c and R3d are not simultaneously hydrogen atom; ring C is represented as follows: X is CH or N; Y is CH or N; R4 is each independently halogen, hydroxy, cyano or the like; p is 0 or 1; q is 0, 1, 2, 3 or 4; R5 is CR5C or N; R6 is CR6C or N; R7 is CR7C or N; R8 is CR8C or N; R9 is CR9C or N; with the proviso that R5, R6, R7, R8 and R9 are not simultaneously N; R5C, R6C, R7C, R8C and R9C are each independently hydrogen atom or the like.Type: ApplicationFiled: September 10, 2020Publication date: October 27, 2022Applicants: Shionogi & Co., Ltd., HSIRI THERAPEUTICS, INC.Inventors: Manabu FUJITANI, Tsutomu IWAKI, Rina NAKAMURA, Marvin J. MILLER, Garrett C. MORASKI
-
Patent number: 11400079Abstract: Bromine induced lactamization of vinyl acetohydroxamates facilitated syntheses of monocyclic ?-lactams suitable for incorporation of a thiomethyl and extended functionality at the C(4) position. Elaboration of the resulting substituted N-hydroxy-2-azetidinones allowed incorporation of functionalized ?-amino substituents appropriate for enhancement of antibiotic activity. Evaluation of antibacterial activity against a panel of Gram-positive and Gram-negative bacteria revealed structure-activity-relationships (SAR) and identification of potent new monobactam antibiotics. The corresponding bis-catechol conjugate, 42, has excellent activity against Gram-negative bacteria including carbapenemase and carbacephalosporinase producing strains of Acinetobacter baumannii which have been listed by the WHO as being of critical concern worldwide.Type: GrantFiled: October 2, 2018Date of Patent: August 2, 2022Assignee: University of Notre Dame du LacInventors: Marvin J. Miller, Serena Carosso, Rui Liu, Patricia Miller
-
Publication number: 20220235047Abstract: The present invention relates to novel combinations. The invention also relates to such combinations for use as pharmaceuticals, for instance in the treatment of bacterial diseases, including diseased caused by pathogenic mycobacteria such as non-tuberculosis mycobacteria. In particular, the present invention relates to a medicament, characterized in that a compound having a cytochrome bc1 inhibitory activity, or its pharmaceutically acceptable salt, is combined with clarithromycin or azithromycin, and clofazimine, or their pharmaceutically acceptable salts.Type: ApplicationFiled: May 28, 2020Publication date: July 28, 2022Applicants: Shionogi & Co., Ltd., HSIRI THERAPEUTICS, INC.Inventors: Kenzo NISHIGUCHI, Satoshi MIYAGAWA, William D. CLAYPOOL, Marvin J. MILLER, Garrett C. MORASKI, Jeffrey S. SCHOREY
-
Publication number: 20220204463Abstract: Substituted nitrobenzothiazinones (BTZs) are potent antituberculosis prodrugs that are reductively activated to produce nitroso moieties that form covalent adducts with a cysteine residue of decaprenylphospholyl-?-D-ribose-2?-oxi-dase (DprE1) of Mycobacterium tuberculosis (Mtb). The resulting cell wall synthesis inhibition is lethal to Mtb, leading to consideration of development of BTZs for clinical use. The hydride-induced reduction of the nitroaromatic proceeds by reversible formation of the corresponding Meisenheimer complex. Herein we demonstrate that chemical reduction of BTZ043 with NaBD4 followed by reoxidation incorporates deuterium into the core nitro aromatic warhead. Subsequent reduction of the deuterated species is not affected, but, as expected, reoxidation is slowed by the deuterium isotope effect, thus prolonging the lifetime of the active nitroso oxidation state.Type: ApplicationFiled: April 3, 2020Publication date: June 30, 2022Applicant: University of Notre Dame du LacInventors: Marvin J. Miller, Viktor KRCHNAK, Rui LIU
-
Publication number: 20220071999Abstract: Described are compounds and compositions that inhibit or target Cyt-bd, and methods of making, using, and assaying same. Also disclosed are compositions, methods and kits including the compounds and compositions that inhibit or target Cyt-bd, and one or more Cyt-bc1:aa3 inhibitor, F1F0-ATP synthase inhibitor, NADH dehydrogenase (NDH-2) inhibitor, NADH dehydrogenase (NDH-2) activator or antibacterial agent.Type: ApplicationFiled: December 19, 2019Publication date: March 10, 2022Applicants: UNIVERSITY OF NOTRE DAME DU LAC, MONTANA STATE UNIVERSITY, NANYANG TECHNOLOGICAL UNIVERSITYInventors: Marvin J. MILLER, Garrett C. MORASKI, Kevin PETHE
-
Publication number: 20220011304Abstract: Described is a biosensor for detection of analytes and methods of using the same for detecting bacterial infection in a subject. The biosensor comprises an array of gold nanoparticles, biotinylated polyethylene glycol thiol, polyethylene glycol thiol, at least one neutravidin molecule, and at least one affinity reagent immobilized on a surface of the at least one neutravidin molecule. The affinity reagent may be an aptamer or a siderophore. The biosensors demonstrate extraordinary selectively and sensitivity for rapid detection of whole-cell bacteria.Type: ApplicationFiled: December 20, 2018Publication date: January 13, 2022Inventors: Jiayun Hu, Paul W. Bohn, Marvin J. Miller, Manuka Ghosh
-
Patent number: 11155542Abstract: The present invention relates to the general field of treatment of infectious diseases of mammals (humans and animals) caused by bacteria, in particular to the treatment of diseases like tuberculosis (TB), Buruli ulcer and leprosy caused by mycobacteria. The invention aims at the generation of a new series of benzothiazinone compounds having the potential to overcome the above mentioned problems. In a preferred embodiment the invention is concerned with compounds of the general formula (I) wherein R1 represents NO2, R2 represents CF3, at least one of the substituents R3 and R4 is OH, SR14, NHR15, CN, N3, a saturated or unsaturated, optionally halogenated, linear or branched aliphatic radical having 1-4 carbon atoms, linear or branched C1-C4 alkoxy, C1-C4 acyl, and the other of R3 and R4 may in addition be hydrogen, R6 represents a 2-methyl-1,4-dioxa-8-azaspiro[4.Type: GrantFiled: September 21, 2017Date of Patent: October 26, 2021Assignees: University of Notre Dame Du LacInventors: Florian Kloss, Sebastian Schieferdecker, Axel Brakhage, Julia Dreisbach, Marvin J. Miller, Ute Mollmann, Kamil Philip Wojtas
-
Patent number: 11149046Abstract: A compound, comprising: an Fe(III)-binding and/or Fe(III)-bound siderophore; one or more optional linker covalently bound to the siderophore; and daptomycin covalently bound to the linker, or, if no linker is present, then to the siderophore; or pharmaceutically acceptable salt or solvate thereof.Type: GrantFiled: September 10, 2015Date of Patent: October 19, 2021Assignee: HSIRI THERAPEUTICS, INC.Inventors: Marvin J. Miller, Yun-Ming Lin, Manuka Ghosh, Patricia A. Miller, Ute Möllmann
-
Publication number: 20210277023Abstract: Provided are antibiotic conjugate compounds of formula (I) and pharmaceutical compositions thereof. Also provided are methods of treating treat bacterial infection, including infections caused by Gram-negative bacteria, by administering compounds of formula (I).Type: ApplicationFiled: August 9, 2018Publication date: September 9, 2021Applicant: UNIVERSITY OF NOTRE DAME DU LACInventors: Marvin J. MILLER, Rui LIU, Patricia MILLER, Sergei VAKULENKO, Nichole K. STEWART, William BOGGESS
-
Publication number: 20210198254Abstract: Described herein are compounds and compositions, and methods of making and their use as effective agents against mycobacterial infections.Type: ApplicationFiled: December 28, 2020Publication date: July 1, 2021Applicant: UNIVERSITY OF NOTRE DAME DU LACInventors: Marvin J. MILLER, Garrett C. MORASKI
-
Patent number: 11014891Abstract: A compound is provided, comprising: an Fe(III)-binding or an Fe(III)-bound siderophore; one or more optional linker covalently bound to the siderophore; a drug; and an Fe(III) to Fe(II) reduction triggered linker bound to the drug and the linker or, if no linker is present, then bound to the drug and the siderophore. Compositions and methods including the compound are also provided.Type: GrantFiled: October 23, 2014Date of Patent: May 25, 2021Assignee: UNIVERSITY OF NOTRE DAME DU LACInventors: Marvin J. Miller, Cheng Ji
-
Patent number: 10919888Abstract: Described herein are compounds and compositions, and methods of making and their use as effective agents against mycobacterial infections.Type: GrantFiled: September 19, 2016Date of Patent: February 16, 2021Assignee: UNIVERSITY OF NOTRE DAME DU LACInventors: Marvin J. Miller, Garrett C. Moraski
-
Patent number: 10913737Abstract: Embodiments relate to the field of chemistry and biochemistry, and, more specifically, to imidazopyridine compounds, synthesis thereof, and methods of using same. Disclosed herein are various imidazo[1,2-a]pyhdine compounds and methods of using the novel compounds to treat or prevent tuberculosis in a subject or to inhibit fungal growth on plant species. Other embodiments include methods of synthesizing imidazo[1,2-a]pyridine compounds, such as the disclosed imidazo[1,2-a]pyridine compounds.Type: GrantFiled: February 5, 2018Date of Patent: February 9, 2021Assignee: UNIVERSITY OF NOTRE DAME DU LACInventors: Marvin J. Miller, Garrett C. Moraski, Lowell D. Markley, George E. Davis
-
Publication number: 20210009583Abstract: A series of imidazopyridine and pyrazolopyridine compounds is provided in which carbon hydrogen bonds have been replaced with isotopic carbon-deuterium bonds, syntheses thereof, compositions thereof, and methods of using such compounds and compositions. Various embodiments provide methods of killing and/or inhibiting the growth of M. tuberculosis and/or M. avium, and methods of treating, preventing, and/or ameliorating M. tuberculosis, M. avium or other mycobacterial infections in a subject like M. leprae or M. ulcerans.Type: ApplicationFiled: March 11, 2019Publication date: January 14, 2021Applicant: UNIVERSITY OF NOTRE DAME DU LACInventors: Rui LIU, Marvin J. MILLER, Garrett C. MORASKI
-
Publication number: 20200407351Abstract: The present invention relates to the general field of treatment of infectious diseases of mammals (humans and animals) caused by bacteria, in particular to the treatment of diseases like tuberculosis (TB), Buruli ulcer and leprosy caused by mycobacteria. The invention aims at the generation of a new series of benzothiazinone compounds having the potential to overcome the above mentioned problems. The invention is in a preferred embodiment concerned with compounds of the general formula (I), wherein the substituents R1 to R15 have the meanings as provided in claim 1 and depending claims.Type: ApplicationFiled: September 21, 2017Publication date: December 31, 2020Inventors: Florian KLOSS, Sebastian SCHIEFERDECKER, Axel BRAKHAGE, Julia DREISBACH, Marvin J. MILLER, Ute MOLLMANN, Kamil Philip WOJTAS
-
Publication number: 20200330438Abstract: Bromine induced lactamization of vinyl acetohydroxamates facilitated syntheses of monocyclic ?-lactams suitable for incorporation of a thiomethyl and extended functionality at the C(4) position. Elaboration of the resulting substituted N-hydroxy-2-azetidinones allowed incorporation of functionalized ?-amino substituents appropriate for enhancement of antibiotic activity. Evaluation of antibacterial activity against a panel of Gram-positive and Gram-negative bacteria revealed structure-activity-relationships (SAR) and identification of potent new monobactam antibiotics. The corresponding bis-catechol conjugate, 42, has excellent activity against Gram-negative bacteria including carbapenemase and carbacephalosporinase producing strains of Acinetobacter baumannii which have been listed by the WHO as being of critical concern worldwide.Type: ApplicationFiled: October 2, 2018Publication date: October 22, 2020Applicant: University of Notre Dame du LacInventors: Marvin J. MILLER, Serena CAROSSO, Rui LIU, Patricia MILLER
-
Publication number: 20190352691Abstract: A device for detecting bacteria in a sample, comprising: a substrate having a surface; and a plurality of Fe(III)-bound or Fe(III)-binding siderophores specific to the bacteria and covalently attached to the surface; wherein the siderophores are selected from the group consisting of one or more natural siderophores, siderophores having one or more of the formulas described herein, or combination thereof. Methods of detection are also provided.Type: ApplicationFiled: December 12, 2018Publication date: November 21, 2019Applicant: UNIVERSITY OF NOTRE DAME DU LACInventors: Marvin J. MILLER, Cheng JI, Paul BOHN, Sean BRANAGAN, Yang YANG
-
Publication number: 20190285627Abstract: The present invention relates to a method and kit for detecting bacteria in a sample. Substrate having a surface comprising an interdigitated Au electrode array and a plurality of siderophores specific to the bacteria and covalently attached to the surface. In one embodiment, the siderophore may contain a free OH (alcohol), amine, or carboxylic acid to which linker may be attached via ester (on the OH), amide (on the amine) or reverse the ester or amide using the siderophore carboxyl. The linker chain can then be short or long with and without heteroatom substitution to improve solubility as needed. The linker can terminate with a thiol which will react with a gold surface. Alternatively, the linker can terminate with another alcohol, amine or acid which can then be attached to corresponding functionality on the surface of choice.Type: ApplicationFiled: October 18, 2018Publication date: September 19, 2019Applicant: UNIVERSITY OF NOTRE DAME DU LACInventors: Marvin J. Miller, Cheng Ji, Paul Bohn, Sean Branagan, Yang Yang