Patents by Inventor Mohammad R. Seyedsayamdost
Mohammad R. Seyedsayamdost 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: 20240051995Abstract: There is currently a high demand for new therapeutic antibiotics with new mechanisms of action. Disclosed are two small molecules, tryglysin A and B, with novel chemical structures and potent antibiotic activity against a narrow spectrum of bacteria. This narrow spectrum of activity indicates the tryglysins could be working through a novel antibiotic mechanism of action. Due to this narrow spectrum, the tryglysins could be used as highly targeted therapeutics to treat or prevent disease without disturbing other important, “beneficial” bacteria within the human microbiome, which is a great improvement over virtually all other clinically used antibiotics that are broad-spectrum. The tryglysins are potent against several streptococcal pathogens, including Streptococcus pneumonia, the leading cause of pneumonia, and Streptococcus mutans, the primary causative agent of tooth decay and gum disease.Type: ApplicationFiled: December 8, 2021Publication date: February 15, 2024Applicant: The Trustees of Princeton UniversityInventors: Mohammad R. SEYEDSAYAMDOST, Michael J. FEDERLE, Brett C. COVINGTON, Leah B. BUSHIN, Britta E. RUED, John AMBROSE
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Patent number: 11813235Abstract: Disclosed are methods for using guanfacine, an analog or derivative of guanfacine, or a pharmaceutically acceptable salt thereof, to reduce the virulence of a bacterial pathogen. When treating a patient, the method generally involves administering to the patient a therapeutically effective dose of guanfacine, an analog or derivative of guanfacine, or a pharmaceutically acceptable salt thereof. An alternative method involves contacting the bacterial pathogen with guanfacine, an analog or derivative of guanfacine, or a pharmaceutically acceptable salt thereof.Type: GrantFiled: March 20, 2020Date of Patent: November 14, 2023Assignee: THE TRUSTEES OF PRINCETON UNIVERSITYInventors: Mohammad R. Seyedsayamdost, Bethany K. Okada, Anran Li
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Publication number: 20230123785Abstract: Microorganisms are prolific producers of natural products, a group of molecules that make up the majority of drugs approved by the FDA in the past 35 years. After decades of mining, the low-hanging fruit has been picked and so discovery of drug-like molecules from microorganisms has come to a near-halt. The reason for this lack of productivity is that most biosynthetic pathways that give rise to natural products are not active under typical laboratory growth conditions. These so-called ‘cryptic’ or ‘silent’ pathways are a major source of new bioactive molecules and methods that reliably activate them could have a profound impact on drug discovery. Disclosed herein is a rapid genetics-free method for eliciting and detecting cryptic metabolites using an imaging mass spectrometry-based approach. An organism of choice is challenged with elicitors from a small molecule library. The molecules elicited are then imaged by mass spec, which allows for rapid identification of cryptic metabolites.Type: ApplicationFiled: December 1, 2022Publication date: April 20, 2023Applicant: The Trustees of Princeton UniversityInventors: Mohammad R. SEYEDSAYAMDOST, Fei XU, Yihan WU, Leah BUSHIN, Katherine Davis
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Patent number: 11629174Abstract: Disclosed is a high-throughput transcriptional assay format in Actinomycete bacteria, and Streptomyces spp. in particular, that leverages eGFP, inserted both at a neutral site and inside the biosynthetic cluster of interest, as a read-out for secondary metabolite synthesis. Using this approach, a silent gene cluster in Streptomyces albus J1074 was induced. The cytotoxins etoposide and ivermectin were revealed as potent inducers, allowing the isolation and structural characterization of nearly 20 novel small molecule products of the chosen cluster. One of these molecules is a novel antifungal, while several others inhibit a cysteine protease implicated in cancer. Studies addressing the mechanism of induction by the two elicitors led to the identification of a pathway-specific transcriptional repressor that silences the gene cluster under normal growth conditions.Type: GrantFiled: May 11, 2018Date of Patent: April 18, 2023Assignee: THE TRUSTEES OF PRINCETON UNIVERSITYInventors: Mohammad R. Seyedsayamdost, Fei Xu, Kyuho Moon, Behnam Nazari
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Publication number: 20230044467Abstract: Bacterial infections evading the current antibiotic arsenal warrant new treatment options. The mainstay treatment for Clostridium difficile infections involves administration of the broad-spectrum antibiotic vancomycin, which also depletes the gut microbiome and its natural defenses. This leads to recurrent C. difficile infections in 20-30% of patients. Alternative treatment options are limited, triggering a perpetual cycle of relapse and recovery that may eventually lead to death. Keratinicyclin B represents a glycopeptide antibiotic chemotype with a mechanism of action that is selective for Clostridia. When combined, vancomycin (or other glycopeptide antibiotic) and keratinicyclin B interact synergistically to inhibit the growth of C. difficile at concentrations far lower than their respective minimal inhibitory concentrations. Such a combination therapy could allow for targeted colonization clearance at low antibiotic doses, thereby minimizing toxicity and reducing the likelihood of relapse.Type: ApplicationFiled: July 26, 2022Publication date: February 9, 2023Applicant: The Trustees of Princeton UniversityInventors: Mohammad R. Seyedsayamdost, Vasiliki T. Chioti, Katherine M. Davis, Kirklin L. McWhorter
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Patent number: 11549950Abstract: Disclosed herein is a rapid genetics-free method for eliciting and detecting cryptic metabolites using an imaging mass spectrometry-based approach. An organism of choice is challenged with elicitors from a small molecule library. The molecules elicited are then imaged by mass spec, which allows for rapid identification of cryptic metabolites. These are then isolated and characterized. Employing the disclosed approach activated production of cryptic glycopeptides from an actinomycete bacterium. The molecules that result, the keratinimicins and keratinicyclins, are metabolites with important structural features. At least two of these, keratinimicins B and C, are highly bioactive against several pathogenic strains. This approach will allow for rapid activation and identification of cryptic metabolites from diverse microorganisms in the future.Type: GrantFiled: July 30, 2018Date of Patent: January 10, 2023Inventors: Mohammad R. Seyedsayamdost, Fei Xu, Yihan Wu, Leah Bushin, Katherine Davis
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Publication number: 20210156840Abstract: Bacteria harbor an immense reservoir of potentially new and therapeutic small molecules in the form of “silent” biosynthetic gene clusters. These clusters can be identified bioinformatically but are at best sparingly expressed under normal laboratory growth conditions; their products are therefore not interrogated during bioactivity screening exercises. An estimated 80-90% of biosynthetic loci are silent, meaning that routine bioactivity screens miss the majority of microbial biosynthetic potential. Disclosed herein is a method that allows access to this vast hidden metabolome, thereby allowing researchers to screen the complete metabolomes of microorganisms in the search of new therapeutic leads. The disclosed approach, “Bioactivity-HiTES”, broadly activates the secondary metabolomes of bacteria and links the cryptic metabolites produced to a desired biological activity.Type: ApplicationFiled: November 20, 2020Publication date: May 27, 2021Applicant: THE TRUSTEES OF PRINCETON UNIVERSITYInventors: Mohammad R. Seyedsayamdost, Kyuho Moon
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Patent number: 10941434Abstract: The majority of clinically used antibiotics and anticancer agents are derived from bacterial small molecules. These molecules are produced by dedicated biosynthetic gene clusters, sets of genes that are responsible for the step-wise generation of the target small molecule. Recent investigations have indicated, to the surprise of many experts, that the majority of these biosynthetic genes are inactive or ‘silent’ for unknown reasons. Thus under typical bacterial culturing conditions, these genes are not expressed and consequently the bioactive small molecule products are not synthesized. Disclosed is a method for high throughput screening of elicitors of cryptic metabolites, a method for producing cryptic metabolites, and a new family of cryptic metabolites, the acybolins, as well as their complete structural elucidation.Type: GrantFiled: August 17, 2018Date of Patent: March 9, 2021Assignee: THE TRUSTEES OF PRINCETON UNIVERSITYInventor: Mohammad R. Seyedsayamdost
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Publication number: 20210041452Abstract: Microorganisms are prolific producers of natural products, a group of molecules that make up the majority of drugs approved by the FDA in the past 35 years. After decades of mining, the low-hanging fruit has been picked and so discovery of drug-like molecules from microorganisms has come to a near-halt. The reason for this lack of productivity is that most biosynthetic pathways that give rise to natural products are not active under typical laboratory growth conditions. These so-called ‘cryptic’ or ‘silent’ pathways are a major source of new bioactive molecules and methods that reliably activate them could have a profound impact on drug discovery. Disclosed herein is a rapid genetics-free method for eliciting and detecting cryptic metabolites using an imaging mass spectrometry-based approach. An organism of choice is challenged with elicitors from a small molecule library. The molecules elicited are then imaged by mass spec, which allows for rapid identification of cryptic metabolites.Type: ApplicationFiled: July 30, 2018Publication date: February 11, 2021Applicant: The Trustees of Princeton UniversityInventors: Mohammad R. SEYEDSAYAMDOST, Fei XU, Yihan WU, Leah BUSHIN, Katherine Davis
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Publication number: 20200297669Abstract: Disclosed are methods for using guanfacine, an analog or derivative of guanfacine, or a pharmaceutically acceptable salt thereof, to reduce the virulence of a bacterial pathogen. When treating a patient, the method generally involves administering to the patient a therapeutically effective dose of guanfacine, an analog or derivative of guanfacine, or a pharmaceutically acceptable salt thereof. An alternative method involves contacting the bacterial pathogen with guanfacine, an analog or derivative of guanfacine, or a pharmaceutically acceptable salt thereof.Type: ApplicationFiled: March 20, 2020Publication date: September 24, 2020Applicant: The Trustees of Princeton UniversityInventors: Mohammad R. Seyedsayamdost, Bethany K. Okada, Anran Li
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Publication number: 20200079823Abstract: Disclosed is a high-throughput transcriptional assay format in Actinomycete bacteria, and Streptomyces spp. in particular, that leverages eGFP, inserted both at a neutral site and inside the biosynthetic cluster of interest, as a read-out for secondary metabolite synthesis. Using this approach, a silent gene cluster in Streptomyces albus J1074 was induced. The cytotoxins etoposide and ivermectin were revealed as potent inducers, allowing the isolation and structural characterization of nearly 20 novel small molecule products of the chosen cluster. One of these molecules is a novel antifungal, while several others inhibit a cysteine protease implicated in cancer. Studies addressing the mechanism of induction by the two elicitors led to the identification of a pathway-specific transcriptional repressor that silences the gene cluster under normal growth conditions.Type: ApplicationFiled: May 11, 2018Publication date: March 12, 2020Applicant: The Trustees of Princeton UniversityInventors: Mohammad R. SEYEDSAYAMDOST, Fei XU, Kyuho MOON, Behnam NAZARI
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Publication number: 20180355397Abstract: The majority of clinically used antibiotics and anticancer agents are derived from bacterial small molecules. These molecules are produced by dedicated biosynthetic gene clusters, sets of genes that are responsible for the step-wise generation of the target small molecule. Recent investigations have indicated, to the surprise of many experts, that the majority of these biosynthetic genes are inactive or ‘silent’ for unknown reasons. Thus under typical bacterial culturing conditions, these genes are not expressed and consequently the bioactive small molecule products are not synthesized. Disclosed is a method for high throughput screening of elicitors of cryptic metabolites, a method for producing cryptic metabolites, and a new family of cryptic metabolites, the acybolins, as well as their complete structural elucidation.Type: ApplicationFiled: August 17, 2018Publication date: December 13, 2018Applicant: The Trustees of Princeton UniversityInventor: Mohammad R. Seyedsayamdost
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Patent number: 10077460Abstract: The majority of clinically used antibiotics and anticancer agents are derived from bacterial small molecules. These molecules are produced by dedicated biosynthetic gene clusters, sets of genes that are responsible for the step-wise generation of the target small molecule. Recent investigations have indicated, to the surprise of many experts, that the majority of these biosynthetic genes are inactive or ‘silent’ for unknown reasons. Thus under typical bacterial culturing conditions, these genes are not expressed and consequently the bioactive small molecule products are not synthesized. Disclosed is a method for high throughput screening of elicitors of cryptic metabolites, a method for producing cryptic metabolites, and a new family of cryptic metabolites, the acybolins, as well as their complete structural elucidation.Type: GrantFiled: March 10, 2015Date of Patent: September 18, 2018Assignee: THE TRUSTEES OF PRINCETON UNIVERSITYInventor: Mohammad R. Seyedsayamdost
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Publication number: 20170022532Abstract: The majority of clinically used antibiotics and anticancer agents are derived from bacterial small molecules. These molecules are produced by dedicated biosynthetic gene clusters, sets of genes that are responsible for the step-wise generation of the target small molecule. Recent investigations have indicated, to the surprise of many experts, that the majority of these biosynthetic genes are inactive or ‘silent’ for unknown reasons. Thus under typical bacterial culturing conditions, these genes are not expressed and consequently the bioactive small molecule products are not synthesized. Disclosed is a method for high throughput screening of elicitors of cryptic metabolites, a method for producing cryptic metabolites, and a new family of cryptic metabolites, the acybolins, as well as their complete structural elucidation.Type: ApplicationFiled: March 10, 2015Publication date: January 26, 2017Applicant: The Trustees of Princeton UniversityInventor: Mohammad R. Seyedsayamdost
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Patent number: 8673591Abstract: This invention provides reductase proteins that comprise NH2Y unnatural amino acid residues, systems of orthogonal elements for incorporating NH2Y into reductases and methods of using NH2Y amino acid residues in reductases as molecular probes for probing reductases function, structure and activity.Type: GrantFiled: October 23, 2008Date of Patent: March 18, 2014Assignees: The Scripps Research Institute, Massachusetts Institute of TechnologyInventors: Mohammad R. Seyedsayamdost, Jianming Xie, Clement Tsz Chan, Lital Alfonta, Peter G. Schultz, Joanne Stubbe
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Patent number: 8222434Abstract: The present inventions are directed to a novel bactobolin analog bactobolin D. The present inventions also are directed to a method of producing a composition comprising at least one bactobolin analog using a bacteria strain comprising a bacterial cell comprising the biosynthetic locus of the bactobolin analog in Burkholderia thailandensis (bta cluster) or a homolog structure (at least 95% sequence identity) thereof, and further isolation and purification of the bactobolin analog. For example, the bacterial strain can be a wild type bacterial strain such as a Burkholderia strain comprising a bta cluster (e.g. Burkholderia thailandensis (e.g. E264, Bt4, and TXDOH) and Burkholderia pseudomallei (e.g. K96243, 1106a, and 1106b).Type: GrantFiled: April 5, 2010Date of Patent: July 17, 2012Assignees: University of Washington through its Center for Commercialization, President and Fellows of Harvard CollegeInventors: E. Peter Greenberg, Josephine R. Chandler, Breck Duerkop, Patricia Silva Lima, Joshua Alan Blodgett, Jon Clardy, Mohammad R. Seyedsayamdost
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Publication number: 20110262949Abstract: This invention provides reductase proteins that comprise NH2Y unnatural amino acid residues, systems of orthogonal elements for incorporating NH2Y into reductases and methods of using NH2Y amino acid residues in reductases as molecular probes for probing reductases function, structure and activity.Type: ApplicationFiled: October 23, 2008Publication date: October 27, 2011Inventors: Mohammad R. Seyedsayamdost, Jianming Xie, Clement Tsz Chan, Lital Alfonta, Peter G. Schultz, Joanne Stubbe
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Publication number: 20090208994Abstract: This invention provides reductase proteins that comprise NH2Y unnatural amino acid residues, systems of orthogonal elements for incorporating NH2Y into reductases and methods of using NH2Y amino acid residues in reductases as molecular probes for probing reductases function, structure and activity.Type: ApplicationFiled: October 23, 2008Publication date: August 20, 2009Applicants: THE SCRIPPS RESEARCH INSTITUTE, MASSACHUSETTS INSTITUTE OF TECHNOLOGYInventors: Mohammad R. Seyedsayamdost, Jianming Xie, Tsz Yan Clement Chan, Lital Alfonta, Peter G. Schultz, Joanne Stubbe