Patents by Inventor Mark W. Dewhirst
Mark W. Dewhirst 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: 20140249097Abstract: The presently disclosed subject matter generally relates to methods and compositions for inhibiting the expression and/or activation of hypoxia-inducible factor 1 (HIF-1) genes in a cancer cell, tissue or tumor. More particularly, the methods disclosed herein relate to inhibition of HIF-1 activation in a tumor, increasing sensitivity of a tumor cell to radiation and/or chemotherapy, delaying tumor growth, inhibiting tumor blood vessel growth, inhibiting inflammatory responses in a cell through the use of compositions that prevent the nitrosylation of HIF-1, and methods for screening for new inhibitors of HIF-1 activation. Additionally, the compositions disclosed herein relate to compositions that can be employed in, and are identified by, the disclosed methods.Type: ApplicationFiled: September 30, 2011Publication date: September 4, 2014Inventors: Mark W. Dewhirst, Yiting Cao
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Publication number: 20140161773Abstract: The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.Type: ApplicationFiled: June 17, 2013Publication date: June 12, 2014Inventors: Mark W. Dewhirst, Jonathan S. Stamler, Timothy J. McMahon, Pierre D. Sonveaux
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Patent number: 8466110Abstract: The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.Type: GrantFiled: April 18, 2012Date of Patent: June 18, 2013Assignee: Duke UniversityInventors: Mark W. Dewhirst, Jonathan S. Stamler, Timothy J. McMahon, Pierre Sonveaux
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Publication number: 20130023587Abstract: Provided are methods for inhibiting survival of a proliferating, quiescent, or hypoxic cancer cell that include administering a compound that inhibits lactate clearance (e.g., lactate catabolism, lactate transport, glutamate release, and/or alanine release) in the proliferating, quiescent, or hypoxic cancer cell. Further provided are methods of reducing the proliferation of a neoplastic cell having increased lactate or decreased glucose concentrations relative to a normal cell. Also provided are methods of treating a subject having cancer, wherein the methods may include administering to the subject an inhibitor of lactate clearance.Type: ApplicationFiled: April 1, 2011Publication date: January 24, 2013Applicant: DUKE UNIVERSITYInventors: Thies Schroeder, Mark W. Dewhirst
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Publication number: 20120225133Abstract: The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.Type: ApplicationFiled: April 18, 2012Publication date: September 6, 2012Applicant: Duke UniversityInventors: Mark W. Dewhirst, Jonathan S. Stamler, Timothy J. McMahon, Pierre Sonveaux
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Patent number: 8198241Abstract: The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.Type: GrantFiled: July 30, 2010Date of Patent: June 12, 2012Assignee: Duke UniversityInventors: Mark W. Dewhirst, Jonathan S. Stamler, Timothy J. McMahon, Pierre Sonveaux
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Publication number: 20120141381Abstract: The invention comprises compositions and methods for loading both magnetic resonance contrast agents and therapeutic agents into liposomes, such as low temperature sensitive liposomes (LTSLs). In certain embodiments, a passive technique is used to load the liposomes. In other embodiments, an active technique is used to load the liposomes. In further embodiments, a magnetic resonance contrast agent and Doxorubicin are loaded into the liposomes. The liposome compositions have higher contrast-agent loadings and are more stable, than those known in the art.Type: ApplicationFiled: February 23, 2010Publication date: June 7, 2012Applicant: Duke University Office of Technology & VentureInventors: Mark W. Dewhirst, Pavel Yarmolenko, Bradford J. Wood, Matthrew R. Dreher, Ayele H. Negussie
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Publication number: 20110110866Abstract: A magnetic resonance imaging (MRI) contrast enhancement agent comprising an elastin-like polypeptide (ELP) and one or more paramagnetic metal ions is disclosed. Also disclosed are methods of preparing ELP MRI contrast enhancement agents, formulations comprising ELP MRI contrast enhancement agents, and methods of using ELP MRI contrast enhancement agents to image biological samples and to image and deliver therapeutic agents to targeted sites in vivo. In some embodiments, the ELP MRI agents can be used in methods related to blood volume determination, in magnetic resonance angiography (MRA), and in vascular transport determinations. The ELP MRI contrast agents can also provide information on the expression of various proteins through affinity targeting or enzymatic crosslinking in order to aid in diagnosis and in the spatial definition of pathologic tissue.Type: ApplicationFiled: April 10, 2008Publication date: May 12, 2011Applicant: Duke UniversityInventors: Ashutosh Chilkoti, Matthew R. Dreher, Daniel E. Meyer, Mark W. Dewhirst
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Publication number: 20110054023Abstract: The presently disclosed subject matter generally relates to methods and compositions for inhibiting the expression and/or activation of hypoxia-inducible factor 1 (HIF-1) genes in a cancer cell, tissue or tumor. More particularly, the methods disclosed herein relate to inhibition of HIF-1 activation in a tumor, increasing sensitivity of a tumor cell to radiation and/or chemotherapy, delaying tumor growth, inhibiting tumor blood vessel growth, inhibiting inflammatory responses in a cell through the use of compositions that prevent the nitrosylation of HIF-1, and methods for screening for new inhibitors of HIF-1 activiation. Additionally, the compositions disclosed herein relate to compositions that can be employed in, and are identified by, the disclosed methods.Type: ApplicationFiled: September 30, 2010Publication date: March 3, 2011Applicant: Duke UniversityInventors: Mark W. Dewhirst, Yiting Cao
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Publication number: 20100298222Abstract: The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.Type: ApplicationFiled: July 30, 2010Publication date: November 25, 2010Applicant: Duke UniversityInventors: Mark W. Dewhirst, Jonathan S. Stamler, Timothy J. McMahon, Pierre D. Sonveaux
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Patent number: 7795219Abstract: The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.Type: GrantFiled: January 7, 2008Date of Patent: September 14, 2010Assignee: Duke UniversityInventors: Mark W. Dewhirst, Jonathan S. Stamler, Timothy J. McMahon, Pierre Sonveaux
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Patent number: 7790204Abstract: The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.Type: GrantFiled: January 7, 2008Date of Patent: September 7, 2010Assignee: Duke UniversityInventors: Mark W. Dewhirst, Jonathan S. Stamler, Timothy J. McMahon, Pierre Sonveaux
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Publication number: 20100203024Abstract: The present invention provides erythrocytes or nucleated erythrocyte precursors from animals or patients with SS or SA hemoglobin or erythroleukemia cells stably transfected with BCAM/Lu which are capable of selectively localizing in tumor vasculature promoting ischemia and occlusion and carrying oncolytic viruses, antitumor proteins, plasmids, toxins and chemotherapy into the tumor milieu. Nucleated erythroid precursors containing SS or SA hemoglobin and transfected with nucleic acids encoding a hypoxia-responsive element and containing nucleic acids encoding expression of oncolytic viruses, superantigens, toxins, viruses, antitumor proteins and chemotherapy are also useful in inducing a potent and specific tumoricidal response. An especially favored carrier is an SS nucleated erythroid precursor transfected with a replication competent oncolytic adenovirus or self-replicating alphavirus expressing a fusogenic membrane glycoprotein or a tumoricidal polypeptide.Type: ApplicationFiled: May 29, 2007Publication date: August 12, 2010Inventors: David S. Terman, Mark W. Dewhirst
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Patent number: 7769423Abstract: Methods and compositions useful for detecting an in vivo blood pool, monitoring the distribution of a compound of interest to a desired site in an organism by magnetic resonance imaging, monitoring the accumulation of a compound of interest at a desired site in vivo by magnetic resonance imaging, and monitoring the release of liposomal contents to an external stimulus at a desired site in vivo by magnetic resonance imaging are disclosed. Some compositions comprise envirosensitive or non-sensitive liposomes. Contrast agents, such as manganese-based compounds, are also disclosed.Type: GrantFiled: December 29, 2006Date of Patent: August 3, 2010Assignee: Duke UniversityInventors: Benjamin L. Viglianti, Mark W. Dewhirst, Ana M. Ponce
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Publication number: 20100151576Abstract: The presently claimed subject matter provides conditionally replication competent adenoviral vectors that confer selective cytotoxicity on cells expressing HIF-1 by infecting cells that allow HIF-1 inducible promoters present within the vectors to function. Also provided are compositions and host cells based upon the vectors, as well as methods of propagating and using the vectors. The presently claimed subject matter further provides a method of inhibiting tumor growth by co-infecting cells in a tumor with a conditionally replication competent adenovirus vector in conjunction with a replication deficient adenovirus vector.Type: ApplicationFiled: February 19, 2010Publication date: June 17, 2010Inventors: Chuan-Yuan Li, Qian Huang, Mark W. Dewhirst
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Patent number: 7672704Abstract: Methods and compositions useful for detecting an in vivo blood pool, monitoring the distribution of a compound of interest to a desired site in an organism by magnetic resonance imaging, monitoring the accumulation of a compound of interest at a desired site in vivo by magnetic resonance imaging, and monitoring the release of liposomal contents to an external stimulus at a desired site in vivo by magnetic resonance imaging are disclosed. Some compositions comprise envirosensitive or non-sensitive liposomes. Contrast agents, such as manganese-based compounds, are also disclosed.Type: GrantFiled: September 11, 2003Date of Patent: March 2, 2010Assignee: Duke UniversityInventors: Benjamin L. Viglianti, Mark W. Dewhirst, James R. MacFall, Zeljko Vujaskovic
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Patent number: 7338670Abstract: The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.Type: GrantFiled: April 13, 2006Date of Patent: March 4, 2008Assignee: Duke UniversityInventors: Mark W. Dewhirst, Jonathan S. Stamler, Timothy J. McMahon, Pierre Sonveaux
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Patent number: 7208138Abstract: Imaging agents for magnetic resonance imaging are disclosed. Methods of monitoring angiogenesis and the growth and remission of tumor tissue are also disclosed. Methods of monitoring blood clot formation and dissolution are additionally disclosed. Methods of monitoring wound healing are further disclosed. A kit for obtaining an image of a biological structure is further disclosed.Type: GrantFiled: December 5, 2005Date of Patent: April 24, 2007Assignees: Duke University, Yeda Research and Development Co., Ltd.Inventors: Zishan Haroon, Mark W. Dewhirst, Charles S. Greenberg, Michal Neeman
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Patent number: 7183262Abstract: A method for controlling in vivo heat-inducible gene expression for provision of therapeutic polypeptide. The method includes the steps of: (a) providing a construct comprising a polynucleotide encoding a therapeutic polypeptide, wherein the polynucleotide is operatively linked to a heat-inducible promoter; (b) administering the construct to a warm-blooded vertebrate at a site at or near the tumor; and (c) applying heat to the site at or near the tumor to express the therapeutic polypeptide, whereby anti-tumor activity is observed.Type: GrantFiled: June 14, 2002Date of Patent: February 27, 2007Assignee: Duke UniversityInventors: Chuan-Yuan Li, Qian Huang, Mark W. Dewhirst
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Patent number: 6972122Abstract: Imaging agents for magnetic resonance imaging are disclosed. Methods of monitoring angiogenesis and the growth and remission of tumor tissue are also disclosed. Methods of monitoring blood clot formation and dissolution are additionally disclosed. Methods of monitoring wound healing are further disclosed. A kit for obtaining an image of a biological structure is further disclosed.Type: GrantFiled: December 18, 2001Date of Patent: December 6, 2005Assignees: Duke University, Yeda Research and Development Co., Ltd.Inventors: Zishan Haroon, Mark W. Dewhirst, Charles S. Greenberg, Michal Neeman