Patents by Inventor Darell D. Bigner

Darell D. Bigner 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: 11813298
    Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.
    Type: Grant
    Filed: July 5, 2022
    Date of Patent: November 14, 2023
    Assignee: Duke University
    Inventors: Matthias Gromeier, John H. Sampson, Darell D. Bigner, Annick Desjardins, Henry S. Friedman
  • Patent number: 11506666
    Abstract: A reliable assay to specifically detect CD155 in tissue sections has widespread use because CD155 is expressed widely among tumor types. Additionally, detected expression of CD 155 in glioblastoma cells is at levels commensurate with susceptibility to PVSRIPO (a poliovirus construct) infection and killing. An anti-CD155 antibody can achieve mono-specific detection of CD155 in immunoblots of tumor homogenates and immunohistochemistry of tumor formalin fixed, paraffin embedded sections. The assay can be used to determine appropriate use of PVSRIPO in oncolytic immunotherapy against cancers.
    Type: Grant
    Filed: October 2, 2017
    Date of Patent: November 22, 2022
    Assignee: Duke University
    Inventors: Darell D. Bigner, Vidyalakshmi Chandramohan, Matthias Gromeier
  • Publication number: 20220339223
    Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.
    Type: Application
    Filed: July 5, 2022
    Publication date: October 27, 2022
    Inventors: Matthias Gromeier, John H. Sampson, Darell D. Bigner, Annick Desjardins, Henry S. Friedman
  • Patent number: 11406677
    Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.
    Type: Grant
    Filed: September 10, 2020
    Date of Patent: August 9, 2022
    Assignee: Duke University
    Inventors: Matthias Gromeier, John H. Sampson, Darell D. Bigner, Annick Desjardins, Henry S. Friedman
  • Patent number: 11311628
    Abstract: D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a recombinant Pseudomonas exotoxin A-based immunotoxin (IT), targeting both wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins overexpressed in glioblastomas. A good laboratory practice (GLP) manufacturing process was developed to produce sufficient material for a Phase I/II clinical trial. D2C7-IT was expressed under the control of the T7 promoter in Escherichia coli BLR (? DE31). D2C7-IT was produced by a 10 L batch fermentation process and was then purified from inclusion bodies using anion exchange, size exclusion, and an endotoxin removal process that achieved a yield of over 300 mg of purified protein.
    Type: Grant
    Filed: October 13, 2017
    Date of Patent: April 26, 2022
    Assignee: Duke University
    Inventors: Darell D. Bigner, Vidyalakshmi Chandramohan, Charles Pegram
  • Patent number: 11306364
    Abstract: We surveyed 1,230 tumors of 60 different types and found that tumors could be divided into types with low (<15%) and high (?15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
    Type: Grant
    Filed: July 14, 2020
    Date of Patent: April 19, 2022
    Assignees: Duke University, The Johns Hopkins University
    Inventors: Hai Yan, Bert Vogelstein, Nickolas Papadopoulos, Kenneth W. Kinzler, Yuchen Jiao, Chetan Bettegowda, Darell D. Bigner, Zachary J. Reitman, Patrick J. Killela
  • Publication number: 20210311063
    Abstract: A reliable assay to specifically detect CD155 in tissue sections has widespread use because CD155 is expressed widely among tumor types. Additionally, detected expression of CD 155 in glioblastoma cells is at levels commensurate with susceptibility to PVSRIPO (a poliovirus construct) infection and killing. An anti-CD155 antibody can achieve mono-specific detection of CD155 in immunoblots of tumor homogenates and immunohistochemistry of tumor formalin fixed, paraffin embedded sections. The assay can be used to determine appropriate use of PVSRIPO in oncolytic immunotherapy against cancers.
    Type: Application
    Filed: October 2, 2017
    Publication date: October 7, 2021
    Applicant: Duke University
    Inventors: Darell D. Bigner, Vidyalakshmi Chandramohan, Matthias Gromeier
  • Patent number: 10894987
    Abstract: We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.
    Type: Grant
    Filed: November 16, 2016
    Date of Patent: January 19, 2021
    Assignees: The Johns Hopkins University, Duke University
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, D. Williams Parsons, Xiaosong Zhang, Jimmy Cheng-Ho Lin, Rebecca J. Leary, Philipp Angenendt, Nickolas Papadopoulos, Victor Velculescu, Giovanni Parmigiani, Rachel Karchin, Sian Jones, Hai Yan, Darell D. Bigner, Chien-Tsun Kuan, Gregory J. Riggins
  • Publication number: 20200405795
    Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.
    Type: Application
    Filed: September 10, 2020
    Publication date: December 31, 2020
    Applicant: Duke University
    Inventors: Matthias Gromeier, John H. Sampson, Darell D. Bigner, Annick Desjardins, Henry S. Friedman
  • Publication number: 20200399708
    Abstract: We surveyed 1,230 tumors of 60 different types and found that tumors could be divided into types with low (<15%) and high (?15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
    Type: Application
    Filed: July 14, 2020
    Publication date: December 24, 2020
    Applicants: Duke University, The Johns Hopkins University
    Inventors: Hai Yan, Bert Vogelstein, Nickolas Papadopoulos, Kenneth W. Kinzler, Yuchen Jiao, Chetan Bettegowda, Darell D. Bigner, Zachary J. Reitman, Patrick J. Killela
  • Publication number: 20200368300
    Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. Combination with immune checkpoint inhibitors increases the anti-tumor effect. Tumors of different types are susceptible to the combination treatment, including but not limited to melanoma, glioglastoma, renal cell carcinoma, prostate cancer, breast cancer, lung cancer, medulloblastoma, and colorectal cancer.
    Type: Application
    Filed: August 11, 2020
    Publication date: November 26, 2020
    Applicant: Duke University
    Inventors: Darell D. Bigner, Matthias Gromeier, Smita Nair, Vidyalakshmi Chandramohan
  • Patent number: 10799543
    Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.
    Type: Grant
    Filed: July 9, 2019
    Date of Patent: October 13, 2020
    Assignee: Duke University
    Inventors: Matthias Gromeier, John H. Sampson, Darell D. Bigner, Annick Desjardins, Henry S. Friedman
  • Patent number: 10744171
    Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. Sequential treatment with the virus construct followed by chemotherapy drugs increases the anti-tumor effect. Tumors of different types are susceptible to the combination treatment, including but not limited to melanoma, glioblastoma, renal cell carcinoma, prostate cancer, breast cancer, lung cancer, medulloblastoma, and colorectal cancer.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: August 18, 2020
    Assignee: Duke University
    Inventors: Darell D. Bigner, Matthias Gromeier, Annick Desjardins, Henry S. Friedman, Allan H. Friedman, John H. Sampson
  • Patent number: 10744170
    Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. Combination with immune checkpoint inhibitors increases the anti-tumor effect. Tumors of different types are susceptible to the combination treatment, including but not limited to melanoma, glioglastoma, renal cell carcinoma, prostate cancer, breast cancer, lung cancer, medulloblastoma, and colorectal cancer.
    Type: Grant
    Filed: October 14, 2016
    Date of Patent: August 18, 2020
    Assignee: Duke University
    Inventors: Darell D. Bigner, Matthias Gromeier, Smita Nair, Vidyalakshmi Chandramohan
  • Patent number: 10711310
    Abstract: We surveyed 1,230 tumors of 60 different types and found that tumors could be divided into types with low (<15%) and high (?15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
    Type: Grant
    Filed: February 18, 2014
    Date of Patent: July 14, 2020
    Assignees: Duke University, The Johns Hopkins University
    Inventors: Hai Yan, Bert Vogelstein, Nickolas Papadopoulos, Kenneth W. Kinzler, Yuchen Jiao, Chetan Bettegowda, Darell D. Bigner, Zachary J. Reitman, Patrick J. Killela
  • Publication number: 20200046847
    Abstract: D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a recombinant Pseudomonas exotoxin A-based immunotoxin (IT), targeting both wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins overexpressed in glioblastomas. A good laboratory practice (GLP) manufacturing process was developed to produce sufficient material for a Phase I/II clinical trial. D2C7-IT was expressed under the control of the T7 promoter in Escherichia coli BLR (? DE3). D2C7-IT was produced by a 10 L batch fermentation process and was then purified from inclusion bodies using anion exchange, size exclusion, and an endotoxin removal process that achieved a yield of over 300 mg of purified protein.
    Type: Application
    Filed: October 13, 2017
    Publication date: February 13, 2020
    Applicant: Duke University
    Inventors: Darell D. Bigner, Vidyalakshmi Chandramohan, Charles Pegram
  • Publication number: 20190343904
    Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.
    Type: Application
    Filed: July 9, 2019
    Publication date: November 14, 2019
    Applicant: Duke University
    Inventors: Matthias Gromeier, John H. Sampson, Darell D. Bigner, Annick Desjardins, Henry S. Friedman
  • Patent number: 10398743
    Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.
    Type: Grant
    Filed: February 9, 2017
    Date of Patent: September 3, 2019
    Assignee: Duke University
    Inventors: Matthias Gromeier, John H. Sampson, Darell D. Bigner, Annick Desjardins, Henry S. Friedman
  • Publication number: 20190105360
    Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. Sequential treatment with the virus construct followed by chemotherapy drugs increases the anti-tumor effect. Tumors of different types are susceptible to the combination treatment, including but not limited to melanoma, glioblastoma, renal cell carcinoma, prostate cancer, breast cancer, lung cancer, medulloblastoma, and colorectal cancer.
    Type: Application
    Filed: March 20, 2017
    Publication date: April 11, 2019
    Applicant: Duke University
    Inventors: Darell D. Bigner, Matthias Gromeier, Annick Desjardins, Henry S. Friedman, Allan H. Friedman, John H. Sampson
  • Publication number: 20180362659
    Abstract: We have constructed a polynucleotide encoding a bispecific antibody engaging molecule which has one arm that specifically engages a tumor cell which expresses the human EGFRvIII mutant protein on its surface, and a second arm that specifically engages T cell activation ligand CD3. The polynucleotide is codon optimized for expression in CHO cells. The subunits of the engaging molecules are organized to achieve greater efficiency. These are promising therapeutic agents.
    Type: Application
    Filed: August 20, 2018
    Publication date: December 20, 2018
    Inventors: Darell D. Bigner, John Sampson, Chien-Tsun Kuan, Mingqing Cai, Bryan D. Choi, Patrick C. Gedeon, Ira H. Pastan