Patents by Inventor Darell Bigner
Darell 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).
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Patent number: 10052382Abstract: High affinity antibodies were made to gangliosides expressed on tumor cells. The antibodies can be used analytically, diagnostically, therapeutically, and theranostically. The antibodies may be used to target cytotoxic reagents to tumor cells, thus minimizing full-body toxicity. The antibodies may also be used with out added cytotoxin. The antibodies may be detectably labeled or labelable for analytic and diagnostic purposes. The combination of specificity and affinity of the antibodies render them particularly useful.Type: GrantFiled: June 2, 2016Date of Patent: August 21, 2018Assignees: Duke University, The United States of America as Represented by the Secretary of Health (NIH)Inventors: Darell Bigner, Chien-Tsun Kuan, Ira H. Pastan, Hailan Piao
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Publication number: 20180195132Abstract: Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins.Type: ApplicationFiled: December 7, 2017Publication date: July 12, 2018Inventors: Bert Vogelstein, Kenneth W. Kinzler, Chetan Bettegowda, Nishant Agrawal, Nickolas Papadopoulos, Darell Bigner, Hai Yan, Roger McLendon
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Patent number: 9982306Abstract: We determined the sequence of ATRX and DAXX in 447 cancers from various sites. We found mutations most commonly in pediatric glioblastoma multiformae (GBM) (11.1%), adult GBM (6.5%), oligodendrogliomas (7.7%) and medulloblastomas (1.5%); and showed that Alternative Lengthening of Telomeres (ALT), a telomerase-independent telomere maintenance mechanism found in cancers that have not activated telomerase, perfectly correlated with somatic mutations of either gene. In contrast, neuroblastomas, and adenocarcinomas of the ovary, breast, and pancreas were negative for mutations in ATRX and DAXX. Alterations in ATRX or DAXX define a specific molecular pathway that is closely associated with an alternative telomere maintenance function in human cancers.Type: GrantFiled: June 28, 2012Date of Patent: May 29, 2018Assignees: Duke University, The Johns Hopkins UniversityInventors: Hai Yan, Darell Bigner, Bert Vogelstein, Kenneth W. Kinzler, Alan Meeker, Ralph Hruban, Nickolas Papadopoulos, Luis Diaz, Yuchen Jiao
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Patent number: 9873917Abstract: Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins.Type: GrantFiled: July 18, 2012Date of Patent: January 23, 2018Assignees: The Johns Hopkins University, Duke UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Chetan Bettegowda, Nishant Agrawal, Nickolas Papadopoulos, Darell Bigner, Hai Yan, Roger McLendon
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Publication number: 20170247765Abstract: Methods that rapidly, sensitively, and specifically detect mutations in IDH1/2 and the TERT promoter employ amplification of particular portions of the genes that experience frequent and exquisitely localized mutations. The ability to distinguish between sequences that differ only by one nucleotide and which may be present in very low ratios is essential for such an assay.Type: ApplicationFiled: August 24, 2015Publication date: August 31, 2017Applicant: Duke UniversityInventors: Hai Yan, Yiping He, Rui Yang, Bill H. Diplas, Landon Hansen, Darell Bigner
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Patent number: 9695479Abstract: Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high density microarrays and sequenced all known protein-coding genes and miRNA genes using Sanger sequencing. We found that, on average, each tumor had 11 gene alterations, markedly fewer than in common adult cancers. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone H3K4 trimethylase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis.Type: GrantFiled: November 8, 2011Date of Patent: July 4, 2017Assignees: The Johns Hopkins University, Duke UniversityInventors: Bert Vogelstein, Kenneth Kinzler, Nickolas Papadopoulos, Donald Williams Parsons, Rebecca J. Leary, Meng Li, Xiaosong Zhang, Sian Jones, Gregory J. Riggins, Victor Velculescu, Darell Bigner, Hai Yan
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Patent number: 9695400Abstract: We provide IDH1 gene-defective cell lines (e.g., IDH1R132H heterozygous and IDH1R132H homozygous) derived from dissociated human astrocytoma samples. The cells can be used alone or in combination with each other or other cell types as a tool for determining the impact of IDH1R132H on cellular biology, tumorigenesis, and metabolic profiles. The cell lines may be used to test and identify therapeutic targets and to screen for molecular therapeutic agents.Type: GrantFiled: October 24, 2011Date of Patent: July 4, 2017Assignee: Duke UniversityInventors: Hai Yan, Darell Bigner, Genglin Jin
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Patent number: 9676858Abstract: We have constructed bispecific antibody engaging molecules which have 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 engaging molecules are highly cytotoxic and antigen-specific. These may be used as therapeutic agents.Type: GrantFiled: June 7, 2013Date of Patent: June 13, 2017Assignees: Duke University, The United States of America as represented by the secretary, Department of Health and Human Services (NIH)Inventors: Darell Bigner, Chien-Tsun Kuan, John Sampson, Bryan Choi, Ira H. Pastan, Patrick C. Gedeon
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Publication number: 20160340741Abstract: Genetic signatures capable of distinguishing among several types of gliomas provide clinically relevant information that can serve as an adjunct to histopathological diagnosis. For example, mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon in primary GBM. The genetic signatures permit the stratification of the glioma patients into distinct cohorts.Type: ApplicationFiled: January 26, 2015Publication date: November 24, 2016Applicant: Duke UniversityInventors: Hai Yan, Darell Bigner, Patrick Killela, Zachary Reitman
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Patent number: 9492564Abstract: We tested the in vitro and in vivo efficacy of a recombinant bispecific immunotoxin that recognizes both EGFRwt and tumor-specific EGFRvIII receptors. A single chain antibody was cloned from a hybridoma and fused to toxin, carrying a C-terminal peptide which increases retention within cells. The binding affinity and specificity of the recombinant bispecific immunotoxin for the EGFRwt and the EGFRvIII proteins was measured. In vitro cytotoxicity was measured. In vivo activity of the recombinant bispecific immunotoxin was evaluated in subcutaneous models and compared to that of an established monospecific immunotoxin. In our preclinical studies, the bispecific recombinant immunotoxin, exhibited significant potential for treating brain tumors.Type: GrantFiled: May 6, 2014Date of Patent: November 15, 2016Assignees: Duke University, The United States of America, as represented by the Secretary of Health and Human Services, National Institutes of HealthInventors: Darell Bigner, Chien-Tsun Kuan, Ira H. Pastan, Charles Peagram
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Publication number: 20160272730Abstract: High affinity antibodies were made to gangliosides expressed on tumor cells. The antibodies can be used analytically, diagnostically, therapeutically, and theranostically. The antibodies may be used to target cytotoxic reagents to tumor cells, thus minimizing full-body toxicity. The antibodies may also be used with out added cytotoxin. The antibodies may be detectably labeled or labelable for analytic and diagnostic purposes. The combination of specificity and affinity of the antibodies render them particularly useful.Type: ApplicationFiled: June 2, 2016Publication date: September 22, 2016Applicants: Duke University, THE GOVERNMENT OF THE UNITED STATES AS REPRESENTED BY THE SECRETARY OF HEALTHInventors: Darell Bigner, Chien-Tsun Kuan, Ira H. Pastan, Hailan Piao
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Patent number: 9441048Abstract: High affinity antibodies were made to gangliosides expressed on tumor cells. The antibodies can be used analytically, diagnostically, therapeutically, and theranostically. The antibodies may be used to target cytotoxic reagents to tumor cells, thus minimizing full-body toxicity. The antibodies may also be used with out added cytotoxin. The antibodies may be detectably labeled or labelable for analytic and diagnostic purposes. The combination of specificity and affinity of the antibodies render them particularly useful.Type: GrantFiled: November 15, 2011Date of Patent: September 13, 2016Assignees: The United States of America as represented by the Secretary of Health and Human Services, Duke UniversityInventors: Darell Bigner, Chien-Tsun Kuan, Ira H. Pastan, Hailan Piao
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Patent number: 9353418Abstract: 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: GrantFiled: December 11, 2013Date of Patent: May 31, 2016Assignees: The Johns Hopkins University, Duke UniversityInventors: 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 Bigner, Chien-Tsun Kuan, Gregory J. Riggins
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Publication number: 20150368353Abstract: Recombinant scFv-immunotoxins target tumor cells expressing human podoplanin but not podoplanin-negative or normal cells. The immunotoxins can be used for treatment of malignant glioma patients or any malignant tumor expressing podoplanin. One such immunotoxin comprises a modified Pseudomonas exotoxin (PE38) attached to the scFv antibody fragment. This immunotoxin can be used as a therapeutic drug for the treatment of malignant gliomas and other cancers.Type: ApplicationFiled: June 1, 2015Publication date: December 24, 2015Inventors: Darell BIGNER, Chien-Tsun KUAN, Ira H. PASTAN, Vidyalakshmi CHANDRAMOHAN
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Patent number: 9074221Abstract: IDH1 gene-defective cell lines (e.g., IDH1R132H heterozygous) have been made from a robust cell line, HCT116. The IDH1 gene-defective cell lines can be used to determine the effect of IDH1R132H on cell biology, tumorigenesis, and cellular metabolic profiles. These cell lines can be used to test potential therapeutic targets and to screen potential therapeutic agents. Kits and xenografts are also contemplated.Type: GrantFiled: October 25, 2011Date of Patent: July 7, 2015Assignee: Duke UniversityInventors: Hai Yan, Darell Bigner, Christopher Gentry Duncan
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Publication number: 20150132306Abstract: We have constructed bispecific antibody engaging molecules which have 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 engaging molecules are highly cytotoxic and antigen-specific. These are promising therapeutic agents.Type: ApplicationFiled: June 7, 2013Publication date: May 14, 2015Inventors: Darell Bigner, Chien-Tsun Kuan, John Sampson, Bryan Choi, Ira H. Pastan
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Publication number: 20150118181Abstract: The concurrent administration of chemotherapy and immunotherapy has been considered a contraindication because of the concern that the induced lymphopenia would ablate therapeutic efficacy of immunotherapy. Temozolomide has been shown to be an effective chemotherapeutic for patients with malignant gliomas and to deprive patients with glioblastoma (GBM) patients of this agent in order to treat with immunotherapy is controversial. Despite conventional dogma, we demonstrate that both chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy. In fact, the temozolomide induced lymphopenia may actually be synergistic with a peptide vaccine.Type: ApplicationFiled: December 9, 2014Publication date: April 30, 2015Applicants: Board of Regents, The University of Texas System, DUKE UNIVERSITYInventors: John H. Sampson, Darell Bigner, Duane A. Mitchell, Amy Heimberger
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Publication number: 20140322248Abstract: We tested the in vitro and in vivo efficacy of a recombinant bispecific immunotoxin that recognizes both EGFRwt and tumor-specific EGFRvIII receptors. A single chain antibody was cloned from a hybridoma and fused to toxin, carrying a C-terminal peptide which increases retention within cells. The binding affinity and specificity of the recombinant bispecific immunotoxin for the EGFRwt and the EGFRvIII proteins was measured. In vitro cytotoxicity was measured. In vivo activity of the recombinant bispecific immunotoxin was evaluated in subcutaneous models and compared to that of an established monospecific immunotoxin. In our preclinical studies, the bispecific recombinant immunotoxin, exhibited significant potential for treating brain tumors.Type: ApplicationFiled: May 6, 2014Publication date: October 30, 2014Inventors: Darell BIGNER, Chien-Tsun KUAN, Ira H. PASTAN, Charles PEAGRAM
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Publication number: 20140227271Abstract: We determined the sequence of ATRX and DAXX in 447 cancers from various sites. We found mutations most commonly in pediatric glioblastoma multiformae (GBM) (11.1%), adult GBM (6.5%), oligodendrogliomas (7.7%) and medulloblastomas (1.5%); and showed that Alternative Lengthening of Telomeres (ALT), a telomerase-independent telomere maintenance mechanism found in cancers that have not activated telomerase, perfectly correlated with somatic mutations of either gene. In contrast, neuroblastomas, and adenocarcinomas of the ovary, breast, and pancreas were negative for mutations in ATRX and DAXX. Alterations in ATRX or DAXX define a specific molecular pathway that is closely associated with an alternative telomere maintenance function in human cancers.Type: ApplicationFiled: June 28, 2012Publication date: August 14, 2014Applicants: DUKE UNIVERSITY, THE JOHNS HOPKINS UNIVERSITYInventors: Hai Yan, Darell Bigner, Bert Vogelstein, Kenneth W. Kinzler, Alan Meeker, Ralph Hruban, Nickolas Papadopoulos, Luis Diaz, Yuchen Jiao
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Publication number: 20140221219Abstract: Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins.Type: ApplicationFiled: July 18, 2012Publication date: August 7, 2014Applicants: DUKE UNIVERSITY, THE JOHNS HOPKINS UNIVERSITYInventors: Bert Vogelstein, Kenneth W. Kinzler, Chetan Bettegowda, Nishant Agrawal, Nickolas Papadopoulos, Darell Bigner, Hai Yan, Roger Mclendon