Patents by Inventor Ralph Hruban
Ralph Hruban 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: 11667976Abstract: TERT promoter mutations occur in both papillary and flat lesion bladder cancers, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and appear to be strongly associated with bladder cancer recurrence. The TERT promoter mutations are useful urinary biomarker for both the early detection and monitoring of bladder neoplasia.Type: GrantFiled: November 13, 2020Date of Patent: June 6, 2023Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, George J. Netto, Ralph Hruban, Isaac A. Kinde
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Patent number: 11285197Abstract: Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.Type: GrantFiled: July 2, 2019Date of Patent: March 29, 2022Assignee: Johns Hopkins UniversityInventors: Elizabeth A. Jaffee, Tzyy-Choou Wu, Chien-Fu Hung, Ralph Hruban
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Patent number: 11254988Abstract: 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: May 25, 2018Date of Patent: February 22, 2022Assignees: The Johns Hopkins University, Duke 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: 20210130908Abstract: TERT promoter mutations occur in both papillary and flat lesion bladder cancers, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and appear to be strongly associated with bladder cancer recurrence. The TERT promoter mutations are useful urinary biomarker for both the early detection and monitoring of bladder neoplasia.Type: ApplicationFiled: November 13, 2020Publication date: May 6, 2021Inventors: Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, George J. Netto, Ralph Hruban, Isaac A. Kinde
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Patent number: 10870890Abstract: TERT promoter mutations occur in both papillary and flat lesion bladder cancers, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and appear to be strongly associated with bladder cancer recurrence. The TERT promoter mutations are useful urinary biomarker for both the early detection and monitoring of bladder neoplasia.Type: GrantFiled: March 22, 2016Date of Patent: December 22, 2020Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, George J. Netto, Ralph Hruban, Isaac A. Kinde
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Publication number: 20200093911Abstract: Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.Type: ApplicationFiled: July 2, 2019Publication date: March 26, 2020Applicant: Johns Hopkins UniversityInventors: Elizabeth A. Jaffee, Tzyy-Choou Wu, Chien-Fu Hung, Ralph Hruban
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Publication number: 20190256920Abstract: More than 2% of adults harbor a pancreatic cyst, a subset of which progress to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and solid pseudo-papillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10=4.6, 27=12, 16=7.6, and 2.9=2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of VHL, a key component of the VHL ubiquitin ligase complex that has previously been associated both with renal cell carcinomas, SCAs, and other neoplasms.Type: ApplicationFiled: May 1, 2017Publication date: August 22, 2019Applicant: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Jian Wu, Ralph Hruban, Anirban Maitra, Marco Dal Molin
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Patent number: 10350282Abstract: Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.Type: GrantFiled: October 25, 2016Date of Patent: July 16, 2019Assignee: The Johns Hopkins UniversityInventors: Elizabeth A. Jaffee, Tzyy-Choou Wu, Chien-Fu Hung, Ralph Hruban
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Publication number: 20190055610Abstract: Pancreatic Neuroendocrine Tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of ten non-familial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. Remarkably, the most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN-1, which encodes menin, a component of a histone methyltransferase complex; and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain associated protein) and ATRX (alpha thalassemia/mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis.Type: ApplicationFiled: November 2, 2018Publication date: February 21, 2019Inventors: Bert Vogelstein, Kenneth W. Kinzler, Victor Velculescu, Luis Diaz, Nickolas Papadopoulos, Yuchen Jiao, Ralph Hruban
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Patent number: 10144971Abstract: Pancreatic Neuroendocrine Tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of ten non-familial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. Remarkably, the most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN-1, which encodes menin, a component of a histone methyltransferase complex; and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain associated protein) and ATRX (alpha thalassemia/mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis.Type: GrantFiled: January 4, 2012Date of Patent: December 4, 2018Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W Kinzler, Victor Velculescu, Luis Diaz, Nikolas Papadopoulos, Yuchen Jiao, Ralph Hruban
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Publication number: 20180334726Abstract: 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: May 25, 2018Publication date: November 22, 2018Inventors: 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: 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: 9976184Abstract: To help reveal the pathogenesis of these lesions, we purified the DNA from Intraductal Papillary Mucinous Neoplasm (IPMN) cyst fluids from 19 patients and searched for mutations in 169 genes commonly altered in human cancers. We identified recurrent mutations at codon 201 of GNAS. We found that GNAS mutations were present in 66% of IPMNs and that either KRAS or GNAS mutations could be identified in 96%. In eight cases, we could investigate invasive adenocarcinomas that developed in association with IPMNs containing GNAS mutations. In seven of these eight cases, the GNAS mutations present in the IPMNs were also found in the invasive lesion. GNAS mutations were not found in other types of cystic neoplasms of the pancreas or in invasive adenocarcinomas not associated with IPMNs. These data suggest that GNAS mutations can inform the diagnosis and management of patients with cystic pancreatic lesions.Type: GrantFiled: June 22, 2012Date of Patent: May 22, 2018Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Jian Wu, Luis Diaz, Nickolas Papadopoulos, Hanno Matthaei, Ralph Hruban, Anirban Maitra
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Patent number: 9637796Abstract: More than 2% of adults harbor a pancreatic cyst, a subset of which progress to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and solid pseudo-papillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10=4.6, 27=12, 16=7.6, and 2.9=2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of VHL, a key component of the VHL ubiquitin ligase complex that has previously been associated both with renal cell carcinomas, SCAs, and other neoplasms.Type: GrantFiled: November 12, 2012Date of Patent: May 2, 2017Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Jian Wu, Ralph Hruban, Anirban Maitra, Marco Dal Molin
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Publication number: 20170072040Abstract: Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.Type: ApplicationFiled: October 25, 2016Publication date: March 16, 2017Applicant: The Johns Hopkins UniversityInventors: Elizabeth A. Jaffee, Tzyy-Choou Wu, Chien-Fu Hung, Ralph Hruban
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Publication number: 20160208340Abstract: TERT promoter mutations occur in both papillary and flat lesion bladder cancers, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and appear to be strongly associated with bladder cancer recurrence. The TERT promoter mutations are useful urinary biomarker for both the early detection and monitoring of bladder neoplasia.Type: ApplicationFiled: March 22, 2016Publication date: July 21, 2016Applicant: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, George J. Netto, Ralph Hruban, Isaac A. Kinde
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Publication number: 20160199473Abstract: Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.Type: ApplicationFiled: March 14, 2016Publication date: July 14, 2016Applicant: The Johns Hopkins UniversityInventors: Elizabeth A. Jaffee, Ralph Hruban
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Patent number: 9315868Abstract: The present invention provides a method for detecting mutations in the PALB2 gene in pancreatic cancer patients and in individuals having a family history of pancreatic cancer. Methods are also provided for diagnosing a predisposition to pancreatic cancer, for predicting a patient's response to pancreatic cancer therapies, and for treating pancreatic cancer, based on presence of a PALB2 mutation or abberant PALB2 gene expression in a patient.Type: GrantFiled: March 5, 2010Date of Patent: April 19, 2016Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, D. Williams Parsons, Sian Jones, Scott Kern, Ralph Hruban, James R. Eshleman, Michael Goggins, Alison Klein, Manuel Hidalgo, Victor E. Velculescu
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Patent number: 9296784Abstract: Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.Type: GrantFiled: October 1, 2013Date of Patent: March 29, 2016Assignee: The Johns Hopkins UniversityInventors: Elizabeth Jaffee, Ralph Hruban
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Publication number: 20160032406Abstract: The present invention provides a method for detecting mutations in the PALB2 gene in pancreatic cancer patients and in individuals having a family history of pancreatic cancer. Methods are also provided for diagnosing a predisposition to pancreatic cancer, for predicting a patient's response to pancreatic cancer therapies, and for treating pancreatic cancer, based on presence of a PALB2 mutation or abberant PALB2 gene expression in a patient.Type: ApplicationFiled: August 7, 2015Publication date: February 4, 2016Inventors: Bert Vogelstein, Kenneth W. Kinzler, D. Williams Parsons, Sian Jones, Scott Kern, Ralph Hruban, James R. Eshleman, Michael Goggins, Alison Klein, Manuel Hidalgo, Victor Velculescu