Patents by Inventor Bert Vogelstein

Bert Vogelstein 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).

  • Publication number: 20190300946
    Abstract: Bottleneck Sequencing System (BotSeqS) is a next-generation sequencing method that simultaneously quantifies rare somatic point mutations across the mitochondrial and nuclear genomes. BotSeqS combines molecular barcoding with a simple dilution step immediately prior to library amplification. BotSeqS can be used to show age and tissue-dependent accumulations of rare mutations and demonstrate that somatic mutational burden in normal tissues can vary by several orders of magnitude, depending on biologic and environmental factors. BotSeqS has been used to show major differences between the mutational patterns of the mitochondrial and nuclear genomes in normal tissues. Lastly, BotSeqS has shown that the mutation spectra of normal tissues were different from each other, but similar to those of the cancers that arose in them.
    Type: Application
    Filed: January 27, 2017
    Publication date: October 3, 2019
    Inventors: Bert Vogelstein, Kenneth Kinzler, Margaret Hoang, Nickolas Papadopoulos
  • Patent number: 10422006
    Abstract: Phosphatidylinositol 3-kinases (PI3Ks) are known to be important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in cancers, we analyzed the sequences of the PI3K gene family and discovered that one family member, PIK3CA, is frequently mutated in cancers of the colon and other organs. The majority of mutations clustered near two positions within the PI3K helical or kinase domains. PIK3CA represents one of the most highly mutated oncogenes yet identified in human cancers and is useful as a diagnostic and therapeutic target.
    Type: Grant
    Filed: October 31, 2014
    Date of Patent: September 24, 2019
    Assignee: The John Hopkins University
    Inventors: Yardena Samuels, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
  • Publication number: 20190256924
    Abstract: Provided herein are methods and materials for detecting and/or treating subject (e.g., a human) having cancer. In some embodiments, methods and materials for identifying a subject as having cancer (e.g., a localized cancer) are provided in which the presence of member(s) of two or more classes of biomarkers are detected. In some embodiments, methods and materials for identifying a subject as having cancer (e.g., a localized cancer) are provided in which the presence of member(s) of at least one class of biomarkers and the presence of aneuploidy are detected. In some embodiments, methods described herein provide increased sensitivity and/or specificity in the detection of cancer in a subject (e.g. a human).
    Type: Application
    Filed: January 17, 2019
    Publication date: August 22, 2019
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Joshua Cohen, Nickolas Papadopoulos, Anne Marie Lennon, Cristian Tomasetti, Yuxuan Wang, Georges Jabboure Netto, Rachel Karchin, Chris Douville, Samir Hanash, Simeon Springer, Arthur Grollman, Kathleen Dickman
  • Publication number: 20190256920
    Abstract: 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: Application
    Filed: May 1, 2017
    Publication date: August 22, 2019
    Applicant: The Johns Hopkins University
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Jian Wu, Ralph Hruban, Anirban Maitra, Marco Dal Molin
  • Publication number: 20190240257
    Abstract: The invention features compositions and methods for identifying functional anti-tumor T cell responses.
    Type: Application
    Filed: October 13, 2017
    Publication date: August 8, 2019
    Inventors: Drew M. Pardoll, Kellie Smith, Franck Housseau, Victor Velculescu, Valsamo Anagnostou, Luis Diaz, Bert Vogelstein, Ken Kinzler, Nickolas Papadopoulos
  • Publication number: 20190106752
    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 gliblastomas 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: Application
    Filed: September 17, 2018
    Publication date: April 11, 2019
    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 Bigner, Chien-Tsun Kuan, Gregory J. Riggins
  • Publication number: 20190055610
    Abstract: 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: Application
    Filed: November 2, 2018
    Publication date: February 21, 2019
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Victor Velculescu, Luis Diaz, Nickolas Papadopoulos, Yuchen Jiao, Ralph Hruban
  • Publication number: 20190023787
    Abstract: Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.
    Type: Application
    Filed: September 27, 2018
    Publication date: January 24, 2019
    Inventors: Luis Diaz, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Dung Le, Drew M. Pardoll, Suzanne L. Topalian
  • Publication number: 20190002987
    Abstract: As cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we assessed the cerebrospinal fluid (CSF) that bathes the CNS for tumor DNA, here termed CSF-tDNA. The results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.
    Type: Application
    Filed: July 12, 2016
    Publication date: January 3, 2019
    Inventors: Chetan BETTEGOWA, Kenneth W. KINZLER, Bert VOGELSTEIN, Yuxuan WANG, Luis DIAZ, Nickolas PAPADOPOULOUS
  • Patent number: 10150991
    Abstract: Improvements on the basic method used for BEAMing increase sensitivity and increase the signal-to-noise ratio. The improvements have permitted the determination of intrinsic error rates of various DNA polymerases and have permitted the detection of rare and subtle mutations in DNA isolated from plasma of cancer patients.
    Type: Grant
    Filed: June 6, 2016
    Date of Patent: December 11, 2018
    Assignee: The Johns Hopkins University
    Inventors: Bert Vogelstein, Frank Diehl, Kenneth W. Kinzler, Meng Li
  • Patent number: 10144971
    Abstract: 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: Grant
    Filed: January 4, 2012
    Date of Patent: December 4, 2018
    Assignee: The Johns Hopkins University
    Inventors: Bert Vogelstein, Kenneth W Kinzler, Victor Velculescu, Luis Diaz, Nikolas Papadopoulos, Yuchen Jiao, Ralph Hruban
  • Publication number: 20180334726
    Abstract: 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: Application
    Filed: May 25, 2018
    Publication date: November 22, 2018
    Inventors: Hai Yan, Darell Bigner, Bert Vogelstein, Kenneth W. Kinzler, Alan Meeker, Ralph Hruban, Nickolas Papadopoulos, Luis Diaz, Yuchen Jiao
  • Publication number: 20180327863
    Abstract: Two genes, ARID1A (AT-rich interactive domain-containing protein 1A) and PPP2R1A (protein-phosphatase 2, regulatory subunit 1, alpha), can be used in methods which are useful for detecting cancer, diagnosing cancer, contributing to a diagnosis of cancer, confirming a diagnosis of cancer, identifying appropriate treatments for cancer, monitoring treatment of cancer, and evaluating treatment protocols for cancer, including ovarian clear cell carcinoma, breast cancer, colon cancer, gastric cancer, lung cancer, medulloblastoma, pancreatic cancer, and prostate cancer.
    Type: Application
    Filed: May 23, 2018
    Publication date: November 15, 2018
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Victor Velculescu, Nickolas Papadopoulos, Sian Jones
  • Publication number: 20180325847
    Abstract: Methods for treating or preventing liver fibrosis in a subject by administering to the subject a therapeutically effective amount of 3-bromopyruvate (3-BrPA) are provided. In addition, methods for promoting the reversal of an activated hepatic stellate cell (HSC) to an inactivated HSC by contacting the activated HSC with at least one 3-bromopyruvate (3-BrPA) molecule are also provided.
    Type: Application
    Filed: November 4, 2016
    Publication date: November 15, 2018
    Inventors: Shanmugasundaram Ganapathy-Kanniappan, Surojit Sur, Bert Vogelstein, Kenneth W. Kinzler, Jean-Francois Geschwind
  • Publication number: 20180327858
    Abstract: The identification of pre-defined mutations expected to be present in a minor fraction of a cell population is important for a variety of basic research and clinical applications. The exponential, analog nature of the polymerase chain reaction is transformed into a linear, digital signal suitable for this purpose. Single molecules can be isolated by dilution and individually amplified; each product is then separately analyzed for the presence of pre-defined mutations. The process provides a reliable and quantitative measure of the proportion of variant sequences within a DNA sample.
    Type: Application
    Filed: May 1, 2018
    Publication date: November 15, 2018
    Inventors: Bert Vogelstein, Kenneth W. Kinzler
  • Publication number: 20180282821
    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 gliblastomas 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: Application
    Filed: March 22, 2018
    Publication date: October 4, 2018
    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 Bigner, Chien-Tsun Kuan, Gregory J. Riggins
  • Publication number: 20180258490
    Abstract: A diagnostic test for ovarian cysts is based on the detection of mutations characteristic of the most common neoplasms giving rise to these lesions. With this test, tumor-specific mutations were detected in the cyst fluids of 19 of 24 (79%) borderline tumors and 28 of 31 (90%) malignant ovarian cancers. In contrast, we detected no mutations in the cyst fluids from 10 non-neoplastic cysts and 12 benign tumors. When categorized by the need for exploratory surgery (i.e., presence of a borderline tumor or malignant cancer), the sensitivity of this test was 85% and the specificity was 100%. These tests could inform the diagnosis of ovarian cysts and improve the clinical management of the large number of women with these lesions.
    Type: Application
    Filed: August 11, 2016
    Publication date: September 13, 2018
    Inventors: Yuxuan Wang, Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, Karin Sundfeldt, Bjorg Kristjansdottir
  • Patent number: 10053729
    Abstract: The present disclosure relates to methods for testing a human for aneuploidy. In some aspects, a plurality of chromosomal sequences in a DNA sample from a human are amplified with a single pair of primers complementary to said chromosomal sequences to form a plurality of amplicons, wherein the plurality of amplicons are not identical, and wherein the plurality of amplicons include sequences on a query chromosome and sequences on a plurality of reference chromosomes. In some aspects, reactions are performed to determine the nucleotide sequence of at least 3 nucleotides of the plurality of amplicons. In some aspects, amplicon nucleotide sequences are matched in silico to genomic sequences at genomic loci. In some aspects, numbers of matching amplicons at individual genomic loci are counted. In some aspects, numbers of amplicons matched to genomic loci on the query chromosome are compared to numbers of amplicons matched to genomic loci on the reference chromosomes.
    Type: Grant
    Filed: March 22, 2013
    Date of Patent: August 21, 2018
    Assignee: The Johns Hopkins University
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac G. Kinde
  • Publication number: 20180195132
    Abstract: 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: Application
    Filed: December 7, 2017
    Publication date: July 12, 2018
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Chetan Bettegowda, Nishant Agrawal, Nickolas Papadopoulos, Darell Bigner, Hai Yan, Roger McLendon
  • Publication number: 20180171413
    Abstract: We queried DNA from saliva or plasma of 93 HNSCC patients, searching for somatic mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% (95% CI, 84% to 99%) of 47 patients. The fractions of patients with detectable tumor DNA in early- and late-stage disease were 100% (n=10) and 95% (n=37), respectively. Saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in the saliva and plasma is a valuable biomarker for detection of HNSCC.
    Type: Application
    Filed: June 16, 2016
    Publication date: June 21, 2018
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, Nishant Agrawal, Yuxuan Wang, Simeon Springer