Patents by Inventor Nickolas Papadopoulos
Nickolas Papadopoulos 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: 20180282821Abstract: 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: ApplicationFiled: March 22, 2018Publication date: October 4, 2018Inventors: 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: 20180258490Abstract: 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: ApplicationFiled: August 11, 2016Publication date: September 13, 2018Inventors: Yuxuan Wang, Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, Karin Sundfeldt, Bjorg Kristjansdottir
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Patent number: 10053729Abstract: 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: GrantFiled: March 22, 2013Date of Patent: August 21, 2018Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac G. Kinde
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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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Publication number: 20180171413Abstract: 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: ApplicationFiled: June 16, 2016Publication date: June 21, 2018Inventors: Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, Nishant Agrawal, Yuxuan Wang, Simeon Springer
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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: 9982304Abstract: 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: GrantFiled: September 6, 2011Date of Patent: May 29, 2018Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Victor Velculescu, Nickolas Papadopoulos, Sian Jones
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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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Publication number: 20180086832Abstract: Mutant epitopes encoded by cancer genes are virtually always located in the interior of cells, making them invisible to conventional antibodies. We generated single chain variable fragments (scFvs) specific for mutant peptides presented on the cell surface by human leukocyte antigen (HLA) molecules. These scFvs can be converted to full-length antibodies, termed MANAbodies, targeting “Mutation Associated Neo-Antigens” bound to HLA. A phage display library representing a highly diverse array of single-chain variable fragment sequences was first designed and constructed. A competitive selection protocol was then used to identify clones specific for peptides bound to pre-defined HLA types. In this way, we obtained scFvs, including one specific for a peptide encoded by a common KRAS mutant and another by a common EGFR mutant. Molecules targeting MANA can be developed that specifically react with mutant peptide-HLA complexes even when these peptides differ by only one amino acid from the normal, wild-type form.Type: ApplicationFiled: March 23, 2016Publication date: March 29, 2018Inventors: Bert Vogelstein, Kenneth W. Kinzler, Shibin Zhou, Luis Diaz, Nickolas Papadopoulos, Andrew Skora, Jackie Douglass, Michael S. Hwang
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Publication number: 20180080062Abstract: Assays can be used to detect mutations found in neoplasms of the pancreas, as well as for other neoplasms and other uses. Nucleic acids can be captured from body fluids such as cyst fluids. Thousands of oligonucleotides can be synthesized in parallel, amplified and ligated together. The ligated products can be further amplified. The amplified, ligated products are used to capture complementary DNA sequences, which can be analyzed, for example by massively parallel sequencing.Type: ApplicationFiled: May 30, 2017Publication date: March 22, 2018Applicant: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Jian Wu
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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: 20170313775Abstract: 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: ApplicationFiled: November 12, 2015Publication date: November 2, 2017Applicant: The Johns Hopkins UniversityInventors: Luis Diaz, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Dung Le
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Publication number: 20170267760Abstract: 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: ApplicationFiled: June 1, 2017Publication date: September 21, 2017Applicant: The Johns Hopkins UniversityInventors: Luis Diaz, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Dung Le
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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: 9670527Abstract: Assays can be used to detect mutations found in neoplasms of the pancreas, as well as for other neoplasms and other uses. Nucleic acids can be captured from body fluids such as cyst fluids. Thousands of oligonucleotides can be synthesized in parallel, amplified and ligated together. The ligated products can be further amplified. The amplified, ligated products are used to capture complementary DNA sequences, which can be analyzed, for example by massively parallel sequencing.Type: GrantFiled: June 28, 2012Date of Patent: June 6, 2017Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Jian Wu
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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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Patent number: 9637779Abstract: Transcription in mammalian cells can be assessed at a genome-wide level, but it has been difficult to reliably determine whether individual transcripts are derived from the Plus- or Minus-strands of chromosomes. This distinction can be critical for understanding the relationship between known transcripts (sense) and the complementary antisense transcripts that may regulate them. Here we describe a technique that can be used to (i) identify the DNA strand of origin for any particular RNA transcript and (ii) quantify the number of sense and antisense transcripts from expressed genes at a global level. We examined five different human cell types and in each case found evidence for antisense transcripts in 2900 to 6400 human genes. The distribution of antisense transcripts was distinct from that of sense transcripts, was non-random across the genome, and differed among cell types.Type: GrantFiled: December 2, 2009Date of Patent: May 2, 2017Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Yiping He, Victor Velculescu, Nickolas Papadopoulos
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Publication number: 20170081730Abstract: 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: ApplicationFiled: November 16, 2016Publication date: March 23, 2017Applicants: 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 D. Bigner, Chien-Tsun Kuan, Gregory J. Riggins
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Publication number: 20170051347Abstract: The identification of mutations that are present in a small fraction of DNA templates is essential for progress in several areas of biomedical research. Though massively parallel sequencing instruments are in principle well-suited to this task, the error rates in such instruments are generally too high to allow confident identification of rare variants. We here describe an approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose. One example of this approach, called “Safe-SeqS” for (Safe-Sequencing System) includes (i) assignment of a unique identifier (UID) to each template molecule; (ii) amplification of each uniquely tagged template molecule to create UID-families; and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are truly mutant (“super-mutants”) if ?95% of them contain the identical mutation.Type: ApplicationFiled: August 18, 2016Publication date: February 23, 2017Applicant: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac Kinde
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Patent number: 9487829Abstract: Error rates in massively parallel sequencing instruments are generally too high to allow confident identification of rare variants. An approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose, called “Safe-SeqS” for (Safe-Sequencing System) includes (i) assignment of a unique identifier (UID) to each template molecule; (ii) amplification of each uniquely tagged template molecule to create UID-families; and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are truly mutant (“super-mutants”) if ?95% of them contain the identical mutation. We illustrate the utility of this approach for determining the fidelity of a polymerase, the accuracy of oligonucleotides synthesized in vitro, and the prevalence of mutations in the nuclear and mitochondrial genomes of normal cells.Type: GrantFiled: July 30, 2015Date of Patent: November 8, 2016Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac Kinde