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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Patent number: 12252743Abstract: 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: GrantFiled: November 13, 2023Date of Patent: March 18, 2025Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac A. Kinde
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Publication number: 20250066860Abstract: 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: ApplicationFiled: August 26, 2024Publication date: February 27, 2025Inventors: Bert Vogelstein, Kenneth W. Kinzler, Joshua David Cohen, Nickolas Papadopoulos, Anne Marie Lennon, Cristian Tomasetti, Yuxuan Wang, Georges Jabboure Netto, Rachel Karchin, Christopher Douville, Samir Hanash, Simeon Springer, Arthur P. Grollman, Kathleen Dickman
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Publication number: 20250034252Abstract: Described herein are methods and compositions for assessing a mammal having or suspected of having cancer and/or for treating a mammal having cancer. For example, molecules including one or more antigen-binding domains (e.g., a single-chain variable fragment (scFv)) that can bind to a modified peptide (e.g., a tumor antigen), as well as method for using such molecules, are provided.Type: ApplicationFiled: December 15, 2022Publication date: January 30, 2025Inventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Shibin Zhou, Sarah DiNapoli, Emily Han-Chung Hsiue, Brian J. Mog, Katharine M. Wright, Sandra B. Gabelli
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Patent number: 12209281Abstract: 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: GrantFiled: June 10, 2022Date of Patent: January 28, 2025Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac A. Kinde
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Publication number: 20250027167Abstract: 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: ApplicationFiled: June 11, 2024Publication date: January 23, 2025Inventors: Chetan Bettegowda, Kenneth W. Kinzler, Bert Vogelstein, Yuxuan Wang, Luis Diaz, Nickolas Papadopoulos
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Publication number: 20250019755Abstract: Provided herein are systems, kits, compositions and methods for sequencing library preparation and sequencing workflow (e.g., for the identification of mutations). In certain embodiments, provides herein systems and methods to identically barcode both strands of templates, and PCR-based enrichment of each strand that does not require hybridization capture.Type: ApplicationFiled: September 27, 2024Publication date: January 16, 2025Inventors: Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Joshua David Cohen
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Patent number: 12195803Abstract: 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: GrantFiled: August 7, 2018Date of Patent: January 14, 2025Assignees: The Johns Hopkins University, Board of Regents, The University of Texas System, The Research Foundation for The State University of New YorkInventors: Bert Vogelstein, Kenneth W. Kinzler, Joshua Cohen, Nickolas Papadopoulos, Anne Marie Lennon, Cristian Tomasetti, Yuxuan Wang, Georges Jabboure Netto, Rachel Karchin, Christopher Douville, Samir Hanash, Simeon Springer, Arthur P. Grollman, Kathleen Dickman
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Publication number: 20250002995Abstract: Massively parallel sequencing of cell-free, maternal plasma DNA was recently demonstrated to be a safe and effective screening method for fetal chromosomal aneuploidies. Here, we report an improved sequencing method achieving significantly increased throughput and decreased cost by replacing laborious sequencing library preparation steps with PCR employing a single primer pair. Using this approach, samples containing as little as 4% trisomy 21 DNA could be readily distinguished from euploid samples.Type: ApplicationFiled: September 12, 2024Publication date: January 2, 2025Inventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac A. Kinde
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Publication number: 20240392381Abstract: 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: April 8, 2024Publication date: November 28, 2024Inventors: 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: 20240352518Abstract: Provided herein are methods for identifying a genetic characteristic, a fragment characteristic and an epigenetic characteristic of a double-stranded DNA molecule in a population of double-stranded DNA molecules by assaying both strands of the double-stranded DNA molecule.Type: ApplicationFiled: August 12, 2022Publication date: October 24, 2024Inventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Austin Mattox, Joshua David Cohen, Yuxuan Wang
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Publication number: 20240345093Abstract: This document provides methods and materials for identifying biomarkers (e.g., peptide biomarkers) that can be used to identify a mammal as having a disease (e.g., cancer). This document also provides methods and materials for identifying and/or treating cancer. For example, this document provides methods and materials for using one or more peptide fragments derived from a peptidyl-prolyl cis-trans isomerase A (PPIA) polypeptide to identify a mammal as having cancer (e.g., ovarian cancer).Type: ApplicationFiled: November 10, 2023Publication date: October 17, 2024Inventors: Bert Vogelstein, Kenneth W. Kinzler, Qing Wang, Nickolas Papadopoulos, Ming Zhang
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Patent number: 12116628Abstract: Massively parallel sequencing of cell-free, maternal plasma DNA was recently demonstrated to be a safe and effective screening method for fetal chromosomal aneuploidies. Here, we report an improved sequencing method achieving significantly increased throughput and decreased cost by replacing laborious sequencing library preparation steps with PCR employing a single primer pair. Using this approach, samples containing as little as 4% trisomy 21 DNA could be readily distinguished from euploid samples.Type: GrantFiled: September 23, 2021Date of Patent: October 15, 2024Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac A. Kinde
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Publication number: 20240309449Abstract: 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: June 10, 2024Publication date: September 19, 2024Inventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac A. Kinde
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Publication number: 20240294648Abstract: This document provides methods and materials for assessing a mammal having or suspected of having cancer and/or for treating a mammal having cancer. For example, molecules including one or more antigen-binding domains (e.g., a single-chain variable fragment (scFv)) that can bind to a modified peptide (e.g., a tumor antigen), as well as method for using such molecules, are provided.Type: ApplicationFiled: September 25, 2023Publication date: September 5, 2024Inventors: Emily Han-Chung Hsiue, Qing Wang, Bert Vogelstein, Kenneth W. Kinzler, Shibin Zhou, Jacqueline Douglass, Michael S. Hwang, Nickolas Papadopoulos
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Publication number: 20240263231Abstract: 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: March 22, 2024Publication date: August 8, 2024Inventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac A. Kinde
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Patent number: 12054781Abstract: 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: GrantFiled: July 12, 2016Date of Patent: August 6, 2024Assignee: The Johns Hopkins UniversityInventors: Chetan Bettegowda, Kenneth W. Kinzler, Bert Vogelstein, Yuxuan Wang, Luis Diaz, Nickolas Papadopoulos
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Patent number: 12006544Abstract: 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: GrantFiled: November 27, 2023Date of Patent: June 11, 2024Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac A. Kinde
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Publication number: 20240166751Abstract: 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: July 12, 2023Publication date: May 23, 2024Inventors: Bert Vogelstein, Kenneth W. Kinzler, Shibin Zhou, Luis Diaz, Nickolas Papadopoulos, Andrew Skora, Jacqueline Douglass, Michael S. Hwang
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Publication number: 20240165155Abstract: This document relates to methods and materials for treating a mammal having cancer. For example, this document provides T cell receptors (TCRs) that can bind to a modified peptide (e.g., a tumor antigen). In some cases, methods of using T cells expressing one or more TCRs that can bind to a modified peptide (e.g., a tumor antigen) to treat a mammal having cancer are provided.Type: ApplicationFiled: March 31, 2022Publication date: May 23, 2024Inventors: Kellie N. Smith, Justina Caushi, Emily Han-Chung Hsiue, Andrew M. Pardoll, Shibin Zhou, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos
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Publication number: 20240148870Abstract: Provided herein are immune cells and methods of use, wherein the immune cells include a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular antigen binding domain that binds specifically to a first epitope; and an inhibitory chimeric antigen receptor (iCAR), wherein the iCAR comprises an extracellular antigen binding domain that binds specifically to a second epitope, wherein the immune cell is activated when the immune cells binds to the first epitope and does not bind to the second epitope; and wherein the immune cell is inactivated when the immune cell binds to the first and second epitopes.Type: ApplicationFiled: March 11, 2022Publication date: May 9, 2024Inventors: Michael S. Hwang, Jacqueline Douglass, Emily Han-Chung Hsiue, Kenneth W. Kinzler, Brian J. Mog, Nickolas Papadopoulos, Alexander H. Pearlman, Bert Vogelstein, Shibin Zhou