Patents by Inventor Kenneth W. Kinzler

Kenneth W. Kinzler 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).

  • Patent number: 11453913
    Abstract: 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: Grant
    Filed: May 19, 2021
    Date of Patent: September 27, 2022
    Assignee: The Johns Hopkins University
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac A. Kinde
  • Patent number: 11439669
    Abstract: The present invention provides, inter alia, methods for treating or ameliorating an effect of a solid tumor present in a human. These methods include administering intratumorally to the human a unit dose of C. novyi, preferably C. novyi NT, colony forming units (CFUs), which contains about 1×103-1×107 CFUs suspended in a pharmaceutically acceptable carrier or solution. Methods for debulking a solid tumor present in a human, methods for ablating a solid tumor present in a human, a method for microscopically precise excision of tumor cells in a human, methods for treating or ameliorating an effect of a solid tumor that has metastasized to one or more sites in a human, unit doses of C. novyi, preferably C. novyi NT, CFUs, and kits for treating or ameliorating an effect of a solid tumor present in a human are also provided.
    Type: Grant
    Filed: March 31, 2020
    Date of Patent: September 13, 2022
    Assignees: BIOMED VALLEY DISCOVERIES, INC., THE JOHNS HOPKINS UNIVERSITY
    Inventors: Saurabh Saha, Shibin Zhou, Bert Vogelstein, Kenneth W. Kinzler
  • Publication number: 20220275086
    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: May 9, 2022
    Publication date: September 1, 2022
    Inventors: Luis Diaz, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Dung Le, Drew M. Pardoll, Suzanne L. Topalian
  • Publication number: 20220259668
    Abstract: This document provides methods and materials for identifying chromosomal anomalies that can be used to identify a mammal as having a disease (e.g., cancer or congenital abnormality). For example, this document provides methods and materials for evaluating sequencing data to identify a mammal as having a disease associated with one or more chromosomal anomalies (e.g., cancer or congenital abnormalities). For example, this document provides methods and materials for evaluating sequencing data that can be used in cancer diagnostics, non-invasive prenatal testing (NIPT), preimplantation genetic diagnosis and evaluation of congenital abnormalities.
    Type: Application
    Filed: May 15, 2020
    Publication date: August 18, 2022
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Christopher Douville, Nickolas Papadopoulos, Cristian Tomasetti
  • Publication number: 20220259312
    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: May 9, 2022
    Publication date: August 18, 2022
    Inventors: Luis Diaz, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Dung Le, Drew M. Pardoll, Suzanne L. Topalian
  • Publication number: 20220220563
    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: January 27, 2022
    Publication date: July 14, 2022
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, Nishant Agrawal, Yuxuan Wang, Simeon Springer
  • Publication number: 20220205048
    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: January 14, 2022
    Publication date: June 30, 2022
    Inventors: Yuxuan Wang, Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, Karin Sundfeldt, Bjorg Kristjansdottir
  • Patent number: 11339219
    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: Grant
    Filed: December 22, 2020
    Date of Patent: May 24, 2022
    Assignee: The Johns Hopkins University
    Inventors: Luis Diaz, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Dung Le, Drew M. Pardoll, Suzanne L. Topalian
  • Patent number: 11325975
    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: Grant
    Filed: December 22, 2020
    Date of Patent: May 10, 2022
    Assignee: The Johns Hopkins University
    Inventors: Luis Diaz, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Dung Le, Drew M. Pardoll, Suzanne L. Topalian
  • Patent number: 11325974
    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: Grant
    Filed: December 22, 2020
    Date of Patent: May 10, 2022
    Assignee: The Johns Hopkins University
    Inventors: Luis Diaz, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Dung Le, Drew M. Pardoll, Suzanne L. Topalian
  • Patent number: 11306364
    Abstract: We surveyed 1,230 tumors of 60 different types and found that tumors could be divided into types with low (<15%) and high (?15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
    Type: Grant
    Filed: July 14, 2020
    Date of Patent: April 19, 2022
    Assignees: Duke University, The Johns Hopkins University
    Inventors: Hai Yan, Bert Vogelstein, Nickolas Papadopoulos, Kenneth W. Kinzler, Yuchen Jiao, Chetan Bettegowda, Darell D. Bigner, Zachary J. Reitman, Patrick J. Killela
  • Patent number: 11286531
    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: Grant
    Filed: August 11, 2016
    Date of Patent: March 29, 2022
    Assignee: The Johns Hopkins University
    Inventors: Yuxuan Wang, Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, Karin Sundfeldt, Bjorg Kristjansdottir
  • Publication number: 20220073977
    Abstract: 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: Application
    Filed: February 12, 2021
    Publication date: March 10, 2022
    Inventors: Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Joshua David Cohen
  • Patent number: 11268153
    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: Grant
    Filed: June 16, 2016
    Date of Patent: March 8, 2022
    Assignee: The Johns Hopkins University
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Luis Diaz, Nickolas Papadopoulos, Nishant Agrawal, Yuxuan Wang, Simeon Springer
  • Publication number: 20220056129
    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 2, 2021
    Publication date: February 24, 2022
    Inventors: Luis Diaz, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Dung Le, Drew M. Pardoll, Suzanne L. Topalian
  • Patent number: 11254988
    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: Grant
    Filed: May 25, 2018
    Date of Patent: February 22, 2022
    Assignees: The Johns Hopkins University, Duke University
    Inventors: Hai Yan, Darell Bigner, Bert Vogelstein, Kenneth W. Kinzler, Alan Meeker, Ralph Hruban, Nickolas Papadopoulos, Luis Diaz, Yuchen Jiao
  • Patent number: 11241402
    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: Grant
    Filed: July 17, 2020
    Date of Patent: February 8, 2022
    Assignee: The Johns Hopkins University
    Inventors: Shanmugasundaram Ganapathy-Kanniappan, Surojit Sur, Bert Vogelstein, Kenneth W. Kinzler, Jean-Francois Geschwind
  • Publication number: 20220010371
    Abstract: 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: Application
    Filed: September 23, 2021
    Publication date: January 13, 2022
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac A. Kinde
  • Publication number: 20210395365
    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 2, 2021
    Publication date: December 23, 2021
    Inventors: Luis Diaz, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Dung Le, Drew M. Pardoll, Suzanne L. Topalian
  • Patent number: 11180803
    Abstract: Though massively parallel sequencing instruments are in principle well-suited to the task of identification of mutations present in a small fraction of DNA templates, the error rates in such 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 is called “Safe-SeqS” for (Safe-Sequencing System) and 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: Grant
    Filed: August 18, 2016
    Date of Patent: November 23, 2021
    Assignee: The Johns Hopkins University
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Isaac Kinde