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: 7745165
    Abstract: Among the genes identified, in a comparison of the global gene expression profile of metastatic colorectal cancer to that of primary cancers, benign colorectal tumors, and normal colorectal epithelium, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in non-metastatic tumors and normal colorectal epithelium. In three of twelve metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provides a new therapeutic target for these intractable lesions.
    Type: Grant
    Filed: June 16, 2004
    Date of Patent: June 29, 2010
    Assignee: The John Hopkins University
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Saurabh Saha, Alberto Bardelli
  • Publication number: 20100136560
    Abstract: Genome-wide analysis of copy number changes in breast and colorectal tumors used approaches that can reliably detect homozygous deletions and amplifications. The number of genes altered by major copy number changes—deletion of all copies or amplification of at least twelve copies per cell—averaged thirteen per tumor. These data were integrated with previous mutation analyses of the Reference Sequence genes in these same tumor types to identify genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations include those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that are useful for cancer diagnosis and therapy.
    Type: Application
    Filed: November 17, 2009
    Publication date: June 3, 2010
    Applicant: The Johns Hopkins University
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Rebecca J. Leary, Victor E. Velculescu
  • Publication number: 20100137413
    Abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. The public miRNA database contains 321 human miRNA sequences, 234 of which have been experimentally verified. To explore the possibility that additional miRNAs are present in the human genome, we have developed an experimental approach called miRNA serial analysis of gene expression (miRAGE) and used it to perform the largest experimental analysis of human miRNAs to date. Sequence analysis of 273,966 small RNA tags from human colorectal cells allowed us to identify 200 known mature miRNAs, 133 novel miRNA candidates, and 112 previously uncharacterized miRNA* forms. To aid in the evaluation of candidate miRNAs, we disrupted the Dicer locus in three human colorectal cancer cell lines and examined known and novel miRNAs in these cells. The miRNAs are useful to diagnose and treat cancers.
    Type: Application
    Filed: February 16, 2007
    Publication date: June 3, 2010
    Applicant: THE JOHNS HOPKINS UNIVERSITY
    Inventors: Jordan Cummins, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
  • Patent number: 7704689
    Abstract: Blockade of mismatch repair in a plant can lead to hypermutation and a new genotype and/or phenotype. One approach used to generate hypermutable plants is through the expression of dominant negative alleles of mismatch repair genes in transgenic plants or derived cells. By introducing these genes into cells and transgenic plants, new cell lines and plant varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. Moreover, methods to inhibit the expression and activity of endogenous plant MMR genes and their encoded products are also useful to generate hypermutable plants.
    Type: Grant
    Filed: May 13, 2005
    Date of Patent: April 27, 2010
    Assignees: The Johns Hopkins University, Morphotek, Inc.
    Inventors: Nicholas C. Nicolaides, Luigi Grasso, Philip M. Sass, Kenneth W. Kinzler, Bert Vogelstein
  • Patent number: 7695969
    Abstract: Bacteria are manipulated to create desirable output traits using dominant negative alleles of mismatch repair proteins. Enhanced hypermutation is achieved by combination of mismatch repair deficiency and exogenously applied mutagens. Stable bacteria containing desirable output traits are obtained by restoring mismatch repair activity to the bacteria.
    Type: Grant
    Filed: February 24, 2006
    Date of Patent: April 13, 2010
    Assignees: The Johns Hopkins University, Morphotek, Inc.
    Inventors: Nicholas C. Nicolaides, Philip M. Sass, Luigi Grasso, Bert Vogelstein, Kenneth W. Kinzler
  • Publication number: 20100041048
    Abstract: DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. We apply a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in body samples of patients. Measurements of ctDNA can be used to reliably monitor tumor dynamics in subjects with cancer, especially those who are undergoing surgery or chemotherapy. This personalized genetic approach can be generally applied.
    Type: Application
    Filed: July 30, 2009
    Publication date: February 18, 2010
    Applicant: The Johns Hopkins University
    Inventors: Frank DIEHL, Luis Diaz, Kenneth W. Kinzler, Bert Vogelstein, Kerstin Schmidt
  • Publication number: 20090186339
    Abstract: Global gene expression patterns have been characterized in normal and cancerous human cells using serial analysis of gene expression (SAGE). Cancer cell-specific, cell-type specific, and ubiquitously expressed genes have been identified. This information can be used to provide combinations of cell type- and cancer-specific gene probes, as well as methods of using these probes to identify particular cell types, screen for useful drugs, reduce cancer-specific gene expression, standardize gene expression, and restore function to a diseased cell or tissue.
    Type: Application
    Filed: February 15, 2005
    Publication date: July 23, 2009
    Applicant: The Johns Hopkins University
    Inventors: Victor E. Velculescu, Bert Vogelstein, Kenneth W. Kinzler
  • Publication number: 20090137427
    Abstract: Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. The enhanced rate of mutation can be further augmented using mutagens. Moreover, the hypermutability of mismatch repair deficient cells can be remedied to stabilize cells or mammals with useful mutations.
    Type: Application
    Filed: October 19, 2007
    Publication date: May 28, 2009
    Applicant: The John Hopkins University School of Medicine
    Inventors: Nicholas C. Nicolaides, Philip M. Sass, Luigi Grasso, Bert Vogelstein, Kenneth W. Kinzler
  • Publication number: 20090123928
    Abstract: Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalogue the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene “mountains” and a much larger number of gene “hills” that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
    Type: Application
    Filed: October 8, 2008
    Publication date: May 14, 2009
    Applicant: The Johns Hopkins University
    Inventors: Laura D. Wood, Williams D. Parsons, Sian Jones, Jimmy Lin, Tobias Sjoblom, Thomas Barber, Giovanni Parmigiani, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
  • Publication number: 20090124795
    Abstract: Mitochondrial mutations occur as a product of contact of a person with an environmental pollutant. Mitochondrial mutations are readily detectable in body fluids. Measurement of mitochondrial mutations in body fluids can be used as a dosimeter to monitor exposure to the environmental pollutant. Mitochondrial mutations can also be detected in cancer patients. Probes and primers containing mutant mitochondrial sequences can be used to monitor patient condition.
    Type: Application
    Filed: April 10, 2008
    Publication date: May 14, 2009
    Applicant: JOHNS HOPKINS UNIVERSITY
    Inventors: Makiko Fliss, David Sidransky, Jin Jen, Kornelia Polyak, Bert Vogelstein, Kenneth W. Kinzler
  • Publication number: 20090117546
    Abstract: Genetic diseases can be diagnosed by detection of mutations in causative genes. Protein truncation assays can be used to detect gene products of truncation-type mutations. However, the sensitivity of the assays is often insufficient to detect mutations present in a sample of DNA at a low frequency. Sensitivity can be increased by dividing samples so that the signal generated by a mutant allele comprises a larger fraction of the total alleles than prior to dividing. Thus a previously undetectable signal generated by the mutant allele can become detectable in the assay. Such increased sensitivity permits detection at early stages and in samples having high levels of other alleles.
    Type: Application
    Filed: February 8, 2007
    Publication date: May 7, 2009
    Applicant: The Johns Hopkins University
    Inventors: C. Giovanni Traverso, Kenneth W. Kinzler, Bert Vogelstein
  • Patent number: 7514216
    Abstract: Yeast cells are mutagenized to obtain desirable mutants. Mutagenesis is mediated by a defective mismatch repair system which can be enhanced using conventional exogenously applied mutagens. Yeast cells with the defective mismatch repair system are hypermutable, but after selection of desired mutant yeast strains, they can be rendered genetically stable by restoring the mismatch repair system to proper functionality.
    Type: Grant
    Filed: July 26, 2005
    Date of Patent: April 7, 2009
    Assignee: The Johns Hopkins University
    Inventors: Nicholas C. Nicolaides, Philip M. Sass, Luigi Grasso, Bert Vogelstein, Kenneth W. Kinzler
  • Publication number: 20090017030
    Abstract: To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed 79 differentially expressed genes, including 46 that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.
    Type: Application
    Filed: October 31, 2007
    Publication date: January 15, 2009
    Applicant: The John Hopkins University
    Inventors: Brad St.Croix, Bert Vogelstein, Kenneth W. Kinzler
  • Publication number: 20080318321
    Abstract: Bacteria are manipulated to create desirable output traits using dominant negative alleles of mismatch repair proteins. Enhanced hypermutation is achieved by combination of mismatch repair deficiency and exogenously applied mutagens. Stable bacteria containing desirable output traits are obtained by restoring mismatch repair activity to the bacteria.
    Type: Application
    Filed: October 31, 2007
    Publication date: December 25, 2008
    Applicants: The Johns Hopkins University, Morphotek, Inc.
    Inventors: Nicholas C. Nicolaides, Philip M. Sass, Luigi Grasso, Bert Vogelstein, Kenneth W. Kinzler
  • Publication number: 20080313754
    Abstract: Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation.
    Type: Application
    Filed: October 11, 2007
    Publication date: December 18, 2008
    Applicant: The Johns Hopkins University
    Inventors: Nicholas Nicolaides, Bert Yogelstein, Kenneth W. Kinzler
  • Publication number: 20080305490
    Abstract: A human gene has been discovered which is genetically altered in human tumor cells. The genetic alteration is gene amplification and leads to a corresponding increase in gene products. Detecting that the gene, designated hMDM2, has become amplified or detecting increased expression of gene products is diagnostic of tumorigenesis. Human MD2 protein binds to human p53 and allows the cell to escape from p53-regulated growth.
    Type: Application
    Filed: July 1, 2008
    Publication date: December 11, 2008
    Applicant: The Johns Hopkins University
    Inventors: Marilee Burrell, David E. Hill, Kenneth W. Kinzler, Bert Vogelstein
  • Publication number: 20080241830
    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: February 23, 2007
    Publication date: October 2, 2008
    Applicant: The Johns Hopkins University
    Inventors: Bert Vogelstein, Kenneth W. Kinzler
  • Publication number: 20080176329
    Abstract: Yeast cells are mutagenized to obtain desirable mutants. Mutagenesis is mediated by a defective mismatch repair system which can be enhanced using conventional exogenously applied mutagens. Yeast cells with the defective mismatch repair system are hypermutable, but after selection of desired mutant yeast strains, they can be rendered genetically stable by restoring the mismatch repair system to proper functionality.
    Type: Application
    Filed: October 31, 2007
    Publication date: July 24, 2008
    Applicants: The Johns Hopkins University, Morphotek, Inc.
    Inventors: Nicholas C. Nicolaides, Philip M. Sass, Luigi Grasso, Bert Vogelstein, Kenneth W. Kinzler
  • Patent number: 7402660
    Abstract: To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed 79 differentially expressed genes, including 46 that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.
    Type: Grant
    Filed: August 1, 2001
    Date of Patent: July 22, 2008
    Assignee: The Johns Hopkins University
    Inventors: Brad St. Croix, Bert Vogelstein, Kenneth W. Kinzler
  • Patent number: RE40948
    Abstract: A human gene termed APC is disclosed. Methods and kits are provided for assessing mutations of the APC gene in human tissues and body samples. APC mutations are found in familial adenomatous polyposis patients as well as in sporadic colorectal cancer patients. APC is expressed in most normal tissues. These results suggest that APC is a tumor suppressor.
    Type: Grant
    Filed: October 24, 2001
    Date of Patent: October 27, 2009
    Assignees: The Johns Hopkins University, Astrazeneca United Kingdom, Ltd., Cancer Institute, Japanese, Foundation for Cancer Research, The University of Utah
    Inventors: Bert Vogelstein, Kenneth W. Kinzler, Hans Albertsen, Rakesh Anand, Mary Carlson, Joanna Groden, Philip Hedge, Geoff Joslyn, Alexander Fred Markham, Yusuke Nakumura, Andrew Thliveris, Raymond White