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).

  • Methods for detection of colorectal cancer
    Patent number: 8029764
    Abstract: Particular genes are aberrantly and consistently expressed in both adenomas and carcinomas of the colon. Products of such genes provide stool and serum markers for colorectal neoplasia. One particular tumor marker, Renal Dipeptidase (RDP), is expressed at high levels in tumors and at greatly reduced levels in normal tissues. The elevated expression of RDP occurs early and remains elevated during the neoplastic process. RDP may therefore be especially useful as a diagnostic tool for the early detection of colorectal neoplasia, even of presymptomatic colorectal neoplasia.
    Type: Grant
    Filed: September 9, 2002
    Date of Patent: October 4, 2011
    Assignee: The Johns Hopkins University
    Inventors: Phillip Buckhaults, Kenneth W. Kinzler, Bert Vogelstein
  • Mutations of the PIK3CA gene in human cancers
    Patent number: 8026053
    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 P13K 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 P13K 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: February 18, 2005
    Date of Patent: September 27, 2011
    Assignee: The Johns Hopkins University
    Inventors: Yardena Samuels, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
  • GENETIC ALTERATIONS IN ISOCITRATE DEHYDROGENASE AND OTHER GENES IN MALIGNANT GLIOMA
    Publication number: 20110229479
    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 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: Application
    Filed: September 3, 2009
    Publication date: September 22, 2011
    Applicants: THE JOHNS HOPKINS UNIVERSITY, DUKE UNIVERSITY
    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
  • Combination bacteriolytic therapy for the treatment of tumors
    Patent number: 8007782
    Abstract: Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sponzlated bacteria.
    Type: Grant
    Filed: October 21, 2004
    Date of Patent: August 30, 2011
    Assignee: The Johns Hopkins University
    Inventors: Long Dang, Chetan Bettegowda, Kenneth W. Kinzler, Bert Vogelstein
  • Digital Amplification
    Publication number: 20110201004
    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: March 24, 2011
    Publication date: August 18, 2011
    Applicant: THE JOHNS HOPKINS UNIVERSITY
    Inventors: Bert VOGELSTEIN, Kenneth W. KINZLER
  • DISEASE DETECTION BY DIGITAL PROTEIN TRUNCATION ASSAYS
    Publication number: 20110195416
    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: March 16, 2011
    Publication date: August 11, 2011
    Applicant: THE JOHNS HOPKINS UNIVERSITY
    Inventors: C. Giovanni Traverso, Kenneth W. Kinzler, Bert Vogelstein
  • Membrane Associated Tumor Endothelium Markers
    Publication number: 20110104059
    Abstract: To gain a better understanding of tumor angiogenesis endothelial cells (ECs) were isolated and gene expression patterns were evaluated. 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 differentially expressed genes, including many 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.
    Type: Application
    Filed: May 6, 2009
    Publication date: May 5, 2011
    Applicant: THE JOHNS HOPKINS UNIVERSITY
    Inventors: Brad ST. CROIX, Kenneth W. KINZLER, Bert VOGELSTEIN
  • Digital amplification
    Patent number: 7915015
    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: Grant
    Filed: November 12, 2009
    Date of Patent: March 29, 2011
    Assignee: The Johns Hopkins University
    Inventors: Bert Vogelstein, Kenneth W. Kinzler
  • Disease detection by protein truncation assays
    Patent number: 7910300
    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: Grant
    Filed: February 8, 2007
    Date of Patent: March 22, 2011
    Assignee: Johns Hopkins University
    Inventors: C. Giovanni Traverso, Kenneth W. Kinzler, Bert Vogelstein
  • P13k pathway mutations in cancer
    Publication number: 20110059434
    Abstract: Given the important role of protein kinases in pathways affecting cellular growth and invasion, we have analyzed 340 serine/threonine kinases for genetic mutations in colorectal cancers. Mutations in eight genes were identified, including three members of the phosphatidylinositol-3-kinase (PI3K) pathway; the alterations in the latter genes each occurred in different tumors and did not overlap with mutations in PIK3CA or other non-serine-threonine kinase (STK) members of the PI3K pathway, suggesting that mutations in any of these genes had equivalent tumorigenic effects. These data demonstrate that the PI3K pathway is a major target for mutational activation in colorectal cancers and provide new opportunities for therapeutic intervention.
    Type: Application
    Filed: May 23, 2006
    Publication date: March 10, 2011
    Inventors: Donald William Parsons, Tian-li Wang, Yardena Samuels, Alberto Bardelli, Christopher Lengauer, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
  • Methods for Beaming
    Publication number: 20110059435
    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: Application
    Filed: February 6, 2006
    Publication date: March 10, 2011
    Applicant: THE JOHN HOPKINS UNIVERSITY
    Inventors: Bert Vogelstein, Frank Diehl, Kenneth W. Kinzler, Ming Li
  • Methods for generating hypermutable microbes
    Patent number: 7892832
    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: October 31, 2007
    Date of Patent: February 22, 2011
    Assignees: The Johns Hopkins University, Morphotek, Inc.
    Inventors: Nicholas C. Nicolaides, Philip M. Sass, Luigi Grasso, Bert Vogelstein, Kenneth W. Kinzler
  • HUMAN TRANSCRIPTOMES
    Publication number: 20110033466
    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: August 18, 2010
    Publication date: February 10, 2011
    Applicant: The Johns Hopkins University
    Inventors: Victor E. Velculescu, Bert Vogelstein, Kenneth W. Kinzler
  • CONSENSUS CODING SEQUENCES OF HUMAN BREAST AND COLORECTAL CANCERS
    Publication number: 20100316995
    Abstract: Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average of ˜90 mutant genes but that only a subset of these contribute to the neoplastic process. Using stringent criteria to delineate this subset, we identified 189 genes (average of 11 per tumor) that were mutated at significant frequency. The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention and monitoring.
    Type: Application
    Filed: August 13, 2007
    Publication date: December 16, 2010
    Applicant: JOHNS HOPKINS UNIVERSITY
    Inventors: Tobias Sjoblom, Sian Jones, D. Williams Parsons, Laura D. Wood, Jimmy Lin, Thomas Barber, Diana Mandelker, Bert Vogelstein, Kenneth W. Kinzler, Victor E. Velculesu
  • Digital amplification
    Patent number: 7824889
    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: Grant
    Filed: February 23, 2007
    Date of Patent: November 2, 2010
    Assignee: The Johns Hopkins University
    Inventors: Bert Vogelstein, Kenneth W. Kinzler
  • Design and synthesis of renal dipeptidase inhibitors
    Patent number: 7785564
    Abstract: Aminophosphinic acid derivatives were synthesized as potential inhibitors of renal dipeptidase, an enzyme overexpressed in benign and malignant colon tumors. Several compounds showed potent enzyme-inhibitory activity. These compounds can be used therapeutically and diagnostically for treatment and detection of tumors.
    Type: Grant
    Filed: July 7, 2005
    Date of Patent: August 31, 2010
    Assignee: The Johns Hopkins University
    Inventors: Saeed R. Khan, Bert Vogelstein, Kenneth W. Kinzler, Hallur Gurulingappa, Phillip Buckhaults
  • Digital Amplification
    Publication number: 20100209921
    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: November 12, 2009
    Publication date: August 19, 2010
    Applicant: THE JOHNS HOPKINS UNIVERSITY
    Inventors: BERT VOGELSTEIN, KENNETH W. KINZLER
  • SINGLE-MOLECULE PCR ON MICROPARTICLES IN WATER-IN-OIL EMULSIONS
    Publication number: 20100190153
    Abstract: Modulation of the viscosity of the oil phase of a microemulsion used for amplification of DNA on a bead increases the homogeneity of product beads and the amount of amplified DNA per bead. Moreover the number of separate microemulsion populations that can be formed in parallel is increased using multi-well plates and mixer mill disruptor machines designed to lyse biological samples.
    Type: Application
    Filed: June 19, 2007
    Publication date: July 29, 2010
    Applicant: The Johns Hopkins University
    Inventors: Frank Diehl, Kenneth W. Kinzler, Bert Vogelstein
  • Tyrosine Kinome
    Publication number: 20100184100
    Abstract: Protein kinases are important signaling molecules involved in tumorigenesis. Mutational analysis of the human tyrosine kinase gene family (98 genes) identified somatic alterations in ?20% of colorectal cancers, with the majority of mutations occurring in NTRK3, FES, GUCY2F and a previously uncharacterized tyrosine kinase gene called MCCK/MLK4. Most alterations were in conserved residues affecting key regions of the kinase domain. These data represent a paradigm for the unbiased analysis of signal transducing genes in cancer and provide useful targets for therapeutic intervention.
    Type: Application
    Filed: February 15, 2010
    Publication date: July 22, 2010
    Applicant: THE JOHNS HOPKINS UNIVERSITY
    Inventors: Alberto Bardelli, Will Parsons, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
  • Methods for generating hypermutable yeast
    Patent number: 7759121
    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: October 31, 2007
    Date of Patent: July 20, 2010
    Assignees: The John Hopkins University, Morphotek, Inc.
    Inventors: Nicholas C. Nicolaides, Philip M. Sass, Luigi Grasso, Bert Vogelstein, Kenneth W. Kinzler