Patents by Inventor Donald M. Crothers

Donald M. Crothers 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: 8318919
    Abstract: Disclosed herein are methods of destabilizing double-stranded nucleic acid hybridization using an enzyme comprising DNA N-glycosylase activity. Also disclosed herein is the detection of a double-stranded target DNA wherein the hybridization of duplex strands has been at least partially disrupted thereby permitting invasion of a probe strand. Also disclosed herein are methods of using an enzyme comprising DNA N-glycosylase activity to generate single-stranded circular nucleic acids.
    Type: Grant
    Filed: May 11, 2009
    Date of Patent: November 27, 2012
    Assignee: Geneohm Sciences, Inc.
    Inventor: Donald M. Crothers
  • Patent number: 7879554
    Abstract: The present disclosure provides methods and compositions for conducting an assay to detect a polynucleotide. In particular, ruthenium complexes having reduction potentials that do not coincide with the reduction potential of molecular oxygen are disclosed and amperometric techniques for their use are described. In preferred embodiments, the ruthenium complex is ruthenium (III) pentaamine pyridine and the polynucleotide that is detected is DNA. Further, techniques for enhancing detectable contrast between hybridized and unhybridized nucleic acids are disclosed. In particular, the use of elongated target strands as well as the use of uncharged probe strands are discussed.
    Type: Grant
    Filed: September 29, 2009
    Date of Patent: February 1, 2011
    Assignee: Geneohm Sciences, Inc.
    Inventors: Donald M. Crothers, R. Erik Holmlin, Honghua Zhang, Chunnian Shi
  • Publication number: 20100018876
    Abstract: The present disclosure provides methods and compositions for conducting an assay to detect a polynucleotide. In particular, ruthenium complexes having reduction potentials that do not coincide with the reduction potential of molecular oxygen are disclosed and amperometric techniques for their use are described. In preferred embodiments, the ruthenium complex is ruthenium (III) pentaamine pyridine and the polynucleotide that is detected is DNA. Further, techniques for enhancing detectable contrast between hybridized and unhybridized nucleic acids are disclosed. In particular, the use of elongated target strands as well as the use of uncharged probe strands are discussed.
    Type: Application
    Filed: September 29, 2009
    Publication date: January 28, 2010
    Applicant: GeneOhm Sciences
    Inventors: Donald M. Crothers, R. Erik Holmlin, Honghua Zhang, Chunnian Shi
  • Patent number: 7615348
    Abstract: The present disclosure provides methods and compositions for conducting an assay to detect a polynucleotide. In particular, ruthenium complexes having reduction potentials that do not coincide with the reduction potential of molecular oxygen are disclosed and amperometric techniques for their use are described. In preferred embodiments, the ruthenium complex is ruthenium (III) pentaamine pyridine and the polynucleotide that is detected is DNA. Further, techniques for enhancing detectable contrast between hybridized and unhybridized nucleic acids are disclosed. In particular, the use of elongated target strands as well as the use of uncharged probe strands are discussed.
    Type: Grant
    Filed: August 8, 2007
    Date of Patent: November 10, 2009
    Assignee: Genohm Sciences
    Inventors: Donald M. Crothers, R. Erik Holmlin, Honghua Zhang, Chunnian Shi
  • Publication number: 20090227473
    Abstract: Disclosed herein are methods of destabilizing double-stranded nucleic acid hybridization using an enzyme comprising DNA N-glycosylase activity. Also disclosed herein is the detection of a double-stranded target DNA wherein the hybridization of duplex strands has been at least partially disrupted thereby permitting invasion of a probe strand. Also disclosed herein are methods of using an enzyme comprising DNA N-glycosylase activity to generate single-stranded circular nucleic acids.
    Type: Application
    Filed: May 11, 2009
    Publication date: September 10, 2009
    Inventor: Donald M. Crothers
  • Patent number: 7531306
    Abstract: Disclosed herein are methods of destabilizing double-stranded nucleic acid hybridization using an enzyme comprising DNA N-glycosylase activity. Also disclosed herein is the detection of a double-stranded target DNA wherein the hybridization of duplex strands has been at least partially disrupted thereby permitting invasion of a probe strand. Also disclosed herein are methods of using an enzyme comprising DNA N-glycosylase activity to generate single-stranded circular nucleic acids.
    Type: Grant
    Filed: November 10, 2004
    Date of Patent: May 12, 2009
    Assignee: Geneohm Sciences, Inc.
    Inventor: Donald M. Crothers
  • Patent number: 7258978
    Abstract: The present disclosure provides methods and compositions for conducting an assay to detect nucleic acid hybridization in the presence of oxygen. In particular, ruthenium complexes having a reduction potential that does not coincide with the reduction potential of molecular oxygen are disclosed and amperometric techniques for their use are described. In preferred embodiments, the ruthenium complex is ruthenium (III) pentaamine pyridine and the nucleic acid hybridization event that is detected is DNA hybridization. Further, techniques for enhancing detectable contrast between hybridized and unhybridized nucleic acids are disclosed. In particular, the use of elongated target strands as well as the use of uncharged probe strands are discussed.
    Type: Grant
    Filed: May 2, 2003
    Date of Patent: August 21, 2007
    Assignee: Geneohm Sciences
    Inventors: Donald M. Crothers, R. Erik Holmlin, Honghua Zhang, Chunnian Shi
  • Patent number: 6815167
    Abstract: The present disclosure relates to methods for generating single-stranded DNA molecules of defined sequence and length. Specifically, a region of template containing target sequence is amplified by PCR or RCA, exogenous sequence is introduced by primers or probes used in amplification, double-stranded amplification products are converted to single-stranded amplification products, and single-stranded amplification products are trimmed to produce short single-stranded DNA molecules of defined sequence and length.
    Type: Grant
    Filed: May 1, 2002
    Date of Patent: November 9, 2004
    Assignee: GeneOhm Sciences
    Inventors: Donald M. Crothers, Carol Koenigsberger
  • Publication number: 20040086894
    Abstract: The present disclosure provides methods and compositions for conducting an assay to detect nucleic acid hybridization in the presence of oxygen. In particular, ruthenium complexes having a reduction potential that does not coincide with the reduction potential of molecular oxygen are disclosed and amperometric techniques for their use are described. In preferred embodiments, the ruthenium complex is ruthenium (III) pentaamine pyridine and the nucleic acid hybridization event that is detected is DNA hybridization. Further, techniques for enhancing detectable contrast between hybridized and unhybridized nucleic acids are disclosed. In particular, the use of elongated target strands as well as the use of uncharged probe strands are discussed.
    Type: Application
    Filed: May 2, 2003
    Publication date: May 6, 2004
    Inventors: Donald M. Crothers, R. Erik Holmlin, Honghua Zhang, Chunnian Shi
  • Publication number: 20040086895
    Abstract: The present disclosure relates to the detection of somatic cell mutations, particularly as part of a method to screen for cancer or precancer. The disclosure includes techniques for extracting and isolating oligonucleotides from a patient and conducting hybridization assays. Preferred embodiments include a combination of the following steps: extracting a biological sample from a patient, purifying a nucleic acid from a biological sample, amplifying a nucleic acid, isolating a nucleic acid in single stranded form, cyclizing a nucleic acid, elongating a nucleic acid, controlling hybridization stringency, amplifying a nucleic acid on a chip, and detecting hybridization.
    Type: Application
    Filed: May 2, 2003
    Publication date: May 6, 2004
    Inventors: Donald M. Crothers, R. Erik Holmlin, Chunnian Shi
  • Publication number: 20040086892
    Abstract: The present invention disclosure provides methods and compositions for a universal tag assay wherein a universal detector having detection probes is incubated with tagged molecules having identifier tags corresponding to targets, and hybridization of an identifier tag to a complementary detection probe indicates the presence of the corresponding target in the material being assayed. In particular, the invention disclosure provides methods and compositions for detecting target nucleotide sequences in a sample by target-dependent manipulations that generate tagged molecules having identifier tags corresponding to target nucleotide sequence, where incubation of tagged molecules with a universal detector having detection probes permits hybridization of identifier tags to complementary detection probes, thereby indicating the presence of the target nucleotide sequence corresponding to each identifier tag.
    Type: Application
    Filed: April 24, 2003
    Publication date: May 6, 2004
    Inventors: Donald M. Crothers, R. Erik Holmlin
  • Publication number: 20030207279
    Abstract: The present disclosure relates to methods for generating single-stranded DNA molecules of defined sequence and length. Specifically, a region of template containing target sequence is amplified by PCR or RCA, exogenous sequence is introduced by primers or probes used in amplification, double-stranded amplification products are converted to single-stranded amplification products, and single-stranded amplification products are trimmed to produce short single-stranded DNA molecules of defined sequence and length.
    Type: Application
    Filed: May 1, 2002
    Publication date: November 6, 2003
    Inventors: Donald M. Crothers, Carol Koenigsberger
  • Patent number: 4959309
    Abstract: A labeled nucleic acid probe comprising (a) a nucleic acid component, (b) a nucleic acid-binding ligand photochemically linked to the nucleic acid component, and (c) a label chemically linked to the nucleic acid-binding ligand. The label can be a specifically bindable ligand such as a hapten or biotin, an enzyme such as a .beta.-galactosidase or horse radish peroxidase, a fluorescent radical, a phycobiliprotein, a luminescent radical, or a radioisotope. The probe can be used in assays of nucleic acids, taking advantage of the ability of the nucleic acid component to hydridize.
    Type: Grant
    Filed: October 9, 1987
    Date of Patent: September 25, 1990
    Assignee: Molecular Diagnostics, Inc.
    Inventors: Nanibhushan Dattagupta, Donald M. Crothers
  • Patent number: 4777129
    Abstract: A nucleic acid detection probe comprising a hybridizable single stranded portion of nucleic acid connected with a non-hybridizable, single or double stranded nucleic acid portion, the non-hybridizable portion preferably including a recognition site for binding by a particular protein. Such recognition site can be a region of singly or doubly stranded nucleic acid specific for a particular nucleic acid binding protein such as lac repressor protein or can be a modified nucleic acid region such as a unique antigenic determinant introduced by interaction of the region with a modifier compound such as an intercalating agent or a platinum-containing ligand. The probe-binding protein can be labeled for ease of detection and in the case of an antigenic determinant binding site can be labeled antibody.
    Type: Grant
    Filed: October 19, 1984
    Date of Patent: October 11, 1988
    Assignee: Molecular Diagnostics, Inc.
    Inventors: Nanibhushan Dattagupta, Peter M. M. Rae, William J. Knowles, Donald M. Crothers
  • Patent number: 4748111
    Abstract: A protein is covalently coupled to a 3'terminal end of a nucleic acid which carries several labels. In an assay the protein will specifically recognize some component of a test system; in an immunoassay the protein can be Protein A which will recognize the FC portion of IgG which is bound to an unknown antigen if present in the test sample.
    Type: Grant
    Filed: March 12, 1984
    Date of Patent: May 31, 1988
    Assignee: Molecular Diagnostics, Inc.
    Inventors: Nanibhushan Dattagupta, William J. Knowles, Vincent T. Marchesi, Donald M. Crothers
  • Patent number: 4737454
    Abstract: A labeled nucleic acid probe comprising (a) a nucleic acid component, (b) a nucleic acid-binding ligand photochemically linked to the nucleic acid component, and (c) a label chemically linked to the nucleic acid-binding ligand. The label can be a specifically bindable ligand such as a hapten or biotin, an enzyme such as a .beta.-galactosidase or horse radish peroxidase, a fluorescent radical, a phycobiliprotein, a luminescent radical, or a radioisotope. The probe can be used in assays of nucleic acids, taking advantage of the ability of the nucleic acid component to hybridize.
    Type: Grant
    Filed: May 18, 1984
    Date of Patent: April 12, 1988
    Assignee: Molecular Diagnostics, Inc.
    Inventors: Nanibhushan Dattagupta, Donald M. Crothers
  • Patent number: 4734363
    Abstract: A process for production of a single strand of a nucleic acid comprising covalently linking to a solid substrate a polynucleotide complementary to the desired strand, hybridizing said polynucleotide with an oligonucleotide, extending the oligonucleotide in direction away from said substrate, denaturing the hybridized polynucleotide and extended oligonucleotide, thereby to free the extended oligonucleotide from the solid substrate, and separating the extended oligonucleotide. The product can be used for making analytical probes.
    Type: Grant
    Filed: November 27, 1984
    Date of Patent: March 29, 1988
    Assignee: Molecular Diagnostics, Inc.
    Inventors: Nanibhushan Dattagupta, Peter M. M. Rae, Donald M. Crothers, Thomas R. Barnett
  • Patent number: 4724202
    Abstract: A detection probe comprising a hybridizable single stranded portion of nucleic acid connected with a non-hybridizable, single or double stranded nucleic acid portion, the non-hybridizable portion preferably including a recognition site for a particular protein.
    Type: Grant
    Filed: December 12, 1983
    Date of Patent: February 9, 1988
    Assignee: Molecular Diagnostics, Inc.
    Inventors: Nanibhushan Dattagupta, Peter M. M. Rae, William J. Knowles, Donald M. Crothers
  • Patent number: 4713326
    Abstract: A solid support capable of binding a nucleic acid thereto upon suitable irradiation, comprising (a) a solid substrate, (b) a photochemically reactive intercalator compound or other nucleic acid-binding ligands, and (c) divalent radical chemically linking the substrate and the ligand (b). Specifically, a hydroxy group-containing solid substrate such as nitrocellulose paper is linked via a bifunctional reagent such as cyanogen bromide or 1,4-butanedioldiglycidyl ether to an amino-substituted angelicin or psoralen or ethidium bromide which in turn is photochemically linked to a nucleic acid. The resulting immobilized nucleic acid probe is capable of hybridizing with complementary nucleic acid fragments and is thereby useful in diagnostic assays.
    Type: Grant
    Filed: May 18, 1984
    Date of Patent: December 15, 1987
    Assignee: Molecular Diagnostics, Inc.
    Inventors: Nanibhushan Dattagupta, Donald M. Crothers
  • Patent number: 4542102
    Abstract: A solid support capable of binding a nucleic acid thereto upon suitable irradiation, comprising (a) a solid substrate, (b) a member selected from the group consisting of a furocoumarin, a phenanthridium halide, and photochemically reactive derivatives thereof, and (c) a divalent radical chemically linking the substrate and the member (b). Specifically, a hydroxy group-containing solid substrate such as nitrocellulose paper is linked via a bifunctional reagent such as cyanogen bromide or 1,4-butanediol diglycidyl ether to an amino-substituted angelicin or psoralen or phenanthridinium bromide which in turn is photochemically linked to a nucleic acid. This is capable of hybridizing with other nucleic acid fragments and is thereby useful in diagnostic assays.
    Type: Grant
    Filed: July 5, 1983
    Date of Patent: September 17, 1985
    Assignee: Molecular Diagnostics, Inc.
    Inventors: Nanibhushan Dattagupta, Donald M. Crothers