Labelled (e.g., Tagged With Radioactive Tracer, Fluorescent Marker, Intercalator, Etc.) Patents (Class 536/26.6)
  • Patent number: 7241897
    Abstract: This invention provides for labeling reagents, labeled targets and processes for preparing labeling reagents. The labeling reagents can take the form of cyanine dyes, xanthene dyes, porphyrin dyes, coumarin dyes or composite dyes. These labeling reagents are useful for labeling probes or targets, including nucleic acids and proteins. These reagents can be usefully applied to protein and nucleic acid probe based assays. They are also applicable to real-time detection processes.
    Type: Grant
    Filed: January 21, 2004
    Date of Patent: July 10, 2007
    Assignee: Enzo Life Sciences, Inc.
    Inventors: Jannis G. Stavrianopoulos, Elazar Rabbam
  • Patent number: 7238530
    Abstract: The invention relates to methods for easily separating single stranded nucleic acid material from double stranded nucleic acid material in a sample containing both. By the right choice of at lease one chaotropic agent, preferably a guanidine salt, at a selected concentration and other suitable conditions such a chelating agents, pH and the like, it is possible to bind double stranded material to a solid phase such as silica particles, whereas single stranded material will not bind under those circumstances. By separating the silica particles from the sample the double stranded nucleic acid material is removed. It can easily be eluted from the silica particles. In a second step the single stranded material may be bound to a solid phase by selecting a different set of conditions. The particles can again be separated from the sample and the single stranded material may now be eluted. For very efficent separations, the process may be repeated.
    Type: Grant
    Filed: January 12, 2001
    Date of Patent: July 3, 2007
    Assignee: bioMerieux SA
    Inventors: Jaap Goudsmit, Cornelis Johannes Andreas Sol, Marcellinus Gualbertus Hubertus Maria Beld, Willem René Boom
  • Patent number: 7238795
    Abstract: The present invention is in the field of nucleic acid binding compounds comprising 7-substituted 7-deaza-8aza-2,6-diamino-purine bases, compounds useful for the preparation of such compounds, various uses thereof and methods for the determination of nucleic acids using said compounds in the field of diagnostics.
    Type: Grant
    Filed: July 31, 2001
    Date of Patent: July 3, 2007
    Assignee: Roche Molecular Systems, Inc.
    Inventors: Frank Seela, Frank Bergmann, Herbert Von Der Eltz, Dieter Heindl, Christoph Seidel, Georg Becher
  • Patent number: 7235650
    Abstract: Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2?-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2?-deoxy-2?-fluoro, 2?-O-methoxy, 2?-O-ethoxy, 2?-O-propoxy, 2?-O-aminoalkoxy or 2?-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3? or the 5? positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.
    Type: Grant
    Filed: October 31, 2002
    Date of Patent: June 26, 2007
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Muthiah Manoharan, Phillip Dan Cook, Clarence Frank Bennett
  • Patent number: 7223851
    Abstract: The present invention relates to a nucleic acid binding polymer which has affinity for nucleic acid molecules such as DNA, RNA, or hybrids thereof. The polymer is comprised of a nucleic acid binding backbone linked to a nucleic acid binding agent, preferably by a linking moiety. The polymer can be used to isolate and purify nucleic acid molecules from a variety of sample types including but not limited to clinical and environmental.
    Type: Grant
    Filed: February 6, 2003
    Date of Patent: May 29, 2007
    Assignee: General Dynamics Advanced Information Systems, Inc.
    Inventors: Kathy Terlesky, Chris Earle
  • Patent number: 7220847
    Abstract: The invention relates to detectable labels useful for detection of nucleotide sequences. Specifically, the invention relates to labeled-imidazole-PEG compounds, such as nucleosides, nucleotides, and nucleic acids incorporating such compounds, and methods utilizing such compounds. The invention further relates to kits comprising labeled imidazole-PEG compounds.
    Type: Grant
    Filed: November 21, 2003
    Date of Patent: May 22, 2007
    Assignee: Roche Molecular Systems, Inc.
    Inventors: Veeraiah Bodepudi, Amar Gupta, Stephen G. Will
  • Patent number: 7217813
    Abstract: The present invention provides a labeled nucleoside having formula: where X represents an aliphatic diamine, and the labeling moiety comprises a label and a spacer, where the spacer is coupled at one end to a platinum atom and at the other end to the label, which spacer comprises a chain having at least four carbon atoms and at least one oxygen atom in the chain. The invention further provides a method for labeling a nucleoside, kits for labeling a nucleoside, and kits for producing a labeled nucleic acid.
    Type: Grant
    Filed: September 27, 2004
    Date of Patent: May 15, 2007
    Assignee: Kreatech Biotechnology B.V.
    Inventors: Hendrick Jan Houthoff, Jan Reedijk, Tinka Jelsma, Robert Jochem Heetebrij, Herman Hendricus Volkers
  • Patent number: 7214489
    Abstract: Methods, compositions and articles of manufacture for assaying a sample for a target polynucleotide are provided. A sample suspected of containing the target polynucleotide is contacted with a polycationic multichromophore and a sensor PNA complementary to the target polynucleotide. The sensor PNA comprises a signaling chromophore to absorb energy from the excited multichromophore and emit light in the presence of the target polynucleotide. The methods can be used in multiplex form. Kits comprising reagents for performing such methods are also provided.
    Type: Grant
    Filed: June 20, 2003
    Date of Patent: May 8, 2007
    Assignee: The Regents of the University of California
    Inventors: Guillermo C. Bazan, Brent S. Gaylord
  • Patent number: 7208587
    Abstract: The invention provides methods of detecting a nucleic acid. The methods comprise contacting the nucleic acid with one or more types of particles having oligonucleotides attached thereto. In one embodiment of the method, the oligonucleotides are attached to nanoparticles and have sequences complementary to portions of the sequence of the nucleic acid. A detectable change (preferably a color change) is brought about as a result of the hybridization of the oligonucleotides on the nanoparticles to the nucleic acid. The invention also provides compositions and kits comprising particles. The invention further provides methods of synthesizing unique nanoparticle-oligonucleotide conjugates, the conjugates produced by the methods, and methods of using the conjugates. In addition, the invention provides nanomaterials and nanostructures comprising nanoparticles and methods of nanofabrication utilizing nanoparticles. Finally, the invention provides a method of separating a selected nucleic acid from other nucleic acids.
    Type: Grant
    Filed: August 13, 2003
    Date of Patent: April 24, 2007
    Assignee: Nanosphere, Inc.
    Inventors: Chad A. Mirkin, Robert L. Letsinger, So-Jung Park
  • Patent number: 7205105
    Abstract: Oligonucleotide probes/conjugates are provided along with method for their use in assays to monitor amplification wherein the signal produced does not rely on 5? nuclease digestion.
    Type: Grant
    Filed: June 6, 2002
    Date of Patent: April 17, 2007
    Assignee: Epoch Biosciences, Inc.
    Inventors: Irina A. Afonina, Yevgeniy S. Belousov, Robert O. Dempcy, Igor V. Kutyavin, Sergey G. Lokhov, Eugeny A. Lukhtanov
  • Patent number: 7186398
    Abstract: A novel nanoscale, metal particle containing Fe atoms and Au atoms in solid solution. The particle is superparamagnetic with a large magnetic susceptibility at room temperature, is resistant to oxidation, and can be readily functionalized for use in diverse applications by attaching organic molecules to its surface.
    Type: Grant
    Filed: February 24, 2003
    Date of Patent: March 6, 2007
    Assignee: Purdue Research Foundation
    Inventors: Ronald P. Andres, Alicia T. Ng
  • Patent number: 7179906
    Abstract: A class of asymmetric monobenzoxanthene compounds useful as fluorescent dyes are disclosed having the structure wherein Y1 and Y2 are individually hydroxyl, amino, imminium, or oxygen, R1–R8 are hydrogen, fluorine, chlorine, alkyl, alkene, alkyne, sulfonate, amino, amido, nitrile, alkoxy, linking group, and combinations thereof, and R9 is acetylene, alkane, alkene, cyano, substituted phenyl, and combinations thereof. The invention further includes novel intermediate compounds useful for the synthesis of asymmetric benzoxanthene compounds having the general structure where substituents R3–R7 correspond to like-referenced substituents in the structure of described above, and Y2 is hydroxyl or amine. In another aspect, the invention includes methods for synthesizing the above dye compounds and intermediates.
    Type: Grant
    Filed: September 5, 2003
    Date of Patent: February 20, 2007
    Assignee: Applera Corporation
    Inventors: Scott C. Benson, Steven M. Menchen, Peter D. Theisen, Kevin M. Hennessey, Vergine C. Furniss, Joan D. Hauser
  • Patent number: 7169939
    Abstract: Novel linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye are provided. These linkers faciliate the efficient transfer of energy between a donor and acceptor dye in an energy transfer dye. One of these linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye has the general structure R21Z1C(O)R22R28 where R21 is a C1-5 alkyl attached to the donor dye, C(O) is a carbonyl group, Z1 is either NH, sulfur or oxygen, R22 is a substituent which includes an alkene, diene, alkyne, a five and six membered ring having at least one unsaturated bond or a fused ring structure which is attached to the carbonyl carbon, and R28 includes a functional group which attaches the linker to the acceptor dye.
    Type: Grant
    Filed: February 26, 2004
    Date of Patent: January 30, 2007
    Assignee: Applera Corporation
    Inventors: Linda G. Lee, Sandra L. Spurgeon, Barnett Rosenblum
  • Patent number: 7169556
    Abstract: The invention provides methods of detecting a nucleic acid. The methods comprise contacting the nucleic acid with one or more types of particles having oligonucleotides attached thereto. In one embodiment of the method, the oligonucleotides are attached to nanoparticles and have sequences complementary to portions of the sequence of the nucleic acid. A detectable change (preferably a color change) is brought about as a result of the hybridization of the oligonucleotides on the nanoparticles to the nucleic acid. The invention also provides compositions and kits comprising particles. The invention further provides methods of synthesizing unique nanoparticle-oligonucleotide conjugates, the conjugates produced by the methods, and methods of using the conjugates. In addition, the invention provides nanomaterials and nanostructures comprising nanoparticles and methods of nanofabrication utilizing nanoparticles. Finally, the invention provides a method of separating a selected nucleic acid from other nucleic acids.
    Type: Grant
    Filed: October 8, 2002
    Date of Patent: January 30, 2007
    Assignee: Nanosphere, Inc.
    Inventors: So-Jung Park, Thomas Andrew Taton, Chad A. Mirkin
  • Patent number: 7166478
    Abstract: This invention provides for labeling reagents, labeled targets and processes for preparing labeling reagents. The labeling reagents can take the form of cyanine dyes, xanthene dyes, porphyrin dyes, coumarin dyes or composite dyes. These labeling reagents are useful for labeling probes or targets, including nucleic acids and proteins. These reagents can be usefully applied to protein and nucleic acid probe based assays. They are also applicable to real-time detection processes.
    Type: Grant
    Filed: March 12, 2002
    Date of Patent: January 23, 2007
    Assignee: Enzo Life Sciences, Inc., c/o Enzo Biochem, Inc.
    Inventors: Jannis G. Stavrianopoulos, Elazar Rabbani
  • Patent number: 7166715
    Abstract: The invention provides an asymmetric cyanine dye compound having the structure including substituted forms thereof, wherein, at least one of R1 and R2 is linking group, X is O, S, or Se, and n ranges from 0 to 2. The invention further provides reporter-quencher dye pairs comprising the asymmetric cyanine dyes, dye-labelled polynucleotides incorporating the asymmetric cyanine dyes, and hybridization detection methods utilizing the dye-labelled polynucleotides.
    Type: Grant
    Filed: May 5, 2004
    Date of Patent: January 23, 2007
    Assignee: Applera Corporation
    Inventors: Linda G. Lee, Ronald J. Graham, Khairuzzaman B. Mullah, Francis T. Haxo
  • Patent number: 7163796
    Abstract: This invention provides for labeling reagents, labeled targets and processes for preparing labeling reagents. The labeling reagents can take the form of cyanine dyes, xanthene dyes, porphyrin dyes, coumarin dyes or composite dyes. These labeling reagents are useful for labeling probes or targets, including nucleic acids and proteins. These reagents can be usefully applied to protein and nucleic acid probe based assays. They are also applicable to real-time detection processes.
    Type: Grant
    Filed: January 23, 2004
    Date of Patent: January 16, 2007
    Assignees: Enzo Life Sciences, Inc., c/o Enzo Biochem, Inc.
    Inventors: Jannis G. Stavrianopoulos, Elazar Rabbani
  • Patent number: 7157572
    Abstract: Novel energy transfer dyes which can be used with shorter wavelength light sources are provided. These dyes include a donor dye with an absorption maxima at a wavelength between about 250 to 450 nm and an acceptor dye which is capable of absorbing energy emitted from the donor dye. One of the energy transfer dyes has a donor dye which is a member of a class of dyes having a coumarin or pyrene ring structure and an acceptor dye which is capable of absorbing energy emitted from the donor dye, wherein the donor dye has an absorption maxima between about 250 and 450 nm and the acceptor dye has an emission maxima at a wavelength greater than about 500 nm.
    Type: Grant
    Filed: February 7, 2003
    Date of Patent: January 2, 2007
    Assignee: Applera Corporation
    Inventor: Linda G Lee
  • Patent number: 7150967
    Abstract: Methods and kits for labeling and detecting thiol containing species and nucleic acids using mercurimethyl-dihydropsoralen compounds and derivatives thereof which intercalate nucleic acids and are highly reactive with thiol containing species are provided. Fluorescent reactions products of the mercurimethyl-dihydropsoralen compounds or derivatives thereof attached to a thiol containing species and nucleic acids fluorescently labeled with these reaction products are also provided.
    Type: Grant
    Filed: April 4, 2003
    Date of Patent: December 19, 2006
    Assignees: University of Medicine & Dentistry of New Jersey, Rutgers, the State University, Lehigh University, Buckman Laboratories International, Inc.
    Inventors: Jeffrey D. Laskin, Christine Martey, Ned Heindel, Marilyn Whittemore, Diane Heck
  • Patent number: 7132519
    Abstract: Releasable tag reagents for use in the detection and analysis of target molecules, particular in mass spectrometric analyses are provided. Also provided are methods of detection that employ releasable tag reagents.
    Type: Grant
    Filed: July 22, 2002
    Date of Patent: November 7, 2006
    Assignee: Sequenom, Inc.
    Inventors: Joseph A. Monforte, Christopher H. Becker, Daniel J. Pollart, Thomas A. Shaler
  • Patent number: 7125975
    Abstract: Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2?-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2?-deoxy-2?-fluoro, 2?-O-methoxy, 2?-O-ethoxy, 2?-O-propoxy, 2?-O-aminoalkoxy or 2?-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3? or the 5? positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.
    Type: Grant
    Filed: January 9, 2004
    Date of Patent: October 24, 2006
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Muthiah Manoharan, Phillip Dan Cook, Clarence Frank Bennett
  • Patent number: 7125982
    Abstract: The present method describes the use of thio-phosphate as a feed source for micro-organisms and multi-cellular organisms. This compound enters into nucleotide pools and ultimately into polymers of both RNA and DNA forming stable phosphorothioate internucleotide linkages. The method enables the microbial synthesis of both plasmid and phage DNA substituted with phosphorothioate. Furthermore, methods are described for the preparation of phosphorothioate oligo mixtures from recombinant phage DNA grown in modified media for use in antisense studies.
    Type: Grant
    Filed: December 5, 2001
    Date of Patent: October 24, 2006
    Assignee: Frayne Consultants
    Inventor: Elizabeth Gay Frayne
  • Patent number: 7122649
    Abstract: Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2?-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2?-deoxy-2?-fluoro, 2?-O-methoxy, 2?-O-ethoxy, 2?-O-propoxy, 2?-O-aminoalkoxy or 2?-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3? or the 5? positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.
    Type: Grant
    Filed: January 9, 2004
    Date of Patent: October 17, 2006
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Muthiah Manoharan, Phillip Dan Cook, Clarence Frank Bennett
  • Patent number: 7118871
    Abstract: Described herein are novel indicator molecules of general formula (1): wherein Q, F, N, Nuc, X1 and X2 are as defined herein, including their tautomeric forms and their additive salts. The present invention also concerns methods for the use of these molecules to monitor nucleic acid amplification in real time and their applications as diagnostics.
    Type: Grant
    Filed: April 9, 2003
    Date of Patent: October 10, 2006
    Inventor: Joseph F. Lawler
  • Patent number: 7109312
    Abstract: The present invention provides a family of dark quenchers, termed Black Hole Quenchers (“BHQs”), that are efficient quenchers of excited state energy but which are themselves substantially non-fluorescent. Also provided are methods of using the BHQs, probes incorporating the BHQs and methods of using the probes.
    Type: Grant
    Filed: July 29, 2005
    Date of Patent: September 19, 2006
    Assignee: Biosearch Technologies, Inc.
    Inventors: Ronald M. Cook, Matt Lyttle, Daren Dick
  • Patent number: 7109316
    Abstract: Oligonucleotide tagged nucleoside triphosphates, OTNTPs, which are substrates for polymerases and or terminal nucleotidyl transferases are provided as well as methods of making these OTNTPs. Further provided are OTNTPs with fluorescent dyes including energy transfer dyes, attached to the oligonucleotide chain, OTNTPs with unnatural bases incorporated in the oligonucleotide sequence and methods for incorporating these OTNTPs in DNA or RNA. Also provided are methods for using the oligonucleotides on OTNTPs for amplifying the oligo sequence on the OTNTP using an amplification method described above. Further provided are reactive bifunctional amidites, methods of making these compounds and methods for detecting single nucleotide polymorphisms using the above OTNTPs. Methods for detecting differential gene expression using the OTNTPs and methods of separating specifically modified DNA or RNA using the OTNTPs are also provided.
    Type: Grant
    Filed: August 23, 2002
    Date of Patent: September 19, 2006
    Assignee: CE Healthcare Bio-Sciences Corp.
    Inventors: Shiv Kumar, Anup Sood, Sudhakar Rao, John Nelson
  • Patent number: 7105661
    Abstract: The invention relates to the use of morpholino-nucleosides of formula: in which R1 represents a nucleic base and R2 represents a group corresponding to one of the following formulae: —(CH2)n—NH2 —(CH2)n—SH —(CH2)n—COOH —(CH2)n—OH —(CH2)n—NH—R3 —(CH2)n—SR3 —(CH2)n—CO—R3 —(CH2)n—OR3 in which n is an interger ranging from 1 to 12 and R3 is a group derived from a label, from a protein, from an enzyme, from a fatty acid or from a peptide, as chain terminators in a process of DNA or RNA sequencing by the Sanger method, or for the labelling of DNA or RNA fragments.
    Type: Grant
    Filed: December 9, 2003
    Date of Patent: September 12, 2006
    Assignees: Commissariat a l'Energie Atomique, Centre National de la Recherche Scientifique
    Inventors: Florence Marciacq, Sylvie Sauvaigo, Jean-François Mouret, Jean-Paul Issartel, Didier Molko
  • Patent number: 7105300
    Abstract: Nucleotides and nucleotide analogs are used in various sequencing by incorporation/sequencing by synthesis methods. Nucleotide analogs comprising 3?-blocking groups are used to provide reversible chain-termination for sequencing by synthesis. Typical blocking groups include phosphate groups and carbamate groups. Fluorescent nucleotides are used to perform sequencing by synthesis with detection by incorporation of the fluorescently labeled nucleotide, optionally followed by photobleaching and intercalating dyes are used to detect addition of a non-labeled nucleotide in sequencing by synthesis with detection by intercalation. Microfluidic devices, including particle arrays, are used in the sequencing methods.
    Type: Grant
    Filed: April 14, 2003
    Date of Patent: September 12, 2006
    Assignee: Caliper Life Sciences, Inc.
    Inventors: J. Wallace Parce, Theo T. Nikiforov, Tammy Burd Mehta, Anne R. Kopf-Sill, Andrea W. Chow, Michael R. Knapp
  • Patent number: 7101986
    Abstract: The invention provides methods for synthesizing oligonucleotides using nucleoside monomers having carbonate protected hydroxyl groups that are deprotected with ?-effect nucleophiles. The ?-effect nucleophile irreversibly cleave the carbonate protecting groups while simultaneously oxidizing the internucleotide phosphite triester linkage to a phosphodiester linkage. The procedure may be carried out in aqueous solution at neutral to mildly basic pH. The method eliminates the need for separate deprotection and oxidation steps, and, since the use of acid to remove protecting groups is unnecessary, acid-induced depurination is avoided. Fluorescent or other readily detectable carbonate protecting groups can be used, enabling monitoring of individual reaction steps during oligonucleotide synthesis. The invention is particularly useful in the highly parallel, microscale synthesis of oligonucleotides.
    Type: Grant
    Filed: August 25, 2003
    Date of Patent: September 5, 2006
    Assignee: Agilent Technologies, Inc.
    Inventors: Douglas J. Dellinger, Marvin H. Caruthers, Jason R. Betley
  • Patent number: 7098320
    Abstract: The invention provides methods of detecting a nucleic acid. The methods comprise contacting the nucleic acid with one or more types of particles having oligonucleotides attached thereto. In one embodiment of the method, the oligonucleotides are attached to nanoparticles and have sequences complementary to portions of the sequence of the nucleic acid. A detectable change (preferably a color change) is brought about as a result of the hybridization of the oligonucleotides on the nanoparticles to the nucleic acid. The invention also provides compositions and kits comprising particles. The invention further provides methods of synthesizing unique nanoparticle-oligonucleotide conjugates, the conjugates produced by the methods, and methods of using the conjugates. In addition, the invention provides nanomaterials and nanostructures comprising nanoparticles and methods of nanofabrication utilizing nanoparticles. Finally, the invention provides a method of separating a selected nucleic acid from other nucleic acids.
    Type: Grant
    Filed: October 11, 2001
    Date of Patent: August 29, 2006
    Assignee: Nanosphere, Inc.
    Inventors: Chad A. Mirkin, Robert L. Letsinger, Robert C. Mucic, James J. Storhoff, Robert Elghanian, Thomas Andrew Taton
  • Patent number: 7098321
    Abstract: The invention discloses compounds of the formula: where n is 1, or 2 to 200 in which case each recurring unit can be the same or different, B is a protected or unprotected base capable of Watson-Crick or of Hoogsteen pairing.
    Type: Grant
    Filed: February 4, 2003
    Date of Patent: August 29, 2006
    Assignee: Isis Innovation Limited
    Inventors: Gordon Lowe, Tirayut Vilaivan
  • Patent number: 7087744
    Abstract: Fluorescent nucleotides useful for labeling nucleic acids which are represented by the formula: X—Y—Z wherein X represents a residue of natural or non-natural nucleotide and the like and binds to Y at a basic moiety of the residue; Y represents a divalent bridging group or a single bond; Z represents a monovalent group derived from a compound represented by the formula (I) wherein R1 to R4 represent an alkyl group; V1 to V6 represent a hydrogen atom or a substituent; L1 to L7 represent a methine group; W represents an oxygen atom, a sulfur atom, —C(R3)(R4)— or —N(R5)— wherein R3 to R5 represents an alkyl group; Q represents a nitrogen atom or —C(V7)— wherein V7 represents a hydrogen atom or a monovalent substituent; M represents a counter ion; m represents a number required to neutralize the charge of the molecule; s, t and u represent 0 or 1 or the like, and binds to Y at a reactive group existing in R1 or R2
    Type: Grant
    Filed: July 17, 2002
    Date of Patent: August 8, 2006
    Assignee: Fuji Photo Film Co., Ltd.
    Inventors: Junji Nishigaki, Kouki Nakamura, Kazuya Takeuchi, Hiroko Inomata, Masayoshi Kojima
  • Patent number: 7087384
    Abstract: The invention relates to a process for reducing the fluorescence quenching caused by the measuring medium in a fluorescence assay, by introducing into said medium of rare earth metal cryptates which are not very sensitive to this fluorescence quenching, said rare earth metal cryptates comprising at least one pyridine radical which is substituted one or more times or unsubstituted. The invention also relates to novel rare earth metal cryptates which are not very sensitive to the fluorescence quenching caused by the measuring medium.
    Type: Grant
    Filed: June 12, 2001
    Date of Patent: August 8, 2006
    Assignee: CIS bio international
    Inventors: Herve Autiero, Herve Bazin, Gerard Mathis
  • Patent number: 7081526
    Abstract: The invention relates to the use of morpholino-nucleosides of formula: in which R1 represents a nucleic base and R2 represents a group corresponding to one of the following formulae: —(CH2)n—NH2 —(CH2)n—SH —(CH2)n—COOH —(CH2)n—OH —(CH2)n—NH—R3 —(CH2)n—SR3 —(CH2)n—CO—R3 —(CH2)n—OR3 in which n is an interger ranging from 1 to 12 and R3 is a group derived from a label, from a protein, from an enzyme, from a fatty acid or from a peptide, as chain terminators in a process of DNA or RNA sequencing by the Sanger method, or for the labelling of DNA or RNA fragments.
    Type: Grant
    Filed: December 9, 2003
    Date of Patent: July 25, 2006
    Assignees: Commissariat a l'Energie Atomique, Centre National de la Recherche Scientifique
    Inventors: Florence Marciacq, Sylvie Sauvaigo, Jean-François Mouret, Jean-Paul Issartel, Didier Molko
  • Patent number: 7078499
    Abstract: Nucleotides comprising a reporter moiety and a polymerase enzyme blocking moiety in which the reporter moiety does not also act as a polymerase enzyme blocking moiety are described. Also described are compounds of Formula (I): wherein W is a phosphate group, B is a base, Y is a linker comprising an enzyme-cleavable group, R2 is a reporter moiety, R3 is selected from H or OH, Z and Z? are selected from H, OH, or a group X—R1, wherein X is a linker comprising an enzyme-cleavable group and R1 is a polymerase enzyme blocking group, provided that at least one of Z and Z? is X—R1.
    Type: Grant
    Filed: May 31, 2001
    Date of Patent: July 18, 2006
    Assignee: GE Healthcare UK Limited
    Inventors: Raj Odedra, Adrian Simmonds, Lee Pickering
  • Patent number: 7074569
    Abstract: The present invention relates generally to nucleobase polymer functionalizing reagents, to mobility-modified sequence-specific nucleobase polymers, to compositions comprising a plurality of mobility-modified sequence-specific nucleobase polymers, and to the use of such polymers and compositions in a variety of assays, such as, for example, for the detection of a plurality of selected nucleotide sequences within one or more target nucleic acids. The mobility-modifying polymers of the present invention include phosphoramidite reagents which can be joined to other mobility-modifying monomers and to sequence-specific oligonucleobase polymers via uncharged phosphate triester linkages. Addition of the mobility-modifying phosphoramidite reagents of the present invention to oligonucleobase polymers results in unexpectedly large effects the mobility of those modified oligonucleobase polymers, especially upon capillary electrophoresis in non-sieving media.
    Type: Grant
    Filed: May 28, 2004
    Date of Patent: July 11, 2006
    Assignee: Applera Corporation
    Inventors: Sam Lee Woo, Ronald J. Graham, Jing Tian
  • Patent number: 7060500
    Abstract: The invention concerns the introduction of predetermined genetic changes in target genes of a living cell by introducing an oligodeoxynucleotide encoding the predetermined change. The oligodeoxynucleotides are effective in animal, plant and bacterial cells. Specific end modifications that greatly increase the effectiveness of the oligodeoxynucleotides in bacteria are described. Surprisingly, unmodified oligodeoxynucleotides can be as effective in mammalian cells, including in vivo hepatocytes, as the modified nucleotides and can be as effective or more effective than chimeric oligonucleotides that consist of a mixture of deoxynucleotides and 2?-O-methyl ribonucleotides.
    Type: Grant
    Filed: November 12, 2002
    Date of Patent: June 13, 2006
    Inventors: Richard A. Metz, Bruce L. Frank, Debra M. Walther
  • Patent number: 7057026
    Abstract: Nucleosides and nucleotides are disclosed that are linked to detectable labels via a cleavable linker group.
    Type: Grant
    Filed: August 23, 2002
    Date of Patent: June 6, 2006
    Assignee: Solexa Limited
    Inventors: Colin Barnes, Shankar Balasubramanian, Xiaohai Liu, Harold Swerdlow, John Milton
  • Patent number: 7057031
    Abstract: Labelled nucleotides and polynucleotides useful in the sequencing of nucleic acids are described. Methods of preparing photocleavable marker nucleotides and photocleavable marker-polynucleotide conjugates are described. Such photocleavable markere nucleotides can be incorporated into nucleic acid so as to create photocleavable marker-polynucleotide conjugates.
    Type: Grant
    Filed: July 12, 2002
    Date of Patent: June 6, 2006
    Assignee: AmberGen, Inc.
    Inventors: Jerzy Olejnik, Edyta Krzymanska-Olejnik, Kenneth J. Rothschild
  • Patent number: 7053208
    Abstract: Probes labeled with 1,2-dioxetane precursors can be employed in a variety of assays. The probes may be nucleic acid, peptide nucleic acid, proteins including enzyme, antibody or antigen, steroid, carbohydrate, drug or non-drug hapten. The probe is provided with a 1,2-dioxetane precursor bound thereto, generally either covalently, or a strong ligand bond. The dioxetane precursor moiety is converted to a bound 1,2-dioxetane by exposure to singlet oxygen. These dioxetane (labels) either spontaneously decompose, or are induced to decompose by an appropriate trigger to release light. The trigger may be a change in pH temperature, or an agent which removes a protective group. Assay formats in which these 1,2-dioxetane labeled probes and referents may be used to include hybridization assays, immuno assays, gel-based assays and Capillary Zone Electrophoresis.
    Type: Grant
    Filed: February 27, 2002
    Date of Patent: May 30, 2006
  • Patent number: 7045610
    Abstract: Modified oligonucleotides are provided containing bases selected from unsubstituted and 3-substituted pyrazolo[3,4-d]pyrimidines and 5-substituted pyrimidines, and optionally have attached minor groove binders and reporter groups.
    Type: Grant
    Filed: February 28, 2001
    Date of Patent: May 16, 2006
    Assignee: Epoch Biosciences, Inc.
    Inventors: Robert O. Dempcy, Alexander A. Gall, Sergey G. Lokhov, Irina A. Afonina, Michael J. Singer, Igor V. Kutyavin, Nicolaas M. J. Vermeulen
  • Patent number: 7038027
    Abstract: The present invention relates to a method of preventing modification of a synthetic oligonucleotide or oligonucleotide analog during removal of at least one ?-cyanoethyl protecting group from the oligonucleotide or oligonucleotide analog. The method involves contacting the oligonucleotide or oligonucleotide analog with a basic solution having at least one acrylonitrile scavenger, such as t-butylamine, at a sufficient temperature and for a sufficient period of time to remove at least one ?-cyanoethyl protecting group. The present invention also relates to a method of producing a synthetic oligonucleotide or oligonucleotide analog.
    Type: Grant
    Filed: June 12, 2001
    Date of Patent: May 2, 2006
    Assignee: Avecia Biotechnology, Inc.
    Inventor: Nanda D. Sinha
  • Patent number: 7029868
    Abstract: Methods of identifying inhibitors of the fusion of two types of cells, particularly when fusion is mediated by the interaction of a viral protein and such cellular proteins as CD4 and chemokine receptors, are disclosed. The methods are suitable for identifying substances that are useful for the treatment and prevention of viral diseases. Particularly preferred methods are useful for the identification of inhibitors of HIV-1 infection.
    Type: Grant
    Filed: February 13, 2001
    Date of Patent: April 18, 2006
    Assignee: Merck & Co., Inc.
    Inventors: Kathleen A. Sullivan, Diana Benincasa, Margaret A. Cascieri, Lyndon J. Mitnaul, Lin-Lin Shiao, Michael R. Tota
  • Patent number: 7022727
    Abstract: The present invention relates to a crystalline form of 6-[(2,2-diphenylethyl)amino]-9-(N-ethyl-?-D-ribofuranosyluronamide)-N-(2-{N?-[1-(2-pyridyl)-4-piperidyl]ureido}ethyl)-9H-purine-2-carboxamide and to a process for the preparation of, compositions containing and the uses of such a crystalline form.
    Type: Grant
    Filed: September 3, 2004
    Date of Patent: April 4, 2006
    Assignee: Pfizer Inc
    Inventors: Terence Vernon Silk, Julian Duncan Smith
  • Patent number: 7018850
    Abstract: The present invention provides luminescent lanthanide metal chelates comprising a metal ion of the lanthanide series and a complexing agent comprising at least one salicylamidyl moiety. Also provided are probes incorporating the salicylamidyl ligands of the invention and methods utilizing the ligands of the invention and probes comprising the ligands of the invention.
    Type: Grant
    Filed: June 7, 2002
    Date of Patent: March 28, 2006
    Assignee: The Regents of the University of California
    Inventors: Kenneth N. Raymond, Stephane Petoud, Seth Cohen, Jide Xu
  • Patent number: 7019129
    Abstract: The present invention provides a family of dark quenchers, termed Black Hole Quenchers (“BHQs”), that are efficient quenchers of excited state energy but which are themselves substantially non-fluorescent. Also provided are methods of using the BHQs, probes incorporating the BHQs and methods of using the probes.
    Type: Grant
    Filed: May 9, 2000
    Date of Patent: March 28, 2006
    Assignee: Biosearch Technologies, Inc.
    Inventors: Ronald M. Cook, Matt Lyttle, Daren Dick
  • Patent number: 7015002
    Abstract: The present invention provides a method of detecting a biological molecule. The method includes reacting a biological molecule sample with an organic EL-dye and measuring the fluorescence of the biological molecule sample labeled with the organic EL-dye. The method provides a highly sensitive method of detecting a biological molecule at lower cost.
    Type: Grant
    Filed: April 13, 2004
    Date of Patent: March 21, 2006
    Inventor: Shinichiro Isobe
  • Patent number: 7011945
    Abstract: A method of identifying nucleic acid samples comprising: providing a mircoarray including a substrate coated with a composition including a population of micro-spheres dispersed in a fluid containing a gelling agent or a precursor to a gelling agent and immobilized at random positions on the substrate, at least one sub-population of said population micro-spheres containing an optical barcode generated from at least one colorant associated with the micro-spheres and including a nucleic acid probe sequence; contacting said array with a target nucleic acid sequence; and detecting the color barcode of said sub-population of micro-spheres due to the interaction of said probe nucleic acid sequence and said target nucleic acid sequence.
    Type: Grant
    Filed: December 21, 2001
    Date of Patent: March 14, 2006
    Assignee: Eastman Kodak Company
    Inventors: Tiecheng A. Qiao, Krishnan Chari, Douglas L. Vizard
  • Patent number: 6986989
    Abstract: The invention provides methods of detecting a nucleic acid. The methods comprise contacting the nucleic acid with one or more types of particles having oligonucleotides attached thereto. In one embodiment of the method, the oligonucleotides are attached to nanoparticles and have sequences complementary to portions of the sequence of the nucleic acid. A detectable change (preferably a color change) is brought about as a result of the hybridization of the oligonucleotides on the nanoparticles to the nucleic acid. The invention also provides compositions and kits comprising particles. The invention further provides methods of synthesizing unique nanoparticle-oligonucleotide conjugates, the conjugates produced by the methods, and methods of using the conjugates. In addition, the invention provides nanomaterials and nanostructures comprising nanoparticles and methods of nanofabrication utilizing nanoparticles. Finally, the invention provides a method of separating a selected nucleic acid from other nucleic acids.
    Type: Grant
    Filed: October 12, 2001
    Date of Patent: January 17, 2006
    Assignee: Nanosphere, Inc.
    Inventors: Chad A. Mirkin, Robert L. Letsinger, Robert C. Mucic, James J. Storhoff, Robert Elghanian, Thomas A. Taton
  • Patent number: 6969761
    Abstract: The invention provides methods of detecting a nucleic acid. The methods comprise contacting the nucleic acid with one or more types of particles having oligonucleotides attached thereto. In one embodiment of the method, the oligonucleotides are attached to nanoparticles and have sequences complementary to portions of the sequence of the nucleic acid. A detectable change (preferably a color change) is brought about as a result of the hybridization of the oligonucleotides on the nanoparticles to the nucleic acid. The invention also provides compositions and kits comprising particles. The invention further provides methods of synthesizing unique nanoparticle-oligonucleotide conjugates, the conjugates produced by the methods, and methods of using the conjugates. In addition, the invention provides nanomaterials and nanostructures comprising nanoparticles and methods of nanofabrication utilizing nanoparticles. Finally, the invention provides a method of separating a selected nucleic acid from other nucleic acids.
    Type: Grant
    Filed: October 12, 2001
    Date of Patent: November 29, 2005
    Assignee: Nanosphere, Inc.
    Inventors: Chad A. Mirkin, Robert L. Letsinger, Robert C. Mucic, James J. Storhoff, Robert Elghanian, Thomas A. Taton