Abstract: Conjugates between a minor groove binding molecule, such as the trimer of 1,2-dihydro-(3H)-pyrrolo[3,2-e]indole-7-carboxylate (CDPI3), and an oligonucleotide form unusually stable hybrids with complementary target sequences, in which the tethered CDPI3 group resides in the minor groove of the duplex. These conjugates can be used as probes and primers. Due to their unusually high binding affinity, conjugates as short as 8-mers can be used as amplification primers with high specificity and efficiency. MGB conjugation also increases the discriminatory power of short oligonucleotides, providing enhanced detection of nucleotide sequence mismatches by short oligonucleotides.
Type:
Grant
Filed:
July 14, 2008
Date of Patent:
September 14, 2010
Assignee:
Elitech Holding B.V.
Inventors:
Joel Hedgpeth, Irina A. Afonina, Igor V. Kutyavin, Eugeny A. Lukhtanov, Evgeniy S. Belousov, Rich B. Meyer, Jr.
Abstract: The present invention is generally directed to the evolution of new metabolic pathways and the enhancement of bioprocessing through a process herein termed recursive sequence recombination. Recursive sequence recombination entails performing iterative cycles of recombination and screening or selection to “evolve” individual genes, whole plasmids or viruses, multigene clusters, or even whole genomes. Such techniques do not require the extensive analysis and computation required by conventional methods for metabolic engineering.
Abstract: The invention provides methods for evolving a polynucleotide toward acquisition of a desired property. Such methods entail incubating a population of parental polynucleotide variants under conditions to generate annealed polynucleotides comprising heteroduplexes. The heteroduplexes are then exposed to a cellular DNA repair system to convert the heteroduplexes to parental polynucleotide variants or recombined polynucleotide variants. The resulting polynucleotides are then screened or selected for the desired property.
Type:
Grant
Filed:
December 7, 2006
Date of Patent:
September 7, 2010
Assignee:
California Institute of Technology
Inventors:
Frances Arnold, Zhixin Shao, Alexander Volkov
Abstract: A method is provided for analyzing nucleic acid comprising the steps of extracting, amplifying and detecting the nucleic acid of interest, wherein one or more internal control nucleic acids which can be detected and discriminated from the nucleic acid of interest are added for each step to a sample prior to the performance of each step, and the success or failure of each step is judged from the detection results obtained for the respective internal control nucleic acids in the detection step. The internal control nucleic acids added prior to each step can be discriminated from each other.
Abstract: The present invention provides a novel method for detection and/or genotyping of nucleic acids that utilizes the specificity of an AP endonuclease. In addition, the present invention provides a novel method for nucleic acid amplification.
Type:
Grant
Filed:
June 28, 2007
Date of Patent:
September 7, 2010
Assignee:
Elitech Holding B.V.
Inventors:
Igor V. Kutyavin, David Milesi, Merl F. Hoekstra
Abstract: The invention provides methods and compositions for detecting and/or quantifying modified nucleic acid oligonucleotides. These methods and compositions are useful for detecting and quantifying diagnostic and/or therapeutic synthetic modified oligonucleotides, such as aptamers, RNAi, siRNA, antisense oligonucleotides or ribozymes in a biological sample.
Type:
Grant
Filed:
July 21, 2005
Date of Patent:
August 31, 2010
Assignee:
Eyetech, Inc.
Inventors:
David T. Shima, Pericles Calias, Gregory S. Robinson, John P. Wing, Lori M. Mullin, Lillian M. Smith, Ervin Sinani
Abstract: Methods are provided for the evolution of proteins of industrial and pharmaceutical interest, including methods for effecting recombination and selection. Compositions produced by these methods are also disclosed.
Type:
Grant
Filed:
February 5, 2008
Date of Patent:
August 17, 2010
Assignee:
Maxygen, Inc.
Inventors:
Phillip A. Patten, Willem P. C. Stemmer
Abstract: The present invention relates to novel methods for isolating a target molecule from a sample suspected of containing the target molecule. The methods of the present invention utilize solid substrates as a means for capturing, separating, and releasing target molecules, such as chemical or biological compounds. The present invention is specifically directed to novel approaches for capturing, separating and releasing such target molecules.
Type:
Grant
Filed:
February 20, 2008
Date of Patent:
August 10, 2010
Assignee:
Investigen, Inc.
Inventors:
Rachel Anne Holmes-Davis, Heather Koshinsky, Miaomiao Wang, Brian David Warner
Abstract: The invention relates to compositions for generating a signal indicative of the presence of a target nucleic acid in a sample, where the compositions include a probe having a 5? region and a 3? flap and a P. furiosus polymerase having 3? exonuclease activity.
Abstract: The present invention relates to a method for assessing a cancerous state of a mammal-derived specimen, which comprises: (1) a first step of measuring a methylation frequency of Fibrillin2 gene contained in a mammal-derived specimen or an index value having the correlation therewith, and (2) a second step of determining a cancerous state of the specimen based on a difference obtained by comparing the measured methylation frequency or the index value having the correlation therewith, with a control; and the like.
Type:
Grant
Filed:
September 15, 2004
Date of Patent:
July 27, 2010
Assignees:
Sumitomo Chemical Company, Limited, Japan as Represented by President of National Cancer Center
Abstract: The present invention provides a method for obtaining or amplifying a polynucleotide (a tester-specific polynucleotide), in which an amount existing in a sample (tester) is larger than the amount existing in another sample (driver), easily and within a short time as well as with high efficiency, a polynucleotide obtained (amplified) by such method, a method for identifying gene mutation in the tester, and a kit to be used in such methods.
Abstract: The invention relates to methods for identifying the sequence of one or more variant nucleotides in a nucleic acid molecule. The method involves cleaving a double-stranded nucleic acid molecule containing a mismatch with a mismatch-specific endonuclease which cleaves on the 3? side of the mismatch, and preserving the integrity of the variant nucleotide by ligating a double-stranded linker with a 3?-overhang to said variant nucleotide. Because the variant nucleotide is immediately adjacent to the linker, PCR and/or sequence-by-synthesis analysis can be readily carried out.
Type:
Grant
Filed:
September 12, 2007
Date of Patent:
July 6, 2010
Assignee:
Transgenomic, Inc.
Inventors:
Paul D. Taylor, Gary F. Gerard, Reyes Candau
Abstract: Improved labeled molecule probes for use in biomedical applications including the sequencing of nucleic acid molecules and methods and apparatuses for their use are detailed. Labeled-probe-assemblies, comprising a probe element, for binding to a target molecule, attached to a label-assembly further comprising a linear series of information encoded structures and means for spatially separating these structures, are presented together with methods for extending the label assemblies such that the information encoded structures can be individually resolved, substantially simultaneously, by a readout device.
Abstract: A hybridization method is provided in which an efficient hybridization reaction can be carried out. Further, there are provided, using this hybridization method, a method for detecting a target gene with high sensitivity and a signal amplifying method for markedly improving the detection sensitivity of the target gene. There is provided a hybridization method comprising the use of oligonucleotides in a reaction solution, the method comprising forming partially a reaction temperature region in the reaction solution and performing a hybridization reaction in the reaction temperature region.
Abstract: The present invention is directed to methods of generating a signal indicative of the presence of a target nucleic acid in a sample by forming a cleavage structure comprising duplex and single-stranded nucleic acid by incubating a sample comprising a target nucleic acid with a thermostable nucleic acid polymerase substantially lacking 5? to 3? exonuclease activity and cleaving said cleavage structure with a thermostable Fen nuclease lacking 5? to 3? synthetic activity to generate a signal.
Abstract: The invention provides a method useful for detection of genetic disorders. The method comprises determining the sequence of alleles of a locus of interest, and quantitating a ratio for the alleles at the locus of interest, wherein the ratio indicates the presence or absence of a chromosomal abnormality. The present invention also provides a non-invasive method for the detection of chromosomal abnormalities in a fetus. The invention is especially useful as a non-invasive method for determining the sequence of fetal DNA. The invention further provides methods of isolation of free DNA from a sample.
Abstract: Nucleic acid sequences and methods for detecting HIV-1 nucleic acid (LTR and pol sequences) in biological samples by detecting amplified nucleic acids are disclosed. Kits comprising nucleic acid oligomers for amplifying HIV-1 nucleic acid present in a biological sample and detecting the amplified nucleic acid are disclosed.
Type:
Grant
Filed:
September 4, 2008
Date of Patent:
May 25, 2010
Assignee:
Gen-Probe Incorporated
Inventors:
Gary G. Bee, Yeasing Y. Yang, Dan Kolk, Cristina Giachetti, Sherrol H. McDonough
Abstract: The invention provides a method useful for detection of genetic disorders. The method comprises determining the sequence of alleles of a locus of interest, and quantitating a ratio for the alleles at the locus of interest, wherein the ratio indicates the presence or absence of a chromosomal abnormality. The present invention also provides a non-invasive method for the detection of chromosomal abnormalities in a fetus. The invention is especially useful as a non-invasive method for determining the sequence of fetal DNA. The invention further provides methods of isolation of free DNA from a sample.
Abstract: The present invention is related to a device, kit and method for pulsing a biological sample with a pulsing agent and subsequently stabilizing the biological sample so pulsed. The invention has application in the fields of medical diagnostics, particularly relating to immunity.
Abstract: Disclosed embodiments concern quantifying a biomolecule conjugated to a nanoparticle. Quantifying typically comprises determining the number of biomolecules per nanoparticle. Any suitable biomolecule can be used, including but not limited to, amino acids, peptides, proteins, haptens, nucleic acids, oligonucleotides, DNA, RNA, and combinations thereof. A single type of biomolecule may be conjugated to the nanoparticle, more than one biomolecule of a particular class may be conjugated to the nanoparticle, or two or more classes of biomolecules may be conjugated to the nanoparticle. Certain disclosed embodiments comprise enzymatically or chemically digesting a biomolecule conjugated to the nanoparticle, or displacing a biomolecule using ligand-exchange chemistry.
Type:
Grant
Filed:
May 4, 2007
Date of Patent:
March 23, 2010
Assignee:
Ventana Medical Systems, Inc.
Inventors:
Xiao-Bo Chen, Christopher Bieniarz, Michael Farrell