Patents Examined by Kenneth Horlick
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Patent number: 9790559Abstract: The present disclosure provides a system and method for the detection of rare mutations and copy number variations in cell free polynucleotides. Generally, the systems and methods comprise sample preparation, or the extraction and isolation of cell free polynucleotide sequences from a bodily fluid; subsequent sequencing of cell free polynucleotides by techniques known in the art; and application of bioinformatics tools to detect rare mutations and copy number variations as compared to a reference. The systems and methods also may contain a database or collection of different rare mutations or copy number variation profiles of different diseases, to be used as additional references in aiding detection of rare mutations, copy number variation profiling or general genetic profiling of a disease.Type: GrantFiled: April 20, 2017Date of Patent: October 17, 2017Assignee: Guardant Health, Inc.Inventor: AmirAli Talasaz
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Patent number: 9777326Abstract: A method of sequencing nucleic acids, which can include steps of (a) providing a substrate comprising a surface having a repeating pattern of features, wherein the features are spatially separated from each other on the surface of the substrate; (b) contacting the repeating pattern of features with a solution of different nucleic acids to seed a subset of the features that contact the solution, wherein each feature in the subset is seeded with a single nucleic acid from the solution, and a plurality of the features that contact the solution are not seeded with a nucleic acid from the solution; (c) amplifying the nucleic acids to form a nucleic acid colony at each of the features in the seeded subset; (d) repeating steps (b) and (c) to increase the number of features that are seeded with a nucleic acid, thereby making an array of different nucleic acid colonies; and (e) detecting sequencing reactions at the different nucleic acid colonies on the surface.Type: GrantFiled: August 15, 2016Date of Patent: October 3, 2017Assignee: ILLUMINA, INC.Inventors: Mostafa Ronaghi, Helmy A. Eltoukhy
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Patent number: 9777266Abstract: Methods for the creation of one or more user-defined mutations that can be located anywhere in a target sequence, such as in a gene are disclosed. These methods can be used on a single-stranded or double-stranded template and, for a single-stranded template, generally include: (a) conducting a first amplification reaction in the presence of a thermostable DNA polymerase and a thermostable DNA ligase to synthesize a mutagenized strand of DNA comprising at least one mutagenic oligonucleotide relative to a complementary single-stranded template DNA comprising a target nucleic acid molecule in a circular DNA vector; (b) conducting a second amplification reaction in the presence of a thermostable DNA polymerase and a thermostable DNA ligase to synthesize a complementary mutant strand of DNA; and (c) degrading the template DNA and non-covalently closed circular nucleic acid molecules to obtain a mutation-containing double-stranded DNA product.Type: GrantFiled: September 2, 2016Date of Patent: October 3, 2017Assignee: THE JOHNS HOPKINS UNIVERSITYInventors: Elad Firnberg, Marc Alan Ostermeier
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Assembly and method for analyzing nucleic acid sequences by way of so-called sequencing-by-synthesis
Patent number: 9777323Abstract: An assembly and a method are disclosed for analyzing nucleic acid sequences by way of so-called sequencing-by-synthesis. According to an embodiment of the invention, a chemical substance group that is released when a nucleotide bonds to a nucleic acid sequence to be sequenced is detected. The reagents are applied by way of a spraying device to a sensor that detects the released substance group. This has the advantage that no lateral flow occurs. The rate of false-negative and false-positive results is significantly reduced. Furthermore, a small amount of the reagent is sufficient to completely wet the sensor. Filling of the supply and discharge lines as for a flow cell is not necessary.Type: GrantFiled: June 13, 2013Date of Patent: October 3, 2017Assignee: SIEMENS AKTIENGESELLSCHAFTInventors: Walter Gumbrecht, Oliver Hayden -
Patent number: 9777330Abstract: Methods are provided for determining the methylation status of GC-rich templates. The methods include use of GC reference standards that allow simultaneous characterization of methylation status and CGG repeat length. The methods are useful for detecting genotypes associated with GC-rich repeats, including Fragile X Syndrome.Type: GrantFiled: October 28, 2011Date of Patent: October 3, 2017Assignee: Asuragen, Inc.Inventors: Gary J. Latham, Liangjing Chen, Andrew Hadd, Sachin Sah, Ru Cao
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Patent number: 9765404Abstract: The present disclosure provides methods for detecting and identifying plant events that contain donor sequences inserted precisely into targeted genomic loci, and plants and plant cells comprising such targeted genomic loci. The method comprises the steps of amplifying a genomic DNA with a first round of PCR to produce a first amplicon from donor sequences inserted in the reverse orientation, amplifying the first amplicon with a second round of PCR and detecting the presence of the second amplicon, wherein the production of the first and second amplicon indicates the presence of the site specific integration event.Type: GrantFiled: September 3, 2014Date of Patent: September 19, 2017Assignee: Dow AgroSciences LLCInventors: Lakshmi Sastry-Dent, W. Michael Ainley, Jayakumar P. Samuel, Zehui Cao, Liu Y. Shen, Cristie M. Dewes
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Patent number: 9758818Abstract: Disclosed herein is a polymerase chain reaction (PCR)-based method for detecting an insertion/deletion variant, as compared with a reference sequence, in a selected region of a target gene in a sample. The target gene has a template strand and a coding strand complementary to the template strand. The method uses a primer set that includes a blocking primer, and a forward primer. The blocking primer and the forward primer are partially overlapping and have different melting temperatures, and the 3?-end of the blocking primer is modified to prevent the extension of the blocking primer during the PCR. Accordingly, under specific PCR conditions, the presence of the PCR product is indicative of the presence of an insertion/deletion mutation in the selected region, and the absence of the PCR product is indicative of the absence of an insertion/deletion mutation in the selected region.Type: GrantFiled: December 30, 2011Date of Patent: September 12, 2017Inventors: Jr-Kai Huang, Chi-Kuan Chen, Tao-Yeuan Wang
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Patent number: 9758815Abstract: A kit for the characterization of chromosomal inversions using single-stranded probes that are either all identical or all complementary to a single-stranded chromatid is described. Reporter species are attached to oligonucleotide strands designed such that they may hybridize to portions of only one of a pair of single-stranded sister chromatids which may be prepared by the CO-FISH procedure. If an inversion has occurred, these marker probes will be detected on the second sister chromatid at the same location as the inversion on the first chromatid. The kit includes non-repetitive probes that are either all identical or all complementary to at least a portion of a target DNA sequence of only one DNA strand of only one chromatid and may in some embodiments include reagents suitable for performing CO-FISH and/or reagents for hybridizing the probes to the target DNA sequence.Type: GrantFiled: July 27, 2015Date of Patent: September 12, 2017Assignees: KROMATID, INC., COLORADO STATE UNIVERSITY RESEARCH FOUNDATIONInventor: F. Andrew Ray
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Patent number: 9745635Abstract: Recurrent gene fusions of androgen regulated genes and ETS family member genes in prostate cancer are described. Compositions and methods having utility in prostate cancer diagnosis, research, and therapy are also provided.Type: GrantFiled: September 24, 2015Date of Patent: August 29, 2017Assignees: THE REGENTS OF THE UNIVERSITY OF MICHIGAN, THE BRIGHAM AND WOMEN'S HOSPITAL, INC.Inventors: Scott Tomlins, Daniel Rhodes, Arul Chinnaiyan, Rohit Mehra, Mark A. Rubin, Xiao-Wei Sun, Sven Perner, Charles Lee, Francesca Demichelis
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Patent number: 9738941Abstract: Methods for screening a multiplicity of respiratory pathogens by isolating nucleic acids from a sample include isolating a nucleic acid from a sample and using solid phase amplification with forward primers SEQ ID NOs: 1 to 16 or 33 or 35 and corresponding reverse primers SEQ ID NOs: 17 to 32 or 34 or 36 along with probes to generate amplicons. The method further includes employing bead sets which are homogenous with respect to bead size and optionally with respect to the intensity of the label. Binding of a particular amplicon to a subset of beads determines the identity of the respiratory pathogen.Type: GrantFiled: October 4, 2012Date of Patent: August 22, 2017Assignee: Genera Biosystems LimitedInventors: Karl Frederick Poetter, Nick Vandegraaff
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Patent number: 9732375Abstract: A molecular detection assay including treating a biological sample directly with a bisulphite agent under conditions that allow cell disruption and nucleic acid treatment; removing the bisulphite agent from the treated sample; and detecting a target nucleic acid in the treated sample.Type: GrantFiled: September 7, 2011Date of Patent: August 15, 2017Assignee: HUMAN GENETIC SIGNATURES PTY. LTD.Inventor: Douglas Spencer Millar
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Patent number: 9719143Abstract: Compositions and methods associated with recurrent MIPOL1-ETV1 genetic rearrangements that are useful for cancer diagnosis and therapy are disclosed.Type: GrantFiled: March 30, 2016Date of Patent: August 1, 2017Assignee: THE REGENTS OF THE UNIVERSITY OF MICHIGANInventors: Arul M. Chinnaiyan, Scott Tomlins, Saravana Mohan Dhanasekaran
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Patent number: 9708657Abstract: The invention is directed to sequence-based profiling of populations of nucleic acids by multiplex amplification and attachment of one or more sequence tags to target nucleic acids anchor copies thereof followed by high-throughput sequencing of the amplification product. In some embodiments, the invention includes successive steps of primer extension, removal of unextended primers and addition of new primers either for amplification (for example by PCR) or for additional primer extension. Some embodiments of the invention are directed to minimal residual disease (MRD) analysis of patients being treated for cancer. Sequence tags incorporated into sequence reads provide an efficient means for determining clonotypes and at the same time provide a convenient means for detecting carry-over contamination from other samples of the same patient or from samples of a different patient which were tested in the same laboratory.Type: GrantFiled: June 27, 2014Date of Patent: July 18, 2017Assignee: Adaptive Biotechnologies Corp.Inventors: Thomas Asbury, Kieran Hervold, Chitra Kotwaliwale, Malek Faham, Martin Moorhead, Li Weng, Tobias Wittkop, Jianbiao Zheng
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Patent number: 9708663Abstract: Provided is uses of SAA1?/?(1.5/1.5) homozygote in prognosis and/diagnosis of liver cirrhosis, and in preparation of a reagent for liver cirrhosis prognosis and/or liver cirrhosis diagnosis. Recognition of liver cirrhosis susceptible populations can be achieved by detection of human SAA1?/? homozygote and non-SAA1?/? homozygote through real-time fluorescence quantitative allele specific PCR.Type: GrantFiled: March 19, 2012Date of Patent: July 18, 2017Assignee: DIASYS DIAGNOSTIC SYSTEMS (SHANGHAI) CO., LTD.Inventors: Rongfang Wang, Jun Wu, Yan Zhang, Zhenbin Qian
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Patent number: 9695466Abstract: The invention relates to methods to reduce the length of a homonucleotide repeat sequence a target DNA sequence. This is done by using an oligonucleotide primer which extends in the unaltered repeat of identical nucleotides of the target polynucleotide, the oligonucleotide primer comprises at the at the 5? side a sequence which hybridizes with the sequence preceding the targeted sequence repeat, but the oligonucleotide primer is not 100% complementary with the sequence repeat in the target sequence.Type: GrantFiled: May 9, 2014Date of Patent: July 4, 2017Assignee: DNAME-ITInventor: Harry Cuppens
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Patent number: 9689044Abstract: Provided herein are MiIP-Seq assays and methods for detecting and/or identifying an immune-stimulating microbe in a patient sample. Also provided herein are methods for diagnosing an infectious disease or identifying a previously uncharacterized microbe in a patient sample. The methods and assays described herein are advantageous over existing methods in that they (i) do not require a culture step for microbe expansion, (ii) are not specific for a particular microbe and can be used to identify a previously uncharacterized microbe, and (iii) permits rapid processing due to the lack of a microbe culture step.Type: GrantFiled: January 26, 2012Date of Patent: June 27, 2017Assignee: The Brigham and Women's Hospital, Inc.Inventors: Richard S. Blumberg, Arthur Kaser
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Patent number: 9683261Abstract: Described herein are compositions for evaluating nucleic acids, standardized mixture for assessing amounts of at least one target nucleic acid in a sample, and kits comprising the same.Type: GrantFiled: March 16, 2015Date of Patent: June 20, 2017Assignee: The University of ToledoInventors: James C. Willey, Erin L. Crawford
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Patent number: 9677122Abstract: The invention provides efficient methods of preparing a target nucleic acid in a form suitable for sequencing. The methods are particularly amenable for preparing high quality nucleic acids for massively parallel sequencing. The methods involve capturing a target nucleic acid from a sample and PCR amplification of the target nucleic acid. The target nucleic acid is captured by binding to a capture probe, which in turn binds to an immobilized probe. The immobilized probe is typically immobilized via a magnetic bead. The captured target nucleic acid is PCR amplified by thermocycling without prior dissociation of the target nucleic acid from the beads. The efficiency of the method lies in part in that both the capture and amplification steps are performed in a single vessel. The amplified nucleic acid can then be sequenced.Type: GrantFiled: February 8, 2016Date of Patent: June 13, 2017Assignee: GEN-PROBE INCORPORATEDInventors: Reinhold Pollner, Shyun-Shyun Lee
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Patent number: 9677069Abstract: The present invention provides methods for creating an array of features on a surface based on content transferred from a plurality of beads to the surface. Nucleic acid content can be transferred using a method including the steps of (a) providing a surface having one or more primer oligonucleotides attached to the surface; (b) providing a pool of beads, wherein beads in the pool have a plurality of templates attached thereto, the plurality comprising multiple copies of a single nucleic acid template sequence; (c) arraying the beads onto the surface by hybridizing the templates to the primer oligonucleotides; and (d) extending the primers to produce copies of the templates attached to the surface.Type: GrantFiled: June 5, 2015Date of Patent: June 13, 2017Assignee: Illumina Cambridge LimitedInventors: Roberto Rigatti, Geoffrey Paul Smith, Jonathan Mark Boutell
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Patent number: 9663820Abstract: This disclosure describes related novel methods for Recombinase-Polymerase Amplification (RPA) of a target DNA that exploit the properties of recombinase and related proteins, to invade double-stranded DNA with single stranded homologous DNA permitting sequence specific priming of DNA polymerase reactions. The disclosed methods have the advantage of not requiring thermocycling or thermophilic enzymes, thus offering easy and affordable implementation and portability relative to other amplification methods. Further disclosed are conditions to enable real-time monitoring of RPA reactions, methods to regulate RPA reactions using light and otherwise, methods to determine the nature of amplified species without a need for gel electrophoresis, methods to improve and optimize signal to noise ratios in RPA reactions, methods to optimize oligonucleotide primer function, methods to control carry-over contamination, and methods to employ sequence-specific third ‘specificity’ probes.Type: GrantFiled: January 6, 2016Date of Patent: May 30, 2017Assignee: Alere San Diego Inc.Inventors: Olaf Piepenburg, Colin H. Williams, Niall A. Armes, Derek L. Stemple