Patent application number | Description | Published |
20080286756 | COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING SEVERE ACUTE RESPIRATORY SYNDROME (SARS) - The present invention relates to the fields of immunochemistry and pharmacology. Methods and compositions are described for the diagnosis and treatment of SARS CoV infection. More specifically, the application discloses nucleic acids and peptides of the spike glycoprotein of SARS CoV that provide prognostic and therapeutic compositions in treatment of individuals contracting, or in danger of contracting SARS CoV. The peptides of the invention are also useful in producing antibodies against the SARS CoV glycoprotein. | 11-20-2008 |
20090170102 | METHODS FOR DETECTING DNA ORIGINATING FROM DIFFERENT INDIVIDUALS - In a first aspect, the present invention features methods for differentiating DNA species originating from different individuals in a biological sample. These methods may be used to differentiate or detect fetal DNA in a maternal sample or to differentiate DNA of an organ donor from DNA of an organ recipient. In preferred embodiments, the DNA species are differentiated by observing epigenetic differences in the DNA species such as differences in DNA methylation. In a second aspect, the present invention features methods of detecting genetic abnormalities in a fetus by detecting fetal DNA in a biological sample obtained from a mother. In a third aspect, the present invention features methods for differentiating DNA species originating from an organ donor from those of an organ recipient. In a fourth aspect, the present invention features kits for differentiating DNA species originating from different individuals in a biological sample. | 07-02-2009 |
20110086357 | Methods for Evaluating a Disease Condition by Nucleic Acid Detection and Fractionation - This invention relates to the discovery that both non-particle and particle associated nucleic acids are present in blood plasma and serum and can be used to evaluate disease conditions. | 04-14-2011 |
20110105353 | Fetal Genomic Analysis From A Maternal Biological Sample - Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided. | 05-05-2011 |
20120003650 | MARKER FOR PRENATAL DIAGNOSIS AND MONITORING - The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status. | 01-05-2012 |
20130059733 | MOLECULAR TESTING OF MULTIPLE PREGNANCIES - Methods, systems, and apparatus are provided for determining zygosity of a multiple-fetus pregnancy using a biological sample taken from the mother. The fetal and maternal DNA in the sample (e.g. plasma) can be analyzed for a particular chromosomal region to identify genetic differences in the fetuses. For example, a normalized parameter for the measure of a primary or secondary allele can show variances for different chromosomal regions when fetuses are dizygotic. Such a variance can be determined relative to an expected value if the fetuses were genetically identical. Statistical methods are provided for analyzing the variation of the normalized parameters to determine fetal DNA concentration and the maternal-fetal mixed genotype at various loci. Parental genotype and haplotype information can also be used to identify inheritance of different parental haplotypes to indicate genetic differences among the fetuses. | 03-07-2013 |
Patent application number | Description | Published |
20080206749 | Methods and kits for diagnosis, prognosis or monitoring of Epstein-Barr virus (EBV)-associated cancer - Disclosed is a non-invasive method for diagnosis, prognosis or monitoring of Epstein-Barr virus (EBV)-associated cancer by detecting and/or quantifying EBV associated nucleic acid fragments in a urine sample from an individual. Kits for diagnosis, prognosis or monitoring of cancer are also disclosed. | 08-28-2008 |
20090061425 | Methods and kits for selectively amplifying, detecting or quantifying target DNA with specific end sequences - Disclosed herein are methods and kits for selectively amplifying, detecting or quantifying a DNA fragment with a specific end sequence, especially generated following restriction enzyme digestion. This method can be used, for example, to detect a hypomethylated DNA fragment. This methods and kits are especially useful in detecting or quantifying a hypomethylated fetal DNA fragment in a maternal plasma sample containing a corresponding hypermethylated maternal DNA fragment. | 03-05-2009 |
20110033841 | METHODS AND KITS FOR DIAGNOSIS, PROGNOSIS OR MONITORING OF EPSTEIN-BARR VIRUS (EBV)-ASSOCIATED CANCER - Disclosed is a non-invasive method for diagnosis, prognosis or monitoring of Epstein-Barr virus (EBV)-associated cancer by detecting and/or quantifying EBV associated nucleic acid fragments in a urine sample from an individual. Kits for diagnosis, prognosis or monitoring of cancer are also disclosed. | 02-10-2011 |
20120225798 | METHOD FOR NON-INVASIVE PRENATAL DIAGNOSIS - The present invention is directed to methods of detecting nucleic acids in a biological sample. The method is based on a novel combination of a base extension reaction, which provides excellent analytical specificity, and a mass spectrometric analysis, which provides excellent specificity. The method can be used, for example, for diagnostic, prognostic and treatment purposes. The method allows accurate detection of nucleic acids that are present in very small amounts in a biological sample. For example, the method of the present invention is preferably used to detect fetal nucleic acid in a maternal blood sample; circulating tumor-specific nucleic acids in a blood, urine or stool sample; and donor-specific nucleic acids in transplant recipients. In another embodiment, one can detect viral, bacterial, fungal, or other foreign nucleic acids in a biological sample. | 09-06-2012 |
20140302506 | METHODS AND KITS FOR SELECTIVELY AMPLIFYING, DETECTING OR QUANTIFYING TARGET DNA WITH SPECIFIC END SEQUENCES - Disclosed herein are methods and kits for selectively amplifying, detecting or quantifying a DNA fragment with a specific end sequence, especially generated following restriction enzyme digestion. This method can be used, for example, to detect a hypomethylated DNA fragment. This methods and kits are especially useful in detecting or quantifying a hypomethylated fetal DNA fragment in a maternal plasma sample containing a corresponding hypermethylated maternal DNA fragment. | 10-09-2014 |
Patent application number | Description | Published |
20130084566 | FETAL METHYLATION MARKERS - This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB2IP, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions. | 04-04-2013 |
20130245961 | METHODS FOR ANALYZING MASSIVELY PARALLEL SEQUENCING DATA FOR NONINVASIVE PRENATAL DIAGNOSIS - This invention provides several ways of managing GC bias that occurs during seequencing and analysis of genomic DNA. Maternal plasma can be used as a source of fetal DNA for analysis. DNA segments or tags obtained from the plasma can be aligned with a chromosomal region of interest and with an artificial reference chromosome assembled from regions of the genome having matching GC content. This technology can be used, for example, to detect and evaluate aneuploidy and other chromosomal abnormalities | 09-19-2013 |
20130253844 | IDENTIFYING A DE NOVO FETAL MUTATION FROM A MATERNAL BIOLOGICAL SAMPLE - Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided. | 09-26-2013 |
20130267425 | NONINVASIVE PRENATAL DIAGNOSIS OF FETAL TRISOMY BY ALLELIC RATIO ANALYSIS USING TARGETED MASSIVELY PARALLEL SEQUENCING - Whether a fetus has an aneuploidy associated with a first chromosome is detected using ratios of alleles detected in a maternal sample having a mixture of maternal and fetal DNA. DNA from the sample is enriched for target regions associated with polymorphic loci and then sequenced. Polymorphic loci (e.g., single nucleotide polymorphisms) in the target regions with fetal-specific alleles are identified on a first chromosome and on one or more reference chromosomes. A first ratio of the fetal-specific alleles and shared alleles is determined for the loci on the first chromosome. A second ratio of the fetal-specific alleles and shared alleles is determined for the loci on the reference chromosome(s). A third ratio of the first and second ratio can be compared to a cutoff to determine whether an aneuploidy is present, and whether the aneuploidy is maternally-derived or paternally-derived. | 10-10-2013 |
20130310263 | DIAGNOSING CANCER USING GENOMIC SEQUENCING - Methods, systems, and apparatus determine whether a first chromosomal region exhibits a deletion or an amplification associated with cancer in a sample from a subject (e.g., where the sample includes a mixture of cell-free DNA from tumor cells and non-malignant cells. Nucleic acid molecules of the biological sample are sequenced. Respective amounts of a clinically-relevant chromosomal region and of background chromosomal region(s) are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether first chromosomal region exhibits a deletion or an amplification associated with cancer. | 11-21-2013 |
20140080715 | NON-INVASIVE DETERMINATION OF METHYLOME OF FETUS OR TUMOR FROM PLASMA - Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer. | 03-20-2014 |
20140100121 | MUTATIONAL ANALYSIS OF PLASMA DNA FOR CANCER DETECTION - A frequency of somatic mutations in a biological sample (e.g., plasma or serum) of a subject undergoing screening or monitoring for cancer, can be compared with that in the constitutional DNA of the same subject. A parameter can derived from these frequencies and used to determine a classification of a level of cancer. False positives can be filtered out by requiring any variant locus to have at least a specified number of variant sequence reads (tags), thereby providing a more accurate parameter. The relative frequencies for different variant loci can be analyzed to determine a level of heterogeneity of tumors in a patient. | 04-10-2014 |
20140195164 | NONINVASIVE PRENATAL MOLECULAR KARYOTYPING FROM MATERNAL PLASMA - Disclosed herein are methods, systems, and apparatus for detecting microamplifications or microdeletions in the genome of a fetus. In some embodiments, the method comprises receiving sequence tags for each of a plurality of DNA fragments in a biological sample; determining genomic positions for the sequence tags; determining whether the density of DNA in each of a plurality of genomic regions is aberrantly high or low; identifying as a microamplification a set of consecutive genomic regions having aberrantly high density; and identifying as a microdeletion a set of consecutive genomic regions having aberrantly low density. The biological sample may be a blood sample obtained noninvasively from a female subject pregnant with the fetus. | 07-10-2014 |
20140315200 | DETERMINING FETAL GENOMES FOR MULTIPLE FETUS PREGNANCIES - Techniques are provided for determining inheritance of maternal and paternal haplotypes in preganncies with multiple fetuses. Maternal inheritance can be determined at loci where the mother is heterozygous and the paternally inherited alleles are known (e.g., the father is homozygous). Two types of loci may be used, where one type has the paternal allele appear on a first maternal haplotype, and another type has the paternal allele appear on a second maternal haplotype. Paternal inheritance can be determined from loci where the father is heterozygous and the maother is homozygous. Amounts of different alleles at each locus can be measured. A comparison of the amounts (e.g., using a fractional concentration of each allele and cutoffs) can be used to determine the haplotype inheritance. A haplotype can be linked to a condition of interest. | 10-23-2014 |
20150087529 | SEQUENCING ANALYSIS OF CIRCULATING DNA TO DETECT AND MONITOR AUTOIMMUNE DISEASES - Systems, methods, and apparatuses are provided for diagnosing auto-immune diseases such as systemic lupus erythematosus (SLE) based on the sizes, methylation levels, and/or genomic characteristics of circulating DNA molecules. Patients provide blood or other tissue samples containing cell-free nucleic molecules for analysis. Massively parallel and/or methylation-aware sequencing can be used to determine the sizes and methylation levels of individual DNA molecules and identify the number of molecules originating from different genomic regions. A level of SLE can be estimated based on: the amount of molecules having sizes below a threshold value; the methylation level(s) of the entire genome or portions of the genome; correlations between the sizes and methylation levels of DNA molecules; and/or comparing the representation of DNA molecules in each of a plurality of genomic regions with a reference value for that region, and determining an amount of genomic regions having increased or decreased measured genomic representation. | 03-26-2015 |
Patent application number | Description | Published |
20130237431 | SIZE-BASED ANALYSIS OF FETAL DNA FRACTION IN MATERNAL PLASMA - A fractional concentration of clinically-relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments at multiple sizes. For example, the fractional concentration of fetal DNA in maternal plasma or tumor DNA in a patient's plasma can be determined. The size of DNA fragments in a sample is shown to be correlated with a proportion of fetal DNA and a proportion of tumor DNA, respectively. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a size parameter and the fractional concentration of the clinically-relevant DNA. For a given sample, a first value of a size parameter can be determined from the sizes of DNA fragments in a sample. A comparison of the first value to the calibration data points can provide the estimate of the fractional concentration of the clinically-relevant DNA. | 09-12-2013 |
20130323731 | DETERMINATION OF THE DEPTH COVERAGE OF THE FETAL GENOME - Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided. | 12-05-2013 |
20130337443 | METHODS FOR DETECTING DNA PRIOGINATING FROM DIFFERENT INDIVIDUALS - In a first aspect, the present invention features methods for differentiating DNA species originating from different individuals in a biological sample. These methods may be used to differentiate or detect fetal DNA in a maternal sample or to differentiate DNA of an organ donor from DNA of an organ recipient. In preferred embodiments, the DNA species are differentiated by observing epigenetic differences in the DNA species such as differences in DNA methylation. In a second aspect, the present invention features methods of detecting genetic abnormalities in a fetus by detecting fetal DNA in a biological sample obtained from a mother. In a third aspect, the present invention features methods for differentiating DNA species originating from an organ donor from those of an organ recipient. In a fourth aspect, the present invention features kits for differentiating DNA species originating from different individuals in a biological sample. | 12-19-2013 |
20140045181 | DETERMINING PERCENTAGE OF FETAL DNA IN MATERNAL SAMPLE - Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The percentage of fetal DNA can be calculated from the same or different data used to determine the cutoff value, and can use a locus where the mother is homozygous and the fetus is heterozygous. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing (SPRT). | 02-13-2014 |
20140080720 | FETAL GENOMIC ANALYSIS THAT ACCOUNTS FOR GC BIAS - Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus. | 03-20-2014 |
20140243212 | MATERNAL PLASMA TRANSCRIPTOME ANALYSIS BY MASSIVELY PARALLEL RNA SEQUENCING - Methods are provided for diagnosing pregnancy-associated disorders, determining allelic ratios, determining maternal or fetal contributions to circulating transcripts, and/or identifying maternal or fetal markers using a sample from a pregnant female subject. Also provided is use of a gene for diagnosing a pregnancy-associated disorder in a pregnant female subject. | 08-28-2014 |