METHOD FOR DETECTING AND QUANTIFYING RARE MUTATIONS/POLYMORPHISMS
    1.
    发明申请
    METHOD FOR DETECTING AND QUANTIFYING RARE MUTATIONS/POLYMORPHISMS 有权
    检测和量化稀有突变/多态性的方法

    公开(公告)号:US20110097712A1

    公开(公告)日:2011-04-28

    申请号:US12496390

    申请日:2009-07-01

    Abstract: The present invention is directed to a method for detecting and quantifying rare mutations in a nucleic acid sample. The nucleic acid molecules under investigation can be either DNA or RNA. The rare mutation can be any type of functional or non-functional nucleic acid change or mutation, such as deletion, insertion, translocation, inversion, one or more base substitution or polymorphism. Therefore, the methods of the present invention are useful in detection of rare mutations in, for example, diagnostic, prognostic and follow-up applications, when the targets are rare known nucleic acid variants mixed in with the wildtype or the more common nucleic acid variant(s).

    Abstract translation: 本发明涉及一种用于检测和定量核酸样品中罕见突变的方法。 正在研究的核酸分子可以是DNA或RNA。 罕见突变可以是任何类型的功能或非功能性核酸变化或突变,例如缺失,插入,易位,反转,一个或多个碱基取代或多态性。 因此,当目标是罕见的已知的与野生型或更常见的核酸变体混合的核酸变体时,本发明的方法可用于检测例如诊断,预后和随访应用中的罕见突变 (s)。

    METHOD FOR DE NOVO DETECTION OF SEQUENCES IN NUCLEIC ACIDS: TARGET SEQUENCING BY FRAGMENTATION
    2.
    发明申请
    METHOD FOR DE NOVO DETECTION OF SEQUENCES IN NUCLEIC ACIDS: TARGET SEQUENCING BY FRAGMENTATION 有权
    在核酸中检测序列的方法:通过分段进行的目标序列

    公开(公告)号:US20090075288A1

    公开(公告)日:2009-03-19

    申请号:US12259376

    申请日:2008-10-28

    CPC classification number: C12Q1/6872 C12Q2525/101 C12Q2523/107

    Abstract: The present invention provides a method for determining nucleic acid sequences of a template nucleic acid that requires no prior knowledge of the nucleic acid sequence present in the template nucleic acid. The method is based on combining information about the mass of a fragment, the mass of any one nucleotide and the combinations thereof, and the sequence specificity of a nucleotide cutter, either enzymatic or chemical cutter, to determine a sequence of a nucleic acid fragment. This method allows for de novo detection of sequences in a target nucleic acid without requiring any prior sequence information. This method is called Partial Sequencing by Fragmentation (PSBF) and it works by fragmenting a target into oligo- or polynucleotides whose masses or lengths are uniquely associated with known sequences. The identities of these sequences are determined solely by the specific fragmentation method used, and are always independent of the target. PSBF can be implemented using electrophoresis, mass spectrometry or any other method that can be used to distinguish the size of the cut nucleic acid sequence fragments.

    Abstract translation: 本发明提供了一种确定模板核酸的核酸序列的方法,其不需要模板核酸中存在的核酸序列的先验知识。 该方法基于组合关于片段的质量,任何一个核苷酸的质量及其组合的信息以及核苷酸切割剂(酶或化学切割机)的序列特异性,以确定核酸片段的序列。 该方法允许从头检测靶核酸中的序列,而不需要任何先前的序列信息。 这种方法被称为通过片段化分段测序(PSBF),它的作用是通过将目标片段分成其质量或长度与已知序列唯一相关的寡核苷酸或多核苷酸。 这些序列的身份完全由所使用的具体碎片方法确定,并且始终与目标无关。 PSBF可以使用电泳,质谱法或可用于区分切割的核酸序列片段的大小的任何其它方法来实现。

    Method for De Novo Detection of Sequences in Nucleic Acids: Target Sequencing by Fragmentation
    3.
    发明申请
    Method for De Novo Detection of Sequences in Nucleic Acids: Target Sequencing by Fragmentation 失效
    核酸序列的新检测方法:通过分段进行靶序列测定

    公开(公告)号:US20080096194A1

    公开(公告)日:2008-04-24

    申请号:US11547765

    申请日:2005-04-08

    CPC classification number: C12Q1/6872 C12Q2525/101 C12Q2523/107

    Abstract: The present invention provides a method for determining nucleic acid sequences of a template nucleic acid that requires no prior knowledge of the nucleic acid sequence present in the template nucleic acid. The method is based on combining information about the mass of a fragment, the mass of any one nucleotide and the combinations thereof, and the sequence specificity of a nucleotide cutter, either enzymatic or chemical cutter, to determine a sequence of a nucleic acid fragment. This method allows for de novo detection of sequences in a target nucleic acid without requiring any prior sequence information. This method is called Partial Sequencing by Fragmentation (PSBF) and it works by fragmenting a target into oligo- or polynucleotides whose masses or lengths are uniquely associated with known sequences. The identities of these sequences are determined solely by the specific fragmentation method used, and are always independent of the target. PSBF can be implemented using electrophoresis, mass spectrometry or any other method that can be used to distinguish the size of the cut nucleic acid sequence fragments.

    Abstract translation: 本发明提供了一种确定模板核酸的核酸序列的方法,其不需要模板核酸中存在的核酸序列的先验知识。 该方法基于组合关于片段的质量,任何一个核苷酸的质量及其组合的信息以及核苷酸切割剂(酶或化学切割机)的序列特异性,以确定核酸片段的序列。 该方法允许从头检测靶核酸中的序列,而不需要任何先前的序列信息。 这种方法被称为通过片段化分段测序(PSBF),它的作用是通过将目标片段分成其质量或长度与已知序列唯一相关的寡核苷酸或多核苷酸。 这些序列的身份完全由所使用的具体碎片方法确定,并且始终与目标无关。 PSBF可以使用电泳,质谱法或可用于区分切割的核酸序列片段的大小的任何其它方法来实现。

    Solid phase sequencing of double-stranded nucleic acids
    8.
    发明授权
    Solid phase sequencing of double-stranded nucleic acids 失效
    双链核酸的固相测序

    公开(公告)号:US06436635B1

    公开(公告)日:2002-08-20

    申请号:US08614151

    申请日:1996-03-12

    Abstract: This invention relates to methods for detecting and sequencing of target double-stranded nucleic acid sequences, to nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probe comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include nucleic acids in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated determination of molecular weights and identification of the target sequence.

    Abstract translation: 本发明涉及用于检测和测序靶双链核酸序列,用于这些方法的核酸探针和探针阵列的方法,以及含有这些探针的试剂盒和系统。 有用的方法包括将代表靶的互补或同源序列的核酸或核酸与核酸探针阵列进行杂交。 这些探针包含在单链部分内的单链部分,任选的双链部分和可变序列。 该组的杂交核酸的分子量可以通过质谱法测定,并且靶标的序列由片段的分子量确定。 可以确定其序列的核酸包括生物样品中的核酸,例如患者活组织检查和环境样品。 探针可以固定在固体支持物例如杂交芯片上以促进分子量的自动测定和靶序列的鉴定。

    Design and synthesis of bispecific reagents: use of double stranded DNAs
as chemically and spatially defined cross-linkers
    10.
    发明授权
    Design and synthesis of bispecific reagents: use of double stranded DNAs as chemically and spatially defined cross-linkers 失效
    双特异性试剂的设计和合成:使用双链DNA作为化学和空间定义的交联剂

    公开(公告)号:US5849878A

    公开(公告)日:1998-12-15

    申请号:US481065

    申请日:1995-06-07

    CPC classification number: C07K16/2812 C07K16/2809 C07K16/468

    Abstract: The invention relates to bis-protein-DNA conjugates. A protein having a specific ligand binding activity is covalently linked to each end of a derivatized DNA molecule. These bis-protein-DNA conjugates can be used for immunoassays, PCR assays and measuring distances between proteins at up to 3.4 A resolution. The invention also relates to methods of synthesizing these bis-protein-DNA conjugates. Synthesis of the conjugates entails derivatizing the 5' or 3' end of a DNA oligonucleotide and covalently linking that DNA to a protein. The DNA can be conjugated to the proteins, including antibodies or Fab' fragments, using disulfide bond linkage.

    Abstract translation: 本发明涉及双蛋白-DNA缀合物。 具有特异性配体结合活性的蛋白质与衍生的DNA分子的每个末端共价连接。 这些双蛋白-DNA缀合物可用于免疫测定,PCR测定和测量蛋白质之间的距离,高达3.4A分辨率。 本发明还涉及合成这些双蛋白-DNA缀合物的方法。 共轭物的合成需要衍生DNA寡核苷酸的5'或3'末端并共价连接该DNA与蛋白质。 使用二硫键可将DNA与蛋白质缀合,包括抗体或Fab'片段。

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