公开(公告)号：US08318460B2

公开(公告)日：2012-11-27

申请号：US12704043

申请日：2010-02-11

Applicant: Charles R Cantor ,  Chunming Ding

Inventor： Charles R Cantor ,  Chunming Ding

IPC: C12Q1/68 ,  C12P19/34 ,  C07H21/02 ,  C07H21/04

CPC classification number: C12Q1/6827 ,  C12Q1/6858 ,  C12Q2600/156 ,  C12Q2527/137 ,  C12Q2537/143 ,  C12Q2565/627

Abstract: The present invention provides an efficient way for high throughput haplotype analysis. Several polymorphic nucleic acid markers, such as SNPs, can be simultaneously and reliably determined through multiplex PCR of single nucleic acid molecules in several parallel single molecule dilutions and the consequent statistical analysis of the results from these parallel single molecule multiplex PCR reactions results in reliable determination of haplotypes present in the subject. The nucleic acid markers can be of any distance to each other on the chromosome. In addition, an approach wherein overlapping DNA markers are analyzed can be used to link smaller haplotypes into larger haplotypes. Consequently, the invention provides a powerful new tool for diagnostic haplotyping and identifying novel haplotypes.

Abstract translation: 本发明提供了高通量单倍型分析的有效方法。 可以通过多个平行的单分子稀释物中的单个核酸分子的多重PCR来同时并可靠地测定几种多态性核酸标记，例如SNP，并且随后对来自这些平行的单分子多重PCR反应的结果的统计分析导致可靠的测定 的单倍体存在于受试者。 核酸标记在染色体上可以彼此有任何距离。 此外，分析重叠的DNA标记物的方法可用于将较小的单倍型连接到较大的单元型中。 因此，本发明为诊断单倍型和鉴定新型单体型提供了强大的新工具。

公开(公告)号：US08304194B2

公开(公告)日：2012-11-06

申请号：US13223923

申请日：2011-09-01

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12Q1/68 ,  C12P19/34

CPC classification number: C12Q1/6851 ,  C12Q2545/107 ,  C12Q2535/125 ,  C12Q2525/186

Abstract: The present invention relates to a method for measuring the amount of a target nucleic acid in a sample using a standard which is designed to have one base difference compared with the gene of interest or a “target nucleic acid sequence.” Use of such standard in combination with a method of “enhancing” the difference in the standard and the test nucleic acid sample using, for example, a base extension reaction carried right at the mutation site allowing amplification of the standard and target nucleic acids with the same efficiency and facilitating quantification of the target nucleic acid. Thereafter a means of quantifying the “enhanced” standard and target nucleic acid samples is used to determine the amount of the target nucleic acid. In the preferred embodiment, the quantification means is Mass Spectrometry.

Abstract translation: 本发明涉及使用与目标基因或靶核酸序列相比设计为具有一个碱基差异的标准物来测量样品中靶核酸量的方法。 使用这种标准物与增加标准差和测试核酸样品的方法的方法结合使用例如在突变位点上携带的碱基延伸反应，允许以相同的效率扩增标准品和靶核酸 并促进靶核酸的定量。 此后，使用量化增强的标准和靶核酸样品的方法来确定靶核酸的量。 在优选实施方案中，定量方法是质谱法。

公开(公告)号：US08153377B2

公开(公告)日：2012-04-10

申请号：US12496390

申请日：2009-07-01

Applicant: Charles R Cantor ,  Chunming Ding

Inventor： Charles R Cantor ,  Chunming Ding

IPC: C12Q1/68

CPC classification number: C12Q1/6827 ,  C12Q2600/156 ,  C12Q2525/186 ,  C12Q2535/125 ,  C12Q2565/627 ,  C12Q2545/101

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）。

公开(公告)号：US20110244451A1

公开(公告)日：2011-10-06

申请号：US12844058

申请日：2010-07-27

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12Q1/68

CPC classification number: C12Q1/6883 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/6876 ,  C12Q2600/154 ,  C12Q2600/156 ,  C12Q2600/166 ,  C12Q2521/331

Abstract: Chromosomal abnormalities are responsible for a significant number of birth defects, including mental retardation. The present invention is related to methods for non-invasive and rapid, prenatal diagnosis of chromosomal abnormalities based on analysis of a maternal blood sample. The invention exploits the differences in DNA between the mother and fetus, for instance differences in their methylation states, as a means to enrich for fetal DNA in maternal plasma sample. The methods described herein can be used to detect chromosomal DNA deletions and duplications. In a preferred embodiment, the methods are used to diagnose chromosomal aneuploidy and related disorders, such as Down's and Turner's Syndrome.

Abstract translation: 染色体异常负责大量的出生缺陷，包括精神发育迟滞。 本发明涉及基于母体血液样品分析的非侵入性和快速，产前诊断染色体异常的方法。 本发明利用母体和胎儿之间的DNA差异，例如甲基化状态的差异，作为富集母体血浆样品中胎儿DNA的手段。 本文描述的方法可用于检测染色体DNA缺失和重复。 在优选的实施方案中，所述方法用于诊断染色体非整倍体和相关疾病，例如唐氏和特纳综合征。

公开(公告)号：US20110124518A1

公开(公告)日：2011-05-26

申请号：US12863169

申请日：2009-01-16

Applicant: Charles R. Cantor

Inventor： Charles R. Cantor

IPC: C40B30/04 ,  C12Q1/68 ,  B82Y15/00

CPC classification number: C12Q1/6818 ,  C12Q1/6816 ,  C12Q1/6869 ,  C12Q2521/501 ,  C12Q2525/161 ,  C12Q2563/185

Abstract: Provided herein are compositions and methods for analysis of nucleic acids, including, methods and compositions for genotyping, haplotyping, sequencing and performing other genetic and epigenetic analyses on nucleic acids, for example. In some embodiments, methods and compositions suitable for whole-genome sequencing on single molecules of nucleic acid are provided. In some embodiments, analysis of single molecules of nucleic acid are performed in conjunction with nanopores and/or nanopore devices.

Abstract translation: 本文提供了用于分析核酸的组合物和方法，包括用于例如基因分型，单倍型，测序和对核酸进行其它遗传和表观遗传学分析的方法和组合物。 在一些实施方案中，提供适用于单分子核酸上的全基因组测序的方法和组合物。 在一些实施方案中，结合纳米孔和/或纳米孔装置进行单分子核酸的分析。

公开(公告)号：US20090305237A1

公开(公告)日：2009-12-10

申请号：US11914970

申请日：2006-05-26

Applicant: Charles R. Cantor ,  Lingang Zhang ,  Simon Kasif

Inventor： Charles R. Cantor ,  Lingang Zhang ,  Simon Kasif

IPC: C12Q1/68

CPC classification number: C12Q1/6816 ,  C12Q1/6809 ,  C12Q2565/627 ,  C12Q2563/167 ,  C12Q2545/114

Abstract: The invention provides a method for detecting and quantifying the amount of target molecules, such as nucleic acids or proteins in a sample. The target molecules are first recognized and bounded by target-specific probes, generally nucleic acids or proteins that bind specifically to the targets, each of which is labeled with a short single-stranded nucleic acid probe, either DNA or RNA, with distinct molecular weight. This label is called an oligonucleotide mass tag. One or several standard oligonucleotide sequences can be designed with similar sequence but distinct molecular weight to those oligonucleotide mass tags. Then the oligonucleotide mass tags associated with bounded probes and the standard sequences are co-amplified using a pair of common primers. The presence and/or amount of each oligonucleotide mass tag, which corresponds to the amount of corresponding target molecule, is determined by a primer extension reaction and quantification of the primer extension product.

Abstract translation: 本发明提供了用于检测和定量样品中靶分子如核酸或蛋白质的量的方法。 目标分子首先被目标特异性探针识别并限制，通常是与靶标特异性结合的核酸或蛋白质，其中每个标记有短单链核酸探针，DNA或RNA，具有不同的分子量 。 该标签称为寡核苷酸质量标签。 可以设计一个或几个标准寡核苷酸序列，其具有与那些寡核苷酸质量标签相似的序列但分子量不同。 然后使用一对普通引物共同扩增与有界探针和标准序列相关的寡核苷酸质粒标签。 通过引物延伸反应和引物延伸产物的定量来确定对应于相应靶分子量的每个寡核苷酸质粒标签的存在和/或量。

公开(公告)号：US07569341B2

公开(公告)日：2009-08-04

申请号：US08967269

申请日：1997-11-07

Applicant: Christof M. Niemeyer ,  Charles R. Cantor ,  Takeshi Sano ,  Cassandra L. Smith

Inventor： Christof M. Niemeyer ,  Charles R. Cantor ,  Takeshi Sano ,  Cassandra L. Smith

IPC: C12Q1/68

CPC classification number: B82Y5/00 ,  A61K47/54 ,  A61K47/55 ,  A61K47/557 ,  A61K47/6949 ,  A61K51/1268 ,  C03C17/30 ,  C03C17/3405 ,  C12Q1/6804 ,  C12Q1/682

Abstract: The invention relates to supramolecular bioconjugates and to methods for assembling and utilizing supramolecular bioconjugates. Supramolecular bioconjugates comprise a plurality of first nucleic acids and a plurality of mediators wherein each mediator comprises a second nucleic acid complementary to a sequence within said plurality of first nucleic acids. To assemble a supramolecular bioconjugate, one or more sets of bioreactive agents are coupled to the plurality of mediators, forming a plurality of bioreactive complexes The plurality of bioreactive complexes are hybridized to the plurality of first nucleic acids to form the supramolecular bioconjugate. Bioconjugates can be used to detect and isolate targets, to screen samples for targets such as antigens, to treat patients with multiple agents or to diagnose disorders in the form of a kit.

Abstract translation: 本发明涉及超分子生物缀合物和组分和利用超分子生物缀合物的方法。 超分子生物缀合物包含多个第一核酸和多个介体，其中每个介体包含与所述多个第一核酸内的序列互补的第二核酸。 为了组装超分子生物缀合物，将一组或多组生物反应剂偶联到多个介体中，形成多个生物反应性复合物。多个生物反应性复合物与多个第一核酸杂交以形成超分子生物缀合物。 生物共轭物可用于检测和分离靶标，筛选靶标如抗原的样品，以治疗患有多种药物的患者或以试剂盒的形式诊断疾病。

公开(公告)号：US07470517B2

公开(公告)日：2008-12-30

申请号：US11547765

申请日：2005-04-08

Applicant: Charles R. Cantor ,  Fouad A. Siddiqi

Inventor： Charles R. Cantor ,  Fouad A. Siddiqi

IPC: C12Q1/68

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。

公开(公告)号：US06869765B2

公开(公告)日：2005-03-22

申请号：US09993346

申请日：2001-11-13

Applicant: Cynthia A. Edwards ,  Charles R. Cantor ,  Beth M. Andrews ,  Lisa M. Turin ,  Kirk E. Fry

Inventor： Cynthia A. Edwards ,  Charles R. Cantor ,  Beth M. Andrews ,  Lisa M. Turin ,  Kirk E. Fry

IPC: C07K14/47 ,  C12N15/10 ,  C12N15/67 ,  C12Q1/68 ,  C12Q1/70

CPC classification number: C12Q1/701 ,  C07K14/47 ,  C12N15/1048 ,  C12N15/67 ,  C12Q1/6811 ,  C12Q1/6813 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q1/705 ,  H01L2924/14 ,  C12Q2525/161 ,  C12Q2525/131 ,  C12Q2537/161 ,  C12Q2522/101 ,  C12Q2521/301

Abstract: The present invention defines a DNA: protein-binding assay useful for screening libraries of synthetic or biological compounds for their ability to bind DNA test sequences. The assay is versatile in that any number of test sequences can be tested by placing the test sequence adjacent to a defined protein binding screening sequence. Binding of molecules to these test sequence changes the binding characteristics of the protein molecule to its cognate binding sequence. When such a molecule binds the test sequence the equilibrium of the DNA:protein complexes is disturbed, generating changes in the concentration of free DNA probe. Numerous exemplary target test sequences (SEQ ID NO:1 to SEQ ID NO:600) are set forth. The assay of the present invention is also useful to characterize the preferred binding sequences of any selected DNA-binding molecule.

Abstract translation: 本发明定义了一种DNA：蛋白结合测定法，用于筛选合成或生物化合物文库结合DNA测试序列的能力。 该测定法是通用的，因为可以通过将测试序列置于与定义的蛋白质结合筛选序列相邻的位置来测试任何数量的测试序列。 分子与这些测试序列的结合改变了蛋白质分子与其同源结合序列的结合特征。 当这样的分子结合测试序列时，DNA：蛋白复合物的平衡受到干扰，产生游离DNA探针浓度的变化。 阐述了许多示例性目标测试序列（SEQ ID NO：1至SEQ ID NO：600）。 本发明的测定也可用于表征任何所选DNA结合分子的优选结合序列。

公开(公告)号：US06207390B1

公开(公告)日：2001-03-27

申请号：US08941100

申请日：1997-10-03

Applicant: Charles R. Cantor ,  Takeshi Sano

Inventor： Charles R. Cantor ,  Takeshi Sano

IPC: G01N3353

CPC classification number: G01N33/538 ,  A61K38/00 ,  C07K14/36 ,  G01N2333/465 ,  Y10S530/808 ,  Y10S530/81

Abstract: The present invention relates to methods for contacting biological targets using a mutated streptavidin protein having a reduced affinity for biotin.

Abstract translation: 本发明涉及使用对生物素具有降低的亲和力的突变链霉抗生物素蛋白接触生物靶标的方法。