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    • 13. 发明授权
    • Screening for functional antisense agents
    • 筛选功能性反义试剂
    • US06416951B1
    • 2002-07-09
    • US09623385
    • 2001-03-26
    • Gunter SchmidtAndrew Hugin Thompson
    • Gunter SchmidtAndrew Hugin Thompson
    • C12Q168
    • C12Q1/6816C12Q1/6837Y10S977/924C12Q2565/601C12Q2563/173C12Q2525/207C12Q2565/515
    • Provided is a method for identifying a functional antisense agent, which method comprises hybridizing an RNA with an aligonucleotide probe and measuring in real time the kinetics of hybridization, wherein the kinetics are measured by either hybridizing in the presence of an intercalation dye and recording a change in the spectroscopic properties of the dye as hybridizing proceeds, or incorporating a label in either the RNA or the probe, attaching the non-labelled RNA or non-labelled probe to a solid support, generating an evanescent wave in the proximity of the non-labelled RNA or non-labelled probe and recording the increase in a signal generated by interaction of the evanescent wave with the label, as hybridization proceeds.
    • 提供了一种用于鉴定功能性反义剂的方法,该方法包括将RNA与寡核苷酸探针杂交并实时测量杂交的动力学,其中通过在插入染料存在下杂交并记录变化来测量动力学 在作为杂交进行的染料的光谱性质中,或者在RNA或探针中掺入标记,将非标记的RNA或未标记的探针附着到固体支持物上,在非接触的情况下产生ev逝波, 标记的RNA或非标记的探针,并记录随着杂交进行而通过ev逝波的相互作用产生的信号与标记的增加。
    • 14. 发明授权
    • Nucleic acid sequencing
    • 核酸测序
    • US07094531B1
    • 2006-08-22
    • US09341641
    • 1998-01-15
    • Gunter SchmidtAndrew Hugin Thompson
    • Gunter SchmidtAndrew Hugin Thompson
    • C12Q1/68C12N15/00C12N15/63C12N1/20C07H21/04
    • C12Q1/6874C12Q1/6872
    • Provided is a method for sequencing DNA, which comprises: (a) obtaining a target DNA population comprising one or more single-stranded DNAs to be sequenced, each of which is present in a unique amount and bears a primer to provide a double-stranded portion of the DNA for ligation thereto; (b) contacting the DNA population with an array of hybridisation probes, each probe comprising a label cleavably attached to a known base sequence of predetermined length, the array containing all possible base sequences of that predetermined length; (c) removing all unligated probes; followed by the steps of: (d) cleaving the ligated probes to release each label; (e) recording the quantity of each label; and (f) activating the extended double-stranded portion to enable ligation thereto; wherein (g) steps (b) to (f) are repeated in a cycle for a sufficient number of times to determine the sequence of the or each single-stranded DNA by determining the sequence of release of each label.
    • 提供了一种用于测序DNA的方法,其包括:(a)获得包含待测序的一个或多个单链DNA的靶DNA群体,其中每一个以独特的量存在并承载引物以提供双链 DNA连接部分; (b)使DNA群体与杂交探针阵列接触,每个探针包含与预定长度的已知碱基序列可切割地连接的标记,该阵列包含该预定长度的所有可能的碱基序列; (c)清除所有未连接的探针; 其次是以下步骤:(d)切割连接的探针以释放每个标签; (e)记录每个标签的数量; 和(f)活化延伸的双链部分以使其能够连接; 其中(g)步骤(b)至(f)在循环中重复足够多次,以通过确定每个标记的释放顺序来确定该单链DNA或每个单链DNA的序列。
    • 16. 发明授权
    • Characterizing polypeptides
    • 表征多肽
    • US06156527A
    • 2000-12-05
    • US341993
    • 1999-09-10
    • Gunter SchmidtAndrew Hugin Thompson
    • Gunter SchmidtAndrew Hugin Thompson
    • C07K1/04C07K1/12C12Q1/37G01N33/68C12Q1/00C12Q1/34
    • C07K1/12G01N33/6818
    • A method for characterizing polypeptides, which comprises: (a) treating a sample comprising a population of one or more polypeptides with a cleavage agent which is known to recognize a specific amino acid residue or sequence in polypeptide chains and to cleave at a cleavage site, whereby the population is cleaved to generate peptide fragments; (b) isolating a population of the peptide fragments which bear at one end a reference terminus comprising either only a C-terminus or only an N-terminus and which bear at the other end the cleavage site proximal to the reference terminus; and c) determining a signature sequence of at least some of the isolated fragments, which signature sequence is the sequence of a predetermined number of amino acid residues running from the cleavage site; wherein the signature sequence and the relative position of the cleavage site to the reference terminus characterize the polypeptide or each polypeptide.
    • PCT No.PCT / GB98 / 00201 Sec。 371 1999年9月10日第 102(e)1999年9月10日PCT PCT 1998年1月23日PCT公布。 第WO98 / 32876号公报 日期1998年7月30日一种用于表征多肽的方法,其包括:(a)用已知识别多肽链中特定氨基酸残基或序列的切割剂处理包含一种或多种多肽群体的样品,并切割 在切割位点,由此群体被切割以产生肽片段; (b)分离一段肽片段,其在一端具有仅包括C末端或仅包含N末端的参考末端,并且在另一端承载靠近参考末端的切割位点; 以及c)确定至少一些所述分离片段的特征序列,所述标记序列是从所述切割位点延伸的预定数量的氨基酸残基的序列; 其中所述切割位点与所述参考端的特征序列和相对位置表征所述多肽或每个多肽。
    • 17. 发明授权
    • Categorising nucleic acids
    • 分类核酸
    • US06297017B1
    • 2001-10-02
    • US09462636
    • 2000-04-10
    • Günter SchmidtAndrew Hugin Thompson
    • Günter SchmidtAndrew Hugin Thompson
    • C12Q168
    • C12Q1/6855C12Q2565/518C12Q2563/131C12Q2531/119
    • The present invention concerns a method for characterizing one or more nucleic acids. This method involves immobilizing double-stranded nucleic acids on a solid phase support and cleaving the immobilized nucleic acids with an endonuclease, such that each cleaved nucleic acid has a double-stranded portion. The cleaved nucleic acids are then denatured to form single-stranded cleaved nucleic acids. One or more oligonucleotide sequences are then hybridized to the resulting single-stranded cleaved nucleic acid. The oligonucleotide sequences used each comprise a pre-determined recognition sequence situated such that it recognizes a sequence which was part of the double-stranded portion of the nucleic acid and a label specific to the recognition sequence. The hybridized oligonucleotide sequences are then extended along the single-stranded portion of the immobilized nucleic acid to form an extended strand which is then denatured from the immobilized strand. The immobilized nucleic acid is then characterized by identifying the size of the extended strand and the identity of the recognition sequence.
    • 本发明涉及用于表征一种或多种核酸的方法。 该方法包括将固定在固相载体上的双链核酸固定并用内切核酸酶切割固定的核酸,使得每个切割的核酸具有双链部分。 然后将切割的核酸变性以形成单链切割的核酸。 然后将一个或多个寡核苷酸序列与所得的单链切割的核酸杂交。 所使用的寡核苷酸序列包含预定的识别序列,其位置使得其识别作为核酸的双链部分的一部分的序列和识别序列特异的标记。 然后将杂交的寡核苷酸序列沿着固定的核酸的单链部分延伸以形成延伸的链,然后将其从固定的链变性。 然后通过鉴定扩展链的大小和识别序列的身份来表征固定的核酸。
    • 18. 发明授权
    • Categorising nucleic acid
    • 分类核酸
    • US06670120B1
    • 2003-12-30
    • US09462635
    • 2000-04-10
    • Günter SchmidtAndrew Hugin Thompson
    • Günter SchmidtAndrew Hugin Thompson
    • C12Q168
    • C12Q1/6869C12Q1/6855C12Q2525/155C12Q2521/301
    • The present invention involves a method for categorizing nucleic acid which comprises: producing a nucleic acid population by action of an endonuclease on double-stranded nucleic acid, such that each nucleic acid in the nucleic acid population has a double-stranded portion; contacting the nucleic acid population with one or more oligonucleotide sequences; and isolating nucleic acid which correctly hybridizes to an oligonucleotide sequence. In the method of the present invention, each oligonucleotide sequence has a pre-determined recognition sequence. Furthermore, the nucleic acid is categorized by its ability to correctly hybridize to oligonucleotide sequences having the recognition sequence, the recognition sequence being situated such that it recognizes a sequence in the double-stranded portion of the nucleic acid. The oligonucleotide sequence can comprise one or more different recognition sequences.
    • 本发明涉及一种用于分类核酸的方法,其包括:通过内切核酸酶在双链核酸上的作用产生核酸群体,使得核酸群体中的每个核酸具有双链部分; 使核酸群体与一个或多个寡核苷酸序列接触; 并分离与寡核苷酸序列正确杂交的核酸。 在本发明的方法中,每个寡核苷酸序列具有预定的识别序列。 此外,核酸通过其与具有识别序列的寡核苷酸序列正确杂交的能力分类,识别序列位于使其识别核酸双链部分中的序列。 寡核苷酸序列可以包含一个或多个不同的识别序列。
    • 20. 发明授权
    • Method for characterizing DNA sequences
    • 表征DNA序列的方法
    • US06225077B1
    • 2001-05-01
    • US09254023
    • 1999-04-20
    • Günter SchmidtAndrew Hugin Thompson
    • Günter SchmidtAndrew Hugin Thompson
    • C12Q144
    • C12N15/1096C12Q1/6837C12Q2525/191C12Q2523/107
    • A method for characterizing cDNA, which comprises: (a) cutting a sample comprising a population of one or more cDNAs or isolated fragments thereof, each having a strand complementary to the 3′ poly-A terminus of an mRNA and bearing a tail, with a first sampling endonuclease at a first sampling site of known displacement from a reference site proximal to the tail to generate from each cDNA or isolated fragment thereof a first and second sub-fragment, each comprising a sticky end sequence of predetermined length and unknown sequence, the first sub-fragment bearing the tail; (b) sorting either the first or second sub-fragments into sub-populations according to their sticky end sequence and recording the sticky end sequence of each sub-population as the first sticky end; (c) cutting the sub-fragments of each sub-population with a second sampling endonuclease, which is the same as or different from the first sampling endonuclease, at second sampling site of known displacement from the first sampling site to generate from each sub-fragment a further sub-fragment comprising a second sticky end sequence of predetermined length and unknown sequence; and (d) determining each second sticky end sequence; wherein the aggregate length of the first and second sticky end sequences of each sub-fragment is from 6 to 10; and wherein the sequences and relative positions of the reference site and first and second sticky ends are utilized to characterize said cDNA or cDNAs.
    • 一种用于表征cDNA的方法,其包括:(a)切割包含一个或多个cDNA群体或其分离片段的样品,每个cDNA或其分离的片段具有与mRNA的3'poly-A末端互补的并具有尾部的链, 在距离参考站点近尾的已知置换的第一采样位点处的第一取样内切核酸酶从每个cDNA或其分离的片段产生第一和第二子片段,每个子片段包含预定长度和未知序列的粘性末端序列, 第一个带有尾巴的子片段; (b)根据第一或第二子片段的粘性末端序列将第一或第二子片段分成亚群,并记录每个子群体的粘性末端序列作为第一粘性末端; (c)在具有与第一采样内切核酸酶相同或不同于第一取样内切核酸酶的第二取样内切核酸酶切割每个亚群体的亚片段时, 将包含预定长度和未知序列的第二粘性末端序列的另外的子片段片段化; 和(d)确定每个第二粘性末端序列; 其中每个子片段的第一和第二粘性末端序列的聚合长度为6至10; 并且其中使用参考部位和第一和第二粘性末端的序列和相对位置来表征所述cDNA或cDNA。