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1. 发明申请

WO1997041442A1 CHEMILUMINESCENT COMPOSITIONS AND THEIR USE IN THE DETECTION OF HYDROGEN PEROXIDE 审中-公开
标题翻译：亮氨酸组合物及其在过氧化氢检测中的应用
公开(公告)号：WO1997041442A1
公开(公告)日：1997-11-06
申请号：PCT/US1997007265
申请日：1997-05-01
申请人： BEHRINGWERKE AKTIENGESELLSCHAFT , ULLMAN, Edwin, F.
发明人： BEHRINGWERKE AKTIENGESELLSCHAFT , SINGH, Sharat
IPC分类号： G01N33/58
CPC分类号： G01N33/5432 , C12Q1/28 , G01N33/582 , G01N33/585
摘要： Compositions, methods and kits are disclosed. The compositions comprise a matrix having incorporated therein a label capable of being modified by singlet oxygen. A catalyst capable of catalyzing the formation of singlet oxygen is bound to the matrix, which permits the diffusion of singlet oxygen therein. The compositions may be used in methods for detecting hydrogen peroxide or a compound capable of generating hydrogen peroxide. A sample suspected of containing such compound is combined with a composition in accordance with the present invention. The combination is subjected to conditions wherein such compound generates hydrogen peroxide. The reaction of singlet oxygen with the label is determined, the reaction thereof indicating the presence of the compound capable of generating hydrogen peroxide.
摘要翻译：公开了组合物，方法和试剂盒。组合物包含其中掺入能够被单线态氧改性的标签的基质。能够催化单线态氧的形成的催化剂与基体结合，这允许单线态氧的扩散。该组合物可用于检测过氧化氢或能够产生过氧化氢的化合物的方法。怀疑含有这种化合物的样品与根据本发明的组合物组合。该组合经受其中这种化合物产生过氧化氢的条件。确定单线态氧与标记物的反应，其反应表明存在能够产生过氧化氢的化合物。

2. 发明申请

WO1996009552A1 METHOD FOR DETECTING ANTIBODIES 审中-公开
标题翻译：检测抗体的方法
公开(公告)号：WO1996009552A1
公开(公告)日：1996-03-28
申请号：PCT/US1995011665
申请日：1995-09-20
申请人： BEHRINGWERKE AKTIENGESELLSCHAFT , ULLMAN, Edwin, F.
发明人： BEHRINGWERKE AKTIENGESELLSCHAFT , VOLD, Barbara, S. , METHA, Harshvardhan, B.
IPC分类号： G01N33/68
CPC分类号： G01N33/54306 , G01N33/573 , Y10S435/962 , Y10S435/971 , Y10S435/975
摘要： This invention pertains to methods to detect antibodies in a sample. The methods use as amount of antigen that is up to 1000, preferably 10 to 100 times the minimum amount antigen that can be reliably detected and that is less than the maximum expected amount of antibodies in the sample. An antigen: antibody complex is formed and becomes bound to a binding agent that does not bind free antigen. The free antigen is then detected as a measure of antibodies present in the sample.
摘要翻译：本发明涉及检测样品中抗体的方法。该方法使用的抗原量高达1000，优选为可靠检测的最小量抗原的10至100倍，并且小于样品中抗体的最大预期量。形成抗原：抗体复合物并结合到不结合游离抗原的结合剂。然后检测游离抗原作为样品中存在的抗体的量度。

3. 发明申请

WO1997023647A1 HOMOGENEOUS AMPLIFICATION AND DETECTION OF NUCLEIC ACIDS 审中-公开
标题翻译：均质放大和核酸检测
公开(公告)号：WO1997023647A1
公开(公告)日：1997-07-03
申请号：PCT/US1996019751
申请日：1996-12-20
申请人： BEHRINGWERKE AKTIENGESELLSCHAFT , ULLMAN, Edwin, F.
发明人： BEHRINGWERKE AKTIENGESELLSCHAFT , LIU, Yen, Ping , PATEL, Rajesh, D. , KURN, Nurith , LIN, Claire , ROSE, Samuel, J.
IPC分类号： C12Q01/68
CPC分类号： C12Q1/6816 , C12Q1/6813 , C12Q1/6818 , C12Q1/686 , C12Q2565/113 , C12Q2563/131 , C12Q2525/161 , C12Q2563/149 , C12Q2563/103 , C12Q2537/101 , C12Q2527/107
摘要： The present invention relates to a method for detecting or amplifying and detecting a target polynucleotide sequence. The method comprises providing in combination (i) a medium suspected of containing the target polynucleotide sequence, (ii) all reagents required for conducting an amplification of the target polynucleotide sequence when amplification is desired, and (iii) two oligonucleotide probes capable of binding to a single strand of the product of the amplification. At least one of the probes has two sequences that either (i) are non-contiguous and bind to contiguous or non-contiguous sites on the single strand or (ii) can bind to non-contiguous sites on the single strand. Each probe may contain a label. The combination is subjected to conditions for amplifying the target polynucleotide sequence. Next, the combination is subjected to conditions under which both of the probes hybridize to one of the strands to form a termolecular complex, which is detected by means of the label.
摘要翻译：本发明涉及检测或扩增和检测靶多核苷酸序列的方法。所述方法包括组合（i）怀疑含有靶多核苷酸序列的培养基，（ii）当需要扩增时进行靶多核苷酸序列扩增所需的所有试剂，和（iii）能够结合到单链的扩增产物。至少一个探针具有以下两个序列：（i）不连续并且结合单链上的连续或非连续位点，或（ii）可以结合单链上的非连续位点。每个探针可能包含一个标签。将该组合进行扩增靶多核苷酸序列的条件。接下来，将该组合进行两个探针与其中一条链杂交以形成通过标记检测的分子复合物的条件。

4. 发明申请

WO1997023646A1 DETECTION OF DIFFERENCES IN NUCLEIC ACIDS 审中-公开
标题翻译：检测核酸中的差异
公开(公告)号：WO1997023646A1
公开(公告)日：1997-07-03
申请号：PCT/US1996019750
申请日：1996-12-20
申请人： BEHRINGWERKE AKTIENGESELLSCHAFT , ULLMAN, Edwin, F.
发明人： BEHRINGWERKE AKTIENGESELLSCHAFT , LISHANSKI, Alla , KURN, Nurith
IPC分类号： C12Q01/68
CPC分类号： C12Q1/6823 , C12Q1/6813 , C12Q1/6818 , C12Q1/6827 , Y10S435/808
摘要： A method is disclosed for detecting the presence of a difference between two related nucleic acid sequences. In the method a complex is formed comprising both strands of each sequence. Each member of at least one pair of non-complementary strands within the complex has labels. The association of the labels as part of the complex is determined as an indication of the presence of a difference between the two related sequences. The complex generally comprises a Holliday junction. In one aspect a medium suspected of containing said two related nucleic acid sequences is treated to provide partial duplexes having non-complementary tailed portions at one end. The double stranded portions of the partial duplexes are identical except for said difference. One of the strands of one of the partial duplexes is complementary to one of the strands of the other of the partial duplexes and the other of the strands of one of the partial duplexes is complementary to the other of the strands of the other of the partial duplexes. The medium is subjected to conditions that permit the binding of the tailed portions of the partial duplexes to each other. If there is a difference in the related nucleic acid sequences, a stable complex is formed comprising a Holliday junction. If no difference exists, the complex dissociates into duplexes. A determination is made whether the stable complex is formed, the presence thereof indicating the presence of the related nucleic acid sequences. The method has application in detecting the presence of a mutation in a target sequence or in detecting the target sequence itself.
摘要翻译：公开了一种用于检测两个相关核酸序列之间的差异的存在的方法。在该方法中，形成包含每个序列的两条链的复合物。复合体内至少一对非互补链的每个成员具有标签。作为复合物的一部分的标记的关联被确定为两个相关序列之间存在差异的指示。该综合体通常包括一个Holliday连接点。在一个方面，处理怀疑含有所述两个相关核酸序列的介质以提供在一端具有非互补尾部的部分双链体。除了所述差异之外，部分双链体的双链部分是相同的。部分双链体之一的链之一与部分双链体中另一个的一条链互补，并且部分双链体之一的其中一条链与另一部分双链体的另一条链互补双链。该介质经受允许部分双链体的尾部与彼此结合的条件。如果相关核酸序列存在差异，则形成包含Holliday结的稳定复合物。如果没有差异，复合物解离成双链体。确定稳定复合物是否形成，其存在表明存在相关的核酸序列。该方法可用于检测靶序列中突变的存在或检测靶序列本身。

5. 发明申请

WO1996040999A1 DETECTION OF NUCLEIC ACIDS BY FORMATION OF TEMPLATE-DEPENDENT PRODUCT 审中-公开
标题翻译：通过形成模板相关产品检测核酸
公开(公告)号：WO1996040999A1
公开(公告)日：1996-12-19
申请号：PCT/US1996008601
申请日：1996-06-05
申请人： BEHRINGWERKE AKTIENGESELLSCHAFT , ULLMAN, Edwin, F.
发明人： BEHRINGWERKE AKTIENGESELLSCHAFT , WESTERN, Linda, Marie , ROSE, Samuel, J.
IPC分类号： C12Q01/68
CPC分类号： C12Q1/6858 , C12Q2535/125
摘要： A method is disclosed for detecting a target polynucleotide sequence. The method comprises incubating an oligonucleotide with the target polynucleotide sequence and a nucleotide polymerase under isothermal conditions wherein at least one nucleotide is added to the 3'-terminus of the oligonucleotide to provide an extended oligonucleotide having the additional nucleotides. The presence of extended oligonucleotide is detected as an indication of the presence of the target polynucleotide sequence. The method has particular application to the detection of DNA.
摘要翻译：公开了一种用于检测靶多核苷酸序列的方法。该方法包括在等温条件下将寡核苷酸与靶多核苷酸序列和核苷酸聚合酶一起温育，其中至少一个核苷酸加入到寡核苷酸的3'末端以提供具有额外核苷酸的延伸寡核苷酸。检测到延伸寡核苷酸的存在作为靶多核苷酸序列存在的指示。该方法特别适用于检测DNA。

6. 发明申请

WO9620287A3 DETECTION OF NUCLEIC ACIDS BY TARGET-CATALYZED PRODUCT FORMATION 审中-公开
标题翻译：通过目标催化产物形成检测核酸
公开(公告)号：WO9620287A3
公开(公告)日：1996-09-06
申请号：PCT/US9516771
申请日：1995-12-22
申请人： BEHRINGWERKE AG , ULLMAN EDWIN F
发明人： ULLMAN EDWIN F , WESTERN LINDA M , ROSE SAMUEL J
IPC分类号： C12Q1/68 , C12Q1/44
CPC分类号： C12Q1/689 , C12Q1/682 , C12Q1/6823 , C12Q2521/319 , C12Q2537/149 , C12Q2521/301 , C12Q2563/101
摘要： A method is disclosed for modifying an oligonucleotide, which method has application to the detection of a polynucleotide analyte. An oligonucleotide is reversibly hybridized with a polynucleotide, for example, a polynucleotide analyte, in the presence of a 5'-nuclease under isothermal conditions. The polynucleotide analyte serves as a recognition element to enable a 5'-nuclease to cleave the oligonucleotide to provide (i) a first fragment that is substantially non-hybridizable to the polynucleotide analyte and (ii) a second fragment that lies 3' of the first fragment (in the intact oligonucleotide) and is substantially hybridizable to the polynucleotide analyte. At least a 100-fold molar excess of the first fragment and/or the second fragment are obtained relative to the molar amount of the polynucleotide analyte. The presence of the first fragment and/or the second fragment is detected, the presence thereof indicating the presence of the polynucleotide analyte. The method has particular application to the detection of a polynucleotide analyte such as DNA. Kits for conducting methods in accordance with the present invention are also disclosed. 00000
摘要翻译：公开了一种修饰寡核苷酸的方法，该方法可用于检测多核苷酸分析物。在等温条件下，在5'-核酸酶的存在下，寡核苷酸与多核苷酸例如多核苷酸分析物可逆地杂交。多核苷酸分析物用作识别元件，以使5'-核酸酶切割寡核苷酸以提供（i）与多核苷酸分析物基本上不可杂交的第一片段和（ii）位于第一片段（在完整寡核苷酸中）并且与多核苷酸分析物基本上可杂交。相对于多核苷酸分析物的摩尔量，获得至少100倍摩尔过量的第一片段和/或第二片段。检测到第一片段和/或第二片段的存在，其存在表明多核苷酸分析物的存在。该方法特别适用于多核苷酸分析物如DNA的检测。还公开了用于根据本发明的方法的套件。 00000

7. 发明申请

WO1996020287A2 DETECTION OF NUCLEIC ACIDS BY TARGET-CATALYZED PRODUCT FORMATION 审中-公开
标题翻译：通过目标催化产物形成检测核酸
公开(公告)号：WO1996020287A2
公开(公告)日：1996-07-04
申请号：PCT/US1995016771
申请日：1995-12-22
申请人： BEHRINGWERKE AKTIENGESELLSCHAFT , ULLMAN, Edwin, F.
发明人： BEHRINGWERKE AKTIENGESELLSCHAFT , WESTERN, Linda, M. , ROSE, Samuel, J.
IPC分类号： C12Q01/68
CPC分类号： C12Q1/689 , C12Q1/682 , C12Q1/6823 , C12Q2521/319 , C12Q2537/149 , C12Q2521/301 , C12Q2563/101
摘要： A method is disclosed for modifying an oligonucleotide, which method has application to the detection of a polynucleotide analyte. An oligonucleotide is reversibly hybridized with a polynucleotide, for example, a polynucleotide analyte, in the presence of a 5'-nuclease under isothermal conditions. The polynucleotide analyte serves as a recognition element to enable a 5'-nuclease to cleave the oligonucleotide to provide (i) a first fragment that is substantially non-hybridizable to the polynucleotide analyte and (ii) a second fragment that lies 3' of the first fragment (in the intact oligonucleotide) and is substantially hybridizable to the polynucleotide analyte. At least a 100-fold molar excess of the first fragment and/or the second fragment are obtained relative to the molar amount of the polynucleotide analyte. The presence of the first fragment and/or the second fragment is detected, the presence thereof indicating the presence of the polynucleotide analyte. The method has particular application to the detection of a polynucleotide analyte such as DNA. Kits for conducting methods in accordance with the present invention are also disclosed.
摘要翻译：公开了一种修饰寡核苷酸的方法，该方法可用于检测多核苷酸分析物。在等温条件下，在5'-核酸酶的存在下，寡核苷酸与多核苷酸例如多核苷酸分析物可逆地杂交。多核苷酸分析物用作识别元件，以使5'-核酸酶切割寡核苷酸以提供（i）与多核苷酸分析物基本上不可杂交的第一片段和（ii）位于第一片段（在完整寡核苷酸中）并且与多核苷酸分析物基本上可杂交。相对于多核苷酸分析物的摩尔量，获得至少100倍摩尔过量的第一片段和/或第二片段。检测到第一片段和/或第二片段的存在，其存在表明多核苷酸分析物的存在。该方法特别适用于多核苷酸分析物如DNA的检测。还公开了用于根据本发明的方法的套件。

8. 发明申请

WO1998028443A1 METHOD FOR POLYNUCLEOTIDE AMPLIFICATION 审中-公开
标题翻译：多核苷酸扩增方法
公开(公告)号：WO1998028443A1
公开(公告)日：1998-07-02
申请号：PCT/US1997023706
申请日：1997-12-17
申请人： DADE BEHRING MARBURG GMBH , ULLMAN, Edwin, F.
发明人： DADE BEHRING MARBURG GMBH , LISHANSKI, Alla , KURN, Nurith
IPC分类号： C12Q01/68
CPC分类号： C12Q1/6848 , C12Q2525/186 , C12Q2525/161 , C12Q2521/325
摘要： The present invention relates to a method for selectively extending an oligonucleotide primer along a specific target polynucleotide sequence in a mixture of polynucleotides. The method comprises providing the modified oligonucleotide having a 3'-end that is not extendable along any polynucleotide and extending the oligonucleotide primer selectively along the specific target polynucleotide sequence by controlling the degradation of the 3'-end of the modified oligonucleotide. In this way extension along polynucleotides other than the specific target polynucleotide sequence is substantially reduced or avoided. In another aspect the invention is an improvement in a method for amplifying a target polynucleotide sequence. The improvement comprises deriving the oligonucleotide primer from a modified oligonucleotide having a portion that hybridizes to the target polynucleotide sequence except for the 3'-end thereof, which has at least one nucleotide analog that is incapable of hybridizing to a polyuncleotide. Kits for carrying out the above methods are also disclosed.
摘要翻译：本发明涉及在多核苷酸的混合物中选择性延伸寡核苷酸引物沿着特异性目标多核苷酸序列的方法。该方法包括提供具有3'端的修饰寡核苷酸，其不能沿着任何多核苷酸延伸，并通过控制修饰寡核苷酸的3'末端的降解，沿特异性靶多核苷酸序列选择性延伸寡核苷酸引物。以这种方式，除特异性靶多核苷酸序列以外的多核苷酸的延伸被显着降低或避免。在另一方面，本发明是扩增靶多核苷酸序列的方法的改进。该改进包括从具有至少一个不能与多核苷酸杂交的核苷酸类似物的除3'-末端以外的靶多核苷酸序列杂交的部分修饰的寡核苷酸导出寡核苷酸引物。还公开了用于实施上述方法的套件。

9. 发明申请

WO1996041000A1 INTERNAL POSITIVE CONTROLS FOR NUCLEIC ACID AMPLIFICATION 审中-公开
标题翻译：用于核酸放大的内部积极控制
公开(公告)号：WO1996041000A1
公开(公告)日：1996-12-19
申请号：PCT/US1996008602
申请日：1996-06-05
申请人： BEHRINGWERKE AKTIENGESELLSCHAFT , ULLMAN, Edwin, F.
发明人： BEHRINGWERKE AKTIENGESELLSCHAFT , WESTERN, Linda, Marie , ROSE, Samuel, J.
IPC分类号： C12Q01/68
CPC分类号： C12Q1/6848 , C12Q2545/107 , C12Q2537/163 , C12Q2525/301
摘要： The present invention relates to an improvement in a method for amplifying a target sequence of a target polynucleotide. The method comprises combining a sample suspected of containing the target polynucleotide with reagents for amplifying the target sequence and subjecting the combination to conditions wherein the target sequence if present is amplified. The present improvement comprises including in the combination a control oligonucleotide and a control polynucleotide that has a sequence that is hybridizable with the control oligonucleotide. When the control oligonucleotide is bound to the control polynucleotide, the ability of a primer to chain extend along the control polynucleotide is reduced. Optionally, the control oligonucleotide is part of the control polynucleotide. The method finds particular application in the area of nucleic acid amplification and detection.
摘要翻译：本发明涉及扩增目标多核苷酸的靶序列的方法的改进。该方法包括将怀疑含有目标多聚核苷酸的样品与用于扩增靶序列的试剂结合，并使该组合进行其中如果存在的靶序列被扩增的条件。本发明的改进包括控制寡核苷酸和具有可与对照寡核苷酸杂交的序列的对照多核苷酸的组合。当对照寡核苷酸与对照多核苷酸结合时，引物向对照多核苷酸延伸的链的能力降低。任选地，对照寡核苷酸是对照多核苷酸的一部分。该方法在核酸扩增和检测领域具有特殊应用。

10. 发明申请

WO1996002672A1 METHOD FOR PREVENTING AMPLIFICATION OF NUCLEIC ACID CONTAMINANTS IN AMPLIFICATION MIXTURES 审中-公开
标题翻译：在放大混合物中防止核酸污染物放大的方法
公开(公告)号：WO1996002672A1
公开(公告)日：1996-02-01
申请号：PCT/US1995008782
申请日：1995-07-18
申请人： BEHRINGWERKE AKTIENGESELLSCHAFT , ULLMAN, Edwin, F.
发明人： BEHRINGWERKE AKTIENGESELLSCHAFT , CHEN, Yan , ROSE, Samuel, J.
IPC分类号： C12Q01/68
CPC分类号： C12Q1/6848 , C12Q2525/197 , C12Q2521/301
摘要： Methods and kits are disclosed for preventing amplification of contaminating copies of nucleic acids during amplification of a nucleic acid suspected of being present in a sample. Modified nucleotides that render copies of the nucleic acid bindable by a member of a specific binding pair, such as a receptor, which does not bind to the nucleic acid, are incorporated into copies of the nucleic acid that are produced during the amplification. The sample is combined with an enzyme conjugate, usually a receptor bound to a nuclease, under conditions wherein prior to the amplification the member of a specific binding pair binds to the copies and the enzyme degrades the copies but not the nucleic acid. The methods and kits have particular application to the determination of a nucleic acid analyte.
摘要翻译：公开了用于在怀疑存在于样品中的核酸扩增期间防止扩增核酸污染拷贝的方法和试剂盒。通过特异性结合对的成员（例如不与核酸结合的受体）结合核酸的拷贝的修饰的核苷酸被并入在扩增过程中产生的核酸的拷贝中。样品与酶缀合物（通常是与核酸酶结合的受体）在条件下结合，在扩增前，特异性结合对的成员与拷贝结合，并且酶降解拷贝而不是核酸。所述方法和试剂盒特别适用于测定核酸分析物。

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