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1. 发明授权

US5262297A Specific binding analytical and separation methods using carboxy containing polymers 失效
标题翻译：使用含羧基聚合物的特异性结合分析和分离方法
公开(公告)号：US5262297A
公开(公告)日：1993-11-16
申请号：US876672
申请日：1992-04-30
申请人： Richard C. Sutton , Susan J. Danielson , John B. Findlay , Fred. T. Oakes , Marsha D. B. Oenick , Ignazio S. Ponticello , Harold C. Warren, III
发明人： Richard C. Sutton , Susan J. Danielson , John B. Findlay , Fred. T. Oakes , Marsha D. B. Oenick , Ignazio S. Ponticello , Harold C. Warren, III
IPC分类号： C12Q1/68 , C12Q1/70 , G01N33/543 , G01N33/545 , G01N83/545 , G01N33/546 , G01N33/547
CPC分类号： G01N33/54313 , C12Q1/6876 , C12Q1/701 , C12Q1/703 , G01N33/545 , Y10S436/804 , Y10S436/814 , Y10S436/817 , Y10S436/818 , Y10S436/824
摘要： Specific binding methods are used for diagnostic assays and purification separations whereby the specific binding capture reagent is prepared from copolymers having highly reactive carboxy groups. These groups are extended from the polymer surface with a linking group having from 8 to 50 atoms in the chain and two or more alkylene, arylene, alkylenearylene or arylenealkylene groups. To these reactive groups is attached a biologically active substance such as a protein or oligonucleotide which then participates in the diagnostic assays or purification separation methods.
摘要翻译：特异性结合方法用于诊断测定和纯化分离，由此特异性结合捕获试剂由具有高反应性羧基的共聚物制备。这些基团从聚合物表面延伸，在链中具有8至50个原子的连接基团和两个或更多个亚烷基，亚芳基，亚烷基亚芳基或亚芳基亚烷基。将这些反应性基团连接到生物活性物质如蛋白质或寡核苷酸上，然后参与诊断测定或纯化分离方法。

2. 发明授权

US5147777A Biologically active reagents prepared from carboxy-containing polymer, analytical element and methods of use 失效
标题翻译：含羧基聚合物制备的生物活性试剂，分析元素和使用方法
公开(公告)号：US5147777A
公开(公告)日：1992-09-15
申请号：US539774
申请日：1990-06-18
申请人： Richard C. Sutton , Susan J. Danielson , John B. Findlay , Fred T. Oakes , Marsha D. B. Oenick , Ignazio S. Ponticello , Harold C. Warren, III
发明人： Richard C. Sutton , Susan J. Danielson , John B. Findlay , Fred T. Oakes , Marsha D. B. Oenick , Ignazio S. Ponticello , Harold C. Warren, III
IPC分类号： C08F8/00 , C08F246/00 , C12Q1/68 , C12Q1/70 , G01N33/53 , G01N33/543 , G01N33/545
CPC分类号： G01N33/54313 , C12Q1/6876 , C12Q1/701 , C12Q1/703 , G01N33/545 , Y10S436/805 , Y10T428/2991 , Y10T428/2998
摘要： Biologically active reagents are prepared from particles of copolymers having highly reactive carboxy or equivalent groups. The reagents are prepared by covalently attaching biologically active substances, for example antibodies, to the particles, directly or indirectly through highly reactive carboxy groups on the particle surface. These reagents are used to advantage in analytical elements, methods for the detection of specific binding ligands (such as immunological species) and immunoassays, and in purification methods as affinity chromatography reagents.

3. 发明授权

US5374516A Avidin-and biotin immobilized reagents and methods of use 失效
标题翻译：抗生物素蛋白和生物素固定化试剂及使用方法
公开(公告)号：US5374516A
公开(公告)日：1994-12-20
申请号：US315086
申请日：1989-02-24
申请人： Richard C. Sutton , Brent A. Burdick , Susan J. Danielson , Harold C. Warren, III , Brian A. Snyder , Gregory J. McClune , Annie L. Wu
发明人： Richard C. Sutton , Brent A. Burdick , Susan J. Danielson , Harold C. Warren, III , Brian A. Snyder , Gregory J. McClune , Annie L. Wu
IPC分类号： G01N33/543 , G01N33/545 , G01N33/546
CPC分类号： G01N33/54306 , G01N33/54313 , G01N33/545 , Y10T428/2991 , Y10T428/2998
摘要： Reagents have been prepared from water-insoluble polymeric particles to which are covalently attached avidin, biotin or an avidin or biotin derivative. The polymeric particles comprise a polymer on at least the outer surface which is derived from at least one ethylenically unsaturated monomer having a reactive activated 2-substituted ethylsulfonyl, vinylsulfonyl or active halogen atom. Covalent attachment of avidin, biotin or an avidin or biotin derivative is effected either directly or indirectly through these reactive groups. The resulting reagent is useful in analytical elements and various analytical methods including agglutination and sandwich assays. The immobilized avidin, biotin or derivative can be used to complex with the corresponding biotin or avidin molecule which may be conjugated to a compound of biological interest.
摘要翻译：试剂由水不溶性聚合物颗粒制备，共价连接的抗生物素蛋白，生物素或抗生物素蛋白或生物素衍生物。聚合物颗粒在至少外表面上包含衍生自至少一种具有反应性活化的2-取代的乙基磺酰基，乙烯基磺酰基或活性卤素原子的烯属不饱和单体的聚合物。亲和素，生物素或抗生物素蛋白或生物素衍生物的共价连接通过这些反应性基团直接或间接地实现。所得试剂可用于分析元件和各种分析方法，包括凝集和夹心测定。固定的抗生物素蛋白，生物素或衍生物可用于与可能与生物学兴趣的化合物缀合的相应生物素或抗生物素蛋白分子复合。

4. 发明授权

US5082780A Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures 失效
标题翻译：可用于混合测定和聚合酶链反应步骤中的探针的寡糖 - 酶联合
公开(公告)号：US5082780A
公开(公告)日：1992-01-21
申请号：US406224
申请日：1989-09-12
申请人： Harold C. Warren, III , Fred T. Oakes
发明人： Harold C. Warren, III , Fred T. Oakes
IPC分类号： C12N9/00 , C07H21/00 , C12N15/09 , C12Q1/68
CPC分类号： C07H21/00
摘要： A covalent conjugate of an enzyme, such as peroxidase, glucose oxidase, alkaline phosphatase and beta-galactosidase, and an oligonucleotide is herein disclosed. This conjugate can be used as a probe in hybridization assays and in polymerase chain reaction procedures.

5. 发明授权

US5272077A Method for preparing a covalent conjugate of an oligonucleotide and an enzyme 失效
标题翻译：制备寡核苷酸和酶的共价缀合物的方法
公开(公告)号：US5272077A
公开(公告)日：1993-12-21
申请号：US58723
申请日：1993-05-10
申请人： Harold C. Warren, III , Fred T. Oakes
发明人： Harold C. Warren, III , Fred T. Oakes
IPC分类号： C07H21/00 , C12N9/96 , C12N9/04 , C12N9/06 , C12N9/08
CPC分类号： C07H21/00
摘要： A method is provided for preparing a covalent conjugate of an oligonucleotide and an enzyme, such as peroxidase. This conjugate can be used as a probe in hybridization assays and in polymerase chain reaction procedures. The method generally comprises the steps of: reacting an enzyme having a reactive amino group with a mercapto-substituted organic compound to form a blocked intermediate, removing the blocking group to form an enzyme reagent, and reacting the enzyme reagent with a functionalized oligonucleotide reagent.
摘要翻译：提供了制备寡核苷酸和酶如过氧化物酶的共价缀合物的方法。该缀合物可用作杂交测定和聚合酶链反应程序中的探针。该方法通常包括以下步骤：使具有反应性氨基的酶与巯基取代的有机化合物反应形成封闭的中间体，除去封闭基团以形成酶试剂，并使酶试剂与官能化的寡核苷酸试剂反应。

6. 发明授权

US5254469A Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures 失效
标题翻译：可用于杂交测定和聚合酶链反应程序中的探针的寡核苷酸 - 酶结合物
公开(公告)号：US5254469A
公开(公告)日：1993-10-19
申请号：US762136
申请日：1991-09-17
申请人： Harold C. Warren, III , Fred T. Oakes
发明人： Harold C. Warren, III , Fred T. Oakes
IPC分类号： C07H21/00 , C12N9/96 , C12N9/04 , C12N9/06 , C12N9/08
CPC分类号： C07H21/00
摘要： A covalent conjugate of an enzyme, such as peroxidase, glucose oxidase, alkaline phosphatase and beta-galactosidase, and an oligonucleotide is herein disclosed. This conjugate can be used as a probe in hybridization assays and in polymerase chain reaction procedures.
摘要翻译：本文公开了酶的共价缀合物，例如过氧化物酶，葡萄糖氧化酶，碱性磷酸酶和β-半乳糖苷酶和寡核苷酸。该缀合物可用作杂交测定和聚合酶链反应程序中的探针。

7. 发明授权

US5328825A Nucleic acid probe, test kit and diagnostic and purification methods 失效
标题翻译：核酸探针，测试试剂盒和诊断和纯化方法
公开(公告)号：US5328825A
公开(公告)日：1994-07-12
申请号：US847447
申请日：1992-03-06
申请人： Harold C. Warren, III , John B. Findlay , Marlene M. King
发明人： Harold C. Warren, III , John B. Findlay , Marlene M. King
IPC分类号： C12N15/09 , C12Q1/68 , C12Q1/70 , G01N33/543 , C07H21/04
CPC分类号： G01N33/54313 , C12Q1/6834 , C12Q1/703
摘要： An oligonucleotide is linked to a particle through a protein or carbohydrate to form a water-insoluble nucleic acid probe. The protein or carbohydrate has a pI of about 6 or less, and has been chemically modified with an acylating, alkylating or sulfonylating agent. The particle surface is substantially free of other proteins or carbohydrates. The probe is useful in various diagnostic and purification methods wherein hybridization of the oligonucleotide with a target nucleic acid is possible. In one instance, the probe can be used to capture a DNA strand which has been amplified using polymerase chain reaction techniques.
摘要翻译：寡核苷酸通过蛋白质或碳水化合物与颗粒连接以形成水不溶性核酸探针。蛋白质或碳水化合物具有约6或更小的pI，并已用酰化，烷基化或磺酰化剂进行化学修饰。颗粒表面基本上不含其他蛋白质或碳水化合物。探针可用于各种诊断和纯化方法，其中寡核苷酸与靶核酸的杂交是可能的。在一个实例中，探针可用于捕获已经使用聚合酶链反应技术扩增的DNA链。

8. 发明授权

US5599715A Lower alcohol sulfate wash solution 失效
标题翻译：低级酒精硫酸盐洗液
公开(公告)号：US5599715A
公开(公告)日：1997-02-04
申请号：US546980
申请日：1990-07-02
申请人： Harold C. Warren, III , Norbert S. Norkus , Margaret J. Smith-Lewis
发明人： Harold C. Warren, III , Norbert S. Norkus , Margaret J. Smith-Lewis
IPC分类号： G01N33/531 , G01N33/537 , G01N33/76 , G01N33/53
CPC分类号： G01N33/76 , G01N33/537 , Y10S435/81 , Y10S435/975 , Y10S436/808 , Y10S436/811 , Y10T436/107497
摘要： An aqueous wash solution is buffered to a pH of from about 5 to about 9 and contains at least about 1.5 weight percent of a compound comprising a lower alcohol sulfate anion having from 6 to 10 carbon atoms and an alkali metal or ammonium cation, such as sodium decyl sulfate. This wash solution is useful in a method for the determination of an immunological ligand, and is not prone to crystallization at lower temperatures. Particularly, it is useful for washing the immunological complex formed between the ligand and a receptor molecule therefor. Unreacted materials can be readily separated from the complex by the washing, particularly if the separation is carried out using a filtration membrane in a test device. A test kit for ligand determination comprises the wash solution as well as one or more receptors for the ligand, at least one of which is labeled for detection. This kit is particularly useful for measuring human chorionic gonadotropin (hCG) as an early indicator of pregnancy.
摘要翻译：将水性洗涤溶液缓冲至约5至约9的pH，并含有至少约1.5重量％的包含具有6至10个碳原子的低级醇硫酸根阴离子和碱金属或铵阳离子的化合物，例如十二烷基硫酸钠。该洗涤溶液可用于测定免疫配体的方法，并且在较低温度下不易于结晶。特别地，用于洗涤配体和受体分子之间形成的免疫复合物是有用的。未反应的材料可以通过洗涤容易地从络合物中分离，特别是如果在测试装置中使用过滤膜进行分离。用于配体测定的测试试剂盒包括洗涤溶液以及配体的一种或多种受体，其中至少一种被标记用于检测。该试剂盒特别适用于测量人绒毛膜促性腺激素（hCG）作为怀孕的早期指标。

9. 发明授权

US5482831A Wash composition containing signal stop reagent, test kit and method of use with peroxidase-labeled specific binding ligand 失效
标题翻译：含有信号停止剂的洗涤组合物，测试试剂盒和使用过氧化物酶标记的特异性结合配体的方法
公开(公告)号：US5482831A
公开(公告)日：1996-01-09
申请号：US72022
申请日：1993-06-07
申请人： Gary L. Snodgrass , Lisa D. Sprague , Harold C. Warren, III , Douglas R. Jones , Thomas R. Kissel
发明人： Gary L. Snodgrass , Lisa D. Sprague , Harold C. Warren, III , Douglas R. Jones , Thomas R. Kissel
IPC分类号： C11D3/32 , C07C243/38 , C11D17/00 , C12Q1/28 , G01N33/531 , G01N33/535 , C12Q1/68 , B65D69/00 , C12Q1/70 , G01N33/53
CPC分类号： C12Q1/28 , C07C243/38 , G01N33/535 , Y10S435/81 , Y10S435/963 , Y10S435/967 , Y10S435/975
摘要： A buffered composition containing a nonionic or anionic surfactant, and a certain amount of a hydroxamic acid (or salt thereof) or an acyl hydrazine can be used as a wash composition in specific binding assays. Such assays include the use of a peroxidase labeled specific binding reactant to form a detectable peroxidase-labeled specific binding complex. The buffered composition and labeled reactant can be supplied in a diagnostic test kit. The hydroxamic acid or acyl hydrazine can be represented by the structure(I):R--CO--NH--R'wherein R is aryl or 6 to 10 carbon atoms in the aromatic nucleus, alkyl of 1 to 7 carbon atoms, cycloalkyl of 5 to 10 carbon atoms in the ring, or heterocyclyl of 5 to 10 atoms in the ring, at least one of which is an oxygen, nitrogen or sulfur atom, and R' is hydroxy or amino.
摘要翻译：含有非离子或阴离子表面活性剂的缓冲组合物和一定量的异羟肟酸（或其盐）或酰肼可用作特异性结合测定中的洗涤组合物。这种测定包括使用过氧化物酶标记的特异性结合反应物形成可检测的过氧化物酶标记的特异性结合复合物。缓冲的组合物和标记的反应物可以在诊断测试试剂盒中提供。异羟肟酸或酰肼可以由结构式（I）表示：R-CO-NH-R'，其中R是芳族核中的6-10个碳原子，1至7个碳原子的烷基，5个环烷基至10个碳原子，或环中为5至10个原子的杂环基，其中至少一个为氧，氮或硫原子，R'为羟基或氨基。

10. 发明授权

US5344753A Dry analytical element and method for the detection of an aminopeptidase or transpeptidase 失效
标题翻译：用于检测氨基肽酶或转肽酶的干燥分析元件和方法
公开(公告)号：US5344753A
公开(公告)日：1994-09-06
申请号：US891150
申请日：1992-06-01
申请人： John C. Mauck , Harold C. Warren, III , John W. Harder
发明人： John C. Mauck , Harold C. Warren, III , John W. Harder
IPC分类号： C12Q1/37 , C12Q1/48 , G01N33/52 , C12Q1/00 , G01N21/00
CPC分类号： C12Q1/37 , G01N33/523 , G01N33/526 , Y10S435/805
摘要： A dry analytical element has been prepared for the assay of leucine aminopeptidase at a pH of 6.5 to 11. The element zone contains an aromatic substrate for the enzyme. This substrate provides an aromatic reactant which has a primary amino group on the aromatic ring in the ortho or para position to an electron donor group. The aromatic reactant is oxidized with an oxidizing compound (such as an oxidase) and the oxidized compound reacts with a ballasted color-forming coupler to provide a dye.
摘要翻译：已经制备了干燥的分析元件，用于在pH为6.5至11的条件下测定亮氨酸氨基肽酶。元件区含有酶的芳族底物。该底物提供芳族反应物，其在芳环上具有与电子给体基团相邻或对位的伯氨基。芳族反应物用氧化性化合物（例如氧化酶）氧化，氧化的化合物与压色成色剂反应以提供染料。

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