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1. 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。

2. 发明授权

US5047318A Imidazole leuco dye composition containing 4'-hydroxyacetanilide, diagnostic kit and method using same 失效
标题翻译：含有4'-羟基乙酰替苯胺的咪唑无色染料组合物，诊断试剂盒及其使用方法
公开(公告)号：US5047318A
公开(公告)日：1991-09-10
申请号：US206258
申请日：1988-06-13
申请人： Brian A. Snyder , Harold C. Warren, III , Gregory J. McClune
发明人： Brian A. Snyder , Harold C. Warren, III , Gregory J. McClune
IPC分类号： G01N33/531 , C12Q1/28 , G01N33/535 , G01N33/536 , G01N33/569 , G01N33/571
CPC分类号： G01N33/571 , C12Q1/28 , G01N33/56911 , C12Q2326/00 , Y10S435/971 , Y10S436/824
摘要： A dye-providing composition is useful in various diagnostic assays wherein a peroxidase-labeled specific binding species is used. This composition is substantially free of peroxidase and such labeled species, and comprises an imidazole leuco dye and 4'-hydroxyacetanilide present in an amount up to about 2.5 mmolar. This composition can be included as part of a diagnostic test kit.

3. 发明授权

US4828978A Agglutination reagent and method of preparing same 失效
标题翻译：凝集试剂及其制备方法
公开(公告)号：US4828978A
公开(公告)日：1989-05-09
申请号：US98432
申请日：1987-09-18
申请人： Harold C. Warren, III , Brian A. Snyder
发明人： Harold C. Warren, III , Brian A. Snyder
IPC分类号： G01N33/543
CPC分类号： G01N33/54313 , Y10S436/818
摘要： An agglutination reagent is prepared by covalently attaching an immunoreactive species to polymeric particles through reactive groups in the species. After attachment, the species is chemically modified with an acylating, alkylating or sulfonylating agent thereby modifying primary or secondary amino groups. The reagent can be used in agglutination assays for a number of analytes, inclusing Streptococcus A antigen, human retroviruses or antibodies, human chorionic gonadotropin and other antibodies or antigens.
摘要翻译：通过将物种中的反应性基团将免疫反应性物质共价连接到聚合物颗粒上来制备凝集试剂。附着后，该物质用酰化，烷基化或磺酰化剂进行化学修饰，从而修饰伯或仲氨基。试剂可用于多种分析物的凝集测定，包括A型链球菌抗原，人类逆转录病毒或抗体，人绒毛膜促性腺激素和其他抗体或抗原。

4. 发明授权

US4812414A Immunoreactive reagent particles having tracer, receptor molecules and protein of pI less than 6 失效
标题翻译：具有示踪剂，受体分子和pI小于6的蛋白质的免疫反应性试剂颗粒
公开(公告)号：US4812414A
公开(公告)日：1989-03-14
申请号：US98250
申请日：1987-09-18
申请人： Harold C. Warren, III , Brian A. Snyder
发明人： Harold C. Warren, III , Brian A. Snyder
IPC分类号： G01N33/543 , G01N33/546 , G01N33/547 , G01N33/569
CPC分类号： G01N33/54313 , Y10S436/825
摘要： A reagent useful in the determination of an immunoreactive species comprises water-insoluble particles having tracer molecules associated therewith. Bound to the outer surface of the particles are: (i) receptor molecules which are reactive with the species, and (ii) molecules of a protein having a pI less than about 6, and which protein is not reactive with either the species or the receptor molecules. The weight ratio of the receptor molecules to the low pI protein molecules is from about 100:1 to about 1:10. This reagent is useful in agglutination and other immunological reactions. A method of preparing the reagent includes providing a suspension of the particles and contacting them with the receptor molecules and low pI protein so as to attach both to the particles. The protein is present in the suspension in an amount such that substantially all of it is attached to the particles. The reagent thus prepared can be used, for example, in agglutination assays for the determination of a multivalent immunoreactive species, such as Streptococcus A antigen.
摘要翻译：可用于测定免疫反应性物质的试剂包括具有与其相关的示踪分子的水不溶性颗粒。与颗粒的外表面结合是：（i）与物质反应的受体分子，和（ii）pI小于约6的蛋白质的分子，并且哪种蛋白质不与物种或受体分子。受体分子与低pI蛋白质分子的重量比为约100:1至约1:10。该试剂可用于凝集和其他免疫反应。制备试剂的方法包括提供颗粒的悬浮液并使其与受体分子和低pI蛋白质接触，以便将它们附着到颗粒上。蛋白质以一定量使其存在于悬浮液中，使得其基本上全部附着于颗粒。如此制备的试剂可以用于例如用于测定多价免疫反应物质例如链球菌A抗原的凝集测定。

5. 发明授权

US5051356A Specific binding composition comprising a low pI protein or carbohydrate and a diagnostic test kit and method of use 失效
标题翻译：包含低pI蛋白或碳水化合物的特异性结合组合物和诊断测试试剂盒及其使用方法
公开(公告)号：US5051356A
公开(公告)日：1991-09-24
申请号：US206257
申请日：1988-06-13
申请人： Harold C. Warren, III , Brian A. Snyder
发明人： Harold C. Warren, III , Brian A. Snyder
IPC分类号： G01N33/531 , G01N33/53 , G01N33/536 , G01N33/569
CPC分类号： G01N33/56944 , G01N33/53 , Y10S435/962 , Y10S435/975 , Y10S436/808
摘要： A specific binding composition comprises a specific binding species and one or more water-soluble proteins or carbohydrates, substantially none of which has a pI greater than about 5. This composition provides improved sensitivity with lower background in diagnostic tests. Preferably, the species is labeled for detection, for example, with an exzyme. The composition can be included with a dye-providing composition in a diagnostic test kit for use in diagnostic methods.

6. 发明授权

US4828980A Membrane structure coated with low pI protein or carbohydrate and methods of making and use 失效
标题翻译：涂有低pI蛋白或碳水化合物的膜结构及制造和使用方法
公开(公告)号：US4828980A
公开(公告)日：1989-05-09
申请号：US98433
申请日：1987-09-18
申请人： Brian A. Snyder , Harold C. Warren, III , Roger W. Nelson
发明人： Brian A. Snyder , Harold C. Warren, III , Roger W. Nelson
IPC分类号： B01D67/00 , G01N33/543 , G01N33/544 , G01N33/548
CPC分类号： B01D67/0088 , G01N33/54393 , G01N33/544 , G01N33/548 , Y10S436/807 , Y10S436/824 , Y10T428/249978 , Y10T428/249979 , Y10T428/24998
摘要： A membrane structure useful in filtration and diagnostic tests includes a microporous membrane formed from a biologically inert material, such as a polyamide, and has a coating comprising one or more water-soluble proteins or carbohydrates. None of the proteins and carbohydrates in the coating has a pI greater than about 5. The membrane structure is prepared by contacting the microporous membrane with the appropriate protein or carbohydrate in an amount sufficient to provide a coating over the entire membrane surface without substantially diminishing the porosity of the membrane. The membrane structure is useful in various diagnostic test procedures, such as agglutination assays.
摘要翻译：用于过滤和诊断测试的膜结构包括由生物惰性材料（例如聚酰胺）形成的微孔膜，并且具有包含一种或多种水溶性蛋白质或碳水化合物的涂层。涂层中的蛋白质和碳水化合物中没有一个pI大于约5.膜结构通过使微孔膜与适当的蛋白质或碳水化合物接触而制备，其量足以在整个膜表面上提供涂层，而基本上不会减少膜的孔隙率。膜结构可用于各种诊断测试程序，例如凝集测定。

7. 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。

8. 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。

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

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.

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