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101. 发明申请

US20050181393A1 Novel chelating agents and highly luminescent and stable chelates and their use 有权
标题翻译：新型螯合剂和高度发光和稳定的螯合物及其用途
公开(公告)号：US20050181393A1
公开(公告)日：2005-08-18
申请号：US11004061
申请日：2004-12-06
申请人： Jari Hovinen , Veli-Matti Mukkala , Harri Hakala , Jari Peuralahti
发明人： Jari Hovinen , Veli-Matti Mukkala , Harri Hakala , Jari Peuralahti
IPC分类号： C07D213/38 , C07D401/14 , C07D471/18 , C07F9/58 , C07F9/6512 , C07F9/6515 , C07F9/6524 , G01N33/532 , C12Q1/68 , C07H21/04
CPC分类号： C07D401/14 , C07D213/38 , C07F9/58 , C07F9/6512 , C07F9/6515 , C07F9/6524 , G01N33/532
摘要： This invention relates to a group of novel chelating agents, novel chelates, biomolecules labeled with said chelates or chelating agents as well as solid supports conjugated with said chelates, chelating agents or labeled biomolecules. Especially the invention relates to novel chelating agents useful in solid phase synthesis of oligonucleotides or oligopeptides and the oligonucleotides and oligopeptides so obtained.
摘要翻译：本发明涉及一组新型螯合剂，新螯合物，用所述螯合物或螯合剂标记的生物分子以及与所述螯合物，螯合剂或标记生物分子缀合的固体支持物。特别地，本发明涉及用于寡核苷酸或寡肽的固相合成的新型螯合剂以及如此获得的寡核苷酸和寡肽。

102. 发明授权

US06913897B2 Kit for conducting an assay to detect a substance using enzymatically-induced decomposition of dioxetanes 失效
标题翻译：用于使用酶促分解二氧杂环丁烷进行测定以检测物质的试剂盒
公开(公告)号：US06913897B2
公开(公告)日：2005-07-05
申请号：US10323667
申请日：2002-12-20
申请人： Irena Y. Bronstein
发明人： Irena Y. Bronstein
IPC分类号： G01N33/532 , C07C43/196 , C07C69/00 , C07D321/00 , C07F9/12 , C07F9/655 , C07F9/6574 , C07H15/203 , C07H15/26 , C12Q1/34 , C12Q1/42 , G01N21/76 , G01N33/533 , G01N33/535 , G01N33/58 , G01N33/76 , G01N33/53 , C07D305/00 , G01N33/537 , G01N33/543
CPC分类号： C07H15/203 , C07D321/00 , C07F9/12 , C07F9/65512 , C07F9/65742 , C07H15/26 , C12Q1/34 , G01N21/76 , G01N33/533 , G01N33/535 , G01N33/581 , G01N33/582 , G01N33/76
摘要： In an assay method in which a member of a specific binding pair is detected by means of an optically detectable reaction, the improvement wherein the optically detectable reaction includes the reaction, with an enzyme, of a dioxetane having the formula where T is a cycloalkyl or polycycloalkyl group bonded to the 4-membered ring portion of the dioxetane by a spiro linkage; Y is a fluorescent chromophore; X is H, alkyl, aryl, aralkyl, alkaryl, heteroalkyl, heteroaryl, cycloalkyl, cycloheteroalkyl, or enzyme-cleavable group; and Z is H or an enzyme-cleavable group, provided that at least one of X or Z must be an enzyme-cleavable group, so that the enzyme cleaves the enzyme-cleavable group from the dioxetane to form a negatively charged substituent bonded to the dioxetane, the negatively charged substituent causing the dioxetane to decompose to form a luminescent substance that includes group Y of said dioxetane.
摘要翻译：在其中通过光学可检测反应检测特异性结合对的成员的测定方法中，其中光学可检测的反应包括与酶具有下式的二氧环乙烷的反应：其中T是环烷基或通过螺键键合到二氧杂环丁烷的4元环部分的多环烷基; Y是荧光发色团; X是H，烷基，芳基，芳烷基，烷芳基，杂烷基，杂芳基，环烷基，环杂烷基或酶切割基团; 并且Z是H或酶切割基团，条件是X或Z中的至少一个必须是酶切割基团，使得酶从二氧杂环丁烷切割酶切割基团以形成键合到二氧杂环丁烷，带负电荷的取代基，导致二氧杂环丁烷分解形成包含所述二氧杂环丁烷的Y基团的发光物质。

103. 发明申请

US20050136491A1 Method of site specific labeling of proteins and uses therefor 审中-公开
标题翻译：蛋白质的位点特异性标记方法及其用途
公开(公告)号：US20050136491A1
公开(公告)日：2005-06-23
申请号：US11013016
申请日：2004-12-15
申请人： Wenfang Chen , Thomas Meek , David Powell , David Tew
发明人： Wenfang Chen , Thomas Meek , David Powell , David Tew
IPC分类号： G01N33/53 , C07K1/02 , C07K14/00 , C12N15/09 , C12P21/02 , C12Q1/02 , G01N21/78 , G01N33/15 , G01N33/50 , G01N33/532 , G01N33/566 , G01N33/58 , G01N33/68 , C07K7/06 , C07K7/08
CPC分类号： G01N33/6845 , C07K1/13 , C07K5/06078 , C07K5/06156 , G01N33/532 , G01N33/68 , G01N33/6842 , G01N33/6848
摘要： Methods for site-specific modification of protein are provided. These methods modify proteins which have been labeled at a particular site by the reaction of a transglutaminase with a glutamine peptide sequence which has been engineered into the protein. The site-specific modification methods of the invention are useful for producing reagents useful in high throughput screening methods and in producing protein delivery vehicles for specifically targeting cellular and non-cellular targets. Also described are improved biotinylation reagents.
摘要翻译：提供蛋白质位点特异性修饰方法。这些方法通过转谷氨酰胺酶与已经工程化成蛋白质的谷氨酰胺肽序列的反应来修饰已经在特定位点被标记的蛋白质。本发明的位点特异性修饰方法可用于生产用于高通量筛选方法的试剂和用于特异性靶向细胞和非细胞靶标的蛋白质递送载体。还描述了改进的生物素化试剂。

104. 发明申请

US20050130243A1 Assay for entactogens 审中-公开
公开(公告)号：US20050130243A1
公开(公告)日：2005-06-16
申请号：US10736004
申请日：2003-12-15
申请人： Yi Zheng , Hshiou-Ting Liu , Yali Yang
发明人： Yi Zheng , Hshiou-Ting Liu , Yali Yang
IPC分类号： A61K39/385 , C07D207/40 , C07D317/48 , C07D317/58 , C07D405/12 , C07K14/47 , C07K16/18 , C07K16/44 , C07K17/06 , G01N33/53 , G01N33/531 , G01N33/532 , G01N33/533 , G01N33/535 , G01N33/537 , G01N33/543 , G01N33/94
CPC分类号： C07D317/48 , C07D317/58 , C07D405/12 , C07K16/44 , G01N33/532 , G01N33/946
摘要： Methods, compositions and kits are disclosed. The methods are directed to determining the presence of entactogen analytes such as, for example, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-methamphetamine (MDMA), 3,4-methylenedioxy-ethylamphetamine (MDEA) and 4-hydroxy-3-methoxy-methamphetamine (HMMA). The method comprises providing in combination in a medium (i) a sample suspected of containing the compound and (ii) an antibody raised against a compound of Formula I that comprises a protein. The medium is examined for the presence a complex comprising the compound and the antibody where the presence of such as complex indicates the presence of the compound in the sample. In one aspect of the above embodiment, the combination further comprises a label conjugate of the compound Formula I.

105. 发明授权

US06902936B2 Acid-labile isotope-coded extractant (ALICE) and its use in quantitative mass spectrometric analysis of protein mixtures 失效
标题翻译：酸不稳定同位素编码提取物（ALICE）及其在蛋白质混合物的定量质谱分析中的应用
公开(公告)号：US06902936B2
公开(公告)日：2005-06-07
申请号：US10045170
申请日：2001-10-22
申请人： Yongchang Qiu , Jack H. Wang , Rodney M. Hewick
发明人： Yongchang Qiu , Jack H. Wang , Rodney M. Hewick
IPC分类号： G01N27/62 , C07D405/12 , G01N1/28 , G01N30/46 , G01N30/72 , G01N30/88 , G01N33/532 , G01N33/58 , G01N33/68 , G01N33/00
CPC分类号： G01N33/6848 , C07D405/12 , G01N30/461 , G01N30/463 , G01N30/468 , G01N30/7233 , G01N33/532 , G01N33/58 , G01N33/6803 , Y10T436/10 , Y10T436/105831 , Y10T436/13 , Y10T436/24 , Y10T436/25125 , B01D15/362 , B01D15/325
摘要： The method of the invention provides novel compounds, termed acid-labile isotope-coded extractants (ALICE), for quantitative mass spectrometric analysis of protein mixtures. The compounds contain a thiol-reactive group that is used to capture cysteine-containing peptides from all peptide mixtures, an acid-labile linker, and a non-biological polymer. One of the two acid-labile linkers is isotopically labeled and therefore enables the direct quantitation of peptides/proteins through mass spectrometric analysis. Because no functional proteins are required to capture peptides, a higher percentage of organic solvent can be used to solubilize the peptides, particularly hydrophobic peptides, through the binding, washing and eluting steps, thus permitting much better recovery of peptides. Moreover, since the peptides are covalently linked to the non-biological polymer (ALICE), more stringent washing is allowed in order to completely remove non-specifically bound species. Finally, peptides captured by ALICE are readily eluted from the polymer support under mild acidic condition with high yield and permit the direct down stream mass spectrometric analysis without any further sample manipulation. In combination with our novel dual column two dimensional liquid chromatography-mass spectrometry (2D-LC-MS/MS) design, the ALICE procedure proves to a general approach for quantitative mass spectrometric analysis of protein mixtures with better dynamic range and sensitivity.
摘要翻译：本发明的方法提供了新的化合物，称为酸不稳定同位素编码的提取物（ALICE），用于蛋白质混合物的定量质谱分析。该化合物含有硫醇反应性基团，其用于从所有肽混合物，酸不稳定接头和非生物聚合物捕获含半胱氨酸的肽。两个酸不稳定接头之一是同位素标记的，因此能够通过质谱分析直接定量肽/蛋白质。由于不需要功能性蛋白来捕获肽，所以可以使用较高百分比的有机溶剂来通过结合，洗涤和洗脱步骤来增溶肽，特别是疏水性肽，从而可以更好地回收肽。此外，由于肽与非生物聚合物（ALICE）共价连接，所以允许更严格的洗涤以完全除去非特异性结合的物质。最后，ALICE捕获的肽在温和的酸性条件下以高产率容易地从聚合物载体上洗脱，并允许直接的下游质谱分析，无需进一步的样品操作。结合我们的双柱二维液相色谱 - 质谱（2D-LC-MS / MS）设计，ALICE方法证明了具有更好的动态范围和灵敏度的蛋白质混合物的定量质谱分析的一般方法。

106. 发明授权

US06890765B2 Particles for immunoassays and methods for treating the same 有权
标题翻译：免疫测定用颗粒及其处理方法
公开(公告)号：US06890765B2
公开(公告)日：2005-05-10
申请号：US10025196
申请日：2001-12-18
申请人： Christopher C. Lawrence , Wei Yuan , Armen B. Shanafelt
发明人： Christopher C. Lawrence , Wei Yuan , Armen B. Shanafelt
IPC分类号： C07K1/10 , C07K17/06 , G01N33/532 , G01N33/543 , G01N33/545 , G01N33/551 , G01N33/553 , G01N33/546 , G01N33/547
CPC分类号： G01N33/54346 , G01N33/532 , G01N33/54353 , Y10S436/825 , Y10S436/826 , Y10S436/909
摘要： A method of treating particles to be used in immunoassays reduces interference in particle agglutination assays. For particles having covalently bound antibodies and residual NHS-ester or sNHS-ester groups on the surface, the reactive esters are treated with an aqueous mixture containing an amine compound of formula (I): H2N—R—X (I). The moiety —X is —NH2, —OH, or —CO2CH2CH3; and R is an alkyl group or an alkyl ether group. When —X is —NH2 or —CO2CH2CH3, R contains from 1 to 20 carbon atoms; and when —X is —OH, R contains from 4 to 20 carbon atoms.
摘要翻译：用于免疫测定中使用的颗粒的处理方法减少了颗粒凝集测定中的干扰。对于表面上具有共价结合的抗体和残留的NHS-酯或sNHS-酯基团的颗粒，用含有式（I）的胺化合物的含水混合物处理反应性酯：<？in-line-formula description =“In “公式”end =“lead”？> H 2 NRX（I）。 <？in-line-formula description =“In-line formula”end =“tail”？> -X部分是-NH 2，-OH或-CO 2， CH 2 CH 2 CH 3; R为烷基或烷基醚基。当-X是-NH 2或-CO 2 CH 2 CH 3时，R包含1至20个碳原子当-X是-OH时，R含有4至20个碳原子。

107. 发明申请

US20050069961A1 Isotope-coded affinity tag 审中-公开
标题翻译：同位素编码亲和力标签
公开(公告)号：US20050069961A1
公开(公告)日：2005-03-31
申请号：US10494997
申请日：2002-10-28
申请人： Oswald Lockoff , Thomas Lehmann , Hans-Georg Lerchen , Dorian Immler , Hans-Ulrich Siegmund
发明人： Oswald Lockoff , Thomas Lehmann , Hans-Georg Lerchen , Dorian Immler , Hans-Ulrich Siegmund
IPC分类号： A61K47/48 , A61K51/08 , G01N33/532 , G01N33/68 , G01N33/53 , C07D498/02
CPC分类号： G01N33/6848 , A61K47/665 , A61K51/088 , B82Y5/00 , G01N33/532
摘要： The invention relates to novel isotope-coded affinity tags for use in mass-spectrometric analysis of proteins. The invention also relates to the production and use of these novel tags.
摘要翻译：本发明涉及用于蛋白质质谱分析的新型同位素编码亲和标签。本发明还涉及这些新型标签的生产和使用。

108. 发明申请

US20050053939A1 Methods and compositions for enhancing detection in determinations employing cleavable electrophoretic tag reagents 审中-公开
标题翻译：用于增强使用可切割电泳标签试剂的测定中检测的方法和组合物
公开(公告)号：US20050053939A1
公开(公告)日：2005-03-10
申请号：US10494879
申请日：2002-11-08
申请人： Ahmed Chenna , Sharat Singh
发明人： Ahmed Chenna , Sharat Singh
IPC分类号： G01N33/532 , C12Q1/68 , G01N33/53
CPC分类号： G01N33/532
摘要： Probe sets for the multiplexed detection of the binding of, or interaction between, one or more ligands and target antiligands are provided. Detection involves the release of identifying tags as a consequence of target recognition. The probe sets include electrophoretic tag probes or e-tag probes, comprising a detection region and a mobility-defining region, both linked to a target-binding moiety. In a multiplexed assay, different released e-tag reporters may be separated and detected providing for target identification. The probes comprise interactive functionalities adjacent the cleaved portion positioned in the probes such that the interactive functionality does not form part of the e-tag reporters. Also described are biopolymers and nucleosides containing such interactive functionalities.
摘要翻译：提供了用于多个检测一个或多个配体和靶抗配糖体的结合或相互作用的探针组。检测涉及到识别标签作为目标识别的结果。探针组包括电泳标签探针或e-标签探针，其包含与靶结合部分连接的检测区域和迁移率定义区域。在多重测定中，可以分离和检测不同的释放的电子标签记录器，以提供目标识别。这些探针包括与位于探针中的切割部分相邻的交互功能，使得交互功能不构成电子标签记录器的一部分。还描述了含有这种相互作用功能的生物聚合物和核苷。

109. 发明授权

US06859570B2 Target analyte sensors utilizing microspheres 有权
标题翻译：使用微球的目标分析物传感器
公开(公告)号：US06859570B2
公开(公告)日：2005-02-22
申请号：US09925292
申请日：2001-08-08
申请人： David R. Walt , Karri L. Michael
发明人： David R. Walt , Karri L. Michael
IPC分类号： G01N21/64 , B01J19/00 , C12M1/40 , C12Q1/00 , C12Q1/68 , C40B40/06 , C40B40/10 , C40B60/14 , G01N1/28 , G01N15/14 , G01N21/77 , G01N33/15 , G01N33/50 , G01N33/53 , G01N33/532 , G01N33/543 , G01N33/566 , G01N33/58 , G01N35/00 , G01N37/00 , G02B6/26
CPC分类号： G01N33/54346 , B01J19/0046 , B01J2219/00317 , B01J2219/00648 , B01J2219/00659 , B01J2219/00722 , B01J2219/00725 , C40B40/06 , C40B40/10 , C40B60/14 , G01N15/1456 , G01N15/1459 , G01N15/1468 , G01N21/6428 , G01N21/6452 , G01N21/7703 , G01N33/543 , G01N2015/1438 , G01N2015/1465 , G01N2035/0097 , Y10S359/90 , Y10S435/808
摘要： A microsphere-based analytic chemistry system and method for making the same is disclosed in which microspheres or particles carrying bioactive agents may be combined randomly or in ordered fashion and dispersed on a substrate to form an array while maintaining the ability to identify the location of bioactive agents and particles within the array using an optically interrogatable, optical signature encoding scheme. A wide variety of modified substrates may be employed which provide either discrete or non-discrete sites for accommodating the microspheres in either random or patterned distributions. The substrates may be constructed from a variety of materials to form either two-dimensional or three-dimensional configurations. In a preferred embodiment, a modified fiber optic bundle or array is employed as a substrate to produce a high density array. The disclosed system and method have utility for detecting target analytes and screening large libraries of bioactive agents.
摘要翻译：公开了一种基于微球的分析化学体系及其制备方法，其中携带生物活性剂的微球或颗粒可以随机或以有序的方式组合并分散在基质上以形成阵列，同时保持识别生物活性物质的位置的能力阵列内的代理和粒子，使用光学可询问的光学签名编码方案。可以使用各种各样的改性底物，其提供用于以随机或图案分布容纳微球体的离散或非离散位点。衬底可以由各种材料构成以形成二维或三维构型。在优选的实施方案中，采用改性的光纤束或阵列作为基底以产生高密度阵列。所公开的系统和方法具有检测目标分析物和筛选大型生物活性剂库的效用。

110. 发明申请

US20050014278A1 Acid-labile isotope-coded extractant (ALICE) and its use in quantitative mass spectrometric analysis of protein mixtures 失效
标题翻译：酸不稳定同位素编码提取物（ALICE）及其在蛋白质混合物的定量质谱分析中的应用
公开(公告)号：US20050014278A1
公开(公告)日：2005-01-20
申请号：US10919365
申请日：2004-08-17
申请人： Yongchang Qiu , Jack Wang , Rodney Hewick
发明人： Yongchang Qiu , Jack Wang , Rodney Hewick
IPC分类号： G01N27/62 , C07D405/12 , G01N1/28 , G01N30/46 , G01N30/72 , G01N30/88 , G01N33/532 , G01N33/58 , G01N33/68 , G01N33/00
CPC分类号： G01N33/6848 , C07D405/12 , G01N30/461 , G01N30/463 , G01N30/468 , G01N30/7233 , G01N33/532 , G01N33/58 , G01N33/6803 , Y10T436/10 , Y10T436/105831 , Y10T436/13 , Y10T436/24 , Y10T436/25125 , B01D15/362 , B01D15/325
摘要： The method of the invention provides novel compounds, termed acid-labile isotope-coded extractants (ALICE), for quantitative mass spectrometric analysis of protein mixtures. The compounds contain a thiol-reactive group that is used to capture cysteine-containing peptides from all peptide mixtures, an acid-labile linker, and a non-biological polymer. One of the two acid-labile linkers is isotopically labeled and therefore enables the direct quantitation of peptides/proteins through mass spectrometric analysis. Because no functional proteins are required to capture peptides, a higher percentage of organic solvent can be used to solubilize the peptides, particularly hydrophobic peptides, through the binding, washing and eluting steps, thus permitting much better recover of peptides. Moreover, since the peptides are covalently linked to the non-biological polymer (ALICE), more stringent washing is allowed in order to completely remove non-specifically bound species. Finally, peptides captured by ALICE are readily eluted from the polymer support under mild acidic condition with high yield and permit the direct down stream mass spectrometric analysis without any further sample manipulation. In combination with our novel dual column two dimensional liquid chromatography- mass spectrometry (2D-LC-MS/MS) design, the ALICE procedure proves to a general approach for quantitative mass spectrometric analysis of protein mixtures with better dynamic range and sensitivity.
摘要翻译：本发明的方法提供了新的化合物，称为酸不稳定同位素编码的提取物（ALICE），用于蛋白质混合物的定量质谱分析。该化合物含有硫醇反应性基团，其用于从所有肽混合物，酸不稳定接头和非生物聚合物捕获含半胱氨酸的肽。两个酸不稳定接头之一是同位素标记的，因此能够通过质谱分析直接定量肽/蛋白质。由于不需要功能蛋白来捕获肽，所以可以使用较高百分比的有机溶剂来通过结合，洗涤和洗脱步骤来增溶肽，特别是疏水性肽，因此可以更好地恢复肽。此外，由于肽与非生物聚合物（ALICE）共价连接，所以允许更严格的洗涤以完全除去非特异性结合的物质。最后，ALICE捕获的肽在温和的酸性条件下以高产率容易地从聚合物载体上洗脱，并允许直接的下游质谱分析，无需进一步的样品操作。结合我们的双柱二维液相色谱 - 质谱（2D-LC-MS / MS）设计，ALICE方法证明了具有更好的动态范围和灵敏度的蛋白质混合物的定量质谱分析的一般方法。

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