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1. 发明授权

US08304195B2 Antibody complexes and methods for immunolabeling 有权
标题翻译：抗体复合物和免疫标记方法
公开(公告)号：US08304195B2
公开(公告)日：2012-11-06
申请号：US12047131
申请日：2008-03-12
申请人： David Hagen , Joseph Beechem , Richard Haugland , Robert Archer , Rosaria Haugland
发明人： David Hagen , Joseph Beechem , Richard Haugland , Robert Archer , Rosaria Haugland
IPC分类号： G01N33/53
CPC分类号： B82Y5/00 , B82Y10/00 , G01N33/53
摘要： The present invention provides labeling reagents and methods for labeling primary antibodies and for detecting a target in a sample using an immuno-labeled complex that comprises a target-binding antibody and one or more labeling reagents. The labeling reagents comprise monovalent antibody fragments or non-antibody monomeric proteins whereby the labeling proteins have affinity for a specific region of the target-binding antibody and are covalently attached to a label. Typically, the labeling reagent is an anti-Fc Fab or Fab′ fragment that was generated by immunizing a goat or rabbit with the Fc fragment of an antibody. The present invention provides for discrete subsets of labeling reagent and immuno-labeled complexes that facilitate the simultaneous detection of multiple targets in a sample wherein the immuno-labeled complexes are distinguished by i) a ratio of label to labeling reagent, or ii) a physical property of said label, or iii) a ratio of labeling reagent to said target-binding antibody, or iv) by said target-binding antibody. This is particularly useful for fluorophore labels that can be attached to labeling reagents and subsequently immuno-labeled complexes in ratios for the detection of multiple targets.
摘要翻译：本发明提供标记试剂和用于标记一抗的标记试剂和使用包含靶结合抗体和一种或多种标记试剂的免疫标记复合物检测样品中靶标的方法。标记试剂包括单价抗体片段或非抗体单体蛋白质，由此标记的蛋白质对靶标结合抗体的特定区域具有亲和力，并且共价连接到标记物上。通常，标记试剂是通过用抗体的Fc片段免疫山羊或兔而产生的抗Fc Fab或Fab'片段。本发明提供标记试剂和免疫标记的复合物的离散子集，其有助于同时检测样品中的多个靶标，其中通过i）标记物与标记试剂的比率来区分免疫标记的复合物，或ii）物理或iii）标记试剂与所述靶结合抗体的比例，或iv）所述靶结合抗体。这对于可以连接到标记试剂和随后的用于检测多个靶的比例的免疫标记的复合物的荧光团标记物特别有用。

2. 发明授权

US08535894B2 Antibody complexes and methods for immunolabeling 有权
标题翻译：抗体复合物和免疫标记方法
公开(公告)号：US08535894B2
公开(公告)日：2013-09-17
申请号：US13610009
申请日：2012-09-11
申请人： Robert Archer , Richard Haugland , Rosaria Haugland , Joseph Beechem , David Hagen
发明人： Robert Archer , Richard Haugland , Rosaria Haugland , Joseph Beechem , David Hagen
IPC分类号： G01N33/53
CPC分类号： B82Y5/00 , B82Y10/00 , G01N33/53
摘要： Provided are labeling reagents and methods for labeling primary antibodies and for detecting a target in a sample using an immuno-labeled complex that comprises a target-binding antibody and one or more labeling reagents. The labeling reagents comprise monovalent antibody fragments or non-antibody monomeric proteins whereby the labeling proteins have affinity for a specific region of the target-binding antibody and are covalently attached to a label. Discrete subsets of labeling reagent and immune-labeled complexes are provided that facilitate the simultaneous detection of multiple targets in a sample-complexes are distinguished by i) a ratio of label to labeling reagent, or ii) a physical property of said label, or iii) a ratio of labeling reagent to said target-binding antibody, or iv) by said target-binding antibody. This is particularly useful for fluorophore labels that can be attached to labeling reagents and subsequently immuno-labeled complexes in ratios for the detection of multiple targets.
摘要翻译：提供标记试剂和用于标记一抗的标记试剂和用于使用包含靶结合抗体和一种或多种标记试剂的免疫标记复合物检测样品中的靶标的方法。标记试剂包括单价抗体片段或非抗体单体蛋白质，由此标记的蛋白质对靶标结合抗体的特定区域具有亲和力，并且共价连接到标记物上。提供标记试剂和免疫标记复合物的离散子集，其有利于同时检测样品中多个靶标的复合物，其特征在于i）标记与标记试剂的比例，或ii）所述标记的物理性质，或iii ）标记试剂与所述靶结合抗体的比例，或iv）所述靶结合抗体。这对于可以连接到标记试剂和随后的用于检测多个靶的比例的免疫标记的复合物的荧光团标记物特别有用。

3. 发明申请

US20050069962A1 Antibody complexes and methods for immunolabeling 审中-公开
标题翻译：抗体复合物和免疫标记方法
公开(公告)号：US20050069962A1
公开(公告)日：2005-03-31
申请号：US10467550
申请日：2002-10-02
申请人： Robert Archer , Joseph Beechem , David Hagen , Richard Haugland , Rosaria Haugland
发明人： Robert Archer , Joseph Beechem , David Hagen , Richard Haugland , Rosaria Haugland
IPC分类号： G01N33/53
CPC分类号： B82Y5/00 , B82Y10/00 , G01N33/53
摘要： The present invention provides labeling reagents and methods for labeling primary antibodies and for detecting a target in a sample using an immuno-labeled complex that comprises a target-binding antibody and one or more labeling reagents. The labeling reagents comprise monovalent antibody fragments or non-antibody monomeric proteins whereby the labeling proteins have affinity for a specific region of the target-binding antibody and are covalently attached to a label. Typically, the labeling reagent is an anti-Fc Fab or Fab′ fragment that was generated by immunizing a goat or rabbit with the Fc fragment of an antibody. The present invention provides for discrete subsets of labeling reagent and immuno-labeled complexes that facilitate the simultaneous detection of multiple targets in a sample wherein the immuno-labeled complexes are distinguished by i) a ratio of label to labeling reagent, or ii) a physical property of said label, or iii) a ratio of labeling reagent to said target-binding antibody, or iv) by said target-binding antibody. This is particularly useful for fluorophore labels that can be attached to labeling reagents and subsequently immuno-labeled complexes in ratios for the detection of multiple targets.
摘要翻译：本发明提供标记试剂和用于标记一抗的标记试剂和使用包含靶结合抗体和一种或多种标记试剂的免疫标记复合物检测样品中靶标的方法。标记试剂包括单价抗体片段或非抗体单体蛋白质，由此标记的蛋白质对靶标结合抗体的特定区域具有亲和力，并且共价连接到标记物上。通常，标记试剂是通过用抗体的Fc片段免疫山羊或兔而产生的抗Fc Fab或Fab'片段。本发明提供标记试剂和免疫标记的复合物的离散子集，其有助于同时检测样品中的多个靶标，其中通过i）标记物与标记试剂的比率来区分免疫标记的复合物，或ii）物理或iii）标记试剂与所述靶结合抗体的比例，或iv）所述靶结合抗体。这对于可以连接到标记试剂和随后的用于检测多个靶的比例的免疫标记的复合物的荧光团标记物特别有用。

4. 发明申请

US20060160068A1 Competitive immunoassay 有权
标题翻译：竞争性免疫测定
公开(公告)号：US20060160068A1
公开(公告)日：2006-07-20
申请号：US10943463
申请日：2004-09-17
申请人： Joseph Beechem , Kyle Gee , David Hagen , Iain Johnson , Hee-Chol Kang , Christina Pastula
发明人： Joseph Beechem , Kyle Gee , David Hagen , Iain Johnson , Hee-Chol Kang , Christina Pastula
IPC分类号： C12Q1/70 , C12Q1/68 , C07K16/46 , C07F5/02 , C07D311/88
CPC分类号： G01N33/542 , C07F9/12 , C07F9/65318 , C07F9/65522 , C07F9/6596 , C07K16/46 , Y10S435/968 , Y10S436/80 , Y10S530/807 , Y10T436/13
摘要： The present invention provides ligand-detection reagents, ligand analogs and methods for determining the presence of a ligand in a sample. The ligand-detection reagent comprises a ligand-binding antibody and a ligand analog to form an antibody-ligand analog complex wherein the ligand analog is covalently bonded to a reporter molecule. This complex may additionally comprise a labeling protein non-covalently bonded to the antibody to form a ternary complex wherein the labeling protein comprises a monovalent antibody fragment or a non-antibody protein that is covalently bonded to a label moiety. The reporter molecule is either quenched by the ligand-binding antibody or by the label moiety of the labeling protein, depending on the reporter molecule and the ligand-binding antibody, wherein the amount of quenching is directly related to the amount of ligand present in the sample. Alternatively, the ligand analog is fluorogenic wherein the ligand analog is essentially non-fluorescent in solution but when bound by the ligand-binding antibody the detectable signal increases. In this instance a decrease in signal, as opposed to the relieving of quenching, is measured for the presence of a target ligand.
摘要翻译：本发明提供配体检测试剂，配体类似物和用于测定样品中配体存在的方法。配体检测试剂包含配体结合抗体和配体类似物以形成抗体 - 配体类似物复合物，其中配体类似物共价键合到报告分子。该复合物还可以包含与抗体非共价键合以形成三元复合物的标记蛋白质，其中标记蛋白质包含共价键合到标记部分的单价抗体片段或非抗体蛋白质。取决于报道分子和配体结合抗体，报告分子被配体结合抗体或标记蛋白的标记部分淬灭，其中淬灭量与存在于样品。或者，配体类似物是荧光的，其中配体类似物在溶液中基本上是非荧光的，但当被配体结合抗体结合时，可检测信号增加。在这种情况下，与目标配体的存在相比，测量了与消除淬灭相反的信号降低。

5. 发明申请

US20070269902A1 Antibody complexes and methods for immunolabeling 审中-公开
标题翻译：抗体复合物和免疫标记方法
公开(公告)号：US20070269902A1
公开(公告)日：2007-11-22
申请号：US10666291
申请日：2003-09-17
申请人： Joseph Beechem , David Hagen , Iain Johnson
发明人： Joseph Beechem , David Hagen , Iain Johnson
IPC分类号： G01N33/00 , C12Q1/68
CPC分类号： B82Y30/00 , B82Y5/00 , B82Y10/00 , G01N33/53 , G01N33/58 , G01N33/6857
摘要： The present invention provides labeling reagents and methods for labeling primary antibodies and for detecting a target in a sample using an immuno-labeled complex that comprises a target-binding antibody and one or more labeling reagents. The labeling reagents comprise monovalent antibody fragments or non-antibody monomeric proteins whereby the labeling reagents have affinity for a specific region of the target-binding antibody and are covalently attached to a label. Typically, the labeling reagent is an anti-Fc Fab or Fab′ fragment that was generated by immunizing a goat or rabbit with the Fc fragment of an antibody. The present invention provides for discrete subsets of labeling reagent and immuno-labeled complexes that facilitate the simultaneous detection of multiple targets in a sample wherein the immuno-labeled complexes are distinguished by i) a ratio of label to labeling reagent, or ii) a physical property of said label, or iii) a ratio of labeling reagent to said target-binding antibody, or iv) by said target-binding antibody. This is particularly useful for fluorophore labels that can be attached to labeling reagents and subsequently immuno-labeled complexes in ratios for the detection of multiple targets.
摘要翻译：本发明提供标记试剂和用于标记一抗的标记试剂和使用包含靶结合抗体和一种或多种标记试剂的免疫标记复合物检测样品中靶标的方法。标记试剂包含单价抗体片段或非抗体单体蛋白质，由此标记试剂对靶结合抗体的特定区域具有亲和力，并且共价连接到标记物上。通常，标记试剂是通过用抗体的Fc片段免疫山羊或兔而产生的抗Fc Fab或Fab'片段。本发明提供标记试剂和免疫标记的复合物的离散子集，其有助于同时检测样品中的多个靶标，其中通过i）标记物与标记试剂的比率来区分免疫标记的复合物，或ii）物理或iii）标记试剂与所述靶结合抗体的比例，或iv）所述靶结合抗体。这对于可以连接到标记试剂和随后的用于检测多个靶的比例的免疫标记的复合物的荧光团标记物特别有用。

6. 发明申请

US20100319594A1 LOW COMBUSTION APPARATUS AND METHOD 有权
标题翻译：低燃烧装置和方法
公开(公告)号：US20100319594A1
公开(公告)日：2010-12-23
申请号：US12850756
申请日：2010-08-05
申请人： Paul Andrew Campbell , David Hagen
发明人： Paul Andrew Campbell , David Hagen
IPC分类号： F23N5/00 , F23N1/02
CPC分类号： F23L7/00 , F02C6/00 , F23C6/047 , F23D14/02 , F23D14/66 , F23D2900/00014 , F23L7/002 , F23L2900/07002 , F23L2900/07008 , F23R3/346 , Y02E20/348
摘要： Clean combustion and equilibration equipment and methods are provided to progressively deliver, combust and equilibrate mixtures of fuel, oxidant and aqueous diluent in a plurality of combustion regions and in one or more equilibration regions to further progress oxidation of products of incomplete combustion, in a manner that sustains combustion while controlling temperatures and residence times sufficiently to reduce CO and NOx emissions to below 25 ppmvd, and preferably to below 3 ppmvd at 15% O2.
摘要翻译：提供清洁的燃烧和平衡设备和方法以逐渐地在多个燃烧区域和一个或多个平衡区域中递送，燃烧和平衡燃料，氧化剂和水稀释剂的混合物，以进一步进行不完全燃烧产物的氧化。其在充分控制温度和停留时间的同时保持燃烧，以将CO和NOx排放降低到低于25ppmvd，并且优选在15％O 2下降低到3ppmvd以下。

7. 发明授权

US07788897B2 Low emissions combustion apparatus and method 有权
标题翻译：低排放燃烧装置及方法
公开(公告)号：US07788897B2
公开(公告)日：2010-09-07
申请号：US11149959
申请日：2005-06-10
申请人： Paul Andrew Campbell , David Hagen
发明人： Paul Andrew Campbell , David Hagen
IPC分类号： F02C3/20 , F02C3/30 , F23R3/34 , F23C5/00 , F23C7/00
CPC分类号： F23L7/00 , F02C6/00 , F23C6/047 , F23D14/02 , F23D14/66 , F23D2900/00014 , F23L7/002 , F23L2900/07002 , F23L2900/07008 , F23R3/346 , Y02E20/348
摘要： Clean combustion and equilibration equipment and methods are provided to progressively deliver, combust and equilibrate mixtures of fuel, oxidant and aqueous diluent in a plurality of combustion regions and in one or more equilibration regions to further progress oxidation of products of incomplete combustion, in a manner that sustains combustion while controlling temperatures and residence times sufficiently to reduce CO and NOx emissions to below 25 ppmvd, and preferably to below 3 ppmvd at 15% O2.
摘要翻译：提供清洁的燃烧和平衡设备和方法以逐渐地在多个燃烧区域和一个或多个平衡区域中递送，燃烧和平衡燃料，氧化剂和水稀释剂的混合物，以进一步进行不完全燃烧产物的氧化。其在充分控制温度和停留时间的同时保持燃烧，以将CO和NOx排放降低到低于25ppmvd，并且优选在15％O 2下降低到3ppmvd以下。

8. 发明授权

US07655409B2 Cyanine dye compounds 有权
标题翻译：花青染料化合物
公开(公告)号：US07655409B2
公开(公告)日：2010-02-02
申请号：US12240218
申请日：2008-09-29
申请人： Jason Dallwig , David Hagen , Shih-Jung Huang , Gerald Thomas , Stephen Yue
发明人： Jason Dallwig , David Hagen , Shih-Jung Huang , Gerald Thomas , Stephen Yue
IPC分类号： C12Q1/68 , C07H21/04 , C07H19/04
CPC分类号： C09B23/02 , C12Q1/6827 , G01N33/582 , Y10T436/143333 , C12Q2527/125 , C12Q2563/107
摘要： Cyanine dye compounds having a negatively charged substituent that are nucleic acid stains, particularly for fluorescent staining of DNA, including compounds having the formula wherein W forms one or two fused 5- or 6-membered aromatic rings, α has a value of 0 or 1, n has a value of 0, or 1, X is O, S, or Se, and D is a pyridinium, or quinolinium moiety, provided that the compound has at least one negatively charged substituent.
摘要翻译：具有带负电荷的取代基的花青染料化合物，特别是用于DNA的荧光染色的带负电荷的取代基，包括具有下式的化合物，其中W形成一个或两个稠合的5-或6-元芳环，α具有0或1的值，n为0或1，X为O，S或Se，D为吡啶鎓或喹啉鎓部分，条件是该化合物具有至少一个带负电荷的取代基。

9. 发明申请

US20060164471A1 Replaceable ink supply 有权
标题翻译：可更换墨水供应
公开(公告)号：US20060164471A1
公开(公告)日：2006-07-27
申请号：US11040541
申请日：2005-01-21
申请人： Anthony Studer , Kevin Almen , David Benson , David Hagen , Cary Bybee
发明人： Anthony Studer , Kevin Almen , David Benson , David Hagen , Cary Bybee
IPC分类号： B41J2/175
CPC分类号： B41J2/17513
摘要： A replaceable ink supply comprises an ink container with an internal chamber formed from a plurality of walls. An ink reservoir block can be located within the internal chamber. Further, a channel can be formed in at least one wall of the internal chamber and the channel having an open side exposing a portion of the ink reservoir block.
摘要翻译：可替换的墨水供应包括具有由多个壁形成的内部腔的墨水容器。储墨器块可以位于内部腔室内。此外，可以在内部室的至少一个壁中形成通道，并且具有暴露墨水容器块的一部分的敞开侧的通道。

10. 发明申请

US20050030892A1 System for providing network load distribution 审中-公开
标题翻译：提供网络负载分配的系统
公开(公告)号：US20050030892A1
公开(公告)日：2005-02-10
申请号：US10874694
申请日：2004-06-23
申请人： David Hagen , Rick Stefanik
发明人： David Hagen , Rick Stefanik
IPC分类号： H04L12/18 , H04L12/46 , H04L29/06 , H04L29/08 , H04L12/26
CPC分类号： H04L12/4641 , H04L12/18 , H04L67/1002
摘要： A system for providing network load distribution including a network having a number of portals that are configured to access portal services hosted by the network and a plurality of control nodes on the network that are configured to establish data connections with the portals on the network. The control nodes form a virtual local area network (VLAN) that includes multicast islands and singlecast bridges for broadcasting data to other nodes on the network. When a portal requests to access a portal service hosted on the network, a portal having the requested service is identified and authenticated by one of the control nodes, and a data connection is established between the identified portal and the requesting portal for sharing the requested service.
摘要翻译：一种用于提供网络负载分配的系统，包括具有被配置为访问由所述网络托管的门户服务的多个门户的网络以及被配置为与所述网络上的所述门户建立数据连接的所述网络上的多个控制节点。控制节点形成虚拟局域网（VLAN），其包括用于向网络上的其他节点广播数据的多播岛和单播桥。当门户网站请求访问在网络上托管的门户网站服务时，具有所请求的服务的门户被其中一个控制节点识别和认证，并且在所识别的门户和请求门户之间建立数据连接以共享所请求的服务。

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