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1. 发明申请

WO2009070331A3 COMPOUNDS AND METHODS FOR THE SELECTIVE INHIBITION OF ABCB1, ABCC1 AND ABCG2 TRANSPORTERS AND THE TREATMENT OF CANCERS, ESPECIALLY DRUG RESISTANT CANCERS AND HIGH THROUGHPUT FLOW CYTOMETRY ASSAY TO DETECT SELECTIVE INHIBITORS 审中-公开
标题翻译：选择性抑制ABCB1，ABCC1和ABCG2转运蛋白以及治疗癌症，特别是抗药性癌症和高通量流式细胞测定以检测选择性抑制剂的化合物和方法
公开(公告)号：WO2009070331A3
公开(公告)日：2009-07-23
申请号：PCT/US2008013209
申请日：2008-11-28
申请人： STC UNM , LARSON RICHARD S , SKLAR LARRY A , EDWARDS BRUCE S , IVNITSKI-STEELE IRENA D , OPREA TUDOR I , LOVATO DEBBIE M , KHAWAJA HADYA M , WINTER STUART S , YOUNG SUSAN M
发明人： SKLAR LARRY A , EDWARDS BRUCE S , IVNITSKI-STEELE IRENA D , OPREA TUDOR I , LOVATO DEBBIE M , KHAWAJA HADYA M , WINTER STUART S , YOUNG SUSAN M
IPC分类号： A61K31/415 , A61K31/12 , A61P35/00
CPC分类号： A61K31/12 , A61K31/415 , A61K45/06 , A61K2300/00
摘要： Compounds disclosed which inhibit ABCBl transporter protein are useful for treating diseases in which ABCBl transporter protein mediates the disease state, including numerous cancers, including hematopoietic cancers, including various leukemias, especially T-lineage acute lymphoblastic leukemia, as well as cancerous tumors, especially forms which exhibit multiple drug resistance. Pharmaceutical compositions which comprise an inhibitor of ABCBl transporter protein and at least one additional anticancer agent, optionally in combination with a pharmaceutically acceptable carrier, additive or excipient are another aspect of the present invention. A flow cytometry based, high-throughput screening (HST) assay that quantifies ABCBl efflux is also disclosed. Methods of identifying inhibitors of ABCBl, ABCG2 and ABCCl transporter proteins are also disclosed.
摘要翻译：公开的抑制ABCB1转运蛋白的化合物可用于治疗其中ABCB1转运蛋白介导疾病状态的疾病，包括多种癌症，包括造血系统癌症，包括各种白血病，尤其是T-系急性淋巴细胞白血病，以及癌性肿瘤，特别是癌表现出多重耐药性。包含ABCB1转运蛋白抑制剂和至少一种另外的抗癌剂，任选地与药学上可接受的载体，添加剂或赋形剂组合的药物组合物是本发明的另一方面。还公开了量化ABCB1流出的基于流式细胞术的高通量筛选（HST）测定法。还公开了鉴定ABCB1，ABCG2和ABCCl转运蛋白的抑制剂的方法。

2. 发明申请

WO2009070331A2 COMPOUNDS AND METHODS FOR THE SELECTIVE INHIBITION OF ABCB1, ABCC1 AND ABCG2 TRANSPORTERS AND THE TREATMENT OF CANCERS, ESPECIALLY DRUG RESISTANT CANCERS AND HIGH THROUGHPUT FLOW CYTOMETRY ASSAY TO DETECT SELECTIVE INHIBITORS 审中-公开
标题翻译：选择性抑制ABCB1，ABCC1和ABCG2转运蛋白的化合物和方法以及癌症治疗，特别是耐药性和高通量流式细胞计数测定来检测选择性抑制剂
公开(公告)号：WO2009070331A2
公开(公告)日：2009-06-04
申请号：PCT/US2008/013209
申请日：2008-11-28
申请人： STC.UNM , LARSON, Richard, S. , SKLAR, Larry, A. , EDWARDS, Bruce, S. , IVNITSKI-STEELE, Irena, D. , OPREA, Tudor, I. , LOVATO, Debbie, M. , KHAWAJA, Hadya, M. , WINTER, Stuart, S. , YOUNG, Susan, M.
发明人： SKLAR, Larry, A. , EDWARDS, Bruce, S. , IVNITSKI-STEELE, Irena, D. , OPREA, Tudor, I. , LOVATO, Debbie, M. , KHAWAJA, Hadya, M. , WINTER, Stuart, S. , YOUNG, Susan, M.
IPC分类号： A61K31/415 , A61K31/12 , A61P35/00
CPC分类号： A61K31/12 , A61K31/415 , A61K45/06 , A61K2300/00
摘要： Compounds disclosed which inhibit ABCBl transporter protein are useful for treating diseases in which ABCBl transporter protein mediates the disease state, including numerous cancers, including hematopoietic cancers, including various leukemias, especially T-lineage acute lymphoblastic leukemia, as well as cancerous tumors, especially forms which exhibit multiple drug resistance. Pharmaceutical compositions which comprise an inhibitor of ABCBl transporter protein and at least one additional anticancer agent, optionally in combination with a pharmaceutically acceptable carrier, additive or excipient are another aspect of the present invention. A flow cytometry based, high-throughput screening (HST) assay that quantifies ABCBl efflux is also disclosed. Methods of identifying inhibitors of ABCBl, ABCG2 and ABCCl transporter proteins are also disclosed.
摘要翻译：公开的抑制ABCB1转运蛋白的化合物可用于治疗其中ABCB1转运蛋白介导疾病状态的疾病，包括许多癌症，包括造血癌，包括各种白血病，特别是T-lineage急性成淋巴细胞性白血病，以及癌性肿瘤，特别是形式其表现出多种耐药性。包含ABCB1转运蛋白抑制剂和任选与药学上可接受的载体，添加剂或赋形剂组合的至少一种另外的抗癌剂的药物组合物是本发明的另一方面。还公开了量化ABCB1流出的基于流式细胞术的高通量筛选（HST）测定。还公开了鉴定ABCB1，ABCG2和ABCC1转运蛋白抑制剂的方法。

3. 发明申请

WO2009005542A3 DETECTION OF BIOAGENTS USING A SHEAR HORIZONTAL SURFACE ACOUSTIC WAVE BIOSENSOR 审中-公开
标题翻译：使用剪切水平表面声波生物传感器检测生物剂
公开(公告)号：WO2009005542A3
公开(公告)日：2009-04-16
申请号：PCT/US2008001721
申请日：2008-02-08
申请人： STC UNM , SANDIA CORP , LARSON RICHARD S , HJELLE BRIAN , HALL PAM R , BROWN DAVID C , BISOFFI MARCO , BROZIK SUSAN M , BRANCH DARREN W , EDWARDS THAYNE L , WHEELER DAVID
发明人： LARSON RICHARD S , HJELLE BRIAN , HALL PAM R , BROWN DAVID C , BISOFFI MARCO , BROZIK SUSAN M , BRANCH DARREN W , EDWARDS THAYNE L , WHEELER DAVID
IPC分类号： C12Q1/34 , C12M3/00
CPC分类号： G01N33/54373 , C12Q1/6825 , G01N29/032 , G01N33/553 , G01N2291/0422
摘要： Viruses and other bioagents are of high medical and biodefense concern and their detection at concentrations well below the threshold necessary to cause health hazards continues to be a challenge with respect to sensitivity, specificity, and selectivity. Ideally, assays for accurate and real time detection of viral agents and other bioagents would not necessitate any pre-processing of the analyte, which would make them applicable for example to bodily fluids (blood, sputum) and man-made as well as naturally occurring bodies of water (pools, rivers). We describe herein a robust biosensor that combines the sensitivity of surface acoustic waves (SAW) generated at a frequency of 325 MHz with the specificity provided by antibodies and other ligands for the detection of viral agents. In preferred embodiments, a lithium tantalate based SAW transducer with silicon dioxide waveguide sensor platform featuring three test and one reference delay lines was used to adsorb antibodies directed against Coxsackie virus B4 or the negative-stranded category A bioagent Sin Nombre virus (SNV), a member of the genus Hantavirus, family Bunyaviridae, negative-stranded RNA viruses. Rapid detection (within seconds) of increasing concentrations of viral particles was linear over a range of order of magnitude for both viruses, although the sensor was approximately 50x104 -fold more sensitive for the detection of SNV. For both pathogens, the sensor's selectivity for its target was not compromised by the presence of confounding Herpes Simplex virus type 1. The biosensor was able to detect SNV at doses lower than the load of virus typically found in a human patient suffering from hantavirus cardiopulmonary syndrome (HCPS). Further, in a proof-of-principle real world application, the SAW biosensor was capable of selectively detecting SNV agents in complex solutions, such as naturally occurring bodies of water (river, sewage effluent) without analyte pre-processing.
摘要翻译：病毒和其他生物制剂对医学和生物防御有很高的关注度，并且它们的检测浓度远低于引起健康危害所必需的阈值，这仍然是灵敏度，特异性和选择性方面的挑战。理想情况下，准确和实时检测病毒剂和其他生物剂的分析不需要对分析物进行任何预处理，这将使其适用于例如体液（血液，痰液）和人造以及自然发生的水体（水池，河流）。我们在此描述了一种鲁棒的生物传感器，其将频率为325MHz的表面声波（SAW）的灵敏度与由抗体和其他配体提供的用于检测病毒剂的特异性相结合。在优选的实施方案中，具有三个测试和一个参考延迟线的具有二氧化硅波导传感器平台的基于钽酸锂的SAW换能器被用于吸附针对柯萨奇病毒B4或负链A类生物因子Sin Nombre病毒（SNV）的抗体，a 汉坦病毒属，布尼亚病毒科，负链RNA病毒成员。对于两种病毒，增加浓度的病毒颗粒的快速检测（数秒内）在一定数量级范围内是线性的，尽管对于检测SNV而言传感器的灵敏度约为50×10 4倍。对于这两种病原体而言，传感器对其靶标的选择性不会由于混杂的1型单纯性疱疹病毒的存在而受到损害。生物传感器能够以比通常在患有汉坦病毒心肺综合征的人类患者中发现的病毒载量低的剂量检测SNV （HCPS）。此外，在原理验证的实际应用中，SAW生物传感器能够选择性检测复杂溶液中的SNV试剂，例如没有分析物预处理的天然存在的水体（河流，污水流出物）。

4. 发明申请

WO2005007821A3 TERTIARY STRUCTURES OF ICA-1/LFA-1 MODULATORS 审中-公开
标题翻译： ICA-1 / LFA-1调制器的初步结构
公开(公告)号：WO2005007821A3
公开(公告)日：2009-04-09
申请号：PCT/US2004021861
申请日：2004-07-07
申请人： STC UNM , LARSON RICHARD S , SILLERUD LAUREL
发明人： LARSON RICHARD S , SILLERUD LAUREL
IPC分类号： G01N33/48 , C07K7/06 , C12N20060101 , G01N33/50 , G01N33/53 , G06F19/00
CPC分类号： C07K7/06 , G01N2333/70525
摘要： The invention provides tertiary structures) of cyclic nonapeptide ICAM-1 inhibitors and methods of using the tertiary structures tp identify additional ICAM-1 inhibitors, particularly non-peptide modulators. The invention also provides methods of treating ICAM1/LFA-1 mediated diseases comprising administ4ring a non-peptide ICAM-1 modulator of the invention to a patient in need thereof.
摘要翻译：本发明提供三级结构）的环状肽IIICAM-1抑制剂和使用三级结构tp的方法鉴定另外的ICAM-1抑制剂，特别是非肽调节剂。本发明还提供了治疗ICAM1 / LFA-1介导的疾病的方法，其包括向有需要的患者施用本发明的非肽ICAM-1调节剂。

5. 发明申请

WO2005010024A3 POTENT PEPTIDE INHIBITORS AND METHODS OF USE 审中-公开
标题翻译：多肽抑制剂及其使用方法
公开(公告)号：WO2005010024A3
公开(公告)日：2005-04-07
申请号：PCT/US2004023536
申请日：2004-07-21
申请人： STC UNM , LARSON RICHARD S
发明人： LARSON RICHARD S
IPC分类号： A61K38/00 , A61K38/08 , C07K20060101 , C07K7/06
CPC分类号： C07K7/06
摘要： The present invention relates to peptide compounds which modulate the interaction of ICAM-1 and LFA-1, and in particular, function as inhibitors of the interaction of integrins, more particularly, LFA-I, and one or several distinct intercellular adhesion molecules (ICAMS), in particular ICAM-1, pharmaceutical compositions comprising effective amounts of these peptide compounds and methods for the treatment and/or prevention of related disease states and conditions which are mediated through ICAM-1/LFA-1 interactions, for example, the interaction of cellular adhesion molecules with integrins and/or the emigration of leukocytes from blood into tissue.
摘要翻译：本发明涉及调节ICAM-1和LFA-1相互作用的肽化合物，特别是作为整联蛋白，更特别是LFA-1和一种或几种不同细胞间粘附分子（ICAMS）相互作用的抑制剂起作用），特别是ICAM-1，包含有效量的这些肽化合物的药物组合物以及用于治疗和/或预防通过ICAM-1 / LFA-1相互作用介导的相关疾病状态和状况的方法，例如相互作用细胞粘附分子与整联蛋白和/或白血球从血液中迁移到组织中。

6. 发明申请

WO2005010024A2 POTENT PEPTIDE INHIBITORS AND METHODS OF USE 审中-公开
标题翻译：磷酸肽抑制剂及其使用方法
公开(公告)号：WO2005010024A2
公开(公告)日：2005-02-03
申请号：PCT/US2004/023536
申请日：2004-07-21
申请人： SCIENCE & TECHNOLOGY CORPORATION @ UNM , LARSON, Richard, S.
发明人： LARSON, Richard, S.
IPC分类号： C07K
CPC分类号： C07K7/06
摘要： The present invention relates to peptide compounds which modulate the interaction of ICAM-1 and LFA-1, and in particular, function as inhibitors of the interaction of integrins, more particularly, LFA-I, and one or several distinct intercellular adhesion molecules (ICAMS), in particular ICAM-1, pharmaceutical compositions comprising effective amounts of these peptide compounds and methods for the treatment and/or prevention of related disease states and conditions which are mediated through ICAM-1/LFA-1 interactions, for example, the interaction of cellular adhesion molecules with integrins and/or the emigration of leukocytes from blood into tissue.
摘要翻译：本发明涉及调节ICAM-1和LFA-1的相互作用的肽化合物，特别是作为整联蛋白，特别是LFA-1和一种或多种不同的细胞间粘附分子（ICAMS）相互作用的抑制剂的功能），特别是ICAM-1，包含有效量的这些肽化合物的药物组合物和通过ICAM-1 / LFA-1相互作用介导的治疗和/或预防相关疾病状态和病症的方法，例如相互作用的细胞粘附分子与整合素和/或白血球从血液迁移到组织中。

7. 发明申请

WO2003095449A1 SMALL MOLECULES FOR INHIBITION OF FUNCTION AND DRUG DELIVERY TO LEUKOCYTES 审中-公开
标题翻译：用于抑制功能和药物递送给小鼠的小分子
公开(公告)号：WO2003095449A1
公开(公告)日：2003-11-20
申请号：PCT/US2003/013849
申请日：2003-05-05
申请人： SCIENCE AND TECHNOLOGY CORPORATION @ UNIVERSITY OF NEW MEXICO , REGENTS OF THE UNIVERSITY OF MINNESOTA , LARSON, Richard, S. , WAGNER, Carston
发明人： LARSON, Richard, S. , WAGNER, Carston
IPC分类号： C07D405/14
CPC分类号： C07D401/12 , B01F13/0059 , B01F13/0093 , B01F13/0096 , B01F15/0201 , B01F15/024 , C07D233/76 , C07D405/12
摘要： The present invention provides a compound and a method of making a compound according to the following formula: where R 1 is an alkyl group having 1 to 12 carbons; R 2 is a urea group; R 3 is an active group, such as fluorescein, a toxin, radiolabel or drug; and R 4 , R 5 and R 6 are each independently a halide group.
摘要翻译：本发明提供一种化合物及其制备方法，其中R1为具有1至12个碳原子的烷基; R2是尿素基团; R3是活性基团，例如荧光素，毒素，放射性标记物或药物; R 4，R 5和R 6各自独立地为卤素基团。

8. 发明申请

WO2011053435A1 CELL DETECTION USING TARGETED NANOPARTICLES AND MAGNETIC PROPERTIES THEREOF 审中-公开
标题翻译：使用目标纳米颗粒的电池检测及其磁性能
公开(公告)号：WO2011053435A1
公开(公告)日：2011-05-05
申请号：PCT/US2010/051417
申请日：2010-10-05
申请人： SCIENTIFIC NANOMEDICINE, INC. , FLYNN, Edward, R. , LARSON, Richard, S.
发明人： FLYNN, Edward, R. , LARSON, Richard, S.
IPC分类号： A61B5/055
CPC分类号： G01N33/54326 , A61B10/02
摘要： The present invention provides methods and apparatuses for detecting or measuring cells or substances present in biological samples The method comprises (a) providing targeted nanoparticles compnsing a magnetic nanoparticle conjugated with a targeting agent that preferentially binds to cells of a first type, (b) introducing the targeted nanoparticles to the sample in a manner that allows bonding of the targeting agents to cells of the first type, (c) subjecting the bound targeting nanoparticles to the operation of a magnetic device to extract the sample cells to which are bound targeted nanoparticles The method can also compnse (a) prepanng a second sample by combining a first sample with a plurality of targeted nanoparticles, (b) subjecting the second sample to an applied magnetic field, and (c) measunng the relaxation of the magnetic field induced in the bound nanoparticles to determine the presence, concentration, or other characteristic of cells of the predetermined type
摘要翻译：本发明提供用于检测或测量存在于生物样品中的细胞或物质的方法和装置。该方法包括（a）提供靶向纳米颗粒，其包含与靶向剂缀合的磁性纳米颗粒，其优先结合第一类型的细胞，（b）引入靶向纳米颗粒以允许靶向剂与第一类型的细胞结合的方式，（c）对结合的靶向纳米颗粒进行磁性装置的操作以提取与其结合的靶向纳米颗粒的样品细胞方法还可以包括（a）通过将第一样品与多个目标纳米颗粒组合来制备第二样品，（b）使第二样品经受施加的磁场，和（c）测量在第二样品中诱导的磁场的松弛以确定预定类型的细胞的存在，浓度或其它特征

9. 发明申请

WO2009005542A2 DETECTION OF BIOAGENTS USING A SHEAR HORIZONTAL SURFACE ACOUSTIC WAVE BIOSENSOR 审中-公开
标题翻译：使用剪切水平表面声波生物传感器检测生物
公开(公告)号：WO2009005542A2
公开(公告)日：2009-01-08
申请号：PCT/US2008/001721
申请日：2008-02-08
申请人： STC.UNM , SANDIA CORPORATION , LARSON, Richard, S. , HJELLE, Brian , HALL, Pam, R. , BROWN, David, C. , BISOFFI, Marco , BROZIK, Susan, M. , BRANCH, Darren, W. , EDWARDS, Thayne, L. , WHEELER, David
发明人： LARSON, Richard, S. , HJELLE, Brian , HALL, Pam, R. , BROWN, David, C. , BISOFFI, Marco , BROZIK, Susan, M. , BRANCH, Darren, W. , EDWARDS, Thayne, L. , WHEELER, David
IPC分类号： C12Q1/70
CPC分类号： G01N33/54373 , C12Q1/6825 , G01N29/032 , G01N33/553 , G01N2291/0422
摘要： Viruses and other bioagents are of high medical and biodefense concern and their detection at concentrations well below the threshold necessary to cause health hazards continues to be a challenge with respect to sensitivity, specificity, and selectivity. Ideally, assays for accurate and real time detection of viral agents and other bioagents would not necessitate any pre-processing of the analyte, which would make them applicable for example to bodily fluids (blood, sputum) and man-made as well as naturally occurring bodies of water (pools, rivers). We describe herein a robust biosensor that combines the sensitivity of surface acoustic waves (SAW) generated at a frequency of 325 MHz with the specificity provided by antibodies and other ligands for the detection of viral agents. In preferred embodiments, a lithium tantalate based SAW transducer with silicon dioxide waveguide sensor platform featuring three test and one reference delay lines was used to adsorb antibodies directed against Coxsackie virus B4 or the negative-stranded category A bioagent Sin Nombre virus (SNV), a member of the genus Hantavirus, family Bunyaviridae , negative-stranded RNA viruses. Rapid detection (within seconds) of increasing concentrations of viral particles was linear over a range of order of magnitude for both viruses, although the sensor was approximately 50x10 4 -fold more sensitive for the detection of SNV. For both pathogens, the sensor's selectivity for its target was not compromised by the presence of confounding Herpes Simplex virus type 1. The biosensor was able to detect SNV at doses lower than the load of virus typically found in a human patient suffering from hantavirus cardiopulmonary syndrome (HCPS). Further, in a proof-of-principle real world application, the SAW biosensor was capable of selectively detecting SNV agents in complex solutions, such as naturally occurring bodies of water (river, sewage effluent) without analyte pre-processing.
摘要翻译：病毒和其他生物制剂具有高度的医学和生物防治问题，其浓度远远低于引起健康危害的阈值的检测在敏感性，特异性和选择性方面仍然是一个挑战。理想情况下，用于准确和实时检测病毒试剂和其他生物标签的测定不需要对分析物进行任何预处理，这将使它们适用于例如体液（血液，痰）和人造的以及天然存在的水体（游泳池，河流）。我们在这里描述了一种强大的生物传感器，其结合了在325MHz频率下产生的表面声波（SAW）的灵敏度与由抗体和其他配体提供的用于检测病毒剂的特异性。在优选实施例中，使用具有三个测试和一个参考延迟线的具有二氧化硅波导传感器平台的基于钽酸锂的SAW换能器来吸附针对柯萨奇病毒B4或负链A类生物剂Sin Nombre病毒（SNV）的抗体，汉坦病毒属，布尼亚病毒科，负链RNA病毒的成员。尽管传感器对于SNV检测的敏感度大约为50x104倍，但对于两种病毒而言，增加浓度的病毒颗粒的快速检测（在几秒钟内）是线性范围的数量级。对于两种病原体，传感器对其目标的选择性不受1型混合型单纯疱疹病毒的存在的影响。生物传感器能够以低于患有汉坦病毒心肺综合征的人类患者的病毒载量的剂量来检测SNV （HCPS）。此外，在原理现实应用中，SAW生物传感器能够选择性地检测复杂解决方案中的SNV试剂，例如天然存在的水体（河流，污水流出物），无需分析物预处理。

10. 发明申请

WO2005007821A2 TERTIARY STRUCTURES OF ICA-1/LFA-1 MODULATORS 审中-公开
标题翻译： ICA-1 / LFA-1调制器的初步结构
公开(公告)号：WO2005007821A2
公开(公告)日：2005-01-27
申请号：PCT/US2004/021861
申请日：2004-07-07
申请人： SCIENCE & TECHNOLOGY CORPORATION @ UNM , LARSON, Richard, S. , SILLERUD, Laurel
发明人： LARSON, Richard, S. , SILLERUD, Laurel
IPC分类号： C12N
CPC分类号： C07K7/06 , G01N2333/70525
摘要： The invention provides tertiary structures) of cyclic nonapeptide ICAM-1 inhibitors and methods of using the tertiary structures tp identify additional ICAM-1 inhibitors, particularly non-peptide modulators. The invention also provides methods of treating ICAM1/LFA-1 mediated diseases comprising administ4ring a non-peptide ICAM-1 modulator of the invention to a patient in need thereof.
摘要翻译：本发明提供三级结构）的环状肽IIICAM-1抑制剂和使用三级结构tp的方法鉴定另外的ICAM-1抑制剂，特别是非肽调节剂。本发明还提供了治疗ICAM1 / LFA-1介导的疾病的方法，其包括向有需要的患者施用本发明的非肽ICAM-1调节剂。

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