公开(公告)号：CA2397485A1

公开(公告)日：2001-07-19

申请号：CA2397485

申请日：2001-01-16

Applicant: STC UNM

Inventor： LARSON RICHARD S

IPC: A61K38/00 ,  A61K38/12 ,  C07K7/06 ,  C07K7/64 ,  C07K1/22

Abstract: Cyclic peptides inhibit LFA-1 interaction with ICAM-1 and are useful in treatment of hematopoietic neoplasms and in adjunct therapy in prevention of retinoic acid syndrome and diseases involving emigration of leukocytes into organ tissue.

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

Applicant: 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

Inventor： 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: C12Q1/34 ,  C12M3/00

CPC classification number: G01N33/54373 ,  C12Q1/6825 ,  G01N29/032 ,  G01N33/553 ,  G01N2291/0422

Abstract: 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.

Abstract translation: 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）。

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

Applicant: STC UNM ,  LARSON RICHARD S ,  SILLERUD LAUREL

Inventor： LARSON RICHARD S ,  SILLERUD LAUREL

IPC: G01N33/48 ,  C07K7/06 ,  C12N20060101 ,  G01N33/50 ,  G01N33/53 ,  G06F19/00

CPC classification number: C07K7/06 ,  G01N2333/70525

Abstract: 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.

Abstract translation: 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。

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

Applicant: STC UNM ,  LARSON RICHARD S

Inventor： LARSON RICHARD S

IPC: A61K38/00 ,  A61K38/08 ,  C07K20060101 ,  C07K7/06

CPC classification number: C07K7/06

Abstract: 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.

Abstract translation: 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。