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1. 发明申请

WO2010056744A3 FLUORESCENT NEUTRALIZATION AND ADHERENCE INHIBITION ASSAYS 审中-公开
标题翻译：荧光中和与粘附抑制试验
公开(公告)号：WO2010056744A3
公开(公告)日：2010-08-19
申请号：PCT/US2009064026
申请日：2009-11-11
申请人： VAXDESIGN CORP , KACHURIN ANATOLY , KACHURINA OLGA , WITTMAN VAUGHAN , TAPIA TENEKUA
发明人： KACHURIN ANATOLY , KACHURINA OLGA , WITTMAN VAUGHAN , TAPIA TENEKUA
IPC分类号： G01N33/533 , G01N33/569
CPC分类号： G01N33/502 , A61K49/085 , C07K14/005 , C12Q1/18 , G01N33/56983 , G01N33/6854 , G01N2333/11 , G01N2500/02 , G01N2500/10
摘要： The present invention comprises rugged, inexpensive, reliable, and sensitive laboratory assays of antibody-based viral neutralization activity and antibody-based viral adherence inhibition activity. The assays use inactivated, fluorescently-labeled virus, allowing the tests to be performed without extensive safety precautions. The interaction of the labeled virus with target cells is monitored using flow cytometric methods. A preferred embodiment uses simple and inexpensive flow cytometry methodologies and equipment, such as bead array readers used as simplified flow cytometers. The assays are rapid, taking no longer than a few hours and are readily conducted by a trained technician. The assays are sensitive because they use labeled viruses at low concentrations and determine neutralizing and blocking capacity of sera and antibody at low concentrations. The methods are appropriate for high-throughput screening of large panels of samples.
摘要翻译：本发明包括基于抗体的病毒中和活性和基于抗体的病毒粘附抑制活性的坚固，廉价，可靠和敏感的实验室测定。该测定法使用灭活的荧光标记病毒，允许在没有广泛的安全预防措施的情况下进行测试。使用流式细胞术方法监测标记的病毒与靶细胞的相互作用。一个优选的实施方案使用简单且便宜的流式细胞术方法学和设备，例如用作简化的流式细胞仪的珠阵列阅读器。分析速度快，不超过几个小时，并且由训练有素的技术人员随时进行。该测定法是敏感的，因为它们使用低浓度的标记病毒并确定低浓度的血清和抗体的中和和阻断能力。该方法适用于大量样品的高通量筛选。

2. 发明申请

WO2011050027A3 SURFACE-ASSISTED HEMAGGLUTINATION AND HEMAGGLUTINATION INHIBITION ASSAYS 审中-公开
标题翻译：表面辅助HEMAGGLUTINATION和HEMAGGLUTINATION抑制测定
公开(公告)号：WO2011050027A3
公开(公告)日：2011-08-18
申请号：PCT/US2010053322
申请日：2010-10-20
申请人： SANOFI PASTEUR VAXDESIGN CORP , KACHURIN ANATOLY , WITTMAN VAUGHAN , NGUYEN MIKE , KACHURINA OLGA , TAPIA TENEKUA , DHIR VIPRA , KAROL ALEXANDER
发明人： KACHURIN ANATOLY , WITTMAN VAUGHAN , NGUYEN MIKE , KACHURINA OLGA , TAPIA TENEKUA , DHIR VIPRA , KAROL ALEXANDER
IPC分类号： G01N33/569 , C07K16/08
CPC分类号： G01N33/56983 , G01N33/54353 , G01N33/54393 , G01N33/555
摘要： Hemagglutination (HA) and hemagglutination inhibition (HAI) functional assays remain important instruments of analysis of virus-cell interaction and protecting efficacy of virus-specific antibodies and sera. However, they demonstrate limited sensitivity towards many viruses, and require significant volumes of viruses, erythrocytes, sera, and antibodies. The present invention comprises new and significantly more sensitive versions of the HA and HAI assays based on observing agglutination on activated surfaces of specifically opsonized plates and ELISA plates rather than in solution. A version of the new assay that uses ELISA plates additionally allows characterizing the affinity of functional antibodies in the tested sera and fluids, which is not possible in the classical HAI assay. The methods of the present invention can also be used to improve the sensitivity of agglutination methods based on latex beads and to develop agglutination methods using target cells other than erythrocytes.
摘要翻译：血细胞凝集（HA）和血细胞凝集抑制（HAI）功能测定仍然是分析病毒 - 细胞相互作用和保护病毒特异性抗体和血清功效的重要手段。然而，它们对许多病毒的敏感性有限，并且需要大量的病毒，红细胞，血清和抗体。本发明包括基于观察特异性调理板和ELISA板的活化表面上的凝集而不是在溶液中的HA和HAI测定的新的和显着更敏感的版本。使用ELISA板的新测定版本另外允许表征所测试的血清和液体中功能性抗体的亲和力，这在经典的HAI测定中是不可能的。本发明的方法也可用于提高基于乳胶珠的凝集方法的灵敏度，并且使用除了红细胞以外的靶细胞产生凝集方法。

3. 发明申请

WO2010002852A2 BEAD ARRAY READER BASED-HEMAGGLUTINATION AND HEMAGGLUTINATION INHIBITION ASSAYS 审中-公开
标题翻译：基于阵列读取器的HEMAGGLUTINATION和HEMAGGLUTINATION抑制测定
公开(公告)号：WO2010002852A2
公开(公告)日：2010-01-07
申请号：PCT/US2009049195
申请日：2009-06-30
申请人： VAXDESIGN CORP , KACHURIN ANATOLY , WITTMAN VAUGHAN , KACHURINA OLGA , TAPIA TENEKUA
发明人： KACHURIN ANATOLY , WITTMAN VAUGHAN , KACHURINA OLGA , TAPIA TENEKUA
IPC分类号： G01N33/50 , C12Q1/02
CPC分类号： G01N33/555 , G01N33/56983 , G01N2333/11
摘要： Hemagglutination assays and hemagglutination inhibition assays were introduced in medical and virology practice more than 60 years ago. Since then, these assays have become important tools for measuring concentrations and strengths of viral cultures, the efficacy of the anti-viral immunization, and for studying the neutralizing capacity of virus-specific antibodies. The present invention comprises an improved hemagglutination inhibition assay (HAI), with at least about a 10-fold increase in sensitivity versus the traditional the HAI, to provide more accurate measurements of components in, for example, fluids from the in vitro MIMIC® system when assessing the effects of anti-viral vaccines (e.g., for seasonal influenza).
摘要翻译： 60多年前，血液凝集试验和血细胞凝集抑制试验被纳入医学和病毒学实践。从那时起，这些检测已经成为测量病毒培养物的浓度和强度，抗病毒免疫功效以及研究病毒特异性抗体中和能力的重要手段。本发明包括改进的血细胞凝集抑制测定（HAI），与传统的HAI相比，灵敏度增加至少约10倍，以提供例如来自体外MIMIC系统的流体中组分的更准确的测量当评估抗病毒疫苗的效果（例如季节性流感）时。

4. 发明申请

WO2009009424A3 RAPID GENERATION OF T CELL-INDEPENDENT ANTIBODY RESPONSES TO T CELL-DEPENDENT ANTIGENS 审中-公开
标题翻译： T细胞依赖性抗体对T细胞依赖性抗原应答的快速生成
公开(公告)号：WO2009009424A3
公开(公告)日：2009-05-22
申请号：PCT/US2008069172
申请日：2008-07-03
申请人： VAXDESIGN CORP , UNIV VIRGINIA COMMONWEALTH , EL SHIKH MOHEY ELDIN MOUSTAFA , EL SAYED RANIA , SZAKAL ANDRAS K , TEW JOHN G , DRAKE III DONALD R , WITTMAN VAUGHAN , EATRIDES JENNIFER , WARREN WILLIAM L
发明人： EL SHIKH MOHEY ELDIN MOUSTAFA , EL SAYED RANIA , SZAKAL ANDRAS K , TEW JOHN G , DRAKE III DONALD R , WITTMAN VAUGHAN , EATRIDES JENNIFER , WARREN WILLIAM L
IPC分类号： G01N33/53 , A61K39/385 , C40B30/06
CPC分类号： G01N33/5052 , A61K39/00 , A61K2039/545 , A61K2039/55505 , A61K2039/6012 , A61K2039/6056 , C07K16/4283 , C12N5/0639 , C12N2503/02 , G01N33/5044 , G01N33/505 , G01N33/5082
摘要： The present invention comprises the use of follicular dendritic cells (FDCs) or FDC-like cells to generate FDC-dependent, but T cell-independent, B cell responses to T cell-dependent antigens, with antigen-specific and polyclonal antibody production in ~48 h. In another embodiment, a germinal center (GC) lymphoid tissue equivalent (LTE) was used to generate~ antigen-specific IgM, followed by switching to IgG. The GC LTE model can be used in vaccine assessment. Dual forms of immunogen were used in the GC LTE and in vivo. Dual immunogens resulted in rapid, specific IgM responses and enhanced IgG responses. This vaccine design approach can be used, for example, to provide rapid IgM protection (~24 48 h) and high-affinity IgG more quickly in people moving to areas with endemic disease, or in people with T cell insufficiencies, who can be immunized to rapidly generate protective IgM.
摘要翻译：本发明包括使用滤泡树突细胞（FDC）或FDC样细胞产生FDC依赖性但不依赖T细胞的B细胞对T细胞依赖性抗原的应答，其中抗原特异性和多克隆抗体产生于〜 48小时。在另一个实施方案中，使用生发中心（GC）淋巴组织当量（LTE）产生抗原特异性IgM，随后转换为IgG。 GC LTE模型可用于疫苗评估。双重形式的免疫原用于GC LTE和体内。双重免疫原导致快速，特异性IgM应答和增强的IgG应答。例如，这种疫苗设计方法可用于在迁入疾病流行地区或T细胞功能不全的人群中更快地提供快速IgM保护（〜24 48 h）和高亲和力IgG，并且可以免疫接种迅速产生保护性IgM。

5. 发明申请

WO2007030451A3 ANTIBODIES AS T CELL RECEPTOR MIMICS, METHODS OF PRODUCTION AND USES THEREOF 审中-公开
标题翻译：抗体作为细胞受体MIMICS，生产方法及其用途
公开(公告)号：WO2007030451A3
公开(公告)日：2009-04-16
申请号：PCT/US2006034547
申请日：2006-09-07
申请人： RECEPTOR LOGIC LTD , WEIDANZ JON A , WITTMAN VAUGHAN
发明人： WEIDANZ JON A , WITTMAN VAUGHAN
IPC分类号： A61K39/00 , A61B5/055 , C07H21/02 , C07K5/10 , C07K16/00 , G01N33/574
CPC分类号： C07K14/70539 , C07K16/00 , C07K16/26 , C07K16/2833 , C07K16/30 , C07K16/32 , C07K2317/32 , C07K2317/34 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2317/92
摘要： The present invention relates to a methodology of producing antibodies that recognize peptides associated with a tumorigenic or disease state, wherein the peptides are displayed in the context of HLA molecules. These antibodies will mimic the specificity of a T cell receptor (TCR) but will have higher binding affinity such that the molecules may be used as therapeutic, diagnostic and research reagents. The method of producing a T-cell receptor mimic of the present invention includes identifying a peptide of interest, wherein the peptide of interest is capable of being presented by an MHC molecule. Then, an immunogen comprising at least one peptide/MHC complex is formed, wherein the peptide of the peptide/MHC complex is the peptide of interest. An effective amount of the immunogen is then administered to a host for eliciting an immune response, and serum collected from the host is assayed to determine if desired antibodies that recognize a three-dimensional presentation of the peptide in the binding groove of the MHC molecule are being produced. The desired antibodies can differentiate the peptide/MHC complex from the MHC molecule alone, the peptide alone, and a complex of MHC and irrelevant peptide. Finally, the desired antibodies are isolated.
摘要翻译：本发明涉及产生识别与致瘤性或疾病状态相关的肽的抗体的方法，其中所述肽在HLA分子的上下文中显示。这些抗体将模拟T细胞受体（TCR）的特异性，但具有较高的结合亲和力，使得该分子可用作治疗，诊断和研究试剂。制备本发明的T细胞受体模拟物的方法包括鉴定感兴趣的肽，其中所述肽能够被MHC分子呈递。然后，形成包含至少一个肽/ MHC复合物的免疫原，其中肽/ MHC复合物的肽是目的肽。然后将有效量的免疫原施用于宿主以引发免疫应答，并测定从宿主收集的血清，以确定是否需要识别在MHC分子的结合槽中肽的三维呈现的所需抗体是正在生产。所需的抗体可以区分肽/ MHC复合物与单独的MHC分子，单独的肽以及MHC和无关肽的复合物。最后，分离所需的抗体。

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