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1. 发明申请

US20090104221A1 RAPID GENERATION OF T CELL-INDEPENDENT ANTIBODY RESPONSES TO T CELL-DEPENDENT ANTIGENS 审中-公开
标题翻译： T细胞独立抗体对T细胞依赖性抗体的快速产生
公开(公告)号：US20090104221A1
公开(公告)日：2009-04-23
申请号：US12167689
申请日：2008-07-03
申请人： Mohey Eldin Moustafa El Shikh , Rania El Sayed , Andras K. Szakal , John G. Tew , Donald R. Drake, III , Vaughan Wittman , Jennifer Eatrides , William L. Warren
发明人： Mohey Eldin Moustafa El Shikh , Rania El Sayed , Andras K. Szakal , John G. Tew , Donald R. Drake, III , Vaughan Wittman , Jennifer Eatrides , William L. Warren
IPC分类号： A61K39/00 , C12Q1/02 , C12P21/00
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状细胞（FDC）或FDC样细胞来产生FDC依赖但与T细胞无关的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在〜 48小时。在另一个实施方案中，使用生发中心（GC）淋巴组织等同物（LTE）产生抗原特异性IgM，随后切换至IgG。 GC LTE模型可用于疫苗评估。免疫原的双重形式用于GC LTE和体内。双重免疫原导致快速，特异性IgM反应和增强的IgG反应。例如，这种疫苗设计方法可以用于在移动到地方性疾病地区的人群中或在具有T细胞功能不足的人群中提供快速的IgM保护（〜24-48小时）和高亲和力IgG 免疫以快速产生保护性IgM。

2. 发明申请

US20070092530A1 Antibodies as T cell receptor mimics, methods of production and uses thereof 审中-公开
标题翻译：作为T细胞受体模拟物的抗体，其生产方法及其用途
公开(公告)号：US20070092530A1
公开(公告)日：2007-04-26
申请号：US11517516
申请日：2006-09-07
申请人： Jon Weidanz , Vaughan Wittman
发明人： Jon Weidanz , Vaughan Wittman
IPC分类号： A61K39/00 , C07H21/04 , C12P21/06 , C07K14/74
CPC分类号： C07K16/18 , A61K39/0011 , A61K2039/605 , C07K14/7051 , C07K16/2833 , C07K16/32 , C07K2317/32 , C07K2317/34 , 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。

3. 发明申请

US20050282877A1 Method of decreasing inflammation in kidney transplantion using angiotensin receptor blockers 审中-公开
标题翻译：使用血管紧张素受体阻断剂减少肾脏移植炎症的方法
公开(公告)号：US20050282877A1
公开(公告)日：2005-12-22
申请号：US11104165
申请日：2005-04-12
申请人： Bryan Becker , Lynn Jacobson , Debra Hullett , Jon Weidanz , Vaughan Wittman
发明人： Bryan Becker , Lynn Jacobson , Debra Hullett , Jon Weidanz , Vaughan Wittman
IPC分类号： A61K31/00 , A61K31/4178 , A61K31/4184
CPC分类号： A61K31/4184 , A61K31/4178
摘要： Disclosed is a method of inhibiting production of IFN-Γ in patients having a transplanted organ. The method involves administering to the patient an amount of an angiotensin receptor-blocking compound, the amount being effective to inhibit production of IFN-Γ by T cells. The method can be used to treat inflammation involving an allograft, to treat chronic allograft nephropathy, and to treat other pathologies associated with allograft rejection.
摘要翻译：公开了在具有移植器官的患者中抑制IFN-γ产生的方法。该方法包括向患者施用一定量的血管紧张素受体阻断化合物，其量有效抑制T细胞产生IFN-γ。该方法可用于治疗涉及同种异体移植物的炎症，治疗慢性同种异体移植肾病，以及治疗与同种异体移植排斥相关的其他病态。

4. 发明授权

US08962256B2 Surface-assisted hemagglutination and hemagglutination inhibition assays 有权
标题翻译：表面辅助血细胞凝集和血细胞凝集抑制试验
公开(公告)号：US08962256B2
公开(公告)日：2015-02-24
申请号：US12908211
申请日：2010-10-20
申请人： Anatoly Kachurin , Vaughan Wittman , Mike N. Nguyen , Olga Kachurina , Tenekua Tapia , Vipra Dhir , Alexander Karol
发明人： Anatoly Kachurin , Vaughan Wittman , Mike N. Nguyen , Olga Kachurina , Tenekua Tapia , Vipra Dhir , Alexander Karol
IPC分类号： G01N33/53 , G01N33/555 , G01N33/569 , G01N33/543
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。

5. 发明授权

US08778347B2 Fluorescent neutralization and adherence inhibition assays 有权
标题翻译：荧光中和和粘附抑制测定
公开(公告)号：US08778347B2
公开(公告)日：2014-07-15
申请号：US12616659
申请日：2009-11-11
申请人： Anatoly Kachurin , Olga Kachurina , Vaughan Wittman , Tenekua Tapia
发明人： Anatoly Kachurin , Olga Kachurina , Vaughan Wittman , Tenekua Tapia
IPC分类号： A01N63/00 , A61K39/42 , A61K39/12 , A61K45/00 , C12Q1/70 , G01N33/53 , C12Q1/02 , C12N7/00 , G01N21/76 , A61K49/00
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，便宜，可靠和灵敏的实验室测定。测定使用灭活的荧光标记的病毒，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病毒与靶细胞的相互作用。优选的实施方案使用简单且便宜的流式细胞术方法和设备，例如用作简化流式细胞仪的珠阵列读数器。测定快速，不超过几个小时，由训练有素的技术人员进行。测定是敏感的，因为它们以低浓度使用标记病毒，并确定低浓度血清和抗体的中和和阻断能力。该方法适用于大面积样品的高通量筛选。

6. 发明申请

US20110097705A1 Surface-assisted hemagglutination and hemagglutination inhibition assays 有权
标题翻译：表面辅助血细胞凝集和血细胞凝集抑制试验
公开(公告)号：US20110097705A1
公开(公告)日：2011-04-28
申请号：US12908211
申请日：2010-10-20
申请人： Anatoly Kachurin , Vaughan Wittman , Mike N. Nguyen , Olga Kachurina , Tenekua Tapia , Vipra Dhir , Alexander Karol
发明人： Anatoly Kachurin , Vaughan Wittman , Mike N. Nguyen , Olga Kachurina , Tenekua Tapia , Vipra Dhir , Alexander Karol
IPC分类号： C12Q1/70 , G01N33/68
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。

7. 发明授权

US5888775A Peptide synthesis and purification by fusion to penI protein or precipitation effective portion thereof 失效
标题翻译：通过与penI蛋白融合或其沉淀有效部分的肽合成和纯化
公开(公告)号：US5888775A
公开(公告)日：1999-03-30
申请号：US235178
申请日：1994-04-29
申请人： Rony Tal , Hing C. Wong , Clayton Casipit , Pierre-Andre Chavaillaz , Vaughan Wittman
发明人： Rony Tal , Hing C. Wong , Clayton Casipit , Pierre-Andre Chavaillaz , Vaughan Wittman
IPC分类号： G01N33/53 , A61K38/00 , A61K39/00 , A61P37/00 , A61P37/04 , C07K1/30 , C07K14/32 , C07K14/465 , C07K14/47 , C12N15/09 , C12N15/62 , C12P21/02 , C12R1/10 , C12R1/19 , G01N33/531 , C07K1/00 , C07K19/00
CPC分类号： C07K14/32 , C07K14/465 , C07K14/4706 , C07K14/4716 , C12N15/62 , C07K2319/50 , C07K2319/72 , C07K2319/80
摘要： The present invention provides novel methods for the synthesis and isolation and purification of a peptide of interest (target peptide). In particular, the invention relates to peptide synthesis, isolation and purification methods that comprise use of penI fusion polypeptides and related gene fusion constructs that encode such polypeptides.
摘要翻译：本发明提供用于合成和分离和纯化目标肽（靶肽）的新方法。特别地，本发明涉及肽合成，分离和纯化方法，其包括使用penI融合多肽和编码这种多肽的相关基因融合构建体。

8. 发明申请

US20060034850A1 Antibodies as T cell receptor mimics, methods of production and uses thereof 审中-公开
公开(公告)号：US20060034850A1
公开(公告)日：2006-02-16
申请号：US11140644
申请日：2005-05-27
申请人： Jon Weidanz , Vaughan Wittman
发明人： Jon Weidanz , Vaughan Wittman
IPC分类号： A61K39/395 , C07H21/04 , C12P21/06 , C07K16/30 , C12N5/06
CPC分类号： C07K16/18 , A61K39/0011 , A61K2039/605 , C07K14/7051 , C07K16/2833 , C07K16/32 , C07K2317/32 , C07K2317/34 , 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.

9. 发明授权

US5763284A Methods for peptide synthesis and purification 失效
标题翻译：肽合成和纯化方法
公开(公告)号：US5763284A
公开(公告)日：1998-06-09
申请号：US428733
申请日：1995-04-25
申请人： Rony Tal , Hing C. Wong , Clayton Casipit , Pierre-Andre Chavaillaz , Vaughan Wittman
发明人： Rony Tal , Hing C. Wong , Clayton Casipit , Pierre-Andre Chavaillaz , Vaughan Wittman
IPC分类号： G01N33/53 , A61K38/00 , A61K39/00 , A61P37/00 , A61P37/04 , C07K1/30 , C07K14/32 , C07K14/465 , C07K14/47 , C12N15/09 , C12N15/62 , C12P21/02 , C12R1/10 , C12R1/19 , G01N33/531 , G01N33/536 , G01N33/68
CPC分类号： C07K14/32 , C07K14/465 , C07K14/4706 , C07K14/4716 , C12N15/62 , C07K2319/50 , C07K2319/72 , C07K2319/80
摘要： The present invention provides novel methods for the synthesis and isolation and purification of a peptide of interest (target peptide). In particular, the invention relates to peptide synthesis, isolation and purification methods that comprise use of penI fusion polypeptides and related gene fusion constructs that encode such polypeptides.
摘要翻译：本发明提供用于合成和分离和纯化目标肽（靶肽）的新方法。特别地，本发明涉及肽合成，分离和纯化方法，其包括使用penI融合多肽和编码这种多肽的相关基因融合构建体。

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