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71. 发明申请

WO1996035446A1 TREATMENT OF ALZHEIMER DISEASE BY MODULATION OF SYNAPSINS 审中-公开
标题翻译：通过调节SYNPSINS治疗阿尔茨海默病
公开(公告)号：WO1996035446A1
公开(公告)日：1996-11-14
申请号：PCT/US1996006835
申请日：1996-05-13
申请人： THE ROCKEFELLER UNIVERSITY , BRIGHAM AND WOMEN'S HOSPITAL
发明人： THE ROCKEFELLER UNIVERSITY , BRIGHAM AND WOMEN'S HOSPITAL , HAN, Hui-Quan , GREENGARD, Paul , KOSIK, Kenneth, S. , FERREIRA, Adriana
IPC分类号： A61K38/18
CPC分类号： A61K31/7076 , A61K38/185 , A61K38/1883
摘要： The role of synapsin II in both the reformation and the maintenance of synaptic connections in cultured hippocampal neurons can be the basis of therapy for neurodegenerative disorder, particularly Alzheimer disease, which involve the disruption of synapses. When synapsin II expression in neurons is blocked by antisense synapsin II oligonucleotides, the ability of hippocampal neurons to reform as well as to maintain synapses is severely disrupted. Antisense suppression of synapsin II after axon formation but immediately before synaptogenesis prevents synapse formation. Suppression of synapsin II after synaptogenesis disrupts the majority of existing synapses. Re-expression of synapsin II in synapsin deficient neurons achieved after removing the antisense oligonucleotides leads to the re-establishment of synaptic connections, providing direct evidence that synapsin II is required for the maintenance and/or restoration of synapses. Thus, therapeutic methods based on the reformation and the maintenance of synapses, including delivery of the synapsin cDNAS or proteins into the patient's nervous system, use of the synapsin cDNAS to promote the synapse forming ability of cells for grafting, and use of agents that increase the expression of, enhancing the activity of, or mimic the activity of, the endogenous synapsins, can provide treatment of neurodegenerative disorders.
摘要翻译：突触素II在培养的海马神经元的突触连接的重建和维持中的作用可以作为神经变性疾病，特别是涉及突触中断的阿尔茨海默氏病的治疗的基础。当突触素II在神经元中的表达被反义突触蛋白II寡核苷酸阻断时，海马神经元改变的能力以及维持突触的能力被严重地破坏。在突触形成之后但紧接在突触发生之前的突触体II的反义抑制阻止突触形成。突触后突触素II的抑制破坏了大多数现有的突触。在去除反义寡核苷酸后实现的突触素缺陷型神经元中突触素II的重新表达导致突触连接的重新建立，提供突触间质II用于维持和/或恢复突触所需的直接证据。因此，基于重建和维持突触的治疗方法，包括将突触素cDNAS或蛋白质递送到患者神经系统中，使用突触素cDNAS来促进细胞用于移植的突触形成能力，并且使用增加的试剂增强内源性突触素的活性或模拟活性的表达可提供治疗神经变性疾病。

72. 发明申请

WO1996003993A2 MODULATION OF THYMOCYTE AND T CELL FUNCTIONAL ACTIVITY 审中-公开
标题翻译： THYMOCYTE和T细胞功能活性的调节
公开(公告)号：WO1996003993A2
公开(公告)日：1996-02-15
申请号：PCT/US1995009915
申请日：1995-08-07
申请人： THE ROCKEFELLER UNIVERSITY , BULLOCH, Karen , McEWEN, Bruce, S.
发明人： THE ROCKEFELLER UNIVERSITY
IPC分类号： A61K31/565
CPC分类号： A61K31/5685 , A61K38/225 , G01N33/5011
摘要： The present invention relates to modulation of cell mediated immune responses, and to modulation or inhibition of thymocyte cancers or thymomas. In a first aspect, the present invention is directed to a method for suppressing an immune response by administering dehydroepiandrosterone (DHEA). In another aspect, the invention relates to a method for enhancing an immune response comprising administering an amount of an inhibitor of calcitonin gene related peptide (CGRP), such as the CGRP antagonist CGRP8-37, or an amount of an inhibitor of DHEA. The invention also provides a method for treating a thymic cancer or thymoma comprising administering an amount of calcitonin gene related peptide (CGRP) effective to induce apoptosis of thymic cancer or thymoma cells. The invention further provides a method for preventing tissue damage comprising administering an amount of an inhibitor of CGRP to inhibit apoptosis of cells in the area of the tissue damage. The invention also relates to a method for identifying an agent capable of inhibiting CGRP-mediated apoptosis.
摘要翻译：本发明涉及细胞介导的免疫应答的调节，以及胸腺细胞癌或胸腺瘤的调节或抑制。在第一方面，本发明涉及通过给予脱氢表雄酮（DHEA）来抑制免疫应答的方法。另一方面，本发明涉及增强免疫应答的方法，包括给予一定量的降钙素基因相关肽（CGRP）抑制剂，例如CGRP拮抗剂CGRP8-37或一定量的DHEA抑制剂。本发明还提供一种治疗胸腺癌或胸腺瘤的方法，包括给予一定量的有效诱导胸腺癌或胸腺瘤细胞凋亡的降钙素基因相关肽（CGRP）。本发明还提供了一种预防组织损伤的方法，包括给予一定量的CGRP抑制剂以抑制组织损伤区域中的细胞凋亡。本发明还涉及鉴定能够抑制CGRP介导的细胞凋亡的药剂的方法。

73. 发明申请

WO1995033467A2 MODULATORS OF PNEUMOCOCCAL ADHERENCE TO PULMONARY AND VASCULAR CELLS AND DIAGNOSTIC AND THERAPEUTIC APPLICATIONS 审中-公开
标题翻译：肺血管密度与血管和血管细胞的调节剂和诊断和治疗应用
公开(公告)号：WO1995033467A2
公开(公告)日：1995-12-14
申请号：PCT/US1995007209
申请日：1995-06-06
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , TUOMANEN, Elaine, I. , CUNDELL, Diana, R.
IPC分类号： A61K31/70
CPC分类号： A61K31/7016 , A61K31/7032 , C12Q1/04 , G01N33/56944 , G01N2333/315 , Y10S435/885 , Y10S435/975 , A61K31/7004 , A61K2300/00
摘要： The present invention relates to compositions and methods for preventing pneumococcal infection. In particular, this invention relates to the identification of the minimum receptor targets of pneumococcal adherence to pulmonary and vascular endothelium, and to compositions and methods for preventing such adherence. In particular, the invention relates to the ability of one or more carbohydrate entities having the following motif or motifs: a disaccharide N-acetyl-D-galactosamine beta 1-3Gal motif, a disaccharide N-acetyl-D-galatosamine beta 1-4Gal motif, and an N-acetyl-D-glucosamine motif, effective to induce elution of adherent S. pneumoniae from host cells. In particular, a composition containing all three motifs can elute about 100 % of pneumococcal bacteria from lung epithelial cells, and from venous endothelial cells. In a particular embodiment, a pharmaceutical composition of the invention can be used to treat pneumococcal infections in which the host cells are lung epithelial cells. For use in blocking adherence to, or eluting adherent bacteria from, lung epithelial cells, the pharmaceutical composition is an aerosol formulation. The invention further provides formulations for parenteral administration for treating systemic blood-borne infections by preventing or reversing binding to venous endothelial cells. The invention further relates to methods and kits for determining the presence of pneumococci in a biological sample from a subject.
摘要翻译：本发明涉及预防肺炎球菌感染的组合物和方法。特别地，本发明涉及肺炎球菌粘附于肺和血管内皮的最小受体靶标的鉴定以及用于预防这种依从性的组合物和方法。特别地，本发明涉及具有以下基序或基序的一个或多个碳水化合物实体的能力：二糖N-乙酰基-D-半乳糖胺β1-3Gal基序，二糖N-乙酰基-D-加兰罗糖胺β1-4Gal 基序和N-乙酰基-D-葡糖胺基序，有效诱导粘附性肺炎链球菌从宿主细胞的洗脱。特别地，含有所有三个基序的组合物可从肺上皮细胞和静脉内皮细胞中洗脱约100％的肺炎球菌细菌。在一个具体实施方案中，本发明的药物组合物可用于治疗其中宿主细胞是肺上皮细胞的肺炎球菌感染。为了用于阻断对肺上皮细胞粘附或洗脱粘附细菌，药物组合物是气溶胶制剂。本发明进一步提供了通过预防或逆转与静脉内皮细胞结合来治疗全身性血源性感染的胃肠外给药制剂。本发明还涉及用于确定来自受试者的生物样品中肺炎球菌的存在的方法和试剂盒。

74. 发明申请

WO1995016039A1 AUXILIARY GENES AND PROTEINS OF METHICILLIN RESISTANT BACTERIA AND ANTAGONISTS THEREOF 审中-公开
标题翻译：甲基抗性细菌的辅助基因和蛋白质及其拮抗剂
公开(公告)号：WO1995016039A1
公开(公告)日：1995-06-15
申请号：PCT/US1994013952
申请日：1994-12-06
申请人： THE ROCKEFELLER UNIVERSITY , DE LENCASTRE, Herminia , TOMASZ, Alexander
发明人： THE ROCKEFELLER UNIVERSITY
IPC分类号： C12N15/31
CPC分类号： C12R1/445 , A61K31/43 , C07K14/31 , C12N15/102 , C12N15/74 , A61K2300/00
摘要： The present invention is directed to the identification of mutant strains of methicillin resistant bacteria, in particular methicillin resistant Staphylococcus aureus, to identify the characteristics of such bacteria and develop drugs that can reverse, inhibit or reduce bacterial resistance to beta lactam antibiotics, e.g., methicillin. The invention particularly relates to identification of a novel mutant strain of methicillin resistant S. aureus that manifests a unique phenotype. The mutant strain lacks unsubstituted pentapeptide and incorporates alanylglutamate- and alanylisoglutamine-containing muropeptides, and accumulates large amounts of the UDP-linked muramyul dipeptide in the cytoplasmic wall precursor pool of the mutant. Based on the phenotypic consequences of the mutation, inhibitors of the lysine addition step in bacterial cell wall biosynthesis are identified as having therapeutic potential for reducing baterial resistance to beta lactam antibiotics, notably methicillin. Accordingly, the invention provides for methods of treatment and corresponding pharmaceutical compositions for treating bacterial, particularly staphylococcal, infections.
摘要翻译：本发明涉及鉴定甲氧西林抗性细菌，特别是耐甲氧西林金黄色葡萄球菌的突变菌株，以鉴定这些细菌的特征并开发可逆转，抑制或降低对β-内酰胺抗生素的细菌耐药性的药物，例如甲氧西林。本发明特别涉及鉴定表现出独特表型的甲氧西林抗性金黄色葡萄球菌的新型突变菌株。突变菌株缺乏未取代的五肽，并掺入含有谷氨酰胺谷氨酸和氨基谷氨酰胺的神经肽，并在突变体的细胞质壁前体池中积聚了大量的UDP连接的胞壁基二肽。基于突变的表型结果，细菌细胞壁生物合成中的赖氨酸加成步骤的抑制剂被鉴定为具有降低对β-内酰胺抗生素（特别是甲氧西林）的耐药性的治疗潜力。因此，本发明提供了用于治疗细菌，特别是葡萄球菌感染的治疗方法和相应的药物组合物。

75. 发明申请

WO1995006732A2 BACTERIAL EXPORTED PROTEINS AND ACELLULAR VACCINES BASED THEREON 审中-公开
标题翻译：细菌出口蛋白质和基于其的细菌疫苗
公开(公告)号：WO1995006732A2
公开(公告)日：1995-03-09
申请号：PCT/US1994009942
申请日：1994-09-01
申请人： THE ROCKEFELLER UNIVERSITY , MASURE, H., Robert , PEARCE, Barbara, J , TUOMANEN, Elaine
发明人： THE ROCKEFELLER UNIVERSITY
IPC分类号： C12N15/52
CPC分类号： C12N9/0008 , A61K39/00 , C07K14/3156 , C07K2319/02 , C12N9/00 , C12N9/14 , C12N15/52 , C12Y102/03003
摘要： The present invention relates to the identification of Gram positive bacterial exported proteins, and the genes encoding such proteins. In particular, the invention relates to adhesion associated exported proteins, and to antigens common to many or all strains of a species of Gram positive bacterium. The invention also relates to acellular vaccines to provide protection from Gram positive bacterial infection using such genes or such proteins, and to antibodies against such proteins for use in diagnosis and passive immune therapy. In specific embodiments, fragments of ten genes encoding exported proteins of S. pneumoniae are disclosed, and the functional activity of some of these proteins in adherence is demonstrated.
摘要翻译：本发明涉及革兰氏阳性菌导出蛋白质的鉴定，以及编码这种蛋白质的基因。特别地，本发明涉及粘附相关的输出蛋白质，以及许多或所有革兰氏阳性细菌菌株共有的抗原。本发明还涉及使用这样的基因或这种蛋白质提供保护免受革兰氏阳性细菌感染的抗细胞疫苗以及用于诊断和被动免疫治疗的这种蛋白质的抗体。在具体实施方案中，公开了编码肺炎链球菌的出口蛋白质的十个基因的片段，并且证明了其中一些蛋白质在粘附中的功能活性。

76. 发明申请

WO1995006721A1 GENE SERUM OPACITY FACTOR 审中-公开
标题翻译：基因血清功能因子
公开(公告)号：WO1995006721A1
公开(公告)日：1995-03-09
申请号：PCT/US1994009926
申请日：1994-08-30
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , FISCHETTI, Vincent, A. , RAKONJAC, Jasna , ROBBINS, John
IPC分类号： C12N09/52
CPC分类号： C12N9/52 , C12Q1/37
摘要： Methods and compositions are provided for cloning and expression of serum opacity factor of Streptococcus pyogenes genes. The portion produced by the recombinant DNA techniques described herein may be employed in qualitative and quantitative testing for high density lipoprotein, as a fibronectin binding factor and for the regulation of high density lipoprotein in a mammal. The gene may further be employed as a molecular probe for accurate identification of opacity factors from various strains of Streptococcus pyogenes.
摘要翻译：提供了用于克隆和表达化脓性链球菌基因的血清不透明因子的方法和组合物。通过本文所述的重组DNA技术产生的部分可用于高密度脂蛋白的定性和定量测试，作为纤连蛋白结合因子，并用于哺乳动物中高密度脂蛋白的调节。该基因可进一步用作分子探针，用于准确鉴定来自各种化脓性链球菌菌株的不透明度因子。

77. 发明申请

WO1993018163A2 DELIVERY AND EXPRESSION OF A HYBRID SURFACE PROTEIN ON THE SURFACE OF GRAM POSITIVE BACTERIA 审中-公开
标题翻译：混合表面蛋白在GRAM阳性细菌表面的递送和表达
公开(公告)号：WO1993018163A2
公开(公告)日：1993-09-16
申请号：PCT/US1993002355
申请日：1993-03-12
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , FISCHETTI, Vincent, A. , POZZI, Gianni , SCHNEEWIND, Olaf
IPC分类号： C12N15/62
CPC分类号： C40B40/02 , A61K39/00 , A61K39/385 , A61K2039/523 , A61K2039/6068 , C07K14/005 , C07K14/28 , C07K14/315 , C07K2319/00 , C07K2319/035 , C07K2319/40 , C12N15/1037 , C12N15/62 , C12N15/746 , C12N2710/20022
摘要： Process is described for the delivery and expression of hybrid surface proteins to the surface of bacteria. The transformed bacteria are useful as vaccines, for the delivery of other active peptides to animal hosts, as diagnostic reagents and for other purposes.
摘要翻译：描述了将杂交表面蛋白递送和表达到细菌表面的过程。转化的细菌可用作疫苗，用于将其它活性肽递送到动物宿主，作为诊断试剂和用于其它目的。

78. 发明申请

WO1993018161A1 RECEPTOR COMPLEXES WITH B29 (IG-BETA OR IG-GAMMA) AND THEIR USES 审中-公开
标题翻译：与B29（IG-BETA或IG-GAMMA）的受体复合物及其用途
公开(公告)号：WO1993018161A1
公开(公告)日：1993-09-16
申请号：PCT/US1993001865
申请日：1993-03-03
申请人： THE ROCKEFELLER UNIVERSITY , NUSSENZWEIG, Michel, C. , COSTA, Thais, E. , FRANKE, Roland, R. , SANCHEZ, Mercedes , MISULOVIN, Ziva
发明人： THE ROCKEFELLER UNIVERSITY
IPC分类号： C12N15/62
CPC分类号： A61K35/15 , A61K35/17 , A61K38/00 , C07K14/58 , C07K14/70503 , C07K14/7051 , C07K16/18 , C07K16/4283 , C12N2740/13011 , G01N33/56977
摘要： Antigen receptors on B-lymphocytes are transfected or reconstructed in cells, such as T-lymphocytes, mast cells, macrophage cells and the like. When the gene coding the immunoglobulin molecule is transfected into any of these host cells with the gene coding the polypeptide B29, such host cells do not require antigen reaction with APCs in the context of MHC to effect an immune response. The cells can also be transfected with an antibody to a particular antigen to modify antigen recognition. Constructs containing the sequences which code for the immunoglobulin and related proteins, therapeutic and diagnostic methods, compositions and kits for performing such methods are also included.
摘要翻译：在淋巴细胞，淋巴细胞，巨噬细胞等细胞中转染或重建B淋巴细胞上的抗原受体。当编码免疫球蛋白分子的基因用编码多肽B29的基因转染到任何这些宿主细胞中时，这样的宿主细胞在MHC的上下文中不需要与APC的抗原反应以实现免疫应答。细胞还可以用针对特定抗原的抗体转染以修饰抗原识别。还包括含有编码免疫球蛋白和相关蛋白的序列的构建体，用于进行此类方法的治疗和诊断方法，组合物和试剂盒。

79. 发明申请

WO1993014198A1 MULTIFUNCTIONAL SURFACE PROTEIN OF STREPTOCOCCI 审中-公开
标题翻译：多功能表面蛋白质
公开(公告)号：WO1993014198A1
公开(公告)日：1993-07-22
申请号：PCT/US1993000082
申请日：1993-01-07
申请人： THE ROCKEFELLER UNIVERSITY , FISCHETTI, Vincent, A. , PANCHOLI, Vijaykumar
发明人： THE ROCKEFELLER UNIVERSITY
IPC分类号： C12N09/02
CPC分类号： C12N9/0008 , A61K39/00 , C07K14/315 , C12Y102/01009
摘要： A novel streptococcal surface protein principally characterized by fibronectin and lysozyme binding activity, but also having glyceraldehyde-3-phosphate dehydrogenase activity, ADP-ribosylating activity and ADP-ribosyl transferase activity are described. It is particularly useful for the preparation of vaccines to protect against streptococcal infections.
摘要翻译：描述了主要由纤连蛋白和溶菌酶结合活性表征，但也具有甘油醛-3-磷酸脱氢酶活性，ADP-核糖基化活性和ADP-核糖基转移酶活性的新型链球菌表面蛋白。它特别适用于疫苗的制备，以防止链球菌感染。

80. 发明申请

WO1993013201A1 LIPOPOLYSACCHARIDE BINDING OPSONIN INHIBITOR AND METHODS OF USE THEREOF 审中-公开
标题翻译：脂多糖联合抑制剂及其使用方法
公开(公告)号：WO1993013201A1
公开(公告)日：1993-07-08
申请号：PCT/US1992011192
申请日：1992-12-23
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , WRIGHT, Samuel, D.
IPC分类号： C12N09/64
CPC分类号： C12N9/6421 , A61K38/00 , C07K16/40
摘要： An agent that inhibits the activity of a lipopolysaccharide binding opsonin is disclosed. The agent has been isolated from plasma and is believed to be a protease that inactivates the opsonin by cleaving it. The agent possesses utility in the treatment of shock and other conditions that may result from the activity of the opsonin in response to host invasion. Diagnostic and therapeutic utilities are proposed, and testing procedures, materials in kit form, recombinant materials and procedures, and pharmaceutical compositions are likewise set forth.
摘要翻译：公开了抑制脂多糖结合调理素活性的试剂。该药物已经从血浆中分离出来，被认为是通过裂解使调理素失活的蛋白酶。该药物可用于治疗由于调理素在宿主入侵时的活动而引起的休克和其他病症。提出了诊断和治疗用途，同样阐述了测试程序，试剂盒形式的材料，重组材料和程序以及药物组合物。

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