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1. 发明申请

WO1997041440A1 METHODS FOR SELECTING AND PRODUCING T CELL PEPTIDE EPITOPES AND VACCINES INCORPORATING SAID SELECTED EPITOPES 审中-公开
标题翻译：选择和产生含有选择性抗原决定簇的T细胞肽抗原和疫苗的方法
公开(公告)号：WO1997041440A1
公开(公告)日：1997-11-06
申请号：PCT/NL1997000229
申请日：1997-04-28
申请人： RIJKSUNIVERSITEIT TE LEIDEN , SEED CAPITAL INVESTMENTS (SCI) B.V. , VAN DER BURG, Sjoerd, Henricus , KAST, Wybe, Martin , TOES, Reinaldus, Everardus, Maria , OFFRINGA, Rienk , MELIEF, Cornelius, Johannes, Maria
发明人： RIJKSUNIVERSITEIT TE LEIDEN , SEED CAPITAL INVESTMENTS (SCI) B.V.
IPC分类号： G01N33/569
CPC分类号： G01N33/56977
摘要： The present invention relates to the field of molecular biology and immunology. In particular it relates to vaccines and methods for providing vaccines which elicit immune responses when administered to a mammal, in particular a human. The preferred elicited immune response is a T cell response, elicited by peptide T cell epitopes. These vaccines find their application in many fields ranging from cancer treatments to treatments of prophylaxis of infectious diseases such as Aids. The present invention provides novel methods for selecting the peptide sequences from an intact antigen which will lead to a proper (T cell) immune response upon administration in a suitable vehicle. The epitopes and vaccines are, of course, also part of the present invention.
摘要翻译：本发明涉及分子生物学和免疫学领域。特别地，本发明涉及用于提供疫苗的疫苗和方法，其在施用于哺乳动物，特别是人时可引起免疫应答。优选的引发免疫应答是由肽T细胞表位引起的T细胞应答。这些疫苗可用于许多领域，从癌症治疗到预防感染性疾病如艾滋病的治疗。本发明提供了从完整抗原中选择肽序列的新方法，该合适的抗原将在合适的载体中施用后导致适当的（T细胞）免疫应答。表位和疫苗当然也是本发明的一部分。

2. 发明申请

WO1997005169A1 HA-2 ANTIGENIC PEPTIDE 审中-公开
标题翻译： HA-2抗原肽
公开(公告)号：WO1997005169A1
公开(公告)日：1997-02-13
申请号：PCT/NL1996000183
申请日：1996-04-25
申请人： RIJKSUNIVERSITEIT TE LEIDEN , THE UNIVERSITY OF VIRGINIA PATENT FOUNDATION , GOULMY, Els, A., J., M. , HUNT, Donald, F. , ENGELHARD, Victor, H.
发明人： RIJKSUNIVERSITEIT TE LEIDEN , THE UNIVERSITY OF VIRGINIA PATENT FOUNDATION
IPC分类号： C07K14/74
CPC分类号： C07K14/70539 , A61K38/00
摘要： The present invention discloses the first peptide sequence of a so-called minor H antigen. The minor H antigens are associated with the Graft versus Host Disease. The peptide and its derivatives find many uses in bone marrow transplantation, organ transplantation and in the treatment of leukemia. The peptide and its derivatives can be incorporated in vaccines, in pharmaceutical formulations and they can be used in diagnostic test kits. The peptide is derived from the HA-2 minor antigen and has the sequence YXGEVXVSV, wherein X represents a leucine or an isoleucine residue. Both donors and recipients in bone marrow transplantation can be treated with the peptides, optionally in combination with other peptides, coupled to carriers, with suitable excipients and/or adjuvants.
摘要翻译：本发明公开了所谓的次要H抗原的第一个肽序列。次要H抗原与移植物抗宿主病有关。该肽及其衍生物在骨髓移植，器官移植和白血病治疗中有很多用途。肽及其衍生物可以掺入疫苗，药物制剂中，并可用于诊断试剂盒。该肽衍生自HA-2次要抗原并具有序列YXGEVXVSV，其中X表示亮氨酸或异亮氨酸残基。骨髓移植中的供体和受体都可以用肽治疗，任选地与其它肽结合，与载体偶联，与合适的赋形剂和/或佐剂组合。

3. 发明申请

WO1993017116A1 AGROBACTERIUM STRAINS CAPABLE OF SITE-SPECIFIC RECOMBINATION 审中-公开
标题翻译：具有特异性重组能力的农杆菌菌株
公开(公告)号：WO1993017116A1
公开(公告)日：1993-09-02
申请号：PCT/EP1993000463
申请日：1993-02-25
申请人： MOGEN INTERNATIONAL N.V. , RIJKSUNIVERSITEIT TE LEIDEN , HOOYKAAS, Paul, Jan, Jacob , MOZO, Teresa
发明人： MOGEN INTERNATIONAL N.V. , RIJKSUNIVERSITEIT TE LEIDEN
IPC分类号： C12N15/74
CPC分类号： C12N15/64 , C12N15/743 , C12N15/8205
摘要： The invention provides Agrobacterium strains capable of producing a site-specific recombinase effecting site-specific recombination of a first and a second recombination site in said Agrobacterium strain, when present therein, comprising a structural DNA sequence encoding said recombinase and a DNA sequence capable of controlling expression in said Agrobacterium strains. Also provided are methods of use of said Agrobacterium strains, in particular for obtaining transformed plants.
摘要翻译：本发明提供了能够产生位点特异性重组酶的农杆菌菌株，其在存在于所述农杆菌菌株中时产生第一和第二重组位点的位点特异性重组，其包含编码所述重组酶的结构DNA序列和能够控制的DNA序列在所述农杆菌菌株中的表达。还提供了所述农杆菌菌株的使用方法，特别是用于获得转化的植物。

4. 发明申请

WO1990010274A1 NEURONAL DATA PROCESSING NETWORK 审中-公开
标题翻译：神经数据处理网络
公开(公告)号：WO1990010274A1
公开(公告)日：1990-09-07
申请号：PCT/NL1990000018
申请日：1990-02-20
申请人： RIJKSUNIVERSITEIT TE LEIDEN , WOLTERS, Gezinus , MURRE, Jacob, Marinus, Jan , PHAF, Rutger, Hans
发明人： RIJKSUNIVERSITEIT TE LEIDEN
IPC分类号： G06F15/80
CPC分类号： G06N3/04 , G06N99/005
摘要： A data processing module or neural network, comprising a plurality of nodes, as well as connections between said nodes, through which connections data weighted by a weighting factor can be transmitted between the nodes, said nodes having an activation value representative of the data received. There are provides at least three types of nodes; a first type (R) adapted to receive external data and at least two of which are present; a second type (V), one of which is always paired with a node of the first type; and a third type (A, E), at least one of which is present. Each node of the first type (R) is connected through a connection with a preferably positive weighting factor (up, low) to the associated node of the second type (V) and to the node of the third type (A, E). Each node of the second type (V) is connected through a connection with a preferably negative weighting factor (flat; cross; high) to the other nodes of the second type (V), to the nodes of the first type (R) not being paired therewith, and to the node of the third type (A, E). The node of the third type (A, E) is connected through connections with a preferably positive weighting factor (strange) to the nodes of the first type.
摘要翻译：包括多个节点的数据处理模块或神经网络以及所述节点之间的连接，通过该数据处理模块或神经网络可以在所述节点之间传送由加权因子加权的连接数据，所述节点具有表示接收到的数据的激活值。提供至少三种类型的节点; 适于接收外部数据的第一类型（R），并且其中至少两个存在; 第二类型（V），其中之一总是与第一类型的节点配对; 和第三类型（A，E），其中至少一个存在。第一类型（R）的每个节点通过具有优选正的加权因子（向上，向下）的连接连接到第二类型（V）的相关联节点并连接到第三类型（A，E）的节点。第二类型（V）的每个节点通过具有优选负加权因子（平坦;交叉;高）到第二类型（V）的其他节点的连接连接到第一类型（R）的节点与第三类型（A，E）配对。第三类型（A，E）的节点通过具有优选正的加权因子（奇数）的连接连接到第一类型的节点。

5. 发明申请

WO1998013378A1 MANNOSYLATED PEPTIDES 审中-公开
标题翻译：人造胶原蛋白
公开(公告)号：WO1998013378A1
公开(公告)日：1998-04-02
申请号：PCT/NL1997000536
申请日：1997-09-25
申请人： RIJKSUNIVERSITEIT TE LEIDEN , KONING, Frits , DRIJFHOUT, Jan, Wouter
发明人： RIJKSUNIVERSITEIT TE LEIDEN
IPC分类号： C07K14/35
CPC分类号： C07K14/70539 , C07K9/00
摘要： T cells mediate specific immune reactions. They recognize (foreign) protein fragments - peptides - that are bound in the peptide binding groove of MHC molecules. These peptide MHC complexes are generated intracellularly and subsquently transported to the cell surface for recognition by T cells. A rate limiting step in the MHC restricted presentation of (foreign) peptides derived from extracellular sources is therefore the uptake of such antigens by antigen presenting cells and the delivery to the intracellular compartment(s) where the MHC-peptide complexes are formed. Professional antigen presenting cells like dendritic cells and macrophages take up antigens by macropinocytosis and mannose receptor mediated endocytosis. We have explored the possibility that the mannosylation of otherwise non-mannosylated antigens would lead to enhanced uptake and MHC restricted presentation of (fragments of) such antigens by mannose receptor positive cells. Using mannose receptor positive cultured human dendritic cells as antigen presenting cells we found that the mannosylation of antigenic peptides resulted in a 300 - 10.000 fold enhanced potency to stimulate MHC class II restricted peptide-specific T cell clones compared to non-mannosylated peptides. These results indicate that mannosylation of antigens leads to selective targeting and subsequent superior presentation by dendritic cells, a result which may be applicable in for example vaccine design.
摘要翻译： T细胞介导特异性免疫反应。他们认识到（外来的）蛋白质片段 - 肽结合在MHC分子的肽结合槽中。这些肽MHC复合物在细胞内和细胞内产生，被T细胞识别。因此，MHC限制性地表达来自细胞外源的（外源）肽的速率限制步骤是抗原呈递细胞对这些抗原的摄取以及递送至其中形成MHC-肽复合物的细胞内区室。专业抗原呈递细胞如树突状细胞和巨噬细胞通过巨噬细胞增多和甘露糖受体介导的内吞作用占据抗原。我们已经探索了其他非甘露糖基化抗原的甘露糖基化可导致甘露糖受体阳性细胞增强摄取和MHC限制性表达（片段）这种抗原的可能性。使用甘露糖受体阳性培养的人树突状细胞作为抗原呈递细胞，我们发现与非甘露糖基化肽相比，抗原肽的甘露糖基化导致刺激MHC II类限制性肽特异性T细胞克隆的增强效力为300-10,000倍。这些结果表明抗原的甘露糖基化导致选择性靶向和随后的树突状细胞的优异表达，其可能适用于例如疫苗设计。

6. 发明申请

WO1997005900A1 CELL DERIVED ANTIGEN PRESENTING VESICLES 审中-公开
标题翻译：细胞衍生的抗原产生的抗生素
公开(公告)号：WO1997005900A1
公开(公告)日：1997-02-20
申请号：PCT/NL1996000317
申请日：1996-08-05
申请人： RIJKSUNIVERSITEIT TE LEIDEN , RIJKSUNIVERSITEIT UTRECHT , GEUZE, Johannes, J. , MELIEF, Cornelis, J., M.
发明人： RIJKSUNIVERSITEIT TE LEIDEN , RIJKSUNIVERSITEIT UTRECHT
IPC分类号： A61K39/385
CPC分类号： A61K39/39 , A61K39/04 , A61K2039/5154 , A61K2039/55555
摘要： The invention provides a novel vehicle for vaccination, in particular peptide vaccination. The new vehicle has been termed an exosome. Exosomes are vesicles derived from MHC class II enriched compartments in antigen presenting cells. The exosomes possess MHC II and/or MHC I molecules at their surface and possibly peptides derived from processed antigens in said MHC's. Thus the exosome is a perfect vaccination vehicle in that it presents the peptide in a natural setting. The peptides present in the exosome in the MHC molecule may be processed by the antigen presenting cell from which the exosome is derived. Empty MHC molecules on exosomes may also be loaded with peptides afterwards.
摘要翻译：本发明提供了用于疫苗接种，特别是肽疫苗接种的新载体。新车被称为外来体。外来体是来自抗原提呈细胞中MHC II类富集区的囊泡。外来体在其表面具有MHC II和/或MHC I分子，并且可能在所述MHC中具有衍生自加工抗原的肽。因此，外来体是完美的疫苗接种载体，因为它在自然环境中呈现肽。存在于MHC分子中的外来体中的肽可以由衍生外来体的抗原呈递细胞进行加工。外来体上的空的MHC分子也可以随后加载肽。

7. 发明申请

WO1992004446A1 CLONING OF CHICKEN ANAEMIA DNA 审中-公开
标题翻译：克隆鸡血清DNA
公开(公告)号：WO1992004446A1
公开(公告)日：1992-03-19
申请号：PCT/NL1991000165
申请日：1991-09-11
申请人： STICHTING CENTRAAL DIERGENEESKUNDIG INSTITUUT , RIJKSUNIVERSITEIT TE LEIDEN , NOTEBORN, Matheus, Hubertus, Maria , DE BOER, Gerben, Foppe
发明人： STICHTING CENTRAAL DIERGENEESKUNDIG INSTITUUT , RIJKSUNIVERSITEIT TE LEIDEN
IPC分类号： C12N15/35
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , A61K48/00 , C12N15/86 , C12N2750/10022 , C12N2750/10043 , C12N2830/00 , C12N2830/008 , C12N2830/60 , G01N33/56983 , G01N33/574 , Y10S424/816 , Y10S435/81
摘要： Recombinant genetic information (DNA or RNA), comprising a Chicken Anaemia Virus (CAV)-specific nucleotide sequence and the use thereof for diagnostics, vaccination or protein production. Recombinant CAV protein and the use thereof for diagnostics, vaccination or production of CAV-specific antibodies. The use of CAV-specific antibodies thus obtained.
摘要翻译：包含鸡贫血病毒（CAV）特异性核苷酸序列的重组遗传信息（DNA或RNA）及其用于诊断，疫苗接种或蛋白质生产的用途。重组CAV蛋白及其用于诊断，接种或产生CAV特异性抗体的用途。使用由此获得的CAV特异性抗体。

8. 发明申请

WO1991004330A1 HUMAN PARVOVIRUS B19 PROTEINS AND VIRUS-LIKE PARTICLES, THEIR PRODUCTION AND THEIR USE IN DIAGNOSTIC ASSAYS AND VACCINES 审中-公开
标题翻译：人类PARVOVIRUS B19蛋白和病毒样颗粒，其生产及其在诊断和疫苗中的使用
公开(公告)号：WO1991004330A1
公开(公告)日：1991-04-04
申请号：PCT/NL1990000130
申请日：1990-09-11
申请人： RIJKSUNIVERSITEIT TE LEIDEN , BROWN, Caroline, Sarah
发明人： RIJKSUNIVERSITEIT TE LEIDEN
IPC分类号： C12N15/35
CPC分类号： C07K14/005 , A61K39/00 , C12N2750/14322 , C12N2750/14323
摘要： The invention relates to the coat proteins VP1 and VP2 of the human parvovirus B19 and virus-like particles consisting of VP2 or of VP1 and VP2. The invention further comprises genetic information in the form of recombinant expression vectors which contain the genes coding for said proteins, and organisms which through genetic manipulation using such vectors have acquired the ability to produce such proteins and/or particles. The invention further comprises uses of such proteins and virus-like particles for diagnostics or vaccination.
摘要翻译：本发明涉及人细小病毒B19的外壳蛋白VP1和VP2以及由VP2或VP1和VP2构成的病毒样颗粒。本发明进一步包含含有编码所述蛋白质的基因的重组表达载体形式的遗传信息，并且通过使用这种载体的遗传操作获得了产生这种蛋白质和/或颗粒的能力的生物体。本发明进一步包括这些蛋白质和病毒样颗粒用于诊断或接种疫苗的用途。

9. 发明申请

WO2003000890A1 GENETIC VASCULOPATHY 审中-公开
标题翻译：遗传性血管病变
公开(公告)号：WO2003000890A1
公开(公告)日：2003-01-03
申请号：PCT/NL2002/000419
申请日：2002-06-24
申请人： RIJKSUNIVERSITEIT TE LEIDEN , FRANTS, Rune, Robert , FERRARI, Michel, Dominique , OPHOFF, Roel , VAN DEN MAAGDENBERG, Arn
发明人： FRANTS, Rune, Robert , FERRARI, Michel, Dominique , OPHOFF, Roel , VAN DEN MAAGDENBERG, Arn
IPC分类号： C12N15/11
CPC分类号： C07K14/47 , C12Q1/6883 , C12Q2600/156
摘要： The invention relates to the field of vasculopathy and the diagnosis and treatment thereof. The invention provides a method for screening for a disease locus associated with vasculopathy in humans comprising testing genomic DNA via linkage analysis for the presence of a polymorphism or an allelic variation within a microsatellite region on chromosome 3p21.1-p21.3 and an isolated and/or recombinant nucleic acid, or fragment thereof, corresponding to or derived from a disease locus associated with vasculopathy which in humans is located on chromosome 3p21.1-p21.3.
摘要翻译：本发明涉及血管病变及其诊断和治疗领域。本发明提供了一种用于筛选与人类血管病变相关的疾病基因座的方法，包括通过连锁分析测试基因组DNA，以确定染色体3p21.1-p21.3上的微卫星区域内存在多态性或等位基因变异， /或与人类位于染色体3p21.1-p21.3上的与血管病变有关的疾病病征相应或衍生的重组核酸或其片段。

10. 发明申请

WO1996033409A1 ON-LINE COUPLING OF BIOCHEMICAL DETECTION TO CONTINUOUS-FLOW SEPARATION TECHNIQUES 审中-公开
标题翻译：生物化学检测对连续流动分离技术的在线耦合
公开(公告)号：WO1996033409A1
公开(公告)日：1996-10-24
申请号：PCT/NL1996000173
申请日：1996-04-19
申请人： RIJKSUNIVERSITEIT TE LEIDEN , VAN DER GREEF, Jan , IRTH, Hubertus , OOSTERKAMP, Aaike, Johannes , LUTZ, Eva, Saskia, Mareike
发明人： RIJKSUNIVERSITEIT TE LEIDEN
IPC分类号： G01N33/53
CPC分类号： G01N30/84 , G01N33/5302 , G01N33/536 , G01N2030/8435 , G01N2030/8804 , G01N2030/8827 , G01N2030/884
摘要： The present invention relates to an on-line detection method comprising the on-line coupling of a fractionation and a biochemical detection technique, which method comprises the addition of a controlled amount of an affinity molecule to the effluent of the fractionation step to react with analytes in the effluent, the subsequent addition of a controlled amount of a detectable ligand capable of binding to the affinity molecule, and detection of the affinity molecule/detectable ligand complex. Further, the invention is directed to an on-line method for the screening of compounds on their binding capability to a known affinity molecule, which method comprises a fractionation step providing an effluent, the addition of a controlled amount of said affinity molecule to the effluent of the fractionation step and effecting a contact time sufficient to allow a reaction with or interaction between the compounds in the effluent, the subsequent addition of a controlled amount of a detectable ligand capable of binding to the affinity molecule, and detection of the affinity molecule/detectable ligand complex.
摘要翻译：本发明涉及一种在线检测方法，其包括分级分离的在线偶联和生物化学检测技术，该方法包括向分级步骤的流出物中添加受控量的亲和分子以与分析物反应在流出物中，随后添加受控量的能够结合亲和分子的可检测配体，以及检测亲和分子/可检测配体复合物。此外，本发明涉及用于筛选化合物对已知亲和分子的结合能力的在线方法，该方法包括提供流出物的分馏步骤，向流出物中加入受控量的所述亲和分子的分级步骤，并且实现足以允许流出物中化合物的反应或相互作用的接触时间，随后加入受控量的能够结合亲和分子的可检测配体，以及检测亲和分子/ 可检测的配体复合物。

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