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1. 发明申请

US20070082362A1 Modified soluble t cell receptor 有权
标题翻译：改良的可溶性T细胞受体
公开(公告)号：US20070082362A1
公开(公告)日：2007-04-12
申请号：US10544448
申请日：2003-07-09
申请人： Bent Jakobsen , Meir Glick
发明人： Bent Jakobsen , Meir Glick
IPC分类号： G01N33/53 , C07H21/04 , C12P21/06 , C07K14/705 , A61K38/17
CPC分类号： C07K14/70539 , A61K38/00 , C07K2319/21 , C07K2319/22 , G01N2333/70539
摘要： The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all or part of a TCR $g(a) chain, except the transmembrane domain thereof, and (ii) all or part of a TCR $g(b) chain, except the transmembrane domain thereof. (i) and (ii) each comprise a functional variable domain and at least a part of the constant domain of the TCR chain, and are linked by a disulphide bond between constant domain residues which is not present in native TCR, characterised in that the sTCR recognises a CD1-antigen complex, a bacterial superantigen or a peptide-MHC/superantigen complex.
摘要翻译：本发明提供可溶性T细胞受体（sTCR），其包含（i）全部或部分TCR $ g（a）链，除了其跨膜结构域，和（ii）全部或部分TCR $ g b）链，除了其跨膜结构域。（i）和（ii）各自包含功能可变结构域和TCR链的恒定结构域的至少一部分，并且通过在天然TCR中不存在的恒定结构域残基之间的二硫键连接，其特征在于， sTCR识别CD1抗原复合物，细菌超抗原或肽-MHC /超抗原复合物。

2. 发明申请

US20060166875A1 Single chain recombinant t cell receptors 有权
标题翻译：单链重组t细胞受体
公开(公告)号：US20060166875A1
公开(公告)日：2006-07-27
申请号：US10530035
申请日：2003-10-03
申请人： Bent Jakobsen , Meir Glick
发明人： Bent Jakobsen , Meir Glick
IPC分类号： A61K38/17 , C07K14/705 , C12P21/06
CPC分类号： C07K14/7051 , A61K38/00 , C07K2319/00 , G01N2500/02
摘要： A single chain T cell receptor (scTCR) comprising an a segment constituted by a TCR α chain variable region sequence fused to the N terminus of a TCR α chain constant region extracellular sequence, a β segment constituted by a TCR β chain variable region fused to the N terminus of a TCR β chain constant region extracellular sequence, and a linker sequence linking the C terminus of the a segment to the N terminus of the β segment, or vice versa, the constant region extracellular sequences of the α and β segments being linked by a disulfide bond, the length of the linker sequence and the position of the disulfide bond being such that the variable region sequences of the α and β segments are mutually orientated substantially as in native αβ T cell receptors. Complexes of two or more such scTCRs, and use of the scTCRs in therapy and in various screening applications are also disclosed.
摘要翻译：包含由TCRα链恒定区细胞外序列的N末端融合的TCRα链可变区序列构成的区段的单链T细胞受体（scTCR），由TCRβ链可变区融合的β区段 TCRβ链恒定区细胞外序列的N末端以及将片段的C末端连接到β片段的N末端的接头序列，反之亦然，α和β片段的恒定区细胞外序列是通过二硫键连接，接头序列的长度和二硫键的位置使得α和β片段的可变区序列基本上如天然字母T细胞受体那样相互取向。还公开了两种或更多种这种scTCR的复合物，以及在治疗和各种筛选应用中使用scTCR。

3. 发明申请

US20060135418A1 Receptors 审中-公开
标题翻译：受体
公开(公告)号：US20060135418A1
公开(公告)日：2006-06-22
申请号：US10535965
申请日：2003-11-25
申请人： Bent Jakobsen , Meir Glick
发明人： Bent Jakobsen , Meir Glick
IPC分类号： A61K38/17 , C07K14/705
CPC分类号： A61K51/088 , A61K38/00 , A61K47/60 , C07K14/7051
摘要： A multivalent T cell receptor (TCR) complex comprising at least two TCRs, linked by a non-peptidic polymer chain or a peptidic linker sequence. Preferably the TCR complex comprises TCR heterodimers having a non-native disulfide bond between constant domain residues, said TCRs being linked via an optionally substituted, polyalkylene glycol linker. Therapeutic agents such as cytotoxic drugs may be attached to such complexes for targeted cell delivery. Such TCR complexes may be used in the diagnosis or treatment of cancer, infectious disease, or autoimmune disease.
摘要翻译：包含至少两个TCR的多价T细胞受体（TCR）复合物，通过非肽聚合物链或肽接头序列连接。优选地，TCR复合物包含在恒定结构域残基之间具有非天然二硫键的TCR异源二聚体，所述TCR通过任选取代的聚亚烷基二醇连接体连接。诸如细胞毒性药物的治疗剂可以连接到这种复合物用于靶细胞递送。这种TCR复合物可用于诊断或治疗癌症，感染性疾病或自身免疫性疾病。

4. 发明申请

US20050009025A1 Substances 有权
标题翻译：物质
公开(公告)号：US20050009025A1
公开(公告)日：2005-01-13
申请号：US10486924
申请日：2002-08-30
申请人： Bent Jakobsen , Meir Glick
发明人： Bent Jakobsen , Meir Glick
IPC分类号： G01N33/53 , A61K9/127 , A61K38/00 , A61K47/48 , A61K48/00 , A61P3/10 , A61P31/12 , A61P31/18 , A61P35/00 , A61P37/02 , C07K14/725 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12P21/02 , G01N33/566 , C12Q1/68 , A61K38/17 , C07K14/705
CPC分类号： C07K14/7051 , A61K38/00
摘要： The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all for part of a TCR α chain, except the transmembrane domain thereof, and (ii) all or part of a TCR β chain, except the transmembrane domain thereof. (i) and (ii) each comprise a functional variable domain and at least a part of the constant domain of the TCR chain, and are linked by a disulphide bond between constant domain residues which is not present in native TCR.
摘要翻译：本发明提供了一种可溶性T细胞受体（sTCR），其包含（i）部分TCRα链，除了其跨膜结构域外，和（ii）全部或部分TCRβ链，除了跨膜结构域其中。（i）和（ii）各自包含功能可变结构域和TCR链的恒定结构域的至少一部分，并且通过在天然TCR中不存在的恒定结构域残基之间的二硫键连接。

5. 发明申请

US20060155115A1 Multivalent T cell receptor complexes 审中-公开
公开(公告)号：US20060155115A1
公开(公告)日：2006-07-13
申请号：US11321894
申请日：2005-12-29
申请人： Bent Jakobsen , Jonathan Boulter
发明人： Bent Jakobsen , Jonathan Boulter
IPC分类号： C07K14/74
CPC分类号： G01N33/56977 , A61K38/00 , A61K47/6425 , C07K14/7051 , C07K19/00 , C07K2319/00 , C07K2319/02
摘要： The present invention relates to a synthetic multivalent T cell receptor complex for binding to a MHC-peptide complex, which multivalent T cell receptor complex comprises a plurality of T cell receptors specific for the MHC-peptide complex. It is preferred that the T cell receptors are refolded recombinant soluble T cell receptors. The synthetic multivalent T cell receptor complex can be used for delivering therapeutic agents or for detecting MHC-peptide complexes, and methods for such uses are also provided.

6. 发明申请

US20120027683A1 DIABETES T CELL RECEPTORS 审中-公开
标题翻译：糖尿病细胞受体
公开(公告)号：US20120027683A1
公开(公告)日：2012-02-02
申请号：US13060230
申请日：2009-09-02
申请人： Neill MacKenzie , Bent Jakobsen , Daniel Williams , Brian Cameron
发明人： Neill MacKenzie , Bent Jakobsen , Daniel Williams , Brian Cameron
IPC分类号： A61K49/00 , A61P3/10 , C12N5/10 , C12N1/21 , C07K14/725 , A61K38/17
CPC分类号： C07K14/7051
摘要： T cell receptors (TCRs) having the property of binding to a murine insulin-derived peptide, LYLVCGERG (SEQ ID NO:62), presented by the murine H-2Kd complex (LYLVCGERG-H-2Kd). The TCRs comprise at least one TCR α chain variable domain and/or at least one TCR β chain variable domain and have a KD for the LYLVCGERG-H-2Kd complex of less than or equal to 1 μM and/or have an off-rate (koff) for the LYLVCGERG-H-2Kd complex of 0.5 S−1 or slower, and use of such TCRs as research tools.
摘要翻译：具有与鼠H-2Kd复合物（LYLVCGERG-H-2Kd）呈递的鼠胰岛素衍生肽LYLVCGERG（SEQ ID NO：62）结合的性质的T细胞受体（TCR）。 TCR包含至少一个TCRα链可变区和/或至少一个TCR和bgr; 并且具有小于或等于1μM的LYLVCGERG-H-2Kd复合物的KD和/或具有0.5S-1或更慢的LYLVCGERG-H-2Kd复合物的脱离率（koff）并使用这种TCR作为研究工具。

7. 发明申请

US20080090251A1 Assays For Superantigens 审中-公开
标题翻译：超抗原测定
公开(公告)号：US20080090251A1
公开(公告)日：2008-04-17
申请号：US11792538
申请日：2005-10-31
申请人： Bent Jakobsen , Nicholas Pumphrey
发明人： Bent Jakobsen , Nicholas Pumphrey
IPC分类号： G01N33/53 , C07K14/74
CPC分类号： C07K14/31 , C07K14/7051 , C07K2319/00 , G01N33/566 , G01N33/56911 , G01N33/56938 , G01N33/56944
摘要： The present invention provides a superantigen quality control assay, particularly for SEA-E120, comprising incubating a standard amount of a superantigen-containing test sample with a standard amount of a soluble TCR which binds the superantigen, separating unbound TCR from the resultant superantigen/TCR-containing sample, quantifying the TCR bound in that sample, and comparing that result with a reference result characterising a control superantigen-containing sample. Also provided are soluble TCRs useful as reagents in said assay.
摘要翻译：本发明提供了超抗原质量控制测定，特别是对于SEA-E120，包括将标准量的含有超抗原的测试样品与标准量的结合超抗原的可溶性TCR孵育，将未结合的TCR与所得超抗原/ TCR 定量样品中的TCR结合，并将该结果与表征含有超抗原的对照样品的参考结果进行比较。还提供了在所述测定中用作试剂的可溶性TCR。

8. 发明申请

US20060093613A1 Soluble T cell receptor 审中-公开
标题翻译：可溶性T细胞受体
公开(公告)号：US20060093613A1
公开(公告)日：2006-05-04
申请号：US11167773
申请日：2005-06-27
申请人： Bent Jakobsen , John Bell , George Gao , Benjamin Willcox , Jonathan Boulter
发明人： Bent Jakobsen , John Bell , George Gao , Benjamin Willcox , Jonathan Boulter
IPC分类号： C07K14/74 , C07H21/04 , C12P21/06 , A61K39/00 , C12N15/74
CPC分类号： G01N33/56977 , A61K38/00 , A61K47/6425 , C07K14/7051 , C07K19/00 , C07K2319/00 , C07K2319/02
摘要： The present invention relates to a recombinant soluble T cell receptor. The T cell receptor (TCR) is refolded and comprises a recombinant TCR α or γ chain extracellular domain having a first heterologous C-terminal dimerization peptide; and a recombinant TCR β or δ chain extracellular domain having a second C-terminal dimerization peptide which is specifically heterodimerized with the first dimerization peptide to form a heterodimerization domain, which may be a coiled coil domain. The invention also provides nucleic acid sequences encoding the recombinant TCR and a method for producing the recombinant TCR. The TCR may be labelled with a detectable label so as to enable the detection of specific MHC-peptide complexes. Alternatively, it can be linked to a therapeutic agent such as a cytotoxic agent or an immunostimulating agent so as to deliver such an agent to the site of a specific MHC-peptide complex.
摘要翻译：本发明涉及重组可溶性T细胞受体。 T细胞受体（TCR）被重折叠并且包含具有第一异源C末端二聚化肽的重组TCRα或γ链细胞外结构域; 和具有第二C末端二聚化肽的重组TCRβ或δ链胞外结构域，其与第一二聚化肽特异性二聚化形成异源二聚化结构域，其可以是卷曲螺旋结构域。本发明还提供了编码重组TCR的核酸序列和用于产生重组TCR的方法。可以用可检测的标记物标记TCR，以便能够检测特异性的MHC-肽复合物。或者，其可以与治疗剂例如细胞毒性剂或免疫刺激剂连接，以便将这种药物递送到特定MHC-肽复合物的位点。

9. 发明申请

US20070191278A1 CD8 AS AN INHIBITOR OF THE CELLULAR IMMUNE SYSTEM 审中-公开
标题翻译： CD8作为细胞免疫系统的抑制剂
公开(公告)号：US20070191278A1
公开(公告)日：2007-08-16
申请号：US11696301
申请日：2007-04-04
申请人： Bent Jakobsen , George Gao , Ulrich Gerth , Andrew Sewell
发明人： Bent Jakobsen , George Gao , Ulrich Gerth , Andrew Sewell
IPC分类号： A61K38/17
CPC分类号： C07K14/70517 , A61K38/00 , C07K2319/00
摘要： This invention is directed to a method for inhibiting cytotoxic T lymphocyte (CTL) activity in which soluble CD8 is used as the inhibitor. The invention is further directed to soluble forms of the CD8 molecule which can be administered to a patient. The method of this invention is particularly useful for immunosuppressive therapy in which inhibition of CTL activity is desirable, for example, in patients undergoing transplantation.
摘要翻译：本发明涉及一种抑制细胞毒性T淋巴细胞（CTL）活性的方法，其中使用可溶性CD8作为抑制剂。本发明还涉及可以给予患者的CD8分子的可溶形式。本发明的方法特别适用于抑制CTL活性的免疫抑制治疗，例如在接受移植的患者中。

10. 发明申请

US20060165707A1 Substances 审中-公开
标题翻译：物质
公开(公告)号：US20060165707A1
公开(公告)日：2006-07-27
申请号：US10480304
申请日：2002-06-19
申请人： Bent Jakobsen , Jonathan Boulter
发明人： Bent Jakobsen , Jonathan Boulter
IPC分类号： A61K39/00 , C07H21/04 , C12P21/06 , C07K14/74 , A61K9/127
CPC分类号： C07K14/70539 , A61K48/00
摘要： The present invention provides a multimers of class I Major Histocompatibility Complexes (MHCs) having a modified P2-microglobulin whose binding to CD8 is inhibited. Such MHCs are capable of inhibiting CD8+ T cell response, particularly by inducing apoptosis or anergy of the T cell. The invention also provides nucleic acids encoding such molecules, and the use of such multimers and nucleic acids in immunosuppressive therapy, in particular as inhibitors of cytotoxic T cell responses.
摘要翻译：本发明提供具有与CD8结合被抑制的经修饰的P2-微球蛋白的I类主要组织相容性复合物（MHC）的多聚体。这样的MHC能够抑制CD8 + T细胞应答，特别是通过诱导T细胞的凋亡或无反应性。本发明还提供编码这种分子的核酸，以及这些多聚体和核酸在免疫抑制治疗中的用途，特别是作为细胞毒性T细胞应答的抑制剂。

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