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1. 发明申请

WO2002077030A3 MODIFIED MHC MOLECULES WHOSE BINDING TO CD8 OR CD4 IS INHIBITED AND USE THEREOF 审中-公开
公开(公告)号：WO2002077030A3
公开(公告)日：2002-10-03
申请号：PCT/GB2002/001499
申请日：2002-03-27
申请人： AVIDEX LIMITED , JAKOBSEN, Bent, Karsten , CAMERON, Brian, John
发明人： JAKOBSEN, Bent, Karsten , CAMERON, Brian, John
IPC分类号： C07K14/74
摘要： The invention provides a method of inhibiting the activity of T cells against a cell presenting molecules of a selected Major Histocompatibility Complex (MHC) type, the method comprising causing the cell to present modified molecules of the selected MHC type whose binding to CD8 or CD4 is inhibited but which can present the same peptide or peptides as unmodified molecules of the MHC type. Such modified molecules are also provided as are nucleic acids encoding them.

2. 发明申请

WO2002077030A2 SUBSTANCES 审中-公开
标题翻译：物质
公开(公告)号：WO2002077030A2
公开(公告)日：2002-10-03
申请号：PCT/GB2002/001499
申请日：2002-03-27
申请人： AVIDEX LIMITED , JAKOBSEN, Bent, Karsten , CAMERON, Brian, John
发明人： JAKOBSEN, Bent, Karsten , CAMERON, Brian, John
IPC分类号： C07K14/74
CPC分类号： C07K14/70539 , A61K38/00
摘要： The invention provides a method of inhibiting the activity of T cells against a cell presenting molecules of a selected Major Histocompatibility Complex (MHC) type, the method comprising causing the cell to present modified molecules of the selected MHC type whose binding to CD8 or CD4 is inhibited but which can present the same peptide or peptides as unmodified molecules of the MHC type. Such modified molecules are also provided as are nucleic acids encoding them.
摘要翻译：本发明提供了一种抑制T细胞抵抗所选择的主要组织相容性复合物（MHC）型分子的细胞的活性的方法，所述方法包括使细胞呈现与CD8或CD4结合的所选择的MHC类型的修饰分子抑制但可以呈现与MHC类型的未修饰分子相同的肽或肽。还提供了这样的修饰分子，就像编码它们的核酸一样。

3. 发明申请

WO2005046679A1 IMMUNO INHIBITORY PYRAZOLONE COMPOUNDS 审中-公开
标题翻译：免疫抑制剂吡唑啉酮化合物
公开(公告)号：WO2005046679A1
公开(公告)日：2005-05-26
申请号：PCT/GB2004/004629
申请日：2004-11-02
申请人： AVIDEX LIMITED , MATTHEWS, Ian, Richard
发明人： MATTHEWS, Ian, Richard
IPC分类号： A61K31/4152
CPC分类号： C04B35/632 , C07D231/22 , C07D401/04 , C07D401/12 , C07D401/14 , C07D403/04 , C07D405/04 , C07D405/14 , C07D413/14
摘要： Compounds of formula (IA) or (IB) are inhibitors of CD80 and useful in immunomodulation therapy: wherein Ar represents an optionally substituted monocyclic or bicyclic aromatic or heteroaromatic group having from 5 to 10 ring atoms; R 1 and R 2 independently represent H, or C l -C 6 alkyl; R 3 represents H; F; CI; Br; -NO 2 ; - CN; C 1 -C 6 alkyl optionally substituted by F or CI; or C 1 -C 6 alkoxy optionally substituted by F; R 4 represents a carboxylic acid group (-COOH) or an ester thereof, or -C(=O)NR 6 R 7 , -NR 7 C(=O)R 6 , -NR 7 C(=O)OR 6 , -NHC(=O)NR 7 R 6 or -NHC(=S)NR 7 R 6 wherein R 6 represents H, or a radical of formula -(Alk) m -Q wherein m is 0 or 1, Alk is an optionally substituted divalent straight or branched C 1 -C 12 alkylene, or C 2 -C 12 alkenylene, or C 2 -C 12 alkynylene radical or a divalent C 3 -C 12 carbocyclic radical, any of which radicals may be interrupted by one or more -0-, -S- or -N(R 8 )- radicals wherein R 8 represents H or C 1 -C 4 alkyl, C 3 -C 4 alkenyl, C 3 -C 4 alkynyl, or C 3 -C 6 cycloalkyl, and Q represents H; -CF 3; -OH; -SH; -NR 8 R 8 wherein each R 8 may be the same or different, or form a ring when taken together with the nitrogen to which they are attached; an ester group; or an optionally substituted aryl, aryloxy, cycloalkyl, cycloalkenyl or heterocyclic group; and R 7 represents H or C 1 -C 6 alkyl; or when taken together with the atom or atoms to which they are attached R 6 and R 7 form a monocyclic heterocyclic ring having 5, 6 or 7 ring atoms; and X represents a bond or a divalent radical of formula -(Z) n -(Alk)- or -(Alk)-(Z) n - wherein Z represents -0-, -S- or -NH-, Alk is as defined in relation to R 6 and n is 0 or 1.
摘要翻译：式（IA）或（IB）的化合物是CD80的抑制剂，可用于免疫调节治疗：其中Ar表示任选取代的具有5至10个环原子的单环或双环芳族或杂芳族基团; R1和R2独立地表示H或C1-C6烷基; R3表示H; F; CI; BR; NO 2; - CN; 任选被F或Cl取代的C 1 -C 6烷基; 或任选被F取代的C 1 -C 6烷氧基; 或-C（= O）NR 6 R 7，-NR 7 C（= O）R 6，-NR 7 C（= O）OR 6，-NHC（= O）NR 7 R 6或-NHC （= S）NR 7 R 6，其中R 6表示H，或式 - （Alk）mQ基团，其中m为0或1，Alk为任选取代的二价直链或支链C 1 -C 12亚烷基或C 2 -C 12亚烯基， C 12亚炔基或二价C 3 -C 12碳环基团，其中任何基团可被一个或多个-O-，-S-或-N（R 8） - 基团中断，其中R 8表示H或C 1 -C 4烷基， C4链烯基，C3-C4炔基或C3-C6环烷基，Q表示H; -CF 3; -OH; -SH; -NR 8 R 8，其中每个R 8可以相同或不同，或者当与它们所连接的氮一起取代时形成环; 酯基; 或任选取代的芳基，芳氧基，环烷基，环烯基或杂环基; 并且R 7表示H或C 1 -C 6烷基; 或者当与它们所连接的原子或原子一起时R6和R7形成具有5,6或7个环原子的单环杂环; 并且X表示式 - （Z）n-（Alk） - 或 - （Alk） - （Z）n-的键或二价基团，其中Z表示-O - ， - S-或-NH-，Alk为关于R6定义，n为0或1。

4. 发明申请

WO2002088740A2 METHOD 审中-公开
标题翻译：方法
公开(公告)号：WO2002088740A2
公开(公告)日：2002-11-07
申请号：PCT/GB2002/001979
申请日：2002-04-30
申请人： AVIDEX LIMITED , JAKOBSEN, Bent, Karsten
发明人： JAKOBSEN, Bent, Karsten
IPC分类号： G01N33/564
CPC分类号： G01N33/6878 , G01N33/564 , G01N2333/70539 , G01N2500/00
摘要： The present invention provides a method for identifying an entity which binds to a peptide-Major Histocompatibility Complex (pMHC) complex. In the method, a pMHC complex is formed between a predetermined MHC and a peptide which is obtained from a protein sequence and is not known to be capable of being complexed with the predetermined MHC. The resulting pMHC is used to screen for an entity which binds to the pMHC complex.
摘要翻译：本发明提供了鉴定结合肽 - 主要组织相容性复合物（pMHC）复合物的实体的方法。在该方法中，在预定的MHC和从蛋白质序列获得的肽之间形成pMHC复合物，并且不知道能够与预定的MHC复合。所得的pMHC用于筛选结合pMHC复合物的实体。

5. 发明申请

WO2003020763A3 SOLUBLE T CELL RECEPTOR 审中-公开
公开(公告)号：WO2003020763A3
公开(公告)日：2003-03-13
申请号：PCT/GB2002/003986
申请日：2002-08-30
申请人： AVIDEX LIMITED , JAKOBSEN, Bent, Karsten , GLICK, Meir
发明人： JAKOBSEN, Bent, Karsten , GLICK, Meir
IPC分类号： C07K14/725
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.

6. 发明申请

WO2003016905A2 METHODS 审中-公开
标题翻译：方法
公开(公告)号：WO2003016905A2
公开(公告)日：2003-02-27
申请号：PCT/GB2002/003753
申请日：2002-08-15
申请人： AVIDEX LIMITED , JAKOBSEN, Bent, Karsten
发明人： JAKOBSEN, Bent, Karsten
IPC分类号： G01N33/53
CPC分类号： G01N33/505
摘要： The present invention provides a method for determining whether a T cell reacts with a predetermined Major Histocompatibility Complex (MHC) type. In the method, a sample comprising said T cell is brought into contat with a plurality of molecules of said MHC type, each MHC molecule being complexed with a peptide antigen whose contribution to a T cell receptor binding the MHC-peptide antigen complex is minimised. Whether said plurality of MHC molecules causes activation of the T cell is then determined. The method can assess allo-specific T cell activity, and may be used in matching transplant and donor patients, as well as in monitoring alloreactive responses following a transplant operation.
摘要翻译：本发明提供了一种用于确定T细胞是否与预定的主要组织相容性复合物（MHC）类型反应的方法。在该方法中，将包含所述T细胞的样品与多个所述MHC类型的分子连接，每个MHC分子与肽抗原复合，其对结合MHC-肽抗原复合物的T细胞受体的贡献最小化。然后确定所述多个MHC分子是否导致T细胞的激活。该方法可以评估异体特异性T细胞活性，并且可用于匹配移植和供体患者，以及在移植手术后监测同种异体反应性反应。

7. 发明申请

WO2002102840A2 SUBSTANCES 审中-公开
标题翻译：物质
公开(公告)号：WO2002102840A2
公开(公告)日：2002-12-27
申请号：PCT/GB2002/002866
申请日：2002-06-19
申请人： AVIDEX LIMITED , JAKOBSEN, Bent, Karsten , BOULTER, Jonathan, Michael
发明人： JAKOBSEN, Bent, Karsten , BOULTER, Jonathan, Michael
IPC分类号： C07K14/00
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细胞反应，特别是通过诱导T细胞的凋亡或无反应性。本发明还提供了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。

8. 发明申请

WO2003020763A2 SUBSTANCES 审中-公开
标题翻译：可溶性细胞受体
公开(公告)号：WO2003020763A2
公开(公告)日：2003-03-13
申请号：PCT/GB2002/003986
申请日：2002-08-30
申请人： AVIDEX LIMITED , JAKOBSEN, Bent, Karsten , GLICK, Meir
发明人： JAKOBSEN, Bent, Karsten , GLICK, Meir
IPC分类号： 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，除了跨膜结构域它们。（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。

9. 发明申请

WO2006016093A1 IMMUNOMODULATING OXOPYRRAZOLOCINNOLINES AS CD80 INHIBITORS 审中-公开
标题翻译：作为CD80抑制剂免疫调节氧化吡咯烷
公开(公告)号：WO2006016093A1
公开(公告)日：2006-02-16
申请号：PCT/GB2004/003422
申请日：2004-08-09
申请人： AVIDEX LIMITED , MATTHEWS, Ian, Richard
发明人： MATTHEWS, Ian, Richard
IPC分类号： C07D487/04
CPC分类号： C07D487/04
摘要： N-(l-Aza-bicyclo[2.2.2]oct-3-yI)-4-(6,9-difluoro-3-oxo-1,3-dihydro-pyrazolo[4,3clcinnolin-2-yI)-benzamide is a CD80 antagonist, useful in the treatment of diseases which benefit from immuno-inhibition.
摘要翻译： N-（1-氮杂 - 二环[2.2.2]辛-3-基）-4-（6,9-二氟-3-氧代-1,3-二氢 - 吡唑并[4,3clcinnolin -2-基） - 苯甲酰胺是可用于治疗受益于免疫抑制的疾病的CD80拮抗剂。

10. 发明申请

WO2004081011A1 IMMUNOMODULATING HETEROCYCLIC COMPOUNDS 审中-公开
标题翻译：免疫调节杂环化合物
公开(公告)号：WO2004081011A1
公开(公告)日：2004-09-23
申请号：PCT/GB2004/001008
申请日：2004-03-10
申请人： AVIDEX LIMITED , MATHEWS, Ian, Richard
发明人： MATHEWS, Ian, Richard
IPC分类号： C07D487/04
CPC分类号： C07D487/04 , C07D519/00
摘要： Compounds of formula (I) are inhibitors of CD80 and useful in immunomodulation therapy: wherein R 1 and R 3 independently represent H; F; CI; Br; -NO 2 ; -CN; C 1 -C 6 alkyl optionally substituted by F or Cl; or C 1 -C 6 alkoxy optionally substituted by F; R 4 represents a carboxylic acid group (-COOH) or an ester thereof, or -C(=O)NR 6 R 7 , -NR 7 C(=O)R 6 , -NR 7 C(=O)OR 6 , -NHC(=O)NR 7 R 6 or -NHC(=S)NR 7 R 6 wherein R 6 represents H, or a radical of formula - (Alk) m -Q wherein m is 0 or 1, Alk is an optionally substituted divalent straight or branched C 1 -C 12 alkylene, or C 2 -C 12 alkenylene, or C 2 -C 12 alkynylene radical or a divalent C 3 -C 12 carbocyclic radical, any of which radicals may contain one or more -O-, -S- or -N(R 8 )- links wherein R 8 represents H or C 1 -C 4 alkyl, C 3- C 4 alkenyl, C 3 -C 4 alkynyl, or C 3 -C 6 cycloalkyl, and Q represents H; -NR 9 R 10 wherein R 9 and R 10 independently represents H; C 1 -C 4 alkyl; C 3 -C 4 alkenyl; C 3 -C 4 alkynyl; C 3 -C 6 cycloalkyl; an ester group; an optionally substituted carbocyclic or heterocyclic group; or R 9 and R 10 form a ring when taken together with the nitrogen to which they are attached, which ring is optionally substituted; and R 7 represents H or C 1 -C 6 alkyl; or when taken together with the atom or atoms to which they are attached R 6 and R 7 form an optionally substituted monocyclic heterocyclic ring having 5, 6 or 7 ring atoms; and X represents a bond or a divalent radical of formula - (Z) n -(Alk)- or - (Alk)-(Z) n - wherein Z represents -O-, -S- or -NH-, Alk is as defined in relation to R 6 and n is 0 or 1.
摘要翻译：式（I）化合物是CD80的抑制剂，可用于免疫调节治疗：其中R1和R3独立地表示H; F; CI; BR; NO 2; -CN; 任选被F或Cl取代的C 1 -C 6烷基; 或任选被F取代的C 1 -C 6烷氧基; 或-C（= O）NR 6 R 7，-NR 7 C（= O）R 6，-NR 7 C（= O）OR 6，-NHC（= O）NR 7 R 6或-NHC （= S）NR 7 R 6，其中R 6表示H，或式 - （Alk）mQ基团，其中m为0或1，Alk为任选取代的二价直链或支链C 1 -C 12亚烷基或C 2 -C 12亚烯基， C 12亚炔基或二价C 3 -C 12碳环基团，其中任何基团可以含有一个或多个-O - ， - S-或-N（R 8） - 键，其中R 8表示H或C 1 -C 4烷基，C 3 -C 4烯基，C 3 -C 4炔基或C 3 -C 6环烷基，Q表示H; -NR 9 R 10，其中R 9和R 10独立地表示H; C 1 -C 4烷基; C3-C4烯基; C3-C4炔基; C3-C6环烷基; 酯基; 任选取代的碳环或杂环基; 当与它们所连接的氮一起取代时，R 9和R 10形成环，该环任选被取代; 并且R 7表示H或C 1 -C 6烷基; 或者当与它们所连接的原子或原子一起时，R6和R7形成任选取代的具有5,6或7个环原子的单环杂环; 并且X表示式 - （Z）n-（Alk） - 或 - （Alk） - （Z）n-的键或二价基团，其中Z表示-O - ， - S-或-NH-，Alk为关于R6定义，n为0或1。

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