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1. 发明申请

WO1998000442A1 SERINE PROTEASE INHIBITORS 审中-公开
标题翻译：丝氨酸蛋白酶抑制剂
公开(公告)号：WO1998000442A1
公开(公告)日：1998-01-08
申请号：PCT/GB1997001574
申请日：1997-06-11
申请人： THROMBOSIS RESEARCH INSTITUTE , DEADMAN, John, Joseph , ELGENDY, Said , GREEN, Donovan , SKORDALAKES, Emmanuel , SCULLY, Michael, Finbarr , GOODWIN, Christopher, Andrew , KAKKAR, Vijay, Vir
发明人： THROMBOSIS RESEARCH INSTITUTE
IPC分类号： C07K14/815
CPC分类号： C07K5/06191 , A61K38/00 , C07K1/042 , C07K14/815
摘要： Bifunctional serine protease inhibitors and methods of preparing boron-containing peptides are provided. The serine protease inhiitors comprise a catalytic site-directed moiety, which binds to and inhibits the active site of a serine protease, and an exosite associating moiety, which are joined by a connector moiety. The catalytic site directed moiety and the exosite associating moiety are capable of binding simultaneously to a molecule of the serine protease.
摘要翻译：提供双功能丝氨酸蛋白酶抑制剂和制备含硼肽的方法。丝氨酸蛋白酶诱导剂包含结合并抑制丝氨酸蛋白酶的活性位点的催化位点定向部分和通过连接体部分连接的外部位点结合部分。催化位点定向部分和外部位点缔合部分能够同时结合丝氨酸蛋白酶分子。

2. 发明申请

WO2002063017A2 INTEGRIN-BINDING CHIMERAS 审中-公开
公开(公告)号：WO2002063017A2
公开(公告)日：2002-08-15
申请号：PCT/GB2002/000500
申请日：2002-02-05
申请人： TRIGEN LIMITED , LU, Xinjie , KAKKAR, Vijay, Vir
发明人： LU, Xinjie , KAKKAR, Vijay, Vir
IPC分类号： C12N15/62
CPC分类号： C07K14/811 , A61K38/17 , C07K14/46 , C07K2319/00 , A61K2300/00
摘要： Products which contain two interlinked functional moieties of which one is an integrin-binding protein (e.g. a snake venom protein) or a homologue thereof. The products comprise a first portion which is an integrin-binding protein, a homologue thereof having a binding activity or a fragment of either which has integrin-binding activity, and, ligated to the first portion, a second portion which has a different function.
摘要翻译：含有两个相互连接的功能部分的产物，其中一个是整联蛋白结合蛋白（例如蛇毒蛋白）或其同源物。产物包含第一部分，其是整联蛋白结合蛋白，其具有结合活性的同源物或具有整联蛋白结合活性的片段，并且与第一部分连接，具有不同功能的第二部分。

3. 发明申请

WO1994029468A1 UNTRANSLATED EXON-1 SEQUENCES OF EUKARYOTIC GENES AS PROMOTERS 审中-公开
标题翻译：作为促销者的非原生动物基因的未定义的EXON-1序列
公开(公告)号：WO1994029468A1
公开(公告)日：1994-12-22
申请号：PCT/GB1994001251
申请日：1994-06-10
申请人： THROMBOSIS RESEARCH INSTITUTE , BLEASDALE, Ciao, Chang , DEMOLIOU-MASON, Catherine , KAKKAR, Vijay, Vir
发明人： THROMBOSIS RESEARCH INSTITUTE
IPC分类号： C12N15/85
CPC分类号： C12N15/85 , A61K48/00 , C07K14/4716 , C12N2830/008 , C12N2830/30 , C12N2830/60 , C12N2830/85 , C12N2830/90
摘要： Untranslated exon 1 sequences of certain eukaryotic genes, particularly SMHC and sTnI genes, without any 5' or 3' flanking sequences, have strong promoter activity in the expression of reporter genes such as CAT and beta -gal in a variety of mammalian host cells, e.g. vascular smooth muscle cells. The invention provides methods of such enhanced gene expression, eukaryotic expression vectors therefor, and use of such promoters in the expression of such genes. The invention has particular applicability to the expression of genes for use in human gene therapy.
摘要翻译：不具有任何5'或3'侧翼序列的某些真核基因，特别是SMHC和sTnI基因的非翻译外显子1序列在各种哺乳动物宿主细胞中的报告基因如CAT和β-gal的表达中具有强启动子活性，例如血管平滑肌细胞。本发明提供了这种增强的基因表达的方法，其真核表达载体以及这些启动子在这些基因表达中的应用。本发明特别适用于用于人基因治疗的基因的表达。

4. 发明申请

WO1995011259A1 PLATELET-DERIVED GROWTH FACTOR ANALOGUES 审中-公开
标题翻译： PLATELET衍生生长因子模拟
公开(公告)号：WO1995011259A1
公开(公告)日：1995-04-27
申请号：PCT/GB1994002331
申请日：1994-10-21
申请人： THROMBOSIS RESEARCH INSTITUTE , JEHANLI, Ahmed, Mohammed, Taki , PATEL, Geeta , OLABIRAN, Yemisi , BRENNAND, David, Mark , KAKKAR, Vijay, Vir
发明人： THROMBOSIS RESEARCH INSTITUTE
IPC分类号： C07K14/49
CPC分类号： C07K14/49 , A61K38/00
摘要： Novel peptide analogues of platelet-derived growth factor, for use in inhibiting or stimulating growth and/or chemotaxis of cells, e.g. smooth muscle cells. The peptides are selected from any of (I) or linked peptides formed from pairs of the above, or such peptides including a spacer element or cyclised or modified forms thereof.
摘要翻译：用于抑制或刺激细胞生长和/或趋化性的血小板衍生生长因子的新肽类似物，例如，平滑肌细胞。肽选自（I）中任一种或由上述成对构成的连接肽，或这些肽包括间隔元件或其环化或修饰形式。

5. 发明申请

WO1992007869A1 INHIBITORS AND SUBSTRATES OF THROMBIN 审中-公开
标题翻译：抑制剂和硫蛋白基质
公开(公告)号：WO1992007869A1
公开(公告)日：1992-05-14
申请号：PCT/GB1991001946
申请日：1991-11-06
申请人： THROMBOSIS RESEARCH INSTITUTE , KAKKAR, Vijay, Vir , DEADMAN, John, Joseph , CLAESON, Goran, Karl , CHENG, Leifeng , CHINO, Naoyashi , ELGENDY, Said, Mohamed, Anwar , SCULLY, Michael, Finbarr
发明人： THROMBOSIS RESEARCH INSTITUTE
IPC分类号： C07K05/08
CPC分类号： C07K5/0207 , A61K38/00 , C07K5/0202 , C07K5/06008 , C07K5/06191 , C07K5/0812 , C07K7/02 , Y02P20/55
摘要： Peptides which act as inhibitors or substrates of thrombin are derived from the formula: D-Phe-Pro-Arg or its analogues, wherein Phe is substituted by (a), wherein Ar1 and Ar2 are the same or different and are selected from the group consisting of phenyl, thienyl, pyridyl, naphthyl, thionaphthyl, indolyl and saturated groups corresponding to these, optionally substituted by up to three groups selected from C1-C3 alkyl and C1-C3 alkoxy, L1 and L2 are the same of different and are selected from the group consisting of CH2, CH2-CH2, O-CH2, S-CH2, Ar-L taken together optionally means H, diphenyl-methyl, fluorenyl or saturated groups corresponding to these, but one of the Ar-L cannot be H when the other Ar-L means H or benzyl, and Arg may be substituted by an amino acid of formula (b), wherein Y = [CH2]n-Q, (c), where Q = H, amino, amidino, imidazole, guanidino or isothioureido and n = 1-5, preferably 3-5, or C3-C9 alkyl and C5-C10 aryl or alkylaryl optionally substituted by up to three groups selected from hydroxy and C1-C4 alkoxy; Z = CN, COR1, (d) or (e), where R1 = H, OH, CH2Cl, CH2-CH2-CO-pip, CF2-CF2-CO-pip, (f), (g), CH2-CH2-CO-Pro-NHEt, CF2-CF2-CO-Pro-NHEt or a chromophoric group e.g. pNA, MCA, R2 and R3 are the same or different and are selected from the group consisting of OH, OR6 and NR6R7, or R2 and R3 taken together represent the residue of a diol; where R6 and R7, which are the same or different, are C1-C10 alkyl, phenyl or C6-C10 arylalkyl, R4 and R5 are the same or different and are selected from R2, R3, Gly-pip, Ala-pip or Gly-Pro-NHEt.
摘要翻译：作为抑制剂或凝血酶底物的肽衍生自下式：D-Phe-Pro-Arg或其类似物，其中Phe被（a）取代，其中Ar1和Ar2相同或不同，并且选自由对应于它们的苯基，噻吩基，吡啶基，萘基，萘基，吲哚基和饱和基团任选被至多三个选自C 1 -C 3烷基和C 1 -C 3烷氧基的基团取代，L 1和L 2是不同的并且被选择由CH 2，CH 2 -CH 2，O-CH 2，S-CH 2，Ar-L组成的基团任选地表示H，二苯基甲基，芴基或对应于它们的饱和基团，但Ar-L中的一个不能是H 当另一个Ar-L表示H或苄基，并且Arg可以被式（b）的氨基酸取代，其中Y = [CH 2] nQ，（c）其中Q = H，氨基，脒基，咪唑，胍基或异硫脲基，n = 1-5，优选3-5，或C 3 -C 9烷基和C 5 -C 10芳基或烷基芳基，任选被至多三个选自羟基和C 1 -C 4烷氧基; Z = CN，COR1，（d）或（e），其中R1 = H，OH，CH2Cl，CH2-CH2-CO-pip，CF2-CF2-CO-pip，（f），（g），CH2-CH2 -CO-Pro-NHEt，CF2-CF2-CO-Pro-NHEt或发色团 pNA，MCA，R2和R3相同或不同，选自OH，OR 6和NR 6 R 7，或者R 2和R 3一起代表二醇的残基; 其中R 6和R 7相同或不同，为C 1 -C 10烷基，苯基或C 6 -C 10芳基烷基，R 4和R 5相同或不同，并且选自R 2，R 3，Gly-pip，Ala-pip或Gly -Pro-NHEt。

6. 发明申请

WO02063017A3 INTEGRIN-BINDING CHIMERAS 审中-公开
公开(公告)号：WO02063017A3
公开(公告)日：2003-10-16
申请号：PCT/GB0200500
申请日：2002-02-05
申请人： TRIGEN LTD , LU XINJIE , KAKKAR VIJAY VIR
发明人： LU XINJIE , KAKKAR VIJAY VIR
IPC分类号： A61K38/00 , A61K38/17 , C07K14/46 , C07K14/81 , C12N15/62 , C07K14/435 , C12N5/10 , C12Q1/68
CPC分类号： C07K14/811 , A61K38/17 , C07K14/46 , C07K2319/00 , A61K2300/00
摘要： Products which contain two interlinked functional moieties of which one is an integrin-binding protein (e.g. a snake venom protein) or a homologue thereof. The products comprise a first portion which is an integrin-binding protein, a homologue thereof having a binding activity or a fragment of either which has integrin-binding activity, and, ligated to the first portion, a second portion which has a different function.
摘要翻译：含有两个相互连接的功能部分的产物，其中一个是整联蛋白结合蛋白（例如蛇毒蛋白）或其同源物。产物包含第一部分，其是整联蛋白结合蛋白，其具有结合活性的同源物或具有整联蛋白结合活性的片段，并且与第一部分连接，具有不同功能的第二部分。

7. 发明申请

WO2002057273A1 SERINE PROTEASE INHIBITORS COMPRISING A HYDROGEN-BOND ACCEPTOR 审中-公开
标题翻译：含有氢键接头的丝氨酸蛋白酶抑制剂
公开(公告)号：WO2002057273A1
公开(公告)日：2002-07-25
申请号：PCT/GB2002/000224
申请日：2002-01-18
申请人： TRIGEN LIMITED , DEADMAN, John, Joseph , SPENCER, John , GREENIDGE, Paulette, Angela , GOODWIN, Christopher, Andrew , KAKKAR, Vijay, Vir , SCULLY, Michael, Finbarr
发明人： DEADMAN, John, Joseph , SPENCER, John , GREENIDGE, Paulette, Angela , GOODWIN, Christopher, Andrew , KAKKAR, Vijay, Vir , SCULLY, Michael, Finbarr
IPC分类号： C07F5/02
CPC分类号： A61K31/69 , A61K31/00 , C07C335/32 , C07F5/02 , C07F5/025 , C07F5/04
摘要： Compounds, useful as protease inhibitors, of the formula (I): where: Ar is a ring or ring system, for example a benzene ring, and may be substituted by one or more moieties in addition to X and LJ; X is a functional group which is a hydrogen-bond acceptor, e.g. a nitro or boronate group BY 1 Y 2 ; L is a linker, most preferably (CR 5 R 6 )-S-; J is a moiety containing a basic nitrogen atom but not containing an amino acid residue, preferably amidino, guanidino, amino, carboxamido, hydroxylamino, or imidazolyl, or an N-substituted analogue thereof.
摘要翻译：用作蛋白酶抑制剂的式（I）化合物：其中：Ar是环或环系，例如苯环，除X和LJ之外，还可被一个或多个部分取代; X是一个官能团，它是一个氢键受体。硝基或硼酸酯基团BY 1 Y 2; L是接头，最优选（CR 5 R 6）-S-; J是含有碱性氮原子但不含有氨基酸残基，优选脒基，胍基，氨基，甲酰氨基，羟基氨基或咪唑基或其N-取代的类似物的部分。

8. 发明申请

WO1998000443A1 THROMBIN INHIBITORS 审中-公开
标题翻译：冷冻抑制剂
公开(公告)号：WO1998000443A1
公开(公告)日：1998-01-08
申请号：PCT/GB1997001575
申请日：1997-06-11
申请人： THROMBOSIS RESEARCH INSTITUTE , DEADMAN, John, Joseph , ELGENDY, Said , GREEN, Donovan , SKORDALAKES, Emmanuel , SCULLY, Michael, Finbarr , GOODWIN, Christopher, Andrew , KAKKAR, Vijay, Vir
发明人： THROMBOSIS RESEARCH INSTITUTE
IPC分类号： C07K14/815
CPC分类号： C07K5/06191 , A61K38/00 , C07K14/815
摘要： Bifunctional peptide thrombin inhibitors and methods of their manufacture are provided. The inhibitors have an anion-binding exosite associating moiety joined to a catalytic site directed moiety. A spacer peptide and a non-peptide linker moiety enable both the anion-binding exosite associating moiety and the catalytic site directed moiety to bind simultaneously to a thrombin molecule thereby permitting the treatment of thrombosis.
摘要翻译：提供双功能肽凝血酶抑制剂及其制造方法。抑制剂具有连接到催化位点定向部分的阴离子结合外部位点缔合部分。间隔肽和非肽接头部分使得阴离子结合的外部位点缔合部分和催化位点指向部分能够同时结合凝血酶分子从而允许治疗血栓形成。

9. 发明申请

WO1994020629A1 EUKARYOTIC EXPRESSION VECTORS DRIVEN BY A MYOSIN HEAVY CHAIN GENE PROMOTER 审中-公开
标题翻译：由MYOSIN HEAVY CHAIN GENE PROMOTER驱动的真核表达载体
公开(公告)号：WO1994020629A1
公开(公告)日：1994-09-15
申请号：PCT/GB1994000489
申请日：1994-03-11
申请人： THROMBOSIS RESEARCH INSTITUTE , BLEASDALE, Ciao, Chang , DEMOLIOU-MASON, Catherine , KAKKAR, Vijay, Vir
发明人： THROMBOSIS RESEARCH INSTITUTE
IPC分类号： C12N15/85
CPC分类号： C12N15/85 , C12N2800/108 , C12N2830/008 , C12N2830/85
摘要： The 5' upstream sequence from position -950 to +78 of the rabbit smooth muscle myosin heavy chain gene (Fig. 2) has strong promoter activity in the expression of reporter genes such as CAT and beta -gal in a variety of mammalian host cells, e.g. vascular smooth muscle cells. The invention provides methods of such enhanced gene expression, eukaryotic expression vectors therefor, and use of the MYOS promoter in the expression of such genes. The invention has particular applicability to the expression of genes for use in human gene therapy.
摘要翻译：兔平滑肌肌球蛋白重链基因的位置-950至+78的5'上游序列（图2）在各种哺乳动物宿主细胞中的报告基因如CAT和β-gal的表达中具有强启动子活性，例如血管平滑肌细胞。本发明提供了这种增强的基因表达的方法，其真核表达载体以及MYOS启动子在这些基因表达中的应用。本发明特别适用于用于人基因治疗的基因的表达。

10. 发明申请

WO1990004970A1 ANTITHROMBOTIC COMPOSITION 审中-公开
标题翻译：抗生素组合物
公开(公告)号：WO1990004970A1
公开(公告)日：1990-05-17
申请号：PCT/EP1989001341
申请日：1989-11-09
申请人： THROMBOSIS RESEARCH INSTITUTE , KAKKAR, Vijay, Vir , SCULLY, Michael, Finbarr
发明人： THROMBOSIS RESEARCH INSTITUTE
IPC分类号： A61K31/725
CPC分类号： A61K31/715
摘要： A pharmaceutical composition comprising a heparinoid, for example dextran sulphate, together with a low molecular weight heparin, in free or fixed combination, is useful as an antithrombotic agent with a low risk of bleeding complications.
摘要翻译：包含类固醇类例如游离或固定组合的类肝素例如硫酸葡聚糖以及低分子量肝素可用作具有低出血并发症风险的抗血栓形成剂。

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