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31. 发明申请

WO1986000926A1 EUCARYOTIC EXPRESSION VECTORS 审中-公开
标题翻译：真实表达载体
公开(公告)号：WO1986000926A1
公开(公告)日：1986-02-13
申请号：PCT/GB1985000325
申请日：1985-07-22
申请人： CELLTECH LIMITED , NASMYTH, Kim, Ashley , MILLER, Allan, Malcolm
发明人： CELLTECH LIMITED
IPC分类号： C12N15/00
CPC分类号： C12N15/85 , C12N15/81
摘要： A eucariotic expression vector includes a controllable repressor operator sequence within the expression control sequence of the vector. The controllable repressor operator sequence represses expression of a heterologous structural gene located downstream of the expression control sequence in the presence of a gene product or a combination of gene products of a yeast mating type locus. This allows control of the expression level of the heterologous structural gene. Controllable repressor operator sequences responsive to the a1/ alpha 2 and alpha 2 gene products of the MATa and MAT alpha yeast mating type locus alleles are described, both derived from genetic material and synthesised chemically.
摘要翻译：显性表达载体包含载体表达控制序列内的可控阻遏物操纵子序列。在基因产物或酵母交配型基因座的基因产物的组合存在下，可控阻遏物操纵子序列抑制位于表达调控序列下游的异源结构基因的表达。这允许控制异源结构基因的表达水平。描述了响应于MATa和MATα酵母交配型基因座等位基因的a1 /α2和α2基因产物的可控阻遏物操纵子序列，均来自遗传物质并化学合成。

32. 发明申请

WO1985003948A1 MACROPHAGE ACTIVATING FACTOR 审中-公开
标题翻译：宏观激励因子
公开(公告)号：WO1985003948A1
公开(公告)日：1985-09-12
申请号：PCT/GB1985000088
申请日：1985-03-04
申请人： CELLTECH LIMITED , REES, Ann, Dorothy, Mary
发明人： CELLTECH LIMITED
IPC分类号： C12P21/00
CPC分类号： C07K14/57 , A61K38/00
摘要： A macrophage activating factor which is antigenically distinct from interferon - gamma . Such macrophage activating factors are produced by culturing cloned human T cell lines TB 68.2.1, TB 68.2.2 and TB 68.2.6.
摘要翻译：与干扰素-γ抗原性不同的巨噬细胞激活因子。通过培养克隆的人T细胞系TB 68.2.1，TB 68.2.2和TB 68.2.6来产生这样的巨噬细胞活化因子。

33. 发明申请

WO1984003712A2 MULTICHAIN POLYPEPTIDES OR PROTEINS AND PROCESSES FOR THEIR PRODUCTION 审中-公开
标题翻译：多聚多肽或蛋白质及其生产过程
公开(公告)号：WO1984003712A2
公开(公告)日：1984-09-27
申请号：PCT/GB1984000094
申请日：1984-03-23
申请人： CELLTECH LIMITED , BOSS, Michael, Alan , KENTEN, John, Henry , EMTAGE, John, Spencer , WOOD, Clive, Ross
发明人： CELLTECH LIMITED
IPC分类号： C12N15/00
CPC分类号： C07K16/462 , A61K38/00 , B01D15/3809 , C07K2317/24 , C12N15/63 , G01N33/531
摘要： Multichain polypeptides or proteins and processes for their production in cells of host organisms which have been transformed by recombinant DNA techniques. According to a first aspect of the present invention, there is provided a process for producing a heterologous multichain polypeptide or protein in a single host cell, which comprises transforming the host cell with DNA sequences coding for each of the polypeptide chains and expressing said polypeptide chains in said transformed host cell. According to another aspect of the present invention there is provided as a product of recombinant DNA technology an Ig heavy or light chain or fragment thereof having an intact variable domain. The invention also provides a process for increasing the level of protein expression in a transformed host cell and vectors and transformed host cells for use in the processes.
摘要翻译：多链蛋白或多肽及其在通过重组DNA技术转化的宿主细胞中生产该多肽的方法。根据本发明的第一方面，描述了一种方法，其允许以产生蛋白或在单个宿主细胞的异源多链多肽，该方法包括转化用的DNA序列编码对每个所述的宿主细胞多肽链并在所述转化的宿主细胞中表达这些多肽链。根据本发明的另一方面，作为重组DNA技术产物获得具有完整可变结构域的重链或轻链Ig链或其片段。本发明还描述了用于提高转化的宿主细胞中蛋白质表达程度的方法以及用于所述方法中的载体和转化的宿主细胞。

34. 发明申请

WO1995002045A2 GELATINASE ANTAGONISTS USED FOR TREATING CANCER 审中-公开
标题翻译：用于治疗癌症的GELATINASE ANTAGONISTS
公开(公告)号：WO1995002045A2
公开(公告)日：1995-01-19
申请号：PCT/GB1994001485
申请日：1994-07-08
申请人： CELLTECH LIMITED , CRABBE, Thomas , DOCHERTY, Andrew, James, Penrose , BAKER, Terence, Seward
发明人： CELLTECH LIMITED
IPC分类号： C12N09/64
CPC分类号： C12N9/6491 , A61K38/00
摘要： This invention describes a method of treating diseases in which gelatinase mediated cell migration and invasion is an essential feature of the pathology of the disease. The method comprises administering an effective amount of an antagonist which inhibits gelatinase mediated cell migration and invasion.
摘要翻译：本发明描述了一种治疗疾病的方法，其中明胶酶介导的细胞迁移和侵袭是疾病病理学的基本特征。该方法包括施用有效量的抑制明胶酶介导的细胞迁移和侵袭的拮抗剂。

35. 发明申请

WO1994020446A1 TRISUBSTITUTED PHENYL DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS AND PROCESSES FOR THEIR PREPARATION 审中-公开
标题翻译：作为磷酸二酯酶抑制剂的三苯甲基衍生物及其制备方法
公开(公告)号：WO1994020446A1
公开(公告)日：1994-09-15
申请号：PCT/GB1994000453
申请日：1994-03-09
申请人： CELLTECH LIMITED
发明人： CELLTECH LIMITED , WARRELLOW, Graham, John , COLE, Valérie, Anne , ALEXANDER, Rikki, Peter
IPC分类号： C07C43/235
CPC分类号： C07D213/30 , C07C255/37 , C07C2601/08 , C07D213/73 , C07D237/08 , C07D241/12
摘要： Compounds of general formula (1) are described wherein Y is a halogen atom or a group -OR , where R is an optionally substituted alkyl group; X is -O-, -S- or -N(R )-, where R is a hydrogen atom or an alkyl group; R is an optionally substituted cycloalkyl or cycloalkenyl group; R and R , which may be the same or different, is each a hydrogen atom or an alkyl, -CO2R (where R is a hydrogen atom or an alkyl, aryl, or aralkyl group), -CONR R (where R and R which may be the same or different is each a hydrogen atom or an alkyl, aryl or aralkyl group), -CSNR R , -CN, -CH2CN group; Z is -(CH2)n- (where n is zero or an integer 1, 2 or 3; R is an optionally substituted monocyclic or bicyclic aryl group optionally containing one or more heteroatoms selected from oxygen, sulphur or nitrogen atoms; R is a hydrogen atom or a hydroxyl group; and the salts, solvates, hydrates, prodrugs and N-oxides thereof. Compounds according to the invention are potent and selective phosphodiesterase type IV inhibitors and are useful in the prophylaxis and treatment of diseases such as asthma where an unwanted inflammatory response or muscular spasm is present.
摘要翻译：描述通式（1）的化合物，其中Y是卤素原子或-OR 1基团，其中R 1是任选取代的烷基; X是-O - ， - S-或-N（R 7） - ，其中R 7是氢原子或烷基; R 2是任选取代的环烷基或环烯基; R 3和R 4可以相同或不同，分别为氢原子或烷基-CO 2 R 8（其中R 8为氢原子或烷基，芳基或芳烷基基团），-CONR 9 R 10（其中R 9和R 10可以相同或不同，分别为氢原子或烷基，芳基或芳烷基），-CSNR 9， R 10，-CN，-CH 2 CN基团; Z为 - （CH 2）n - （其中n为零或整数1,2或3; R 5为任选含有一个或多个选自氧，硫或氮原子的杂原子的任选取代的单环或双环芳基; R 6是氢原子或羟基;以及其盐，溶剂合物，水合物，前药和N-氧化物。根据本发明的化合物是有效和选择性的磷酸二酯酶IV型抑制剂，并且可用于预防和治疗诸如哮喘的疾病，其中存在不想要的炎症反应或肌肉痉挛。

36. 发明申请

WO1993005145A1 CELL CULTURE PROCESS AND MEDIUM FOR THE GROWTH OF ADHERENT ANIMAL CELLS 审中-公开
标题翻译：细胞培养过程和中等量的附加动物细胞生长
公开(公告)号：WO1993005145A1
公开(公告)日：1993-03-18
申请号：PCT/GB1992001571
申请日：1992-08-28
申请人： CELLTECH LIMITED , BORASTON, Robert, Charles
发明人： CELLTECH LIMITED
IPC分类号： C12N05/00
CPC分类号： C12N5/0018 , C12N2500/05 , C12N2500/12
摘要： Adherent animal cells are grown in suspension in a nutrient medium in which the molar ratio of total inorganic ions and total amino acids is substantially reduced when compared with the corresponding ratio in known nutrient media, and is maintained at a level at which little or no cell aggregation occurs.
摘要翻译：粘附动物细胞悬浮在生长培养基中生长，其中总的无机离子和总氨基酸的摩尔比与已知营养培养基中相应的比例相比显着降低，并且保持在很少或没有细胞的水平聚合发生。

37. 发明申请

WO1992011383A1 RECOMBINANT ANTIBODIES SPECIFIC FOR TNF'alpha' 审中-公开
标题翻译： TNFα特异性的重组抗体
公开(公告)号：WO1992011383A1
公开(公告)日：1992-07-09
申请号：PCT/GB1991002300
申请日：1991-12-20
申请人： CELLTECH LIMITED , ADAIR, John, Robert , ATHWAL, Diljeet, Singh , EMTAGE, John, Spencer , BODMER, Mark, William
发明人： CELLTECH LIMITED
IPC分类号： C12P21/08
CPC分类号： C07K16/241 , A61K38/00 , C07K16/461 , C07K2317/24 , C07K2317/565 , C07K2317/567 , C07K2319/00 , C07K2319/035
摘要： Recombinant, in particular humanised, e.g. humanised chimeric and CDR-grafted humanised, antibody molecules having specificity for human TNFα, are provided for use in diagnosis and therapy. In particular the antibody molecules have antigen binding sites derived from murine monoclonal antibodies CB0006, CB0010, hTNF3 or 101.4. Preferred CDR-grafted humanised anti-hTNFα antibodies comprise variable region domains comprising human acceptor framework and donor antigen binding regions and wherein the frameworks comprise donor residues at specific positions. The antibody molecules may be used for therapeutic treatment of human patients suffering from or at risk of disorders associated with undesirably high levels of TNF, in particular for treatment of immunoregulatory and inflammatory disorders or of septic, endotoxic or cardiovascular shock.

38. 发明申请

WO1991009967A1 HUMANISED ANTIBODIES 审中-公开
标题翻译：人类抗体
公开(公告)号：WO1991009967A1
公开(公告)日：1991-07-11
申请号：PCT/GB1990002017
申请日：1990-12-21
申请人： CELLTECH LIMITED , ADAIR, John, Robert , ATHWAL, Diljeet, Singh , EMTAGE, John, Spencer
发明人： CELLTECH LIMITED
IPC分类号： C12P21/08
CPC分类号： C07K14/7051 , A61K38/00 , C07K16/18 , C07K16/241 , C07K16/2803 , C07K16/2809 , C07K16/2812 , C07K16/461 , C07K16/465 , C07K2317/24 , C07K2319/00 , C07K2319/02
摘要： CDR-grafted antibody heavy and light chains comprise acceptor framework and donor antigen binding regions, the heavy chains comprising donor residues at at least one of positions (6, 23) and/or (24, 48) and/or (49, 71) and/or (73, 75) and/or (76) and/or (78) and (88) and/or (91). The CDR-grafted light chains comprise donor residues at at least one of positions (1) and/or (3) and (46) and/or (47) or at at least one of positons (46, 48, 58) and (71). The CDR-grafted antibodies are preferably humanised antibodies, having non human, e.g. rodent, donor and human acceptor frameworks, and may be used for in vivo therapy and diagnosis. A generally applicable protocol is disclosed for obtaining CDR-grafted antibodies.
摘要翻译： CDR移植的抗体重链和轻链包含受体框架和供体抗原结合区，所述重链在位置（6,23）和/或（24,48）和/或（49,71）中的至少一个处包含供体残基，和/或（73,75）和/或（76）和/或（78）和（88）和/或（91）。 CDR移植的轻链在位置（1）和/或（3）和（46）和/或（47）或至少一个位置（46,48,58）和（ 71）。 CDR移植的抗体优选是人源化抗体，其具有非人类，例如，啮齿动物，供体和人受体框架，并可用于体内治疗和诊断。公开了一种普遍适用的方案来获得CDR-移植的抗体。

39. 发明申请

WO1990011782A2 IMMUNOCONJUGATES AND PRODRUGS AND THEIR USE IN ASSOCIATION FOR DRUG DELIVERY 审中-公开
标题翻译：免疫调节剂和药物及其在药物输送协会中的使用
公开(公告)号：WO1990011782A2
公开(公告)日：1990-10-18
申请号：PCT/GB1990000519
申请日：1990-04-05
申请人： CELLTECH LIMITED , EATON, Michael, Anthony, William , ALEXANDER, Rikki, Peter , PRATT, Andrew, John
发明人： CELLTECH LIMITED
IPC分类号： A61K47/48
CPC分类号： B82Y5/00 , A61K47/54 , A61K47/552 , A61K47/555 , A61K47/6899 , C07K2319/00 , C12N9/78
摘要： A drug delivery system is described in which an immunoconjugate and a prodrug are used in association with each other to deliver a drug to a host target site such as a tumour. The immunoconjugate comprises an antibody or antibody fragment to which is attached a β-lactamase or an active fragment thereof. The prodrug is a cyclic amide derivative of a drug or an unstable precursor thereof in which the drug or precursor is attached to the remainder of the prodrug such that it forms a leaving group which on hydrolysis of the prodrug is eliminated as the active drug or unstable precursor. Particular prodrugs include penicillin or cephalosporin derivatives and other β-lactams to which are attached any physiologically active substances, particularly antineoplastic agents, antiviral, antibacterial or antifungal compounds. In use the immunoconjugate is administered first such that it localises at the host target site. Subsequent administration of the prodrug results in β-lactamase catalysed hydrolysis of the prodrug at the target site with release of the active drug or unstable precursor.

40. 发明申请

WO1990010077A1 VECTOR FOR INTEGRATION SITE INDEPENDENT GENE EXPRESSION IN MAMMALIAN HOST CELLS 审中-公开
标题翻译：集成站点的独立基因表达载体在MAMMALIAN HOST细胞
公开(公告)号：WO1990010077A1
公开(公告)日：1990-09-07
申请号：PCT/GB1990000286
申请日：1990-02-22
申请人： CELLTECH LIMITED , ECCLES, Sarah, Jane , GROSVELD, Franklin, Gerardus
发明人： CELLTECH LIMITED
IPC分类号： C12N15/85
CPC分类号： C12N15/85 , A61K48/00
摘要： A vector for the integration of a gene into the genetic material of a mammalian host cell such that the gene may be expressed by the host cell. The vector comprises a promoter and the gene and an immunoglobulin dominant control region derived from the mouse lambda immunoglobulin gene locus capable of eliciting host cell-type restricted, integration site independent, copy number dependent expression of the said gene. The DNaseI super hypersensitive site exemplified are i) about 2.35 kb upstream of the CAP site of the rearranged lambda 1 gene, ii) about 2.5 kb upstream of the genomic V lambda 2 segment or iii) about 30 kb downstream of the rearranged lambda 1 gene. Mammalian host cells transformed with the vector are disclosed as are transgenic mammals transformed with the vector and a method of producing a polypeptide comprising culturing a transformed mammalian cell. A method of gene therapy comprising the steps of i) removing stem cells from the body of a mammal, ii) optionally killing stem cells remaining in the body, iii) transforming the removed stem cells with the vector containing a gene deficient or absent in the body, and iv) replacing the transformed stem cells in the body is also disclosed. Also disclosed is functional mouse immunoglobulin lambda 1 enhancer consisting of a DNA sequence comprising all or a functional part of the DNA sequence between the EcoRI site 3.8 kb downstream of the Xho I site in the rearranged mouse lambda 1 gene and the SnaBI site 10 kb downstream of this Xho I site. The functional mouse immunoglobulin lambda 1 enhancer may comprise all or a functional part of i) the 1.3 kb first HindIII to HindIII DNA fragment downstream of the EcoRI site 3.8 kb downstream of the Xho I site in the rearranged mouse lambda 1 gene, ii) the 3.3 kb HindIII to HindIII DNA fragment downstream of the EcoRI site 3.8 kb downstream of the Xho I site in the rearranged mouse lambda 1 gene and spanning the SnaBI site 10 kb downstream of this Xho I site.
摘要翻译：用于将基因整合到哺乳动物宿主细胞的遗传物质中的载体，使得该基因可以由宿主细胞表达。该载体包含启动子和该基因以及衍生自小鼠λ免疫球蛋白基因座的免疫球蛋白优势对照区，其能够引发所述基因的宿主细胞型限制性，整合位点独立性，拷贝数依赖性表达。示例的DNaseI超级超敏感位点是i）在重排的λ1基因的CAP位点上游约2.35kb，ii）基因组Vλ2片段上游约2.5kb或iii）重排的λ1基因下游约30kb 。公开了用载体转化的哺乳动物宿主细胞，是用载体转化的转基因哺乳动物以及产生多肽的方法，包括培养转化的哺乳动物细胞。一种基因治疗方法，包括以下步骤：i）从哺乳动物体内除去干细胞，ii）任选地杀死残留在体内的干细胞，iii）用含有缺失或缺失基因的载体转化去除的干细胞身体和iv）替换体内转化的干细胞也被公开。还公开了功能性小鼠免疫球蛋白λ1增强子，其由包含重排的小鼠λ1基因中Xho I位点下游的3.8kb EcoRI位点与下游10kb的SnaBI位点之间的DNA序列的全部或功能部分的DNA序列组成的这个Xho我的网站。功能性小鼠免疫球蛋白λ1增强子可以包含i）在重排的小鼠λ1基因中Xho I位点下游3.8kb的EcoRI位点下游的1.3kb第一HindIII至HindIII DNA片段的全部或功能部分，ii）在重排的小鼠λ1基因的Xho I位点下游的EcoRI位点下游的3.3kb HindIII至HindIII DNA片段，跨越该Xho I位点下游10kb的SnaBI位点。

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