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61. 发明申请

WO1991016081A1 TETRA-AZA MACROCYCLES, PROCESSES FOR THEIR PREPARATION AND THEIR USE IN MAGNETIC RESONANCE IMAGING 审中-公开
标题翻译： TETRA-AZA MACROCYCLES，其制备方法及其在磁共振成像中的应用
公开(公告)号：WO1991016081A1
公开(公告)日：1991-10-31
申请号：PCT/GB1991000605
申请日：1991-04-18
申请人： CELLTECH LIMITED , PARKER, David , BEELEY, Nigel, Robert, Arnold
发明人： CELLTECH LIMITED
IPC分类号： A61K49/00
CPC分类号： A61K49/06 , C07D257/02 , C07F9/6524 , Y10S514/836
摘要： Metal complex of tetra-aza macrocycles of formula (1) wherein Alk?1, Alk2, Alk3¿ and Alk4, which may be the same or different, is each a C¿1-4? alkylene chain optionally substituted by one or more optionally substituted C1-6 alkyl groups; and R?1, R2, R3 and R4¿ which may be the same or different is each a hydrogen atom or a group AlkR5 where Alk is an optionally substituted straight or branched C¿1-6? alkyl group and R?5¿ is a hydrogen atom or a -CO¿2?H,-CONR?6R7¿ [where R?6 and R7¿, which may be the same or different, is each a hydrogen atom or a C¿1-6? alkyl group] or -P(X?1)(X2R8)R9¿ group where X?1 and X2¿, which may be the same or different is each an oxygen or sulphur atom, R8 is a hydrogen atom or an alkyl group and R9 is an aliphatic, aromatic or heteroaromatic group, with the proviso that at least two of R?1, R2, R3 and R4¿ is a group -AlkP(X?1)(X2R8)R9¿ or one of R?1, R2, R3 and R4¿ is a group -AlkP(X?1)(X2R8)R9¿ and at least one of the remaining groups R?1, R2, R3 and R4¿ is a group -AlkCO¿2?H or -AlkCONR?6R7¿, or a salt thereof, for use as contrast agents in nuclear magnetic resonance imaging are described.

62. 发明申请

WO1991000285A1 TRI-AZA MACROCYCLES AND PROCESSES FOR THEIR PREPARATION 审中-公开
标题翻译： TRI-AZA MACROCYCLES及其制备方法
公开(公告)号：WO1991000285A1
公开(公告)日：1991-01-10
申请号：PCT/GB1990000982
申请日：1990-06-25
申请人： CELLTECH LIMITED , PARKER, David , EATON, Michael, Anthony, William
发明人： CELLTECH LIMITED
IPC分类号： C07F09/6515
CPC分类号： C07D255/02 , C07F9/6515
摘要： Tri-aza macrocycles of formula (1), wherein m and n, which may be the same or different, is each zero or an integer 1, 2, or 3; p is zero or an integer 1 or 2; q is zero or an integer from 1 to 6 inclusive; R?1, R2 and R3¿, which may be the same or different, is each a hydrogen atom or a group -CO¿2?H or -P(O)(XH)R?4¿ (where X is an oxygen or sulpher atom and R4 is a hydrogen atom or an alkyl or alkoxy group), with the proviso that at least one of R?1, R2 and R3¿ is a -P(O)(XH)R4 group; L is a covalent bond or a linker group; Z is a hydrogen atom or a reactive functional group; and metal complexes and/or salts thereof; are described together with processes for their preparation and compositions containing them. The compounds are useful as imaging agents, and in the treatment of abnormal cell disorders, such as in the treatment of tumours, and may be coupled to other molecules, such as proteins, for use in diagnosis and therapy.

63. 发明申请

WO1990012815A1 THERAPEUTIC COMPOUNDS, COMPOSITIONS AND USES THEREOF 审中-公开
标题翻译：治疗化合物，组合物及其用途
公开(公告)号：WO1990012815A1
公开(公告)日：1990-11-01
申请号：PCT/GB1990000594
申请日：1990-04-19
申请人： CELLTECH LIMITED , RIDDELL, Alistair, James
发明人： CELLTECH LIMITED
IPC分类号： C07K99/46
CPC分类号： A61K38/225
摘要： The use of calcitonin gene-related peptide in achieving the controlled reduction of blood pressure while maintaining cerebrovascular blood supply is described. This activity of CGRP makes it especially suitable for use in the treatment of malignant hypertension and hypertension following cardiac surgery.
摘要翻译：描述了降钙素基因相关肽在保持脑血管供血的同时实现血压控制降低的用途。 CGRP的这种活性使其特别适用于治疗心脏手术后的恶性高血压和高血压。

64. 发明申请

WO1990010700A1 MODIFIED ANTIBODIES 审中-公开
标题翻译：改良抗体
公开(公告)号：WO1990010700A1
公开(公告)日：1990-09-20
申请号：PCT/GB1990000375
申请日：1990-03-13
申请人： CELLTECH LIMITED , ADAIR, David, Robert , KING, David, John , YARRANTON, Geoffrey, Thomas
发明人： CELLTECH LIMITED
IPC分类号： C12N15/13
CPC分类号： C07K16/00 , A61K38/00
摘要： There is provided a modified antibody having an altered number of glycosylation sites as compared to the number in the equivalent natural antibody. Preferably the modified antibody is produced by recombinant DNA techniques involving the production of an expression vector containing a DNA sequence encoding a modified antibody chain having an altered number of glycosylation sites. The DNA sequence may be prepared from the natural antibody gene by site-directed mutagenesis. Preferably the modified antibody chain has an increased number of glycosylation sites; for instance a modified Fab, Fab' or (Fab')2 antibody with a glycosylation site introduced into the CL or CHl domain thereof. Altering the degree of glycosylation alters properties of the antibodies, e.g. blood clearance rate, when used in vivo; generally the greater the degree of glycosylation the slower the blood clearance. The altered antibodies may be used for the preparation of compositions for use in diagnosis, e.g. in vivo diagnosis and imaging, or in therapy; glycosylation minus/reduced antibodies being preferred for diagnostic uses and glycosylation plus/increased antibodies being preferred for therapeutic application.

65. 发明申请

WO1990009379A1 AZA-MACROCYCLES AND PROCESSES FOR THEIR PREPARATION 审中-公开
标题翻译： AZA-MACROCYCLES及其制备方法
公开(公告)号：WO1990009379A1
公开(公告)日：1990-08-23
申请号：PCT/GB1990000219
申请日：1990-02-12
申请人： CELLTECH LIMITED , PARKER, David , BEELEY, Nigel, Robert, Arnold , MILLICAN, Thomas, Andrew
发明人： CELLTECH LIMITED
IPC分类号： C07D257/02
CPC分类号： C07D403/12 , C07D255/02 , C07D257/02
摘要： Aza macrocycles of formula (1) wherein A is a group -(CH2)p- or -(CH2)pN(R)(CH2)q- where R is a group -CH(R4)X4; m, n, p, and q, which may be the same or different, is each an integer 2 or 3; R?1, R2, R3 and R4¿, which may be the same or different, is each a group -CO¿2?H, -P(R?5)O¿2H (where R5 is a hydrogen atom or an alkyl or alkoxy group), -PO¿3?H2 or -CONR?6R7¿ (where R?6 and R7¿, which may be the same or different, is each a hydrogen atom or an alkyl group); X?1, X2, X3, X4¿, which may be the same or different, is each a hydrogen atom or an alkyl group, or a linker group, with the proviso that at least one of X?1, X2, X3 or X4¿ is a linker group; and protected derivatives and metal complexes and/or salts thereof; are described together with processes for their preparation and compositions containing them. The compounds are useful for imaging and in the treatment of abnormal cell disorders, such as in the treatment of tumors, and may be coupled to other molecules such as proteins for use in diagnosis and therapy.

66. 发明申请

WO1990009196A1 CROSS-LINKED ANTIBODIES AND PROCESSES FOR THEIR PREPARATION 审中-公开
标题翻译：交联抗体及其制备方法
公开(公告)号：WO1990009196A1
公开(公告)日：1990-08-23
申请号：PCT/GB1990000214
申请日：1990-02-12
申请人： CELLTECH LIMITED , RHIND, Stephen, Keith
发明人： CELLTECH LIMITED
IPC分类号： A61K47/48
CPC分类号： A61K51/1093 , A61K47/6877 , A61K51/1087 , A61K2123/00
摘要： Cross-linked labelled antibody conjugates are described which have at least one non-disulphide interchain bridge. The bridge may be the residue of a homo- or heterofunctional cross-linking reagent, and is located away from the antigen binding domains of the antibody. The antibody conjugates have an enhanced binding capacity and in vivo have good blood clearance and, in the presence of a tumour high tumour: blood and tumour: bone ratios. The conjugates are of use in the diagnosis and therapy of e.g. tumours and may be prepared by reaction of a cross-linking reagent with an antibody.

67. 发明申请

WO1990009195A1 CROSS-LINKED ANTIBODIES AND PROCESSES FOR THEIR PREPARATION 审中-公开
标题翻译：交联抗体及其制备方法
公开(公告)号：WO1990009195A1
公开(公告)日：1990-08-23
申请号：PCT/GB1990000213
申请日：1990-02-12
申请人： CELLTECH LIMITED , RHIND, Stephen, Keith , MILLAR, Kenneth , MILLICAN, Thomas, Andrew
发明人： CELLTECH LIMITED
IPC分类号： A61K47/48
CPC分类号： A61K51/1093 , A61K47/6851 , A61K47/6877 , A61K51/1045 , A61K51/1087 , A61K2123/00
摘要： Cross-linked antibody conjugates are described which have at least one interchain bridge containing a reporter or effector molecule. The bridge may be the residue of a homo- or heterofunctional cross-linking reagent, and is located away from the antigen binding domains of the antibody. The antibody conjugates have an enhanced binding capacity and in vivo have good blood clearance and, in the presence of a tumour high tumour: blood and tumour: bone ratios. The conjugates are of use in the diagnosis and therapy of e.g. tumours and may be prepared by reaction of a cross-linking reagent with an antibody.
摘要翻译：公开了交联抗体缀合物，其具有至少一个含有报道分子或效应分子的体间桥。该桥可以是同官能或异官能交联剂的残基，并且位于抗体的抗原结合结构域的对面。抗体缀合物具有改善的结合能力，并具有良好的血液净化系数，并且在存在肿瘤的情况下具有优异的肿瘤/血液和肿瘤/骨比例。这些缀合物可用于肿瘤的诊断和治疗，并可通过使交联剂与抗体反应来制备。

68. 发明申请

WO1990008191A1 RECOMBINANT DNA METHOD AND HOST CELLS 审中-公开
标题翻译：重组DNA方法和宿主细胞
公开(公告)号：WO1990008191A1
公开(公告)日：1990-07-26
申请号：PCT/GB1990000032
申请日：1990-01-10
申请人： CELLTECH LIMITED , COCKETT, Mark, Ian , BEBBINGTON, Christopher, Robert , YARRANTON, Geoffrey, Thomas
发明人： CELLTECH LIMITED
IPC分类号： C12N15/85
CPC分类号： C12N15/85 , C12N2800/108
摘要： The present invention provides a process and host cell for use in increasing the amount of a desired protein produced by a cell line. The process and the cell line use a first transcription unit containing a gene for a transactivator protein to control the transactivation of a second transcription unit such that the amount of desired protein expression can be increased without affecting adversely cell growth. Preferred transactivatior proteins are derived from E1A.

69. 发明申请

WO1989001975A1 RECOMBINANT ANTIBODIES AND METHODS FOR THEIR PRODUCTION 审中-公开
标题翻译：重组抗体及其生产方法
公开(公告)号：WO1989001975A1
公开(公告)日：1989-03-09
申请号：PCT/GB1988000695
申请日：1988-08-24
申请人： CELLTECH LIMITED , CATTANEO, Antonino , NEUBERGER, Michael, Samuel
发明人： CELLTECH LIMITED
IPC分类号： C12P21/00
CPC分类号： C07K16/00 , A61K38/00 , C07K16/40
摘要： There is provided a process for the production of an assembled polymeric recombinant antibody having its constant regions derived from an IgM, characterised in that the process is carried out in the absence of J-chain or any active gene coding therefor. Preferably, the host cell is an actively secreting cell, such as a glial cell, so that the transformed cell can be transplanted into the brain.
摘要翻译：提供了一种制备其具有源自IgM的恒定区的组装的聚合物重组抗体的方法，其特征在于该方法在不存在J链或任何其编码的活性基因的情况下进行。优选地，宿主细胞是主动分泌的细胞，例如胶质细胞，使得转化的细胞可以移植到脑中。

70. 发明申请

WO1988000615A1 PROCESS FOR PURIFYING A PLASMINOGEN ACTIVATOR 审中-公开
标题翻译：纯化激活剂的方法
公开(公告)号：WO1988000615A1
公开(公告)日：1988-01-28
申请号：PCT/GB1987000498
申请日：1987-07-15
申请人： CELLTECH LIMITED , KENNEY, Andrew, Charles , PERRY, Angela, Joyce , WHITE, Susan , MARSTON, Fiona, Angela, Olinda
发明人： CELLTECH LIMITED
IPC分类号： C12N09/64
CPC分类号： C12N9/6459 , C12Y304/21069
摘要： Process for the purification of tPA comprising: applying a mother solution containing tPA to a highly anionic chromatography medium (HACM) equilibrated with a buffer at 25mS ionic strength or lower and at a pH between 4 and 7; eluting the tPA from the highly anionic chromatography medium with a high ionic strength buffer; applying the eluate from the highly anionic chromatography medium to an affinity chromatography medium (ACM), comprising an anti-tPA antibody covalently bound to a chromatography material, equilibrated with a buffer at pH 5 to 10; and eluting the tPA from the affinity chromatography medium with a buffer which disrupts the binding of the antibody to the tPA. Preferably, the mother solution is the supernatant from a culture of a eukaryotic cell line which has been transformed by recombinant DNA technology so that it is able to express and secrete tPA. Advantageously the mother solution is processed as soon as it is harvested and all the process steps are carried out as quickly as possible, the mother solution contains a serine protease inhibitor, and all the solutions contain a detergent and are kept at as low a pH as possible.
摘要翻译：用于纯化tPA的方法，包括：将含有tPA的母液施加到用25mS离子强度或更低的pH在4至7之间的缓冲液平衡的高度阴离子色谱介质（HACM）上; 用高离子强度缓冲液从高度阴离子色谱介质中洗脱tPA; 将洗脱液从高度阴离子色谱介质施加到亲和层析介质（ACM），其包含与pH 5至10的缓冲液平衡的与色谱材料共价结合的抗tPA抗体; 并用缓冲液从亲和层析介质中洗脱tPA，破坏抗体与tPA的结合。优选地，母液是通过重组DNA技术转化的真核细胞系的培养物的上清液，使得其能够表达和分泌tPA。有利的是，一旦收获母液即可迅速处理母液，母液中含有丝氨酸蛋白酶抑制剂，所有溶液都含有洗涤剂，并保持在pH 可能。

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