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1. 发明申请

WO1997040141A2 ISOLATION OF ENZYMES 审中-公开
标题翻译：酶的分离
公开(公告)号：WO1997040141A2
公开(公告)日：1997-10-30
申请号：PCT/GB1997001153
申请日：1997-04-25
申请人： MEDICAL RESEARCH COUNCIL , NERI, Dario , DEMARTIS, Salvatore , HUBER, Adrian , VITI, Francesca , TAWFIK, Dan, S. , WINTER, Gregory, Paul
发明人： MEDICAL RESEARCH COUNCIL
IPC分类号： C12N09/00
CPC分类号： C12N15/1086 , C07K14/4728 , C07K14/72 , C07K2319/00 , C12N9/00 , C12N9/0002 , C12N9/1088 , C12N9/1205 , C12N15/1037 , C40B40/02
摘要： The present invention relates to a method of isolating an enzyme having a desired chemical or biological activity, the method comprising linking the enzyme to a substrate for the enzyme, reacting the enzyme and substrate such that a product is produced which remains linked to the enzyme and isolating the enzyme by selectively isolating the product linked to the enzyme.
摘要翻译：本发明涉及一种分离具有所需化学或生物活性的酶的方法，该方法包括将酶与酶的底物连接，使酶和底物反应，使得产生与酶连接的产物，通过选择性分离与酶连接的产物来分离酶。

2. 发明申请

WO1995012672A1 MANUFACTURE AND USE OF POLYPEPTIDES TAGGED USING BINDING MOLECULES 审中-公开
标题翻译：使用结合分子标记的多肽的制备和使用
公开(公告)号：WO1995012672A1
公开(公告)日：1995-05-11
申请号：PCT/GB1994002420
申请日：1994-11-04
申请人： MEDICAL RESEARCH COUNCIL , NERI, Dario , WINTER, Gregory, Paul , DE LALLA, Claudia
发明人： MEDICAL RESEARCH COUNCIL
IPC分类号： C12N15/12
CPC分类号： C07K14/4728 , C07K14/43568 , C07K14/47 , C07K2319/00 , G01N33/68
摘要： Molecules comprise (i) a polypeptide (such as calmodulin) which has calcium-dependent binding affinity for ligand and (ii) another polypeptide, the polypeptides preferably being joined by a peptide bond and produced by recombinant expression from a gene fusion. The molecules are useful in detection, immobilisation, targeting and purification, cell-labelling, and band-shift assays for determining binding of a member of a specific binding pair (sbp) for complementary sbp member. For purposes of band-shift assays, polypeptide (i) need not have calcium-dependent binding affinity for a ligand, but should have a dissociation constant for a ligand of 10nM or less, measured at a pH of between 6 and 9 at 20 DEG C. In an alternative embodiment, a calmodulin-binding polypeptide which is, or is derived from, mastoparan is joined, as polypeptide (i) instead of a binding polypeptide, to the other polypeptide.
摘要翻译：分子包含（i）对配体具有钙依赖性结合亲和力的多肽（例如钙调素）和（ii）另一种多肽，所述多肽优选通过肽键连接并通过基因融合体的重组表达产生。这些分子可用于检测，固定，靶向和纯化，细胞标记和带状移位测定，以确定用于互补sbp成员的特异性结合对（sbp）的成员的结合。为了频移测定的目的，多肽（i）不需要对配体具有钙依赖性结合亲和力，但是对于配体的解离常数为10nM或更低，在pH为6至9的20℃下测量。 C.在替代实施方案中，将多肽（i）代替结合多肽连接到另一多肽中，所述钙调蛋白结合多肽或其衍生自mastoparan的钙调蛋白结合多肽与其他多肽相连接。

3. 发明申请

WO1994006920A1 RECOMBINANT VIRUSES DISPLAYING A NONVIRAL POLYPEPTIDE ON THEIR EXTERNAL SURFACE 审中-公开
标题翻译：在其外表面上显示非天然多肽的重组病毒
公开(公告)号：WO1994006920A1
公开(公告)日：1994-03-31
申请号：PCT/GB1993001992
申请日：1993-09-22
申请人： MEDICAL RESEARCH COUNCIL , RUSSELL, Stephen, James , HAWKINS, Robert, Edward , WINTER, Gregory, Paul
发明人： MEDICAL RESEARCH COUNCIL
IPC分类号： C12N15/86
CPC分类号： C40B40/02 , A61K48/00 , C12N15/1037 , C12N15/86 , C12N15/87 , C12N2740/13043 , C12N2740/13045 , C12N2810/859
摘要： We have made retrovirus particles displaying a functional antibody fragment. We fused the gene encoding an antibody fragment directed against a hapten with that encoding the viral envelope protein (Pr80env) of the ecotropic Moloney murine leukemia virus. The fusion gene was co-expressed in ecotropic retroviral packaging cells with a retroviral plasmid carrying the neomycin phosphotransferase gene (neo), and retroviral particles with specific hapten biding activities were recovered. Furthermore the hapten-binding particles were able to transfer the neo gene and the antibody-envelope fusion gene to mouse fibroblasts. In principle, the display of antibody fragments on the surface of recombinant retroviral particles could be used to target virus to cells for gene delivery, or to retain the virus in target tissues, or for the construction of libraries of viral display packages.
摘要翻译：我们已经制备出显示功能性抗体片段的逆转录病毒颗粒。我们将编码针对半抗原的抗体片段的基因与编码亲和性莫洛尼鼠白血病病毒的病毒包膜蛋白（Pr80env）的基因融合。融合基因在携带新霉素磷酸转移酶基因（neo）的逆转录病毒质粒的亲和逆转录病毒包装细胞中共表达，并回收具有特异性半抗原活性的逆转录病毒颗粒。此外，半抗原结合颗粒能够将neo基因和抗体 - 包膜融合基因转移至小鼠成纤维细胞。原则上，重组逆转录病毒颗粒表面上的抗体片段的显示可用于将病毒靶向到细胞进行基因递送，或将病毒保留在靶组织中，或用于构建病毒显示包的文库。

4. 发明申请

WO1993011236A1 PRODUCTION OF ANTI-SELF ANTIBODIES FROM ANTIBODY SEGMENT REPERTOIRES AND DISPLAYED ON PHAGE 审中-公开
标题翻译：从抗体部分代码产生抗自身抗体并在噬菌体上显示
公开(公告)号：WO1993011236A1
公开(公告)日：1993-06-10
申请号：PCT/GB1992002240
申请日：1992-12-02
申请人： MEDICAL RESEARCH COUNCIL , CAMBRIDGE ANTIBODY TECHNOLOGY LIMITED , GRIFFITHS, Andrew, David , HOOGENBOOM, Hendricus, Renerus, Jacobus, Mattheus , MARKS, James, David , McCAFFERTY, John , WINTER, Gregory, Paul , GRIGG, Geoffrey, Walter
发明人： MEDICAL RESEARCH COUNCIL , CAMBRIDGE ANTIBODY TECHNOLOGY LIMITED
IPC分类号： C12N15/13
CPC分类号： C40B40/02 , B01J2219/00718 , C07K16/005 , C07K16/18 , C07K16/22 , C07K16/241 , C07K16/26 , C07K16/28 , C07K16/2812 , C07K16/2863 , C07K16/2866 , C07K16/3007 , C07K16/3092 , C07K16/34 , C07K16/40 , C07K16/4208 , C07K16/4241 , C07K16/44 , C07K16/462 , C07K16/468 , C07K2317/21 , C07K2317/24 , C07K2317/55 , C07K2317/622 , C07K2317/92 , C07K2319/00 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037 , C12N15/62 , Y10S530/867
摘要： Methods are disclosed for the production of anti-self antibodies and antibody fragments, being antibodies or fragments of a particular species of mammal which bind self-antigens of that species. Methods comprise providing a library of replicable genetic display packages (rgdps), such as filamentous phage, each rgdp displaying at its surface a member of a specific binding pair which is an antibody or antibody fragment, and each rgdp containing nucleic acid sequence derived from a species of mammal. The nucleic acid sequence in each rgdp encodes a polypeptide chain which is a component part of the sbp member displayed at the surface of that rgdp. Anti-self antibody fragments are selected by binding with a self antigen from the said species of mammal. The displayed antibody fragments may be scFv, Fd, Fab or any other fragment which has the capability of binding antigen. Nucleic acid libraries used may be derived from a rearranged V-gene sequences of unimmunised mammal. Synthetic or artificial libraries are described and shown to be useful.
摘要翻译：公开了用于产生抗自身抗体和抗体片段的方法，其是结合该物种的自身抗原的哺乳动物特定种类的抗体或片段。方法包括提供可复制的遗传显示包（rgdps）文库，例如丝状噬菌体，每个rgdp在其表面上显示作为抗体或抗体片段的特异性结合对的成员，以及每个含rgdp的核酸序列衍生自哺乳动物的种类每个rgdp中的核酸序列编码多肽链，其是在该rgdp的表面显示的sbp成员的组成部分。通过与来自所述哺乳动物种的自身抗原结合来选择抗自身抗体片段。显示的抗体片段可以是scFv，Fd，Fab或具有结合抗原能力的任何其它片段。所使用的核酸文库可以来源于未免疫的哺乳动物的重新排列的V基因序列。描述和显示合成或人造文库是有用的。

5. 发明申请

WO1989007452A1 IMPROVEMENTS IN OR RELATING TO ANTIBODIES 审中-公开
标题翻译：改善或相关于抗体
公开(公告)号：WO1989007452A1
公开(公告)日：1989-08-24
申请号：PCT/GB1989000113
申请日：1989-02-10
申请人： MEDICAL RESEARCH COUNCIL , WALDMANN, Herman , CLARK, Michael, Ronald , WINTER, Gregory, Paul , RIECHMANN, Lutz
发明人： MEDICAL RESEARCH COUNCIL
IPC分类号： A61K39/395
CPC分类号： C07K16/465 , A61K38/00 , C07K16/2893 , C07K2317/24 , C07K2317/732 , C07K2317/734 , C07K2319/02
摘要： An antibody is produced, which will bind effectively with the antigen Campath-1, and which has at least one complementarity determining region of rat origin, as identified in Figure 2, which may be combined with a range of different foreign variable domain framework regions as desired, including framework regions of human origin.

6. 发明申请

WO1995001438A1 SBP MEMBERS WITH A CHEMICAL MOIETY COVALENTLY BOUND WITHIN THE BINDING SITE; PRODUCTION AND SELECTION THEREOF 审中-公开
标题翻译：具有化学环境的SBP成员在联合场合中共同界定; 生产和选择
公开(公告)号：WO1995001438A1
公开(公告)日：1995-01-12
申请号：PCT/GB1994001422
申请日：1994-06-30
申请人： MEDICAL RESEARCH COUNCIL , JESPERS, Laurent, Stephane, Anne, Therese , WINTER, Gregory, Paul , BONNERT, Timothy, Peter , SIMON, Thomas, Martin
发明人： MEDICAL RESEARCH COUNCIL
IPC分类号： C12N15/13
CPC分类号： C12N15/1037 , C07K16/18 , C12N9/0002
摘要： Repertoires of first specific binding pair (sbp) members wherein each first sbp member has a chemical moiety bound covalently at an amino acid residue within the binding site are made and may be displayed at the surface of an organism such as a bacteriophage. Methods of making such repertoires may involve the provision of a population of encoding nucleic acid molecules wherein a codon encoding a selectively or preferentially modifiable amino acid is introduced in the region encoding the binding site, for instance by mutation or gene construction. First sbp member (e.g. antibodies) wherein binding to second sbp member (e.g. antigen) is enhanced in or dependant on the presence of the chemical moiety in the binding site may be selected from the repertoires.
摘要翻译：制备第一特异性结合对（sbp）成员的第一特异性结合对（sbp）成员的汇编，其中每个第一sbp成员具有在结合位点内的氨基酸残基处共价结合的化学部分，并且可以显示在诸如噬菌体的生物体的表面。制备这样的所有谱的方法可能涉及提供编码核酸分子的群体，其中编码选择性或优先可修饰的氨基酸的密码子例如通过突变或基因构建被引入编码结合位点的区域中。其中结合第二sbp成员（例如抗原）的第一sbp成员（例如抗体）在结合位点中增加或依赖于化学部分的存在可以选自所有组成成分。

7. 发明申请

WO1994013804A1 MULTIVALENT AND MULTISPECIFIC BINDING PROTEINS, THEIR MANUFACTURE AND USE 审中-公开
标题翻译：多功能和多重结合蛋白质，其制造和使用
公开(公告)号：WO1994013804A1
公开(公告)日：1994-06-23
申请号：PCT/GB1993002492
申请日：1993-12-03
申请人： CAMBRIDGE ANTIBODY TECHNOLOGY LIMITED , MEDICAL RESEARCH COUNCIL , HOLLIGER, Kaspar-Philipp , GRIFFITHS, Andrew, David , HOOGENBOOM, Hendricus, Renerus, Jacobus, Matheus , MALMQVIST, Magnus , MARKS, James, David , McGUINNESS, Brian, Timothy , POPE, Anthony, Richard , PROSPERO, Terence, Derek , WINTER, Gregory, Paul
发明人： CAMBRIDGE ANTIBODY TECHNOLOGY LIMITED , MEDICAL RESEARCH COUNCIL
IPC分类号： C12N15/13
CPC分类号： C07K16/005 , A61K38/00 , C07K16/00 , C07K16/40 , C07K16/44 , C07K16/468 , C07K2317/34 , C07K2317/622 , C07K2317/626 , C07K2319/00 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037 , C12N15/113 , C12N2310/111 , C12N2310/1241 , C12N2310/127 , C40B40/02
摘要： Polypeptides comprising a first domain, which comprises a binding region of an immunoglobulin heavy chain variable region, and a second domain, which comprises a binding region of an immunoglobulin light chain variable region, the domains being linked but incapable of associating with each other to form an antigen binding site, associate to form antigen binding multimers, such as dimers, which may be multivalent or have multispecificity. The domains may be linked by a short peptide linker or may be joined directly together. Bispecific dimers may have longer linkers. Methods of preparation of the polypeptides and multimers and diverse repertoires thereof, and their display on the surface of bacteriophage for easy selection of binders of interest, are disclosed, along with many utilities.
摘要翻译：包含第一结构域的多肽，其包含免疫球蛋白重链可变区的结合区和第二结构域，其包含免疫球蛋白轻链可变区的结合区，所述结构域被连接但不能彼此缔合形成抗原结合位点，缔合以形成抗原结合多聚体，例如二聚体，其可以是多价的或具有多特异性。结构域可以通过短肽接头连接，或者可以直接连接在一起。双特异性二聚体可以具有更长的接头。公开了多肽和多聚体及其多种组成成分的制备方法，以及它们在噬菌体表面上的显示以便于选择感兴趣的粘合剂，以及许多实用性。

8. 发明申请

WO1994008008A1 IMPROVEMENTS IN OR RELATING TO IMMUNE RESPONSE MODIFICATION 审中-公开
标题翻译：改进或相关于免疫反应修改
公开(公告)号：WO1994008008A1
公开(公告)日：1994-04-14
申请号：PCT/GB1993002054
申请日：1993-10-04
申请人： MEDICAL RESEARCH COUNCIL , HAWKINS, Robert, Edward , RUSSELL, Stephen, James , STEVENSON, Freda, Katherine , WINTER, Gregory, Paul
发明人： MEDICAL RESEARCH COUNCIL
IPC分类号： C12N15/13
CPC分类号： C07K16/4208 , A61K39/00 , C07K16/18 , C07K16/42 , C07K2319/02
摘要： Disclosed is a method of making an immunomodulatory composition to modulate the immune response against a disease marker, comprising: identifying the nucleic acid sequence encoding the disease marker by analysis of a suitable sample from a patient and extracellularly cloning therefrom; inserting said nucleic acid into a suitable vector; and administering said vector to a patient so as to cause expression of the disease marker in a form which interacts with the immune system. Also disclosed is a method of modifying the immune response of an individual and compositions for use in performing the method.
摘要翻译：公开了一种制备免疫调节组合物以调节针对疾病标志物的免疫应答的方法，其包括：通过分析来自患者的合适样品并从其中进行细胞外克隆来鉴定编码疾病标志物的核酸序列; 将所述核酸插入合适的载体中; 并将所述载体施用于患者，以便以与免疫系统相互作用的形式引起疾病标志物的表达。还公开了一种修饰用于实施该方法的个体和组合物的免疫应答的方法。

9. 发明申请

WO1993025909A1 IMPROVEMENTS IN OR RELATING TO ANALYTE DETECTION 审中-公开
标题翻译：在分析检测中或与分析检测相关的改进
公开(公告)号：WO1993025909A1
公开(公告)日：1993-12-23
申请号：PCT/GB1993001242
申请日：1993-06-11
申请人： PHARMACIA BIOSENSOR AB , MALMQVIST, Magnus , WINTER, Gregory, Paul
发明人： PHARMACIA BIOSENSOR AB
IPC分类号： G01N33/543
CPC分类号： G01N33/6857 , G01N21/553 , G01N33/54373 , Y10S435/808 , Y10S436/805 , Y10S436/807 , Y10S436/824 , Y10T436/117497
摘要： Disclosed is apparatus for detecting the presence of an analyte of interest in a sample, comprising an immobilised binding partner comprising a solid support and a reversibly binding receptor which is capable of binding to the analyte of interest thereby causing a measurable change in a property of the immobilised binding partner, and detection means for detecting the measurable change and a method for detecting the presence of an analyte of interest.
摘要翻译：公开了一种用于检测样品中感兴趣分析物的存在的装置，其包含固定的结合配偶体，其包含固体支持物和可逆结合受体，所述受体结合受体能够结合感兴趣的分析物，从而导致可测量的用于检测可测量的变化的检测装置和用于检测感兴趣的分析物的存在的方法。

10. 发明申请

WO1993006213A1 PRODUCTION OF CHIMERIC ANTIBODIES - A COMBINATORIAL APPROACH 审中-公开
标题翻译：生产抗体 - 组合方法
公开(公告)号：WO1993006213A1
公开(公告)日：1993-04-01
申请号：PCT/GB1992001755
申请日：1992-09-23
申请人： MEDICAL RESEARCH COUNCIL , CAMBRIDGE ANTIBODY TECHNOLOGY LIMITED , HOOGENBOOM, Hendricus, Renerus, Jacobus, Matteus , BAIER, Michael , JESPERS, Laurent, Stephane, Anne, Therese , WINTER, Gregory, Paul
发明人： MEDICAL RESEARCH COUNCIL , CAMBRIDGE ANTIBODY TECHNOLOGY LIMITED
IPC分类号： C12N15/00
CPC分类号： C40B40/02 , B01J2219/00718 , C07K16/00 , C07K16/005 , C07K16/18 , C07K16/22 , C07K16/241 , C07K16/28 , C07K16/2812 , C07K16/2863 , C07K16/2866 , C07K16/3007 , C07K16/40 , C07K16/4208 , C07K16/462 , C07K16/468 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/622 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037
摘要： Methods are disclosed which may be used for the production of antibodies, or antibody fragments, which have the same binding specificity as a parent antibody but which have increased human characteristics. Humanised antibodies may be obtained by chain shuffling, perhaps using phage display technology. In one embodiment, a polypeptide comprising a heavy or light chain variable domain of a non-human antibody specific for an antigen of interest is combined with a repertoire of human complementary (light or heavy) chain variable domains. Hybrid pairings which are specific for the antigen of interest are selected. Human chains from the selected pairings may then be combined with a repertoire of human complementary variable domains (heavy or light) and humanised antibody polypeptide dimers can then be selected for binding specificity for antigen. The methods may be combined with CDR-imprinting. In another embodiment, component part of an antigen-binding site of a non-human antibody known to bind a particular antigen is combined with a repertoire of component parts of an antigen-binding site of human antibody, forming a library of antibody polypeptide dimers with antigen-binding sites. Hybrids selected from this library may be used in a second humanising shuffling step, or may already be of sufficient human character to be of value, perhaps after some modification to increase human character still further.
摘要翻译：公开了可用于生产具有与亲本抗体相同的结合特异性但具有增加的人类特征的抗体或抗体片段的方法。人源化抗体可以通过链式洗牌获得，也许使用噬菌体展示技术。在一个实施方案中，将包含感兴趣抗原特异性的非人抗体的重链或轻链可变结构域的多肽与人互补（轻链或重链）可变域的所有组成部分组合。选择对感兴趣的抗原特异的杂交配对。然后将所选配对的人链与人互补可变结构域（重或轻）的组合组合，然后可以选择人源化抗体多肽二聚体以结合抗原的特异性。这些方法可以与CDR-印记组合。在另一个实施方案中，已知结合特定抗原的非人抗体的抗原结合位点的组成部分与人抗体的抗原结合位点的组成部分的组成部分组合，形成抗体多肽二聚体文库，抗原结合位点。从该图书馆中选出的杂种可以用于第二次人性化洗牌步骤中，或者可能已经具有足够的人性以具有价值，可能在经过一些修改以增加人的性格之后。

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