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21. 发明申请

WO0230945A3 CONCATENATED NUCLEIC ACID SEQUENCES 审中-公开
标题翻译：结合核酸序列
公开(公告)号：WO0230945A3
公开(公告)日：2002-07-18
申请号：PCT/GB0104615
申请日：2001-10-15
申请人： MEDICAL RES COUNCIL , WINTER GREGORY , JESPERS LAURENT , LASTERS IGNACE , WANG PETER
发明人： WINTER GREGORY , JESPERS LAURENT , LASTERS IGNACE , WANG PETER
IPC分类号： C12N15/10 , C12N15/66 , C40B40/02
CPC分类号： C40B40/02 , C12N15/10 , C12N15/1037 , C12N15/66
摘要： An in vitro method for constructing a concatenated head-to-tail repertoire of target nucleic acid sequences is revealed. In particular, the method relates to cycles of concatenation whereby after a single cycle of concatenation, not more than two identical copies of each target nucleic acid sequences are linked together head-to-tail on the same molecule of DNA. The present method ensures that each molecule of a concatenated repertoire is derived from a single template target sequence of the starting repertoire.
摘要翻译：揭示了用于构建目标核酸序列的连接的头对头序列的体外方法。特别地，该方法涉及级联的循环，其中在单次循环的连接后，每个靶核酸序列的不超过两个相同的拷贝在DNA的相同分子上以头对尾连接在一起。本发明的方法确保连接的所有组成部分的每个分子来自起始集合体的单个模板目标序列。

22. 发明申请

WO9958655A3 PHAGE DISPLAY SELECTION SYSTEM FOR FOLDED PROTEINS 审中-公开
标题翻译：用于折叠蛋白质的PHAGE显示选择系统
公开(公告)号：WO9958655A3
公开(公告)日：2000-01-27
申请号：PCT/GB9901526
申请日：1999-05-13
申请人： MEDICAL RES COUNCIL , RIECHMANN LUTZ , KRISTENSEN PETER , JESTIN JEAN LUC , WINTER GREGORY PAUL
发明人： RIECHMANN LUTZ , KRISTENSEN PETER , JESTIN JEAN-LUC , WINTER GREGORY PAUL
IPC分类号： C12N15/00 , C12N7/01 , C12N7/02 , C12N15/10 , C12N15/62 , C40B40/02
CPC分类号： C40B40/02 , C07K2319/02 , C07K2319/41 , C07K2319/43 , C07K2319/50 , C07K2319/70 , C07K2319/735 , C12N15/1037 , C12N15/62
摘要： The present invention concerns a method for the selection of a virus comprising the steps of: (a) providing a virus encoding and displaying a fusion polypeptide, said fusion polypeptide comprising a heterologous polypeptide inserted into the sequence of a viral coat protein polypeptide, wherein said virus comprises a cleavable site located within a displayed polypeptide; (b) exposing the virus to a cleaving agent; (c) propagating the virus comprising intact fusion protein.
摘要翻译：本发明涉及一种选择病毒的方法，包括以下步骤：（a）提供编码和显示融合多肽的病毒，所述融合多肽包含插入到病毒外壳蛋白多肽序列中的异源多肽，其中所述病毒包含位于显示的多肽内的可切割位点; （b）将病毒暴露于裂解剂; （c）扩增包含完整融合蛋白的病毒。

23. 发明申请

WO9740141A3 ISOLATION OF ENZYMES 审中-公开
标题翻译：酶的分离
公开(公告)号：WO9740141A3
公开(公告)日：1998-01-08
申请号：PCT/GB9701153
申请日：1997-04-25
申请人： MEDICAL RES COUNCIL , NERI DARIO , DEMARTIS SALVATORE , HUBER ADRIAN , VITI FRANCESCA , TAWFIK DAN S , WINTER GREGORY PAUL
发明人： NERI DARIO , DEMARTIS SALVATORE , HUBER ADRIAN , VITI FRANCESCA , TAWFIK DAN S , WINTER GREGORY PAUL
IPC分类号： C12N15/09 , C07K14/47 , C07K14/72 , C12N9/00 , C12N9/10 , C12N9/12 , C12N15/10 , C40B40/02 , C12N15/00 , C12N15/62
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.

24. 发明申请

WO1994009131A1 RECOMBINANT SPECIFIC BINDING PROTEIN 审中-公开
标题翻译：重组特异性结合蛋白
公开(公告)号：WO1994009131A1
公开(公告)日：1994-04-28
申请号：PCT/GB1993002133
申请日：1993-10-15
申请人： SCOTGEN LIMITED , HARRIS, William, Joseph , EMERY, Stephen, Charles , WINTER, Gregory, Paul , CARR, Francis, Joseph , MCGREGOR, Duncan, Patrick
发明人： SCOTGEN LIMITED
IPC分类号： C12N15/12
CPC分类号： C07K16/468 , A61K38/00
摘要： A specific binding protein having first and second binding regions, e.g. antibody Fv fragments, which specifically recognise and bind to target entities, said binding regions being contained at least in part on respectively first and second polypeptide chains, said chains additionally incorporating respectively first and second associating domains, e.g. antibody VH and VL domains, which are capable of binding to each other, causing the first and second polypeptide chains to combine, thereby providing a single protein incorporating the binding specificities of said first and second binding regions. The first and second binding regions may recognise different target entities, giving a bispecific binding protein. Preferably the associating domains are derived from a human protein (i.e. one which has been exposed to the human immune system), so that the protein is less likely to provoke the human immune system when administered therapeutically. The binding protein is suitably produced by recombinant DNA expression.
摘要翻译：具有第一和第二结合区的特异性结合蛋白，例如抗体Fv片段，其特异性识别并结合靶物质，所述结合区至少部分地分别包含第一和第二多肽链，所述链另外包含第一和第二缔合结构域，例如，抗体VH和VL结构域，其能够彼此结合，导致第一和第二多肽链结合，从而提供掺入所述第一和第二结合区的结合特异性的单一蛋白质。第一和第二结合区可以识别不同的靶实体，得到双特异性结合蛋白。优选地，缔合结构域衍生自人蛋白质（即已经暴露于人类免疫系统的蛋白质），使得当治疗施用时蛋白质不太可能引起人免疫系统。结合蛋白通过重组DNA表达适当地产生。

25. 发明申请

WO1993019172A1 METHODS FOR PRODUCING MEMBERS OF SPECIFIC BINDING PAIRS 审中-公开
标题翻译：用于生产特定绑定对的成员的方法
公开(公告)号：WO1993019172A1
公开(公告)日：1993-09-30
申请号：PCT/GB1993000605
申请日：1993-03-24
申请人： CAMBRIDGE ANTIBODY TECHNOLOGY LIMITED , MEDICAL RESEARCH COUNCIL , JOHNSON, Kevin, Stuart , WINTER, Gregory, Paul , GRIFFITHS, Andrew, David , SMITH, Andrew, John, Hammond , WATERHOUSE, Peter
发明人： CAMBRIDGE ANTIBODY TECHNOLOGY LIMITED , MEDICAL RESEARCH COUNCIL
IPC分类号： C12N15/00
CPC分类号： C40B40/02 , B01J2219/00718 , 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 , C07K2317/55 , C07K2317/622 , C07K2319/00 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037 , C12N15/62
摘要： Methods, recombinant host cells and kits are disclosed for the production of members of specific binding pairs (sbp), e.g. antibodies, using display on the surface of secreted replicable genetic display packages (rgdps), e.g. filamentous phage. To produce a library of great diversity recombination occurs between first and second vectors comprising nucleic acid encoding first and second polypeptide chains of sbp members respectively, thereby producing recombinant vectors each encoding both a first and a second polypeptide chain component of an sbp member. The recombination may take place in vitro or intracellularly and may be site-specific, e.g. involving use of the l &cir& _o &cir& _x &cir& _P sequence and mutants thereof. Recombination may take place after prior screening or selecting for rgdps displaying sbp members which bind complementary sbp member of interest.
摘要翻译：公开了用于产生特异性结合对（sbp）成员的重组宿主细胞和试剂盒，例如，抗体，使用分泌的可复制遗传显示包（rgdps）的表面上的显示。丝状噬菌体为了产生大量多样性的文库，在包含分别编码sbp成员的第一和第二多肽链的核酸的第一和第二载体之间发生重组，从而产生每个编码sbp成员的第一和第二多肽链组分的重组载体。重组可以在体外或细胞内发生，并且可以是位点特异性的，例如，涉及使用l＆cir＆_o＆cir＆_x＆cir＆_P序列及其突变体。重组可能在先前的筛选或选择rgdps显示sbp成员之后发生，该成员绑定了感兴趣的补充sbp成员。

26. 发明申请

WO1993017105A1 ALTERED ANTIBODIES, PRODUCTS AND PROCESSES RELATING THERETO 审中-公开
标题翻译：改变的抗体，产品和工艺与此有关
公开(公告)号：WO1993017105A1
公开(公告)日：1993-09-02
申请号：PCT/GB1993000363
申请日：1993-02-19
申请人： SCOTGEN LIMITED , WINTER, Gregory, Paul , CARR, Francis, Joseph , HARRIS, William, Joseph
发明人： SCOTGEN LIMITED
IPC分类号： C12N15/13
CPC分类号： C07K16/1027 , A61K38/00 , C07K16/465 , C07K2317/24
摘要： The present invention relates to altered antibodies which are substantially immuno silent by virtue of their containing selected germ-line amino acid residues which replace one or more corresponding somatically mutated residues in a native antibody. In a process for making a gene for use in preparing such an antibody, one or more somatically mutated amino acid residues in a native antibody are identified as suitable candidate(s) for alteration. A nucleotide coding sequence is made which codes for selected germ-line amino acid residues to replace the one or more somatically mutated amino acid residues. The altered antibody can have variable (V) regions which comprise complementarity determining regions (CDRs) which provide the antibody with capacity to bind a specific antigen; and a selected and predominantly germ-line framework. In processes for making a gene for use in the preparation of such an antibody, there are the steps of (i) obtaining CDR encoding nucleotide sequences which encode CDRs with specificity for the specific antigen and (ii) combining these CDR encoding nucleotide sequences with framework encoding nucleotide sequences which encode the selected germ-line framework.
摘要翻译：本发明涉及通过其含有选择的天然抗体中一个或多个相应的体细胞突变残基的选择的种系氨基酸残基基本上免疫沉默的抗体。在制备用于制备这种抗体的基因的方法中，天然抗体中的一个或多个体细胞突变的氨基酸残基被鉴定为用于改变的合适的候选物。编码编码选择的种系氨基酸残基以代替一个或多个体细胞突变的氨基酸残基的核苷酸编码序列。改变的抗体可以具有可变（V）区，其包含提供抗体结合特异性抗原的能力的互补决定区（CDR）; 和所选择的并且主要种系框架。在制备用于制备这种抗体的基因的方法中，存在以下步骤：（i）获得CDR编码核苷酸序列，其编码对特异性抗原具有特异性的CDR，以及（ii）将这些CDR编码核苷酸序列与框架编码所选择的种系框架编码核苷酸序列。

27. 发明申请

WO1993001289A1 HUMANIZED INTERLEUKIN-2 RECEPTORS ANTIBODIES 审中-公开
标题翻译：人类白细胞介素-2受体抗体
公开(公告)号：WO1993001289A1
公开(公告)日：1993-01-21
申请号：PCT/GB1992001258
申请日：1992-07-10
申请人： THE WELLCOME FOUNDATION LIMITED , WALDMANN, Herman , WINTER, Gregory, Paul , CROWE, James, Scott , LEWIS, Alan, Peter
发明人： THE WELLCOME FOUNDATION LIMITED
IPC分类号： C12N15/13
CPC分类号： C07K16/2866 , A61K38/00
摘要： A DNA molecule, for example an expression vector, encoding at least one chain of a humanised antibody capable of binding to the human IL-2 receptor and having complementarity determining regions (CDRs) of defined amino acid sequence. The antibody itself may be used in treating a T-cell mediated disease state, for example graft versus host disease or an autoimmune disease.
摘要翻译： DNA分子，例如表达载体，其编码能够结合人IL-2受体并具有限定的氨基酸序列的互补决定区（CDR）的人源化抗体的至少一条链。抗体本身可用于治疗T细胞介导的疾病状态，例如移植物抗宿主病或自身免疫性疾病。

28. 发明申请

WO1992020791A1 METHODS FOR PRODUCING MEMBERS OF SPECIFIC BINDING PAIRS 审中-公开
标题翻译：用于生产特定绑定对的成员的方法
公开(公告)号：WO1992020791A1
公开(公告)日：1992-11-26
申请号：PCT/GB1992000883
申请日：1992-05-15
申请人： CAMBRIDGE ANTIBODY TECHNOLOGY LIMITED , MEDICAL RESEARCH COUNCIL , WINTER, Gregory, Paul , JOHNSON, Kevin, Stuart , GRIFFITHS, Andrew, David , SMITH, Andrew, John, Hammond
发明人： CAMBRIDGE ANTIBODY TECHNOLOGY LIMITED , MEDICAL RESEARCH COUNCIL
IPC分类号： C12N15/00
CPC分类号： C40B40/02 , B01J2219/00718 , C07K16/00 , C07K16/18 , C07K16/22 , C07K16/241 , C07K16/28 , C07K16/2812 , C07K16/2863 , C07K16/2866 , C07K16/3007 , C07K16/34 , C07K16/40 , C07K16/4208 , C07K16/44 , C07K16/462 , C07K16/468 , C07K19/00 , C07K2317/21 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/622 , C07K2319/00 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037 , C12N15/62 , C12N15/73 , G01N33/53 , G01N33/6857
摘要： The invention provides methods and kits for producing specific binding pairs (sbp) members. Populations of polypeptide chain components of sbp members are combined to form libraries of sbps displayed by secreted replicable genetic display packages (rgdp). At least one of the polypeptide chains is expressed as a fusion with a component of an rgdp which thereby displays that polypeptide chain at the surface of rgdp. At least one population of polypeptide chains is expressed from nucleic acid which is capable of being packaged using a component of an rgdp, whereby the genetic material of rgdps produced encodes a polypeptide chain. The methods enable production of libraries of multimeric sbp members from a very large number of possible combinations. In one embodiment of the invention a method employs "chain shuffling" in the production of sbp members of desired specificity for a counterpart sbp member. Selection procedures are also described.
摘要翻译：本发明提供用于产生特异性结合对（sbp）成员的方法和试剂盒。将sbp成员的多肽链组分的群体组合以形成由分泌的可复制的遗传显示包（rgdp）显示的sbps的文库。至少一个多肽链表达为与rgdp的组分的融合物，由此在rgdp的表面显示该多肽链。至少一个多肽链群由能够使用rgdp的组分包装的核酸表达，由此产生的rgdps的遗传物质编码多肽链。该方法能够从非常大量的可能组合生产多聚体sbp成员的文库。在本发明的一个实施方案中，一种方法在生产对于对应物质成员的所需特异性的sbp成员中使用“链洗牌”。还描述了选择程序。

29. 发明申请

WO2010089115A8 MULTISPECIFIC PEPTIDES 审中-公开
标题翻译：多功能肽
公开(公告)号：WO2010089115A8
公开(公告)日：2011-12-22
申请号：PCT/EP2010000689
申请日：2010-02-04
申请人： MEDICAL RES COUNCIL , WINTER GREGORY PAUL , HEINIS CHRISTIAN , BERNARD ELISE , LOAKES DAVID , TITE JOHN PAUL , VAYSBURD MARINA , TEUFEL DANIEL PAUL , RIECHMANN LUTZ
发明人： WINTER GREGORY PAUL , HEINIS CHRISTIAN , BERNARD ELISE , LOAKES DAVID , TITE JOHN PAUL , VAYSBURD MARINA , TEUFEL DANIEL PAUL , RIECHMANN LUTZ
IPC分类号： A61K47/48 , G01N33/68
CPC分类号： C12N15/1037 , A61K47/55 , A61K47/64 , A61K47/643 , C07K14/001 , C12N15/1044 , C12N15/1058 , C40B40/08 , C40B40/10 , C40B50/06 , G01N33/531
摘要： The invention relates to a method for providing a multispecific peptide ligand comprising a polypeptide covalently linked to a molecular scaffold at three or more amino acid residues and capable of binding to two or more separate targets, comprising the steps of: (a) providing a first repertoire of polypeptides, each polypeptide comprising two or more reactive groups capable of covalent linkage to a molecular scaffold, and at least one loop which comprises a sequence of two or more amino acids subtended between two of said reactive groups; (b) providing a second repertoire of polypeptides as described in (a); (c) joining at least one loop of one or more members of the first repertoire to at least one loop of one or more members of the second repertoire to form at least one polypeptide comprising two loops, and (d) conjugating the composite polypeptide(s) to a molecular scaffold at at least three amino acid positions.
摘要翻译：本发明涉及一种提供多特异性肽配体的方法，所述多特异性肽配体包含在三个或更多个氨基酸残基处共价连接到分子支架并能够结合两个或更多个单独靶标的多肽，包括以下步骤：（a）提供第一多肽的所有组成部分，每个多肽包含两个或更多个能够与分子支架共价连接的反应性基团，以及至少一个环，其包含两个或更多个氨基酸的序列，对应于两个所述反应性基团; （b）提供如（a）所述的第二组多肽; （c）将第一组合物中的一个或多个成员的至少一个环连接到第二组合物的一个或多个成员的至少一个环，以形成至少一个包含两个环的多肽，和（d）将复合多肽（ s）至少在三个氨基酸位置分子支架。

30. 发明申请

WO2010089115A1 MULTISPECIFIC PEPTIDES 审中-公开
标题翻译：多功能肽
公开(公告)号：WO2010089115A1
公开(公告)日：2010-08-12
申请号：PCT/EP2010/000689
申请日：2010-02-04
申请人： MEDICAL RESEARCH COUNCIL , WINTER, Gregory Paul , HEINIS, Christian , BERNARD, Elise , LOAKES, David , TITE, John Paul , VAYSBURD, Marina , TEUFEL, Daniel Paul
发明人： WINTER, Gregory Paul , HEINIS, Christian , BERNARD, Elise , LOAKES, David , TITE, John Paul , VAYSBURD, Marina , TEUFEL, Daniel Paul
IPC分类号： A61K47/48 , G01N33/68
CPC分类号： C12N15/1037 , A61K47/55 , A61K47/64 , A61K47/643 , C07K14/001 , C12N15/1044 , C12N15/1058 , C40B40/08 , C40B40/10 , C40B50/06 , G01N33/531
摘要： The invention relates to a method for providing a multispecific peptide ligand comprising a polypeptide covalently linked to a molecular scaffold at three or more amino acid residues and capable of binding to two or more separate targets, comprising the steps of: (a) providing a first repertoire of polypeptides, each polypeptide comprising two or more reactive groups capable of covalent linkage to a molecular scaffold, and at least one loop which comprises a sequence of two or more amino acids subtended between two of said reactive groups; (b) providing a second repertoire of polypeptides as described in (a); (c) joining at least one loop of one or more members of the first repertoire to at least one loop of one or more members of the second repertoire to form at least one polypeptide comprising two loops, and (d) conjugating the composite polypeptide(s) to a molecular scaffold at at least three amino acid positions.
摘要翻译：本发明涉及一种提供多特异性肽配体的方法，所述多特异性肽配体包含在三个或更多个氨基酸残基处共价连接到分子支架并能够结合两个或更多个单独靶标的多肽，包括以下步骤：（a）提供第一多肽的所有组成部分，每个多肽包含两个或更多个能够与分子支架共价连接的反应性基团，以及至少一个环，其包含两个或更多个氨基酸的序列，对应于两个所述反应性基团; （b）提供如（a）所述的第二组多肽; （c）将第一组合物中的一个或多个成员的至少一个环连接到第二组合物的一个或多个成员的至少一个环，以形成至少一个包含两个环的多肽，和（d）将复合多肽（ s）至少在三个氨基酸位置分子支架。

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