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11.发明公开Production of anti-self antibodies from antibody segment repertoires and displayed on phage 失效从抗体片段库制备抗自身抗体并显示在噬菌体上
公开(公告)号：EP2224006A1
公开(公告)日：2010-09-01
申请号：EP10002988.3
申请日：1992-12-02
发明人： Griffiths, Andrew David , Hoogenboom, Hendricus Renerus Jacobus M. , Marks, James David , McCafferty, John , Winter, Gregory Paul , Grigg, Geoffrey Walter
CPC分类号： C07K16/005 , B01J2219/00718 , C07K16/18 , C07K16/241 , C07K16/26 , C07K16/28 , C07K16/2812 , C07K16/2863 , C07K16/2866 , C07K16/3007 , C07K16/3092 , C07K16/34 , C07K16/4241 , C07K2317/24 , C07K2317/55 , C07K2317/622 , C07K2319/41 , C07K2319/735
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，抗体或抗体片段是与该种类的自身抗原结合的特定哺乳动物物种的抗体或片段。 方法包括提供可复制遗传展示包装（rgdps）的文库，例如丝状噬菌体，每个rgdp在其表面展示为抗体或抗体片段的特异性结合对的成员，并且每个rgdp含有源自 哺乳动物的物种。 每个rgdp中的核酸序列编码多肽链，该多肽链是在该rgdp表面处显示的sbp成员的组成部分。 通过与来自所述哺乳动物物种的自身抗原结合来选择抗自身抗体片段。 展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他片段。 使用的核酸文库可以来源于未经免疫的哺乳动物的重排V基因序列。 描述并显示合成或人造文库是有用的。
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公开(公告)号：EP2055777A3
公开(公告)日：2009-05-13
申请号：EP09001901.9
申请日：1991-07-10
发明人： McCafferty, John , Pope, Anthony Richard , Johnson, Kevin Stuart , Hoogenboom, Hendricus Renerus Jacobus Mattheus , Griffiths, Andrew David , Jackson, Ronald Henry , Holliger, Kaspar Philipp , Marks, James David , Clackson, Timothy Piers , Chiswell, David John , Winter, Gregory Paul , Bonnert, Timothy Peter
CPC分类号： C07K16/005 , B01J2219/00718 , C07K16/00 , C07K16/18 , C07K16/26 , C07K16/34 , C07K16/40 , C07K16/44 , C07K16/462 , C07K16/468 , C07K19/00 , C07K2317/21 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/62 , C07K2317/622 , C07K2317/92 , C07K2319/00 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037 , C12N15/62 , C12N15/73 , C40B40/02 , G01N33/53 , G01N33/6857 , Y10S530/867
摘要： A member of a specific binding pair (sbp) is identified by expressing DNA encoding a genetically diverse population of such sbp members in recombinant host cells in which the sbp members are displayed in functional form at the surface of a secreted recombinant genetic display package (rgdp) containing DNA encoding the sbp member or a polypeptide component thereof, by virtue of the sbp member or a polypeptide component thereof being expressed as a fusion with a capsid component of the rgdp. The displayed sbps may be selected by affinity with a complementary sbp member, and the DNA recovered from selected rgdps for expression of the selected sbp members. Antibody sbp members may be thus obtained, with the different chains thereof expressed, one fused to the capsid component and the other in free form for association with the fusion partner polypeptide. A phagemid may be used as an expression vector, with said capsid fusion helping to package the phagemid DNA. Using this method libraries of DNA encoding respective chains of such multimeric sbp members may be combined, thereby obtaining a much greater genetic diversity in the sbp members than could easily be obtained by conventional methods.
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公开(公告)号：EP2055777A2
公开(公告)日：2009-05-06
申请号：EP09001901.9
申请日：1991-07-10
发明人： McCafferty, John , Pope, Anthony Richard , Johnson, Kevin Stuart , Hoogenboom, Hendricus Renerus Jacobus Mattheus , Griffiths, Andrew David , Jackson, Ronald Henry , Holliger, Kaspar Philipp , Marks, James David , Clackson, Timothy Piers , Chiswell, David John , Winter, Gregory Paul , Bonnert, Timothy Peter
CPC分类号： C07K16/005 , B01J2219/00718 , C07K16/00 , C07K16/18 , C07K16/26 , C07K16/34 , C07K16/40 , C07K16/44 , C07K16/462 , C07K16/468 , C07K19/00 , C07K2317/21 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/62 , C07K2317/622 , C07K2317/92 , C07K2319/00 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037 , C12N15/62 , C12N15/73 , C40B40/02 , G01N33/53 , G01N33/6857 , Y10S530/867
摘要： A member of a specific binding pair (sbp) is identified by expressing DNA encoding a genetically diverse population of such sbp members in recombinant host cells in which the sbp members are displayed in functional form at the surface of a secreted recombinant genetic display package (rgdp) containing DNA encoding the sbp member or a polypeptide component thereof, by virtue of the sbp member or a polypeptide component thereof being expressed as a fusion with a capsid component of the rgdp. The displayed sbps may be selected by affinity with a complementary sbp member, and the DNA recovered from selected rgdps for expression of the selected sbp members. Antibody sbp members may be thus obtained, with the different chains thereof expressed, one fused to the capsid component and the other in free form for association with the fusion partner polypeptide. A phagemid may be used as an expression vector, with said capsid fusion helping to package the phagemid DNA. Using this method libraries of DNA encoding respective chains of such multimeric sbp members may be combined, thereby obtaining a much greater genetic diversity in the sbp members than could easily be obtained by conventional methods.
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公开(公告)号：EP1754787B1
公开(公告)日：2012-01-25
申请号：EP06018386.0
申请日：1991-07-10
发明人： McCafferty, John , Pope, Anthony Richard , Johnson, Kevin Stuart , Hoogenboom, Hendricus Renerus Jacobus Mattheus , Griffiths, Andrew David , Jackson, Ronald Henry , Holliger, Kaspar Philipp , Marks, James David , Clackson, Timothy Piers , Chiswell, David John , Winter, Gregory Paul , Bonnert, Timothy Peter
CPC分类号： C07K16/005 , B01J2219/00718 , C07K16/00 , C07K16/18 , C07K16/26 , C07K16/34 , C07K16/40 , C07K16/44 , C07K16/462 , C07K16/468 , C07K19/00 , C07K2317/21 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/62 , C07K2317/622 , C07K2317/92 , C07K2319/00 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037 , C12N15/62 , C12N15/73 , C40B40/02 , G01N33/53 , G01N33/6857 , Y10S530/867
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公开(公告)号：EP0368684B2
公开(公告)日：2004-09-29
申请号：EP89311731.7
申请日：1989-11-13
CPC分类号： C07K16/461 , A61K38/00 , C07K2317/24 , C12Q1/6876
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公开(公告)号：EP1433846B1
公开(公告)日：2007-04-04
申请号：EP04005419.9
申请日：1991-07-10
发明人： McCafferty, John , Pope, Anthony Richard , Johnson, Kevin Stuart , Hoogenboom, Hendricus Renerus Jacobus Mattheus , Griffiths, Andrew David , Jackson, Ronald Henry , Holliger, Kaspar Philipp , Marks, James David , Clackson, Timothy Piers , Chiswell, David John , Winter, Gregory Paul , Bonnert, Timothy Peter
CPC分类号： C07K16/005 , B01J2219/00718 , C07K16/00 , C07K16/18 , C07K16/26 , C07K16/34 , C07K16/40 , C07K16/44 , C07K16/462 , C07K16/468 , C07K19/00 , C07K2317/21 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/62 , C07K2317/622 , C07K2317/92 , C07K2319/00 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037 , C12N15/62 , C12N15/73 , C40B40/02 , G01N33/53 , G01N33/6857 , Y10S530/867
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17.发明公开Phagemid-based method of producing filamentous bacteriophage particles displaying antibody molecules and the corresponding bacteriophage particles. 失效用于生产通过使用噬菌粒和由此产生的噬菌体颗粒的丝状噬菌体抗体呈递的方法。
公开(公告)号：EP1433846A3
公开(公告)日：2004-09-22
申请号：EP04005419.9
申请日：1991-07-10
发明人： McCafferty, John , Pope, Anthony Richard , Johnson, Kevin Stuart , Hoogenboom, Hendricus Renerus Jacobus Mattheus , Griffiths, Andrew David , Jackson, Ronald Henry , Holliger, Kaspar Philipp , Marks, James David , Clackson, Timothy Piers , Chiswell, David John , Winter, Gregory Paul , Bonnert, Timothy Peter
CPC分类号： C07K16/005 , B01J2219/00718 , C07K16/00 , C07K16/18 , C07K16/26 , C07K16/34 , C07K16/40 , C07K16/44 , C07K16/462 , C07K16/468 , C07K19/00 , C07K2317/21 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/62 , C07K2317/622 , C07K2317/92 , C07K2319/00 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037 , C12N15/62 , C12N15/73 , C40B40/02 , G01N33/53 , G01N33/6857 , Y10S530/867
摘要： A member of a specific binding pair (sbp) is identified by expressing DNA encoding a genetically diverse population of such sbp members in recombinant host cells in which the sbp members are displayed.in functional form at the surface of a secreted recombinant genetic display package (rgdp) containing DNA encoding the sbp member or a polypeptide component thereof, by virtue of the sbp member or a polypeptide component thereof being expressed as a fusion with a capsid component of the rgdp. The displayed sbps may be selected by affinity with a complementary sbp member, and the DNA recovered from selected rgdps for expression of the selected sbp members. Antibody sbp members may be thus obtained, with the different chains thereof expressed, one fused to the capsid component and the other in free form for association with the fusion partner polypeptide. A phagemid may be used as an expression vector, with said capsid fusion helping to package the phagemid DNA. Using this method libraries of DNA encoding respective chains of such multimeric sbp members may be combined, thereby obtaining a much greater genetic diversity in the sbp members than could easily be obtained by conventional methods.
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18.发明公开Phagemid-based method of producing filamentous bacteriophage particles displaying antibody molecules and the corresponding bacteriophage particles. 失效Bakteriophagenpartikeln，die dAbspräsentieren
公开(公告)号：EP1433846A2
公开(公告)日：2004-06-30
申请号：EP04005419.9
申请日：1991-07-10
发明人： McCafferty, John , Pope, Anthony Richard , Johnson, Kevin Stuart , Hoogenboom, Hendricus Renerus Jacobus Mattheus , Griffiths, Andrew David , Jackson, Ronald Henry , Holliger, Kaspar Philipp , Marks, James David , Clackson, Timothy Piers , Chiswell, David John , Winter, Gregory Paul , Bonnert, Timothy Peter
CPC分类号： C07K16/005 , B01J2219/00718 , C07K16/00 , C07K16/18 , C07K16/26 , C07K16/34 , C07K16/40 , C07K16/44 , C07K16/462 , C07K16/468 , C07K19/00 , C07K2317/21 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/62 , C07K2317/622 , C07K2317/92 , C07K2319/00 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037 , C12N15/62 , C12N15/73 , C40B40/02 , G01N33/53 , G01N33/6857 , Y10S530/867
摘要： A member of a specific binding pair (sbp) is identified by expressing DNA encoding a genetically diverse population of such sbp members in recombinant host cells in which the sbp members are displayed.in functional form at the surface of a secreted recombinant genetic display package (rgdp) containing DNA encoding the sbp member or a polypeptide component thereof, by virtue of the sbp member or a polypeptide component thereof being expressed as a fusion with a capsid component of the rgdp. The displayed sbps may be selected by affinity with a complementary sbp member, and the DNA recovered from selected rgdps for expression of the selected sbp members. Antibody sbp members may be thus obtained, with the different chains thereof expressed, one fused to the capsid component and the other in free form for association with the fusion partner polypeptide. A phagemid may be used as an expression vector, with said capsid fusion helping to package the phagemid DNA. Using this method libraries of DNA encoding respective chains of such multimeric sbp members may be combined, thereby obtaining a much greater genetic diversity in the sbp members than could easily be obtained by conventional methods.
摘要翻译： 通过表达在编码sbp成员的重组宿主细胞中编码这样的sbp成员的遗传多样性群体的DNA来鉴定特异性结合对（sbp）的成员。以功能形式在分泌的重组遗传显示包的表面 rgdp），其含有编码sbp成员或其多肽组分的DNA，其中sbp成员或其多肽组分被表达为与rgdp的衣壳组分的融合物。 显示的sbps可以通过与互补sbp成员的亲和力来选择，并且从所选的rgdps中恢复的DNA用于表达所选择的sbp成员。 因此可以获得抗体sbp成员，其中不同的链表达，一个与衣壳组分融合，另一个与游离形式融合，用于与融合伴侣多肽结合。 噬菌粒可以用作表达载体，所述衣壳融合有助于包装噬菌粒DNA。 使用这种方法，可以组合编码这种多聚体sbp成员的各个链的DNA文库，从而在sbp成员中获得比通过常规方法容易获得的更大的遗传多样性。
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公开(公告)号：EP0239400B1
公开(公告)日：1994-08-03
申请号：EP87302620.7
申请日：1987-03-26
发明人： Winter, Gregory Paul
CPC分类号： C07K16/464 , C07K2317/24 , C07K2319/00
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20.发明公开Recombinant antibodies and methods for their production 失效RekombinanteAntikörperund Verfahren zu deren Herstellung。
公开(公告)号：EP0239400A2
公开(公告)日：1987-09-30
申请号：EP87302620.7
申请日：1987-03-26
发明人： Winter, Gregory Paul
CPC分类号： C07K16/464 , C07K2317/24 , C07K2319/00
摘要： An altered antibody is produced by replacing the complementarity determining regions (CDRs) of a variable region of an immunoglobulin (Ig) with the CDRs from an Ig of different specificity, using recombinant DNA techniques. The gene coding sequences for producing the altered antibody may be produced by site-directed mutagenesis using long oligonucleotides.
摘要翻译： 使用重组DNA技术，通过用不同特异性的Ig替代免疫球蛋白（Ig）的可变区的互补决定区（CDR）与CDR不同而产生改变的抗体。 用于产生改变的抗体的基因编码序列可以通过使用长寡核苷酸的定点诱变产生。
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