公开(公告)号：US20120129710A1

公开(公告)日：2012-05-24

申请号：US13165300

申请日：2011-06-21

申请人： John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kasper Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

发明人： John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kasper Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

IPC分类号： C40B30/04 ,  C12N7/01 ,  G01N33/53 ,  C12N15/63

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： 特异性结合对（sbp）的成员通过在重组宿主细胞中表达编码这种sbp成员的遗传多样性群体的DNA来鉴定，其中sbp成员以分泌重组遗传显示包（rgdp）的表面以功能形式显示 ），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可以通过与补充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，从而获得在sbp成员中比通过常规方法容易地获得的更大的遗传多样性。

公开(公告)号：US06916605B1

公开(公告)日：2005-07-12

申请号：US09196522

申请日：1998-11-20

申请人： John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kaspar Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

发明人： John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kaspar Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

IPC分类号： C07K16/00 ,  C07K16/18 ,  C07K16/34 ,  C07K16/40 ,  C07K16/44 ,  C07K16/46 ,  C07K19/00 ,  C12N15/10 ,  C12N15/62 ,  C12N15/73 ,  C40B40/02 ,  G01N33/53 ,  G01N33/68 ,  C12Q1/70 ,  C07H21/02 ,  C12N15/00

CPC分类号： C40B40/02 ,  B01J2219/00718 ,  C07K16/00 ,  C07K16/18 ,  C07K16/34 ,  C07K16/40 ,  C07K16/44 ,  C07K16/462 ,  C07K16/468 ,  C07K19/00 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/41 ,  C07K2319/735 ,  C12N15/1037 ,  C12N15/62 ,  C12N15/73 ,  G01N33/53 ,  G01N33/6857

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： 特异性结合对（sbp）的成员通过在重组宿主细胞中表达编码这种sbp成员的遗传多样性群体的DNA来鉴定，其中sbp成员以分泌重组遗传显示包（rgdp）的表面以功能形式显示 ），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可以通过与补充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，从而获得在sbp成员中比通过常规方法容易地获得的更大的遗传多样性。

公开(公告)号：US5885793A

公开(公告)日：1999-03-23

申请号：US244597

申请日：1994-10-26

申请人： Andrew David Griffiths ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  James David Marks ,  John McCafferty ,  Gregory Paul Winter ,  Geoffrey Walter Grigg

发明人： Andrew David Griffiths ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  James David Marks ,  John McCafferty ,  Gregory Paul Winter ,  Geoffrey Walter Grigg

IPC分类号： G01N33/531 ,  C07K14/00 ,  C07K16/00 ,  C07K16/18 ,  C07K16/22 ,  C07K16/24 ,  C07K16/26 ,  C07K16/28 ,  C07K16/30 ,  C07K16/34 ,  C07K16/40 ,  C07K16/42 ,  C07K16/46 ,  C07K19/00 ,  C12N7/01 ,  C12N15/09 ,  C12N15/10 ,  C12N15/13 ,  C12N15/62 ,  C12P21/08 ,  C12R1/19 ,  C40B40/02 ,  G01N33/564 ,  G01N33/577 ,  G01N33/68 ,  C07H21/04 ,  C12P21/06

CPC分类号： C40B40/02 ,  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 ,  C12N15/1037 ,  C12N15/62 ,  B01J2219/00718 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/41 ,  C07K2319/735 ,  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： PCT No.PCT / GB92 / 02240 Sec。 371日期：1994年10月26日 102（e）日期1994年10月26日PCT提交1992年12月2日PCT公布。 出版物WO93 / 11236 日期1993年6月10日公开了用于产生抗自身抗体和抗体片段的方法，所述抗自身抗体和抗体片段是结合该物种的自身抗原的特定哺乳动物种类的抗体或片段。 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。

公开(公告)号：US20100317540A1

公开(公告)日：2010-12-16

申请号：US12772829

申请日：2010-05-03

申请人： JOHN MCCAFFERTY ,  ANTHONY RICHARD POPE ,  KEVIN STUART JOHNSON ,  HENDRICUS RENERUS JACOBUS MATTHEUS HOOGENBOOM ,  ANDREW DAVID GRIFFITHS ,  RONALD HENRY JACKSON ,  KASPER PHILIPP HOLLIGER ,  JAMES DAVID MARKS ,  TIMOTHY PIERS CLACKSON ,  DAVID JOHN CHISWELL ,  GREGORY PAUL WINTER ,  TIMOTHY PETER BONNERT

发明人： JOHN MCCAFFERTY ,  ANTHONY RICHARD POPE ,  KEVIN STUART JOHNSON ,  HENDRICUS RENERUS JACOBUS MATTHEUS HOOGENBOOM ,  ANDREW DAVID GRIFFITHS ,  RONALD HENRY JACKSON ,  KASPER PHILIPP HOLLIGER ,  JAMES DAVID MARKS ,  TIMOTHY PIERS CLACKSON ,  DAVID JOHN CHISWELL ,  GREGORY PAUL WINTER ,  TIMOTHY PETER BONNERT

IPC分类号： C40B30/04 ,  C12N15/63 ,  C12N7/01 ,  G01N33/50

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.

公开(公告)号：US07723270B1

公开(公告)日：2010-05-25

申请号：US09417478

申请日：1999-10-13

申请人： John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Henricus Renerus Jacobus Mattheus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kasper Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

发明人： John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Henricus Renerus Jacobus Mattheus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kasper Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

IPC分类号： C40B40/02 ,  C12P21/08 ,  A23J1/00 ,  C07H21/02 ,  C07H21/00 ,  C12Q1/68

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： 特异性结合对（sbp）的成员通过在重组宿主细胞中表达编码这种sbp成员的遗传多样性群体的DNA来鉴定，其中sbp成员以分泌重组遗传显示包（rgdp）的表面以功能形式显示 ），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可以通过与补充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，从而获得在sbp成员中比通过常规方法容易地获得的更大的遗传多样性。

公开(公告)号：US20090325815A1

公开(公告)日：2009-12-31

申请号：US12488343

申请日：2009-06-19

申请人： Andrew David Griffiths ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  James David Marks ,  John McCafferty ,  Gregory Paul Winter ,  Geoffrey Walter Grigg

发明人： Andrew David Griffiths ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  James David Marks ,  John McCafferty ,  Gregory Paul Winter ,  Geoffrey Walter Grigg

IPC分类号： C40B30/04

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 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 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 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特定哺乳动物种类的抗体或片段。 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在其作为抗体或抗体片段的特异性结合对的表面成员显示，并且每个含有rgdp的核酸序列衍生自物种 的哺乳动物。 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。 所用的核酸文库可能来源于未免疫哺乳动物的重排的V基因序列。 描述和显示合成或人造文库是有用的。

公开(公告)号：US20090155810A1

公开(公告)日：2009-06-18

申请号：US11555464

申请日：2006-11-01

申请人： John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Hendricus Renerus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kasper Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

发明人： John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Hendricus Renerus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kasper Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

IPC分类号： G01N33/53 ,  C12N15/63

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： 特异性结合对（sbp）的成员通过在重组宿主细胞中表达编码这种sbp成员的遗传多样性群体的DNA来鉴定，其中sbp成员以分泌重组遗传显示包（rgdp）的表面以功能形式显示 ），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可以通过与补充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，从而获得在sbp成员中比通过常规方法容易地获得的更大的遗传多样性。

公开(公告)号：US06582915B1

公开(公告)日：2003-06-24

申请号：US09723756

申请日：2000-11-28

申请人： Andrew David Griffiths ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  James David Marks ,  John McCafferty ,  Gregory Paul Winter ,  Geoffrey Walter Grigg

发明人： Andrew David Griffiths ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  James David Marks ,  John McCafferty ,  Gregory Paul Winter ,  Geoffrey Walter Grigg

IPC分类号： C12Q168

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特定哺乳动物种类的抗体或片段。 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。

公开(公告)号：US06521404B1

公开(公告)日：2003-02-18

申请号：US09197224

申请日：1998-11-20

申请人： Andrew David Griffiths ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  James David Marks ,  John McCafferty ,  Gregory Paul Winter ,  Geoffrey Walter Grigg

发明人： Andrew David Griffiths ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  James David Marks ,  John McCafferty ,  Gregory Paul Winter ,  Geoffrey Walter Grigg

IPC分类号： C12Q168

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特定哺乳动物种类的抗体或片段。 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在其表面显示特异性结合对的成员，其是抗体或抗体片段，并且每个含rgdp的核酸序列衍生自物种 的哺乳动物。 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。

公开(公告)号：US06172197B2

公开(公告)日：2001-01-09

申请号：US08484893

申请日：1995-06-07

申请人： John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Henricus Renerus Jacobus Mattheus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kaspar Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

发明人： John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Henricus Renerus Jacobus Mattheus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kaspar Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

IPC分类号： C07K1600

CPC分类号： C07K16/468 ,  C07K16/18 ,  C07K16/462 ,  C07K2317/24 ,  C07K2319/02 ,  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： 特异性结合对（sbp）的成员通过在重组宿主细胞中表达编码这种sbp成员的遗传多样性群体的DNA来鉴定，其中sbp成员以分泌重组遗传显示包（rgdp）的表面以功能形式显示 ），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。 可以通过与互补sbp成员的亲和力来选择显示的sbps，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，用于与融合配偶体多肽结合。 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。