公开(公告)号：US07195866B2

公开(公告)日：2007-03-27

申请号：US10326495

申请日：2002-12-19

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

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

IPC: C12N15/00 ,  C12P21/06 ,  C12P21/08 ,  C12Q1/70 ,  G01N33/53

CPC classification number: 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

Abstract: 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 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.

Abstract translation: 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：US07063943B1

公开(公告)日：2006-06-20

申请号：US09196673

申请日：1998-11-20

Applicant: 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

Inventor： 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: C12Q1/70 ,  C12Q1/68 ,  C12N15/00 ,  C07H21/04

CPC classification number: C40B40/02 ,  C12N15/1037

Abstract: 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：US06555313B1

公开(公告)日：2003-04-29

申请号：US09572392

申请日：2000-05-16

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

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

IPC: C12Q170

CPC classification number: 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

Abstract: Methods are disclosed for the production of human self-antibodies and antibody fragments, which bind human antigens. 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. Human antibodies or antibody fragments are selected by binding with human antigens. The displayed antibody fragments may be scFv, Fd, Fab or any other fragment which has the capability of binding to and is a human antigen. Nucleic acid libraries used may be derived from V-gene sequences of unimmunised humans. Part or all of the nucleic acid may be derived from oligonucleotide synthesis.

Abstract translation: 公开了用于生产结合人抗原的人自身抗体和抗体片段的方法。 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。 通过与人抗原结合来选择人抗体或抗体片段。 显示的抗体片段可以是scFv，Fd，Fab或具有结合并且是人抗原能力的任何其它片段。 所用的核酸文库可以衍生自未免疫的人的V-基因序列。 部分或全部核酸可以衍生自寡核苷酸合成。

公开(公告)号：US06544731B1

公开(公告)日：2003-04-08

申请号：US09197221

申请日：1998-11-20

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

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

IPC: C12N700

CPC classification number: 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

Abstract: 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.

Abstract translation: 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：US20120129710A1

公开(公告)日：2012-05-24

申请号：US13165300

申请日：2011-06-21

Applicant: 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

Inventor： 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: C40B30/04 ,  C12N7/01 ,  G01N33/53 ,  C12N15/63

CPC classification number: 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

Abstract: 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.

Abstract translation: 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：US20110216540A1

公开(公告)日：2011-09-08

申请号：US13039953

申请日：2011-03-03

Applicant: John McCafferty, JR.

Inventor： John McCafferty, JR.

IPC: F21V17/02 ,  F21V7/00

CPC classification number: F21V7/00 ,  F21V17/02

Abstract: A lamp light director reflector (LLDR) for being installed on a lamp having a light bulb including a housing having a convex exterior surface and a convex reflective interior surface; a hole on a top portion of the exterior surface configured to accommodate a harp nut base of the lamp therein, in a first position; and a slit on the top portion of the exterior surface configured to accommodate a harp of the lamp therein, in a second position wherein the housing is configured to be installed on the lamp such that the reflective interior surface faces the light bulb of the lamp. The first position is at a top of the lamp harp resting upon the harp, and the lamp harp passes through the slit in the second position resting atop the lamp bulb.

Abstract translation: 一种灯光指示反射器（LLDR），用于安装在具有灯泡的灯上，所述灯具包括具有凸形外表面和凸反射内表面的壳体; 在外表面的顶部上的孔，被构造成在其中容纳灯的竖琴螺母底座，处于第一位置; 以及在所述外表面的顶部上的狭缝，其被构造成在其中容纳所述灯的竖琴，其中所述壳体被配置为安装在所述灯上，使得所述反射内表面面向所述灯的灯泡。 第一个位置是放置在竖琴上的灯泡竖琴的顶部，而灯管竖立在灯泡顶部的第二位置上通过狭缝。

公开(公告)号：US20080050359A1

公开(公告)日：2008-02-28

申请号：US11625750

申请日：2007-01-22

Applicant: Andrew Griffiths ,  Hendricus Renerus Jacobus Hoogenboom ,  James Marks ,  John McCafferty ,  Gregory Winter ,  Geoffrey Grigg

Inventor： Andrew Griffiths ,  Hendricus Renerus Jacobus Hoogenboom ,  James Marks ,  John McCafferty ,  Gregory Winter ,  Geoffrey Grigg

IPC: A61K31/395 ,  A61P43/00 ,  C07K16/00 ,  C40B20/08

CPC classification number: 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

Abstract: 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.

Abstract translation: 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：US20070232790A1

公开(公告)日：2007-10-04

申请号：US11625769

申请日：2007-01-22

Applicant: ANDREW GRIFFITHS ,  Hendricus Renerus Hoogenboom ,  James Marks ,  John McCafferty ,  Gregory Winter ,  Geoffrey Grigg

Inventor： ANDREW GRIFFITHS ,  Hendricus Renerus Hoogenboom ,  James Marks ,  John McCafferty ,  Gregory Winter ,  Geoffrey Grigg

IPC: C07K16/18

CPC classification number: 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

Abstract: 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.

Abstract translation: 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：US06916605B1

公开(公告)日：2005-07-12

申请号：US09196522

申请日：1998-11-20

Applicant: 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

Inventor： 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: 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 classification number: 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

Abstract: 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.

Abstract translation: 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

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

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

IPC: 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 classification number: 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

Abstract: 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.

Abstract translation: 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。