公开(公告)号：WO2006037960A3

公开(公告)日：2006-08-03

申请号：PCT/GB2005003752

申请日：2005-09-29

Applicant: AVIDEX LTD ,  JAKOBSEN BENT KARSTEN ,  ANDERSEN TORBEN BENT

Inventor： JAKOBSEN BENT KARSTEN ,  ANDERSEN TORBEN BENT

IPC: C07K14/725 ,  A61K35/14 ,  A61P35/00 ,  A61P37/02 ,  C12N5/08 ,  C12N5/10 ,  C12N15/12 ,  G01N33/566

CPC classification number: C07K14/7051 ,  A61K47/6425 ,  C07K2319/00

Abstract: The present invention provides a dimeric TCR (dTCR) or single-chain TCR (scTCR) associated with selected therapeutic agents, wherein said TCR comprises a first segment constituted by an amino acid sequence corresponding to a TCR a chain variable domain sequence fused to the N terminus of an amino acid sequence corresponding to a TCR a chain constant domain extracellular sequence, a second segment constituted by an amino acid sequence corresponding to a TCR ß chain variable domain fused to the N terminus of an amino acid sequence corresponding to TCR ß chain constant domain extracellular sequence, a disulfide bond between the first and second chains, said disulfide bond being one which has no equivalent in native aß T cell receptors, and in the case of said scTCRs further comprising a linker sequence linking the C terminus of the first segment to the N terminus of the second segment, or vice versa, the length of the linker sequence and the position of the disulfide bond being such that the variable domain sequences of the first and second segments are mutually orientated substantially as in native aß T cell receptors.

Abstract translation: 本发明提供与所选择的治疗剂相关的二聚TCR（dTCR）或单链TCR（scTCR），其中所述TCR包含由对应于TCR的氨基酸序列构成的第一片段，与N融合的链可变结构域序列 对应于TCR链段恒定域细胞外序列的氨基酸序列的末端，由与对应于TCRß链常数的氨基酸序列的N末端融合的TCRß链可变结构域相对应的氨基酸序列构成的第二区段 结构域细胞外序列，第一和第二链之间的二硫键，所述二硫键是在天然αT细胞受体中不具有等同物的二硫键，并且在所述scTCR的情况下还包含连接第一链节的C末端的连接体序列 到第二段的N末端，反之亦然，接头序列的长度和二硫键的位置是这样的 在第一和第二片段的可变结构域序列基本上如在天然αT细胞受体中相互取向。

公开(公告)号：WO2006037960A2

公开(公告)日：2006-04-13

申请号：PCT/GB2005/003752

申请日：2005-09-29

Applicant: AVIDEX LTD. ,  JAKOBSEN, Bent, Karsten ,  ANDERSEN, Torben, Bent

Inventor： JAKOBSEN, Bent, Karsten ,  ANDERSEN, Torben, Bent

IPC: C07K14/705 ,  A61K47/48

CPC classification number: C07K14/7051 ,  A61K47/6425 ,  C07K2319/00

Abstract: The present invention provides a dimeric TCR (dTCR) or single-chain TCR (scTCR) associated with selected therapeutic agents, wherein said TCR comprises a first segment constituted by an amino acid sequence corresponding to a TCR α chain variable domain sequence fused to the N terminus of an amino acid sequence corresponding to a TCR α chain constant domain extracellular sequence, a second segment constituted by an amino acid sequence corresponding to a TCR ß chain variable domain fused to the N terminus of an amino acid sequence corresponding to TCR ß chain constant domain extracellular sequence, a disulfide bond between the first and second chains, said disulfide bond being one which has no equivalent in native αβ T cell receptors, and in the case of said scTCRs further comprising a linker sequence linking the C terminus of the first segment to the N terminus of the second segment, or vice versa, the length of the linker sequence and the position of the disulfide bond being such that the variable domain sequences of the first and second segments are mutually orientated substantially as in native αβ T cell receptors.

Abstract translation: 本发明提供了与选择的治疗剂相关的二聚体TCR（dTCR）或单链TCR（scTCR），其中所述TCR包含由对应于TCRα的氨基酸序列构成的第一片段 与对应于TCRα链恒定结构域细胞外序列的氨基酸序列的N末端融合的第二链可变结构域序列，由对应于TCR＆amp; SzIig的氨基酸序列构成的第二片段; 链可变结构域融合于对应于TCR＆amp; szlig的氨基酸序列的N末端; 链恒定结构域胞外序列，第一链和第二链之间的二硫键，所述二硫键是在天然αβT细胞受体中不具有等同物的二硫键，并且在所述scTCR的情况下还包含连接序列的C端 第一区段与第二区段的N末端反之亦然，反之亦然，接头序列的长度和二硫键的位置使得第一和第二区段的可变结构域序列基本上如天然αβT 细胞受体。

公开(公告)号：WO2005116074A2

公开(公告)日：2005-12-08

申请号：PCT/GB2005/001948

申请日：2005-05-18

Applicant: AVIDEX LTD ,  BOULTER, Jonathan, Michael ,  ANDERSEN, Torben, Bent ,  JAKOBSEN, Bent, Karsten ,  MOLLOY, Peter, Eamon ,  LI, Yi

Inventor： BOULTER, Jonathan, Michael ,  ANDERSEN, Torben, Bent ,  JAKOBSEN, Bent, Karsten ,  MOLLOY, Peter, Eamon ,  LI, Yi

IPC: C07K14/725

CPC classification number: C40B40/02 ,  C07K14/7051 ,  C07K2319/00 ,  C12N15/1037 ,  C12N15/1041 ,  G01N2333/7051 ,  G01N2333/70539

Abstract: A diverse library of nucleoproteins each displaying on its surface a polypeptide comprising a native TCR α variable domain sequence or native TCR ß variable domain sequence, in which library the diversity resides in the variety of native TCR α variable domain or native TCR ß variable domain sequences displayed. Such a library is useful for identifying a ligand or ligands of a target peptide-MHC or CD1-antigen.

Abstract translation: 一种多样化的核蛋白文库，每个文库都在其表面上显示包含天然TCRα可变结构域序列或天然TCRβ可变结构域序列的多肽，其中文库多样性存在于多种天然TCRα可变结构域或天然TCRβ可变结构域序列 显示。 这种文库可用于鉴定靶肽-MHC或CD1抗原的配体或配体。

公开(公告)号：WO2004044004A3

公开(公告)日：2004-05-27

申请号：PCT/GB2003/004636

申请日：2003-10-30

Applicant: AVIDEX LIMITED ,  JAKOBSEN, Bent, Karsten ,  ANDERSEN, Torben, Bent ,  MOLLOY, Peter, Eamon ,  LI, Yi ,  BOULTER, Jonathan, Michael

Inventor： JAKOBSEN, Bent, Karsten ,  ANDERSEN, Torben, Bent ,  MOLLOY, Peter, Eamon ,  LI, Yi ,  BOULTER, Jonathan, Michael

IPC: C07K14/705

Abstract: A proteinaceous particle, for example a bacteriophage, ribosome or cell, displaying on its surface a T-cell receptor (TCR). The displayed TCR is preferably a heterodimer having a non-native disulfide bond between constant domain residues. Such display particles may be used for the creation of diverse TCR libraries for the identificaton of high affinity TCRs. Several high affinities are disclosed.

公开(公告)号：WO2005116074A3

公开(公告)日：2006-01-19

申请号：PCT/GB2005001948

申请日：2005-05-18

Applicant: AVIDEX LTD ,  BOULTER JONATHAN MICHAEL ,  ANDERSEN TORBEN BENT ,  JAKOBSEN BENT KARSTEN ,  MOLLOY PETER EAMON ,  LI YI

Inventor： BOULTER JONATHAN MICHAEL ,  ANDERSEN TORBEN BENT ,  JAKOBSEN BENT KARSTEN ,  MOLLOY PETER EAMON ,  LI YI

IPC: C07K14/725 ,  C12N15/10 ,  C40B40/02 ,  G01N33/68

CPC classification number: C40B40/02 ,  C07K14/7051 ,  C07K2319/00 ,  C12N15/1037 ,  C12N15/1041 ,  G01N2333/7051 ,  G01N2333/70539

Abstract: A diverse library of nucleoproteins each displaying on its surface a polypeptide comprising a native TCR a variable domain sequence or native TCR ß variable domain sequence, in which library the diversity resides in the variety of native TCR a variable domain or native TCR ß variable domain sequences displayed. Such a library is useful for identifying a ligand or ligands of a target peptide-MHC or CD1-antigen.

Abstract translation: 一种多样化的核蛋白文库，每个文库都在其表面上显示包含天然TCR的可变结构域序列或天然TCRβ可变结构域序列的多肽，其中文库多样性存在于多种天然TCR中，可变域或天然TCRβ可变结构域序列 显示。 这种文库可用于鉴定靶肽-MHC或CD1抗原的配体或配体。

公开(公告)号：WO2004044004A2

公开(公告)日：2004-05-27

申请号：PCT/GB0304636

申请日：2003-10-30

Applicant: AVIDEX LTD ,  JAKOBSEN BENT KARSTEN ,  ANDERSEN TORBEN BENT ,  MOLLOY PETER EAMON ,  LI YI ,  BOULTER JONATHAN MICHAEL

Inventor： JAKOBSEN BENT KARSTEN ,  ANDERSEN TORBEN BENT ,  MOLLOY PETER EAMON ,  LI YI ,  BOULTER JONATHAN MICHAEL

IPC: A61K38/00 ,  C07K14/725 ,  C12N7/00 ,  C12N15/10 ,  C40B40/02 ,  C07K14/705

CPC classification number: C12N15/1037 ,  A61K38/00 ,  C07K14/7051 ,  C12N7/00 ,  C12N15/1041 ,  C12N15/1058 ,  C12N2795/18121 ,  C12N2795/18143 ,  C40B40/02 ,  C40B40/10

Abstract: A proteinaceous particle, for example a bacteriophage, ribosome or cell, displaying on its surface a T-cell receptor (TCR). The displayed TCR is preferably a heterodimer having a non-native disulfide bond between constant domain residues. Such display particles may be used for the creation of diverse TCR libraries for the identificaton of high affinity TCRs. Several high affinities are disclosed.

Abstract translation: 蛋白质颗粒，例如噬菌体，核糖体或细胞，其表面上展示T细胞受体（TCR）。 展示的TCR优选是在恒定结构域残基之间具有非天然二硫键的异二聚体。 这种显示颗粒可用于产生用于鉴定高亲和力TCR的不同TCR文库。 披露了几个很高的亲和力。