Antibody constructs for CDH19 and CD3

Patent metadata

Field	Value
Publication number	US-10059766-B2
Application number	US-201414761839-A
Country	US
Kind code	B2
Filing date	Jan 27, 2014
Priority date	Jan 25, 2013
Publication date	Aug 28, 2018
Grant date	Aug 28, 2018

Abstract

The invention provides a bispecific antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell. Moreover, the invention provides a nucleic acid encoding the antibody construct, a vector comprising the nucleic acid and a host cell transformed or transfected with the vector. Furthermore, the invention provides a process for the production of the bispecific antibody construct, a medical use of the antibody construct and a kit comprising the antibody construct. The bispecific antibody construct may be useful in the treatment of melanoma.

First claim

The invention claimed is:

1. An isolated multispecific antibody construct or an oligomer thereof comprising a first binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3on the surface of a T cell, wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:
(a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 94, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 95, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 96, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 262, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 263 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 264;
(b) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 100, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 101, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 102, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 268, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 269 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 270;
(c) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 118, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 119, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 120, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 286, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 287 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 288;
(d) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 154, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 155, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 156, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 322, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 323 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 324;
(e) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 100, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 101, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 912, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 268, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 269 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 270;
(f) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 100, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 101, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 913, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 268, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 269 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 270;
(g) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 94, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 95, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 910, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 262, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 263 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 264;
(h) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 94, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 95, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 911, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 262, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 263 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 264;
(i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 118, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 119, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 120, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 286, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 287 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 288;
(j) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 118, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 914, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 120, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 286, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 287 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 288;
(k) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 154, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 155, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 920, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 322, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 323 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 324;
(l) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 996, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 997, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 998, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 999, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1000 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1001;
(m) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1048, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1049, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1050, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1051, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1052 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1053;
(n) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1087, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1088, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1089, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1090, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1091 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1092;
(o) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1608, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1609, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1610, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1611, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1612 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1613;
(p) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1621, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1622, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1623, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1624, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1625 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1626;
(q) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1634, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1635, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1636, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1637, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1638 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1639;
(r) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1673, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1674, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1675, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1676, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1677 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1678;
(s) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1686, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1687, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1688, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1689, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1690 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 1691;
(t) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1699, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 1700, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 1701, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1702, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 1703 and CDR-L3 comprising the amino acid sequence of SEQ ID

Assignees

• Amgen Res Munich Gmbh
• Amgen Inc

Inventors

• Xiao Shouhua
• Pan Zheng
• Wickramasinghe Dineli
• Jeffries M Shawn
• King Chadwick Terence
• Chan Brian Mingtung
• Kufer Peter
• LUTTERBÜSE Ralf
• Raum Tobias
• Hoffmann Patrick
• Rau Doris
• Kischel Roman
• Lemon Bryan
• Wesche Holger

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/04

  specific for metastasis · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K2317/31

  multispecific · CPC title