Antibody constructs for CDH19 and CD3

Patent metadata

Field	Value
Publication number	US-9765157-B2
Application number	US-201514815861-A
Country	US
Kind code	B2
Filing date	Jul 31, 2015
Priority date	Jul 31, 2014
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

Abstract

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

First claim

The invention claimed is:

1. A bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on 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)(i) CDR-H1 as depicted in SEQ ID NO: 14, CDR-H2 as depicted in SEQ ID NO: 15, CDR-H3 as depicted in SEQ ID NO: 16, CDR-L1 as depicted in SEQ ID NO: 17, CDR-L2 as depicted in SEQ ID NO: 18 and CDR-L3 as depicted in SEQ ID NO: 19;
(a)(ii) CDR-H1 as depicted in SEQ ID NO: 27, CDR-H2 as depicted in SEQ ID NO: 28, CDR-H3 as depicted in SEQ ID NO: 29, CDR-L1 as depicted in SEQ ID NO: 30, CDR-L2 as depicted in SEQ ID NO: 31 and CDR-L3 as depicted in SEQ ID NO: 32;
(a)(iii) CDR-H1 as depicted in SEQ ID NO: 40, CDR-H2 as depicted in SEQ ID NO: 41, CDR-H3 as depicted in SEQ ID NO: 42, CDR-L1 as depicted in SEQ ID NO: 43, CDR-L2 as depicted in SEQ ID NO: 44 and CDR-L3 as depicted in SEQ ID NO: 45;
(a)(iv) CDR-H1 as depicted in SEQ ID NO: 53, CDR-H2 as depicted in SEQ ID NO: 54, CDR-H3 as depicted in SEQ ID NO: 55, CDR-L1 as depicted in SEQ ID NO: 56, CDR-L2 as depicted in SEQ ID NO: 57 and CDR-L3 as depicted in SEQ ID NO: 58;
(a)(v) CDR-H1 as depicted in SEQ ID NO: 66, CDR-H2 as depicted in SEQ ID NO: 67, CDR-H3 as depicted in SEQ ID NO: 68, CDR-L1 as depicted in SEQ ID NO: 69, CDR-L2 as depicted in SEQ ID NO: 70 and CDR-L3 as depicted in SEQ ID NO: 71;
(a)(vi) CDR-H1 as depicted in SEQ ID NO: 79, CDR-H2 as depicted in SEQ ID NO: 80, CDR-H3 as depicted in SEQ ID NO: 81, CDR-L1 as depicted in SEQ ID NO: 82, CDR-L2 as depicted in SEQ ID NO: 83 and CDR-L3 as depicted in SEQ ID NO: 84;
(a)(vii) CDR-H1 as depicted in SEQ ID NO: 92, CDR-H2 as depicted in SEQ ID NO: 93, CDR-H3 as depicted in SEQ ID NO: 94, CDR-L1 as depicted in SEQ ID NO: 95, CDR-L2 as depicted in SEQ ID NO: 96 and CDR-L3 as depicted in SEQ ID NO: 97;
(a)(viii) CDR-H1 as depicted in SEQ ID NO: 105, CDR-H2 as depicted in SEQ ID NO: 106, CDR-H3 as depicted in SEQ ID NO: 107, CDR-L1 as depicted in SEQ ID NO: 108, CDR-L2 as depicted in SEQ ID NO: 109 and CDR-L3 as depicted in SEQ ID NO: 110;
(a)(ix) CDR-H1 as depicted in SEQ ID NO: 118, CDR-H2 as depicted in SEQ ID NO: 119, CDR-H3 as depicted in SEQ ID NO: 120, CDR-L1 as depicted in SEQ ID NO: 121, CDR-L2 as depicted in SEQ ID NO: 122 and CDR-L3 as depicted in SEQ ID NO: 123;
(a)(x) CDR-H1 as depicted in SEQ ID NO: 131, CDR-H2 as depicted in SEQ ID NO: 132, CDR-H3 as depicted in SEQ ID NO: 133, CDR-L1 as depicted in SEQ ID NO: 134, CDR-L2 as depicted in SEQ ID NO: 135 and CDR-L3 as depicted in SEQ ID NO: 136;
(a)(xi) CDR-H1 as depicted in SEQ ID NO: 144, CDR-H2 as depicted in SEQ ID NO: 145, CDR-H3 as depicted in SEQ ID NO: 146, CDR-L1 as depicted in SEQ ID NO: 147, CDR-L2 as depicted in SEQ ID NO: 148 and CDR-L3 as depicted in SEQ ID NO: 149;
(a)(xii) CDR-H1 as depicted in SEQ ID NO: 157, CDR-H2 as depicted in SEQ ID NO: 158, CDR-H3 as depicted in SEQ ID NO: 159, CDR-L1 as depicted in SEQ ID NO: 160, CDR-L2 as depicted in SEQ ID NO: 161 and CDR-L3 as depicted in SEQ ID NO: 162,
(a)(xiii) CDR-H1 as depicted in SEQ ID NO: 170, CDR-H2 as depicted in SEQ ID NO: 171, CDR-H3 as depicted in SEQ ID NO: 172, CDR-L1 as depicted in SEQ ID NO: 173, CDR-L2 as depicted in SEQ ID NO: 174 and CDR-L3 as depicted in SEQ ID NO: 175;
(a)(xiv) CDR-H1 as depicted in SEQ ID NO: 183, CDR-H2 as depicted in SEQ ID NO: 184, CDR-H3 as depicted in SEQ ID NO: 185, CDR-L1 as depicted in SEQ ID NO: 186, CDR-L2 as depicted in SEQ ID NO: 187 and CDR-L3 as depicted in SEQ ID NO: 188;
(a)(xv) CDR-H1 as depicted in SEQ ID NO: 196, CDR-H2 as depicted in SEQ ID NO: 197, CDR-H3 as depicted in SEQ ID NO: 198, CDR-L1 as depicted in SEQ ID NO: 199, CDR-L2 as depicted in SEQ ID NO: 200 and CDR-L3 as depicted in SEQ ID NO: 201;
(a)(xvi) CDR-H1 as depicted in SEQ ID NO: 209, CDR-H2 as depicted in SEQ ID NO: 210, CDR-H3 as depicted in SEQ ID NO: 211, CDR-L1 as depicted in SEQ ID NO: 212, CDR-L2 as depicted in SEQ ID NO: 213 and CDR-L3 as depicted in SEQ ID NO: 214;
(a)(xvii) CDR-H1 as depicted in SEQ ID NO: 222, CDR-H2 as depicted in SEQ ID NO: 223, CDR-H3 as depicted in SEQ ID NO: 224, CDR-L1 as depicted in SEQ ID NO: 225, CDR-L2 as depicted in SEQ ID NO: 226 and CDR-L3 as depicted in SEQ ID NO: 227;
(a)(xviii) CDR-H1 as depicted in SEQ ID NO: 235, CDR-H2 as depicted in SEQ ID NO: 236, CDR-H3 as depicted in SEQ ID NO: 237, CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3 as depicted in SEQ ID NO: 240;
(a)(xix) CDR-H1as depicted in SEQ ID NO: 248, CDR-H2 as depicted in SEQ ID NO: 249, CDR-H3 as depicted in SEQ ID NO: 250, CDR-L1 as depicted in SEQ ID NO: 251, CDR-L2 as depicted in SEQ ID NO: 252 and CDR-L3 as depicted in SEQ ID NO: 253;
(a)(xx) CDR-H1 as depicted in SEQ ID NO: 261, CDR-H2 as depicted in SEQ ID NO: 262, CDR-H3 as depicted in SEQ ID NO: 263, CDR-L1 as depicted in SEQ ID NO: 264, CDR-L2 as depicted in SEQ ID NO: 265 and CDR-L3 as depicted in SEQ ID NO: 266;
(a)(xxi) CDR-H1 as depicted in SEQ ID NO: 274, CDR-H2 as depicted in SEQ ID NO: 275, CDR-H3 as depicted in SEQ ID NO: 276, CDR-L1 as depicted in SEQ ID NO: 277, CDR-L2 as depicted in SEQ ID NO: 278 and CDR-L3 as depicted in SEQ ID NO: 279;
(a)(xxii) CDR-H1 as depicted in SEQ ID NO: 287, CDR-H2 as depicted in SEQ ID NO: 288, CDR-H3 as depicted in SEQ ID NO: 289, CDR-L1 as depicted in SEQ ID NO: 290, CDR-L2 as depicted in SEQ ID NO: 291 and CDR-L3 as depicted in SEQ ID NO: 292;
(a)(xxiii) CDR-H1 as depicted in SEQ ID NO: 300, CDR-H2 as depicted in SEQ ID NO: 301, CDR-H3 as depicted in SEQ ID NO: 302, CDR-L1 as depicted in SEQ ID NO: 303, CDR-L2 as depicted in SEQ ID NO: 304 and CDR-L3 as depicted in SEQ ID NO: 305;
(a)(xxiv) CDR-H1 as depicted in SEQ ID NO: 313, CDR-H2 as depicted in SEQ ID NO: 314, CDR-H3 as depicted in SEQ ID NO: 315, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 318;
(a)(xxv) CDR-H1 as depicted in SEQ ID NO: 508, CDR-H2 as depicted in SEQ ID NO: 509, CDR-H3 as depicted in SEQ ID NO: 510, CDR-L1 as depicted in SEQ ID NO: 511, CDR-L2 as depicted in SEQ ID NO: 512 and CDR-L3 as depicted in SEQ ID NO: 513;
(a)(xxvi) CDR-H1 as depicted in SEQ ID NO: 521, CDR-H2 as depicted in SEQ ID NO: 522, CDR-H3 as depicted in SEQ ID NO: 523, CDR-L1 as depicted in SEQ ID NO: 524, CDR-L2 as depicted in SEQ ID NO: 525 and CDR-L3 as depicted in SEQ ID NO: 526;
(a)(xxvii) CDR-H1 as depicted in SEQ ID NO: 534, CDR-H2 as depicted in SEQ ID NO: 535, CDR-H3 as depicted in SEQ ID NO: 536, CDR-L1 as depicted in SEQ ID NO: 537, CDR-L2 as depicted in SEQ ID NO: 538 and CDR-L3 as depicted in SEQ ID NO: 539;
(a)(xxviii) CDR-H1 as depicted in SEQ ID NO: 547, CDR-H2 as depicted in SEQ ID NO: 548, CDR-H3 as depicted in SEQ ID NO: 549, CDR-L1 as depicted in SEQ ID NO: 550, CDR-L2 as depicted in SEQ ID NO: 551 and CDR-L3 as depicted in SEQ ID NO: 552;
(a)(xxix) CDR-H1 as depicted in SEQ ID NO: 560, CDR-H2 as depicted in SEQ ID NO: 561, CDR-H3 as depicted in SEQ ID NO: 562, CDR-L1 as depicted in SEQ ID NO: 563, CDR-L2 as depicted in SEQ ID NO: 564 and CDR-L3 as depicted in SEQ ID NO: 565;
(a)(xxx) CDR-H1 as depicted in SEQ ID NO: 573, CDR-H2 as depicted in SEQ ID NO: 574, CDR-H3 as depicted in SEQ ID NO: 575, CDR-L1 as depicted in SEQ ID NO: 576, CDR-L2 as depicted in SEQ ID NO: 577 and CDR-L3 as depicted in SEQ ID NO: 578; and
(a)(xxxi) CDR-H1 as depicted in SEQ ID NO: 586 CDR-H2 as depicted in SEQ ID NO: 587, CDR-H3 as depicted in SEQ ID NO: 588, CDR-L1 as depicted in SEQ ID NO: 589, CDR-L2 as depicted in SEQ ID NO: 590 and CDR-L3 as depicted in SEQ ID NO: 591; and
(b)(i) CDR-H1 as depicted in SEQ ID NO: 1, CDR-H2 as depicted in SEQ ID NO: 2, CDR-H3 as

Assignees

• Amgen Inc
• Amgen Res Munich Gmbh

Inventors

• Xiao Shouhua
• Pan Zheng
• Wickramasinghe Dineli
• Kufer Peter
• Hoffmann Patrick
• Raum Tobias
• LUTTERBÜSE Ralf
• Nahrwold Elisabeth
• Blumel Claudia

Classifications

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• A61P35/04

  specific for metastasis · CPC title