US 2018/0002450 A1 · Antibody Constructs For CDH19 and CD3

Abstract

The present invention provides to 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. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Claims6

Dependent claims

1-14. (canceled)

A method for treating or ameliorating a melanoma disease, comprising the step of administering to a subject in need thereof 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 set forth in SEQ ID NO:
14, CDR-H2 as set forth in SEQ ID NO:
15, CDR-H3 as set forth in SEQ ID NO:
16, CDR-L1 as set forth in SEQ ID NO:
17, CDR-L2 as set forth in SEQ ID NO:
18 and CDR-L3 as set forth in SEQ ID NO:
19;
(a)(ii) CDR-H1 as set forth in SEQ ID NO:
27, CDR-H2 as set forth in SEQ ID NO:
28, CDR-H3 as set forth in SEQ ID NO:
29, CDR-L1 as set forth in SEQ ID NO:
30, CDR-L2 as set forth in SEQ ID NO:
31 and CDR-L3 as set forth in SEQ ID NO:
32;
(a)(iii) CDR-H1 as set forth in SEQ ID NO:
40, CDR-H2 as set forth in SEQ ID NO:
41, CDR-H3 as set forth in SEQ ID NO:
42, CDR-L1 as set forth in SEQ ID NO:
43, CDR-L2 as set forth in SEQ ID NO:
44 and CDR-L3 as set forth in SEQ ID NO:
45;
(a)(iv) CDR-H1 as set forth in SEQ ID NO:
53, CDR-H2 as set forth in SEQ ID NO:
54, CDR-H3 as set forth in SEQ ID NO:
55, CDR-L1 as set forth in SEQ ID NO:
56, CDR-L2 as set forth in SEQ ID NO:
57 and CDR-L3 as set forth in SEQ ID NO:
58;
(a)(v) CDR-H1 as set forth in SEQ ID NO:
66, CDR-H2 as set forth in SEQ ID NO:
67, CDR-H3 as set forth in SEQ ID NO:
68, CDR-L1 as set forth in SEQ ID NO:
69, CDR-L2 as set forth in SEQ ID NO:
70 and CDR-L3 as set forth in SEQ ID NO:
71;
(a)(vi) CDR-H1 as set forth in SEQ ID NO:
79, CDR-H2 as set forth in SEQ ID NO:
80, CDR-H3 as set forth in SEQ ID NO:
81, CDR-L1 as set forth in SEQ ID NO:
82, CDR-L2 as set forth in SEQ ID NO:
83 and CDR-L3 as set forth in SEQ ID NO:
84;
(a)(vii) CDR-H1 as set forth in SEQ ID NO:
92, CDR-H2 as set forth in SEQ ID NO:
93, CDR-H3 as set forth in SEQ ID NO:
94, CDR-L1 as set forth in SEQ ID NO:
95, CDR-L2 as set forth in SEQ ID NO:
96 and CDR-L3 as set forth in SEQ ID NO:
97;
(a)(viii) CDR-H1 as set forth in SEQ ID NO:
105, CDR-H2 as set forth in SEQ ID NO:
106, CDR-H3 as set forth in SEQ ID NO:
107, CDR-L1 as set forth in SEQ ID NO:
108, CDR-L2 as set forth in SEQ ID NO:
109 and CDR-L3 as set forth in SEQ ID NO:
110;
(a)(ix) CDR-H1 as set forth in SEQ ID NO:
118, CDR-H2 as set forth in SEQ ID NO:
119, CDR-H3 as set forth in SEQ ID NO:
120, CDR-L1 as set forth in SEQ ID NO:
121, CDR-L2 as set forth in SEQ ID NO:
122 and CDR-L3 as set forth in SEQ ID NO:
123;
(a)(x) CDR-H1 as set forth in SEQ ID NO:
131, CDR-H2 as set forth in SEQ ID NO:
132, CDR-H3 as set forth in SEQ ID NO:
133, CDR-L1 as set forth in SEQ ID NO:
134, CDR-L2 as set forth in SEQ ID NO:
135 and CDR-L3 as set forth in SEQ ID NO:
136;
(a)(xi) CDR-H1 as set forth in SEQ ID NO:
144, CDR-H2 as set forth in SEQ ID NO:
145, CDR-H3 as set forth in SEQ ID NO:
146, CDR-L1 as set forth in SEQ ID NO:
147, CDR-L2 as set forth in SEQ ID NO:
148 and CDR-L3 as set forth in SEQ ID NO:
149;
(a)(xii) CDR-H1 as set forth in SEQ ID NO:
157, CDR-H2 as set forth in SEQ ID NO:
158, CDR-H3 as set forth in SEQ ID NO:
159, CDR-L1 as set forth in SEQ ID NO:
160, CDR-L2 as set forth in SEQ ID NO:
161 and CDR-L3 as set forth in SEQ ID NO:
162,
(a)(xiii) CDR-H1 as set forth in SEQ ID NO:
170, CDR-H2 as set forth in SEQ ID NO:
171, CDR-H3 as set forth in SEQ ID NO:
172, CDR-L1 as set forth in SEQ ID NO:
173, CDR-L2 as set forth in SEQ ID NO:
174 and CDR-L3 as set forth in SEQ ID NO:
175;
(a)(xiv) CDR-H1 as set forth in SEQ ID NO:
183, CDR-H2 as set forth in SEQ ID NO:
184, CDR-H3 as set forth in SEQ ID NO:
185, CDR-L1 as set forth in SEQ ID NO:
186, CDR-L2 as set forth in SEQ ID NO:
187 and CDR-L3 as set forth in SEQ ID NO:
188;
(a)(xv) CDR-H1 as set forth in SEQ ID NO:
196, CDR-H2 as set forth in SEQ ID NO:
197, CDR-H3 as set forth in SEQ ID NO:
198, CDR-L1 as set forth in SEQ ID NO:
199, CDR-L2 as set forth in SEQ ID NO:
200 and CDR-L3 as set forth in SEQ ID NO:
201;
(a)(xvi) CDR-H1 as set forth in SEQ ID NO:
209, CDR-H2 as set forth in SEQ ID NO:
210, CDR-H3 as set forth in SEQ ID NO:
211, CDR-L1 as set forth in SEQ ID NO:
212, CDR-L2 as set forth in SEQ ID NO:
213 and CDR-L3 as set forth in SEQ ID NO:
214;
(a)(xvii) CDR-H1 as set forth in SEQ ID NO:
222, CDR-H2 as set forth in SEQ ID NO:
223, CDR-H3 as set forth in SEQ ID NO:
224, CDR-L1 as set forth in SEQ ID NO:
225, CDR-L2 as set forth in SEQ ID NO:
226 and CDR-L3 as set forth in SEQ ID NO:
227;
(a)(xviii) CDR-H1 as set forth in SEQ ID NO:
235, CDR-H2 as set forth in SEQ ID NO:
236, CDR-H3 as set forth in SEQ ID NO:
237, CDR-L1 as set forth in SEQ ID NO:
238, CDR-L2 as set forth in SEQ ID NO:
239 and CDR-L3 as set forth in SEQ ID NO:
240;
(a)(xix) CDR-H1 as set forth in SEQ ID NO:
248, CDR-H2 as set forth in SEQ ID NO:
249, CDR-H3 as set forth in SEQ ID NO:
250, CDR-L1 as set forth in SEQ ID NO:
251, CDR-L2 as set forth in SEQ ID NO:
252 and CDR-L3 as set forth in SEQ ID NO:
253;
(a)(xx) CDR-H1 as set forth in SEQ ID NO:
261, CDR-H2 as set forth in SEQ ID NO:
262, CDR-H3 as set forth in SEQ ID NO:
263, CDR-L1 as set forth in SEQ ID NO:
264, CDR-L2 as set forth in SEQ ID NO:
265 and CDR-L3 as set forth in SEQ ID NO:
266;
(a)(xxi) CDR-H1 as set forth in SEQ ID NO:
274, CDR-H2 as set forth in SEQ ID NO:
275, CDR-H3 as set forth in SEQ ID NO:
276, CDR-L1 as set forth in SEQ ID NO:
277, CDR-L2 as set forth in SEQ ID NO:
278 and CDR-L3 as set forth in SEQ ID NO:
279;
(a)(xxii) CDR-H1 as set forth in SEQ ID NO:
287, CDR-H2 as set forth in SEQ ID NO:
288, CDR-H3 as set forth in SEQ ID NO:
289, CDR-L1 as set forth in SEQ ID NO:
290, CDR-L2 as set forth in SEQ ID NO:
291 and CDR-L3 as set forth in SEQ ID NO:
292;
(a)(xxiii) CDR-H1 as set forth in SEQ ID NO:
300, CDR-H2 as set forth in SEQ ID NO:
301, CDR-H3 as set forth in SEQ ID NO:
302, CDR-L1 as set forth in SEQ ID NO:
303, CDR-L2 as set forth in SEQ ID NO:
304 and CDR-L3 as set forth in SEQ ID NO:
305;
(a)(xxiv) CDR-H1 as set forth in SEQ ID NO:
313, CDR-H2 as set forth in SEQ ID NO:
314, CDR-H3 as set forth in SEQ ID NO:
315, CDR-L1 as set forth in SEQ ID NO:
316, CDR-L2 as set forth in SEQ ID NO:
317 and CDR-L3 as set forth in SEQ ID NO:
318;
(b)(i) CDR-H1 as set forth in SEQ ID NO:
508, CDR-H2 as set forth in SEQ ID NO:
509, CDR-H3 as set forth in SEQ ID NO:
510, CDR-L1 as set forth in SEQ ID NO:
511, CDR-L2 as set forth in SEQ ID NO:
512 and CDR-L3 as set forth in SEQ ID NO:
513;
(b)(ii) CDR-H1 as set forth in SEQ ID NO:
521, CDR-H2 as set forth in SEQ ID NO:
522, CDR-H3 as set forth in SEQ ID NO:
523, CDR-L1 as set forth in SEQ ID NO:
524, CDR-L2 as set forth in SEQ ID NO:
525 and CDR-L3 as set forth in SEQ ID NO:
526;
(b)(iii) CDR-H1 as set forth in SEQ ID NO:
534, CDR-H2 as set forth in SEQ ID NO:
535, CDR-H3 as set forth in SEQ ID NO:
536, CDR-L1 as set forth in SEQ ID NO:
537, CDR-L2 as set forth in SEQ ID NO:
538 and CDR-L3 as set forth in SEQ ID NO:
539;
(b)(iv) CDR-H1 as set forth in SEQ ID NO:
547, CDR-H2 as set forth in SEQ ID NO:
548, CDR-H3 as set forth in SEQ ID NO:
549, CDR-L1 as set forth in SEQ ID NO:
550, CDR-L2 as set forth in SEQ ID NO:
551 and CDR-L3 as set forth in SEQ ID NO:
552;
(b)(v) CDR-H1 as set forth in SEQ ID NO:
560, CDR-H2 as set forth in SEQ ID NO:
561, CDR-H3 as set forth in SEQ ID NO:
562, CDR-L1 as set forth in SEQ ID NO:
563, CDR-L2 as set forth in SEQ ID NO:
564 and CDR-L3 as set forth in SEQ ID NO:
565;
(b)(vi) CDR-H1 as set forth in SEQ ID NO:
573, CDR-H2 as set forth in SEQ ID NO:
574, CDR-H3 as set forth in SEQ ID NO:
575, CDR-L1 as set forth in SEQ ID NO:
576, CDR-L2 as set forth in SEQ ID NO:
577 and CDR-L3 as set forth in SEQ ID NO:
578;
and
(b)(vii) CDR-H1 as set forth in SEQ ID NO:
586 CDR-H2 as set forth in SEQ ID NO:
587, CDR-H3 as set forth in SEQ ID NO:
588, CDR-L1 as set forth in SEQ ID NO:
589, CDR-L2 as set forth in SEQ ID NO:
590 and CDR-L3 as set forth in SEQ ID NO:
591;
and
(b)(viii) CDR-H1 as set forth in SEQ ID NO:
1, CDR-H2 as set forth in SEQ ID NO:
2, CDR-H3 as set forth in SEQ ID NO:
3, CDR-L1 as set forth in SEQ ID NO:
4, CDR-L2 as set forth in SEQ ID NO:
5 and CDR-L3 as set forth in SEQ ID NO:
6;
(b)(ix) CDR-H1 as set forth in SEQ ID NO:
326, CDR-H2 as set forth in SEQ ID NO:
327, CDR-H3 as set forth in SEQ ID NO:
328, CDR-L1 as set forth in SEQ ID NO:
329, CDR-L2 as set forth in SEQ ID NO:
330 and CDR-L3 as set forth in SEQ ID NO:
331;
(b)(x) CDR-H1 as set forth in SEQ ID NO:
339, CDR-H2 as set forth in SEQ ID NO:
340, CDR-H3 as set forth in SEQ ID NO:
341, CDR-L1 as set forth in SEQ ID NO:
342, CDR-L2 as set forth in SEQ ID NO:
343 and CDR-L3 as set forth in SEQ ID NO:
344,
(b)(xi) CDR-H1 as set forth in SEQ ID NO:
352, CDR-H2 as set forth in SEQ ID NO:
353, CDR-H3 as set forth in SEQ ID NO:
354, CDR-L1 as set forth in SEQ ID NO:
355, CDR-L2 as set forth in SEQ ID NO:
356 and CDR-L3 as set forth in SEQ ID NO:
357;
(b)(xii) CDR-H1 as set forth in SEQ ID NO:
365, CDR-H2 as set forth in SEQ ID NO:
366, CDR-H3 as set forth in SEQ ID NO:
367, CDR-L1 as set forth in SEQ ID NO:
368, CDR-L2 as set forth in SEQ ID NO:
369 and CDR-L3 as set forth in SEQ ID NO:
370;
(b)(xiii) CDR-H1 as set forth in SEQ ID NO:
378, CDR-H2 as set forth in SEQ ID NO:
379, CDR-H3 as set forth in SEQ ID NO:
380, CDR-L1 as set forth in SEQ ID NO:
381, CDR-L2 as set forth in SEQ ID NO:
382 and CDR-L3 as set forth in SEQ ID NO:
383;
(b)(xiv) CDR-H1 as set forth in SEQ ID NO:
391, CDR-H2 as set forth in SEQ ID NO:
392, CDR-H3 as set forth in SEQ ID NO:
393, CDR-L1 as set forth in SEQ ID NO:
394, CDR-L2 as set forth in SEQ ID NO:
395 and CDR-L3 as set forth in SEQ ID NO:
396;
(b)(xv) CDR-H1 as set forth in SEQ ID NO:
404, CDR-H2 as set forth in SEQ ID NO:
405, CDR-H3 as set forth in SEQ ID NO:
406, CDR-L1 as set forth in SEQ ID NO:
407, CDR-L2 as set forth in SEQ ID NO:
408 and CDR-L3 as set forth in SEQ ID NO:
409;
(b)(xvi) CDR-H1 as set forth in SEQ ID NO:
417, CDR-H2 as set forth in SEQ ID NO:
418, CDR-H3 as set forth in SEQ ID NO:
419, CDR-L1 as set forth in SEQ ID NO:
420, CDR-L2 as set forth in SEQ ID NO:
421 and CDR-L3 as set forth in SEQ ID NO:
422;
(b)(xvii) CDR-H1 as set forth in SEQ ID NO:
430, CDR-H2 as set forth in SEQ ID NO:
431, CDR-H3 as set forth in SEQ ID NO:
432, CDR-L1 as set forth in SEQ ID NO:
433, CDR-L2 as set forth in SEQ ID NO:
434 and CDR-L3 as set forth in SEQ ID NO:
435;
(b)(xviii) CDR-H1 as set forth in SEQ ID NO:
443, CDR-H2 as set forth in SEQ ID NO:
444, CDR-H3 as set forth in SEQ ID NO:
445, CDR-L1 as set forth in SEQ ID NO:
446, CDR-L2 as set forth in SEQ ID NO:
447 and CDR-L3 as set forth in SEQ ID NO:
448;
(b)(xix) CDR-H1 as set forth in SEQ ID NO:
456, CDR-H2 as set forth in SEQ ID NO:
457, CDR-H3 as set forth in SEQ ID NO:
458, CDR-L1 as set forth in SEQ ID NO:
459, CDR-L2 as set forth in SEQ ID NO:
460 and CDR-L3 as set forth in SEQ ID NO:
461,
(b)(xix) CDR-H1 as set forth in SEQ ID NO:
482, CDR-H2 as set forth in SEQ ID NO:
483, CDR-H3 as set forth in SEQ ID NO:
484, CDR-L1 as set forth in SEQ ID NO:
485, CDR-L2 as set forth in SEQ ID NO:
486 and CDR-L3 as set forth in SEQ ID NO:
487;
(b)(xxi) CDR-H1 as set forth in SEQ ID NO:
495, CDR-H2 as set forth in SEQ ID NO:
496, CDR-H3 as set forth in SEQ ID NO:
497, CDR-L1 as set forth in SEQ ID NO:
498, CDR-L2 as set forth in SEQ ID NO:
499 and CDR-L3 as set forth in SEQ ID NO:
500;
and
(b)(xxii) CDR-H1 as set forth in SEQ ID NO:
599, CDR-H2 as set forth in SEQ ID NO:
600, CDR-H3 as set forth in SEQ ID NO:
601, CDR-L1 as set forth in SEQ ID NO:
602, CDR-L2 as set forth in SEQ ID NO:
603 and CDR-L3 as set forth in SEQ ID NO:
604.

323 more elements

Dependencies are inferred from the claim text.

Facts

Application

15/673,539Filed 10 Aug 2017

Priority

31 Jul 2014

Published

4 Jan 2018

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07K 16/468
Hybrid immunoglobulins: immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
A61K 47/60
Obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes: the organic…
A61P 35/00
Antineoplastic agents
A61P 35/04
Antineoplastic agents: specific for metastasis

Family

Application62/031,770Us provisional application · filed 31 Jul 2014

Application14/815,861Division · filed 31 Jul 2015

Application15/673,539Division

US 12,297,292 B2Related patent

US 2016/0032019 A1Published application

US 9,765,157 B2Related patent

US 2018/0002450 A1This patent

From the US filing history. Foreign family members aren’t listed.

Antibody Constructs For CDH19 and CD3

Life of this patent

Antibody Constructs For CDH19 and CD3

Life of this patent

Abstract

Claims6