US 10,238,748 B2Granted

Anti-CDH6 antibody drug conjugates

AssigneeNovartis AG

InventorsCarl Uli Bialucha, Scott Collins, Clemens Dürr, Tiancen Hu, Mary Jo Janatpour, Matthew John Meyer

Life of this patent

Estimating the term…

Abstract

The present invention relates to anti-CDH6 antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer.

Claims7

Dependent claims

A method of treating an CDH6 positive cancer in a patient in need thereof, comprising administering to said patient an antibody drug conjugate of the formula:

or a pharmaceutical composition thereof;
wherein;
n is an integer from 1 to 10 and said Ab is an antibody or antigen binding fragment thereof comprising:
(i) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:224, (b) a LCDR2 of SEQ ID NO:225, (c) a LCDR3 of SEQ ID NO:226;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:
227, (e) a HCDR2 of SEQ ID NO:
228, and (f) a HCDR3 of SEQ ID NO:229;
(ii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:210, (b) a LCDR2 of SEQ ID NO:211, (c) a LCDR3 of SEQ ID NO:212;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:213, (e) a HCDR2 of SEQ ID NO:
214, and (f) a HCDR3 of SEQ ID NO:215;
(iii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:266, (b) a LCDR2 of SEQ ID NO:267, (c) a LCDR3 of SEQ ID NO:268;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:
269, (e) a HCDR2 of SEQ ID NO:270, and (f) a HCDR3 of SEQ ID NO:
271;
(iv) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:308, (b) a LCDR2 of SEQ ID NO:309, (c) a LCDR3 of SEQ ID NO:310;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:311, (e) a HCDR2 of SEQ ID NO:312, and (f) a HCDR3 of SEQ ID NO:313;
(v) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:14, (b) a LCDR2 of SEQ ID NO:15, (c) a LCDR3 of SEQ ID NO:16;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:17, (e) a HCDR2 of SEQ ID NO:18, and (f) a HCDR3 of SEQ ID NO:19;
(vi) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:28, (b) a LCDR2 of SEQ ID NO:29, (c) a LCDR3 of SEQ ID NO:30;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:31, (e) a HCDR2 of SEQ ID NO:32, and (f) a HCDR3 of SEQ ID NO:33;
(vii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:42, (b) a LCDR2 of SEQ ID NO:43, (c) a LCDR3 of SEQ ID NO:44;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:45, (e) a HCDR2 of SEQ ID NO:46, and (f) a HCDR3 of SEQ ID NO:47;
(viii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:56, (b) a LCDR2 of SEQ ID NO:57, (c) a LCDR3 of SEQ ID NO:58;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:59, (e) a HCDR2of SEQ ID NO:60, and (f) a HCDR3 of SEQ ID NO:61;
(ix) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:70, (b) a LCDR2 of SEQ ID NO:71, (c) a LCDR3 of SEQ ID NO:72;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:73, (e) a HCDR2 of SEQ ID NO:74, and (f) a HCDR3 of SEQ ID NO:75;
(x) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:84, (b) a LCDR2 of SEQ ID NO:85, (c) a LCDR3 of SEQ ID NO:86;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:87, (e) a HCDR2 of SEQ ID NO:
88, and (f) a HCDR3 of SEQ ID NO:
89;
(xi) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:98, (b) a LCDR2 of SEQ ID NO:99, (c) a LCDR3 of SEQ ID NO:100;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:101, (e) a HCDR2 of SEQ ID NO:102, and (f) a HCDR3 of SEQ ID NO:103;
(xii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:112, (b) a LCDR2 of SEQ ID NO:113, (c) a LCDR3 of SEQ ID NO:114;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:115, (e) a HCDR2 of SEQ ID NO:116, and (f) a HCDR3 of SEQ ID NO:117;
(xiii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:126, (b) a LCDR2 of SEQ ID NO:127, (c) a LCDR3 of SEQ ID NO:128;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:129, (e) a HCDR2 of SEQ ID NO:130, and (f) a HCDR3 of SEQ ID NO:131;
(xiv) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:140, (b) a LCDR2 of SEQ ID NO:141, (c) a LCDR3 of SEQ ID NO:142;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:143, (e) a HCDR2 of SEQ ID NO:144, and (f) a HCDR3 of SEQ ID NO:145;
(xv) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:154, (b) a LCDR2 of SEQ ID NO:155, (c) a LCDR3 of SEQ ID NO:156;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:157, (e) a HCDR2 of SEQ ID NO:158, and (f) a HCDR3 of SEQ ID NO:159;
(xvi) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:168, (b) a LCDR2 of SEQ ID NO:169, (c) a LCDR3 of SEQ ID NO:170;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:171, (e) a HCDR2 of SEQ ID NO:172, and (f) a HCDR3 of SEQ ID NO:173;
(xvii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:182, (b) a LCDR2 of SEQ ID NO:183, (c) a LCDR3 of SEQ ID NO:184;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:185, (e) a HCDR2 of SEQ ID NO:86, and (f) a HCDR3 of SEQ ID NO:187;
(xviii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:196, (b) a LCDR2 of SEQ ID NO:197, (c) a LCDR3 of SEQ ID NO:198;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:199, (e) a HCDR2 of SEQ ID NO:200, and (f) a HCDR3 of SEQ ID NO:201;
(xix) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:238, (b) a LCDR2 of SEQ ID NO:239, (c) a LCDR3 of SEQ ID NO:240;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:241, (e) a HCDR2 of SEQ ID NO:242, and (f) a HCDR3 of SEQ ID NO:243;
(xx) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:252, (b) a LCDR2 of SEQ ID NO:253, (c) a LCDR3 of SEQ ID NO:254;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:255, (e) a HCDR2 of SEQ ID NO:256, and (f) a HCDR3 of SEQ ID NO:257;
(xxi) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:280, (b) a LCDR2 of SEQ ID NO:281, (c) a LCDR3 of SEQ ID NO:282;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:283, (e) a HCDR2 of SEQ ID NO:284, and (f) a HCDR3 of SEQ ID NO:285;
(xxii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:294, (b) a LCDR2 of SEQ ID NO:295, (c) a LCDR3 of SEQ ID NO:296;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:297, (e) a HCDR2 of SEQ ID NO:298, and (f) a HCDR3 of SEQ ID NO:299;
or
(xxiii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:322, (b) a LCDR2 of SEQ ID NO:323, (c) a LCDR3 of SEQ ID NO:324;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:325, (e) a HCDR2 of SEQ ID NO:326, and (f) a HCDR3 of SEQ ID NO:327.

77 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/502,478Filed 7 Aug 2015 · us provisional application
Priority: 12 Aug 2014
Published: US 2017/0224836 A110 Aug 2017
Granted: 26 Mar 2019
Term ends: Not estimatedThe source records don’t support an estimate.

Classification35 codes

C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
A61K 31/428
Thiazoles: condensed with carbocyclic rings
A61K 31/4738
Quinolines; Isoquinolines: ortho- or peri-condensed with heterocyclic ring systems
A61K 31/519
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with heterocyclic rings

Family

Application62/036,382Us provisional application · filed 12 Aug 2014
US 2017/0224836 A1Pre-grant publication · published 10 Aug 2017
US 10,238,748 B2This patent

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

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Abstract

The present invention relates to anti-CDH6 antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer.

A method of treating an CDH6 positive cancer in a patient in need thereof, comprising administering to said patient an antibody drug conjugate of the formula:

or a pharmaceutical composition thereof;
wherein;
n is an integer from 1 to 10 and said Ab is an antibody or antigen binding fragment thereof comprising:
(i) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:224, (b) a LCDR2 of SEQ ID NO:225, (c) a LCDR3 of SEQ ID NO:226;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:
227, (e) a HCDR2 of SEQ ID NO:
228, and (f) a HCDR3 of SEQ ID NO:229;
(ii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:210, (b) a LCDR2 of SEQ ID NO:211, (c) a LCDR3 of SEQ ID NO:212;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:213, (e) a HCDR2 of SEQ ID NO:
214, and (f) a HCDR3 of SEQ ID NO:215;
(iii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:266, (b) a LCDR2 of SEQ ID NO:267, (c) a LCDR3 of SEQ ID NO:268;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:
269, (e) a HCDR2 of SEQ ID NO:270, and (f) a HCDR3 of SEQ ID NO:
271;
(iv) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:308, (b) a LCDR2 of SEQ ID NO:309, (c) a LCDR3 of SEQ ID NO:310;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:311, (e) a HCDR2 of SEQ ID NO:312, and (f) a HCDR3 of SEQ ID NO:313;
(v) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:14, (b) a LCDR2 of SEQ ID NO:15, (c) a LCDR3 of SEQ ID NO:16;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:17, (e) a HCDR2 of SEQ ID NO:18, and (f) a HCDR3 of SEQ ID NO:19;
(vi) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:28, (b) a LCDR2 of SEQ ID NO:29, (c) a LCDR3 of SEQ ID NO:30;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:31, (e) a HCDR2 of SEQ ID NO:32, and (f) a HCDR3 of SEQ ID NO:33;
(vii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:42, (b) a LCDR2 of SEQ ID NO:43, (c) a LCDR3 of SEQ ID NO:44;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:45, (e) a HCDR2 of SEQ ID NO:46, and (f) a HCDR3 of SEQ ID NO:47;
(viii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:56, (b) a LCDR2 of SEQ ID NO:57, (c) a LCDR3 of SEQ ID NO:58;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:59, (e) a HCDR2of SEQ ID NO:60, and (f) a HCDR3 of SEQ ID NO:61;
(ix) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:70, (b) a LCDR2 of SEQ ID NO:71, (c) a LCDR3 of SEQ ID NO:72;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:73, (e) a HCDR2 of SEQ ID NO:74, and (f) a HCDR3 of SEQ ID NO:75;
(x) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:84, (b) a LCDR2 of SEQ ID NO:85, (c) a LCDR3 of SEQ ID NO:86;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:87, (e) a HCDR2 of SEQ ID NO:
88, and (f) a HCDR3 of SEQ ID NO:
89;
(xi) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:98, (b) a LCDR2 of SEQ ID NO:99, (c) a LCDR3 of SEQ ID NO:100;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:101, (e) a HCDR2 of SEQ ID NO:102, and (f) a HCDR3 of SEQ ID NO:103;
(xii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:112, (b) a LCDR2 of SEQ ID NO:113, (c) a LCDR3 of SEQ ID NO:114;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:115, (e) a HCDR2 of SEQ ID NO:116, and (f) a HCDR3 of SEQ ID NO:117;
(xiii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:126, (b) a LCDR2 of SEQ ID NO:127, (c) a LCDR3 of SEQ ID NO:128;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:129, (e) a HCDR2 of SEQ ID NO:130, and (f) a HCDR3 of SEQ ID NO:131;
(xiv) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:140, (b) a LCDR2 of SEQ ID NO:141, (c) a LCDR3 of SEQ ID NO:142;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:143, (e) a HCDR2 of SEQ ID NO:144, and (f) a HCDR3 of SEQ ID NO:145;
(xv) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:154, (b) a LCDR2 of SEQ ID NO:155, (c) a LCDR3 of SEQ ID NO:156;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:157, (e) a HCDR2 of SEQ ID NO:158, and (f) a HCDR3 of SEQ ID NO:159;
(xvi) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:168, (b) a LCDR2 of SEQ ID NO:169, (c) a LCDR3 of SEQ ID NO:170;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:171, (e) a HCDR2 of SEQ ID NO:172, and (f) a HCDR3 of SEQ ID NO:173;
(xvii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:182, (b) a LCDR2 of SEQ ID NO:183, (c) a LCDR3 of SEQ ID NO:184;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:185, (e) a HCDR2 of SEQ ID NO:86, and (f) a HCDR3 of SEQ ID NO:187;
(xviii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:196, (b) a LCDR2 of SEQ ID NO:197, (c) a LCDR3 of SEQ ID NO:198;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:199, (e) a HCDR2 of SEQ ID NO:200, and (f) a HCDR3 of SEQ ID NO:201;
(xix) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:238, (b) a LCDR2 of SEQ ID NO:239, (c) a LCDR3 of SEQ ID NO:240;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:241, (e) a HCDR2 of SEQ ID NO:242, and (f) a HCDR3 of SEQ ID NO:243;
(xx) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:252, (b) a LCDR2 of SEQ ID NO:253, (c) a LCDR3 of SEQ ID NO:254;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:255, (e) a HCDR2 of SEQ ID NO:256, and (f) a HCDR3 of SEQ ID NO:257;
(xxi) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:280, (b) a LCDR2 of SEQ ID NO:281, (c) a LCDR3 of SEQ ID NO:282;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:283, (e) a HCDR2 of SEQ ID NO:284, and (f) a HCDR3 of SEQ ID NO:285;
(xxii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:294, (b) a LCDR2 of SEQ ID NO:295, (c) a LCDR3 of SEQ ID NO:296;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:297, (e) a HCDR2 of SEQ ID NO:298, and (f) a HCDR3 of SEQ ID NO:299;
or
(xxiii) a light chain variable region that comprises (a) a LCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO:322, (b) a LCDR2 of SEQ ID NO:323, (c) a LCDR3 of SEQ ID NO:324;
and a heavy chain variable region that comprises:
(d) a HCDR1 of SEQ ID NO:325, (e) a HCDR2 of SEQ ID NO:326, and (f) a HCDR3 of SEQ ID NO:327.

77 more elements

Facts

Application

15/502,478Filed 7 Aug 2015 · us provisional application

Priority

12 Aug 2014

Published

US 2017/0224836 A110 Aug 2017

Granted

26 Mar 2019

Term ends

Not estimatedThe source records don’t support an estimate.

Classification35 codes

C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
A61K 31/428
Thiazoles: condensed with carbocyclic rings
A61K 31/4738
Quinolines; Isoquinolines: ortho- or peri-condensed with heterocyclic ring systems
A61K 31/519
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with heterocyclic rings