Anti-CEACAM6 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-11866495-B2
Application number	US-202016776329-A
Country	US
Kind code	B2
Filing date	Jan 29, 2020
Priority date	Mar 23, 2015
Publication date	Jan 9, 2024
Grant date	Jan 9, 2024

Abstract

The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for human and Macaca fascicularis CEACAM6 (Carcinoembryonic antigen-related cell adhesion molecule 6, CD66c, Non-specific crossreacting antigen, NCA, NCA-50/90), and which do not significantly cross-react with the closely related human CEACAM1, human CEACAM3, and human CEACAM5. The invention further provides methods to generate this kind of antibodies.The antibodies, accordingly, can be used to treat cancer and other disorders and conditions associated with expression of the CEACAM6. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use.

First claim

The invention claimed is:

1. An isolated antibody or antigen-binding fragment thereof specifically binding to human CEACAM6, wherein said antibody or antigen-binding fragment:
i. binds to an epitope of human CEACAM6, wherein said epitope comprises the amino acid residues GIn60, Asn61, Arg62, Ile63, Va183, Ile84, Gly85, Thr90, Ser127, Asp128 and Leu129 of SEQ ID NO: 179, and
ii. binds to a human CEACAM6 protein comprising an Ile63Leu mutation and does not bind to a human CEACAM6 protein comprising an 11 e63Phe mutation according to SEQ ID NO: 179, and
wherein the antibody or antigen-binding fragment includes
a) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:48, an H-CDR2 comprising SEQ ID NO:49, and an H-CDR3 comprising SEQ ID NO:50 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:52, a L-CDR2 comprising SEQ ID NO:53, and a L-CDR3 comprising SEQ ID NO:54; or
b) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:106, an H-CDR2 comprising SEQ ID NO:107, and an H-CDR3 comprising SEQ ID NO:108 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:110, a L-CDR2 comprising SEQ ID NO:111, and a L-CDR3 comprising SEQ ID NO:112; or
c) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:4, an H-CDR2 comprising SEQ ID NO:5, and an H-CDR3 comprising SEQ ID NO:6 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:8, a L-CDR2 comprising SEQ ID NO:9, and a L-CDR3 comprising SEQ ID NO:10; or
d) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:34, an H-CDR2 comprising SEQ ID NO:35, and an H-CDR3 comprising SEQ ID NO:36 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:38, a L-CDR2 comprising SEQ ID NO:39, and a L-CDR3 comprising SEQ ID NO:40; or
e) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:120, an H-CDR2 comprising SEQ ID NO:121, and an H-CDR3 comprising SEQ ID NO:122 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:124, a L-CDR2 comprising SEQ ID NO:125, and a L-CDR3 comprising SEQ ID NO:126; or
f) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:24, an H-CDR2 comprising SEQ ID NO:25, and an H-CDR3 comprising SEQ ID NO:26 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:28, a L-CDR2 comprising SEQ ID NO:29, and a L-CDR3 comprising SEQ ID NO:30; or
g) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:76, an H-CDR2 comprising SEQ ID NO:77, and an H-CDR3 comprising SEQ ID NO:78 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:80, a L-CDR2 comprising SEQ ID NO:81, and a L-CDR3 comprising SEQ ID NO:82; or
h) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:134, an H-CDR2 comprising SEQ ID NO:135, and an H-CDR3 comprising SEQ ID NO:136 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:138, a L-CDR2 comprising SEQ ID NO:139, and a L-CDR3 comprising SEQ ID NO:140; or
i) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:148, an H-CDR2 comprising SEQ ID NO:149, and an H-CDR3 comprising SEQ ID NO:150 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:152, a L-CDR2 comprising SEQ ID NO:153, and a L-CDR3 comprising SEQ ID NO:154; or
j) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:14, an H-CDR2 comprising SEQ ID NO:15, and an H-CDR3 comprising SEQ ID NO:16 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:18, a L-CDR2 comprising SEQ ID NO:19, and a L-CDR3 comprising SEQ ID NO:20; or
k) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:62, an H-CDR2 comprising SEQ ID NO:63, and an H-CDR3 comprising SEQ ID NO:64 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:66, a L-CDR2 comprising SEQ ID NO:67, and a L-CDR3 comprising SEQ ID NO:68; or
l) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:92, an H-CDR2 comprising SEQ ID NO:93, and an H-CDR3 comprising SEQ ID NO:94 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:96, a L-CDR2 comprising SEQ ID NO:97, and a L-CDR3 comprising SEQ ID NO:98.

2. The antibody or antigen-binding fragment according to claim 1 , which is an IgG antibody.

3. The antibody or antigen-binding fragment according to claim 1 , which is a scFv, Fab, Fab′, or F(ab′)2 fragment.

4. The antibody or antigen-binding fragment according to claim 1 , which is a monoclonal antibody or antigen-binding fragment.

5. The antibody or antigen-binding fragment according to claim 1 , which is a human, humanized or chimeric antibody or antigen-binding fragment.

6. An antibody-drug conjugate, comprising an antibody or antigen binding fragment according to claim 1 .

7. An isolated nucleic acid that encodes the antibody or antigen-binding fragment according to claim 1 .

8. A vector comprising a nucleic acid according to claim 7 .

9. An isolated cell expressing an antibody or antigen-binding fragment according to claim 1 .

10. An isolated cell according to claim 9 , wherein said cell is a prokaryotic or a eukaryotic cell.

11. A method of producing an antibody or antigen-binding fragment thereof specifically binding to human CEACAM6 comprising culturing of a cell according to claim 9 and purifying the antibody or antigen-binding fragment thereof.

12. A pharmaceutical composition comprising an antibody or antigen-binding fragment according to claim 1 .

13. A combination of a pharmaceutical composition according to claim 12 and one or more therapeutically active compounds.

14. A method for treating cancer expressing CEACAM6, comprising administering to a subject in need thereof an effective amount of the antibody or antigen-binding fragment according to claim 1 .

15. A method for treating cancer expressing CEACAM6, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 12 .

16. A method for treating cancer expressing CEACAM6, comprising administering to a subject in need thereof an effective amount of the combination according to claim 13 .

17. A pharmaceutical composition comprising an antibody-drug conjugate according to claim 6 .

18. A combination of a pharmaceutical composition according to claim 17 and one or more therapeutically active compounds.

19. A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 17 .

20. A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the combination according to claim 18 .

Assignees

• Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen Rechts

Inventors

• Willuda Jörg
• Trautwein Mark
• Gritzan Uwe
• Freiberg Christoph
• Dittmer Frank
• Schönfeld Dorian
• Glück Julian Marius
• Pinkert Jessica
• Gutierrez Eva-Maria
• Golfier Sven
• Holton Simon
• Beckhove Philip
• Ge Yingzi

Classifications

• A61K40/4266

  Carcinoembryonic antigen [CEA] · CPC title

• A61K40/4254

  Adhesion molecules, e.g. NRCAM, EpCAM or cadherins · CPC title

• A61K40/424

  Apoptosis related proteins, e.g. survivin or livin · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title