Anti-CEACAM6 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-11773164-B2
Application number	US-202016776326-A
Country	US
Kind code	B2
Filing date	Jan 29, 2020
Priority date	Mar 23, 2015
Publication date	Oct 3, 2023
Grant date	Oct 3, 2023

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 anti-CEACAM6 antibody or antigen-binding fragment thereof comprising:
ii. 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
iii. 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
iv. 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
v. 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
vi. 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
vii. 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
viii. 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
ix. 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
x. 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
xi. 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
xii. 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 D NO:97, and a L-CDR3 comprising SEQ ID NO:98.

2. The antibody or antigen-binding fragment according to claim 1 comprising:
ii. a variable heavy chain sequence as presented by SEQ ID NO: 105 and a variable light chain sequence as presented by SEQ ID NO: 109, or
iii. a variable heavy chain sequence as presented by SEQ ID NO: 3 and a variable light chain sequence as presented by SEQ ID NO: 7, or
iv. a variable heavy chain sequence as presented by SEQ ID NO: 33 and a variable light chain sequence as presented by SEQ ID NO: 37, or
v. a variable heavy chain sequence as presented by SEQ ID NO: 119 and a variable light chain sequence as presented by SEQ ID NO: 123, or
vi. a variable heavy chain sequence as presented by SEQ ID NO: 23 and a variable light chain sequence as presented by SEQ ID NO: 27, or
vii. a variable heavy chain sequence as presented by SEQ ID NO: 75 and a variable light chain sequence as presented by SEQ ID NO: 79, or
viii. a variable heavy chain sequence as presented by SEQ ID NO: 133 and a variable light chain sequence as presented by SEQ ID NO: 137, or
ix. a variable heavy chain sequence as presented by SEQ ID NO: 147 and a variable light chain sequence as presented by SEQ ID NO: 151, or
x. a variable heavy chain sequence as presented by SEQ ID NO: 13 and a variable light chain sequence as presented by SEQ ID NO: 17, or
xi. a variable heavy chain sequence as presented by SEQ ID NO: 61 and a variable light chain sequence as presented by SEQ ID NO: 65, or
xii. a variable heavy chain sequence as presented by SEQ ID NO: 91 and a variable light chain sequence as presented by SEQ ID NO: 95.

3. The antibody according to claim 1 comprising:
ii. a heavy chain region corresponding to SEQ ID NO: 115 and a light chain region corresponding to SEQ ID NO: 116, or
iii. a heavy chain region corresponding to SEQ ID NO: 43 and a light chain region corresponding to SEQ ID NO: 44, or
iv. a heavy chain region corresponding to SEQ ID NO: 129 and a light chain region corresponding to SEQ ID NO: 130, or
v. a heavy chain region corresponding to SEQ ID NO: 85 and a light chain region corresponding to SEQ ID NO: 86, or
vi. a heavy chain region corresponding to SEQ ID NO: 143 and a light chain region corresponding to SEQ ID NO: 144, or
vii. a heavy chain region corresponding to SEQ ID NO: 157 and a light chain region corresponding to SEQ ID NO: 158, or
viii. a heavy chain region corresponding to SEQ ID NO: 71 and a light chain region corresponding to SEQ ID NO: 72, or
ix. a heavy chain region corresponding to SEQ ID NO: 101 and a light chain region corresponding to SEQ ID NO: 102.

4. The antibody according to claim 1 , which is an IgG antibody.

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

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

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

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

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

10. A vector comprising a nucleic acid according to claim 9 .

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

12. The isolated cell according to claim 11 , wherein said cell is a prokaryotic or a eukaryotic cell.

13. A method of producing an anti-CEACAM6 antibody or antigen-binding fragment comprising culturing of the cell according to claim 11 and purifying the anti-CEACAM6 antibody or antigen-binding fragment.

14. A pharmaceutical composition comprising the antibody or antigen-binding fragment according to claim 1 .

15. A combination of the pharmaceutical composition according to claim 14 and one or mor

Assignees

• Bayer Pharma AG
• Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen Rechts

Inventors

• Willuda Jörg
• Trautwein Mark
• Gritzan Uwe
• Freiberg Christoph
• Dittmer Frank
• Schönfeld Dorian
• Glück Julian
• 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