Anti-cntn4 antibody and uses thereof

Abstract

The present invention relates to an anti-CNTN4 antibody or an antigen-binding fragment thereof, and uses thereof.

Description

Anti-CNTN4 Antibody and Uses This invention relates to an anti-CNTN4 antibody or an antigen-binding fragment thereof, and its uses.

Claims

1. An anti-CNTN4 antibody or an antigen-binding fragment thereof, comprising: heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 1; heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 4; heavy chain CDR3 having any one amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 8 to 18, and 21 to 35; light chain CDR1 having the amino acid sequence of SEQ ID NO: 2 or 3; light chain CDR2 having the amino acid sequence of SEQ ID NO: 5; and light chain CDR3 having any one amino acid sequence selected from the group consisting of SEQ ID NOs: 7, 19, and 20.

2. The anti-CNTN4 antibody or an antigen-binding fragment thereof of claim 1, which comprises 101) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 6, 2, 5, and 7, respectively; 102) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 8, 2, 5, and 7, respectively; 103) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 9, 2, 5, and 7, respectively; 104) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 10, 2, 5, and 7, respectively; 105) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1,4, 11, 2, 5, and 7, respectively; 106) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 12, 2, 5, and 7, respectively; 107) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 13, 2, 5, and 7, respectively; 108) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 14, 2, 5, and 7, respectively; 109) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 15, 2, 5, and 7, respectively; 110) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1,4, 16, 2, 5, and 7, respectively; 111) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 17, 2, 5, and 7, respectively; 112) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 18, 3, 5, and 7, respectively; 113) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 18, 2, 5, and 19, respectively; 114) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 18, 2, 5, and 20, respectively; 201) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 21, 3, 5, and 20, respectively; 202) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 22, 3, 5, and 20, respectively; 203) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 23, 3, 5, and 20, respectively; 204) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 24, 3, 5, and 20, respectively; 205) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 21, 2, 5, and 20, respectively; 206) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 25, 3, 5, and 20, respectively; 207) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 26, 2, 5, and 20, respectively; 208) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 27, 2, 5, and 20, respectively; 209) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 26, 3, 5, and 20, respectively; 210) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 28, 3, 5, and 20, respectively; 211) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 27, 3, 5, and 20, respectively; 212) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 9, 3, 5, and 20, respectively; 213) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 29, 2, 5, and 20, respectively; 214) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 30, 2, 5, and 20, respectively; 215) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 31, 2, 5, and 20, respectively; 216) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 32, 3, 5, and 20, respectively; 217) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 33, 2, 5, and 20, respectively; 218) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 34, 3, 5, and 20, respectively; or 219) heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3, which have the amino acid sequences of SEQ ID NOs: 1, 4, 35, 2, 5, and 20, respectively.

3. The anti-CNTN4 antibody or an antigen-binding fragment thereof of claim 1, which comprises a heavy chain variable region having any one amino acid sequence selected from the group consisting of SEQ ID NOs: 36, 38 to 48, 52, and 54 to 67; and a light chain variable region having any one amino acid sequence selected from the group consisting of SEQ ID NOs: 37, 49 to 51, and 53.

4. The anti-CNTN4 antibody or an antigen-binding fragment thereof of claim 1, which comprises A101) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 36 and 37, respectively; A102) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 38 and 37, respectively; A103) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 39 and 37, respectively; A104) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 40 and 37, respectively; A105) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 41 and 37, respectively; A106) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 42 and 37, respectively; A107) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 43 and 37, respectively; A108) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 44 and 37, respectively; A109) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 45 and 37, respectively; A110) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 46 and 37, respectively; A111) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 47 and 37, respectively; A112) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 48 and 49, respectively; A113) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 48 and 50, respectively; A114) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 48 and 51, respectively; A201) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 52 and 53, respectively; A202) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 54 and 53, respectively; A203) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 55 and 53, respectively; A204) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 56 and 53, respectively; A205) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 52 and 51, respectively; A206) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 57 and 53, respectively; A207) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 58 and 51, respectively; A208) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 59 and 51, respectively; A209) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 58 and 53, respectively; A210) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 60 and 53, respectively; A211) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 59 and 53, respectively; A212) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 39 and 53, respectively; A213) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 61 and 51, respectively; A214) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 62 and 51, respectively; A215) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 63 and 51, respectively; A216) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 64 and 53, respectively; A217) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 65 and 51, respectively; A218) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 66 and 53, respectively; or A219) a heavy chain variable region and a light chain variable region, which have the amino acid sequences of SEQ ID NOs: 67 and 51, respectively.

5. The anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4, which specifically binds to the CNTN4 protein.

6. The anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4, which binds to the CNTN4 protein with an equilibrium dissociation constant (KD) of 1 x 10-8 M or less.

7. The anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4, which binds to the CNTN4 protein with an EC50 of 100 nM or less.

8. The anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4, wherein the antigen-binding fragment is Fab, Fab', Fab'-SH, Fv, a single-chain variable fragment (scFv), an F(ab')2 fragment, VL, VH, a diabody, a triabody, a tetrabody, a minibody ((scFV-CH3)2), IgG ΔCH2, scFv-Fc, (scFv)2-Fc, a fynomer, dual-affinity re-targeting (DART), or TRIDENT.

9. The anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4, wherein the antibody is a chimeric antibody, a humanized antibody, or a human antibody.

10. An antibody-drug conjugate comprising the anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4.

11. A nucleic acid molecule that encodes the anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4.

12. A recombinant expression vector comprising the nucleic acid molecule of claim 11.

13. A pharmaceutical composition for preventing or treating cancer, comprising the anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4.

14. The pharmaceutical composition of claim 13, wherien the cancer is cancer that expresses CNTN4.

15. A pharmaceutical composition for preventing or treating cancer, comprising: the anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4; and an additional anti-cancer agent.

16. The pharmaceutical composition of claim 15, wherein the additional anti-cancer agent is an immune checkpoint inhibitor or a chemotherapeutic agent.

17. The pharmaceutical composition of claim 16, wherein the immune checkpoint inhibitor is one or more selected from the group consisting of an anti-CTLA-4 antibody, an anti-PD-1 antibody, and an anti-PD-L1 antibody.

18. The pharmaceutical composition of claim 15, wherein the anti-CNTN4 antibody or an antigen-binding fragment thereof and the additional anti-cancer agent are simultaneously administered as one preparation, or simultaneously or sequentially administered as separate preparations.

19. A pharmaceutical composition for preventing or treating cancer, comprising: the anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4, which is used together with an additional anticancer therapy.

20. The pharmaceutical composition of claim 19, wherein the additional anticancer therapy is one or more selected from the group consisting of an immune checkpoint inhibitor, a chemotherapeutic agent, and radiation therapy.

21. A method of preventing or treating cancer in a subject, comprising: administering the anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4 to a subject.

22. A use of the anti-CNTN4 antibody or an antigen-binding fragment thereof of any one of claims 1 to 4 for preparing a drug for preventing or treating cancer.

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