Antibodies that bind CD39 and uses thereof
The present disclosure relates to anti-CD39 antibodies, and antigen binding portions thereof and their use in treating cancer.
1. An isolated antibody that binds to CD39, wherein the antibody comprises:
i. (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 27; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 28; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 29; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 37; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 38; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 39; or
ii. (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 30; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 31; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 32; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 40; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 41; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 42.
2. The antibody of claim 1 , which comprises a heavy chain variable region (V H ) and a light chain variable region (V L ), wherein:
the V H is at least 90% identical to the amino acid sequence of SEQ ID NO: 33 and the V L is at least 90% identical to the amino acid sequence of SEQ ID NO: 43.
3. The antibody of claim 1 , which comprises a heavy chain and a light chain, wherein:
the heavy chain is at least 90% identical to the amino acid sequence of SEQ ID NO: 35, 47, 49, or 51 and the light chain is at least 90% identical to the amino acid sequence of SEQ ID NO: 45.
4. The antibody of claim 1 , which comprises a heavy chain and a light chain, wherein:
the heavy chain comprises the amino acid sequence of SEQ ID NO: 35, 47, 49, or 51 and the light chain comprises the amino acid sequence of SEQ ID NO: 45.
5. The antibody of claim 1 , wherein
a. the antibody increases proliferation of a lymphocyte, optionally wherein the lymphocyte is a tumor-infiltrating lymphocyte, or CD4+ T cell; and/or
b. the antibody enhances expression of one or more dendritic cell activation markers; and/or
c. wherein the antibody enhances secretion of one or more cytokines from dendritic cells and/or
d. wherein the antibody cross-reacts with cynomolgus CD39.
6. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
7. The antibody of claim 1 , wherein the antibody is an antibody fragment selected from a Fab, Fab′, Fv, scFv or (Fab′) 2 fragment.
8. The antibody of claim 1 , wherein the antibody is a full length antibody.
9. A pharmaceutical composition comprising the anti-CD39 antibody of claim 1 and a pharmaceutically acceptable carrier.
10. A kit comprising the anti-CD39 antibody of claim 1 .
11. An isolated antibody that binds to CD39, which comprises a heavy chain variable region (V H ) and a light chain variable region (V L ), wherein:
the V H comprises the amino acid sequence of SEQ ID NO: 33 and the V L comprises the amino acid sequence of SEQ ID NO: 43.
12. The antibody of claim 11 , which comprises a heavy chain and a light chain, wherein: the heavy chain is at least 90% identical to the amino acid sequence of SEQ ID NO: 35, 47, 49, or 51 and the light chain is at least 90% identical to the amino acid sequence of SEQ ID NO: 45.
13. The antibody of claim 11 , which comprises a heavy chain and a light chain, wherein: the heavy chain comprises the amino acid sequence of SEQ ID NO: 35, 47, 49, or 51 and the light chain comprises the amino acid sequence of SEQ ID NO: 45.
14. The antibody of claim 11 , wherein
a. the antibody increases proliferation of a lymphocyte, optionally wherein the lymphocyte is a tumor-infiltrating lymphocyte, or CD4+ T cell; and/or
b. the antibody enhances expression of one or more dendritic cell activation markers; and/or
c. wherein the antibody enhances secretion of one or more cytokines from dendritic cells and/or
d. wherein the antibody cross-reacts with cynomolgus CD39.
15. The antibody of claim 11 , wherein the antibody is a monoclonal antibody.
16. The antibody of claim 11 , wherein the antibody is an antibody fragment selected from a Fab, Fab′, Fv, scFv or (Fab′) 2 fragment.
17. The antibody of claim 11 , wherein the antibody is a full length antibody.
18. A pharmaceutical composition comprising the anti-CD39 antibody of claim 11 and a pharmaceutically acceptable carrier.
19. A kit comprising the anti-CD39 antibody of claim 11 .