Compositions and methods for anti-PACAP antibodies
The present disclosure generally relates to anti-PACAP antibodies, pharmaceutical compositions comprising such antibodies, and methods of producing and using such antibodies.
1. An anti-pituitary adenylate-cyclase-activating polypeptide (PACAP) antibody, wherein said antibody comprises heavy chain variable region (VH)-CDR1, VH-CDR2, and VH-CDR3 sequences set forth in SEQ ID NOs: 9, 2, and 3, respectively; and light chain variable region (VL)-CDR1, VL-CDR2, and VL-CDR3 sequence set forth in SEQ ID NOs: 10, 5, and 6, respectively.
2. The antibody of claim 1 , comprising the heavy chain and light chain framework region (FR) sequences derived from human gene IGHV1-69*01 and IGKV4-1*01, respectively, and functional variants thereof.
3. The antibody of claim 1 , comprising heavy chain framework region (VHFR)-1, VHFR-2, VHFR-3, and VHFR-4 sequences set forth in SEQ ID NOs: 29-32, respectively; and light chain framework region (VLFR)-1, VLFR-2, VLFR-3, and VLFR-4 sequences set forth in SEQ ID NOs: 33-36, respectively.
4. The antibody of claim 1 , comprising a VH sequence that is about 90%, about 95%, or about 99% identical to a sequence selected from SEQ ID NOs: 11 and 12, and a VL sequence that is about 90%, about 95%, or about 99% identical to a sequence selected from SEQ ID NOs: 20 and 21.
5. The antibody of claim 1 , comprising a VH sequence selected from SEQ ID NOs: 11 and 12 and a VL sequence selected from SEQ ID NOs: 20 and 21.
6. The antibody of claim 1 , comprising a VH sequence of SEQ ID NO: 11 or SEQ ID NO: 12, wherein the VH sequence has Glutamine (Q) instead of Glutamic Acid (E) at residue 1 of SEQ ID NO: 11 or 12.
7. The antibody of claim 1 , comprising a heavy chain constant region sequence selected from the group consisting of SEQ ID NOs: 37-51 or 76 and a light chain constant region sequence selected from SEQ ID NOs: 23 and 24.
8. The antibody of claim 1 , wherein the antibody is human, of humanized.
9. The antibody of claim 1 , wherein the antibody has low or no immunogenicity profile.
10. The antibody of claim 1 , wherein the antibody has a humanness score greater than or equal to about 89%.
11. The antibody of claim 1 , wherein the antibody has a KD lower than or equal to about 5×10 −11 molar (M) as measured by SPR at 37° C.
12. The antibody of claim 1 , wherein the antibody or antigen-binding fragment thereof has a KD lower than or equal to about 3×10 −11 molar (M) as measured by SPR at 37° C.
13. The antibody of claim 1 , comprising a full length heavy chain sequence and a full length light chain sequence that is about 90%, about 95%, or about 99% identical to the sequences selected from the group consisting of:
a) SEQ ID NOs: 70 and 71, respectively;
b) SEQ ID NOs: 74 and 71, respectively;
c) SEQ ID NOs: 75 and 71, respectively;
d) SEQ ID NOs: 72 and 73, respectively;
e) SEQ ID NOs: 70 and 73, respectively; and
f) SEQ ID NOs: 72 and 71, respectively.
14. The antibody of claim 1 , comprising a full length heavy chain sequence and a full length light chain sequence selected from the group consisting of:
a) SEQ ID NOs: 70 and 71, respectively;
b) SEQ ID NOs: 74 and 71, respectively;
c) SEQ ID NOs: 75 and 71, respectively;
d) SEQ ID NOs: 72 and 73, respectively;
e) SEQ ID NOs: 70 and 73, respectively; and
f) SEQ ID NOs: 72 and 71, respectively.
15. The antibody of claim 1 , wherein the heavy chain sequence has Glutamine (Q) instead of Glutamic Acid (E) at residue 1 of SEQ ID NOs: 70 72, 74, and 75.
16. The antibody of claim 1 , wherein the antibody is an antagonist of PACAP.
17. The antibody of claim 1 , wherein the antibody specifically binds to PACAP.
18. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
19. A method of treating a condition in an individual, comprising administering to the individual a therapeutically effective amount of the pharmaceutical composition of claim 18 , wherein the condition is headache.
20. An anti-PACAP antibody, wherein said antibody comprises VH-CDR1, VH-CDR2, and VH-CDR3 sequences and VL-CDR1, VL-CDR2, and VL-CDR3 sequences selected from the group consisting of:
a) SEQ ID NOs: 1, 2, and 3 and SEQ ID NO: 4, 5, and 6, respectively;
b) SEQ ID NOs: 7, 2, and 3 and SEQ ID NO: 8, 5, and 6, respectively;
c) SEQ ID NOs: 1, 2, and 3 and SEQ ID NO: 8, 5, and 6, respectively; and
d) SEQ ID NOs: 7, 2, and 3 and SEQ ID NO: 4, 5, and 6, respectively.