IL-17A antibodies
Interleukin-17A (IL-17A) antibody antagonists, polynucleotides encoding IL-17A antibody antagonists or fragments thereof, and methods of making and using the foregoing are disclosed.
1. An isolated antibody or fragment thereof that binds specifically to human IL-17A, comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH region comprises the HCDR1, HCDR2 and HCDR3 having the amino acid sequences as shown in SEQ ID NOs:25, 46 and 61, respectively; and the VL region comprises the LCDR1, LCDR2, and LCDR3 having the amino acid sequences as shown in SEQ ID NOs:3, 6 and 22, respectively; and wherein
in SEQ ID NO:46,
Xaa1 may be Ala, Gly, Thr or Val;
Xaa3 may be Asn or Ser;
Xaa4 may be Gly, Met, Lys, Ile, Leu or His;
Xaa5 may be Leu, Asp, Ala, His, Thr, Gly or Ser;
Xaa6 may be Gly or Ser;
Xaa7 may be Thr, Gly, Tyr or Asp;
Xaa8 may be His, Trp, Tyr or Phe;
Xaa9 may be Lys, Thr or Ile; and
Xaa10 may be Tyr, Phe or Asn;
in SEQ ID NO:61,
Xaa may be Met, Leu or Thr; and
in SEQ ID NO:22,
Xaa is Met, Leu, Thr or Tyr.
2. The isolated antibody or fragment of claim 1 , wherein the antibody comprises the HCDR1, HCDR2 and HCDR3 amino acid sequences as shown in:
a. SEQ ID NOs: 25, 37 and 58, respectively;
b. SEQ ID NOs: 25, 38 and 58, respectively;
c. SEQ ID NOs: 25, 39 and 58, respectively;
d. SEQ ID NOs: 25, 40 and 58, respectively;
e. SEQ ID NOs: 25, 41 and 58, respectively;
f. SEQ ID NOs: 25, 42 and 58, respectively;
g. SEQ ID NOs: 25, 43 and 58, respectively;
h. SEQ ID NOs: 25, 41 and 59, respectively;
i. SEQ ID NOs: 25, 41 and 60, respectively;
j. SEQ ID NOs: 25, 43 and 60, respectively;
k. SEQ ID NOs: 25, 44 and 58, respectively; or
l. SEQ ID NOs: 25, 45 and 58, respectively; and
the LCDR1, LCDR2, and LCDR3 amino acid sequences as shown in:
m. SEQ ID NOs: 3, 6 and 18, respectively;
n. SEQ ID NOs: 3, 6 and 19, respectively;
o. SEQ ID NOs: 3, 6 and 20, respectively; or
p. SEQ ID NOs: 3, 6 and 21, respectively.
3. An isolated monoclonal antibody or fragment thereof that binds specifically to human IL-17A that competes for human IL-17A binding with a monoclonal antibody comprising the heavy chain CDR 1, 2 and 3 (HCDR1, HCDR2 and HCDR3) amino acid sequences as shown in SEQ ID NOs: 25, 43 and 60, respectively, and the light chain CDR 1, 2 and 3 (LCDR1, LCDR2 and LCDR3) amino acid sequences as shown in SEQ ID NOs: 3, 6 and 18, respectively.
4. The isolated antibody or fragment of claim 3 or 1 , wherein the antibody is fully human.
5. The isolated antibody or fragment of claim 3 or 1 , wherein the antibody is conjugated to polyethylene glycol.
6. The isolated antibody or fragment of claim 3 or 1 , having an IgG1 or IgG4 isotype.
7. The isolated antibody or fragment of claim 3 or 1 , wherein the Fc domain comprises S229P, P235A or L236A mutations in the Fc domain.
8. A pharmaceutical composition comprising the isolated antibody or fragment of claim 3 or 1 and a pharmaceutically acceptable carrier.
9. An isolated antibody or fragment thereof that binds specifically to human IL-17A comprising a VH and a VL, wherein the antibody comprises:
a. the HCDR1, HCDR2 and HCDR3 amino acid sequences as shown in SEQ ID NOs: 25, 43 and 60, respectively and
the LCDR1, LCDR2, and LCDR3 amino acid sequences as shown in SEQ ID NOs: 3, 6 and 18, respectively; or
b. the VH of SEQ ID NO: 86; or
c. the VL of SEQ ID NO: 79; or
d. the VH of SEQ ID NO: 86 and the VL of SEQ ID NO: 79.
10. An isolated antibody or fragment thereof that binds specifically to human IL-17A, comprising a VH and a VL, wherein the antibody comprises the VH having the amino acid sequence shown in SEQ ID NO: 86.
11. The isolated antibody or fragment of claim 10 , wherein the antibody comprises the VL having the amino acid sequence shown in SEQ ID NO: 79.
12. An isolated antibody or fragment thereof that binds specifically to human IL-17A, comprising a VH and a VL, wherein the antibody comprises the VL having the amino acid sequence shown in SEQ ID NO: 79.
13. An isolated antibody or fragment thereof that binds specifically to human IL-17A, comprising a VH and a VL, wherein the antibody comprises the VH which is at least 95% identical to the VH having the amino acid sequence shown in SEQ ID NO: 86.
14. An isolated antibody or fragment thereof that binds specifically to human IL-17A, comprising a VH and a VL, wherein the antibody comprises the VL which is at least 95% identical to the variable region having the amino acid sequence shown in SEQ ID NO: 79.
15. An isolated antibody or fragment thereof that binds specifically to human IL-17A, comprising an antibody heavy chain having the amino acid sequence shown in SEQ ID NO: 100.
16. An isolated antibody or fragment thereof that binds specifically to IL-17A, comprising an antibody light chain having the amino acid sequence shown in SEQ ID NO: 90.