IL-17A-binding polypeptides

10934,335

15/538890

January 12, 2016

The present disclosure relates to a class of engineered polypeptides having a binding affinity for interleukin-17A (IL-17A), and provides an IL-17A binding polypeptide comprising the sequence EX2DX4AX6X7EIX10X11 LPNL X16X17X18QX20X21AFIX25 X26LX28X29. Also disclosed is the use of such an interleukin-17A binding polypeptide as a diagnostic, prognostic and/or therapeutic agent.

AFFIBODY AB (Solna, SE)

AFFIBODY AB (Solna, SE)

1. An IL-17A binding polypeptide, comprising an IL-17A binding motif BM, which motif consists of an amino acid sequence selected from: i) EX 2 DX 4 AX 6 X 7 EIX 10 X 11 LPNL X 16 X 17 X 18 QX 20 X 21 AFIX 25 X 26 LX 28 X 29 (SEQ ID NO:1295) wherein, independently from each other, X 2 is selected from A, H, M and Y; X 4 is selected from A, D, E, F, K, L, M, N, Q, R, S and Y; X 6 is selected from A, Q and W; X 7 is selected from F, I, L, M, V, W and Y; X 10 is selected from A and W; X 11 is selected from A, D, E, F, G, L, M, N, Q, S, T and Y; X 16 is selected from N and T; X 17 is selected from H, W and Y; X 18 is selected from A, D, E, H and V; X 20 is selected from A, G, Q, S and W; X 21 is selected from A, D, E, F, H, K, N, R, T, V, W and Y; X 25 is selected from A, D, E, G, H, I, L, M, N, Q, R, S, T and V; X 26 is selected from K and S; X 28 is selected from I, L, N and R; and X 29 is selected from D and R; and ii) an amino acid sequence which has at least 96% identity to the sequence defined in i).

2. The IL-17A binding polypeptide according to claim 1 , wherein, in sequence i), X 2 is selected from A, H and M; X 4 is selected from A, D, E, F, L, M, N, Q, R and Y; X 11 is selected from A, D, E, F, G, L, M, N, S, T and Y; X 18 is selected from A, D, E and V; X 20 is selected from A, G, Q and W; X 21 is selected from E, F, H, N, R, T, V, W and Y; X 25 is selected from A, D, E, G, H, I, L, N, Q, R, S, T and V; and X 28 is selected from I, N and R.

3. The IL-17A binding polypeptide according to claim 2 , wherein, in sequence i), X 16 is T; X 17 is W; X 21 is selected from E, F, H, W, T and Y; X 25 is selected from A, D, E, G, H, I, L, N, Q, R, S and T; X 26 is K; and X 29 is D.

4. The IL-17A binding polypeptide according to claim 1 , wherein sequence i) consists of amino acids 8 to 36 of any one of SEQ ID NO:1-1216.

5. The IL-17A binding polypeptide according to claim 1 , which comprises a binding module, BMod, consisting of the amino acid sequence K-[BM]-DPSQS X a X b LLX c EAKKLX d X e X f Q (SEQ ID NO: 1296) wherein [BM] is the IL-17A binding motif as defined in claim 1 provided that X 29 is D; X a is selected from A and S; X b is selected from N and E; X c is selected from A, S and C; X d is selected from E, N and S; X e is selected from D, E and S; and X f is selected from A and S.

6. The IL-17A binding polypeptide according to claim 5 , wherein said BMod consists of amino acids 7 to 55 of any one of SEQ ID NO:1-1216.

7. The IL-17A binding polypeptide according to claim 5 , which comprises the amino acid sequence: YA-[BMod]-AP (SEQ ID NO:1298); wherein [BMod] is the binding module as defined in claim 5 .

8. The IL-17A binding polypeptide according to claim 1 , which comprises the amino acid sequence: VDAKYAK-[BM]-DPSQSSELLSEAKKLNDSQAPK (SEQ ID NO:1281); wherein [BM] is the IL-17A binding motif as defined in claim 1 .

9. The IL-17A binding polypeptide according to claim 5 , which comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1-1216.

10. The IL-17A binding polypeptide according to claim 1 , which comprises the amino acid sequence: AEAKYAK-[BM]-DPSQSSELLSEAKKLNDSQAPK (SEQ ID NO:1259); wherein [BM] is the IL-17A binding motif as defined in claim 1 .

11. The IL-17A binding polypeptide according to claim 10 , which comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1217-1222.

12. The IL-17A binding polypeptide according to claim 1 , which binds to IL-17A with a K D value of at most 1×10 −6 M.

13. A fusion protein or conjugate comprising a first moiety consisting of the IL-17A binding polypeptide according to claim 1 ; and a second moiety consisting of a polypeptide having a desired biological activity.

14. A composition comprising the IL-17A binding polypeptide according to claim 1 or the fusion protein or conjugate according to claim 13 , and at least one pharmaceutically acceptable excipient or carrier.

15. A medicament, diagnostic agent or prognostic agent comprising the IL-17A binding polypeptide according to claim 1 or the fusion protein or conjugate according to claim 13 .

16. A complex, comprising at least one IL-17A binding polypeptide according to claim 1 or at least one fusion protein or conjugate according to claim 13 , and at least one antibody or an antigen binding fragment thereof.

17. A composition comprising complex according to claim 16 and at least one pharmaceutically acceptable excipient or carrier.

18. A medicament, diagnostic agent or prognostic agent comprising the complex according to claim 16 .

19. A polynucleotide encoding the IL-17A binding polypeptide according to claim 1 .

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