Stable polypeptides binding to human complement C5

1. A polypeptide capable of binding human complement component 5 (C5), said polypeptide comprising the amino acid sequence

(SEQ ID NO: 289)

[BM]-[L2]-QSX 42 X 43 LLX 46 EAKKLX 2 X 3 X 54 Q

wherein, independently of each other, [BM] is a C5 binding motif comprising the amino acid sequence

(SEQ ID NO: 292)

EX 9 X 10 X 11 AX 13 X 14 EIDX 18 LPNLX 23 X 24 X 25

QWX 28 AFIX 32 X 33 LX 35 ;

wherein, independently of each other,

X 9 is selected from H, Q, S, T and V;

X 10 is selected from I, L, M and V;

X 11 is selected from A, D, E, H, K, L, N, Q, R, S, T and Y;

X 13 is selected from N and W; X 14 is selected from A, D, E, H, N, Q, R, S and T;

X 18 is selected from A, E, G, H, K, L, Q, R, S, T and Y;

X 23 is selected from N and T;

X 24 is selected from I, L and V;

X 25 is selected from A, D, E, H, K, N, Q, R, S and T;

X 28 is selected from I, L and V; X 32 is selected from D, E, G, H, N, S and T;

X 33 is selected from K and S; and X 35 is selected from A, D, E, H, N, Q, S, T and Y; and

[L2] is selected from DDPS and RQPE;

X 42 is selected from A and S;

X 43 is selected from N and E;

X 46 is selected from A, S and C;

X 52 is selected from E, N and S;

X 53 is selected from D, E and S,

provided that X 53 is not D when X 52 is N; and X 54 is selected from A and S.

2. The polypeptide according to claim 1 , said polypeptide comprising the amino acid sequence

(SEQ ID NO: 290)

AEAKYAK-[BM]-[L2]-QSX 42 X 43 LLX 46 EAKKLX 2 X 53 X 54 QAP

wherein, independently of each other, [BM], [L2], X 42 , X 43 , X 46 , X 52 , X 53 and X 54 are as defined in claim 1 .

3. The polypeptide according to claim 1 , wherein X 52 and X 53 are independently selected from E and S.

4. The polypeptide according to claim 3 , wherein (a) X 52 is S and X 53 is E, or (b) X 52 is E and X 53 is S.

5. The polypeptide according to claim 1 , wherein X 52 is S and X 53 is D.

6. The polypeptide according to claim 1 , wherein X 52 is N and X 53 is E.

7. The polypeptide according to claim 1 comprising the amino acid sequence

(SEQ ID NO: 294)

AEAKYAKEX 9 X 10 X 11 AX 13 X 14 EIDX 18 LPNLX 23 X 24 X 25 QWX 28

AFIX 32 X 33 LX 35 -[L2]-QSX 42 X 43 LLX 46 EAKKLX 52 X 53 X 54 QAP;

wherein, independently of each other,

X 9 is selected from H, Q, S, T and V;

X 10 is selected from I, L, M and V;

X 11 is selected from A, D, E, H, K, L, N, Q, R, S, T and Y;

X 13 is selected from N and W;

X 14 is selected from A, D, E, H, N, Q, R, S and T;

X 18 is selected from A, E, G, H, K, L, Q, R, S, T and Y;

X 23 is selected from N and T;

X 24 is selected from I, L and V;

X 25 is selected from A, D, E, H, K, N, Q, R, S and T;

X 28 is selected from I, L and V;

X 32 is selected from D, E, G, H, N, S and T;

X 33 is selected from K and S;

X 35 is selected from A, D, E, H, N, Q, S, T and Y;

[L2] is selected from DDPS and RQPE;

X 42 is selected from A and S;

X 43 is selected from N and E;

X 46 is selected from A, S and C;

X 52 is selected from E, N and S;

X 53 is selected from D, E and S, provided that X 53 is not D when X 52 is N; and X 54 is selected from A and S.

8. The polypeptide according to claim 1 , wherein at least one of the following conditions is fulfilled:

X 9 is V,

X 10 is L,

X 11 is E,

X 13 is W,

X 14 is D,

X 18 is R,

X 23 is T,

X 24 is I,

X 25 is E,

X 28 is L,

X 32 is N,

X 33 is K,

X 35 is D,

[L2] is DDPS,

X 42 is S,

X 43 is E,

X 46 is S,

X 54 is S.

9. The polypeptide according to claim 1 , wherein [BM] comprises the amino acid sequence selected from the group consisting of positions 1-28 in SEQ ID NOS: 1-248.

10. The polypeptide according to claim 9 , wherein [BM] comprises the amino acid sequence shown as positions 1-28 in SEQ ID NO: 1.

11. The polypeptide according to claim 1 , selected from a polypeptide comprising the amino sequence shown as SEQ ID NO: 260, SEQ ID NO: 265, SEQ ID NO: 266, or SEQ ID NO: 267.

12. A compound capable of binding C5, said compound comprising:

a) at least one C5 binding polypeptide, said polypeptide comprising the amino acid sequence

(SEQ ID NO: 296)

[BM]-[L2]-QSX 42 X 43 LLX 46 EAKKLX 52 X 53 X 54 Q

wherein, independently of each other, [BM] is a CS binding motif comprising the amino acid sequence

(SEQ ID NO: 292)

EX 9 X 10 X 11 AX 13 X 14 EIDX 18 LPNLX 23 X 24 X 25

QWX 28 AFIX 32 X 33 LX 35 ;

wherein, independently of each other,

X 9 is selected from H, Q, S, T and V;

X 10 is selected from I, L, M and V;

X 11 is selected from A, D, E, H, K, L, N, Q, R, S, T and Y;

X 13 is selected from N and W;

X 14 is selected from A, D, E, H, N, Q, R, S and T;

X 18 is selected from A, E, G, H, K, L, Q, R, S, T and Y;

X 23 is selected from N and T;

X 24 is selected from I, L and V;

X 25 is selected from A, D, E, H, K, N, Q, R, S and T;

X 28 is selected from I, L and V;

X 32 is selected from D, E, G, H, N, S and T;

X 33 is selected from K and S; and

X 35 is selected from A, D, E, H, N, Q, S, T and Y;

[L2] is selected from DDPS and RQPE;

X 42 is selected from A and S;

X 43 is selected from N and E;

X 46 is selected from A, S and C;

X 52 is selected from E, N and S;

X 53 is selected from D, E and S;

X 54 is selected from A and S;

b) at least one albumin binding domain of streptococcal protein G; and

c) at least one linking moiety for linking said at least one albumin binding domain to the C or N terminal of said at least one C5 binding polypeptide; wherein the linking moiety comprises KVEGS (SEQ ID NO:297) or KVAGS (SEQ ID NO:298); or wherein said linking moiety is absent.

13. A compound capable of binding C5, said compound comprising:

a) at least one C5 binding polypeptide, said polypeptide comprising the amino acid sequence

(SEQ ID NO: 296)

[BM]-[L2]-QSX 42 X 43 LLX 46 EAKKLX 52 X 53 X 54 Q

wherein, independently of each other,

[BM] is a C5 binding motif comprising the amino acid sequence

(SEQ ID NO: 292)

EX 9 X 10 X 11 AX 13 X 14 EIDX 18 LPNLX 23 X 24 X 25

QWX 28 AFIX 32 X 33 LX 35 ;

wherein, independently of each other,

X 9 is selected from H, Q, S, T and V;

X 10 is selected from I, L, M and V;

X 11 is selected from A, D, E, H, K, L, N, Q, R, S, T and Y;

X 13 is selected from N and W;

X 14 is selected from A, D, E, H, N, Q, R, S and T;

X 15 is selected from A, E, G, H, K, L, Q, R, S, T and Y;

X 23 is selected from N and T;

X 24 is selected from I, L and V;

X 25 is selected from A, D, E, H, K, N, Q, R, S and T;

X 28 is selected from I, L and V;

X 32 is selected from D, E, G, H, N, S and T;

X 33 is selected from K and S; and

X 35 is selected from A, D, E, H, N, Q, S, T and Y; and

[L2] is RQPE;

X 42 is selected from A and S;

X 43 is selected from N and E;

X 46 is selected from A, S and C;

X 52 is selected from E, N and S;

X 53 is selected from D, E and S;

X 54 is selected from A and S;

b) at least one albumin binding domain of streptococcal protein G; and

c) optionally, at least one linking moiety for linking said at least one albumin binding domain to the C or N terminal of said at least one C5 binding polypeptide.

14. The polypeptide according to claim 7 , wherein at least one of the following conditions is fulfilled:

X 9 is V,

X 10 is L,

X 11 is E,

X 13 is W,

X 14 is D,

X 15 is R,

X 23 is T,

X 24 is I,

X 25 is E,

X 28 is L,

X 32 is N,

X 33 is K,

X 35 is D,

[L2] is DDPS,

X 42 is S,

X 43 is E,

X 46 is S,

X 54 is S.