Polypeptides binding to human complement C5

1. A C5 binding polypeptide, comprising a C5 binding motif, BM, which motif consists of an amino acid sequence selected from

i)

(SEQ ID NO: 763)

EX 2 X 3 X 4 A X 6 X 7 EID X 11 LPNL X 16 X 17 X 18 QW X 21 AFIX 25  X 26 LX 28 D, 

wherein, independently of each other,

X 2 is selected from H, Q, S, T and V;

X 3 is selected from I, L, M and V;

X 4 is selected from A, D, E, H, K, L, N, Q, R, S, T and Y;

X 6 is selected from N and W;

X 7 is selected from A, D, E, H, N, Q, R, S and T;

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

X 16 is selected from N and T;

X 17 is selected from I, L and V;

X 18 is selected from A, D, E, H, K, N, Q, R, S and T;

X 21 is selected from I, L and V;

X 25 is selected from D, E, G, H, N, S and T;

X 26 is selected from K and S;

X 28 is selected from A, D, E, H, N, Q, S, T and Y;

and

ii) an amino acid sequence which has at least 86% identity to the sequence defined in i), wherein the polypeptide binds to C5.

2. A C5 binding polypeptide according to claim 1 , wherein the amino acid sequence i) fulfills at least four of the following eight conditions I-VIII:

I. X 2 is V;

II. X 3 is selected from I and L;

III. X 6 is

IV. X 7 is selected from D and N;

V. X 17 is selected from I and L;

VI. X 21 is L;

VII. X 25 is N;

VIII. X 28 is D.

3. The C5 binding polypeptide according to claim 1 , wherein the amino acid sequence is selected from any one of SEQ ID NO:1-248.

4. The C5 binding polypeptide according to claim 3 , wherein the amino acid sequence is selected from any one of SEQ ID NO:1-12, SEQ ID NO:20, SEQ ID NO:23-24, SEQ ID NO:26-28, SEQ ID NO:32-35, SEQ ID NO:38-39, SEQ ID NO:41, SEQ ID NO:46, SEQ ID NO:49, SEQ ID NO:56-57, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:78-79, SEQ ID NO:87, SEQ ID NO:92, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:119, SEQ ID NO:125, SEQ ID NO:141, SEQ ID NO:151, SEQ ID NO:161, SEQ ID NO:166, SEQ ID NO:187, SEQ ID NO:197, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:215 and SEQ ID NO:243.

5. The C5 binding polypeptide according to claim 4 , wherein the amino acid sequence is selected from any one of SEQ ID NO:1-12.

6. The C5 binding polypeptide according to claim 1 , in which said C5 binding motif forms part of a three-helix bundle protein domain.

7. A C5 binding polypeptide, which comprises the amino acid sequence:

(SEQ ID NO: 764)

K-[ BM ]-DPSQS X a X b LLX c  EAKKL NDX d Q; 

or an amino acid sequence which has at least 79% identity to SEQ ID NO: 764,

wherein

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 A and S; and

wherein [BM] is a C5 binding motif, which motif consists of the amino acid sequence EX 2 X 3 X 4 A X 6 X 7 EID X 11 LPNL X 16 X 17 X 18 QW X 21 AFIX 25 X 26 LX 28 D (SEQ ID NO: 763), or an amino acid sequence which has at least 86% identity to SEQ ID NO:763,

wherein independently of each other:

X 2 is selected from H, Q, S, T and V;

X 3 is selected from I, L, M and V;

X 4 is selected from A, D, E, H, K, L, N, Q, R, S, T and Y;

X 6 is selected from N and W;

X 7 is selected from A, D, E, H, N, Q, R, S and T;

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

X 16 is selected from N and T;

X 17 is selected from I, L and V;

X 18 is selected from A, D, E, H, K, N, Q, R, S and T;

X 21 is selected from I, L and V;

X 25 is selected from D, E, G, H, N, S and T;

X 26 is selected from K and S;

X 28 is selected from A, D, E, H, N, Q, S, T and Y; and

wherein the [BM] motif binds to C5.

8. The C5 binding polypeptide according to claim 7 , wherein the amino acid sequence is selected from any one of SEQ ID NO:249-496.

9. The C5 binding polypeptide according to claim 8 , wherein the amino acid sequence is selected from any one of SEQ ID NO:249-260, SEQ ID NO:268, SEQ ID NO:271-272, SEQ ID NO:274-276, SEQ ID NO:280-283, SEQ ID NO:286-287, SEQ ID NO:289, SEQ ID NO:294, SEQ ID NO:297, SEQ ID NO:304-305, SEQ ID NO:307, SEQ ID NO:314, SEQ ID NO:326-327, SEQ ID NO:335, SEQ ID NO:340, SEQ ID NO:354, SEQ ID NO:358, SEQ ID NO:367, SEQ ID NO:373, SEQ ID NO:389, SEQ ID NO:399, SEQ ID NO:409, SEQ ID NO:414, SEQ ID NO:435, SEQ ID NO:445, SEQ ID NO:451, SEQ ID NO:453, SEQ ID NO:463 and SEQ ID NO:491.

10. The C5 binding polypeptide according to claim 9 , wherein the amino acid sequence is selected from any one of SEQ ID NO:249-260.

11. The C5 binding polypeptide according to claim 10 , wherein the amino acid sequence is selected from any one of SEQ ID NO:497-757.

12. The C5 binding polypeptide according to claim 11 , wherein the amino acid sequence is selected from any one of SEQ ID NO:497-508, SEQ ID NO:516, SEQ ID NO:519-520, SEQ ID NO:522-524, SEQ ID NO:528-531, SEQ ID NO:534-535, SEQ ID NO:537, SEQ ID NO:542, SEQ ID NO:545, SEQ ID NO:552-553, SEQ ID NO:555, SEQ ID NO:562, SEQ ID NO:574-575, SEQ ID NO:583, SEQ ID NO:588, SEQ ID NO:602, SEQ ID NO:606, SEQ ID NO:615, SEQ ID NO:621, SEQ ID NO:637, SEQ ID NO:647, SEQ ID NO:657, SEQ ID NO:662, SEQ ID NO:683, SEQ ID NO:693, SEQ ID NO:699, SEQ ID NO:701, SEQ ID NO:711, SEQ ID NO:739 and SEQ ID NO:746-757.

13. The C5 binding polypeptide according to claim 12 , wherein the amino acid sequence is selected from any one of SEQ ID NO:497-508 and SEQ ID NO:746-757.

14. The C5 binding polypeptide according to claim 13 , wherein the amino acid sequence is selected from any one of SEQ ID NO:497, SEQ ID NO:498, SEQ ID NO:499, SEQ ID NO:500, SEQ ID NO:501, SEQ ID NO:746, SEQ ID NO:747, SEQ ID NO:748, SEQ ID NO:750 and SEQ ID NO:753.

15. The C5 binding polypeptide according to claim 1 , which inhibits cleavage of C5.

16. The C5 binding polypeptide according to claim 1 , wherein the C5 binding polypeptide binds to C5 such that the K D value of the interaction is at most 1×10 −6 M.

17. The C5 binding polypeptide according to claim 1 , comprising further C terminal and/or N terminal amino acids that improve production, purification, stabilization in vivo or in vitro, coupling, or detection of the polypeptide.

18. The C5 binding polypeptide according to claim 1 , wherein the polypeptide is in multimeric form, comprising at least two C5 binding polypeptide monomer units, the amino acid sequences of which may be the same or different.

19. A C5 binding compound, comprising at least one C5 binding polypeptide according to claim 1 ; at least one albumin binding domain of streptococcal protein G, or a derivative thereof; and at least one linking moiety for linking said at least one albumin binding domain or derivative thereof to the C or N terminal of said at least one C5 binding polypeptide.

20. The C5 binding compound according to claim 19 , having a structure selected from

[CBP1]-[L1]-[ALBD];

[CBP1]-[CBP2]-[L1]-[ALBD];

[CBP1]-[L1]-[ALBD]-[L2]-[CBP2];

[ALBD]-[L1]-[CBP1];

[ALBD]-[L1]-[CBP1]-[CBP2];

[CBP1]-[L1]-[CBP2]-[L2]-[ALBD]; and

[ALBD]-[L1]-[CBP1]-[L2]-[CBP2]

wherein, independently of each other,

[CBP1] and [CBP2] are C5 binding polypeptides which may be the same or different;

[L1] and [L2] are linking moieties which may be the same or different; and

[ALBD] is an albumin binding domain of streptococcal protein G, or derivative thereof.

21. The C5 binding compound according to claim 20 , wherein the linking moiety is selected from G; GS; [G 2 S] n ; [G 3 S] n (SEQ ID NO:783); [G 4 S] n (SEQ ID NO:784); GS[G 4 S] n (SEQ ID NO:785); [S 2 G] m ; [S 3 G] m (SEQ ID NO:786); [S 4 G] m (SEQ ID NO:787); and VDGS (SEQ ID NO:788);

wherein n is 0-7; and

wherein m is 0-7.

22. The C5 binding compound according to claim 19 , wherein said albumin binding domain is as set out in SEQ ID NO:759.

23. The C5 binding compound according to claim 19 , wherein each of said C5 binding polypeptides is independently selected from any one of SEQ ID NO:497-757.

24. A polynucleotide encoding a polypeptide according to claim 1 .

25. A polynucleotide encoding a compound according to claim 19 .

26. A combination of a C5 binding polypeptide according to claim 1 with a therapeutic agent.

27. A combination of a C5 binding compound according to claim 19 with a therapeutic agent.

28. A method of treatment of a C5 related condition, comprising administering a C5 binding polypeptide according to claim 1 , a C5 binding compound according to claim 19 , or the combination according to claim 26 , to a mammalian subject in need thereof.

29. The method of treatment according to claim 28 , in which binding of the C5 binding polypeptide, the C5 binding compound or the combination to C5 inhibits cleavage of C5.

30. The method of treatment according to claim 28 , wherein said C5 related condition is selected from inflammatory disease; autoimmune disease; infectious disease; cardiovascular disease; neurodegenerative disorders; cancer; graft injury; wounds; eye disease; kidney disease; pulmonary diseases; hematological diseases; allergic diseases and dermatological diseases.

31. The method of treatment according to claim 30 , wherein said C5 related condition is paroxysmal nocturnal hemoglobinuria (PNH).

32. The method of treatment according to claim 28 , wherein said C5 binding polypeptide is administered intravenously, subcutaneously, by inhalation, nasally, orally, intravitreally, or topically.

33. The C5 binding polypeptide according to claim 1 , wherein the C5 binding polypeptide binds to C5 such that the K D value of the interaction is at most 1×10 −7 M.

34. The C5 binding polypeptide according to claim 1 , wherein the C5 binding polypeptide binds to C5 such that the K D value of the interaction is at most 1×10 −8 M.

35. The C5 binding polypeptide according to claim 1 , wherein the C5 binding polypeptide binds to C5 such that the K D value of the interaction is at most 1×10 −9 M.