# US 2019/0167760 A1 · Polypeptides binding to human complement c5

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- Number: US 2019/0167760 A1
- Document ID: US20190167760A1
- Status: Published application
- Kind: A1
- Application number: 16/228,181
- Filed: 2018-12-20
- Published: 2019-06-06
- Earliest claimed: 2012-02-20
- Assignees: Swedish Orphan Biovitrum AB (publ)
- Applicants: Swedish Orphan Biovitrum AB (publ)
- Inventors: Charlotta Berghard; Magnus Berglund; Patrik Strömberg; Malin Lindborg; Elin Gunneriusson; Joachim Feldwisch
- Web page: https://patentgrep.com/patent/US20190167760A1

## CPC

- A61K 38/164: {from bacteria}
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- A61K 47/68: the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K 47/6801: {Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent}
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/00: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K 14/195: from bacteria
- C07K 14/31: from Staphylococcus (G)
- C07K 14/315: from Streptococcus (G), e.g. Enterococci
- C07K 14/47: from mammals
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes}
- C07K 2319/00: Fusion polypeptide
- C07K 2319/31: fusions, other than Fc, for prolonged plasma life, e.g. albumin
- C07K 2319/70: containing domain for protein-protein interaction
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention relates to C5 binding polypeptides, comprising a C5 binding motif, BM, which motif consists of an amino acid sequence selected from i) EX2X3X4A X6 X7EID X11LPNL X16X17X18QW X21AFIX25X26LX28D, and ii) an amino acid sequence which has at least 86% identity to the sequence defined in i), wherein the polypeptide binds to C5. The present invention moreover relates to C5 binding polypeptides for use in therapy, such as for use in treatment of a C5 related condition, and to methods of treatment.

## Claims

### Claim 1

C5 binding polypeptide, comprising a C5 binding motif, BM, which motif consists of an amino acid sequence selected from
i) EX2X3X4A X6X7EID X11LPNL X16X17X18QW X21AFIX25
X26LX28D,
wherein, independently of each other,
X2 is selected from H, Q, S, T and V;
X3 is selected from I, L, M and V;
X4 is selected from A, D, E, H, K, L, N, Q, R, S, T and Y;
X6 is selected from N and W;
X7 is selected from A, D, E, H, N, Q, R, S and T;
X11 is selected from A, E, G, H, K, L, Q, R, S, T and Y;
X16 is selected from N and T;
X17 is selected from I, L and V;
X18 is selected from A, D, E, H, K, N, Q, R, S and T;
X21 is selected from I, L and V;
X25 is selected from D, E, G, H, N, S and T;
X26 is selected from K and S;
X28 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.

### Claim 2 (depends on 1)

C5 binding polypeptide according to claim 1, wherein X2 is selected from H, T and V.

### Claim 3 (depends on 2)

C5 binding polypeptide according to claim 2, wherein X2 is selected from T and V.

### Claim 4 (depends on 3)

C5 binding polypeptide according to claim 3, wherein X2 is V.

### Claim 5

C5 binding polypeptide according to any preceding claim, wherein X3 is selected from I, L and V.

### Claim 6 (depends on 5)

C5 binding polypeptide according to claim 5, wherein X3 is selected from I and L.

### Claim 7 (depends on 6)

C5 binding polypeptide according to claim 6, wherein X3 is I.

### Claim 8 (depends on 6)

C5 binding polypeptide according to claim 6, wherein X3 is L.

### Claim 9

C5 binding polypeptide according to any preceding claim, wherein X4 is selected from A, D, E, K, L, Q and R.

### Claim 10 (depends on 9)

C5 binding polypeptide according to claim 9, wherein X4 is selected from A, D, E, K and R.

### Claim 11 (depends on 10)

C5 binding polypeptide according to claim 10, wherein X4 is selected from D and E.

### Claim 12

C5 binding polypeptide according to any preceding claim, wherein X6 is W.

### Claim 13

C5 binding polypeptide according to any preceding claim, wherein X7 is selected from A, D, N and T.

### Claim 14 (depends on 13)

C5 binding polypeptide according to claim 13, wherein X7 is selected from D and N.

### Claim 15 (depends on 14)

C5 binding polypeptide according to claim 14, wherein X7 is D.

### Claim 16 (depends on 14)

C5 binding polypeptide according to claim 14, wherein X7 is N.

### Claim 17

C5 binding polypeptide according to any preceding claim, wherein XII is selected from A, H, K, Q, R and S.

### Claim 18 (depends on 17)

C5 binding polypeptide according to claim 17, wherein X11 is selected from A, H, K and R.

### Claim 19 (depends on 18)

C5 binding polypeptide according to claim 18, wherein X11 is selected from A, K and R.

### Claim 20 (depends on 19)

C5 binding polypeptide according to claim 19, wherein X11 is selected from K and R

### Claim 21

C5 binding polypeptide according to any preceding claim, wherein X16 is T.

### Claim 22

C5 binding polypeptide according to any preceding claim, wherein X17 is selected from I and L.

### Claim 23 (depends on 22)

C5 binding polypeptide according to claim 22, wherein X17 is I.

### Claim 24 (depends on 22)

C5 binding polypeptide according to claim 22, wherein X17 is L.

### Claim 25

C5 binding polypeptide according to any preceding claim, wherein X18 is selected from A, D, E, N, Q, S and T.

### Claim 26 (depends on 25)

C5 binding polypeptide according to claim 25, wherein X18 is selected from A, D, E, Q and S.

### Claim 27 (depends on 26)

C5 binding polypeptide according to claim 26, wherein X18 is selected from D, E and Q.

### Claim 28 (depends on 27)

C5 binding polypeptide according to claim 27, wherein X18 is selected from D and E.

### Claim 29 (depends on 28)

C5 binding polypeptide according to claim 28, wherein X18 is D.

### Claim 30 (depends on 28)

C5 binding polypeptide according to claim 28, wherein X18 is E.

### Claim 31

C5 binding polypeptide according to any preceding claim, wherein X21 is selected from I and L.

### Claim 32 (depends on 31)

C5 binding polypeptide according to claim 31, wherein X21 is I.

### Claim 33 (depends on 31)

C5 binding polypeptide according to claim 31, wherein X21 is L.

### Claim 34

C5 binding polypeptide according to any preceding claim, wherein X25 is selected from E, H, N and T.

### Claim 35 (depends on 34)

C5 binding polypeptide according to claim 34, wherein X25 is selected from E and N.

### Claim 36 (depends on 35)

C5 binding polypeptide according to claim 35, wherein X25 is N.

### Claim 37

C5 binding polypeptide according to any preceding claim, wherein X26 is K.

### Claim 38

C5 binding polypeptide according to any preceding claim, wherein X28 is selected from A, D, E, H, N, Q and S.

### Claim 39 (depends on 38)

C5 binding polypeptide according to claim 38, wherein X28 is selected from A, D, E and

### Claim 40 (depends on 39)

C5 binding polypeptide according to claim 39, wherein X28 is selected from A, D and E.

### Claim 41 (depends on 40)

C5 binding polypeptide according to claim 40, wherein X28 is selected from D and E.

### Claim 42 (depends on 41)

C5 binding polypeptide according to claim 41, wherein X28 is D.

### Claim 43 (depends on 8, 9, 10, 11)

C5 binding polypeptide according to any one of claims 8-11, wherein X3X4 is selected from LE and LD.

### Claim 44 (depends on 22, 23, 24, 25, 26, 27, 28, 29, 30)

C5 binding polypeptide according to any one of claims 22-30, wherein X17X18 is selected from IE and LD.

### Claim 45

C5 binding polypeptide according to any one of the preceding claims, wherein the amino acid i) fulfills at least four of the following eight conditions I-VIII:
I. X2 is V;
II. X3 is selected from I and L;
III. X6 is W;
IV. X7 is selected from D and N;
V. X17 is selected from I and L;
VI. X21 is L;
VII. X25 is N;
VIII. X28 is D.

### Claim 46 (depends on 45)

C5 binding polypeptide according to claim 45, wherein the amino acid sequence i) fulfills at least five of the eight conditions I-VIII.

### Claim 47 (depends on 46)

C5 binding polypeptide according to claim 46, wherein the amino acid sequence i) fulfills at least six of the eight conditions I-VIII.

### Claim 48 (depends on 47)

C5 binding polypeptide according to claim 47, wherein the amino acid sequence i) fulfills at least seven of the eight conditions I-VIII.

### Claim 49 (depends on 48)

C5 binding polypeptide according to claim 48, wherein the amino acid sequence i) fulfills all of the eight conditions I-VIII.

### Claim 50

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

### Claim 51 (depends on 50)

C5 binding polypeptide according to claim 50, 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.

### Claim 52 (depends on 51)

C5 binding polypeptide according to claim 51, wherein the amino acid sequence is selected from any one of SEQ ID NO:1-12.

### Claim 53 (depends on 52)

C5 binding polypeptide according to claim 52, wherein the amino acid sequence is selected from any one of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4 and SEQ ID NO:5.

### Claim 54 (depends on 53)

C5 binding polypeptide according to claim 53, wherein the amino acid sequence is selected from SEQ ID NO:1 and SEQ ID NO:4.

### Claim 55

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

### Claim 56 (depends on 55)

C5 binding polypeptide according to claim 55, in which said C5 binding motif essentially forms part of two alpha helices with an interconnecting loop, within said three-helix bundle protein domain.

### Claim 57 (depends on 55, 56)

C5 binding polypeptide according to claim 55 or 56, in which said three-helix bundle protein domain is selected from domains of Protein A from Staphylococcus aureus and derivatives thereof.

### Claim 58 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54)

C5 binding polypeptide according to any preceding claim, which comprises an amino acid sequence selected from:
i) K-[BM]-DPSQS XaXbLLXc EAKKL NDXdQ;
wherein
[BM] is a C5 binding motif as defined in any one of claims 1-54;
Xa is selected from A and S;
Xb is selected from N and E;
Xc is selected from A, S and C;
Xd is selected from A and S; and
ii) an amino acid sequence which has at least 79% identity to any one of the sequences defined above.

### Claim 59 (depends on 58)

C5 binding polypeptide according to claim 58, wherein Xa is A.

### Claim 60 (depends on 58)

C5 binding polypeptide according to claim 58, wherein Xa is S.

### Claim 61 (depends on 58, 59, 60)

C5 binding polypeptide according to any one of claims 58-60, wherein Xb is N.

### Claim 62 (depends on 58, 59, 60)

C5 binding polypeptide according to any one of claims 58-60, wherein Xb is E.

### Claim 63 (depends on 58, 59, 60, 61, 62)

C5 binding polypeptide according to any one of claims 58-62, wherein Xc is A.

### Claim 64 (depends on 58, 59, 60, 61, 62)

C5 binding polypeptide according to any one of claims 58-62, wherein Xc is S.

### Claim 65 (depends on 58, 59, 60, 61, 62)

C5 binding polypeptide according to any one of claims 58-62, wherein Xd is C.

### Claim 66 (depends on 58, 59, 60, 61, 62, 63, 64, 65)

C5 binding polypeptide according to any one of claims 58-65, wherein Xd is A.

### Claim 67 (depends on 58, 59, 60, 61, 62, 63, 64, 65)

C5 binding polypeptide according to any one of claims 58-65, wherein Xd is S.

### Claim 68 (depends on 58)

C5 binding polypeptide according to claim 58, wherein Xa is A; Xb is N; Xc is A and Xd is A.

### Claim 69 (depends on 58)

C5 binding polypeptide according to claim 58, wherein Xa is A; Xb is N; Xc is C and Xd is A.

### Claim 70 (depends on 58)

C5 binding polypeptide according to claim 58, wherein Xa is S; Xb is E; Xc is S and Xd is S.

### Claim 71 (depends on 58)

C5 binding polypeptide according to claim 58, wherein Xa is S; Xb is E; Xc is C and Xd is S.

### Claim 72 (depends on 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71)

C5 binding polypeptide according to any one of claims 58-71, wherein the amino acid sequence is selected from any one of SEQ ID NO:249-496.

### Claim 73 (depends on 72)

C5 binding polypeptide according to claim 72, 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.

### Claim 74 (depends on 73)

C5 binding polypeptide according to claim 73, wherein the amino acid sequence is selected from any one of SEQ ID NO:249-260.

### Claim 75 (depends on 74)

C5 binding polypeptide according to claim 74, wherein the amino acid sequence is selected from any one of SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252 and SEQ ID NO:253.

### Claim 76 (depends on 75)

C5 binding polypeptide according to claim 75, wherein the amino acid sequence is selected from any one of SEQ ID NO:249 and SEQ ID NO:252.

### Claim 77 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)

C5 binding polypeptide according to any one of claims 1-57, which comprises an amino acid sequence selected from:
i) YAK-[BM]-DPSQS SELLXc EAKKL NDSQA P;
wherein [BM] is a C5 binding motif as defined in any one of claims 1-54 and Xc is selected from S and C; and
ii) an amino acid sequence which has at least 81% identity to any one of the sequences defined above.

### Claim 78 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)

C5 binding polypeptide according to any one of claims 1-57, which comprises an amino acid sequence selected from:
i) FNK-[BM]-DPSQS ANLLXc EAKKL NDAQA P;
wherein [BM] is a C5 binding motif as defined in any one of claims 1-54 and Xc is selected from A and C; and
ii) an amino acid sequence which has at least 81% identity to any one of the sequences defined above.

### Claim 79 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)

C5 binding polypeptide according to any one of claims 1-57, wherein the amino acid sequence is selected from any one of SEQ ID NO:497-757.

### Claim 80 (depends on 79)

C5 binding polypeptide according to claim 79, 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:71 1, SEQ ID NO:739 and SEQ ID NO:746-757.

### Claim 81 (depends on 80)

C5 binding polypeptide according to claim 80, wherein the amino acid sequence is selected from any one of SEQ ID NO:497-508 and SEQ ID NO:746-757.

### Claim 82 (depends on 81)

C5 binding polypeptide according to claim 81, 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.

### Claim 83 (depends on 82)

C5 binding polypeptide according to claim 82, wherein the amino acid sequence is selected from any one of SEQ ID NO:497 and SEQ ID NO:500, SEQ ID NO:748 and SEQ ID NO:753.

### Claim 84

C5 binding polypeptide according to any preceding claim, which inhibits cleavage of C5.

### Claim 85

C5 binding polypeptide according to any preceding claim, wherein the C5 binding polypeptide binds to C5 such that the KD value of the interaction is at most 1×10−6 M, such as at most 1×10−7 M, such as at most 1×10−8 M, such as at most 1×10−9 M.

### Claim 86

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

### Claim 87

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

### Claim 88 (depends on 87)

C5 binding polypeptide according to claim 87, in which the C5 binding polypeptide monomer units are expressed as a fusion protein.

### Claim 89 (depends on 87, 88)

C5 binding polypeptide according to claim 87 or 88, in dimeric form.

### Claim 90

C5 binding compound, comprising at least one C5 binding polypeptide according to any preceding claim; 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 domain or derivative thereof to the C or N terminal of said at least one C5 binding polypeptide.

### Claim 91 (depends on 90)

C5 binding compound according to claim 90, 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.

### Claim 92 (depends on 91)

C5 binding compound according to claim 91, having a structure selected from
[CBP1]-[L1]-[ALBD];
[CBP1]-[CBP2]-[L1]-[ALBD]; and
[CBP1]-[L1]-[ALBD]-[L2]-[CBP2].

### Claim 93 (depends on 91)

C5 binding compound according to claim 91, wherein the linking moiety is selected from G, GS; [G2S]n; [G3S]n; [G4S]n; GS[G4S]n, wherein n is 0-7; [S2G]m; [S3G]m;[S4G]m;
wherein m is 0-7, and VDGS.

### Claim 94 (depends on 93)

C5 binding compound according to claim 93, wherein the linking moiety is selected from GS and GS[G4S]2.

### Claim 95 (depends on 90, 91, 92, 93, 94)

C5 binding compound according to any one of claims 90-94, wherein said albumin-binding domain is as set out in SEQ ID NO:759.

### Claim 96 (depends on 79, 80, 81, 82, 83, 90, 91, 92, 93, 94, 95)

C5 binding compound according to any one of claims 90-95, wherein each of said C5 binding polypeptides is independently selected from a polypeptide as defined in any one of claims 79-83.

### Claim 97 (depends on 83, 96)

C5 binding compound according to claim 96, wherein each of said C5 binding polypeptides is independently selected from a polypeptide as defined in claim 83.

### Claim 98 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97)

Polynucleotide encoding a polypeptide according to any one of claims 1-89 or a compound according to any one of claims 90-97.

### Claim 99 (depends on 98)

Expression vector comprising a polynucleotide according to claim 98.

### Claim 100 (depends on 99)

Host cell comprising an expression vector according to claim 99.

### Claim 101 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97)

Combination of a C5 binding polypeptide according to any one of claims 1-89 or a C5 binding compound according to any one of claims 90-97 with a therapeutic agent.

### Claim 102 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 101)

C5 binding polypeptide according to any one of claims 1-89, C5 binding compound according to any one of claims 90-97 or combination according to claim 101 for use in therapy.

### Claim 103 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 101)

C5 binding polypeptide according to any one of claims 1-89, C5 binding compound according to any one of claims 90-97 or combination according to claim 101 for treatment of a C5 related condition.

### Claim 104 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 101)

C5 binding polypeptide according to any one of claims 1-89, C5 binding compound according to any one of claims 90-97 or combination according to claim 101 for treatment of a C5 related condition 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.

### Claim 105 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 101)

C5 binding polypeptide according to any one of claims 1-89, C5 binding compound according to any one of claims 90-97 or combination according to claim 101 for treatment of paroxysmal nocturnal hemoglobinuria (PNH).

### Claim 106 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 101)

Method of treatment of a C5 related condition, comprising administering a C5 binding polypeptide according to any one of claims 1-89, C5 binding compound according to any one of claims 90-97 or combination according to claim 101 to a mammalian subject in need thereof.

### Claim 107 (depends on 106)

Method of treatment according to claim 106, in which binding of the C5 binding polypeptide, the C5 binding compound or the combination to C5 inhibits cleavage of C5.

### Claim 108 (depends on 106, 107)

Method of treatment according to claim 106 or 107, 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.

### Claim 109 (depends on 108)

Method of treatment according to claim 108, wherein said C5 related condition is paroxysmal nocturnal hemoglobinuria (PNH).

### Claim 110 (depends on 106, 107, 108, 109)

Method of treatment according to any one of claims 106 to 109, wherein the said C5 binding polypeptide is administered intravenously, subcutaneously, by inhalation, nasally, orally, intravitreally, or topically.