Polypeptides for complement inhibition
AssigneesAffilogic, Apellis Pharmaceuticals, Inc.
InventorsMathieu Cinier, Anne Chevrel, Olivier Kitten, Lukas Scheibler
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Abstract
Proteins comprising a C3 and/or C3b binding polypeptide and a VEGF inhibitor, and their use in treating complement-mediated disorders, are described.
Claims40
A protein comprising (i) a C3 and/or C3b binding polypeptide and (ii) a VEGF inhibitor, wherein the amino acid sequence of the C3 and/or C3b binding polypeptide has between 4 and 22 substitutions as compared to the Sac7d family consensus sequence of SEQ ID NO:
- 16, wherein the amino acid sequence of the C3 and/or C3b binding polypeptide comprises amino acids 2-60 of SEQ ID NO:
- 77, wherein X at positions 2, 3, 4, 6, 15, 17, 18, 31, 37-39, 57, 58, 59 and 61-68 are as set forth below:
- Position
- Amino Acid
- (2) . . . (2)
- X is V, A or T
- (3) . . . (3)
- X is T or K
- (4) . . . (4)
- X is - or K
- (6) . . . (6)
- X is R or K
- (15) . . . (15)
- X is E or Q
- (17) . . . (17)
- X is D or E
- (18) . . . (18)
- X is T or I
- (31) . . . (31)
- X is V or I
- (37) . . . (39)
- X X X is EGG, DN- or DQ-
- (57) . . . (57)
- X is M or L
- (58) . . . (58)
- X is Q, D or E
- (59) . . . (59)
- X is M, K, or L
- (61) . . . (68)
- XXXXXXXX is -------K,
- EKS--GKK (SEQ ID NO:
- 82),
- EK---QKK (SEQ ID NO:
- 83),
- ARAEREKK (SEQ ID NO:
- 79),
- ARAERE-K (SEQ ID NO:
- 81),
- ARAERE-- (SEQ ID NO:
- 80),
- ARA-EKKK (SEQ ID NO:
- 84),
- E-----KK, ACAEREKK (SEQ
- ID NO:
- 85) or ACA-EKKK
- (SEQ ID NO:
- 86)
- and wherein SEQ ID NO:
- 77 comprises Y at position 25, W at position 44, and at least one of the following:
- E, A, or D at position 8;
- A at position 9;
- T at position 10;
- Y, A, or S at position 22;
- Q, N, or A at position 23;
- S, V, or T at position 27;
- E or D at position 30;
- A, I, L, V, Y, M, F or H at position 32;
- A, T or S at position 34;
- T or I at position 42;
- A, I, L, V, Y, M, F or H at position 46;
- and
- S at position 48.
-25. (canceled)
-29. (canceled)
-36. (canceled)
A protein comprising (i) a C3 and/or C3b binding polypeptide and (ii) a VEGF inhibitor, wherein the C3 and/or C3b binding polypeptide comprises amino acids 2-58 of the sequence MVKVKFXXXGEEKEVXTSKIXXVXRXGKXVXFTYDDXGKXGXGXVXEKDAPKELLD MLARAEREKK (SEQ ID NO:
- 65), wherein each X independently represents any amino acid, and wherein SEQ ID NO:
- 65 comprises:
- (i) D or E at position 16;
- (ii) E or Q at position 37;
- and
- (iii) Y at position 24, W at position 42, or both.
-58. (canceled)
-62. (canceled)
-66. (canceled)
-70. (canceled)
(canceled)
A protein comprising (i) a C3 and/or C3b binding polypeptide comprising amino acids 2-58 of any one of SEQ ID NOs:
- 22, 23, or 24,
- wherein the amino acid sequence comprises D or A at position 7, A at position 8, T at position 9, S or A at position 21, A or N at position 22, Y at position 24, T or V at position 26, D at position 29, L at position 31, S at position 33, I at position 40, W at position 42, Y at position 44, and S at position 46 and (ii) a VEGF inhibitor.
-81. (canceled)
-86. (canceled)
-94. (canceled)
-98. (canceled)
-117. (canceled)
-136. (canceled)
Dependencies are inferred from the claim text.