Complement receptor 2 targeted complement modulators
View Patent ↗Modulation of the complement system represents a therapeutic modality for numerous pathologic conditions associated with complement activation. In a strategy to prepare complement inhibitors that are targeted to sites of complement activation and disease, compositions comprising a complement inhibitor linked to complement receptor (CR) 2 are disclosed. The disclosed are compositions can be used in methods of treating pathogenic diseases and inflammatory conditions by modulating the complement system.
1. A composition comprising a construct, wherein the construct comprises:
(a) a complement receptor 2 (CR2) or a fragment thereof, wherein the fragment contains at least the first two N-terminal short consensus repeat (SCR) domains of the CR2 protein; and
(b) a modulator of complement activity, wherein the modulator comprises CD59.
2. The composition of claim 1 , wherein the construct is a fusion protein.
3. The composition of claim 1 , wherein the composition comprises SEQ ID NO. 12.
4. The composition of claim 1 , wherein the composition comprises SEQ ID NO. 8.
5. The composition of claim 1 , wherein the complement modulator is murine CD59 or human CD59.
6. The composition of claim 1 , wherein the construct is an immunoconjugate.
7. The composition of claim 2 , wherein the CR2 or a fragment thereof is fused to the N-terminus of the modulator of complement activity.
8. The composition of claim 2 , wherein the CR2 or a fragment thereof is fused to the C-terminus of the modulator of complement activity.
9. The composition of claim 1 , wherein the CR2 or a fragment thereof comprises a full-length CR2 protein.
10. The composition of claim 1 , wherein the CR2 or a fragment thereof comprises the four N-terminal SCR domains of the CR2 protein.
11. The composition of claim 1 , wherein the complement modulator comprises the extracellular region of CD59.
12. A nucleotide sequence encoding a fusion protein comprising: (a) a complement receptor 2 (CR2) or a fragment thereof, wherein the fragment contains at least the first two N-terminal short consensus repeat (SCR) domains of the CR2 protein; and (b) a modulator of complement activity, wherein the modulator comprises CD59.