COMPLEMENT RECEPTOR 2 TARGETED COMPLEMENT MODULATORS
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 - 29 . (canceled)
30 . A method of treating a condition affected by complement in a subject comprising administering to the subject a composition comprising a construct, wherein the construct comprises:
(a) a CR2 or a fragment thereof, wherein the fragment comprises at least the first two N-terminal short consensus repeat (SCR) domains of the CR2 protein; and
(b) a modulator of compliment activity, wherein the modulator comprises CD59.
31 . The method of claim 30 , wherein the condition is a cancer.
32 . (canceled)
33 . The method of claim 30 , wherein the condition is selected from the group consisting of a viral infection, a bacterial infection, a parasitic infection, and a fungal infection.
34 - 40 . (canceled)
41 . The method of claim 30 , wherein the condition is an inflammatory condition.
42 - 55 . (canceled)
56 . A method of treating an inflammatory condition in a subject by administering to the subject a composition comprising a construct, wherein the construct comprises:
(a) a 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 compliment activity, wherein the modulator comprises CD59.
57 . The method of claim 56 , wherein the inflammatory condition is stroke.
58 . The method of claim 56 , wherein the inflammatory condition is ischemia reperfusion injury.
59 - 82 . (canceled)
83 . The method of claim 30 , wherein the construct is a fusion protein.
84 . The method of claim 30 , wherein the composition comprises SEQ ID NO:12.
85 . The method of claim 30 , wherein the composition comprises SEQ ID NO:8
86 . The method of claim 30 , wherein the complement modulator is murine CD59 or human CD59.
87 . The method of claim 30 , wherein the construct is an immunoconjugate.
88 . The method of claim 83 , wherein the CR2 or a fragment thereof is fused to the N-terminus of CD59.
89 . The method of claim 83 , wherein the CR2 or a fragment thereof is fused to the C-terminus of CD59.
90 . The method of claim 30 , wherein the CR2 or a fragment thereof comprises a full-length CR2 protein.
91 . The method of claim 30 , wherein the CR2 or a fragment thereof comprises the four N-terminal SCR domains of the CR2 protein.
92 . The method of claim 30 , wherein the complement modulator comprises the extracellular region of CD59.
93 . The method of claim 56 , wherein the construct is a fusion protein.
94 . The method of claim 56 , wherein the composition comprises SEQ ID NO:12.
95 . The method of claim 56 , wherein the composition comprises SEQ ID NO:8
96 . The method of claim 56 , wherein the complement modulator is murine CD59 or human CD59.
97 . The method of claim 56 , wherein the construct is an immunoconjugate.
98 . The method of claim 93 , wherein the CR2 or a fragment thereof is fused to the N-terminus of CD59.
99 . The method of claim 93 , wherein the CR2 or a fragment thereof is fused to the C-terminus of CD59.
100 . The method of claim 56 , wherein the CR2 or a fragment thereof comprises a full-length CR2 protein.
101 . The method of claim 56 , wherein the CR2 or a fragment thereof comprises the four N-terminal SCR domains of the CR2 protein.
102 . The method of claim 56 , wherein the complement modulator comprises the extracellular region of CD59.