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 - 47 . (canceled)
48 . A construct comprising CR2 and a modulator of complement activity.
49 . The construct of claim 48 , wherein the construct is a fusion protein.
50 . The construct of claim 48 , wherein the modulator of complement activity comprises a complement inhibitor.
51 . The construct of claim 50 , wherein the complement inhibitor comprises the first four SCR domains of decay accelerating factor (DAF).
52 . The construct of claim 50 , wherein the complement inhibitor comprises the four SCR domains of the extracellular region of MCP.
53 . The construct of claim 50 , wherein the complement inhibitor comprises the five N-terminal SCR domains Crry.
54 . The construct of claim of claim 48 , wherein the modulator of complement activity comprises a complement activator.
55 . The construct of claim 54 , wherein the complement activator comprises human IgG1 or a fragment thereof.
56 . The construct of claim 55 , wherein the complement activator comprises IgG1 Fc.
57 . The construct of claim 54 , wherein the complement activator comprises human IgM or a fragment thereof.
58 . The construct of claim 57 , wherein the complement activator comprises IgM Fc.
59 . The construct of claim 54 , wherein the complement activator comprises mouse IgG3 or a fragment thereof.
60 . The construct of claim 59 , wherein the complement activator comprises IgG3 Fc.
61 . The construct of claim 54 , wherein the complement activator comprises CVF.
62 . The construct of claim 48 , wherein the construct is an immunoconjugate.
63 . A method of treating a condition affected by complement in a subject comprising administering to the subject the construct of claim 50 .
64 . The method of claim 63 , wherein the condition is selected from the group consisting of: a viral infection, a bacterial infection, a parasitic infection, a fungal infection, and an inflammatory condition.
65 . The method of claim 64 , wherein the subject is a human.
66 . A method of treating a condition affected by complement in a subject comprising administering to the subject the construct of claim 54 .
67 . The method of claim 66 , wherein the condition is cancer.
68 . The method of claim 67 , wherein the subject is a human.
69 . A method of reducing complement-mediated damage comprising administering to a subject the construct of claim 50 .
70 . A method of enhancing complement-mediated damage comprising administering to a subject the construct of claim 54 .