| 摘要 |
Disclosed is a soluble composition capable of targeted delivery of a complement modulator to sites of complement system activation comprising a construct, wherein the construct comprises: (a) a complement receptor 2 (CR2) portion comprising at least the first two N-terminal short consensus repeat (SCR) domains of CR2; and (b) a complement modulator portion; wherein the CR2 portion contains at least one amino acid substitution selected from the group consisting of N11 and Y64 relative to SEQ ID NO: 2 that decreases binding affinity of the construct for EBV gp350 and/or at least one amino acid substitution selected from the group consisting of S42 and K50 relative to SEQ ID NO: 2 that decreases binding affinity of the construct for Interferon-alpha (IFNα), and wherein the construct exhibits comparable binding affinity for at least one complement component 3 (C3) proteolytic fragment as compared to a construct in which the CR2 portion does not contain the at least one amino acid substitution. Further disclosed is a method for making a construct that selectively binds to one or more C3 proteolytic fragments but does not selectively bind to EBV gp350 or IFNα, wherein the method comprises: (a) mutating one or more amino acids in a complement receptor 2 (CR2) portion of the construct at a position selected from the group consisting of: N11 and Y64 relative to SEQ ID NO: 2; and (b) mutating one or more amino acids in a complement receptor 2 (CR2) portion of the construct at a position selected from the group consisting of: S42 and K50 relative to SEQ ID NO: 2, wherein the construct comprises: (i) a complement receptor 2 (CR2) portion comprising at least the first two N-terminal SCR domains of the CR2 protein; and (ii) a complement modulator portion. |
