Abstract: Disclosed are chimeric proteins that are useful for inhibiting complement. The chimeric protein termed VCPFc is a fusion protein in which (i) an immunoglobulin Fc region is fused to (ii) a polypeptide that comprises a portion of a vaccinia virus complement control protein which binds complement components C4b and C3b, but not iC3b rosettes. This protein can be used in xenograft transplantation methods (e.g., by treating the donor mammal or organ) and in methods for treating complement-mediated disorders (e.g., inflammation) generally. In a second chimeric protein, a transmembrane anchoring domain is fused to a polypeptide that comprises a portion of a vaccinia virus complement control protein which binds complement components C4b and C3b, but not iC3b rosettes. The transmembrane anchoring domain can be, for example, short consensus regions 3 through 15 of human complement receptor 2 protein.

Abstract: Disclosed are chimeric proteins that are useful for inhibiting complement. The chimeric protein termed VCPFc is a fusion protein in which (i) an immunoglobulin Fc region is fused to (ii) a polypeptide that comprises a portion of a vaccinia virus complement control protein which binds complement components C4b and C3b, but not iC3b rosettes. This protein can be use in xenograft transplantation methods (e.g., by treating the donor mammal or organ) and in methods for treating complement-mediated disorders (e.g., inflammation) generally. In a second chimeric protein, a transmembrane anchoring domain is fused to a polypeptide that comprises a portion of a vaccinia virus complement control protein which binds complement components C4b and C3b, but not iC3b rosettes. The transmembrane anchoring domain can be, for example, short consensus regions 3 through 15 of human complement receptor 2 protein.

Abstract: Interference with formation of the complement-based membrane attack complex (MAC) will mitigate or even prevent tissue injury associated with the effects of complement in inflammation and graft rejection. Passive treatment of xenograft recipients at the time of and after transplantation with antibody against C-6, which interrupts the sequence of binding steps that form MAC, has been observed to suppress hyperacute xenograft rejection with no adverse signs or symptoms in the xenograft recipient. The present invention provides a method for interfering with MAC formation in transplant recipients, by administering compounds which interrupt one or more of the binding reactions between C5b and C6-C9, so that the MAC cannot form.