Smallpox inhibitor of complement enzymes (SPICE) protein and methods of inhibiting complement activation
AssigneesThe Trustees of the University of Pennsylvania, The University of Pittsburgh of the Commonwealth of Pennsylvania
InventorsAriella M. Rosengard, Joseph M. Ahearn
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Abstract
The invention provides a complement inhibitor derived from variola, called smallpox inhibitor of complement enzymes (SPICE) and SPICE-related proteins, such as fusion proteins. These proteins are useful in the treatment of complement-mediated conditions, such as hyperacutc rejection of xenografts.
Claims16
A SPICE-related fusion protein comprising at least one polypeptide moiety attached to at least a complement-inhibiting portion of smallpox inhibitor of complement enzymes (SPICE) protein (SEQ ID. NO:4), said portion including four short consensus repeats (SCRs) of SPICE, wherein said protein inhibits complement activation.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a protein that inhibits complement activation in an amount effective to inhibit human complement activation, wherein said protein consist of
- a) smallpox inhibitor of complement enzymes (SPICE) protein (SEQ ID NO:4),
- b) a fragment of SPICE, said fragment comprising at least a complement-inhibiting portion of SPICE, said portion including four short consensus repeats (SCRs) of SPICE, wherein said protein inhibits complement activation, and
- c) a SPICE-related fusion protein comprising at least one polypeptide moiety attached to at least a complement-inhibiting portion of SPICE protein (SEQ ID NO:4), said portion including four SCRs of SPICE.
A method of inhibiting complement activation comprising exposing complement to a protein that inhibits complement activation in an amount effective to inhibit complement activation, wherein said protein consist of
- a) smallpox inhibitor of complement enzymes (SPICE) protein (SEQ ID NO:4),
- b) a fragment of SPICE, said fragment comprising at least a complement-inhibiting portion of SPICE, said portion including four short consensus repeats (SCRs) of SPICE, wherein said protein inhibits complement activation, and
- c) a SPICE-related fusion protein comprising at least one polypeptide moiety attached to at least a complement-inhibiting portion of SPICE protein (SEQ ID NO:4), said portion including four SCRs of SPICE.
A method of inhibiting complement activation in blood in an extracorporeal blood loop, said method comprising the step of coating the surface of said blood loop that is exposed to blood with a protein that inhibits compliment activation, wherein said protein consist of
- a) smallpox inhibitor of complement enzymes (SPICE) protein (SEQ ID NO:4),
- b) a fragment of SPICE, said fragment comprising at least a complement-inhibiting portion of SPICE, said portion including four short consensus repeats (SCRs) of SPICE, wherein said protein inhibits complement activation, and
- c) a SPICE-related fusion protein comprising at least one polypeptide moiety attached to at least a complement-inhibiting portion of SPICE protein (SEQ ID NO:4), said portion including four SCRs of SPICE.
A blood product comprising at least a serum fraction of human blood and an amount of a protein that inhibits complement activation, wherein said protein consist of
- a) smallpox inhibitor of complement enzymes (SPICE) protein (SEQ ID NO:4),
- b) a fragment of SPICE, said fragment comprising at least a complement-inhibiting portion of SPICE, said portion including four short consensus repeats (SCRs) of SPICE, wherein said protein inhibits complement activation, and
- c) a SPICE-related fusion protein comprising at least one polypeptide moiety attached to at least a complement-inhibiting portion of SPICE protein (SEQ ID NO:4), said portion including four SCRs of SPICE.
A method of inhibiting complement activation in a human blood product, said method comprising the step of administering to said product a protein that inhibits complement activation, wherein the protein consist of
- a) smallpox inhibitor of complement enzymes (SPICE) protein (SEQ ID NO:4),
- b) a fragment of SPICE, said fragment comprising at least a complement-inhibiting portion of SPICE said portion including four short consensus repeats (SCRs) of SPICE, wherein said protein inhibits complement activation, and
- c) a SPICE-related fusion protein comprising at least one polypeptide moiety attached to at least a complement-inhibiting portion of SPICE protein (SEQ ID NO:4), said portion including four SCRs of SPICE.
Dependencies are inferred from the claim text.