Center for Technology Commercialization

Muteins of the C5a Anaphylatoxin and Their Pharmaceutical Uses

(CHMC Ref. Id: 2004-0806)

Overview:

The complement system is a central part of innate immunity that is critical to inflammation and host defense. Systemic activation or activation of complement factor C5 in tissues results in the generation of the C5a anaphylatoxin. Dr. Joerg Koehl has discovered a C5a receptor antagonist (C5aRA), wherein the amino acid residue normally residing at position 69 is mutated, which binds C5aR/C5L2 with high affinity, but lacks the ability to activate these receptors. The C5aRA is a potent inhibitor of C5aR-mediated functions both in vitro and in vivo (murine and swine models) and has been shown to block immune complex-mediated inflammation in the lung, skin and peritoneum, protect from the development of intestinal and renal schemia/reperfusion injury, and markedly reduce T cell recruitment in contact allergy. One preferred C5aRA comprises 70-73 amino acids, an Arg, Cys, Tyr, or Ser at C-terminums, Ala substitution at position 27, and Arg at position 69.

It has also been shown that C5aRA improves graft and recipient survival and structural integrity of the graft, and reduces graft inflammation during cold ischemia in the cogenic kidney transplant model.

A method for making commercial size quantities of the C5aRA has also been developed.

Applications:

Therapy to treat inflammatory conditions such as polymicrobial sepsis, immune complex disease (SLE), rheumatoid arthritis, allergic asthma, DTH-responses and ischemia/reperfusion injury
Organ transplant preservation solutions
Research tool

Advantages: