Down-regulation resistant C3 convertase
AssigneeImutran Limited
InventorsTimothy Charles Farries, Richard Alexander Harrison
Life of this patent
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Abstract
Native complement pathway proteins modified such that the protein is capable of forming a down-regulation resistant C3 convertase. Preferably the modified protein is a modified human C3 protein. DNA sequences encoding such proteins are also provided, together with DNA constructs. Conjugates comprising such proteins and a specific binding moiety, for example an antibody, are also described, as are uses of such proteins and/or conjugates in therapy.
Claims27
A modified human C3 protein which is capable of forming a stable C3 convertase wherein said modified protein is selected from the group consisting of:
- (a) a C3 protein comprising one or more mutations in the region defined by amino acid residues 992-1005 of native human C3 (SEQ. ID. NO:22), whereby the C3b and C31 products, or their derived C3 convertases, are resistant to the complement inhibitory activity of Factor H;
- (b) a C3 protein comprising one or more mutations in the region defined by amino acid residues 1546-1663 of native human C3 (SEQ. ID. NO:22), said protein having reduced susceptibility to Factor H and/or Factor I, relative to native human C3;
- (c) a C3 protein comprising one or more mutations at amino acid residues 954 and/or 955 of native human C3 (SEQ. ID. NO:22), said protein having reduced susceptibility to cofactor-dependent Factor I-mediated cleavage at this position;
- and
- (d) a C3 protein comprising mutations in native human C3 (SEQ. ID. NO:22) selected from any combination of the mutations specified in (a), (b), and (c).
Dependencies are inferred from the claim text.