Down-regulation resistant C3 convertase
AssigneeImutran Limited
InventorsTimothy C. Farries, Richard A. 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.
Claims50
A native complement pathway protein modified such that the protein is capable of forming a down-regulation resistant C3 convertase.
A protein according to any preceding claim which has reduced susceptibility to Factor H and/or Factor I relative to native human C3, said protein having one or more amino acid changes relative to native human C3 in the region corresponding to amino residues 752-754 and/or residues 758-780 of native human C3.
A protein according to any preceding claim having amino acid changes relative to native human C3 at amino acid residues corresponding to residues 1427, 1431 and/or 1433 of native human C3.
A protein according to any preceding claim which includes one or more mutations relative to amino acid residues 992-1005 (EDAVDAERLKHLIV) of human C3, such that the C3b and C3i products, or their derived C3 convertases, are resistant to the complement inhibitory activity of Factor H.
A protein according to any preceding claim which includes one or more mutations relative to amino acid residues 1152-1155 (QEAK) of human C3, such that the C3b and C3i products, or their derived C3 convertases, are resistant to the complement inhibitory activity of Factor H.
A protein according to any preceding claim which has one or more amino acid deletions, substitutions or insertions relative to amino acids 1546-1663 of native human C3;
- wherein said protein has reduced susceptibility to Factor H and/or Factor I, relative to native human C3.
A protein according to any preceding claim which has one or more amino acid deletions substitutions or insertions relative to amino acid residues 954 and/or 955 of native human C3 and which has a reduced susceptibility to cofactor-dependent (e.g. CR1 or Factor H) Factor I-mediated cleavage at this position.
A fragment or a variant of a protein according to any preceding claim, said fragment or variant having C3 convertase activity and also having resistance to the complement inhibitory activity of Factor H, Factor I, CR1, MCP and/or DAF.
Dependencies are inferred from the claim text.