Adprotech Limited

Vivienne Frances Cox

Richard Anthony Godwin Smith

Danuta Ewa Irena Mossakowska

Pamela Jane Elizabeth Rowling

Replacement of codons in DNA encoding the first three SCRs of LHR-A of CR1 with others encoding the predicted amino acids in the CR1-like sequence can give rise to chimeric genes which can be expressed to give active complement inhibitors with functional complement inhibitory, including anti-haemolytic activity. There is provided a soluble polypeptide comprising, in sequence, one to four short consensus repeats (SCR) selected from SCR 1, 2, 3 and 4 of long homologous repeat A (LHR-A) as the only structurally and functionally intact SCR domains of CR1 and including at least SCR3, in which one or more of the native amino acids are substituted with the following: Val 4, Asp 19, Scr 53, Lys 57, Ala 74, Asp 79, Arg 84, Pro 91, Asn 109, Lys 116, Val 119, Ala 132, Thr 137, Ile 139, Ser 140, Tyr 143, His 153, Leu 156, Arg 159, Lys 161, Lys 177, Gly 230, Ser 235, His 236.

Complement receptor type 1 (CR1)-like sequences

The invention provides a linear concatamer of at least two non-identical DNA sequences which, by virtue of third base redundancy of the genetic code of the codons, each encode the same polypeptide of at least 30 amino acids; wherein the concatamer comprises or consists of a nucleic acid sequence which codes for an oligomer of said polypeptides in a continuous reading frame. A single invariant cysteine codon may be added to one DNA sequence to encode a polypeptide derivative with a unique unpaired cysteine. The concatamer may be fused to one or more sequences encoding one or more antigens. The DNA sequences in the concatamer may encode the compliment C3 fragment C3d or an analogue thereof. The invention also provides an expression vector comprising the concatamer nucleic acid sequence and regulatory or other sequences for expression of any oligomeric polypeptide encoded thereby, as well as a host cell comprising the expression vector. The invention can also provide a method of including a immune response to an antigen in the human or animal by administering a concatamer or administering a vector. Thus the invention can provide a pharmaceutical composition in the form of a DNA vaccine.

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Herts, United Kingdom

Vivienne Frances Cox