Muteins of the c5a anaphylatoxin, nucleic acid molecules encoding such muteins, and pharmaceutical uses of muteins of the c5a anaphylatoxin
AssigneeCincinnati Children's Hospital Medical Center
InventorMagnus Otto
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Abstract
The present invention refers to muteins of the C5a anaphylatoxin (C5a) which are C5a receptor antagonists, to nucleic acid molecules comprising a nucleotide sequence encoding such muteins of C5a anaphylatoxin, to host cells containing a nucleic acid molecule comprising a nucleotide sequence encoding such muteins of the C5a anaphylatoxin as well as to a pharmaceutical composition comprising a mutein of the C5a anaphylatoxin acting as a C5a receptor antagonists. A mutein of the invention is a C5a receptor antagonist wherein the amino acid residue naturally occurring at sequence position 69 is mutated.
Claims32
A mutein of the C5a anaphylatoxin which is a C5a receptor antagonist wherein the amino acid residue naturally occurring at sequence position 69 is mutated.
Mutein of the human C5a anaphylatoxin having the amino acid sequence of SEQ ID NO:
- 14 (C5a-(1-66, Cys27Ala)-A8B);
- SEQ ID NO:
- 15 (C5a-(1-66, Cys27Ala)-A8B-Leu70);
- SEQ ID NO:
- 18 (C5a-(1-66, Cys27Ala)-A8B-Cys71);
- SEQ ID NO:
- 17 (C5a-(1-66, Cys27Ala)-A8B-Cys73);
- SEQ ID NO:
- 18 (C5a-(1-66, Cys27Ala)-A8B-Leu70-Tyr73);
- SEQ ID NO:
- 19 (C5a-(1-66, Cys27Ala)-A8B-Lys69-Ala70);
- SEQ ID NO:
- 20 (C5a-(1-66, Cys27Arg)-A8B8-Arg27);
- SEQ ID NO:
- 21 (C5a-(1-66, Cys27Ala)-A8B-Del71-73);
- SEQ ID NO:
- 22 (C5a-(1-66, Cys-3, Gly-2, -1, Cys27Ala)-A8B);
- or SEQ ID NO:39 (C5a-(1-66, Cys27Ala)-A5a).
A nucleic acid molecule comprising a nucleotide sequence encoding a mutein of SEQ ID NO:
- 14, SEQ ID NO:15, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 18, SEQ IQ NO:
- 19, SEQ ID NO:
- 20, SEQ ID) NO:
- 21 or SEQ ID NO:
- 22.
Method for producing a mutein which is a C5a receptor antagonist comprising the steps of
- (a) introducing into a nucleic acid molecule encoding the C5a anaphylatoxin (C5a) polypeptide a nucleotide sequence mutating the residue at sequence position 69 of the C5a polypeptide, and
- (b) introducing the obtained nucleic acid molecule for expression into a suitable host cell or into a suitable cell extract or cell lysate.
Dependencies are inferred from the claim text.