Muteins of C5a anaphylatoxin and methods of inhibiting C5a
AssigneeCincinnati Children's Hospital Medical Center
InventorsMagnus Otto, Jörg Köhl
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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.
Claims12
A mutein of the C5a anaphylatoxin which is a C5a receptor antagonist and which comprises a Cys27Ala mutation at position 27 and a C-terminal amino acid sequence wherein the amino acid residue naturally occurring at position 69 is mutated wherein the numbering of the amino acid sequence refers to the amino acid position defined by SEQ ID NO 13;
- wherein the C-terminal amino acid sequence is selected from SEQ ID NO:
- 41, SEQ ID NO:
- 42, SEQ ID NO:
- 43, SEQ ID NO:
- 44, SEQ ID NO:
- 45, SEQ ID NO:
- 46, SEQ ID NO:
- 47, and SEQ ID NO:
- 48, wherein the C-terminal amino acid sequence begins at position 67 with reference to SEQ ID NO 13;
- and
- wherein the fusion proteins of the mutein of SEQ ID NO:
- 14 with Jun/Fos and/or with Jun/Fos and the minor coat protein of the filamentous M13 phage fused to the N-terminus of the mutein are excluded.
A C5a receptor antagonist comprising a human C5a anaphylatoxin comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
- 14;
- SEQ ID NO:
- 15;
- SEQ ID NO:
- 16;
- SEQ ID NO:
- 17;
- SEQ ID NO:
- 18;
- SEQ ID NO:
- 19;
- SEQ ID NO:
- 20;
- SEQ ID NO:
- 21;
- SEQ ID NO:
- 22;
- and SEQ ID NO:39.
A mutein of SEQ ID NO 13 which is a C5a receptor antagonist and which comprises a mutation at position 27 selected from Cys27Ala and Cys27Arg, wherein the numbering of the position is defined by SEQ ID NO:
- 13, and a C-terminal amino acid sequence selected from SEQ ID NO:
- 41, SEQ ID NO:
- 42, SEQ ID NO:
- 43, SEQ ID NO:
- 44, SEQ ID NO:
- 45, SEQ ID NO:
- 46, SEQ ID NO:
- 47, and SEQ ID NO:
- 48, wherein the C-terminal amino acid sequence begins at position 67 with reference to SEQ ID NO 13.
Dependencies are inferred from the claim text.