SAA domain-specific antibodies and peptide antagonists and use thereof to treat inflammatory diseases
View Patent ↗Isolated SAA peptides, fusion proteins and compositions comprising such are provided as are domain-specific SAA antibodies. Methods of treating sepsis and endotoxemia are also provided.
1. A method of treating sepsis or endotoxemia in a subject, comprising administering to the subject an amount of a composition comprising an isolated non-naturally occurring peptide of 6 to 18 consecutive amino acids consisting of (i) 6 to 18 consecutive amino acids of SEQ ID NO:1, (ii) 6 to 18 consecutive amino acids of SEQ ID NO:2, (iii) 6 to 18 consecutive amino acids of SEQ ID NO:3, or (iv) 6 to 18 consecutive amino acids of SEQ ID NO:4, but not consisting of SEQ ID NO:10, 11 or 12, or (v) a fusion protein comprising such peptide set forth in (i), (ii), (iii) or (iv) which is bound to a functional domain of a second peptide, polypeptide or protein, effective to treat sepsis or endotoxemia.
2. The method of claim 1 , wherein the composition comprising the fusion protein is administered.
3. The method of claim 1 , wherein the composition comprising the isolated peptide is administered.
4. The method of claim 1 , wherein the peptide comprises SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8 or SEQ ID NO:9.
5. The method of claim 1 , wherein the peptide comprises SEQ ID NO:5.
6. The method of claim 1 , wherein all amino acid residues of the peptide are D-amino acids.
7. The method of claim 1 , wherein all amino acid residues of the peptide are L-amino acids.
8. The method of claim 1 , wherein the composition comprising a carrier is administered.
9. The method of claim 8 , wherein the carrier is a pharmaceutically acceptable carrier.
10. The method of claim 1 , wherein the fusion protein comprises the isolated peptide bonded via a peptide bond at an N-terminal thereof or a C-terminal thereof to a second peptide, polypeptide or protein.
11. The method of claim 10 , wherein the isolated peptide is bonded via a peptide bond at an N-terminal thereof or a C-terminal thereof to the immunoglobulin fragment crystallizable region (Fc).
12. The method of claim 11 , wherein the Fc has a sequence identical to a human Fc.
13. A method of increasing likelihood of a subject surviving sepsis or endotoxemia, comprising administering to the subject an amount of a composition comprising an isolated non-naturally occurring peptide of 6 to 18 consecutive amino acids consisting of (i) 6 to 18 consecutive amino acids of SEQ ID NO:1, (ii) 6 to 18 consecutive amino acids of SEQ ID NO:2, (iii) 6 to 18 consecutive amino acids of SEQ ID NO:3, or (iv) 6 to 18 consecutive amino acids of SEQ ID NO:4, but not consisting of SEQ ID NO:10, 11 or 12, or (v) a fusion protein comprising such peptide set forth in (i), (ii), (iii) or (iv) which is bound to a functional domain of a second peptide, polypeptide or protein, effective to increase likelihood of a subject surviving sepsis or endotoxemia.