Fusion proteins comprising P3 of bacteriophage
The invention relates to agents and to pharmaceutical compositions for reducing the formation of amyloid and/or for promoting the disaggregation of an proteins. The compositions may also be used to detect amyloid.
1. A method of treating a patient for a disease or condition by administering to the patient a fusion protein comprising an amyloid binding fragment of g3p and an Fc fragment of an immunoglobulin, wherein the fusion protein comprises:
(a) amino acids 21-506 of SEQ ID NO:9;
(b) amino acids 22-506 of SEQ ID NO:9;
(c) amino acids 23-506 of SEQ ID NO:9;
(d) amino acids 21-505 of SEQ ID NO:9;
(e) amino acids 22-505 of SEQ ID NO:9;
(f) amino acids 23-505 of SEQ ID NO:9;
(g) amino acids 21-506 of SEQ ID NO:11;
(h) amino acids 22-506 of SEQ ID NO:11;
(i) amino acids 23-506 of SEQ ID NO:11;
(j) amino acids 21-505 of SEQ ID NO:11;
(k) amino acids 22-505 of SEQ ID NO:11;
(l) amino acids 23-505 of SEQ ID NO:11;
(m) amino acids 21-509 of SEQ ID NO:13;
(n) amino acids 22-509 of SEQ ID NO:13;
(o) amino acids 23-509 of SEQ ID NO:13;
(p) amino acids 21-508 of SEQ ID NO:13;
(q) amino acids 22-508 of SEQ ID NO:13;
(r) amino acids 23-508 of SEQ ID NO:13;
(s) amino acids 21-528 of SEQ ID NO:31;
(t) amino acids 22-528 of SEQ ID NO:31;
(u) amino acids 23-528 of SEQ ID NO:31;
(v) amino acids 21-527 of SEQ ID NO:31;
(w) amino acids 22-527 of SEQ ID NO:31;
(x) amino acids 23-527 of SEQ ID NO:31; or
(y) a mutant or variant that is at least 95% identical to the amino acid sequence of any one of (a)-(x) and is capable of binding to amyloid; and
wherein the disease or condition is selected from peripheral amyloidosis, familial amyloidotic polyneuropathy (FAP), Finnish form of FAP (aggregation of gelsolin), familial amyloidotic cardiomyopathy (FAC), senile systemic amyloidosis (SSA), islet amyloid polypeptide (IAPP) amyloidosis, and disease characterized by formation of amyloid protein by aggregation of IgG light chain.
2. The method of claim 1 , wherein the mutant or variant of (y) has no more than 10 amino acid differences as compared to the amino acid sequence of any one of (a)-(x).
3. The method of claim 1 , wherein the mutant or variant of (y) has up to 5 amino acid substitutions as compared to the amino acid sequence of any one of (a)-(x).
4. The method of claim 1 , wherein the fusion protein comprises amino acids 21-509 of SEQ ID NO:13 or a mutant or variant thereof having up to 5 amino acid substitutions.
5. The method of claim 1 , wherein the fusion protein comprises amino acids 22-509 of SEQ ID NO:13 or a mutant or variant thereof having up to 5 amino acid substitutions.
6. The method of claim 1 , wherein the fusion protein comprises amino acids 23-509 of SEQ ID NO:13 or a mutant or variant thereof having up to 5 amino acid substitutions.
7. The method of claim 1 , wherein the fusion protein comprises amino acids 21-508 of SEQ ID NO:13 or a mutant or variant thereof having up to 5 amino acid substitutions.
8. The method of claim 1 , wherein the fusion protein comprises amino acids 22-508 of SEQ ID NO:13 or a mutant or variant thereof having up to 5 amino acid substitutions.
9. The method of claim 1 , wherein the fusion protein comprises amino acids 23-508 of SEQ ID NO:13 or a mutant or variant thereof having up to 5 amino acid substitutions.
10. The method of claim 1 , wherein the disease or condition is selected from the group consisting of FAP, Finnish form of FAP, and FAC.
11. The method of claim 1 , wherein the disease or condition is SSA or peripheral amyloidosis.
12. The method of claim 1 , wherein the disease or condition is IAPP amyloidosis.
13. The method of claim 1 , wherein the disease or condition is a disease characterized by formation of amyloid protein by aggregation of IgG light chain.