| CPC C07K 14/4703 (2013.01) [A61K 47/68 (2017.08); A61K 38/00 (2013.01); C07K 2319/20 (2013.01)] | 26 Claims |
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1. A method of treating a disease associated with misfolded and/or aggregated amyloid protein, comprising administering to a subject in need thereof a polypeptide comprising a variant of starting amino acid sequence SEQ ID NO: 16, wherein the variant differs from SEQ ID NO: 16 by one or more sets of amino acid changes selected from:
a) substitution of T50 with any amino acid and H55T;
b) N137G;
c) N142A;
d) R143V and Q144N; or
R143V, Q144N, and A146V; or
R143V, Q144N, and A146T; or
R143V, Q144N, and A146K; and
e) Q156V, G157N, ΔT158, ΔD159, ΔP160, and V161G; or
Q156Y, G157N, ΔT158, ΔD159, ΔP160, and V161G; or
G157N, ΔT158, ΔD159, ΔP160, and V161G; or
ΔT158, ΔD159, ΔP160, and V161G;
wherein the variant optionally further differs from SEQ ID NO: 16 by one or more sets of amino acid changes selected from:
f) AM1; or
ΔM1 and ΔA2; and
g) substitution of N38 with any amino acid other than cysteine; or
substitution of N38 with any amino acid other than cysteine, and substitution of G40 with any amino acid other than cysteine; or
substitution of G40 with any amino acid other than cysteine, threonine, or serine.
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