US 12,247,055 B2
General amyloid interaction motif (GAIM)
Rajaraman Krishnan, Ashland, MA (US); Eva Asp, Newton, MA (US); Ming Proschitsky, Winchester, MA (US); and Richard Fisher, Cambridge, MA (US)
Assigned to Amyl Therapeutics SRL, Seraing (BE)
Filed by Amyl Therapeutics SRL, Seraing (BE)
Filed on May 19, 2023, as Appl. No. 18/320,697.
Application 18/320,697 is a continuation of application No. 17/251,351, granted, now 11,692,017, previously published as PCT/US2019/037179, filed on Jun. 14, 2019.
Claims priority of provisional application 62/749,499, filed on Oct. 23, 2018.
Claims priority of provisional application 62/685,757, filed on Jun. 15, 2018.
Prior Publication US 2023/0279064 A1, Sep. 7, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/47 (2006.01); A61K 38/00 (2006.01); A61K 47/68 (2017.01)
CPC C07K 14/4703 (2013.01) [A61K 47/68 (2017.08); A61K 38/00 (2013.01); C07K 2319/20 (2013.01)] 26 Claims
 
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.