US 12,331,102 B2
APOA-1 fusion polypeptides and related compositions
Martha S. Hayden-Ledbetter, Shoreline, WA (US); and Jeffrey A. Ledbetter, Shoreline, WA (US)
Assigned to Theripion, Inc., Shoreline, WA (US)
Filed by Theripion, Inc., Shoreline, WA (US)
Filed on Mar. 1, 2018, as Appl. No. 15/909,314.
Application 15/909,314 is a continuation in part of application No. PCT/US2016/050405, filed on Sep. 6, 2016.
Claims priority of provisional application 62/215,256, filed on Sep. 8, 2015.
Prior Publication US 2018/0201664 A1, Jul. 19, 2018
Int. Cl. C07K 14/775 (2006.01); C07K 19/00 (2006.01); C12N 9/18 (2006.01); C12N 9/22 (2006.01); C12N 15/62 (2006.01)
CPC C07K 14/775 (2013.01) [C12N 9/18 (2013.01); C12N 9/22 (2013.01); C12N 15/62 (2013.01); C12Y 301/01002 (2013.01); C12Y 301/01047 (2013.01); C12Y 301/08001 (2013.01); C07K 2319/30 (2013.01); C12Y 301/27005 (2013.01)] 30 Claims
 
1. A fusion polypeptide comprising, from an amino-terminal position to a carboxyl-terminal position, ApoA1-L1-D, wherein:
ApoA1 is a first polypeptide segment comprising the amino acid sequence shown in residues 19-267 or 25-267 of SEQ ID NO:2, wherein said first polypeptide segment has cholesterol efflux activity;
L1 is a first polypeptide linker consisting of 16 to 36 amino acid residues; and
D is an immunoglobulin Fc region,
wherein the fusion polypeptide has increased cholesterol efflux activity as compared to the ApoA1-L1-D fusion polypeptide in which L1 is a two amino acid linker or is absent, and
wherein the fusion polypeptide comprises the amino acid sequence shown in
(i) residues 19-525, 19-524, 25-525, or 25-524 of SEQ ID NO:2,
(ii) residues 19-525, 19-524, 25-525, or 25-524 of SEQ ID NO:13,
(iii) residues 19-515, 19-514, 25-515, or 25-514 of SEQ ID NO:22,
(iv) residues 19-520, 19-519, 25-520, or 25-519 of SEQ ID NO:26, or
(v) residues 19-535, 19-534, 25-535, or 25-534 of SEQ ID NO:24.