US 12,258,596 B2
Polynucleotides encoding paraoxonase fusion polypeptides
Jeffrey A. Ledbetter, Shoreline, WA (US); and Martha S. Hayden-Ledbetter, Shoreline, WA (US)
Assigned to Theripion, Inc., Shoreline, WA (US)
Filed by Theripion, Inc., Shoreline, WA (US)
Filed on Oct. 22, 2024, as Appl. No. 18/923,463.
Application 18/923,463 is a division of application No. 18/546,413, granted, now 12,180,521, previously published as PCT/US2022/016723, filed on Feb. 17, 2022.
Claims priority of provisional application 63/151,272, filed on Feb. 19, 2021.
Claims priority of provisional application 63/151,236, filed on Feb. 19, 2021.
Prior Publication US 2025/0059525 A1, Feb. 20, 2025
Int. Cl. C12N 9/22 (2006.01); A61P 11/00 (2006.01); C07K 16/24 (2006.01); C12N 9/16 (2006.01); A61K 38/00 (2006.01)
CPC C12N 9/22 (2013.01) [A61P 11/00 (2018.01); C07K 16/241 (2013.01); C12N 9/16 (2013.01); C12Y 301/08001 (2013.01); A61K 38/00 (2013.01); C07K 2317/31 (2013.01); C07K 2317/622 (2013.01); C07K 2319/01 (2013.01); C07K 2319/30 (2013.01); C12Y 301/21001 (2013.01)] 24 Claims
 
1. A polynucleotide encoding a fusion polypeptide, wherein the fusion polypeptide comprises, from an amino terminal position to a carboxyl terminal position, T-L1-X-L2-P, wherein:
T is a first biologically active polypeptide selected from the group consisting of
a cytotoxic T-lymphocyte associated molecule-4 (CTLA-4) extracellular domain, and
a CD40 extracellular domain;
L1 is a first polypeptide linker, wherein L1 is optionally present;
X is an immunoglobulin heavy chain constant region, wherein the immunoglobulin heavy chain constant region is capable of forming dimers and specifically binding the neonatal Fc receptor (FcRn);
L2 is a second polypeptide linker comprising at least eight amino acid residues; and
P is a biologically active paraoxonase, wherein the paraoxonase has at least 95% identity with the amino acid sequence shown in residues 16-355 or 26-355 of SEQ ID NO:6, and wherein the paraoxonase does not contain an amino terminal leader sequence corresponding to residues 1-15 of SEQ ID NO:6;
wherein the fusion polypeptide comprises an amino acid sequence having at least 95% identity with the amino acid sequence shown in
(i) residues 21-736 of SEQ ID NO:66,
(ii) residues 21-804 of SEQ ID NO:74,
(iii) residues 21-804 of SEQ ID NO:78,
(iv) residues 21-804 of SEQ ID NO:82,
(v) residues 21-804 of SEQ ID NO:86, or
(vi) residues 21-804 of SEQ ID NO:90.