US 12,145,974 B2
Dual-target fusion proteins comprising FGF21 and GLP-1, connected through a Fc portion of an immunoglobulin
Chao Chen, Dongguan (CN); Shushan Lin, Dongguan (CN); Yu Li, Dongguan (CN); Xiaofeng Chen, Dongguan (CN); Liang Liu, Dongguan (CN); and Zheng Fu, Dongguan (CN)
Assigned to SUNSHINE LAKE PHARMA CO., LTD., Guangdong (CN)
Appl. No. 16/485,153
Filed by SUNSHINE LAKE PHARMA CO., LTD., Guangdong (CN)
PCT Filed Mar. 14, 2018, PCT No. PCT/CN2018/078925
§ 371(c)(1), (2) Date Aug. 10, 2019,
PCT Pub. No. WO2018/166461, PCT Pub. Date Sep. 20, 2018.
Claims priority of application No. 201710148158.7 (CN), filed on Mar. 14, 2017; and application No. 201810129427.X (CN), filed on Feb. 8, 2018.
Prior Publication US 2022/0127322 A1, Apr. 28, 2022
Int. Cl. A61K 38/18 (2006.01); A61P 3/04 (2006.01); C07K 14/50 (2006.01); C07K 14/605 (2006.01)
CPC C07K 14/605 (2013.01) [A61P 3/04 (2018.01); C07K 14/50 (2013.01); C07K 2319/30 (2013.01)] 18 Claims
 
1. A fusion protein comprising or consisting of:
a) a first polypeptide, wherein the first polypeptide is glucagon-like peptide-1 (GLP-1) or an analogue thereof;
b) a second polypeptide, wherein the second polypeptide is an IgG4 Fc portion comprising the amino acid sequence of SEQ ID NO: 2, or a variant thereof; and
c) a third polypeptide, wherein the third polypeptide is fibroblast growth factor 21 (FGF21) comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof,
wherein the first polypeptide is linked to the second polypeptide via a first linker and the third polypeptide is linked to the second polypeptide via a second linker; and
wherein the variant of SEQ ID NO: 2 further comprises any one or more mutations selected from E233P and N297A, as compared to the wild-type IgG4 Fc; and
wherein the variant of SEQ ID NO: 6 further comprises one or more mutations at one or more sites selected from the group consisting of 167, 175 and 179; wherein the amino acid mutation at position 167 is selected from the group consisting of S167H and S167C; wherein the amino acid mutation at position 175 is selected from the group consisting of R175L, R175H and R175P; and wherein the amino acid mutation at position 179 is selected from the group consisting of Y179S and Y179F.