US 11,752,216 B2
Insulin analog complex with reduced affinity for insulin receptor and use thereof
Young Jin Park, Hwaseong-si (KR); In Young Choi, Hwaseong-si (KR); Sung Youb Jung, Hwaseong-si (KR); and Se Chang Kwon, Hwaseong-si (KR)
Assigned to HANMI PHARM. CO., LTD., Hwaseong-si (KR)
Appl. No. 16/495,884
Filed by HANMI PHARM. CO., LTD., Hwaseong-si (KR)
PCT Filed Mar. 23, 2018, PCT No. PCT/KR2018/003489
§ 371(c)(1), (2) Date Sep. 20, 2019,
PCT Pub. No. WO2018/174668, PCT Pub. Date Sep. 27, 2018.
Claims priority of application No. 10-2017-0037101 (KR), filed on Mar. 23, 2017.
Prior Publication US 2020/0101171 A1, Apr. 2, 2020
Int. Cl. C07K 14/62 (2006.01); A61K 47/68 (2017.01); A61K 47/60 (2017.01); A61P 3/10 (2006.01); A61K 38/00 (2006.01)
CPC A61K 47/6883 (2017.08) [A61K 47/60 (2017.08); A61P 3/10 (2018.01); C07K 14/62 (2013.01); A61K 38/00 (2013.01)] 19 Claims
 
1. A conjugate of Formula 1:
X-La-F  [Formula 1]
wherein in Formula 1,
X is an insulin analog consisting of an A-chain of SEQ ID NO: 55 of Formula 2 and a B-chain of SEQ ID NO: 56 of Formula 3 with the proviso that the peptide where the A-chain coincides with SEQ ID NO: 53 while the B-chain also coincides with SEQ ID NO: 54 is excluded;
L is a linker;
a is 0 or a natural number, with the proviso that when a is 2 or greater, each L is independent from each other;
F is a substance capable of increasing the half-life of X; and
X, L, and F are linked to each other by a covalent bond in the order of Formula 1:
[Formula 2]
(SEQ ID NO: 55)
Xaa1-Ile-Val-Glu-Xaa5-Cys-Cys-Thr-Ser-Ile-Cys-
Xaa12-Leu-Xaa14-Gln-Xaa16-Glu-Asn-Xaa19-Cys-Xaa21 
[Formula 3]
(SEQ ID NO: 56)
Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-
Glu-Ala-Leu-Xaa16-Leu-Val-Cys-Gly-Glu-Arg-Gly-
Phe-Xaa25-Tyr-Xaa27-Xaa28-Lys-Thr
wherein:
in Formula 2, Xaa1 is glycine, Xaa5 is glutamine, Xaa12 is serine, Xaa14 is aspartic acid, Xaa16 is leucine, Xaa19 is tyrosine, and Xaa21 is asparagine; and
in Formula 3, Xaa16 is tyrosine, Xaa25 is phenylalanine, Xaa27 is threonine, and Xaa28 is proline.