WO 723026CPCT CN CN202210259967.6 2022-03-16 BEIJING TUOJIE BIOPHARMACEUTICAL CO., LTD. BEIJING TUOJIE BIOPHARMACEUTICAL CO., LTD. HUMAN INSULIN ANALOGUE, AND FUSION PROTEIN THEREOF AND MEDICAL USE THEREOF 55 26 AA PAT source 1..26 mol_type protein note Insulin B-chain analog organism synthetic construct VARIANT 3 note X is selected from the group consisting of N, G, and K VARIANT 9 note X is selected from the group consisting of S and E VARIANT 16 note X is selected from the group consisting of Y, H, and E VARIANT 17 note X is selected from the group consisting of H, R, L, and E VARIANT 25 note X is selected from the group consisting of F and H FVXQHLCGXHLVEALXXVCGERGFXY 21 AA PAT source 1..21 mol_type protein note Insulin A-chain analog organism synthetic construct VARIANT 8 note Z is selected from the group consisting of T, H, and E VARIANT 14 note Z is selected from the group consisting of Y, D, S, and E VARIANT 21 note Z is selected from the group consisting of G and N GIVEQCCZSICSLZQLENYCZ 11 AA PAT source 1..11 mol_type protein note Linker organism synthetic construct GGGGGGSGGGG 58 AA PAT source 1..58 mol_type protein note Human insulin analog 1 organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHYGGGGGGSGGGGGIVEQCCESICSLEQLENYCG 58 AA PAT source 1..58 mol_type protein note Human insulin analog 2 organism synthetic construct FVNQHLCGSHLVEALYLVCGERGFHYGGGGGGSGGGGGIVEQCCHSICSLEQLENYCG 58 AA PAT source 1..58 mol_type protein note Human insulin analog 3 organism synthetic construct FVNQHLCGSHLVEALHLVCGERGFHYGGGGGGSGGGGGIVEQCCTSICSLEQLENYCN 58 AA PAT source 1..58 mol_type protein note Human insulin analog 4 organism synthetic construct FVKQHLCGEHLVEALYLVCGERGFHYGGGGGGSGGGGGIVEQCCESICSLEQLENYCG 57 AA PAT source 1..57 mol_type protein note Human insulin analog 5 organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHYGGGGGSGGGGGIVEQCCESICSLEQLENYCG 58 AA PAT source 1..58 mol_type protein note Human insulin analog 6 organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHYGGGGGGSGGGGGIVEQCCESICSLEQLENYCN 20 AA PAT source 1..20 mol_type protein note Linker sequence for fusion of human insulin analog with Fc organism synthetic construct GGGGQGGGGQGGGGQGGGGG 20 AA PAT source 1..20 mol_type protein note Linker sequence for fusion of human insulin analog with Fc organism synthetic construct HGGGQGGGGQGGGGQGGGGG 25 AA PAT source 1..25 mol_type protein note Linker sequence for fusion of human insulin analog with Fc organism synthetic construct GGGGQGGGGQGGGGQGGGGQGGGGQ 32 AA PAT source 1..32 mol_type protein note Linker sequence for fusion of human insulin analog with Fc organism synthetic construct PGPQPGPQPGPQPGPQPGPQPGPQPGPQPGPQ 25 AA PAT source 1..25 mol_type protein note Linker sequence for fusion of human insulin analog with Fc organism synthetic construct GGGGQGGGGQGGGGQGGGGGQGGGG 20 AA PAT source 1..20 mol_type protein note Linker sequence for fusion of human insulin analog with Fc organism synthetic construct GGGGAGGGGAGGGGAGGGGG 34 AA PAT source 1..34 mol_type protein note Linker sequence for fusion of human insulin analog with Fc organism synthetic construct GGGGQGGGGQGGGGQGGGGQGGPCPPCPAPEAAG 221 AA PAT source 1..221 mol_type protein note IgG2 Fc1 organism Homo sapiens ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 210 AA PAT source 1..210 mol_type protein note IgG2 Fc2 organism Homo sapiens GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 299 AA PAT source 1..299 mol_type protein note Fusion protein 1 organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHYGGGGGGSGGGGGIVEQCCESICSLEQLENYCGGGGGQGGGGQGGGGQGGGGGECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 299 AA PAT source 1..299 mol_type protein note Fusion protein 2 organism synthetic construct FVNQHLCGSHLVEALYLVCGERGFHYGGGGGGSGGGGGIVEQCCHSICSLEQLENYCGGGGGQGGGGQGGGGQGGGGGECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 299 AA PAT source 1..299 mol_type protein note Fusion protein 3 organism synthetic construct FVNQHLCGSHLVEALHLVCGERGFHYGGGGGGSGGGGGIVEQCCTSICSLEQLENYCNGGGGQGGGGQGGGGQGGGGGECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 299 AA PAT source 1..299 mol_type protein note Fusion protein 4 organism synthetic construct FVKQHLCGEHLVEALYLVCGERGFHYGGGGGGSGGGGGIVEQCCESICSLEQLENYCGGGGGQGGGGQGGGGQGGGGGECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 304 AA PAT source 1..304 mol_type protein note Fusion protein 5 organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHYGGGGGGSGGGGGIVEQCCESICSLEQLENYCGGGGGQGGGGQGGGGQGGGGQGGGGQECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 298 AA PAT source 1..298 mol_type protein note Fusion protein 6 organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHYGGGGGSGGGGGIVEQCCESICSLEQLENYCGGGGGQGGGGQGGGGQGGGGGECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 311 AA PAT source 1..311 mol_type protein note Fusion protein 7 organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHYGGGGGGSGGGGGIVEQCCESICSLEQLENYCGPGPQPGPQPGPQPGPQPGPQPGPQPGPQPGPQECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 299 AA PAT source 1..299 mol_type protein note Fusion protein 8 organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHYGGGGGGSGGGGGIVEQCCESICSLEQLENYCGGGGGAGGGGAGGGGAGGGGGECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 299 AA PAT source 1..299 mol_type protein note Fusion protein 9 organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHYGGGGGGSGGGGGIVEQCCESICSLEQLENYCNHGGGQGGGGQGGGGQGGGGGECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 299 AA PAT source 1..299 mol_type protein note LY3209590 organism synthetic construct FVNQHLCGSHLVEALELVCGERGFHYGGGGGGSGGGGGIVEQCCTSTCSLDQLENYCGGGGGQGGGGQGGGGQGGGGGECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 21 AA PAT source 1..21 mol_type protein note A-chain organism Homo sapiens GIVEQCCTSICSLYQLENYCN 30 AA PAT source 1..30 mol_type protein note B-chain organism Homo sapiens FVNQHLCGSHLVEALYLVCGERGFFYTPKT 26 AA PAT source 1..26 mol_type protein note Insulin B-chain analog organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHY 26 AA PAT source 1..26 mol_type protein note Insulin B-chain analog organism synthetic construct FVNQHLCGSHLVEALYLVCGERGFHY 26 AA PAT source 1..26 mol_type protein note Insulin B-chain analog organism synthetic construct FVNQHLCGSHLVEALHLVCGERGFHY 26 AA PAT source 1..26 mol_type protein note Insulin B-chain analog organism synthetic construct FVKQHLCGEHLVEALYLVCGERGFHY 26 AA PAT source 1..26 mol_type protein note Insulin B-chain analog organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHY 26 AA PAT source 1..26 mol_type protein note Insulin B-chain analog organism synthetic construct FVNQHLCGEHLVEALYLVCGERGFHY 21 AA PAT source 1..21 mol_type protein note Insulin A in insulin analog organism synthetic construct GIVEQCCESICSLEQLENYCG 21 AA PAT source 1..21 mol_type protein note Insulin A in insulin analog organism synthetic construct GIVEQCCHSICSLEQLENYCG 21 AA PAT source 1..21 mol_type protein note Insulin A in insulin analog organism synthetic construct GIVEQCCTSICSLEQLENYCN 21 AA PAT source 1..21 mol_type protein note Insulin A in insulin analog organism synthetic construct GIVEQCCESICSLEQLENYCG 21 AA PAT source 1..21 mol_type protein note Insulin A in insulin analog organism synthetic construct GIVEQCCESICSLEQLENYCG 21 AA PAT source 1..21 mol_type protein note Insulin A in insulin analog organism synthetic construct GIVEQCCESICSLEQLENYCN 29 AA PAT source 1..29 mol_type protein note Insulin B-chain analog organism synthetic construct VARIANT 3 note X is selected from the group consisting of N, G, and K VARIANT 9 note X is selected from the group consisting of S and E VARIANT 16 note X is selected from the group consisting of Y, H, and E VARIANT 17 note X is selected from the group consisting of H, R, L, and E VARIANT 25 note X is selected from the group consisting of F and H VARIANT 26 note X is selected from the group consisting of G, T, S, H, V, and Y, or is absent VARIANT 27 note X is selected from the group consisting of G, E, P, K, D, S, and H, or is absent VARIANT 28 note X is selected from the group consisting of G, E, K, P, Q, D, and H, or is absent VARIANT 29 note X is selected from the group consisting of G, T, S, E, K, and A, or is absent FVXQHLCGXHLVEALXXVCGERGFXXXXX 22 AA PAT source 1..22 mol_type protein note Insulin A-chain analog organism synthetic construct VARIANT 8 note Z is selected from the group consisting of T, H, and E VARIANT 14 note Z is selected from the group consisting of Y, D, S, and E VARIANT 21 note Z is selected from the group consisting of G and N VARIANT 22 note Z is any natural amino acid or is absent GIVEQCCZSICSLZQLENYCZZ 7 AA PAT source 1..7 mol_type protein note Linker organism synthetic construct GGSGGGG 6 AA PAT source 1..6 mol_type protein note Linker organism synthetic construct GSGGGG 5 AA PAT source 1..5 mol_type protein note Linker organism synthetic construct GGGGG 232 AA PAT source 1..232 mol_type protein note Human IgG1 Fc region 1 organism Homo sapiens EPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 232 AA PAT source 1..232 mol_type protein note Human IgG1 Fc region 2 organism Homo sapiens EPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 229 AA PAT source 1..229 mol_type protein note Human IgG4 Fc region 1 organism Homo sapiens ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 229 AA PAT source 1..229 mol_type protein note Human IgG4 Fc region 2 organism Homo sapiens ESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 10 AA PAT source 1..10 mol_type protein note Linker organism synthetic construct GGGGGSGGGG 5 AA PAT source 1..5 mol_type protein note Linker organism synthetic construct GGGGS 4 AA PAT source 1..4 mol_type protein note Linker organism synthetic construct ASGS 4 AA PAT source 1..4 mol_type protein note Linker organism synthetic construct REGION 1..4 note (PGPQ)s, wherein s is selected from the group consisting of integers of 1-10 (e.g., 1, 2, 3, 4, 5, or 6) PGPQ