US 12,084,485 B2
Long acting glucagon like polypeptide-1 (GLP-1) receptor agonists and methods of use
William Blackwell, Boston, MA (US); Ved P. Srivastava, Boston, MA (US); and Mark Paulik, Boston, MA (US)
Assigned to I2O Therapeutics, Inc., Cambridge, MA (US)
Filed by Intarcia Therapeutics, Inc., Boston, MA (US)
Filed on Dec. 16, 2021, as Appl. No. 17/553,381.
Claims priority of provisional application 63/126,736, filed on Dec. 17, 2020.
Prior Publication US 2023/0063420 A1, Mar. 2, 2023
Int. Cl. A61K 38/00 (2006.01); A61K 9/00 (2006.01); A61K 38/26 (2006.01); A61P 1/16 (2006.01); A61P 1/18 (2006.01); A61P 3/04 (2006.01); A61P 25/00 (2006.01); C07K 14/605 (2006.01)
CPC C07K 14/605 (2013.01) [A61K 9/0004 (2013.01); A61K 38/26 (2013.01); A61P 1/16 (2018.01); A61P 3/04 (2018.01)] 28 Claims
 
1. An isolated polypeptide, comprising the amino acid sequence HX2X3GTX6X7X8X9X10SX12X13X14EX16X17X18X19X20X21FIX24WLKX28GGPX32SGAPPPS-(OH/N H2) (SEQ ID NO: 200) or a pharmaceutically acceptable salt thereof, wherein:
X2 is A, 2-aminoisobutyric acid (Aib), or G;
X3 is E or N-methyl Glu;
X6 is For Y;
X7 is S or T;
X8 is diaminopimelic acid (Dap), E, K, N, N-methyl Ser, Q, S, s, or Y;
X9 is D or E;
X10 is I, L, N-methyl Leu, or V;
X12 is E, K, Q, or S;
X13 is Aib, E, K, Q, S, W, or Y;
X14 is Y;
X16 is 2,4-diaminobutanoic acid (Dab), Dap, E, K, k, or ornithine (Orn);
X17 is E, K, or Q;
X18 is A, K, S, or Y;
X19 is A, K, or V;
X20 is E, K, or R;
X21 is Aib, E, H, K, L, Q, or Y;
X24 is A, Aib, E, K, Q, S, or Y;
X28 is D, E, K, N, Q, S, or Y; and
X32 is Dap, H, K, R, or S;
wherein when X16 is Dab, Dap, K, or Orn, it is covalently bound to a lipophilic substituent, optionally via a spacer;
wherein when X16 is E, at least one of X17, X18, X19, X20, or X21 is K and covalently bound to a lipophilic substituent, optionally via a spacer; and
wherein the peptide optionally further comprises a lactam bridge formed via an amide bond between the side chains of K and E at positions X17 and X21; at positions X21 and X17; at positions X21 and X28; at positions X28 and X21; at positions X20 and X24; at positions X24 and X20; or at positions X12 and X16.