US 12,440,574 B2
Muscle targeting complexes and formulations for treating myotonic dystrophy
Scott Hilderbrand, Waltham, MA (US); Timothy Weeden, Waltham, MA (US); John Najim, Waltham, MA (US); Stefano Zanotti, Waltham, MA (US); Romesh R. Subramanian, Framingham, MA (US); Mohammed T. Qatanani, Waltham, MA (US); Cody A. Desjardins, Waltham, MA (US); Kim Tang, Waltham, MA (US); and Brendan Quinn, Boston, MA (US)
Assigned to Dyne Therapeutics, Inc., Waltham, MA (US)
Filed by Dyne Therapeutics, Inc., Waltham, MA (US)
Filed on Feb. 8, 2024, as Appl. No. 18/436,078.
Application 18/436,078 is a division of application No. 18/303,506, filed on Apr. 19, 2023, granted, now 11,931,421.
Application 18/303,506 is a continuation of application No. PCT/US2023/065753, filed on Apr. 14, 2023.
Claims priority of provisional application 63/331,727, filed on Apr. 15, 2022.
Prior Publication US 2024/0252666 A1, Aug. 1, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/68 (2017.01); A61K 47/54 (2017.01); A61P 21/00 (2006.01)
CPC A61K 47/6807 (2017.08) [A61K 47/545 (2017.08); A61K 47/548 (2017.08); A61K 47/6849 (2017.08); A61P 21/00 (2018.01)] 22 Claims
 
1. A complex comprising a structure of formula (I): [R1]n1—R2, wherein each R1 comprises a group of the formula (Ib):

OG Complex Work Unit Chemistry
wherein the oligonucleotide of formula (Ib) comprises a sequence of CAGCGCCCACCAGUCA (SEQ ID NO: 21), wherein for each nucleoside, N, of the oligonucleotide, +N represents an LNA ribonucleoside, dN represents a 2′-deoxyribonucleoside, oN represents a 2′-O-methoxyethyl (MOE) modified ribonucleoside, oC represents a 5-methyl-2′-MOE-cytidine, +C represents a 5-methyl-2′-4′-bicyclic-cytidine, wherein the 2′ and 4′ positions of the sugar are bridged via a methylene, oU represents a 5-methyl-2′-MOE-uridine, and wherein represents a phosphorothioate internucleoside linkage;
wherein R2 comprises a Fab comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 19 and a light chain comprising the amino acid sequence of SEQ ID NO: 20;
wherein R1 is covalently linked at attachment point A to R2, wherein n1 is an integer representing the number of instances of R1, and wherein each instance of R1 is covalently linked to a different amino acid residue of the Fab.