Granted Patent B2

US 12,697,394 · App. 19/306,247 · Granted Aug 4, 2026

Inventors: Scott Hilderbrand (Waltham, MA); Timothy Weeden (Waltham, MA); John Najim (Waltham, MA); Stefano Zanotti (Waltham, MA); Romesh R. Subramanian (Framingham, MA); Mohammed T. Qatanani (Waltham, MA); Cody A. Desjardins (Waltham, MA); Kim Tang (Belmont, MA); Brendan Quinn (Waltham, MA)

Assignee: Dyne Therapeutics, Inc.

A61K47/6807A61K47/545A61K47/548A61K47/6849A61P21/00C07K16/2881C12N15/1137C12Y207/11001C07K2317/55C12N2310/11C12N2310/315C12N2310/321C12N2310/3231C12N2310/3341C12N2310/335C12N2310/3513

Abstract

Claims (25)

1 . A complex comprising a structure of the formula (Id):

wherein the oligonucleotide of formula (Id) 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 R 2 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 n1 is an integer representing the number of instances of the group enclosed by square brackets, wherein each instance of the group enclosed by square brackets is covalently linked to a different amino acid residue of the Fab.

2 . The complex of claim 1 , wherein each different amino acid residue is a lysine.

3 . The complex of claim 1 , wherein the heavy chain of the Fab comprises an N-terminal pyroglutamate.

4 . The complex of claim 1 , wherein n1 is 1-5.

5 . A composition comprising the complex of claim 1 .

6 . The composition of claim 5 , wherein the oligonucleotide is in a salt form.

7 . The composition of claim 6 , wherein the oligonucleotide is in a sodium salt form, potassium salt form, or magnesium salt form.

8 . The composition of claim 5 , wherein each different amino acid residue is a lysine.

9 . The composition of claim 5 , wherein the heavy chain of the Fab comprises an N-terminal pyroglutamate.

10 . The composition of claim 5 , wherein the composition is formulated for intravenous administration.

11 . A method of reducing DMPK expression in a subject, the method comprising administering to the subject an effective amount of a composition comprising the complex of claim 1 .

12 . A method of treating myotonic dystrophy in a subject, the method comprising administering to the subject an effective amount of a composition comprising the complex of claim 1 .

13 . The method of claim 12 , wherein the subject has an expansion of a disease-associated repeat of a DMPK allele that is associated with myotonic dystrophy.

14 . The method of claim 13 , wherein the disease-associated repeat comprises repeating units of a CTG trinucleotide sequence.

15 . The method of claim 11 , wherein each different amino acid residue is a lysine.

16 . The method of claim 11 , wherein the heavy chain of the Fab comprises an N-terminal pyroglutamate.

17 . The method of claim 11 , wherein the composition is formulated for intravenous administration.

18 . The method of claim 11 , wherein the subject is human.

19 . The method of claim 12 , wherein each different amino acid residue is a lysine.

20 . The method of claim 12 , wherein the heavy chain of the Fab comprises an N-terminal pyroglutamate.

21 . The method of claim 12 , wherein the composition is formulated for intravenous administration.

22 . The method of claim 12 , wherein the subject is human.

Assignments (3)

Continuity (5)

References Cited (400)