Granted Patent B2

US 12,440,574 · App. 18/436,078 · Granted Oct 14, 2025

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 (Waltham, MA); Brendan Quinn (Boston, MA)

Assignee: Dyne Therapeutics, Inc.

A61K47/6807A61K47/545A61K47/548A61K47/6849A61P21/00

Abstract

Claims (25)

1. A complex comprising a structure of formula (I): [R 1 ] n1 —R 2 , wherein each R 1 comprises a group of the formula (Ib):

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 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 R 1 is covalently linked at attachment point A to R 2 , wherein n1 is an integer representing the number of instances of R 1 , and wherein each instance of R 1 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. A composition comprising the complex of claim 1 .

5. The composition of claim 4 , wherein the oligonucleotide is in a salt form.

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

7. 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 .

8. 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 .

9. The method of claim 8 , wherein the subject has an expansion of a disease-associated repeat of a DMPK allele that is associated with myotonic dystrophy.

10. The method of claim 9 , wherein the disease-associated repeat comprises repeating units of a CTG trinucleotide sequence.

11. The method of claim 7 , wherein each different amino acid residue is a lysine.

12. The method of claim 7 , wherein the heavy chain of the Fab comprises an N-terminal pyroglutamate.

13. The method of claim 7 , wherein the composition is formulated for intravenous administration.

14. The method of claim 7 , wherein the subject is human.

15. The method of claim 8 , wherein each different amino acid residue is a lysine.

16. The method of claim 8 , wherein the heavy chain of the Fab comprises an N-terminal pyroglutamate.

17. The method of claim 8 , wherein the composition is formulated for intravenous administration.

18. The method of claim 8 , wherein the subject is human.

19. The composition of claim 4 , wherein each different amino acid residue is a lysine.

20. The composition of claim 4 , wherein the heavy chain of the Fab comprises an N-terminal pyroglutamate.

21. The composition of claim 4 , wherein the composition is formulated for intravenous administration.

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

Assignments (2)

Continuity (4)

References Cited (400)

Cited By (3)

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