Granted Patent B2

US 12,691,177 · App. 17/726,971 · Granted Jul 28, 2026

Inventor: Edward J. Hennessy (Westwood, MA)

Assignee: ModernaTX, Inc.

A61K47/22A61J1/1468A61K9/0019A61K9/127A61K31/7105A61K31/711

Abstract

Claims (50)

1 . A stabilized pharmaceutical composition, comprising:

a nucleic acid and a compound of Formula I′:

or a tautomer, solvate, or salt thereof, wherein:

each of R 1 , R 2 , R 3 , and R 4 are independently selected from —OH and —OC 1-4 alkyl, wherein the —OC 1-4 alkyl is optionally substituted with one or more —OH, —C(O)OH, —NR′R″, or —C(O)NR′R″, and wherein at least one of R 1 , R 2 , R 3 , and R 4 is —OH, —OC 2-4 alkyl, or —OC 1-4 alkyl substituted with one or more —OH, —C(O)OH, —NR′R″, or —C(O)NR′R″;

each instance of R′ is independently H or —C 1-4 alkyl, wherein the —C 1-4 alkyl is optionally substituted with one or more —OH;

each instance of R″ is independently H or —C 1-4 alkyl;

optionally wherein R′ and R″ taken together form a 5 to 6 membered heterocycle with one or more O or N heteroatoms, wherein the heterocycle is optionally substituted with one or more —C 1-4 alkyl or —OH;

optionally wherein R 1 and R 2 together with the intervening atoms form a 5-membered ring;

R 5 is H, —C 1-4 alkyl, or C 3-7 cycloalkyl; and

X is a pharmaceutically acceptable anion.

2 . The stabilized pharmaceutical composition of claim 1 ,

wherein the compound of Formula I′ is of Formula I:

 or a tautomer, solvate, or salt thereof.

3 . The composition of claim 1 , wherein:

R 1 , R 2 , and R 3 are independently —OC 1-4 alkyl; and

R 4 is —OH or —OC 1-4 alkyl, wherein the —OC 1-4 alkyl is substituted with one or more —OH, —C(O)OH, —NR′R″, or —C(O)NR′R″.

4 . The composition of claim 3 , wherein:

R 1 , R 2 , and R 3 are —OCH 3 .

5 . The composition of claim 3 , wherein R 4 is —OC 1-4 alkyl substituted with one or more —OH, —C(O)OH, —NR′R″, or —C(O)NR′R″.

6 . A stabilized pharmaceutical composition, comprising a nucleic acid and a compound selected from:

and tautomers, solvates and salts thereof;

wherein each compound further comprises a pharmaceutically acceptable anion x.

7 . The composition of claim 1 , wherein X is chloride.

8 . The composition of claim 1 , wherein the compound, or tautomer, solvate, or salt thereof, contains fewer than 100 ppm of elemental metals.

9 . The composition of claim 1 , wherein the nucleic acid is DNA or RNA.

10 . The composition of claim 1 , further comprising an ionizable amino lipid, a PEG-lipid, a structural lipid, and/or a phospholipid.

11 . The composition of claim 1 , wherein the composition comprises lipid nanoparticles (LNPs).

12 . The composition of claim 1 , wherein the compound, or tautomer, solvate, or salt thereof, is present at a concentration of less than about 10 mM.

13 . A method of treating a disease in a subject in need thereof, comprising administering to the subject a composition of claim 1 .

14 . The method according to claim 13 , wherein the disease is caused by an infectious agent, is caused by or associated with a virus, or is caused by or associated with a malignant cell.

15 . A method for producing a protein in a subject, comprising:

administering a composition claim 1 to the subject, wherein the nucleic acid is an mRNA and wherein the mRNA encodes for the production of the protein in the subject.

16 . A pharmaceutically acceptable method of processing an mRNA-lipid nanoparticle for therapeutic injection, comprising combining an mRNA, a lipid nanoparticle, and a compound of Formula I′:

or a tautomer, solvate, or salt thereof, wherein:

each of R 1 , R 2 , R 3 , and R 4 are independently selected from —OH and —OC 1-4 alkyl, wherein the —OC 1-4 alkyl is optionally substituted with one or more —OH, —C(O)OH, —NR′R″, or —C(O)NR′R″, and wherein at least one of R 1 , R 2 , R 3 , and R 4 is —OH, —OC 2-4 alkyl, or —OC 1-4 alkyl substituted with one or more —OH, —C(O)OH, —NR′R″, or —C(O)NR′R″;

each instance of R′ is independently H or —C 1-4 alkyl, wherein the —C 1-4 alkyl is optionally substituted with one or more —OH;

each instance of R″ is independently H or —C 1-4 alkyl;

optionally wherein R′ and R″ taken together form a 5 to 6 membered heterocycle with one or more O or N heteroatoms, wherein the heterocycle is optionally substituted with one or more —C 1-4 alkyl or —OH;

optionally wherein R 1 and R 2 together with the intervening atoms form a 5-membered ring;

R 5 is H, —C 1-4 alkyl, or C 3-7 cycloalkyl; and

X is a pharmaceutically acceptable anion.

17 . A syringe or cartridge, comprising a composition of claim 1 .

18 . An infusion pump, comprising a composition of claim 1 .

19 . A photoprotective container comprising the stabilized pharmaceutical composition of claim 1 .

20 . The composition of claim 1 , wherein at least one of R 1 , R 2 , R 3 , and R 4 is —OC 1-4 alkyl substituted with one or more —OH, —C(O)OH, —NR′R″, or —C(O)NR′R″.

21 . The composition of claim 1 , wherein the compound is selected from:

and tautomers, solvates, and salts thereof;

wherein each compound further comprises a pharmaceutically acceptable anion X.

22 . The composition of claim 6 , wherein X is chloride.

23 . The composition of claim 21 , wherein X is chloride.

Assignments (2)

Continuity (3)

References Cited (215)