IP Library › Granted Patent US 12,419,901
Granted Patent B2
US 12,419,901 · App. 18/167,308 · Granted Sep 23, 2025

Prodrugs of deoxynucleosides for treatment of diseases caused by unbalanced nucleotide pools

Inventor: Daniel DiPietro (Brooklyn, NY)
Assignee: UCB BIOSCIENCES, INC.
A61K31/7076A61K31/7072A61P43/00A61K9/0053
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Quick Facts
Patent No.
US 12,419,901
App. No.
18/167,308
Granted
Sep 23, 2025
Kind
B2
Abstract

Deoxynucleotide prodrugs for treatment of diseases characterized by unbalanced nucleotide pools are provided herein.

Claims (29)

1. A method for treating a mitochondrial DNA depletion syndrome (MDS) in a subject in need thereof comprising administering to the subject a therapeutically effective amount of at least one prodrug of Formula III:

wherein Base refers to an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group;

R 1 and R 2 are independent selected from hydrogen; phosphate; straight chained, branched, or cyclic alkyl; acyl; CO-alkyl; CO-alkoxyalkyl; CO-aryloxyalkyl; CO-substituted aryl; sulfonate ester; alkylsulfonyl; arylsulfonyl; aralkylsulfonyl; a lipid; a phospholipid; an amino acid; a carbohydrate; a peptide; and cholesterol; and

wherein at least one of R 1 and R 2 is not hydrogen, and wherein R 1 and R 2 is not a modified phosphate.

2. The method of claim 1 , wherein the prodrug is a compound of Formula IIIa:

wherein R is the side chain of an amino acid.

3. The method of claim 1 , wherein at least two prodrugs are administered.

4. The method of claim 3 , wherein the weight ratio of one prodrug to another prodrug is 50/50, 5/95, 10/90, 15/85, 20/80, 25/75, 30/70, 35/65, 40/60, 45/55, 55/45, 60/40, 65/35, 70/30, 75/25, 80/20, 85/15, 90/10 or 95/5.

5. The method of claim 1 , wherein the prodrug is administered in the form of a pharmaceutical composition.

6. The method of claim 1 , wherein the mitochondrial DNA depletion syndrome (MDS) is POLG or POLG2.

7. The method of claim 1 , wherein the method of administration is oral.

8. The method of claim 1 , wherein the therapeutically effective amount administered is from about 200 mg/kg/day to about 1,000 mg/kg/day.

9. The method of claim 1 , wherein the prodrug or a composition comprising the prodrug is administered at least once per day.

10. The method of claim 1 , wherein the dose administered is from about 200 mg/kg/day to about 1,000 mg/kg/day.

11. The method of claim 1 , wherein the prodrug or composition comprising the same is administered at least once per day.

12. The method of claim 1 , wherein the at least one prodrug is selected from the group consisting of:

13. The method of claim 3 , wherein the at least two prodrugs are:

14. The method of claim 2 , wherein Base is selected from the group consisting of cytosine, thymine, guanine, and adenine.

15. The method of claim 1 , wherein R 1 and R 2 are CO-alkyl.

16. The method of claim 15 , wherein alkyl is isopropyl.

17. The method of claim 1 , wherein the prodrug is a compound of Formula IIIb:

wherein Base refers to an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group.

18. The method of claim 17 , wherein Base is selected from the group consisting of cytosine, thymine, guanine, and adenine.

19. The method of claim 1 , wherein the prodrug is a compound of Formula IIIc:

wherein Base refers to an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group;

Ra is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl; and

R is CH(CH 3 ) 2 .

20. The method of claim 19 , wherein Ra is isopropyl.

21. The method of claim 20 , wherein Base is selected from the group consisting of cytosine, thymine, guanine, and adenine.

Assignments (4)
ASSIGNMENT OF ASSIGNOR’S INTEREST RESUBMISSION - ID: 508557651 Recorded Jul 12, 2024
From: ZOGENIX, INC.
To: UCB BIOSCIENCES, INC.
Reel/Frame 068311/0739 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 16, 2023
From: ZOGENIX MDS, INC.
To: ZOGENIX, INC.
Reel/Frame 065590/0802 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 21, 2023
From: DIPIETRO, DANIEL
To: MODIS THERAPEUTICS INC.
Reel/Frame 062755/0421 →
CHANGE OF NAME Recorded Feb 21, 2023
From: MODIS THERAPEUTICS INC.
To: ZOGENIX MDS, INC.
Reel/Frame 062814/0257 →
Continuity (3)
Continuation 17046865
Provisional Application 62656861 · Apr 12, 2018
Related Publication 20230181616A1 · Jun 15, 2023
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