IP Library › Granted Patent US 12,485,136
Granted Patent B2
US 12,485,136 · App. 17/299,277 · Granted Dec 2, 2025

Methods for the treatment of trinucleotide repeat expansion disorders associated with MLH3 activity

Inventors: Nessan Anthony Bermingham (Cambridge, MA); Brian R. Bettencourt (Cambridge, MA); Peter Edward Bialek (Cambridge, MA)
Assignee: Takeda Pharmaceuticals U.S.A., Inc.
A61K31/7125A61P25/28C12N15/113
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Quick Facts
Patent No.
US 12,485,136
App. No.
17/299,277
Granted
Dec 2, 2025
Kind
B2
Abstract

The present disclosure features useful compositions and methods to treat repeat expansion disorders, e.g., in a subject in need thereof. In some aspects, the compositions and methods described herein are useful in the treatment of disorders associated with MLH3 activity.

Claims (9)

1 . A single-stranded oligonucleotide of 20 linked nucleosides wherein the nucleobase sequence consists of SEQ ID NO: 515, 1302, or 2491, wherein all thymidines at positions 1-5 and 16-20 of the nucleobase sequence are substituted with 5-methyl-2′-O-methoxyethyl-uridine and all cytidines at positions 6-15 are substituted with 5-methyl-2′-O-methoxyethyl-cytidine, and wherein the backbone is fully phosphorothioate-modified.

2 . The oligonucleotide of claim 1 , further comprising a pseudouridine or 5-methoxyuridine.

3 . The oligonucleotide of claim 1 , further comprising an alternative sugar moiety, wherein the alternative sugar moiety is 2′-O-methyl or a bicyclic nucleic acid.

4 . A pharmaceutical composition comprising the oligonucleotide of claim 1 and a pharmaceutically acceptable carrier or excipient.

5 . A method of treating, preventing, or delaying the progression of a trinucleotide repeat expansion disorder in a subject in need thereof, the method comprising administering the oligonucleotide of claim 1 to the subject.

6 . The method of claim 5 , wherein the trinucleotide repeat expansion disorder is a polyglutamine disease.

7 . The method of claim 5 , wherein the trinucleotide repeat expansion disorder is a non-polyglutamine disease.

8 . A method of preventing or delaying the progression of a trinucleotide repeat expansion disorder in a subject, the method comprising administering to the subject an oligonucleotide of claim 1 in an amount effective to delay progression of a trinucleotide repeat expansion disorder of the subject.

9 . The method of claim 8 , wherein the trinucleotide repeat expansion disorder is selected from the group consisting of dentatorubropallidoluysian atrophy, Huntington's disease, spinal and bulbar muscular atrophy, spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, spinocerebellar ataxia type 6, spinocerebellar ataxia type 7, spinocerebellar ataxia type 17, Huntington's disease-like 2, fragile X syndrome, fragile X-associated tremor/ataxia syndrome, fragile XE mental retardation, Friedreich's ataxia, myotonic dystrophy type 1, spinocerebellar ataxia type 8, spinocerebellar ataxia type 12, oculopharyngeal muscular dystrophy, Fragile X-associated premature ovarian failure, FRA2A syndrome, FRA7A syndrome, and early infantile epileptic encephalopathy.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 20, 2024
From: BERMINGHAM, NESSAN ANTHONY; BETTENCOURT, BRIAN R.; BIALEK, PETER EDWARD
To: TRIPLET THERAPEUTICS, INC.
Reel/Frame 069347/0124 →
PATENT ASSIGNMENT AGREEMENT Recorded Nov 3, 2023
From: TRIPLET ABC, LLC
To: TAKEDA PHARMACEUTICALS U.S.A., INC.
Reel/Frame 065453/0515 →
PATENT ASSIGNMENT AGREEMENT Recorded Nov 3, 2023
From: TRIPLET THERAPEUTICS, INC.
To: TRIPLET ABC, LLC
Reel/Frame 065453/0549 →
Continuity (3)
Provisional Application 62877104 · Jul 22, 2019
Provisional Application 62774777 · Dec 3, 2018
Related Publication 20230042436A1 · Feb 9, 2023
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