IP Library › Granted Patent US 12,521,412
Granted Patent B2
US 12,521,412 · App. 17/268,654 · Granted Jan 13, 2026

Nucleic acids and nucleic acid analogs for treating, preventing, and disrupting pathological polynucleotide-binding protein inclusions

Inventors: Christopher Donnelly (Pittsburgh, PA); Jacob Mann (Pittsburgh, PA); James Shorter (Philadelphia, PA); Lin Guo (Philadelphia, PA); Bede Portz (Philadelphia, PA)
Assignees: UNIVERSITY OF PITTSBURGH OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION; THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
A61K31/7088A61P25/28
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Quick Facts
Patent No.
US 12,521,412
App. No.
17/268,654
Granted
Jan 13, 2026
Kind
B2
Abstract

Disclosed herein are methods to treat a neurodegenerative disease comprising administering to a subject with a neurodegenerative disease a therapeutically effective amount of a polynucleotide that binds a nucleic acid-binding polypeptide, wherein the nucleic acid-binding polypeptide can aggregate in cells and is associated with a neurodegenerative disease. Also disclosed are methods to inhibit protein aggregation in a cell comprising contacting the cell with a composition comprising a polynucleotide that binds a nucleic acid-binding polypeptide, wherein the nucleic acid-binding polypeptide can aggregate in cells and is associated with a neurodegenerative disease. Additionally disclosed are compositions comprising a polynucleotide that binds a nucleic acid-binding polypeptide, wherein the nucleic acid-binding polypeptide can aggregate in cells and is associated with a neurodegenerative disease.

Claims (18)

1 . A method to inhibit nucleic acid-binding polypeptide aggregation in a neuronal cell comprising contacting the neuronal cell with a composition comprising a polynucleotide that binds the nucleic acid-binding polypeptide, wherein the nucleic acid-binding polypeptide aggregates in the neuronal cell and is associated with a neurodegenerative disease, wherein the nucleic acid-binding polypeptide is Fused in Sarcoma RNA binding protein (FUS), and wherein the neurodegenerative disease is selected from Multisystem Proteinopathy, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Alzheimer's Disease, Chronic Traumatic Encephalopathy, Traumatic Brain Injury, Cortical Basal Degeneration, and Huntington's Disease, wherein the polynucleotide comprises SEQ ID NO: 96.

2 . The method of claim 1 , wherein the neurodegenerative disease is Amyotrophic Lateral Sclerosis or Frontotemporal Dementia.

3 . The method of claim 1 , wherein the method reduces a rate of aggregation of the nucleic acid-binding polypeptide or an amount of aggregate of the nucleic acid-binding polypeptide in the neuronal cell compared to an untreated control.

4 . A method to inhibit nucleic acid-binding polypeptide aggregation in a neuronal cell comprising contacting the neuronal cell with a composition comprising a polynucleotide that binds the nucleic acid-binding polypeptide, wherein the nucleic acid-binding polypeptide aggregates in the neuronal cell and is associated with a neurodegenerative disease, wherein the nucleic acid-binding polypeptide is FUS, and wherein the neurodegenerative disease is selected from Multisystem Proteinopathy, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Alzheimer's Disease, Chronic Traumatic Encephalopathy, Traumatic Brain Injury, Cortical Basal Degeneration, and Huntington's Disease, wherein the polynucleotide comprises SEQ ID NO: 97.

5 . The method of claim 4 , wherein the neurodegenerative disease is Amyotrophic Lateral Sclerosis or Frontotemporal Dementia.

6 . The method of claim 4 , wherein the method reduces a rate of aggregation of the nucleic acid-binding polypeptide or an amount of aggregate of the nucleic acid-binding polypeptide in the neuronal cell compared to an untreated control.

7 . A method to inhibit nucleic acid-binding polypeptide aggregation in a neuronal cell comprising contacting the neuronal cell with a composition comprising a polynucleotide that binds the nucleic acid-binding polypeptide, wherein the nucleic acid-binding polypeptide aggregates in the neuronal cell and is associated with a neurodegenerative disease, wherein the nucleic acid-binding polypeptide is FUS, and wherein the neurodegenerative disease is selected from Multisystem Proteinopathy, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Alzheimer's Disease, Chronic Traumatic Encephalopathy, Traumatic Brain Injury, Cortical Basal Degeneration, and Huntington's Disease, wherein the polynucleotide comprises SEQ ID NO: 98.

8 . The method of claim 7 , wherein the neurodegenerative disease is Amyotrophic Lateral Sclerosis or Frontotemporal Dementia.

9 . The method of claim 7 , wherein the method reduces a rate of aggregation of the nucleic acid-binding polypeptide or an amount of aggregate of the nucleic acid-binding polypeptide in the neuronal cell compared to an untreated control.

10 . A method to inhibit nucleic acid-binding polypeptide aggregation in a neuronal cell comprising contacting the neuronal cell with a composition comprising a polynucleotide that binds the nucleic acid-binding polypeptide, wherein the nucleic acid-binding polypeptide aggregates in the neuronal cell and is associated with a neurodegenerative disease, wherein the nucleic acid-binding polypeptide is FUS, and wherein the neurodegenerative disease is selected from Multisystem Proteinopathy, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Alzheimer's Disease, Chronic Traumatic Encephalopathy, Traumatic Brain Injury, Cortical Basal Degeneration, and Huntington's Disease, wherein the polynucleotide comprises SEQ ID NO: 99.

11 . The method of claim 10 , wherein the neurodegenerative disease is Amyotrophic Lateral Sclerosis or Frontotemporal Dementia.

12 . The method of claim 10 , wherein the method reduces a rate of aggregation of the nucleic acid-binding polypeptide or an amount of aggregate of the nucleic acid-binding polypeptide in the neuronal cell compared to an untreated control.

13 . A method to inhibit nucleic acid-binding polypeptide aggregation in a neuronal cell comprising contacting the neuronal cell with a composition comprising a polynucleotide that binds the nucleic acid-binding polypeptide, wherein the nucleic acid-binding polypeptide aggregates in the neuronal cell and is associated with a neurodegenerative disease, wherein the nucleic acid-binding polypeptide is FUS, and wherein the neurodegenerative disease is selected from Multisystem Proteinopathy, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Alzheimer's Disease, Chronic Traumatic Encephalopathy, Traumatic Brain Injury, Cortical Basal Degeneration, and Huntington's Disease, wherein the polynucleotide comprises SEQ ID NO: 100.

14 . The method of claim 13 , wherein the neurodegenerative disease is Amyotrophic Lateral Sclerosis or Frontotemporal Dementia.

15 . The method of claim 13 , wherein the method reduces a rate of aggregation of the nucleic acid-binding polypeptide or an amount of aggregate of the nucleic acid-binding polypeptide in the neuronal cell compared to an untreated control.

16 . A method to inhibit nucleic acid-binding polypeptide aggregation in a neuronal cell comprising contacting the neuronal cell with a composition comprising a polynucleotide that binds the nucleic acid-binding polypeptide, wherein the nucleic acid-binding polypeptide aggregates in the neuronal cell and is associated with a neurodegenerative disease, wherein the nucleic acid-binding polypeptide is FUS, and wherein the neurodegenerative disease is selected from Multisystem Proteinopathy, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Alzheimer's Disease, Chronic Traumatic Encephalopathy, Traumatic Brain Injury, Cortical Basal Degeneration, and Huntington's Disease, wherein the polynucleotide comprises SEQ ID NO: 101.

17 . The method of claim 16 , wherein the neurodegenerative disease is Amyotrophic Lateral Sclerosis or Frontotemporal Dementia.

18 . The method of claim 16 , wherein the method reduces a rate of aggregation of the nucleic acid-binding polypeptide or an amount of aggregate of the nucleic acid-binding polypeptide in the neuronal cell compared to an untreated control.

Assignments (3)
CONFIRMATORY LICENSE Recorded Nov 22, 2023
From: UNIVERSITY OF PITTSBURGH
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065664/0434 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 19, 2021
From: DONNELLY, CHRISTOPHER; MANN, JACOB
To: UNIVERSITY OF PITTSBURGH-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 055334/0608 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 19, 2021
From: SHORTER, JAMES; GUO, LIN; PORTZ, BEDE
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 055334/0823 →
Continuity (2)
Provisional Application 62764828 · Aug 16, 2018
Related Publication 20210169914A1 · Jun 10, 2021
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