IP Library › Granted Patent US 12,570,963
Granted Patent B2
US 12,570,963 · App. 18/298,529 · Granted Mar 10, 2026

Gene therapies for lysosomal disorders

Inventors: Asa Abeliovich (New York, NY); Laura Heckman (New York, NY); Herve Rhinn (New York, NY)
Assignee: PREVAIL THERAPEUTICS, INC.
C12N7/00A61K9/0019A61K9/0085A61K35/76A61K35/761A61K48/0058A61K48/0075A61P25/16C07K14/005C07K14/435C07K14/47C07K14/61C07K14/70503A61K39/23C07H21/04C12N15/86C12N15/8645C12N2750/14121C12N2750/14122C12N2750/14143C12N2830/48C12N2830/50C12Y302/01045
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Quick Facts
Patent No.
US 12,570,963
App. No.
18/298,529
Granted
Mar 10, 2026
Kind
B2
Abstract

The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof alone or in combination with one or more PD-associated genes. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

Claims (26)

1 . A method for expressing PGRN protein in the central nervous system of a subject, the method comprising administering to the subject a rAAV comprising:

(i) an AAV9 capsid protein; and

(ii) a rAAV vector comprising a nucleic acid comprising an expression construct comprising a promoter operably linked to a transgene insert encoding a PGRN protein, wherein the transgene insert comprises the nucleotide sequence of SEQ ID NO: 68.

2 . The method of claim 1 , wherein the promoter is a chicken beta actin (CBA) promoter.

3 . The method of claim 1 , wherein the rAAV vector further comprises a cytomegalovirus (CMV) enhancer.

4 . The method of claim 1 , wherein the rAAV vector further comprises a Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE).

5 . The method of claim 1 , wherein the rAAV vector further comprises a Bovine Growth Hormone polyA signal tail.

6 . The method of claim 1 , wherein the nucleic acid comprises two adeno-associated virus inverted terminal repeats (ITR) sequences flanking the expression construct.

7 . The method of claim 6 , wherein each ITR sequence is a wild-type AAV2 ITR sequence.

8 . The method of claim 6 , wherein each ITR sequence comprises a “D” region (SEQ ID NO: 27) that is proximal to the expression construct.

9 . The method of claim 6 , wherein at least one of the ITR sequences comprises a “D” region (SEQ ID NO: 27) positioned on the outside of the ITR sequence relative to the expression construct.

10 . The method of claim 6 , wherein the ITR sequence positioned 5′ relative to the expression construct comprises a “D” region (SEQ ID NO: 27) that is proximal to the expression construct, and the ITR sequence positioned 3′ relative to the expression construct comprises a “D” region (SEQ ID NO: 27) positioned on the outside of the ITR sequence relative to the expression construct.

11 . The method of claim 10 , wherein the nucleic acid sequence of the 5′ ITR is nucleotides 1-145 of SEQ ID NO: 1 and the nucleic acid sequence of the 3′ ITR is nucleic nucleotides 3867-4011 of SEQ ID NO: 1.

12 . The method of claim 10 , wherein the rAAV vector further comprises a region between the 5′ ITR and the expression construct, wherein the region has the sequence set forth in SEQ ID NO: 28.

13 . The method of claim 1 , wherein the rAAV is administered by intra-cisterna magna injection.

14 . A method for expressing PGRN protein in the central nervous system of a subject, the method comprising administering to the subject a rAAV comprising:

(i) an AAV9 capsid protein; and

(ii) a rAAV vector comprising a nucleic acid comprising, in 5′ to 3′ order:

(a) a first ITR;

(b) a CMV enhancer;

(c) a CBA promoter;

(d) a transgene insert encoding a PGRN protein, wherein the transgene insert comprises the nucleotide sequence of SEQ ID NO: 68;

(e) a WPRE;

(f) a Bovine Growth Hormone polyA signal tail; and

(g) a second ITR.

15 . The method of claim 14 , wherein the rAAV is administered by intra-cisterna magna injection.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 12, 2023
From: ABELIOVICH, ASA; HECKMAN, LAURA; RHINN, HERVE
To: PREVAIL THERAPEUTICS, INC.
Reel/Frame 063296/0734 →
Continuity (9)
Division 16904909 · Jun 18, 2020
Continuation 16690320 · Nov 21, 2019
Continuation PCTUS2018054227 · Oct 3, 2018
Provisional Application 62567301 · Oct 3, 2017
Provisional Application 62567311 · Oct 3, 2017
Provisional Application 62567296 · Oct 3, 2017
Provisional Application 62567310 · Oct 3, 2017
Provisional Application 62567319 · Oct 3, 2017
Related Publication 20230287358A1 · Sep 14, 2023
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