US 2026/0275314 A1 · COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISORDERS RELATED TO GLUCOSYLCERAMIDASE BETA 1 DEFICIENCY

Abstract

The disclosure relates to compositions and methods for, inter alia, altering, e.g., enhancing, the level of GBA1 protein via delivery using an adeno-associated viral (AAV) capsid variant. The compositions and methods of the present disclosure are useful, inter alia, in the treatment of subjects who have, have been diagnosed with, or are at risk of having a GBA1-related disorder, e.g., Parkinson's Disease (PD), Gaucher Disease (GD), Parkinson's Disease Dementia (PDD), Dementia with Lewy Bodies (DLB), or Lewy Body Dementia (LBD).

Claims180

Dependent claims

An adeno-associated virus (AAV) particle comprising:

a) an AAV capsid variant comprising an amino acid sequence having the following formula:
[N1]-[N2]-[N3], wherein:
(i) optionally [N1] comprises X1, X2, and X3, wherein at least one of X1, X2, or X3 is G:
(ii) [N2] comprises the amino acid sequence of SPH;
and
(iii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid;
and
b) a viral genome comprising a β-glucocerebrosidase 1 (GBA1)-encoding sequence.

5 more elements

An adeno-associated virus (AAV) particle comprising a viral genome comprising the nucleotide sequence of SEQ ID NO:

2001 and an AAV capsid variant comprising:
(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO:
4;
(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO:
4;
and/or
(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO:
4.

5 more elements

An adeno-associated virus (AAV) particle comprising a viral genome comprising the nucleotide sequence of SEQ ID NO:

2001 and an AAV capsid variant comprising:
(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO:
36;
(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO:
36;
and/or
(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO:
36.

5 more elements

An adeno-associated virus (AAV) particle comprising a viral genome comprising the nucleotide sequence of SEQ ID NO:

2002 and an AAV capsid variant comprising:
(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO:
4;
(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO:
4;
and/or
(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO:
4.

5 more elements

An adeno-associated virus (AAV) particle comprising a viral genome comprising the nucleotide sequence of SEQ ID NO:

2002 and an AAV capsid variant comprising:
(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO:
36;
(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO:
36;
and/or
(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO:
36.

5 more elements

Dependencies are inferred from the claim text.

Facts

Application

19/167,963Filed 1 May 2024

Priority

3 May 2023

Published

17 Sep 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification16 codes

C12N 9/2402
Acting on glycosyl compounds: hydrolysing O- and S- glycosyl compounds
A61K 48/0041
Wherein the non-active part clearly interacts with the delivered nucleic acid: the non-active part being polymeric
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…
C07K 14/005
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof: from viruses

Compositions and methods for the treatment of disorders related to glucosylceramidase beta 1 deficiency

Life of this patent

Compositions and methods for the treatment of disorders related to glucosylceramidase beta 1 deficiency

Life of this patent

Abstract

Claims180