Adenoassociated virus vectors for the treatment of mucopolysaccharidoses

Patent metadata

Field	Value
Publication number	US-11338046-B2
Application number	US-201716337953-A
Country	US
Kind code	B2
Filing date	Sep 22, 2017
Priority date	Sep 30, 2016
Publication date	May 24, 2022
Grant date	May 24, 2022

Abstract

The present invention provides new adeno-associated virus-derived vectors and pharmaceutical compositions containing the same for the treatment of lysosomal storage disorders and specially, for the treatment of mucopolysaccharidoses Type IIID.

First claim

The invention claimed is:

1. A polynucleotide comprising an expression cassette, wherein the expression cassette comprises a transcriptional regulatory region comprising a promoter operatively linked to a nucleotide sequence as set forth in SEQ ID NO: 4 encoding the N-acetylglucosamine 6-sulfatase (GNS) protein.

2. The polynucleotide of claim 1 wherein the promoter is a constitutive promoter.

3. The polynucleotide of claim 2 , wherein the promoter is the CAG promoter.

4. The polynucleotide of claim 1 , wherein the expression cassette is flanked by adeno-associated virus inverted terminal repeats (ITRs).

5. A vector comprising the polynucleotide of claim 1 , wherein the vector is an adeno-associated viral vector.

6. The vector of claim 5 , wherein the vector is an Adeno-associated Viral Vector of serotype 9 (AAV9).

7. A pharmaceutical composition comprising a therapeutically effective amount of the vector of claim 5 , and a pharmaceutically acceptable carrier and/or adjuvant.

8. A method for the treatment and/or prevention of mucopolysaccharidosis type IIID in a subject in need thereof comprising administering to the subject, the pharmaceutical composition of claim 7 .

9. A method for the treatment and/or prevention of mucopolysaccharidosis type IIID in a subject in need thereof comprising administering to the subject, the vector of claim 5 .

10. A pharmaceutical composition comprising a therapeutically effective amount of the polynucleotide of claim 1 , and a pharmaceutically acceptable carrier and/or adjuvant.

11. A method for the treatment and/or prevention of mucopolysaccharidosis type IIID in a subject in need thereof comprising administering to the subject, the pharmaceutical composition of claim 10 .

12. A method for the treatment and/or prevention of mucopolysaccharidosis type IIID in a subject in need thereof comprising administering to the subject, the polynucleotide of claim 1 .

13. A method for obtaining a recombinant adeno-associated viral vector (AAV) comprising the polynucleotide of claim 1 , comprising the steps of:
(i) providing a cell comprising the polynucleotide of claim 1 , AAV cap proteins, AAV rep proteins and, optionally, viral proteins upon which AAV is dependent for replication,
(ii) maintaining the cell under conditions adequate for assembly of the AAV; and
(iii) purifying the adeno-associated viral vector produced by the cell.

14. A plasmid pAAV-CAG-ohGNS-version3 having accession number DSM 32345, as set forth in SEQ ID NO: 8.

Assignees

• Esteve Pharmaceuticals Sa
• Univ Barcelona Autonoma

Inventors

• Roca Lecha Carles
• Haurigot-Mendonça Virginia A
• Bosch Tubert Fàtima

Classifications

• C12N9/16 Primary

  acting on ester bonds (3.1) · CPC title

• C12Y301/06014

  N-Acetylglucosamine-6-sulfatase (3.1.6.14) · CPC title

• A01K2217/075

  inducing loss of function, i.e. knock out · CPC title

• A61K48/0066 Primary

  Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid · CPC title

• C12N2830/90

  avian · CPC title