Adenoassociated virus vectors for the treatment of mucopolysaccharidoses type IV A

Patent metadata

Field	Value
Publication number	US-12146169-B2
Application number	US-201917059723-A
Country	US
Kind code	B2
Filing date	May 27, 2019
Priority date	May 30, 2018
Publication date	Nov 19, 2024
Grant date	Nov 19, 2024

Abstract

The present invention provides new polynucleotide sequences, adeno-associated virus-derived vectors and pharmaceutical compositions containing the same for the treatment of lysosomal storage disorders and specially, for the treatment of mucopolysaccharidosis type IVA or Morquio A syndrome.

First claim

The invention claimed is:

1. An isolated polynucleotide having a nucleotide sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 5, and SEQ ID NO: 7, wherein the polynucleotide encodes a functional human galactosamine (N-acetyl)-6-sulfatase.

2. An expression vector comprising a polynucleotide of claim 1 .

3. The expression vector of claim 2 , wherein the expression vector comprises a promoter element operatively linked to the polynucleotide, wherein the promoter is selected from a CAG promoter, a hAAT promoter and a CMV promoter.

4. The expression vector of claim 3 , wherein the promoter is a CAG promoter.

5. The expression vector of claim 2 , wherein the vector is a recombinant Adeno-associated virus (AAV) vector.

6. The expression vector of claim 5 , wherein the recombinant AAV vector is selected from AAV2, AAV5, AAV7, AAV8, AAV9, AAV10 and AAVrh10.

7. The expression vector of claim 2 , wherein the vector is selected from the group consisting of the plasmid pAAV-CAG-ohGALNS-version1 as set forth in SEQ ID NO: 4, the plasmid pAAV-CAG-ohGALNS-version2 as set forth in SEQ ID NO: 6, and the plasmid pAAV-CAG-ohGALNS-version3 as set forth in SEQ ID NO: 8.

8. A pharmaceutical composition comprising a therapeutically effective amount of the expression vector of claim 2 .

9. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition is in a form for intravenous administration.

10. A method of treating mucopolysaccharidosis type IVA or Morquio A syndrome in a subject in need thereof, comprising administering the expression vector of claim 5 , alone or in combination with one or more pharmaceutically acceptable excipients.

11. The method of claim 10 , wherein the expression vector is administered intravenously.

12. A method for obtaining a recombinant expression vector comprising the steps of:
(i) providing a cell comprising a polynucleotide of claim 1 , AAV cap proteins, AAV rep proteins and, 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.

Assignees

• Esteve Pharmaceuticals Sa
• Univ Barcelona Autonoma

Inventors

• Bosch Tubert Maria Fátima
• Sanchez Clares Victor
• Ribera Sanchez Albert
• Haurigot Virginia A

Classifications

• C12Y301/06004

  N-Acetylgalactosamine-6-sulfatase (3.1.6.4) · CPC title

• C12N2750/14152

  relating to complementing cells and packaging systems for producing virus or viral particles · CPC title

• C12N2750/14143

  viral genome or elements thereof as genetic vector · CPC title

• C12N15/86 Primary

  Viral vectors · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title