Highly potent acid alpha-glucosidase with enhanced carbohydrates

Patent metadata

Field	Value
Publication number	US-11591583-B2
Application number	US-202217665179-A
Country	US
Kind code	B2
Filing date	Feb 4, 2022
Priority date	Sep 30, 2014
Publication date	Feb 28, 2023
Grant date	Feb 28, 2023

Abstract

Recombinant human alpha glucosidase (rhGAA) composition derived from CHO cells that contains a more optimized glycan composition consisting of a higher amount of rhGAA containing N-glycans carrying mannose-6-phosphate (M6P) or bis-M6P than conventional rhGAAs, along with low amount of non-phosphorylated high mannose glycans, and low amount of terminal galactose on complex oligosaccharides. Compositions containing the rhGAA, and methods of use are described.

First claim

What is claimed is:

1. A composition comprising recombinant human alpha glucosidase (rhGAA), wherein 40%-60% of the N-glycans on the rhGAA are complex type N-glycans, and wherein each rhGAA molecule on average comprises at least one bis-phosphorylated mannose-6-phosphate (bis-M6P glycan).

2. The composition of claim 1 , wherein at least 17% of the total glycans on the rhGAA are bis-M6P glycans.

3. The composition of claim 1 , wherein the rhGAA comprises the amino acid sequence that is at least 90% identical to SEQ ID NO: 4.

4. The composition of claim 1 , wherein the rhGAA comprises at least 3.0 mol mannose-6-phosphate (M6P) residues per mol rhGAA.

5. The composition of claim 4 , wherein the rhGAA comprises at least 4.0 mol M6P residues per mol rhGAA.

6. The composition of claim 4 , wherein the rhGAA comprises at least 5.0 mol M6P residues per mol rhGAA.

7. The composition of claim 4 , wherein the rhGAA comprises at least 6.0 mol M6P residues per mol rhGAA.

8. The composition of claim 4 , wherein the rhGAA comprises at least 7.0 mol M6P residues per mol rhGAA.

9. The composition of claim 4 , wherein the rhGAA comprises from 3.0 mol to 6.0 mol M6P residues per mol rhGAA.

10. The composition of claim 4 , wherein the rhGAA comprises from 3.0 mol to 7.0 mol M6P residues per mol rhGAA.

11. A pharmaceutical composition comprising the rhGAA of claim 1 and at least one pharmaceutically acceptable carrier or excipient.

12. The pharmaceutical composition of claim 11 , wherein the pharmaceutically acceptable carrier is water.

13. The pharmaceutical composition of claim 11 , wherein the composition is in the form of a lyophilized powder.

14. The pharmaceutical composition of claim 11 , wherein the composition comprises mannitol.

15. The pharmaceutical composition of claim 11 , wherein the composition comprises polysorbate 80.

16. The pharmaceutical composition of claim 11 , wherein the composition comprises a pH buffer.

Assignees

• Amicus Therapeutics Inc

Inventors

• Gotschall Russell
• Do Hung V

Classifications

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• A61K38/47

  acting on glycosyl compounds (3.2), e.g. cellulases, lactases · CPC title

• C12N9/2402 Primary

  hydrolysing O- and S- glycosyl compounds (3.2.1) · CPC title

• C12Y302/0102

  Alpha-glucosidase (3.2.1.20) · CPC title