Crystal forms of sialic acid or salt or solvate thereof

Patent metadata

Field	Value
Publication number	US-10385085-B2
Application number	US-201615265215-A
Country	US
Kind code	B2
Filing date	Sep 14, 2016
Priority date	Sep 14, 2015
Publication date	Aug 20, 2019
Grant date	Aug 20, 2019

Abstract

The present invention includes crystalline forms of N-acetylneuraminic acid (NeuAc) and crystalline forms of salts and/or solvates of N-acetylneuraminic acid (NeuAc). Furthermore, the present invention provides compositions comprising these crystalline forms and therapeutic use of the crystalline forms.

First claim

The invention claimed is:

1. A crystalline form of N-acetylneuraminic acid (NeuAc), wherein the crystalline form is polymorphic Form 1 which exhibits an X-ray powder diffraction pattern comprising peaks at about 10.34±0.3; 17.91±0.3; and 22.06±0.3 degrees two-theta.

2. The crystalline form of claim 1 , which exhibits an X-ray powder diffraction pattern further comprising peaks at about 5.95±0.3 and 11.93±0.3.

3. The crystalline form of claim 1 , which exhibits an X-ray powder diffraction pattern further comprising one or more peaks at degree two-theta selected from the group consisting of: 5.95±0.3; 11.93±0.3; 14.12±0.3; 19.84±0.3; 20.72±0.3; 21.31±0.3; 24.73±0.3; and 29.60±0.3.

4. The crystalline form of claim 1 , which exhibits a Differential Scanning calorimetry (DSC) thermogram having an endotherm with an onset of about 188.6° C.

5. The crystalline form of claim 1 , which is anhydrous.

6. A dosage form comprising the crystalline form of claim 1 .

7. The dosage form of claim 6 , which is an oral unit dosage form.

8. The dosage form of claim 7 , wherein the oral dosage form contains the crystalline form in an amount equivalent to about 100 mg to about 1000 mg of NeuAc.

9. The dosage form of claim 8 , wherein the oral dosage form contains the crystalline form in an amount equivalent to about 325 mg or 500 mg of NeuAc.

10. A pharmaceutical composition comprising the crystalline form of claim 1 and a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10 , wherein the crystalline form has a chemical purity of about 98.5% or higher.

12. The pharmaceutical composition of claim 10 , wherein the crystalline form has a polymorphic purity of about 50% or higher.

13. The pharmaceutical composition of claim 10 , wherein the crystalline form has a polymorphic purity of 95% or higher.

14. The pharmaceutical composition of claim 10 , wherein the crystalline form contains:
ethanol in an amount of about 1.0% or less; or
acetic acid in an amount of about 1.0% or less; and/or
N-acetyl-D-glucosamine in an amount of about 0.5% or less.

15. The pharmaceutical composition of claim 10 , wherein the crystalline form contains;
polymorphic Form 2 of NeuAc in an amount of about 0.5% or less; or
polymorphic Form 3 of NeuAc in an amount of about 0.5% or less; and/or
polymorphic Form 4 of NeuAc in an amount of about 0.5% or less.

16. A method for treating a sialic acid deficiency comprising administering to a patient in need of such treatment a therapeutically effective amount of the crystalline form of claim 1 .

Assignees

• Ultragenyx Pharmaceutical Inc

Inventors

• Klopp John
• Reece Hayley
• Arlin Jean-Baptiste
• Reisinger-Becker Corinna Marie
• Dufour Fabrice

Classifications

• A61P31/16

  for influenza or rhinoviruses · CPC title

• A61P31/12

  Antivirals · CPC title

• C07H13/04

  having the esterifying carboxyl radicals attached to acyclic carbon atoms · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07H15/12 Primary

  attached to a nitrogen atom of the saccharide radical · CPC title