Claims for Patent: 10,188,697

Summary for Patent: 10,188,697

Title:	Glycopeptide compositions
Abstract:	Solutions comprising a glycopeptide antibiotic, for example Vancomycin, and an amino acid or amino acid derivative such as N-acetyl-Glycine or N-acetyl-D-Alanine are provided. These solutions are stable or stabilized for long-term periods at conditions of normal use and storage, and can be formulated as pharmaceutical solutions for use in subjects. Methods of manufacturing and using these solutions are also provided, as are methods of stabilizing a glycopeptide antibiotic, for example Vancomycin, using amino acids or amino acid derivatives such as N-acetyl-Glycine or N-acetyl-D-Alanine.
Inventor(s):	Jasprica; Ivona (Zagreb, HR), Keser; Sabina (Zagreb, HR), Pindric; Katarina (Sesvete, HR)
Assignee:	XELLIA PHARMACEUTICALS APS (Kobenhavn S, DK)
Application Number:	15/524,653
Patent Claims:	1. A pharmaceutical composition comprising a glycopeptide antibiotic; an excipient selected from N-acetyl-D-Alanine and N-acetyl-Glycine; and an amino acid. 2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is for parenteral administration. 3. The pharmaceutical composition of claim 1, in the form of a liquid pharmaceutical composition. 4. The pharmaceutical composition of claim 3, wherein the liquid pharmaceutical composition is an aqueous pharmaceutical composition. 5. The pharmaceutical composition of claim 1 wherein the amino acid is selected from Glycine, Alanine, Serine, Leucine, Valine, Lysine, Arginine and Ornithine. 6. The pharmaceutical composition of claim 1, wherein the amino acid is selected from D-Alanine, D-Serine, D-Leucine, D-Valine, L-Lysine, D-Lysine, L-Ornithine, D-Ornithine and L-Arginine. 7. The pharmaceutical composition of claim 6, wherein the amino acid is selected from L-Lysine, D-Lysine, L-Ornithine, D-Ornithine and L-Arginine. 8. The pharmaceutical composition of claim 7, wherein the amino acid is selected from L-Lysine and D-Lysine. 9. The pharmaceutical composition of claim 1, having a pH of about 3-6. 10. The pharmaceutical composition of claim 1, wherein the concentration of the glycopeptide antibiotic is 0.1-1% w/V; and wherein N-acetyl-D-Alanine is present in a molar ratio of 1.1-40:1 to the glycopeptide antibiotic. 11. The pharmaceutical composition of claim 1, wherein the concentration of the glycopeptide antibiotic is 1-10% w/V; and wherein N-acetyl-D-Alanine is present in a molar ratio of 1.1-40:1 to the glycopeptide antibiotic. 12. The pharmaceutical composition of claim 1, wherein the glycopeptide antibiotic is Vancomycin, Teicoplanin, Telavancin, Dalbavancin or Oritavancin. 13. The pharmaceutical composition of claim 4, wherein the pharmaceutical composition is stable for at least 4 weeks at 25 degrees Celsius, wherein stability is demonstrated by determining the amount of the glycopeptide antibiotic remaining in the pharmaceutical composition after at least 4 weeks at 25 degrees Celsius wherein the amount of glycopeptide antibiotic remaining in the pharmaceutical solution is between about 85% and 100%. 14. A method for treating bacterial infections in a subject, comprising administering an aqueous pharmaceutical composition comprising a glycopeptide antibiotic, an excipient selected from N-acetyl-D-Alanine and N-acetyl-Glycine, and an amino acid. 15. The method of claim 14, wherein the pharmaceutical composition is administered parenterally. 16. A method for stabilizing a glycopeptide antibiotic in a pharmaceutical solution, comprising mixing N-acetyl-D-Alanine or N-acetyl Glycine, the glycopeptide antibiotic, and an amino acid. 17. The method of claim 16, wherein the N-acetyl-D-Alanine or N-acetyl Glycine is added to a solution comprising the glycopeptide antibiotic, or the glycopeptide antibiotic is added to a solution comprising the N-acetyl-D-Alanine or N-acetyl-Glycine. 18. The method of claim 16, wherein the N-acetyl-D-Alanine is added to a solution comprising the glycopeptide antibiotic, or the glycopeptide antibiotic is added to a solution comprising the N-acetyl-D-Alanine. 19. The method of claim 16, wherein the pharmaceutical solution is for parenteral administration. 20. The method of claim 16, wherein the pharmaceutical solution is stable for at least 4 weeks at 25 degrees Celsius, wherein stability is demonstrated by determining the amount of the glycopeptide antibiotic remaining in the pharmaceutical solution after at least 4 weeks at 25 degrees Celsius, wherein the amount of glycopeptide antibiotic remaining in the pharmaceutical solution is between about 85% and 100%. 21. The pharmaceutical composition of claim 1, wherein the molar ratio of the amino acid to glycopeptide antibiotic is about 0.5:1 to 40:1. 22. The pharmaceutical composition of claim 1, wherein the concentration of the glycopeptide antibiotic is about 0.1-20% w/V. 23. The pharmaceutical composition of claim 1, comprising about 0.5-15% w/V of the glycopeptide antibiotic, wherein the molar ratio of the N-acetyl-D-Alanine to the glycopeptide antibiotic is about 1:1 to 40:1. 24. The pharmaceutical composition of claim 1, comprising about 0.5-15% w/V glycopeptide antibiotic, wherein the molar ratio of the N-acetyl-D-Alanine to the glycopeptide antibiotic is about 1:1 to 40:1. 25. The pharmaceutical composition of claim 1, comprising about 0.5-15% w/V glycopeptide antibiotic, wherein the molar ratio of the N-acetyl-D-Alanine to the glycopeptide antibiotic is about 1:1 to 40:1, wherein the pharmaceutical composition has a pH of about 3-6 and comprises an amino acid selected from Serine, Leucine, Valine, Lysine, Arginine and Ornithine. 26. The method of claim 14, wherein the pharmaceutical composition comprises about 0.5-15% w/V of the glycopeptide antibiotic, wherein the molar ratio of the N-acetyl-D-Alanine to the glycopeptide antibiotic is about 1:1 to 40:1.