Claims for Patent: 11,759,497

Summary for Patent: 11,759,497

Title:	Daptomycin formulations
Abstract:	The present invention relates to compositions comprising daptomycin and at least one amino acid, methods of providing such compositions and the uses thereof.
Inventor(s):	Anita BEVETEK MOCNIK, Stipica TOMIC, Barbara FUMIC
Assignee:	Xellia d o o , Hikma Pharmaceuticals USA Inc
Application Number:	US16/642,462
Patent Claims:	1. A lyophilized pharmaceutical composition comprising: a) daptomycin b) histidine and c) at least one of the following amino acids or amino acid combinations: arginine, lysine plus arginine, ornithine, phenylalanine plus tryptophan and proline plus alanine, or pharmaceutically acceptable salts thereof; wherein the molar ratio of daptomycin to each amino acid of b) and c) is from about 1:1 to about 1:5 and wherein the composition is a stable lyophilized composition having no more than a 2.0% increase of total impurities from an initial time point to 45 hours at 60° C. as determined by HPLC. 2. The lyophilized pharmaceutical composition according to claim 1, wherein histidine is in form of histidine hydrochloride. 3. The lyophilized pharmaceutical composition according to claim 1, wherein the composition comprises daptomycin, histidine and arginine or pharmaceutically acceptable salts thereof. 4. A method of making a pharmaceutical composition comprising reconstituting the lyophilized pharmaceutical composition according to claim 1 with a liquid diluent, wherein a concentration of daptomycin after reconstitution is from about 0.5 mg/mL to about 500 mg/mL. 5. The method of claim 4, wherein a concentration of daptomycin after reconstitution is from about 20 mg/mL to about 400 mg/mL. 6. The method of claim 4, wherein a concentration of daptomycin after reconstitution is from about 50 mg/mL to about 300 mg/mL. 7. The lyophilized pharmaceutical composition according to claim 1, wherein a molar ratio of daptomycin to each amino acid or a pharmaceutically acceptable salt thereof is from about 1:2 to about 1:5. 8. The lyophilized pharmaceutical composition according to claim 1, wherein a molar ratio of daptomycin to each amino acid or a pharmaceutically acceptable salt thereof is from about 1:3 to about 1:5. 9. The lyophilized pharmaceutical composition according to claim 1, further comprising one or more pharmaceutically acceptable excipients selected from antioxidants, surfactants, lipids, sugars, amino sugars, complexing agents, preservatives, stabilizers, bulking agents, buffers, diluents, vehicles and solubilizers. 10. A process for manufacturing compositions according to claim 1, providing a solution of daptomycin and at least one amino acid, adjusting the pH of such solution to pH from about 3 to about 9 with a suitable pH adjusting agent and lyophilizing or spray drying or fluid bed drying such composition to obtain lyophilized composition. 11. The process for manufacturing compositions according to claim 10, wherein pH is adjusted with a suitable pH adjusting agent to pH from about 4 to about 7. 12. A lyophilized pharmaceutical composition comprising: a) daptomycin, b) histidine and c) at least one of the following amino acids or amino acid combinations: arginine, lysine plus arginine, ornithine, phenylalanine plus tryptophan and proline plus alanine or a pharmaceutically acceptable salt thereof; wherein the molar ratio of daptomycin to at least one of amino acids of b) and c) is from about 1:1 to about 1:5 and wherein the composition is a stable lyophilized composition having no more than a 2.0% increase of total impurities from an initial time point to 45 hours at 60° C. as determined by HPLC. 13. The lyophilized pharmaceutical composition according to claim 12, wherein the molar ratio of daptomycin to at least one of amino acids is about 1:2 to about 1:5. 14. The lyophilized pharmaceutical composition according to claim 12, wherein the molar ratio of daptomycin to at least one of amino acids is about 1:3 to about 1:5.