Claims for Patent: 9,707,176

Summary for Patent: 9,707,176

Title:	Pharmaceutical composition comprising a GLP-1 agonist and methionine
Abstract:	A liquid composition comprising a GLP-1 agonist or/and a pharmacologically tolerable salt thereof and, optionally, at least one pharmaceutically acceptable excipient, wherein the composition comprises methionine, as add-on therapy with metformin and/or with long-acting insulin/insulin derivates where appropriate.
Inventor(s):	Brunner-Schwarz; Anette (Frankfurt, DE), Mueller; Werner (Frankfurt am Main, DE), Siefke-Henzler; Verena (Frankfurt am Main, DE)
Assignee:	SANOFI-AVENTIS DEUTSCHLAND GMBH (Frankfurt am Main, DE)
Application Number:	13/509,507
Patent Claims:	1. An aqueous liquid pharmaceutical composition comprising: (a) 0.01 mg/mL to 1.5 mg/mL desPro.sup.36exendin-4(1-39)-Lys.sub.6-NH.sub.2 ("AVE0010") and/or a pharmacologically tolerable salt thereof; (b) methionine; and (c) water, wherein the composition is substantially free of histidine. 2. The aqueous liquid composition of claim 1, wherein the composition further comprises a pharmaceutically acceptable preservative. 3. The aqueous liquid composition of claim 2, wherein the pharmaceutically acceptable preservative is m-cresol. 4. The aqueous liquid composition of claim 1, wherein the composition further comprises glycerol. 5. The aqueous liquid composition of claim 1, wherein the pH of the composition ranges from 3.5 to 5. 6. The aqueous liquid composition of claim 1, wherein the concentration of methionine ranges from 0.5 mg/mL to 20 mg/mL. 7. The aqueous liquid composition of claim 6, wherein the concentration of methionine ranges from 1 mg/mL to 5 mg/mL. 8. The aqueous liquid composition of claim 1, wherein the composition exhibits chemical integrity after storage for 6 months at a temperature of +25.degree. C. 9. The aqueous liquid composition of claim 8, wherein at least 80% of the liquid composition's active substance is in a substantially chemically unchanged form after storage for 6 months at a temperature of +25.degree. C. 10. The aqueous liquid composition of claim 8, wherein the percentage of oxidized methionine with respect to the entire methionine content of the GLP-1 agonist after storage for 6 months at a temperature of +25.degree. C. is below 0.7%. 11. The aqueous liquid composition of claim 8, wherein the proportion of total impurities with respect to the entire mass of the GLP-1 agonist present in the composition after storage for 6 months at +25.degree. C. is below 10%. 12. The aqueous liquid composition of claim 8, wherein the proportion of proteins of high molecular weight with respect to the entire mass of the GLP-1 agonist in the composition after storage for 6 months at +25.degree. C. is below 0.8%. 13. The aqueous liquid composition of claim 1, comprising: (a) 0.01 mg/mL to 1.5 mg/mL AVE0010 and/or a pharmacologically tolerable salt thereof; (b) sodium acetate; (c) m-cresol; (d) L-methionine; (e) glycerol; and water, wherein the composition is substantially free of histidine. 14. The aqueous liquid composition of claim 13, wherein the composition is substantially free of ethylenediaminetetraacetic acid (EDTA). 15. The aqueous liquid composition of claim 13, wherein the concentration of AVE0010 is about 0.01 mg/mL to about 0.5 mg/mL. 16. The aqueous liquid composition of claim 13, wherein the composition has a pH of about 4.5. 17. The aqueous liquid composition of claim 1, wherein the composition is an injectable composition. 18. The aqueous liquid composition of claim 1, wherein the composition further comprises at least one pharmaceutically acceptable excipient. 19. The aqueous liquid composition of claim 1, wherein the composition is suitable for parenteral administration. 20. The aqueous liquid composition of claim 1, wherein the composition is substantially free of ethylenediaminetetraacetic acid (EDTA). 21. The aqueous liquid composition of claim 1, wherein the composition comprises at least 50% w/w of water. 22. The aqueous liquid composition of claim 1, further comprising a buffer. 23. The aqueous liquid composition of claim 22, wherein the buffer is acetate, phosphate, or citrate. 24. The aqueous liquid composition of claim 22, wherein the buffer is acetate. 25. The aqueous liquid composition of claim 1, wherein the concentration of AVE0010 is about 50 .mu.g/mL to about 100 .mu.g/mL. 26. The aqueous liquid composition of claim 1, wherein the concentration of AVE0010 is about 33 .mu.g/mL to about 50 .mu.g/mL. 27. The aqueous liquid composition of claim 1, wherein the concentration of AVE0010 is about 0.01 mg/mL to about 0.5 mg/mL. 28. The aqueous liquid composition of claim 1, wherein the concentration of AVE0010 is about 33 .mu.g/mL. 29. The aqueous liquid composition of claim 1, wherein the concentration of AVE0010 is about 50 .mu.g/mL. 30. The aqueous liquid composition of claim 1, wherein the concentration of AVE0010 is about 100 .mu.g/mL.