Pharmaceutical composition comprising a GLP-1 agonist and methionine

• US 9,707,176 B2
• Filed: 11/11/2010
• Issued: 07/18/2017
• Est. Priority Date: 11/13/2009
• Status: Active Grant

• Current Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Original Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Inventors: Brunner-Schwarz, Anette, Mueller, Werner, Siefke-Henzler, Verena
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US13/509,507
• Publication Number:
  US 20120283179A1
• Time in Patent Office: 2,441 Days
• CPC Class Codes: A61K 38/2278 Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

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.

Claims

1. An aqueous liquid pharmaceutical composition comprising:

(a) 0.01 mg/mL to 1.5 mg/mL desPro³⁶exendin-4(1-39)-Lys₆-NH₂ (“

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°

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°

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°

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°

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°

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 μ

g/mL to about 100 μ

g/mL.

26. The aqueous liquid composition of claim 1, wherein the concentration of AVE0010 is about 33 μ

g/mL to about 50 μ

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 μ

g/mL.

29. The aqueous liquid composition of claim 1, wherein the concentration of AVE0010 is about 50 μ

g/mL.

30. The aqueous liquid composition of claim 1, wherein the concentration of AVE0010 is about 100 μ

g/mL.