Gip / glpi agonist compositions

Abstract

The present invention relates to GIP / GLP1 agonist compositions. The present invention is a GIP / GLP1 co-agonist peptide pharmaceutical composition for subcutaneous injection. The composition comprises tirzepatide, NaCl, and disodium hydrogen phosphate. The composition provides commercially acceptable shelf-life stability, use-life stability, and an acceptable patient injection site experience. An alternative composition comprises tirzepatide, propylene glycol, and disodium hydrogen phosphate, which also provides acceptable shelf-life stability.

Description

[0001] This application is a divisional application. The parent application is the application filed on June 14, 2019, with application number 201980042455.0 and invention title "GIP / GLP1 agonist composition". Technical Field

[0002] This invention relates to a GIP / GLP1 co-agonist peptide pharmaceutical composition for subcutaneous injection. The composition comprises tirzepatide, NaCl, and disodium hydrogen phosphate. The composition provides commercially acceptable shelf-life stability, in-use stability, and is associated with acceptable patient injection site experience. Alternative compositions comprise tirzepatide, propylene glycol, and disodium hydrogen phosphate, which also provide acceptable shelf-life stability. Background of the Invention

[0003] Diabetes mellitus is a chronic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. In type 2 diabetes (“T2D”), the combined effects of impaired insulin secretion and insulin resistance are associated with elevated blood glucose levels. Telposide is a GIP / GLP1 co-agonist peptide that can be used to treat diabetes. Telposide can also be used to treat obesity.

[0004] US9474780 broadly describes compositions containing a GIP / GLP1 agonist administered via the parenteral route. US9474780 describes and claims protection for telpolide. There is a need for telpolide compositions that provide acceptable stability and an acceptable patient injection site experience. Summary of the Invention

[0005] The present invention addresses these needs by providing pharmaceutically acceptable compositions of telpolide or pharmaceutically acceptable salts thereof; said compositions comprising: a reagent selected from NaCl and propylene glycol; and disodium hydrogen phosphate.

[0006] In one embodiment, the reagent is NaCl. In one embodiment, the concentration of the NaCl is from about 6.2 mg / mL to about 9.5 mg / mL. In one embodiment, the concentration of the NaCl is from about 7.0 mg / mL to about 9.0 mg / mL. In one embodiment, the concentration of the NaCl is about 8.2 mg / mL.

[0007] In one embodiment, the reagent is propylene glycol. In one embodiment, the concentration of the propylene glycol is from about 12.0 mg / mL to about 18.0 mg / mL. In one embodiment, the concentration of the propylene glycol is from about 14.0 mg / mL to about 16.0 mg / mL. In one embodiment, the concentration of the propylene glycol is about 15.0 mg / mL.

[0008] In one embodiment, the concentration of disodium hydrogen phosphate is from about 0.67 mg / mL to about 2.68 mg / mL. In one embodiment, the concentration of disodium hydrogen phosphate is from about 1.0 mg / mL to about 3.0 mg / mL. In one embodiment, the concentration of disodium hydrogen phosphate is about 1.34 mg / mL.

[0009] In one embodiment, the concentration of the telpolide is from about 5 mg / mL to about 30 mg / mL and the reagent is NaCl. In one embodiment, the concentration of the telpolide is from about 10 mg / mL to about 30 mg / mL. In one embodiment, the concentration of the telpolide is from about 5 mg / mL to about 30 mg / mL; the concentration of the NaCl is from about 8.2 mg / mL; and the concentration of disodium hydrogen phosphate is from about 0.67 mg / mL to about 2.68 mg / mL. In one embodiment, the concentration of the telpolide is from about 5 mg / mL to about 30 mg / mL; the concentration of the NaCl is from about 8.2 mg / mL; the concentration of disodium hydrogen phosphate is from about 0.67 mg / mL to about 2.68 mg / mL; and the composition is provided in a single-use automated injection device.

[0010] In one embodiment, the concentration of the telpokines is from about 5 mg / mL to about 30 mg / mL; and the reagent is propylene glycol. In one embodiment, the concentration of the telpokines is from about 5 mg / mL to about 30 mg / mL; the concentration of the propylene glycol is from about 12.0 mg / mL to about 18.0 mg / mL; and the concentration of the disodium hydrogen phosphate is about 1.34 mg / mL. In one embodiment, the concentration of the telpokines is from about 5 mg / mL to about 30 mg / mL; the concentration of the propylene glycol is about 15.0 mg / mL; and the concentration of the disodium hydrogen phosphate is about 1.34 mg / mL.

[0011] In one embodiment, the concentration of the telpokinesin is from about 5 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the telpokinesin is from about 10 mg / mL to about 30 mg / mL. In one embodiment, the concentration of the telpokinesin is selected from 5, 10, 15, 20, 25, and 30 mg / mL. In one embodiment, 0.5 mL or less of the composition is administered as a dose. In one embodiment, the concentration of the telpokinesin is selected from 10, 20, and 30 mg / mL.

[0012] In one embodiment, the composition of the telpolide further comprises a preservative. In one embodiment, the composition of the telpolide comprises telpolide, disodium hydrogen phosphate, propylene glycol, and a preservative. In one embodiment, the preservative is selected from m-cresol and phenol. In one embodiment, the concentration of m-cresol is from about 2.0 mg / mL to about 4.0 mg / mL. In one embodiment, the concentration of m-cresol is from about 3.0 mg / mL to about 3.5 mg / mL. In one embodiment, the concentration of m-cresol is about 3.15 mg / mL. In one embodiment, the concentration of phenol is from about 3.0 mg / mL to about 7.0 mg / mL. In one embodiment, the concentration of phenol is from about 4.0 mg / mL to about 6.0 mg / mL. In one embodiment, the concentration of phenol is about 5.0 mg / mL. In one embodiment, a telposide composition is provided, wherein the concentration of telposide is from about 5 mg / mL to about 30 mg / mL; the concentration of propylene glycol is from about 12.0 mg / mL to about 18.0 mg / mL; the concentration of disodium hydrogen phosphate is from about 0.67 mg / mL to about 2.68 mg / mL; and the concentration of m-cresol is from about 2.0 mg / mL to about 4.0 mg / mL. In one embodiment, the concentration of m-cresol is about 3.15 mg / mL. In another embodiment, a telposide composition is provided, wherein the concentration of telposide is from about 5 mg / mL to about 30 mg / mL; the concentration of propylene glycol is from about 12.0 mg / mL to about 18.0 mg / mL; the concentration of disodium hydrogen phosphate is from about 0.67 mg / mL to about 2.68 mg / mL; and the concentration of phenol is from about 3.0 mg / mL to about 7.0 mg / mL. In one embodiment, a telpokines composition is provided, wherein the concentration of telpokines is from about 5 mg / mL to about 30 mg / mL; the concentration of propylene glycol is from about 12.0 mg / mL to about 18.0 mg / mL; the concentration of disodium hydrogen phosphate is from about 0.67 mg / mL to about 2.68 mg / mL; and the concentration of phenol is about 5.0 mg / mL.

[0013] In one embodiment, the dose of the telpolide composition is administered approximately once a week. In another embodiment, the dose of the telpolide composition is administered once every seven days.

[0014] In one embodiment, a method for treating diabetes is provided, the method comprising administering an effective dose of the above-described composition to a person in need.

[0015] In one embodiment, a method for treating obesity is provided, the method comprising administering an effective dose of one of the above-described compositions to a person in need. In one embodiment, a method for providing therapeutic weight loss is provided, the method comprising administering an effective dose of one of the above-described compositions to a person in need. In one embodiment, a method for treating a condition mediated by GIP / GLP1 co-agonist activity is provided, the method comprising administering an effective dose of one of the above-described compositions to a person in need.

[0016] In one embodiment, one of the above-described compositions is provided for use in pharmaceutical form.

[0017] In one embodiment, one of the above-described compositions is provided for treating diabetes. In one embodiment, one of the above-described compositions is provided for treating obesity.

[0018] In one embodiment, one of the above-described compositions is provided for providing therapeutic weight loss. In another embodiment, one of the above-described compositions is provided for providing non-therapeutic weight loss.

[0019] According to another aspect of the invention, an article of manufacture comprising one of the above-described compositions is provided. In some embodiments, the article is a multi-purpose vial. In some embodiments, the article is a pre-filled syringe. In some embodiments, the article is an autoinjector (“autoinjector”). Examples of autoinjectors, as contemplated herein, are proposed in U.S. Patent 8,734,394.

[0020] As used herein, “telpolide” means the GIP / GLP1 co-agonist peptide described in US 9,474,780 and by CAS Registry No. 2023788-19-2. The telpolide described in Example 1 of US 9474,780 has the following sequence: YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS Where X1 is Aib; X2 is Aib; and K at position 20 is represented by (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2). 18 -CO2H is chemically modified by conjugating the ε-amino group of the K side chain; and the C-terminal amino acid is amidated to form a C-terminal primary amide (SEQ ID NO: 1).

[0021] When used herein, "pharmaceutically acceptable salt" is well known to those skilled in the art. In one embodiment, the pharmaceutically acceptable salt is telposide trifluoroacetate.

[0022] When used herein, the term "surfactant-free" means that the composition contains no added surfactant, or contains only trace amounts of surfactant. de minimis ) added surfactant.

[0023] When used herein, the term "propylene glycol" is well known to those skilled in the art. Propylene glycol is also represented by the formula C3H8O2.

[0024] The compositions of the present invention have a concentration of telpolide from 5 mg / mL to 30 mg / mL. The compositions of the present invention may have specific concentrations of 5, 10, 15, 20, 25, and 30 mg / mL. Such compositions can be provided in pre-filled syringes. Such pre-filled syringes can be used for half a milliliter of such composition / patient / dose. The dosage of the telpolide composition can be administered using a dosing regimen determined by a clinician.

[0025] The composition is initially sterile during production. If supplied in reusable vials or cartridges, an antimicrobial preservative compound or mixture of compounds compatible with the other components of the composition may be added at sufficient concentrations to meet applicable regulatory antimicrobial preservative requirements. Pharmaceutically acceptable preservatives are well known in the art (see, for example, Remington: The Science and Practice of Pharmacy (DB Troy, Editor, 21st ed., Lippincott, Williams & Wilkins, 2006). In one embodiment, the preservative is m-cresol. In one embodiment, the preservative is phenol. Compositions for single-use prefilled syringes do not require preservatives. In one embodiment, the composition does not contain a surfactant.

[0026] The pH of the telpokines compositions of the present invention is typically 6.5 to 7.5, and the pH is adjusted using physiologically suitable acids and bases, as this may be necessary to achieve the desired pH. In one embodiment, the pH target is 6.7 to 7.3. Patient injection site experience is a consideration when subcutaneously administering the composition. It is desirable to select compositions associated with an acceptable patient injection site experience. For example, NaCl and citrate have been associated with painful stimulation at the injection site. (Laursen, T.; Hansen, B.; Fisker, S. Pain perception after subcutaneous injections of media containing different buffers.) Basic & Clinical Pharmacology & Toxicology 2006, 98 , (2), 218-221.), (Fransson, J.; Espander‐Jansson, Local tolerance of subcutaneous injections. Journal of Pharmacy and Pharmacology 1996, 48 (10), 1012-1015.) When the composition is applied, it is further desirable to match the fluid tension (i.e., weight osmolality) at the injection site as closely as possible, because solutions that are not approximately isotonic with the fluid will produce a painful stinging sensation upon application. It is desirable that the composition is approximately isotonic with the fluid at the injection site. The compositions of the present invention comprising telpolide, NaCl, and disodium hydrogen phosphate are associated with an acceptable patient injection site experience. Similarly, compositions comprising telpolide, propylene glycol, and disodium hydrogen phosphate are associated with an acceptable patient injection site experience.

[0027] In one embodiment, the pH is adjusted with a base to promote dissolution in a buffer solution. It may be necessary to add an acid to the composition to adjust the pH to a desired range. In one embodiment, NaOH is used to promote the dissolution of telpolide in a buffer solution. In one embodiment, HCl is added to adjust the pH of the composition containing the dissolved telpolide to a desired range.

[0028] The compositions of the present invention are typically administered subcutaneously. The compositions are typically administered using pre-filled disposable pen-type, reusable pen-type, or automated pen-type syringes. Reusable vials or pump devices can also be used to administer the compositions. In one embodiment, the device is the automated injection device claimed in U.S. Patent 8,734,394.

[0029] Compositions containing telpotetamide, NaCl, and disodium hydrogen phosphate offer the desired shelf-life stability and provide patients with an acceptable injection site experience. Similarly, compositions containing telpotetamide, propylene glycol, and disodium hydrogen phosphate offer the desired shelf-life stability and provide patients with an acceptable injection site experience. As used herein, “shelf-life stability” is determined under controlled conditions at approximately 5 degrees Celsius. Compositions containing telpotetamide, NaCl, and disodium hydrogen phosphate offer acceptable use-life stability. Similarly, compositions containing telpotetamide, propylene glycol, and disodium hydrogen phosphate offer acceptable use-life stability. As used herein, the term “use-life stability” refers to the stability of a composition determined under controlled conditions at 25 degrees Celsius or approximately 25 degrees Celsius, or at 40 degrees Celsius or approximately 40 degrees Celsius.

[0030] Example

[0031] Example #1 – Composition containing NaCl

[0032] The compositions are prepared essentially as described herein. Compositions containing 5, 10, 15, 20, 15, and 30 mg / mL of telpolide each contain the ingredients listed in Table 1. Optionally, an acid or base may be added to achieve the desired pH range. Appropriate amounts (q.s.) Add water to a total final volume of one milliliter.

[0033] Table 1. Preparations of telpolide, phosphate, and NaCl Use 5 mM phosphate buffer

[0034] Example #2 – Composition containing propylene glycol

[0035] The compositions are prepared essentially as described herein. Compositions providing 5, 10, 15, 20, 15, and 30 mg of telpolide per mL each contain the ingredients listed in Table 2. Optionally, an acid or base may be added to achieve the desired pH range. Appropriate amounts are required. (q.s.) Add water to a total final volume of one milliliter.

[0036] Table 2. Formulations of telpolide, phosphate, and propylene glycol Use 5 mM phosphate buffer

[0037] Stability Study of Size Exclusion Chromatography (SEC) during Use

[0038] This procedure was performed using an isoclinality size exclusion HPLC method with UV detection at 214 nm, designed to determine the relative amounts of telpolide monomers and total aggregates. Monomers and aggregates are reported as percentages of peak area relative to the total area. The stability of this procedure is indicated by its ability to separate known impurities from telpolide. This study compared alternative compositions with the compositions of the present invention prepared as shown in Table 3. The stability of this study is shown in Table 4.

[0039] Stability studies of comparative alternative compositions: Table 3 Use 10 mM phosphate buffer Table 4. Thiopeptide monomers (% peak area) determined by size exclusion chromatography (SEC)

[0040] Storage stability study

[0041] RP-HPLC: This procedure is a gradient reversed-phase HPLC method using UV detection at 214 nm, designed to determine the amount, identity, and purity of telpolide in pharmaceutical products. Identity is determined by matching the retention time of the main peak to the retention time of the main peak in an external reference standard. Amount is determined by comparing the main peak area to the corresponding peak in the external reference standard. Impurities and related substances are reported as a percentage of peak area relative to the total peak area. The stability indicator of this procedure is determined by its ability to separate known impurities from telpolide. As shown in Table 4, compositions containing NaCl as a tonicity agent provide acceptable shelf-life stability.

[0042] Size Exclusion Chromatography (SEC) Storage Stability Study

[0043] The size exclusion stability study methods and RP-HPLC described above were used to compare compositions containing NaCl as a tensile and stabilizing agent with compositions containing propylene glycol as a tensile and stabilizing agent. This study illustrates the acceptable shelf-life stability of the compositions of the present invention containing either NaCl or propylene glycol as reagents. Table 5 lists the compositions used in this study. Table 6 shows the stability from this study.

[0044] Table 5. Comparison of NaCl and Propylene Glycol 5 mM phosphate buffer was used in this study. Table 6. Comparison of NaCl and propylene glycol as reagents in telpoide formulations with monomer (% peak area) determined by SEC and purity determined by RP-HPLC.

[0045] Injection pain research: All compositions were prepared as described in Table 7. Each solution composition vial was kept at room temperature for approximately 30 minutes, but no more than 4 hours. The reconstituted lyophilized composition was used immediately. All injections were performed in rotation across the four quadrants of the abdomen in the following order: lower left quadrant; lower right quadrant; upper left quadrant; and upper right quadrant. A syringe with a 29-gauge needle was used to administer the composition from the vial. The subject grasped the skin fold at the injection site and then inserted the needle at approximately a 45-degree angle. A second person used a stopwatch to measure the duration of the injection. The subject slowly advanced the plunger of the syringe until 0.5 mL of the composition was injected. The target injection time was 4 seconds, but no more than 5 seconds. After the injection, the needle was withdrawn from the skin, releasing the skin from the subject's grasp. The subject assessed pain immediately after each injection. Pain measurements were assessed using a 100-mm validated visual analog scale (VAS). The VAS is a well-validated tool for assessing injection site pain (Williamson, A.; Hoggart, Pain: A review of three commonly used pain rating scales). Journal of Clinical Nursing 2005, 14 (7), 798-804). The VAS is represented as a 10-cm (100-mm) line, anchored by verbal descriptive terms, typically “painless” and “worst imaginable pain.” Subjects were asked to mark the 100-mm line to indicate pain intensity at time points, following clinical instructions. Staff used calipers to measure the distance from 0 to the mark placed on the VAS by the subject and recorded the measurements in the source file. Results from this study are shown in Table 8. Mild pain intensity indication (compared to moderate or severe) reflects the acceptable patient injection site experience.

[0046] Table 7 5 mM phosphate buffer was used in this study. Table 8. VAS Pain Score

[0047] sequence

[0048] SEQ ID NO:1

[0049] Telpoeptide

[0050] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS

[0051] Where X1 is Aib; X2 is Aib; and K at position 20 is represented by (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2). 18 -CO2H is chemically modified by conjugating the ε-amino group of the K side chain; and the C-terminal amino acid is amidated to form a C-terminal primary amide.

Claims

1. A pharmaceutical composition comprising: telpolide or its pharmaceutically acceptable salt; Reagents selected from NaCl and propylene glycol; and Disodium hydrogen phosphate.

2. The pharmaceutical composition claimed in claim 1, wherein the concentration of said telpolide or a pharmaceutically acceptable salt thereof is from about 5 mg / mL to about 30 mg / mL.

3. The pharmaceutical composition claimed in claim 2, wherein the concentration of the disodium hydrogen phosphate is from about 1.0 mg / mL to about 3.0 mg / mL.

4. The pharmaceutical composition claimed in claim 3, wherein the concentration of the disodium hydrogen phosphate is from about 0.67 mg / mL to about 2.68 mg / mL.

5. The pharmaceutical composition claimed in claim 4, wherein the concentration of the disodium hydrogen phosphate is about 1.34 mg / mL.

6. The pharmaceutical composition claimed in claim 1, wherein the concentration of said telpolide or a pharmaceutically acceptable salt thereof is selected from 5, 10, 15, 20, 25 and 30 mg / mL.

7. The pharmaceutical composition claimed in claim 6, wherein the concentration of said telpolide or a pharmaceutically acceptable salt thereof is selected from 10, 20, and 30 mg / mL.

8. The pharmaceutical composition claimed in claim 7, wherein the reagent is NaCl.

9. The pharmaceutical composition claimed in claim 8, wherein the concentration of NaCl is from about 6.2 mg / mL to about 9.5 mg / mL.

10. The pharmaceutical composition claimed in claim 9, wherein the concentration of NaCl is from about 7.0 mg / mL to about 9.0 mg / mL.

11. The pharmaceutical composition claimed in claim 10, wherein the concentration of NaCl is about 8.2 mg / mL.

12. The pharmaceutical composition claimed in claim 1, wherein the concentration of telpolide or a pharmaceutically acceptable salt thereof is from about 5 mg / mL to about 30 mg / mL; the concentration of disodium hydrogen phosphate is from about 0.67 mg / mL to about 2.68 mg / mL; and the concentration of NaCl is from about 6.2 mg / mL to about 9.5 mg / mL.

13. The pharmaceutical composition claimed in claim 12, wherein the concentration of telpolide or a pharmaceutically acceptable salt thereof is from about 5 mg / mL to about 30 mg / mL; the concentration of disodium hydrogen phosphate is about 1.34 mg / mL; and the concentration of NaCl is about 8.2 mg / mL.

14. The pharmaceutical composition claimed in claim 13, wherein the composition is provided in an automated injection device.

15. The pharmaceutical composition claimed in claim 1, wherein the reagent is propylene glycol.

16. The pharmaceutical composition claimed in claim 15, wherein the concentration of propylene glycol is from about 12.0 mg / mL to about 18.0 mg / mL.

17. The pharmaceutical composition claimed in claim 16, wherein the concentration of propylene glycol is from about 14.0 mg / mL to about 16.0 mg / mL.

18. The pharmaceutical composition claimed in claim 17, wherein the concentration of propylene glycol is about 15.0 mg / mL.

19. The pharmaceutical composition claimed in claim 1, wherein the concentration of telpolide or a pharmaceutically acceptable salt thereof is from about 5 mg / mL to about 30 mg / mL; the concentration of disodium hydrogen phosphate is from about 0.67 mg / mL to about 2.68 mg / mL; and the concentration of propylene glycol is from about 14.0 mg / mL to about 16.0 mg / mL.

20. The pharmaceutical composition claimed in claim 19, wherein the concentration of telpolide or a pharmaceutically acceptable salt thereof is from about 5 mg / mL to about 30 mg / mL; the concentration of disodium hydrogen phosphate is from about 1.34 mg / mL; and the concentration of propylene glycol is from about 15.0 mg / mL.

21. The pharmaceutical composition claimed in claim 20, wherein the composition is provided in an automated injection device.

22. The pharmaceutical composition claimed in claim 21, wherein the pH of the composition is about 6.5 to about 7.

5.

23. The pharmaceutical composition claimed in claim 22, wherein the pH is about 6.7 to about 7.

3.

24. The pharmaceutical composition claimed in claim 23, wherein the composition further comprises one or more preservatives.

25. The pharmaceutical composition claimed in claim 24, wherein the composition further comprises a preservative selected from m-cresol and phenol.

26. The pharmaceutical composition claimed in claim 25, wherein the preservative is m-cresol.

27. The pharmaceutical composition claimed in claim 26, wherein the concentration of m-cresol is from about 2.0 mg / mL to about 4.0 mg / mL.

28. The pharmaceutical composition claimed in claim 27, wherein the concentration of m-cresol is about 3.15 mg / mL.

29. The pharmaceutical composition claimed in claim 25, wherein the preservative is phenol.

30. The pharmaceutical composition claimed in claim 29, wherein the concentration of said phenol is from about 3.0 mg / mL to about 7.0 mg / mL.

31. The pharmaceutical composition claimed in claim 30, wherein the concentration of said phenol is about 5.0 mg / mL.

32. The pharmaceutical composition claimed in claim 1, wherein the concentration of telposide or a pharmaceutically acceptable salt thereof is from about 5 mg / mL to about 30 mg / mL; the concentration of disodium hydrogen phosphate is from about 0.67 mg / mL to about 2.68 mg / mL; the concentration of propylene glycol is from about 12.0 mg / mL to about 15.0 mg / mL; and further comprises about 2.0 mg / mL to about 4.0 mg / mL of m-cresol.

33. The pharmaceutical composition claimed in claim 1, wherein the concentration of telposide or a pharmaceutically acceptable salt thereof is from about 5 mg / mL to about 30 mg / mL; the concentration of disodium hydrogen phosphate is from about 0.67 mg / mL to about 2.68 mg / mL; the concentration of propylene glycol is from about 12.0 mg / mL to about 18.0 mg / mL; and further comprises about 3.0 mg / mL to about 7.0 mg / mL of phenol.

34. The pharmaceutical composition claimed in claim 33, wherein the volume of the composition is about 0.5 mL.

35. The pharmaceutical composition claimed in claim 34, wherein the composition is administered using an automated injection device.

36. A method of treating diabetes, the method comprising administering to a person in need an effective dose of the pharmaceutical composition claimed in claim 33.

37. The method for treating diabetes as claimed in claim 36, wherein the dose is administered using an automated injection device.

38. The method of treating diabetes as claimed in claim 37, wherein the dose is administered once weekly.

39. A method for treating obesity, the method comprising administering an effective dose of the pharmaceutical composition claimed in claim 33 to a person in need.

40. The method for treating diabetes as claimed in claim 39, wherein the dose is administered using an automated injection device.

41. The method of treating obesity as claimed in claim 40, wherein the dose is administered once weekly.

42. The pharmaceutical composition claimed in claim 33, for the treatment of diabetes.

43. The pharmaceutical composition claimed in claim 33, for the treatment of obesity.

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