GIP / GLP1 agonist composition

Abstract

This invention provides a pharmaceutical GIP / GLP1 coagonist peptide composition for subcutaneous injection used to treat obesity. [Solution] A pharmaceutical composition for treating obesity is provided, comprising tilzepatide or a pharmaceutically acceptable salt thereof, a drug selected from the group consisting of NaCl and propylene glycol, and dibasic sodium phosphate.

Description

Background Art

[0001] The present invention relates to a pharmaceutical GIP / GLP1 co-agonist peptide composition for subcutaneous injection . The composition comprises tirzepatide, NaCl, and dibasic sodium phosphate. The compositio n provides commercially acceptable shelf-life stability and in-use stability, and is associate d with an acceptable patient injection site experience. An alternative composition comprises tirz epatide, propylene glycol, and dibasic sodium phosphate, and also provides acceptable shelf-life stability.

[0002] Diabetes mellitus is a chronic disorder characterized by hyperglycemia resulting from defects i n insulin secretion, insulin action, or both. In type 2 diabetes ("T2D"), the combined effect of insufficient insulin secretion and insulin resistance is associated with elevated blood gluco se levels. Tirzepatide is a GIP / GLP1 co-agonist peptide useful for the treatment of diabetes. Ti rzepatide is useful for the treatment of obesity.

[0003] US9474780 generally describes compositions containing GIP / GLP1 agonists administered by th e parenteral route. US9474780 describes and claims tirzepatide. A tirzepatide composition that provides acceptable stability and an acceptable patient injection site experience is desired. is desired.

[0004] The present invention meets these needs by providing a pharmaceutically acceptable composition of tirzepatide, or a pharmaceutically acceptable salt thereof, comprising an agent selected fr om the group consisting of NaCl and propylene glycol, and dibasic sodium phosphate. They are trying to satisfy it.

[0005] In one embodiment, the drug is NaCl. In one embodiment, the NaCl concentration is approximately 6. The concentration ranges from 2 mg / mL to approximately 9.5 mg / mL. In one embodiment, the NaCl concentration is approximately 7.0 The concentration is approximately 9.0 mg / mL. In one embodiment, the NaCl concentration is approximately 8.2 mg / mL. It is g / mL.

[0006] In one embodiment, the agent is propylene glycol. The glycol concentration is approximately 12.0 mg / mL to approximately 18.0 mg / mL. In one embodiment... The propylene glycol concentration is approximately 14.0 mg / mL to 16.0 mg / mL. In one embodiment, the propylene glycol concentration is approximately 15.0 mg / mL.

[0007] In one embodiment, the dibasic sodium phosphate concentration is approximately 0.67 mg / mL to approximately 2.6 The concentration is 8 mg / mL. In one embodiment, the dibasic sodium phosphate is approximately 1.0 mg / mL. L is approximately 3.0 mg / mL. In one embodiment, dibasic sodium phosphate is approximately 1. The concentration is 34 mg / mL.

[0008] In one embodiment, the tilzepatide concentration is approximately 5 mg / mL to approximately 30 mg / mL, and the drug The agent is NaCl. In one embodiment, the tilzepatide concentration is approximately 10 mg / mL to approximately 3 It is 0 mg / mL. In one embodiment, the tilzepatide concentration is approximately 5 mg / mL to approximately 30 mg / mL. The concentration is g / mL, and the NaCl concentration is approximately 8.2 mg / mL, and dibasic sodium phosphate The concentration is approximately 0.67 mg / mL to approximately 2.68 mg / mL. In one embodiment, The zepatide concentration is approximately 5 mg / mL to approximately 30 mg / mL, and the NaCl concentration is approximately 8.2 The concentration is mg / mL, and the dibasic sodium phosphate concentration ranges from approximately 0.67 mg / mL to approximately 2.6 The concentration is 8 mg / mL, and the composition is supplied in a single-use auto-injector.

[0009] In one embodiment, the tilzepatide concentration is approximately 5 mg / mL to approximately 30 mg / mL, and the drug The agent is propylene glycol. In one embodiment, the concentration of tilzepatide is approximately 5 mg / mL. The concentration is approximately 30 mg / mL, while propylene glycol is approximately 12.0 mg / mL to 18 mg / mL. The concentration is 0 mg / mL, and the dibasic sodium phosphate concentration is approximately 1.34 mg / mL. In one embodiment, the tilzepatide concentration is approximately 5 mg / mL to approximately 30 mg / mL, and The pyrene glycol concentration is approximately 15.0 mg / mL, and the dibasic sodium phosphate concentration is, It is approximately 1.34 mg / mL.

[0010] In one embodiment, the tilzepatide concentration is approximately 5 mg / mL to approximately 30 mg / mL. In a typical embodiment, the tilzepatide concentration is approximately 10 mg / mL to approximately 30 mg / mL. In one embodiment, the tilzepatide concentrations are 5, 10, 15, 20, 25, and 30 mg / It is selected from the group consisting of mL. In one embodiment, a composition of 0.5 mL or less is used as the dose. It is administered as follows. In one embodiment, the tilzepatide concentrations are 10, 20, and 30 mg / m². It is selected from the group consisting of L.

[0011] In one embodiment, the tilzepatide composition further comprises a preservative. Zepatide composition: tilzepatide, dibasic sodium phosphate, propylene glycol, and a preservative. In one embodiment, the preservative is selected from metacresol and phenol from the group consisting of. In one embodiment, the metacresol concentration is from about 2.0 mg / mL to about 4.0 mg / mL. In one embodiment, the metacresol concentration is about 3.0 mg / m L to about 3.5 mg / mL. In one embodiment, the metacresol concentration is about 3.15 m g / mL. In one embodiment, the phenol concentration is from about 3.0 mg / mL to about 7.0 m g / mL. In one embodiment, the phenol concentration is from about 4.0 mg / mL to about 6.0 m g / mL. In one embodiment, the phenol concentration is about 5.0 mg / mL. In one embodim ent, a tirzepatide composition is provided, wherein the tirzepatide concentration is from about 5 mg / mL to about 30 mg / mL, and the propylene glycol concentration is from about 12.0 mg / mL to about 18. 0 mg / mL, and the dibasic sodium phosphate concentration is from about 0.67 to about 2.68 mg / mL, and the metacresol concentration is from about 2.0 mg / mL to about 4.0 mg / mL. In one embodiment, the metacresol concentration is about 3.15 mg / mL. In one embodiment , a tirzepatide composition is provided, wherein the tirzepatide concentration is from about 5 mg / mL to about 30 mg / mL, and the propylene glycol concentration is from about 12.0 mg / mL to about 18.0 mg / m L, and the dibasic sodium phosphate concentration is from about 0.67 to about 2.68 mg / mL , and the phenol concentration is from about 3.0 mg / mL to about 7.0 mg / mL. In one embodiment , a tirzepatide composition is provided, wherein the tirzepatide concentration is from about 5 mg / mL to about 30 mg / mL, and the propylene glycol concentration is from about 12.0 mg / mL to about 18.0 mg / m L, and the dibasic sodium phosphate concentration is from about 0.67 to about 2.68 mg / mL and the phenol concentration is about 5.0 mg / mL.

[0012] In one embodiment, the dose of the tirzepatide composition is administered about once a week. In one embodi ment, the dose of the tirzepatide composition is administered once every 7 days.

[0013] In one embodiment, there is provided a method of treating diabetes, comprising administering to a human in need thereof an effective dose of one of the above compositions.

[0014] In one embodiment, there is provided a method of treating obesity, comprising administering to a human in need thereof an effective dose of one of the above compositions. In one embodiment, the pres ent invention provides a method of providing therapeutic weight loss, comprising administering to a human in need thereof an effective dose of one of the above compositions. In one embodiment, GIP / GLP-1 there is provided a method of treating a condition mediated by co-agonist activity, comprising administering to a human in need thereof an effective dose of one of the above compositions.

[0015] In one embodiment, there is provided one of the above compositions for use as a medicament.

[0016] In one embodiment, there is provided one of the above compositions for use in the treatment of diabetes . In one embodiment, there is provided one of the above compositions for use in the treatment of obesity .

[0017] In one embodiment, there is provided one of the above compositions for use in providing therapeutic weight loss . In one embodiment, there is provided one of the above compositions for use in providing non-therapeutic weight loss .

[0018] A manufactured article comprising one of the above compositions is provided according to another aspect of the present invention. In a particular embodiment, the manufactured product is a reusable vial. The article is a pre-filled syringe. In certain embodiments, the manufactured article is an automated injector. ("Automatic syringe"). Examples of automatic syringes as intended herein are those specified in US8. It is presented in issue 734,394.

[0019] As used herein, “Tilzepatide” refers to the substance described in US9,474,780. GIP / GLP1, as described by CAS Registry Number: 2023788-19-2 This refers to agonist peptides. Chilzepatide has the following sequence, as described in Example 1 of US9474,780: YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPP S In the equation, X1 is Aib, X2 is Aib, and the 20th K is (2-[2-(2 -amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2) Chemically modified through the bonding of the K side chain to the epsilon-amino group with 18-CO2H, The C-terminal amino acid is amidated as a primary C-terminal amide (SEQ ID NO: 1).

[0020] As used herein, “pharmaceutically acceptable salt” is well known to those skilled in the art. In terms of application form, it is a pharmaceutically acceptable salt, which is trifluoroacetate tylzepatide salt.

[0021] As used herein, the term “surfactant-free” means that the composition contains no added surfactants. This means that the product contains no surfactants or only a very small amount of added surfactants. ru.

[0022] As used herein, the term "propylene glycol" is well known to those skilled in the art. be.

[0023] Propylene glycol is also represented by the formula:C3H8O2.

[0024] The composition of the present invention has a concentration of tilzepatide 30 of 5 mg / mL to 30 mg / mL. The compositions of the present invention are available in specific concentrations of 5, 10, 15, 20, 25, and 30 mg / mL. Such compositions are likely to have [specific properties]. Such compositions may be provided in pre-filled syringes. Such pre-filled syringes contain 0.5 milliliters per patient dose. Such compositions may be useful for administering. A certain dose of the tilzepatide composition may be useful for a physician. It may be administered using a medication schedule determined by [the relevant authority].

[0025] The composition is sterile when first manufactured. Multiple-use vials or cartridges. If provided, an antimicrobial preservative compound or compound mixture that is compatible with the other components of the composition. The compound may be added in sufficient strength to meet applicable regulatory antimicrobial preservative requirements. (Pharmacological) The preservatives that are permissible are well known in the art. (For example, Remingto n:The Science and Practice of Pharmacy(D .B. Troy, Editor, 21st Edition, Lippincott, W See Illiams & Wilkins, 2006. In one embodiment, a preservative In one embodiment, the preservative is phenol. The composition for refillable syringes does not require preservatives. In one embodiment, the composition It does not contain surfactants.

[0026] The pH of the tilzepatide composition of the present invention is typically 6.5 to 7.5, and the desired pH is... Adjust using physiologically appropriate acids and bases as needed to achieve H In one embodiment, the pH target is 6.7 to 7.3. The patient's experience at the injection site is This is a consideration for compositions administered subcutaneously, related to the experience of acceptable patient injection sites. It is desirable to select a composition. For example, NaCl and citrate are painful at the injection site. It is associated with a stimulating sensation accompanied by pain. (Laursen, T.; Hansen, B.; Fi sker,S.Pain perception after subcutaneou s injections of media containing differe nt buffers.Basic&Clinical Pharmacology&T oxicology 2006,98,(2),218-221.), (Francso n,J.;Espander-Jansson,A.Local tolerance of subcutaneous injections.Journal of Ph armacy and pharmacology 1996,48,(10),101 2-1015.) Solutions that are not nearly isotonic with body fluids can cause painful irritation when administered. Therefore, when administering the composition, the tonicity (i.e., osmotic pressure) of the body fluids at the injection site may be affected. It is even more desirable to make the composition as close to the body fluid as possible. The composition should be nearly isotonic with body fluids at the injection site. It is desirable that it contains tilzepatide, NaCl, and dibasic sodium phosphate. This composition is associated with the acceptable patient injection site experience. Similarly, tilzepatide A composition comprising propylene glycol and dibasic sodium phosphate is acceptable. This is related to the patient's experience with injection sites.

[0027] In one embodiment, the pH is adjusted using a base to facilitate dissolution in the buffer solution. The addition of acid to the composition may be necessary to adjust the pH to a desired pH range. In this embodiment, NaOH is used to facilitate the dissolution of tilzepatide in the buffer. In one embodiment, HCl is used to adjust the pH of the composition containing dissolved tilzepatide to a desired level. It is added to adjust the pH range.

[0028] The compositions of the present invention are typically administered subcutaneously. The compositions are typically pre-filled. It is administered using a disposable pen, a reusable pen, or an automatic pen syringe. The product may be administered using a reusable vial or pump device. In one embodiment, The device is an automated injector as described by U.S. Patent No. 8,734,394. .

[0029] A composition comprising tilzepatide, NaCl, and dibasic sodium phosphate is desirable. It provides shelf-life stability and a patient-acceptable injection site experience. Similarly, chill A composition comprising zepatide, propylene glycol, and dibasic sodium phosphate is desired. It provides stable shelf life and a patient-acceptable injection site experience. When used in books, "shelf life stability" is measured under controlled conditions at approximately 5 degrees Celsius. A composition containing tylzepatide, NaCl, and dibasic sodium phosphate is acceptable. It provides stability during use. Similarly, tilzepatide, propylene glycol, and Compositions containing dibasic sodium phosphate provide acceptable stability during use. When used in a specification, the term “stability in use” refers to approximately 25 degrees Celsius or approximately 25 degrees Celsius. This refers to the stability of the composition measured under controlled conditions at 40 degrees Celsius.

[0030] Example #1 - Composition containing NaCl The composition is prepared substantially as described herein. 5, 10, 15, 20, Compositions containing 15 and 30 mg / mL of tilzepatide are listed in Table 1, respectively. It contains the following components. To achieve the desired pH range, an acid or base may be optionally added. A suitable amount (qs) of water is added to the total final volume of 1 milliliter. [Table 1]

[0031] Example #2 - Composition containing propylene glycol The composition is prepared substantially as described herein. 5, 10, 15, 20, Compositions providing 15 and 30 mg / mL of tilzepatide are shown in Table 2, respectively. Contains the listed ingredients. To achieve the desired pH range, an acid or base may be optionally added. An appropriate amount of water is added to bring the total final volume to 1 milliliter. [Table 2]

[0032] Stability testing during use of size exclusion chromatography (SEC) This procedure is a non-gradient size exclusion HPLC method with UV detection at 214 nm. Designed to determine the relative amounts of luzepatide monomers and total aggregates. Aggregates are reported as a peak area percentage relative to the total area. The procedure is as follows: This indicates stability, measured by its ability to decompose known impurities from nitrates. This test compares the alternative composition with the composition of the present invention, which was prepared as shown in Table 3. Compare the stability of the alternative compositions. The stability from this test is shown in Table 4. Experience: [Table 3] [Table 4]

[0033] Storage life stability test RP-HPLC: This procedure is a gradient reversed-phase HPLC method with UV detection at 214 nm, and the drug product It is designed to determine the amount, identity, and purity of the tilzepatide contained within. Identity is determined by By matching the in-peak retention time with the main peak retention time of the external reference standard, This is determined by the ratio of the main peak area to the corresponding peak in the external reference standard. Determined by comparison. Impurities and related substances are represented as the peak area percentage relative to the total area. It is reported as follows: The procedure is based on its ability to decompose known impurities from tilzepatide. This indicates the stability to be judged. As shown in Table 4, Na as the isotonic agent. Compositions containing Cl offer acceptable stability during use.

[0034] Size exclusion chromatography (SEC) shelf life stability testing The size exclusion stability test method and RP-HPLC described herein use an isotonic agent. A composition containing NaCl as a stabilizer, and propylene as an isotonic agent and stabilizer. This test is applied to compare with compositions containing glycol. This test is applied to compositions containing NaCl. or the permissible shelf life of the composition of the present invention comprising propylene glycol as a pharmaceutical agent. The stability of the composition used in this test is illustrated in Table 5. The stability is shown in Table 6. [Table 5] [Table 6]

[0035] Post-injection pain test: All compositions are prepared as shown in Table 7. Each solution composition vial is Reconstitution The freeze-dried composition is ready for immediate use. All injections should be administered within the four quadrants of the abdomen. Rotate in the following order: lower left quadrant, lower right quadrant, upper left quadrant, and upper right quadrant. Use a 29 gauge needle. The syringe is used to administer the composition from the vial. The folds are pinched according to the target, and the needle is inserted at an angle of approximately 45 degrees. The second person uses a stopwatch to measure the length of the injection time. The target is 0.5m. Slowly push the plunger of the syringe until the composition L is injected. The target duration is 4 seconds, and no more than 5 seconds. The needle is removed from the skin after injection. The skin is released from the pinch of the target. The target is assessed for pain immediately after each injection. The measurement is assessed using a 100mm validated visual analog scale (VAS) for pain. VAS is a well-validated tool for evaluating injection site pain (Willi amson, A.; Hoggart, B. Pain: A review of thre e commonly used pain rating scales.Journ al of Clinical Nursing 2005,14,(7),798-8 04). VAS uses language descriptors, typically "no pain" and "worst pain imaginable." Therefore, it is presented as a fixed, 10cm (100mm) line. The subjects were marked on the 100mm line, indicating pain intensity at each point in time as clinically relevant. This is required. Staff members use calipers to perform VA on a target from scratch. Measure the distance to the mark placed on S and record the measurement in the source document. The results from the trial are shown in Table 8. The acceptable patient experience at injection sites is (moderate or This is reflected by an index of mild pain intensity (compared to severe pain). [Table 7] [Table 8] [Table 9] [Table 10]

[0036] array Sequence ID 1: Tilzepatide YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPP S In the formula, X1 is Aib, X2 is Aib, and the 20th K is (2-[2-( 2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2 ) Chemically modified through the bonding of the K side chain to the epsilon-amino group with 18-CO2H The C-terminal amino acid is amidated as a primary C-terminal amide.

Claims

1. Chilzepatide, or a pharmaceutically acceptable salt thereof, A drug selected from the group consisting of NaCl and propylene glycol, A pharmaceutical composition comprising dibasic sodium phosphate.

2. The concentration of the aforementioned tilzepatide, or a pharmaceutically acceptable salt thereof, is approximately 5 to approximately 30 mg / m³. The pharmaceutical composition according to claim 1, wherein L.

3. The aforementioned dibasic sodium phosphate concentration is approximately 1.0 mg / mL to approximately 3.0 mg / mL. The pharmaceutical composition according to claim 2.

4. The aforementioned dibasic sodium phosphate concentration is approximately 0.67 mg / mL to approximately 2.68 mg / mL The pharmaceutical composition according to claim 3.

5. The dibasic sodium phosphate concentration is approximately 1.34 mg / mL, as described in claim 4. The pharmaceutical composition.

6. The concentrations of the aforementioned tilzepatide, or its pharmaceutically acceptable salt, are 5, 10, 15, and 20 A pharmaceutically acceptable combination according to claim 1, selected from the group consisting of 25 and 30 mg / mL. A finished product.

7. The concentrations of tilzepatide or its pharmaceutically acceptable salt are 10, 20, and 3 The pharmaceutical composition according to claim 6, selected from the group consisting of 0 mg / mL.

8. The pharmaceutical composition according to claim 7, wherein the drug is NaCl.

9. Claim 8, wherein the concentration of NaCl is approximately 6.2 mg / mL to approximately 9.5 mg / mL. The pharmaceutical composition described.

10. Claim 9, wherein the concentration of NaCl is approximately 7.0 mg / mL to approximately 9.0 mg / mL. The pharmaceutical composition described.

11. The pharmaceutical composition according to claim 10, wherein the NaCl concentration is approximately 8.2 mg / mL.

12. The concentration of tilzepatide, or its pharmaceutically acceptable salt, is approximately 5 mg / mL to approximately 30 mg / mL. The concentration is g / mL, and the dibasic sodium phosphate concentration ranges from approximately 0.67 mg / mL to approximately 2.68 mg / mL. The concentration is mg / mL, and the NaCl concentration is approximately 6.2 mg / mL to approximately 9.5 mg / mL. The pharmaceutical composition according to claim 1.

13. The concentration of tilzepatide, or its pharmaceutically acceptable salt, is approximately 5 mg / mL to approximately 30 mg / mL. The concentration is g / mL, and the dibasic sodium phosphate concentration is approximately 1.34 mg / mL. The pharmaceutical composition according to claim 12, wherein the Cl concentration is approximately 8.2 mg / mL.

14. The pharmaceutical composition according to claim 13, wherein the composition is provided by an automated injection device.

15. The pharmaceutical composition according to claim 1, wherein the agent is propylene glycol.

16. The concentration of the aforementioned propylene glycol is approximately 12.0 mg / mL to approximately 18.0 mg / mL. A pharmaceutical composition according to claim 15.

17. The concentration of the aforementioned propylene glycol is approximately 14.0 mg / mL to approximately 16.0 mg / mL. A pharmaceutical composition according to claim 16.

18. The present invention according to claim 17, wherein the concentration of the propylene glycol is approximately 15.0 mg / mL. The pharmaceutical composition.

19. The concentration of tilzepatide, or its pharmaceutically acceptable salt, is approximately 5 mg / mL to approximately 30 mg / mL. The concentration is g / mL, and the dibasic sodium phosphate concentration ranges from approximately 0.67 mg / mL to approximately 2.68 mg / mL. The concentration is in mg / mL, and the propylene glycol concentration ranges from approximately 14.0 mg / mL to approximately 16.0 mg / mL. The pharmaceutical composition according to claim 1, wherein the concentration is g / mL.

20. The concentration of tilzepatide, or its pharmaceutically acceptable salt, is approximately 5 mg / mL to approximately 30 mg / mL. The concentration is g / mL, and the dibasic sodium phosphate concentration is approximately 1.34 mg / mL. The pharmaceutical composition according to claim 19, wherein the pyrene glycol concentration is approximately 15.0 mg / mL. thing.

21. The pharmaceutical composition according to claim 20, wherein the composition is provided by an automated injection device.

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

5.

23. The pharmaceutical composition according to claim 22, wherein the pH is approximately 6.7 to approximately 7.

3.

24. The pharmaceutical composition according to claim 23, further comprising one or more preservatives.

25. The composition contains a preservative selected from the group consisting of metacresol and phenol. The pharmaceutical composition according to claim 24, comprising the above.

26. The pharmaceutical composition according to claim 25, wherein the preservative is metacresol.

27. The claim states that the metacresol concentration is approximately 2.0 mg / mL to approximately 4.0 mg / mL. The pharmaceutical composition described in 26.

28. The pharmaceutical product according to claim 27, wherein the metacresol concentration is approximately 3.15 mg / mL. composition.

29. The pharmaceutical composition according to claim 25, wherein the preservative is phenol.

30. Claim 29, wherein the phenol concentration is approximately 3.0 mg / mL to approximately 7.0 mg / mL The pharmaceutical composition described in [reference].

31. The pharmaceutical composition according to claim 30, wherein the phenol concentration is approximately 5.0 mg / mL. 。

32. The concentration of tilzepatide, or its pharmaceutically acceptable salt, is approximately 5 mg / mL to approximately 30 mg / mL. The concentration is g / mL, and the dibasic sodium phosphate is approximately 0.67 to approximately 2.68 mg / mL. The propylene glycol content is approximately 12.0 mg / mL to approximately 15.0 mg / mL, and The claim 1 further comprises 2.0 mg / mL to about 4.0 mg / mL of metacresol. The pharmaceutical composition.

33. The concentration of tilzepatide, or its pharmaceutically acceptable salt, is approximately 5 mg / mL to approximately 30 mg / mL. The concentration is g / mL, and the dibasic sodium phosphate is approximately 0.67 to approximately 2.68 mg / mL. The propylene glycol content is approximately 12.0 mg / mL to approximately 18.0 mg / mL, and The drug according to claim 1, further comprising 3.0 mg / mL to about 7.0 mg / mL of phenol. chemical composition.

34. The pharmaceutical composition according to claim 33, wherein the volume of the composition dose is approximately 0.5 mL.

35. The pharmaceutical composition according to claim 34, wherein the composition is administered using an automated injection device. 。

36. A method for treating diabetes, wherein an effective dose is provided to a person who needs it, as described in claim 33. A method comprising administering the listed pharmaceutical composition.

37. The aforementioned dose is administered using an automated injection device, for the treatment of diabetes according to claim 36. How to do it.

38. The method for treating diabetes according to claim 37, wherein the aforementioned dose is administered once a week.

39. A method for treating obesity, provided to a person in need, in an effective dose as described in claim 33. A method comprising administering a pharmaceutical composition.

40. The treatment of obesity according to claim 39, wherein the aforementioned dose is administered using an automated injection device. method.

41. The method for treating obesity according to claim 40, wherein the aforementioned dose is administered once a week.

42. The pharmaceutical composition according to claim 33 for use in the treatment of diabetes.

43. The pharmaceutical composition according to claim 33 for use in the treatment of obesity.

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