Tilpotide compositions and uses

Abstract

Provided are compositions and methods of administering such a tilpotide composition comprising tilpotide or a salt thereof at a concentration selected from the group consisting of 2.5 mg / mL, 40 mg / mL, and 50 mg / mL; naCl; and disodium hydrogen phosphate.

Description

[0001] The present invention relates to the field of medicine. More specifically, the present invention relates to methods of using novel doses of telpotide and pharmaceutically aesthetic compositions comprising such doses. The compositions provide commercially acceptable shelf-life stability, stability in use and are associated with an acceptable patient experience.

[0002] Diabetes is a chronic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. In type 2 diabetes ("T2D"), the combination of impaired insulin secretion and insulin resistance is associated with elevated blood glucose levels.

[0003] Mounjaro TMThe active ingredient in tebuconazole is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide 1 (GLP1) receptor agonist (GIP / GLP1), which is approved for use as an adjunct to diet and exercise to improve glycemic control in patients with T2D. Tebuconazole is approved as a clear, colorless to slightly yellow liquid for subcutaneous injection. Using a starting dose of 2.5 mg once a week, once-weekly tebuconazole doses of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg are administered; after 4 weeks, increase to 5 mg subcutaneously once a week; after at least 4 weeks on the current dose, increase the dose in increments of 2.5 mg. The maximum approved dose is 15 mg subcutaneously once a week. Tebuconazole was studied in a Phase 3 development program, and in 2022, the once-weekly dose received regulatory approval in the United States (US), the European Union, and other jurisdictions for the treatment of T2D. Since its approval in 2022, these doses of tirpotide have been used to treat many patients with T2D. These doses have been studied in thousands of patients for long-term weight management. Although therapy with currently approved tirpotide enabled essentially all patients included in the Phase 3 program to achieve glycemic goals (regardless of the use of other T2D concomitant medications), and patients with obesity or overweight in the Phase 3 study achieved a 15.7% weight loss, a large number of patients receiving approved therapy require additional long-term weight management to achieve weight management treatment goals. A large number of patients receiving approved therapy require additional weight management benefits. These patients cannot achieve their weight management goals using currently approved medications and / or doses of medications that can reduce weight. Gastrointestinal adverse reactions have been reported to limit higher doses of drugs with GLP1 receptor agonist activity. The U.S. label for tirpotide (May 2022) indicates that the use of tirpotide may be associated with gastrointestinal adverse reactions, sometimes severe. A dosing regimen is needed that allows higher tirpotide doses to be administered with an acceptable patient experience. There is an important medical need for pharmaceutical agents to achieve additional weight management while maintaining an overall acceptable risk / benefit profile and patient tolerability.

[0004] There is a need for pharmaceutical compositions with higher doses of telpotide that are storage stable for at least 6 months.

[0005] Peptides have unique physicochemical properties that often pose challenges to achieving stable, pharmaceutically aesthetic compositions. For example, peptide self-association, aggregation, surface adsorption, solubility, and chemical stability present unique challenges to achieving desired peptide compositions. Bak et al., "Physicochemical and Formulation Developability Assessment for Therapeutic Peptide Delivery—APrimer-PMC (nih.gov)" AAPS J. 2015 Jan;17(1):144–155.

[0006] These compositions, dosages, and methods provide these benefits while maintaining an acceptable safety risk and adverse effect profile.

[0007] The present invention provides a pharmaceutically acceptable composition of telpotide or a pharmaceutically acceptable salt thereof, comprising greater than 30 mg / mL of telpotide or a pharmaceutically acceptable salt thereof, a tonicity agent and sodium phosphate.

[0008] In one embodiment, the composition is of telpotide or a pharmaceutically acceptable salt thereof, comprising greater than 30 mg / mL of telpotide or a pharmaceutically acceptable salt thereof, a tonicity agent, and disodium hydrogen phosphate.

[0009] In one embodiment, the composition is a telpotide or a pharmaceutically acceptable salt thereof, comprising greater than 30 mg / mL and up to 60 mg / mL of telpotide or a pharmaceutically acceptable salt thereof, a tonicity agent, and disodium hydrogen phosphate.

[0010] In one embodiment, the tonicity agent is NaCl. In one embodiment, the NaCl concentration is about 7 mg / mL to about 9 mg / mL. In one embodiment, the NaCl concentration is about 7.4 mg / mL to about 9.0 mg / mL. In one embodiment, the NaCl concentration is about 8.2 mg / mL.

[0011] In one embodiment, the sodium phosphate dibasic concentration is about 0.7 mg / mL to about 1.5 mg / mL. In one embodiment, the sodium phosphate dibasic concentration is about 1.34 mg / mL.

[0012] In one embodiment, the concentration of telpotide or its salt is about 40 mg / mL to about 50 mg / mL. In one embodiment, the concentration of telpotide or its pharmaceutically acceptable salt is about 40 mg / mL. In one embodiment, the concentration of telpotide or its salt is about 50 mg / mL. In one embodiment, the concentration of telpotide or its salt is about 2.5 mg / mL. In one embodiment, the concentration of telpotide or its pharmaceutically acceptable salt is 40 mg / mL-50 mg / mL. In one embodiment, the concentration of telpotide or its pharmaceutically acceptable salt is 40 mg / mL. In one embodiment, the concentration of telpotide or its pharmaceutically acceptable salt is 50 mg / mL. In one embodiment, the concentration of telpotide or its pharmaceutically acceptable salt is 2.5 mg / mL.

[0013] In one embodiment, the concentration of telpotide or a pharmaceutically acceptable salt thereof is from about 40 mg / mL to about 60 mg / mL. In one embodiment, the concentration of telpotide or a pharmaceutically acceptable salt thereof is about 55 mg / mL. In one embodiment, the concentration of telpotide or a pharmaceutically acceptable salt thereof is about 60 mg / mL. In one embodiment, the concentration of telpotide or a pharmaceutically acceptable salt thereof is 60 mg / mL. In one embodiment, the concentration of telpotide or a pharmaceutically acceptable salt thereof is 55 mg / mL. In one embodiment, or the concentration of a pharmaceutically acceptable salt thereof is from 40 mg / mL to 60 mg / mL. In one embodiment, telpotide or a pharmaceutically acceptable salt thereof is telpotide, which is a free base.

[0014] In one embodiment, the concentration of telpoitide or its salt is about 40 mg / mL to about 50 mg / mL; the NaCl concentration is about 8.2 mg / mL and the sodium phosphate dibasic concentration is about 1.34 mg / mL. In one embodiment, the concentration of telpoitide or its salt is about 2.5 mg / mL; the NaCl concentration is about 8.2 mg / mL and the sodium phosphate dibasic concentration is about 1.2 mg / mL to about 1.34 mg / mL. In one embodiment, the concentration of telpoitide or its pharmaceutically acceptable salt is about 40 mg / mL; the NaCl concentration is about 8.2 mg / mL and the sodium phosphate dibasic concentration is about 1.34 mg / mL. In one embodiment, the concentration of telpoitide or its pharmaceutically acceptable salt is about 50 mg / mL; the NaCl concentration is about 8.2 mg / mL and the sodium phosphate dibasic concentration is about 1.34 mg / mL. In one embodiment, the concentration of telpoitide or a pharmaceutically acceptable salt thereof is about 2.5 mg / mL; the concentration of NaCl is about 8.2 mg / mL, and the concentration of sodium phosphate dibasic is about 1.34 mg / mL. In one embodiment, the concentration of telpoitide is about 40 mg / mL; the concentration of NaCl is about 8.2 mg / mL, and the concentration of sodium phosphate dibasic is about 1.34 mg / mL, and the composition is present in a single-use automatic injection device. In one embodiment, the concentration of telpoitide is about 50 mg / mL; the concentration of NaCl is about 8.2 mg / mL, and the concentration of sodium phosphate dibasic is about 1.34 mg / mL, and the composition is present in a single-use automatic injection device. In one embodiment, the concentration of telpoitide is about 2.5 mg / mL; the concentration of NaCl is about 8.2 mg / mL, and the concentration of sodium phosphate dibasic is about 1.34 mg / mL, and the composition is present in a single-use automatic injection device.

[0015] In one embodiment, the concentration of tirpotide or a pharmaceutically acceptable salt thereof in the composition is selected from 2.5, 40 and 50 mg / mL. In one embodiment, tirpotide or a pharmaceutically acceptable salt thereof is administered as a 0.5 mL dose. In one embodiment, the composition comprises tirpotide or a pharmaceutically acceptable salt thereof, which is formulated to deliver 1.25 mg / dose. In one embodiment, the concentration of tirpotide or a pharmaceutically acceptable salt thereof is selected from 1.25 mg / 0.5 mL, 20 mg / 0.5 mL and 25 mg / 0.5 mL. In one embodiment, the concentration of tirpotide or a pharmaceutically acceptable salt thereof is 30 mg / 0.5 mL. In one embodiment, the concentration of tirpotide or a pharmaceutically acceptable salt thereof is the concentration of tirpotide as a free base.

[0016] In one embodiment, a method of treating chronic obesity in a subject in need thereof comprises administering 1.25 mg of telpotide or a pharmaceutically acceptable salt thereof for a minimum of four weeks.

[0017] In one embodiment, a method of treating chronic obesity in a pediatric subject in need thereof comprises administering 1.25 mg of telpotide or a pharmaceutically acceptable salt thereof for a minimum of four weeks.

[0018] In one embodiment, a method of treating type 2 diabetes in a subject in need thereof comprises administering 1.25 mg of telpotide or a pharmaceutically acceptable salt thereof for a minimum of four weeks.

[0019] In one embodiment, a method of treating type 2 diabetes in a pediatric subject in need thereof comprises administering 1.25 mg of telpotide or a pharmaceutically acceptable salt thereof for a minimum of four weeks.

[0020] In one embodiment, a method for long-term weight management in a pediatric subject comprises administering 1.25 mg of telpotide or a pharmaceutically acceptable salt thereof to a subject in need thereof for a minimum of four weeks.

[0021] In one embodiment, a method for long-term weight management in a subject in need of additional weight management; wherein the subject suffers from obesity, the method comprising:

[0022] Identify subjects with obesity who require additional weight management;

[0023] administering to the subject a weekly dose of at least 15 mg of telpotide or a pharmaceutically acceptable salt thereof for a minimum of four weeks; and

[0024] After at least four weeks of administration of once weekly doses of at least 15 mg of telpotide or a pharmaceutically acceptable salt thereof, administering a once weekly dose of telpotide or a pharmaceutically acceptable salt thereof that is greater than the last dose of 5 mg; wherein the maximum once weekly dose of telpotide or a pharmaceutically acceptable salt thereof is 25 mg.

[0025] The present invention provides a method for long-term weight management in a subject in need of additional weight management, comprising: identifying a subject who desires weight management and is in need of additional weight management; comprising:

[0026] a) administering to the subject a dose of telpotide or a pharmaceutically acceptable salt thereof of >15 mg and <20 mg once a week for a minimum of four weeks; and

[0027] Increase the dose to 20 mg once a week.

[0028] Thus, the present invention provides a method for long-term weight management in a subject in need of additional weight management, comprising:

[0029] a) Identify subjects who require additional weight management;

[0030] b) administering to the subject a dose of 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week for a minimum of four weeks; and

[0031] c) increasing the dose by administering to said subject a dose of 25 mg of telpotide or a pharmaceutically acceptable salt thereof once per week.

[0032] Methods for long-term weight management in subjects requiring additional weight management are provided, including:

[0033] a) Identifying subjects who desire weight management and require additional weight management;

[0034] b) administering to the subject a dose of 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week for a minimum of four weeks; and

[0035] c) increasing the dose by administering to said subject a dose of 25 mg of telpotide or a pharmaceutically acceptable salt thereof once per week.

[0036] In one aspect, a method of long-term weight management in a subject in need of additional weight management is provided, comprising:

[0037] a) Identify people with a starting BMI > 30kg / m 2 and subjects who require additional weight management;

[0038] b) increasing the dose by administering to said subject a dose of 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week.

[0039] In another aspect, the present invention provides a method of providing long-term weight management to a subject in need thereof, comprising:

[0040] a) identifying subjects who have been previously treated with at least 15 mg of telpotide or a pharmaceutically acceptable salt thereof, once a week for a minimum of four weeks; and

[0041] b) increasing the dose by administering 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week.

[0042] In another aspect, the present invention provides a method of providing long-term weight management to a subject in need thereof, comprising:

[0043] a) identifying subjects who have been previously treated with at least 20 mg of telpotide or a pharmaceutically acceptable salt thereof, once a week for a minimum of four weeks; and

[0044] b) increasing the dose by administering 25 mg of telpotide or a pharmaceutically acceptable salt thereof once a week.

[0045] In another aspect, the present invention provides a use of telpotide in the preparation of a medicament for improving glycemic control in a subject having type 2 diabetes (T2D) and being treated with a 15 mg dose of telpotide once weekly but requiring additional glycemic control, comprising: increasing the dose of telpotide administered to 20 mg once weekly.

[0046] In another aspect, the present invention provides a use of telpotide in the preparation of a medicament for improving glycemic control in a subject having type 2 diabetes (T2D) and being treated with a 20 mg dose of telpotide once weekly but requiring additional glycemic control, comprising: increasing the dose of telpotide administered to 25 mg once weekly.

[0047] In another aspect, the present invention provides a use of telpotide in the preparation of a medicament for providing long-term weight management to a subject in need thereof, comprising:

[0048] a) administering 15 mg of tepoxetine to the subject once a week for a minimum of four weeks;

[0049] b) increasing the dose of telpotide by administering 20 mg of telpotide to the subject once a week for a minimum of four weeks; and

[0050] c) Increase this dose by administering 25 mg of telpotide once a week.

[0051] In another aspect, the present invention provides a use of telpotide in the preparation of a medicament for providing long-term weight management to a subject in need thereof, comprising:

[0052] a) identifying subjects who have previously been treated with 15 mg of telpotide or a pharmaceutically acceptable salt thereof, once a week for a minimum of four weeks; and

[0053] b) increasing the dose by administering 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week.

[0054] In another aspect, the present invention provides a use of telpotide in the preparation of a medicament for providing long-term weight management to a subject in need thereof, comprising:

[0055] a) identifying subjects who have previously been treated with 20 mg of telpotide or a pharmaceutically acceptable salt thereof, once a week for a minimum of four weeks; and

[0056] b) increasing the dose by administering 25 mg of telpotide or a pharmaceutically acceptable salt thereof once a week.

[0057] In one embodiment, a dose of the telpotide composition is administered about once per week. In one embodiment, a dose of the telpotide composition is administered once every seven days.

[0058] In one embodiment, a method of treating diabetes is provided, comprising administering an effective dose of one of the compositions described above to a human in need thereof.

[0059] In one embodiment, a method of treating obesity is provided, comprising administering to a person in need thereof an effective dose of one of the above compositions comprising 40 mg / mL of telpotide or a pharmaceutically acceptable salt thereof. In one embodiment, a method of treating obesity is provided, comprising administering to a person in need thereof an effective dose of one of the above compositions comprising 50 mg / mL of telpotide or a pharmaceutically acceptable salt thereof. In one embodiment, a method of providing therapeutic weight loss is provided, comprising administering to a person in need thereof an effective dose of one of the above compositions. In one embodiment, a method of providing therapeutic weight loss is provided, comprising administering to a person in need thereof an effective dose of a composition comprising 40 mg / mL of telpotide or a pharmaceutically acceptable salt thereof. In one embodiment, telpotide is a free base.

[0060] In one embodiment, a method for additional weight management in a subject in need thereof, wherein the subject has a BMI of > 27kg / m 2 and at least one weight-related comorbidity; the method comprising:

[0061] administering to the subject a dose of 2.5 mg of telpotide; or a pharmaceutically acceptable salt thereof, once a week for at least 4 weeks;

[0062] After 4 weeks, the dose of telpotide or a pharmaceutically acceptable salt thereof is increased by administering a dose of 5 mg once a week;

[0063] After at least 4 weeks at the current dose, increase that dose in 2.5 mg increments;

[0064] If additional weight management is required after at least 4 weeks of 15 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly;

[0065] then after at least 4 weeks at the current dose, increase that dose in 5.0 mg increments; and

[0066] The maximum dose is 25 mg subcutaneously once weekly of telpotide or a pharmaceutically acceptable salt thereof.

[0067] In one embodiment, a method for additional weight management in a subject in need thereof, wherein the subject has a BMI of >27kg / m 2 and at least one weight-related comorbidity; the method comprising:

[0068] administering to the subject a dose of 2.5 mg of telpotide; or a pharmaceutically acceptable salt thereof, once a week for at least 4 weeks;

[0069] After 4 weeks, the dose of telpotide or a pharmaceutically acceptable salt thereof is increased to once weekly doses by administering a 5 mg dose;

[0070] After at least 4 weeks at the current dose, increase that dose in 2.5 mg increments;

[0071] If additional weight management is required after at least 4 weeks of 15 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly;

[0072] After at least 4 weeks at the current dose, increase the dose in 2.5 mg increments by administering a 17.5 mg once-weekly tepoxetine dose for at least 4 weeks;

[0073] If additional weight management is needed, increase the dose in 2.5 mg increments after at least 4 weeks at the current dose; and

[0074] The maximum dose is 25 mg subcutaneously once weekly of telpotide or a pharmaceutically acceptable salt thereof.

[0075] In one embodiment, a method for additional weight management in a subject in need thereof, wherein the subject has a BMI of > 30kg / m 2 ; The method comprises:

[0076] administering to the subject a dose of 2.5 mg of telpotide; or a pharmaceutically acceptable salt thereof, once a week for at least 4 weeks;

[0077] After 4 weeks, increase the weekly dose of telpotide or a pharmaceutically acceptable salt thereof by administering a 5 mg dose;

[0078] After at least 4 weeks at the current dose, increase that dose in 2.5 mg increments;

[0079] If additional weight management is required after at least 4 weeks of 15 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly;

[0080] After at least 4 weeks at the current dose, increase the dose in 2.5 mg increments by administering a 17.5 mg once weekly dose of telpotide for at least 4 weeks;

[0081] If additional weight management is needed, after at least 4 weeks at the current dose, increase that dose in 2.5 mg increments; and

[0082] The maximum dose is 25 mg subcutaneously once weekly of telpotide or a pharmaceutically acceptable salt thereof.

[0083] In one embodiment, a method for additional weight management in a subject with obesity in need thereof; comprising:

[0084] administering to the subject a dose of 2.5 mg of telpotide once weekly;

[0085] After 4 weeks, this dose was increased by administering 5 mg of tepoxetine once weekly;

[0086] After 4 weeks at the current dose, increase the dose in 2.5 mg increments;

[0087] After at least 4 weeks of 15 mg of tepoxetine once weekly;

[0088] After at least 4 weeks at the current dose, increase that dose in 5.0 mg increments; and

[0089] The maximum dose is 25 mg subcutaneous telpotide once a week.

[0090] In one embodiment, for use in patients with a BMI > 27kg / m 2 Methods for additional weight management in subjects in need thereof with at least one weight-related comorbidity; including:

[0091] administering to the subject a dose of 2.5 mg of telpotide or a pharmaceutically acceptable salt thereof once a week;

[0092] After 4 weeks, increase the weekly dose of telportolide or a pharmaceutically acceptable salt thereof to 5 mg;

[0093] Increase the dose in 2.5 mg increments after at least 4 weeks at the current dose;

[0094] After at least 4 weeks of 15 mg of telpotide or a pharmaceutically acceptable salt thereof once a week;

[0095] Increase the dose in 5.0 mg increments after at least 4 weeks at the current dose; and

[0096] The maximum dose is 25 mg subcutaneously once a week of telpotide or a pharmaceutically acceptable salt thereof.

[0097] In one embodiment, a method of providing therapeutic weight loss is provided, comprising administering to a human in need thereof an effective amount of a composition comprising 40 mg / mL of telpotide or a pharmaceutically acceptable salt thereof. In one embodiment, a method of providing therapeutic weight loss is provided, comprising administering to a human in need thereof an effective amount of a composition comprising 50 mg / mL of telpotide or a pharmaceutically acceptable salt thereof. In one embodiment, a method of providing therapeutic weight loss is provided, comprising administering to a human in need thereof an effective amount of a composition comprising 60 mg / mL of telpotide or a pharmaceutically acceptable salt thereof. In one embodiment, telpotide or a pharmaceutically acceptable salt thereof is telpotide free base.

[0098] In one embodiment, a method for treating obesity in a subject having > 30kg / m 2 The method comprises administering 40 mg / mL of telportide or a pharmaceutically acceptable salt thereof. In one embodiment, the method is a method for treating obesity in a subject, the subject having > 30kg / m 2 The method comprises administering 50 mg / mL of tepote or a pharmaceutically acceptable salt thereof. In one embodiment, the method is a method for treating an overweight subject having an initial body mass index (BMI) of > 27kg / m 2 Initial BMI, including those with BMI ≥ 27 kg / m 2 The overweight subject has at least one weight-related comorbid condition. In one embodiment, the weight-related comorbid condition is at least one condition selected from hypertension, type 2 diabetes, and dyslipidemia. In one embodiment, the method for treating obesity in a subject, the subject has > 30kg / m 2 In one embodiment, the method of treating obesity in a subject has > 27kg / m 2 The initial body mass index (BMI) of 1.5 mg / kg was calculated using the tepolamine free base form.

[0099] In one embodiment, a method for treating a pediatric patient having an initial body mass index that is 95% or more normalized for age and sex, the method comprising administering an effective amount of telpotide or a pharmaceutically acceptable salt thereof once a week. In one embodiment, a method for treating a pediatric patient having an initial body mass index that is 95% or more normalized for age and sex, the method comprising administering an effective amount of telpotide or a pharmaceutically acceptable salt thereof once a week. In one embodiment, a method for treating a pediatric patient having an initial body mass index that is 95% or more normalized for age and sex, the method comprising administering an effective amount of telpotide or a pharmaceutically acceptable salt thereof once a week. In one embodiment, a method for treating a pediatric patient having an initial body mass index that is 95% or more normalized for age and sex, the method comprising administering 2.5 mg / mL of telpotide or a pharmaceutically acceptable salt thereof for at least 4 weeks. In one embodiment, a method for treating a pediatric patient having an initial body mass index that is 95% or more normalized for age and sex, comprising administering 1.25 mg of telpotide or a pharmaceutically acceptable salt thereof. In one embodiment, a method for long-term weight management of a pediatric subject, wherein the subject has an initial BMI normalized for age and sex. > 85% or more, have at least one weight-related comorbidity. In one embodiment, is a method of treating a pediatric patient, wherein teilpotide is in free base form.

[0100] In one embodiment, having an initial BMI > 30kg / m 2 A subject with an initial BMI of > 30kg / m 2 A subject with an initial BMI of > 30kg / m 2 of subjects achieved at least 20% weight loss.

[0101] In one embodiment, a patient with type 2 diabetes and an initial BMI > 27kg / m 2 In one embodiment, a subject with type 2 diabetes and an initial BMI > 27kg / m 2 In one embodiment, subjects with type 2 diabetes and an initial BMI > 27kg / m 2 of subjects achieved at least 20% weight loss.

[0102] In one embodiment, patients with weight-related comorbidities and initial BMI > 27kg / m2 In one embodiment, subjects with weight-related comorbidities and initial BMI > 27kg / m 2 In one embodiment, subjects with weight-related comorbidities and initial BMI > 27kg / m 2 of subjects achieved at least 20% weight loss.

[0103] In one embodiment, to treat a patient having an initial body mass index (BMI) > 30kg / m 2 A method for treating obesity in a subject comprising administering 40 mg / mL of telportide or a pharmaceutically acceptable salt thereof, wherein the subject achieves at least 15% weight loss. In one embodiment, for treating a subject having an initial body mass index (BMI) of > 30kg / m 2 A method for treating obesity in a subject comprising administering 50 mg / mL of telportide or a pharmaceutically acceptable salt thereof, wherein the subject achieves at least 15% weight loss. In one embodiment, for treating a subject having an initial body mass index (BMI) of > 30kg / m 2 A method for treating obesity in a subject comprising administering 40 mg / mL of telportide or a pharmaceutically acceptable salt thereof, wherein the subject achieves at least 20% weight loss. In one embodiment, for treating a subject having an initial body mass index (BMI) of > 30kg / m 2 A method for treating obesity in a subject comprising administering 50 mg / mL of telpol or a pharmaceutically acceptable salt thereof, wherein the subject achieves at least 20% weight loss. In one embodiment, for treating a subject with type 2 diabetes and an initial BMI ≥ 27 kg / m 2 A method for treating an overweight subject comprising administering 40 mg / mL of tepoxetine or a pharmaceutically acceptable salt thereof, wherein the subject has an initial BMI ≥ 27 kg / m 2 and < 30kg / m 2 In one embodiment, for the treatment of patients with type 2 diabetes and an initial BMI ≥ 27 kg / m 2 A method for treating overweight subjects, comprising administering 50 mg / mL of tepoxetine or a pharmaceutically acceptable salt thereof, wherein the subjects have an initial BMI ≥ 27 kg / m 2 and < 30kg / m 2In one embodiment, for the treatment of patients with type 2 diabetes and an initial BMI ≥ 27 kg / m 2 A method for treating an overweight subject comprising administering 40 mg / mL of tepoxetine or a pharmaceutically acceptable salt thereof, wherein the subject has an initial BMI ≥ 27 kg / m 2 and < 30kg / m 2 In one embodiment, for the treatment of patients with type 2 diabetes and an initial BMI ≥ 27 kg / m 2 A method for treating overweight subjects, comprising administering 50 mg / mL of tepoxetine or a pharmaceutically acceptable salt thereof, wherein the subjects have an initial BMI ≥ 27 kg / m 2 and < 30kg / m 2 In one embodiment, the method of treating an overweight subject, wherein telpotide is in free base form. In one embodiment, the method of treating obesity, wherein telpotide is in free base form. In one embodiment, telpotide or a pharmaceutically acceptable salt thereof is administered in the form of 0.5 mL of the composition.

[0104] In one embodiment, for the treatment of patients with weight-related comorbidities and an initial BMI ≥ 27 kg / m 2 A method for treating an overweight subject comprising administering 40 mg / mL of tepoxetine or a pharmaceutically acceptable salt thereof, wherein the subject has an initial BMI ≥ 27 kg / m 2 and < 30kg / m 2 In one embodiment, for the treatment of patients with weight-related comorbidities and an initial BMI ≥ 27 kg / m 2 A method for treating overweight subjects, comprising administering 50 mg / mL of tepoxetine or a pharmaceutically acceptable salt thereof, wherein the subjects have an initial BMI ≥ 27 kg / m 2 and < 30kg / m 2 In one embodiment, for the treatment of patients with weight-related comorbidities and an initial BMI ≥ 27 kg / m 2 A method for treating an overweight subject comprising administering 40 mg / mL of tepoxetine or a pharmaceutically acceptable salt thereof, wherein the subject has an initial BMI ≥ 27 kg / m 2 and < 30kg / m 2In one embodiment, for the treatment of patients with weight-related comorbidities and an initial BMI ≥ 27 kg / m 2 A method for treating overweight subjects, comprising administering 50 mg / mL of tepoxetine or a pharmaceutically acceptable salt thereof, wherein the subjects have an initial BMI ≥ 27 kg / m 2 and < 30kg / m 2 of overweight subjects achieved at least 20% weight loss.

[0105] In certain embodiments, the weight-related comorbidity is at least one selected from hypertension, dyslipidemia, prediabetes, type 2 diabetes, obstructive sleep apnea, and cardiovascular disease.

[0106] In certain embodiments, the weight-related comorbidity is at least one condition selected from hypertension, type 2 diabetes, and dyslipidemia.

[0107] In one embodiment, there is provided one of the above compositions for use as a medicament.

[0108] In one embodiment, one of the above compositions is provided for use in treating diabetes. In one embodiment, one of the above compositions is provided for use in treating obesity.

[0109] In one embodiment, one of the above compositions is provided for use in providing therapeutic weight loss. In one embodiment, one of the above compositions is provided for use in providing non-therapeutic weight loss.

[0110] According to another aspect of the present invention, there is provided an article comprising one of the above compositions. In certain embodiments, the article is a multi-use vial. In certain embodiments, the article is a pre-filled syringe. In certain embodiments, the article is an automatic injection device ("auto-injector"). As is of interest herein, examples of auto-injectors are provided in U.S. Patent No. 8,734,394.

[0111] As used herein, "obesity" refers to a body mass index (BMI) greater than or equal to 30 kg / m 2 As used herein, "weight management" refers to behaviors, techniques, and physiological processes that contribute to a person's ability to maintain a healthy weight. A healthy weight for a particular patient can be determined through consultation with a healthcare professional; however, the World Health Organization generally defines "overweight" as a BMI greater than 25 kg / m 2 In certain embodiments, a subject in need of long-term weight management may refer to a subject having an initial BMI greater than or equal to 27 kg / m 2In certain embodiments, a subject in need of long-term weight management is a subject with an initial BMI greater than or equal to 27 kg / m 2 Subjects with at least one weight-related comorbidity. Long-term weight management therapy promotes the ability of patients to achieve their healthy weight goals. In one embodiment, "long-term weight management" refers to, for example, that the subject achieves his healthy weight goal and maintains his weight within his healthy weight target range for a certain period of time. In one embodiment, "long-term weight management" refers to that the subject achieves his healthy weight goal and maintains his weight within his healthy weight target range for at least 3 months. In one embodiment, the subject achieves his healthy weight goal and maintains his weight within his healthy weight target range for at least 6 months. In one embodiment, "long-term weight management" refers to that the subject achieves his healthy weight goal and maintains his weight within his healthy weight target range for at least 1 year. In one embodiment, "long-term weight management" refers to that the patient achieves his healthy weight goal and usually maintains his weight within his healthy weight target range. As used herein, "usually maintaining weight" refers to that most of the time, the subject's weight is within their healthy weight target range. In one embodiment, "usually maintaining weight" refers to that the subject's weight gain does not exceed 15% of his healthy target weight within a specified time period. In one embodiment, "long-term weight management" refers to that the patient achieves his healthy weight goal and improves at least one weight-related comorbidity indicator. In one embodiment, "long-term weight management" means that the patient has achieved their healthy weight goal, or the patient has lost weight and achieved the treatment goal for at least one weight-related comorbidity. As used herein, a subject who "requires additional long-term weight management" is unable to achieve their desired weight loss goal. In certain embodiments, "requires additional weight management" means that the subject is unable to achieve their healthy weight goal using at least 15 mg of telpotide once a week. In certain embodiments, "requires additional weight management" means that the subject is unable to achieve their healthy weight goal and achieve their treatment goals for at least one weight-related comorbidity using at least 15 mg of telpotide once a week. In certain embodiments, a "pediatric patient in need of long-term weight management" is a pediatric subject with an initial body mass index of 95% or more standardized for age and sex.

[0112] In certain embodiments, a "pediatric patient in need of long-term weight management" is a patient with age- and sex-standardized >85% of the initial body mass index with at least one weight-related comorbidity. As used herein, "pediatric" preferably may refer to a subject under the age of 20 years. In certain embodiments, "pediatric" refers to a subject older than 12 years. In certain embodiments, "pediatric" refers to a subject under the age of 18 years. In certain embodiments, a "pediatric patient in need of long-term weight management" is a pediatric subject with an initial body mass index of 90% or more normalized for age and sex.

[0113] As used herein, "Telpotide" refers to a GIP / GLP1 co-agonist peptide as described in US 9,474,780 and described by CAS Registry Number: 2023788-19-2. Telpotide is described in Example 1 of US 9,474,780 and has the following sequence:

[0114] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS

[0115] wherein X1 is Aib; X2 is Aib; K at position 20 is chemically modified by conjugating (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2)18-CO2H to the ε-amino group of the K side chain; and the C-terminal amino acid is amidated to a C-terminal primary amide (SEQ ID NO: 1).

[0116] In certain embodiments of the present invention, "telpoitide" refers to a compound of formula (SEQ ID NO: 1):

[0117]

[0118] In certain embodiments of the present invention, SEQ ID NO: 2) refers to a GIP / GLP1 co-agonist compound or a pharmaceutically acceptable salt thereof:

[0119] YX1EGTFTSDYSIX2LDKIAQKAX3VQWLIAGGPSSGAPPPS;

[0120] in

[0121] X1 is Aib;

[0122] X2 is Aib;

[0123] The K at position 20 is chemically modified by conjugating a C16-C20 fatty acid or its derivative to the ε-amino group of the K side chain;

[0124] X3 is Phe;

[0125] And the C-terminal amino acid is optionally amidated to a C-terminal primary amide.

[0126] In certain embodiments, as used herein, SEQ ID NO: 3 refers to a GIP / GLP1 co-agonist compound or a pharmaceutically acceptable salt thereof:

[0127] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS (SEQ ID NO: 3) wherein X1 is Aib; X2 is Aib; and K at position 20 is chemically modified by conjugating to the ε-amino group of the K side chain with a fatty acid selected from the following:

[0128]

[0129] And the C-terminal amino acid is optionally amidated to a C-terminal primary amide.

[0130] As used herein, the term "C16-C20 fatty acid" refers to a diacid having 16-20 carbon atoms. In one embodiment, the C16-C20 fatty acid suitable for use herein may be a saturated diacid. In one embodiment, the fatty acid is C20. In one embodiment, the fatty acid is ([2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu) a -CO-(CH2) b -CO2H, wherein a is 1-2 and b is 10-18.

[0131] In certain embodiments, the C16-C20 fatty acid is:

[0132]

[0133] In certain embodiments, the C16-C20 fatty acid is:

[0134]

[0135] In certain embodiments, the C16-C20 fatty acid is:

[0136]

[0137] As used herein, "derivative" refers to an atom or a group of atoms replaced by another atom or a group of atoms. As used herein, "derivative" can be a structural analog of a C16-C20 fatty acid.

[0138] In certain embodiments, telpotide (SEQ ID NO: 1) is preferred.

[0139] As used herein, "pharmaceutically acceptable salts" are well known to those skilled in the art. In one embodiment, is a pharmaceutically acceptable salt which is telpotide trifluoroacetate.

[0140] As used herein, the term "surfactant-free" means that the composition contains no added surfactant, or contains only de minimis added surfactant.

[0141] The composition of the present invention has a concentration of telpotide or a pharmaceutically acceptable salt thereof of 32 mg / mL to 55 mg / mL. The composition of the present invention has a concentration of telpotide or a pharmaceutically acceptable salt thereof of 36 mg / mL to 55 mg / mL. In one embodiment, the concentration of telpotide or a pharmaceutically acceptable salt thereof is from about 40 mg / mL to about 60 mg / mL. In one embodiment, the concentration of telpotide is selected from 40 mg / mL and 60 mg / mL. In one embodiment, the concentration of telpotide or a pharmaceutically acceptable salt thereof is from about 40 mg / mL to about 60 mg / mL. In one embodiment, the concentration of telpotide is selected from 40 mg / mL and 50 mg / mL. Such compositions may be present in a prefilled syringe or an automatic injector device. Such prefilled syringes may be used to administer half a milliliter of such compositions per patient per dose.

[0142] The compositions of the present invention have a concentration of SEQ ID NO:2 or a pharmaceutically acceptable salt thereof of 32 mg / mL to 55 mg / mL. The compositions of the present invention have a concentration of SEQ ID NO:2 or a pharmaceutically acceptable salt thereof of 36 mg / mL to 55 mg / mL. In one embodiment, the concentration of SEQ ID NO:2 or a pharmaceutically acceptable salt thereof is from about 40 mg / mL to about 60 mg / mL. In one embodiment, the concentration of SEQ ID NO:2 is selected from 40 mg / mL and 60 mg / mL. In one embodiment, the concentration of SEQ ID NO:2 or a pharmaceutically acceptable salt thereof is from about 40 mg / mL to about 60 mg / mL. In one embodiment, the concentration of SEQ ID NO:2 is selected from 40 mg / mL and 50 mg / mL.

[0143] The composition of the present invention has a concentration of SEQ ID NO:3 or a pharmaceutically acceptable salt thereof of 32 mg / mL to 55 mg / mL. The composition of the present invention has a concentration of SEQ ID NO:3 or a pharmaceutically acceptable salt thereof of 36 mg / mL to 55 mg / mL. In one embodiment, the concentration of SEQ ID NO:3 or a pharmaceutically acceptable salt thereof is from about 40 mg / mL to about 60 mg / mL. In one embodiment, the concentration of SEQ ID NO:3 is selected from 40 mg / mL and 60 mg / mL. In one embodiment, the concentration of SEQ ID NO:3 or a pharmaceutically acceptable salt thereof is from about 40 mg / mL to about 60 mg / mL. In one embodiment, the concentration of SEQ ID NO:3 is selected from 40 mg / mL and 50 mg / mL. Such compositions may be present in prefilled syringes or automatic injector devices. Such prefilled syringes may be used to administer half a milliliter of such compositions per patient per dose.

[0144] The composition of the present invention has a concentration of SEQ ID NO:4 or a pharmaceutically acceptable salt thereof of 32 mg / mL to 55 mg / mL. The composition of the present invention has a concentration of SEQ ID NO:4 or a pharmaceutically acceptable salt thereof of 36 mg / mL to 55 mg / mL. In one embodiment, the concentration of SEQ ID NO:4 or a pharmaceutically acceptable salt thereof is from about 40 mg / mL to about 60 mg / mL. In one embodiment, the concentration of SEQ ID NO:4 is selected from 40 mg / mL and 60 mg / mL. In one embodiment, the concentration of SEQ ID NO:4 or a pharmaceutically acceptable salt thereof is from about 40 mg / mL to about 60 mg / mL. In one embodiment, the concentration of SEQ ID NO:4 is selected from 40 mg / mL and 50 mg / mL. Such compositions may be present in prefilled syringes or automatic injector devices. Such prefilled syringes may be used to administer half a milliliter of such compositions per patient per dose.

[0145] These compositions are sterile when first produced. If provided in a multiple use vial or cartridge, an antimicrobial preservative compound or compound mixture compatible with the other ingredients of the composition can be added in sufficient concentration 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 (DBTroy edited, 21st edition, Lippincott, Williams & Wilkins, 2006). In one embodiment, the preservative is meta-cresol. In one embodiment, the preservative is phenol. The composition for a single prefilled syringe of the present invention, wherein the composition does not require a preservative. In one embodiment, the composition does not contain a surfactant.

[0146] The pH of the telpotide compositions of the invention is typically between 6.5 and 7.5 and is adjusted using physiologically appropriate acids and bases as may be necessary to achieve the desired pH. In one embodiment, the pH target for the composition of telpotide or a pharmaceutically acceptable salt thereof is between 6.7 and 7.3. Patient injection site experience is a consideration for subcutaneously administered compositions. It is desirable to select a composition that is associated with an acceptable patient injection site experience. For example, sodium chloride and citrate are associated with painful stinging 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 administering the composition, it is also desirable to match the tonicity (i.e., weight molar osmotic pressure concentration) of the body fluid at the injection site as closely as possible, because solutions that are not approximately isotonic with the body fluid will produce a painful stinging sensation when administered. Ideally, the composition is approximately isotonic with the body fluid at the injection site. The present composition comprising telpotide or a pharmaceutically acceptable salt thereof, NaCl and disodium hydrogen phosphate is associated with an acceptable patient injection site experience.

[0147] The pH of the SEQ ID NO:2 compositions of the invention is typically between 6.5 and 7.5, and is adjusted using physiologically appropriate acids and bases as may be necessary to achieve the desired pH. In one embodiment, the pH target for the SEQ ID NO:2 composition is between 6.7 and 7.3.

[0148] The pH of the SEQ ID NO:3 compositions of the invention is typically between 6.5 and 7.5, and is adjusted using physiologically appropriate acids and bases as may be necessary to achieve the desired pH. In one embodiment, the pH of the SEQ ID NO:3 composition is targeted to be between 6.7 and 7.3.

[0149] The pH of the SEQ ID NO:4 compositions of the invention is typically between 6.5 and 7.5, and is adjusted using physiologically appropriate acids and bases as may be necessary to achieve the desired pH. In one embodiment, the pH of the SEQ ID NO:4 composition is targeted to be between 6.7 and 7.3.

[0150] In one embodiment, a base is used to adjust the pH to facilitate dissolution in a buffer solution. It may be necessary to add an acid to the composition to adjust the pH to a desired pH range. In one embodiment, NaOH is used to facilitate dissolution of telpotide or a pharmaceutically acceptable salt thereof in a buffer. In one embodiment, HCl is added to adjust the pH of the composition comprising dissolved telpotide or a pharmaceutically acceptable salt thereof to a desired pH range.

[0151] The compositions of the present invention are typically administered subcutaneously. The compositions are typically administered using a prefilled disposable pen, a reusable pen, or an automatic pen-type syringe. The compositions can be administered using a multiple-use vial, a single-use vial, or a pump device. In one embodiment, the device is an automatic injection device as claimed in U.S. Patent No. 8,734,394.

[0152] Compositions comprising 40 mg / mL telpoitide or 50 mg / mL telpoitide, NaCl and disodium hydrogen phosphate provide the desired shelf-life stability and provide an acceptable injection site experience for patients. Likewise, compositions comprising 2.5 mg / mL telpoitide, NaCl and disodium hydrogen phosphate provide the desired shelf-life stability and provide an acceptable injection site experience for patients. As used herein, "shelf-life stability" is measured under controlled conditions of about 5 degrees Celsius. Compositions comprising 40 mg / mL telpoitide, NaCl and disodium hydrogen phosphate provide acceptable use stability. Likewise, compositions comprising 50 mg / mL telpoitide, NaCl and disodium hydrogen phosphate provide acceptable use stability. As used herein, the term "in-use stability" refers to the stability of a composition measured under controlled conditions, at or about 25 degrees Celsius or at or about 30 degrees Celsius. As used herein, "shelf-life stability" means that the degradation of telpotide at about 5 degrees Celsius is within the acceptable range of degradation products approved by a regulatory agency, as measured using at least one method described herein. As used herein, "in-use stability" means that the degradation of telpotide at about 25 degrees Celsius is within the acceptable range of degradation products approved by a regulatory agency, as measured using at least one method described herein. In certain embodiments, the regulatory agency is the United States Food and Drug Administration.

[0153] Although in some cases, increasing the drug dose may achieve improved efficacy, increasing the drug dose also carries a greater risk of side effects. For example, administration of GIP / GLP-1 receptor agonists is known to carry a risk of nausea and / or diarrhea. Therefore, any increase in dose must strike a balance between sufficiently improving efficacy without causing unacceptable safety or tolerability issues.

[0154] It has been found that increasing doses of 20 mg or 25 mg of telpoitide once a week can provide enhanced efficacy over doses of up to 15 mg. In certain embodiments, the subject achieves at least 17% weight loss. In certain embodiments, the subject achieves at least 20% weight loss. In certain embodiments, the subject achieves at least 22% weight loss. If the dosing regimen provided herein is used for administration, a telpoitide dose of 20 mg or 25 mg once a week can be administered with acceptable safety and tolerability characteristics. Therefore, the present invention provides administration of a telpoitide dose of at least 15 mg once a week for 4 weeks, followed by administration of 20 mg for at least 4 weeks, and when the 20 mg and 25 mg doses are administered, acceptable safety and tolerability characteristics are obtained. In subjects initiating telpotide treatment for the first time, the dosing regimen starts with a dose of 2.5 mg once weekly for at least 4 weeks, then increases the dose to 5 mg once weekly for at least 4 weeks, then increases the dose to 7.5 mg once weekly for at least 4 weeks, then increases the dose to 10 mg once weekly for at least 4 weeks, then increases the dose to 12.5 mg for at least 4 weeks, then increases the dose to 15 mg for at least 4 weeks, then increases the dose to 20 mg for at least 4 weeks, and then optionally increases the dose to 25 mg once weekly. However, in subjects who are already taking telpotide but require additional weight management, the dosing regimen does not require a reduction in the subject's current dose. For example, in subjects who are already receiving 15 mg of telpotide once weekly but require additional weight management, the regimen does not require a reduction in the dose to 2.5 mg, but instead continues to increase the dose to 20 mg once weekly for at least 4 weeks, and then optionally increases to 25 mg. Likewise, in subjects who are already receiving 20 mg of telpotide once weekly but require additional weight management, the regimen does not require a reduction in dose to 2.5 mg or 15 mg once weekly, but instead continues to increase the dose to 25 mg. However, for any of the above embodiments of the dosing regimen, the dose is preferably not increased to the next subsequent dose in progression until the current dose has been administered for at least 4 weeks. In certain embodiments, the dose is increased to 20 mg of telpotide once weekly without administering a 17.5 mg telpotide dose once weekly. In certain embodiments, the dose is increased to 20 mg of telpotide once weekly without administering a 17.5 mg telpotide dose once weekly for 4 weeks prior to the first 20 mg telpotide dose once weekly. In certain embodiments, the dose is increased to 25 mg of telpotide once weekly without administering a 22.5 mg telpotide dose once weekly. In certain embodiments, the dose is increased to 25 mg of telpotide once weekly without administering a 22.5 mg telpotide dose once weekly for 4 weeks prior to the first 25 mg telpotide dose once weekly.In certain embodiments, 25 mg telpotide is administered once weekly, a 17.5 mg dose is not administered, and a 22.5 mg dose is not administered. In certain embodiments, a 25 mg telpotide dose is administered once weekly in less than 4 weeks after the first 20 mg telpotide dose once weekly.

[0155] In addition, increasing the concentration of telpotide may require other modifications to the composition, and thus the present invention also provides compositions comprising increased doses of telpotide that remain chemically and physically stable - and meet current product specifications - throughout the 2-year refrigerated storage period and the maximum use period. In one embodiment, the composition is stable for at least 3 months. In one embodiment, the composition is stable for at least 6 months. In one embodiment, the composition is stable at 5 degrees Celsius for at least 3 months. In one embodiment, the composition is stable at 30 degrees Celsius for at least 6 months. In one embodiment, the composition is stable at 5 degrees Celsius for about 2 years. In one embodiment, the composition is stable at 30 degrees Celsius for about 2 years. In one embodiment, the composition is at least 90% pure active agent at the end of the storage period. In one embodiment, the composition is at least 95% pure active agent at the end of the storage period. In one embodiment, the composition is at least 90% pure telpotide after about 2 years at 5 degrees Celsius. In one embodiment, the composition is at least 90% pure telpotide after about 2 years at 30 degrees Celsius. In one embodiment, the composition is at least 95% pure telpotide after at least 6 months at 5 degrees Celsius. In one embodiment, the composition is at least 95% pure telpotide after at least 6 months at 30 degrees Celsius.

[0156] Likewise, lowering the telpotide concentration may require additional modifications to the composition, and thus the present invention also provides a composition comprising 2.5 mg / mL telpotide that remains chemically and physically stable—and meets current product specifications—throughout the 2-year refrigerated storage period and maximum usage period.

[0157] The telpotide composition studied in the Phase 3 clinical trial is provided in the form of a 0.5 mL aqueous solution containing a dose of telpotide selected from 2.5, 5, 7.5, 10, 12.5 and 15 mg. In one embodiment, a lower dose composition containing a dose of telpotide of 1.25 mg. Such a lower dose composition may be beneficial for pediatric patients or patients in need of such a dose. In one embodiment, a higher dose composition containing a dose selected from 20 mg and 25 mg of telpotide. The 1.25, 20 and 25 mg dose compositions need to provide protection against physical stress and ensure that telpotide maintains physical stability during the product shelf life, 2 years under refrigerated conditions and during maximum use.

[0158] As used herein, "shelf life" refers to the time that a material can be stored and remain suitable for use. As used herein, "suitable for use" means that the percentage purity of telpotide as determined by reverse phase HPLC is within the regulatory approval specifications for degradation products. As used herein, "purity" refers to the percentage of active pharmaceutical ingredient remaining in a composition after a certain period of time. In certain embodiments, the shelf life is 2 years at 30 degrees Celsius. In certain embodiments, the shelf life is 2 years at 5 degrees Celsius. In certain embodiments, the shelf life is at least 6 months at 5 degrees Celsius. In certain embodiments, the shelf life is at least 6 months at 30 degrees Celsius. In certain embodiments, a telpotide purity of 92% as determined by reverse phase HPLC is suitable for use. In certain embodiments, a telpotide purity of about 95% as determined by reverse phase HPLC is suitable for use. In certain embodiments, a telpotide purity of about 90% as determined by reverse phase HPLC is suitable for use. In certain embodiments, a telpotide purity of about 85% as determined by reverse phase HPLC is suitable for use. In certain embodiments, teilpotide is suitable for use when it is about 80% pure as determined by reverse phase HPLC.

[0159] As used herein, the term "about" refers to an amount within ten percent (10%) of a stated number, wherein the contemplated amount may potentially be within 10% less than the stated amount, or within 10% more than the stated amount.

[0160] As used herein, the terms "treatment," "treat," "treating," and the like are meant to include slowing or reducing the progression of a disease, disorder, or condition. These terms also include alleviating, ameliorating, attenuating, eliminating, or alleviating one or more symptoms of a disease or condition, even if the disease or condition is not actually eliminated and even if the progression of the disease or condition itself is not slowed or reversed.

[0161] A "subject" refers to a mammal, preferably a human, suffering from a disease, disorder or condition, who may benefit from treatment with an increased dose of telpotide.

[0162] "Glycemic control" means maintaining or reducing a subject's HbA1c level; "improving" glycemic control means reducing HbA1c; and "additional" glycemic control means requiring a reduction in HbA1c.

[0163] "Long-term weight management" refers to desired weight loss. "Long-term weight management" may refer to treatment that reduces a subject's BMI to approach or reach a healthy weight goal for the subject. "HbA1c" refers to glycated hemoglobin levels, which are produced when hemoglobin combines with glucose in the blood. HbA1c levels are a common indicator of glycemic control in diabetic patients, where reduced HbA1c levels generally indicate improved glycemic control. In the context of the methods of the present invention, the methods of the present invention result in a reduction in HbA1c.

[0164] In certain embodiments of the present invention, the dosages and dosing regimens of telpoxetine described herein are provided for use in treating obesity, long-term weight management, and / or non-therapeutic weight loss in a subject in need thereof. In certain embodiments, the subject has a telpoxetine weight of greater than about 25 kg / m 2 In certain embodiments, the subject has a body mass index (BMI) greater than about 26 kg / m 2 In certain embodiments, the subject has a body mass index (BMI) greater than about 27 kg / m 2 In certain embodiments, the subject also has one or more weight-related comorbidities, such as T2D, hypertension, and / or dyslipidemia.

[0165] In certain embodiments, the dosages and dosing regimens described herein are provided for the treatment of other diseases or conditions, such as fatty liver disease (FLD), nonalcoholic steatohepatitis (NASH), or chronic kidney disease (CKD).

[0166] In certain embodiments, provided are teilpotide dosages and dosing regimens described herein for use in preventing and / or treating cognitive disorders and / or neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and / or multiple sclerosis.

[0167] The methods of treatment and uses described herein may be provided in combination, simultaneously or sequentially, with other T2D treatments, including oral T2D medications, such as metformin, and / or other injectable medications, including rapid-acting insulin or basal insulin.

[0168] Example #1 - Compositions containing NaCl

[0169] The compositions were prepared essentially as described herein. Compositions comprising 2.5, 40 or 50 mg / mL of telpotide each comprised the ingredients listed in Table 1. Compositions suitable for clinical use are shown in Table 2. Acid or base is optionally added to achieve the desired pH range. Water is added qs to a total final volume of one milliliter.

[0170] Table 1. Formulations of telpotide, phosphate, and NaCl

[0171] Element Concentration (mg / mL) Telportide 2.5,40,50 Disodium hydrogen phosphate* 1.34 NaCl 8.2

[0172] *Use 5 mM phosphate buffer.

[0173] Table 2

[0174] Composition Preparation of NaCl Preparation of NaCl Telportide (mg / mL) 40 50 <![CDATA[Sodium hydrogen phosphate 7H2O (mg / mL)]]> 1.34 1.34 NaCl(mg / mL) 8.2 8.2 water Appropriate amount to mL Appropriate amount to mL

[0175]

[0176]

[0177] Example #2 - Compositions containing NaCl

[0178]

[0179] Stability study of size exclusion chromatography (SEC)

[0180] This method is an isocratic size exclusion HPLC method with UV detection at 214 nm and is intended to determine the relative amounts of telpotide monomer and total aggregates. Monomer and aggregates are reported as a percentage of the peak area to the total area. This method is stability-indicating as measured by its ability to separate known impurities from telpotide. This study compared alternative compositions to the compositions of the present invention, prepared as shown in Table 1.

[0181] Storage stability study RP-HPLC:

[0182] This method is a gradient reverse phase HPLC method with UV detection at 214 nm and is intended to determine the amount, identity and purity of tepoltide in a drug product. A high performance liquid chromatography (HPLC) equipped with a UV detector, a refrigerated autosampler, a gradient analysis pump, a column heater and an appropriate data collection system was used with a peptide (core-shell) 2.6 μm, 4.6 x 250 mm column. Mobile phase A was 0.1% (v / v) trifluoroacetic acid (TFA) in water. Mobile phase B was 0.1% TFA in acetonitrile (ACN). The diluent was 5 mM sodium phosphate, 140 mM NaCl at pH 7. A flow rate and gradient of 1.2 mL / min was used. The autosampler was at 5 °C + 3℃. Column temperature is 60℃ +2°C, using a 10 μL injection volume (approximately 10 μg) and a run time of approximately 60 minutes. Identity is determined by matching the retention time of the major peak to that of the external reference standard. Quantification is performed by comparing the area of ​​the major peak to the corresponding peak in the external reference standard. Impurities and related substances are reported as a percentage of the peak area to the total peak area. The method measures stability by separating known impurities from telpotide. A composition comprising 50 mg / mL telpotide with NaCl as a tonicity agent can provide acceptable stability for use for at least 6 months, as shown by greater than 89% telpotide purity at 6 months at 30°C.

[0183] As shown in the results below, compositions comprising 50 mg / mL or 60 mg / mL teilpoitide with sodium chloride as a tonicity agent provided an acceptable shelf life of at least 6 months at both 5° C. and 25° C. These studies showed that within the range of pH 6.5 to pH 7.5, an acceptable shelf life of at least 6 months was shown in the studies reported below using 30 mg / 0.5 NaCl as a tonicity agent.

[0184] Comparison of purity at high strength (25 mg / 0.5 mL) with 2.5 mg / 0.5 mL and 15 mg / 0.5 mL by RP-HPLC (30 °C)

[0185]

[0186] *RP-HPLC precision is 0.33%. The 0.1% value is within the error range.

[0187] Comparison of purity at high strength (25 mg / 0.5 mL and 30 mg / 0.5 mL) with 2.5 mg / 0.5 mL and 15 mg / 0.5 mL by RP-HPLC (25°C)

[0188]

[0189] Size Exclusion Chromatography (SEC) Storage Stability Study

[0190] The size exclusion stability study method described above and RP-HPLC were used to evaluate a composition comprising 2.5 mg / mL of telpotide and NaCl as a tonicity and stabilizer to ensure the in-use stability of the lower concentration composition. The size exclusion stability study method was applied to higher doses to evaluate the in-use stability. Size exclusion chromatography was used to measure telpotide aggregation, so that the percentage of telpotide monomers could be determined. This method uses size exclusion HPLC with UV detection and is an indicator of stability. The HPLC was equipped with a UV detector, a cryo-autosampler, a BEH (3.5μm, 7.8mm x300mm) size exclusion chromatography column with temperature controlled column compartment and data collection system. Size exclusion chromatography was performed using a 10mM sodium citrate reference standard at pH 6.5. The mobile phase was a solution of 0.05% trifluoroacetic acid (TFA) in 50% acetonitrile (ACN). The column temperature was maintained at 25°C and the autosampler temperature was between 2-8°C. The flow rate was 0.5mL / min. The detection wavelength was 214nm. The run time after equilibrium was approximately 30 minutes. Validation was completed and the system suitability was checked using check standard injections throughout the analytical process, after blanks, subsequent injections, and at the end of the run. The monomer percentage was determined using the formula = (monomer peak area / total protein peak area) * 100. The percentage of total high molecular weight species can be determined using the following formula: (∑ high molecular weight peak area (peak after monomer) * 100) / total protein peak area. The following results support that tepoltide aggregation is less than 1% at all strengths studied at 5°C for at least 6 months of storage. The results support that tepoltide aggregation is 1% or less at all strengths studied at 30°C for at least 6 months of storage.

[0191] Comparison of high strength (25 mg / 0.5 mL) with 2.5 mg / 0.5 mL and 15 mg / 0.5 mL by SEC HMWS (30 °C)

[0192]

[0193] **The size exclusion chromatography percentages in the table represent the percentage of telpotide aggregation.

[0194] Comparison of high strength (25 mg / 0.5 mL and 30 mg / 0.5 mL) with 2.5 mg / 0.5 mL and 15 mg / 0.5 mL by SEC HMWS (25 °C)

[0195]

[0196]

[0197] **The size exclusion chromatography percentages in the table represent the aggregation percentage of tepol peptide.

[0198] Example 3

[0199] Clinical Research

[0200] A randomized, double-blind, placebo-controlled study was used to evaluate the efficacy and safety of 20 mg and 25 mg of tepoxetine per week. In this study, participants had type 2 diabetes and obesity (class II obesity). This study included 1) a screening period; 2) a dose escalation period; 3) a high-dose treatment period; 4) an extension period; and 5) a post-treatment follow-up period. All doses were administered using a subcutaneous injection. All participants in this study must have been treated with metformin for at least 3 months before screening, with a minimum dose of 1500 mg / day. The pre-screening dose and formulation (short-acting or long-acting) of metformin should be maintained during the screening period and randomization process. During this study, participants were asked about any gastrointestinal symptoms.

[0201] Phase I - Screening

[0202] All screening activities must be performed within a 35-day window period. The purpose of the screening procedure is to determine eligibility and obtain blood samples for laboratory evaluations required to confirm eligibility. Once eligibility is confirmed, a dilated funduscopy is performed by an ophthalmologist or optometrist. Participants are given a paper diary and begin recording their blood glucose measurements and any hypoglycemic events. Within 2 weeks of each visit, two 7-point blood glucose measurements are collected on 2 non-consecutive days. The 7-point blood glucose measurement consists of measurements before and 2 hours after each of the 3 main meals on the same day and at bedtime.

[0203] Phase II – Dose escalation

[0204] After randomization, participants will be trained to self-administer the study product. The date, time, and location of the first dose of the study intervention will be recorded. Participants will receive diabetes and weight management counseling at this visit. Beginning with randomization, all participants will receive the study intervention according to their randomized group during a 24-week dose escalation period. Subjects will receive dose escalation of tepoltide consisting of a dosing schedule that begins at a dose of 2.5 mg per week for 4 weeks and increases in 2.5 mg increments such that subjects receive weekly doses of 2.5 mg (4 weeks), 5 mg (4 weeks), 7.5 mg (4 weeks), 10 mg (4 weeks), 12.5 mg (4 weeks), and 15 mg (4 weeks). Subjects randomized to placebo will receive placebo throughout the dose escalation period.

[0205] Any discontinuation or reduction of metformin during the trial should be properly documented and archived. Participants were considered nonadherent to the protocol if they had a dose change or discontinuation of metformin for reasons other than severe, persistent hypoglycemia, contraindications to country-specific labeling, or short-term discontinuation of metformin consistent with country-specific labeling.

[0206] Phase III - High-dose therapy

[0207] Participants who were randomized to telpotide at Visit 3 and who did not discontinue the study intervention were randomized to a maintenance dose of telpotide (15 mg, 20 mg, or 25 mg) at Visit 9. Higher doses of telpotide (greater than 15 mg / week) were escalated in 5-mg increments every 4 weeks until the randomized dose of 20 mg or 25 mg was reached. To achieve the assigned dose, all participants were required to receive 2 injections once weekly starting at Week 24 (i.e., 20 mg once weekly using a 2-10 mg fixed-dose pen, followed by 25 mg once weekly using a 10 mg fixed-dose pen and a 15 mg fixed-dose pen to provide the desired total weekly dose).

[0208] These participants will receive the study intervention according to their randomized group during the 20-week high-dose phase. Participants who were randomized to placebo at Visit 3 will undergo a mock rerandomization at Visit 9 and continue to receive placebo during the treatment period. Participants who permanently discontinue the study intervention before Visit 9 will not be rerandomized and will continue in the study until Visit 14.

[0209] Phase IV - Primary Endpoint (Visit 14)

[0210] Participants randomized to placebo at Visit 3 will not be assigned an intervention and will complete the treatment period at Visit 14. These participants will complete all 14 visit procedures and have a safety follow-up at Week 48. Participants who discontinued the study intervention before Visit 9 (based on the minute of randomization) will complete the treatment period at this visit. These participants will complete all 14 visit procedures and have a safety follow-up at Week 48. All other participants randomized to teilpotide will complete the Visit 14 procedure and continue in the study during the 36-week extension period.

[0211] Phase V - Extended Phase

[0212] At Visit 9 (second randomization), all participants randomized to the maintenance dose of tepol will complete all visits in the extension phase and complete safety follow-up at Week 84. The extension to Week 80 allows for 52 weeks of treatment at the highest dose achieved during dose escalation.

[0213] Follow-up after treatment

[0214] All post-treatment safety visits will be conducted approximately 4 weeks after the last treatment visit or final assessment visit. All participants are required to complete the safety visit.

[0215] Concomitant therapy.

[0216] Metformin was selected as a required concomitant antihyperglycemic agent. The minimum dose was at least 1500 mg / day before adding additional therapy to ensure the maximum efficacy of metformin. Except for special circumstances, participants were instructed to maintain metformin throughout the treatment period until the last dose of randomized treatment.

[0217] Some embodiments are the following:

[0218] 1. (Embodiment 1) A pharmaceutical composition comprising SEQ ID NO: 2 or a pharmaceutically acceptable salt thereof; wherein the compound concentration of SEQ ID NO: 2 is selected from about 2.5 mg / mL, about 40 mg / mL, about 50 mg / mL and about 60 mg / mL; NaCl; and sodium hydrogen phosphate.

[0219] 2. A pharmaceutical composition comprising SEQ ID NO: 2 or a pharmaceutically acceptable salt thereof; wherein the compound concentration of SEQ ID NO: 2 is selected from about 2.5 mg / mL, about 40 mg / mL and about 50 mg / mL; NaCl; and sodium hydrogen phosphate.

[0220] 3. The pharmaceutical composition of embodiment 1, wherein the concentration of the compound of SEQ ID NO: 2 or a pharmaceutically acceptable salt thereof is about 40 mg / mL or about 50 mg / mL.

[0221] 4. The pharmaceutical composition of embodiment 1, wherein the concentration of the compound of SEQ ID NO: 2 or a pharmaceutically acceptable salt thereof is about 2.5 mg / mL.

[0222] 5. The pharmaceutical composition of any one of embodiments 3-4, wherein the concentration of sodium hydrogen phosphate is about 0.7 mg / mL to about 1.5 mg / mL.

[0223] 6. The pharmaceutical composition of embodiment 5, wherein the concentration of disodium hydrogen phosphate is about 1.34 mg / mL.

[0224] 7. The pharmaceutical composition exemplified in embodiment 6, wherein the concentration of the compound of SEQ ID NO: 2 or a pharmaceutically acceptable salt thereof is selected from about 2.5 mg / mL, about 40 mg / mL and about 50 mg / mL.

[0225] 8. The pharmaceutical composition as illustrated in embodiment 7, wherein the concentration of the compound of SEQ ID NO: 2 or a pharmaceutically acceptable salt thereof is selected from 40 and 50 mg / mL.

[0226] 9. The pharmaceutical composition of embodiment 7, wherein the NaCl concentration is about 7 mg / mL to about 9 mg / mL.

[0227] 10. The pharmaceutical composition of embodiment 9, wherein the NaCl concentration is about 7.4 mg / mL to about 9.0 mg / mL.

[0228] 11. The pharmaceutical composition of embodiment 10, wherein the NaCl concentration is about 8.2 mg / mL.

[0229] 12. The pharmaceutical composition of embodiment 1, wherein the concentration of the compound of SEQ ID NO: 2 or a pharmaceutically acceptable salt thereof is selected from 2.5, 40 and 50 mg / mL; the concentration of disodium hydrogen phosphate is about 0.7 mg / mL to about 1.5 mg / mL; and the concentration of NaCl is about 7 mg / mL to about 9 mg / mL.

[0230] 13. The pharmaceutical composition of embodiment 12, wherein the concentration of the compound of SEQ ID NO: 2 or a pharmaceutically acceptable salt thereof is selected from 2.5, 40 and 50 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.

[0231] 14. The pharmaceutical composition of embodiment 13, wherein the composition is provided in an automatic injection device.

[0232] 15. The pharmaceutical composition of embodiment 13, wherein the pH of the composition is about 6.5 to about 7.5.

[0233] 16. The pharmaceutical composition of embodiment 15, wherein the pH is from about 6.7 to about 7.3.

[0234] 17. The pharmaceutical composition of embodiment 16 further comprises one or more preservatives.

[0235] 18. The pharmaceutical composition as exemplified in embodiment 17, 19. wherein the composition further comprises a preservative selected from the group consisting of m-cresol and phenol.

[0236] 20. The pharmaceutical composition of embodiment 1, wherein the concentration of the compound of SEQ ID NO: 2 or a pharmaceutically acceptable salt thereof is selected from about 2.5 mg / mL, 40 mg / mL and 50 mg / mL; the sodium hydrogen phosphate is about 0.7 to about 1.5 mg / mL; and the NaCl is about 7 mg / mL to about 9 mg / mL.

[0237] 21. The pharmaceutical composition of embodiment 20, wherein the dosage of the composition is about 0.5 mL.

[0238] 22. The pharmaceutical composition of embodiment 20, wherein the composition is administered using an automatic injection device.

[0239] 23. The pharmaceutical composition as exemplified in any one of embodiments 1-22, wherein the compound is SEQ ID NO: 2.

[0240] 24. A method for treating diabetes, comprising administering an effective dose of the pharmaceutical composition exemplified in embodiment 20 to a person in need thereof.

[0241] 25. The method for treating diabetes as exemplified in embodiment 24, wherein the dose is administered once a week.

[0242] 26. A method for treating obesity, comprising administering an effective dose of the pharmaceutical composition exemplified in embodiment 20 to a person in need thereof.

[0243] 27. The method for treating obesity as exemplified in embodiment 26, wherein the dose is administered using an automatic injection device.

[0244] 28. The method for treating obesity as exemplified in embodiment 26, wherein the dose is administered once a week.

[0245] 29. The pharmaceutical composition as exemplified in embodiment 20, for use in treating T2D.

[0246] 30. The pharmaceutical composition according to embodiment 20, used for treating obesity.

[0247] 31. A method for long-term weight management in a subject who is obese and in need of additional weight management, comprising:

[0248] Identify subjects who have obesity and require additional weight management;

[0249] administering to the subject a dose of at least 15 mg of a compound of SEQ ID NO: 2 once a week for a minimum of 4 weeks; and

[0250] After administering a 15 mg once weekly dose of SEQ ID NO: 2 for at least 4 weeks, administering a once weekly dose of SEQ ID NO: 2 selected from 20 mg and 25 mg.

[0251] 32. The method of long-term weight management as exemplified in embodiment 31, wherein the dose of SEQ ID NO: 2 once a week is 20 mg.

[0252] 33. The method for long-term weight management as exemplified in embodiment 31, comprising:

[0253] administering to the subject a dose of 20 mg of the compound of SEQ ID NO: 2 once a week for a minimum of 4 weeks; and

[0254] After administering a 20 mg once weekly dose of SEQ ID NO: 2 for at least 4 weeks, a once weekly dose of SEQ ID NO: 2 of 25 mg was administered.

[0255] 34. Methods for long-term weight management for subjects requiring additional weight management, including:

[0256] Identify subjects who require additional weight management;

[0257] administering to the subject a once weekly dose of 15 mg of the compound of SEQ ID NO: 2; and

[0258] At least 1 week later, administering to the subject a weekly dose of SEQ ID NO: 2 of 20 mg for at least 2 weeks; and

[0259] At least 2 weeks later, the subject is administered a once-weekly dose of SEQ ID NO: 2, which is 25 mg.

[0260] 35. A pharmaceutical composition comprising SEQ ID NO:3 or a pharmaceutically acceptable salt thereof; wherein the compound concentration of SEQ ID NO:3 is selected from about 2.5 mg / mL, about 40 mg / mL, about 50 mg / mL and about 60 mg / mL; NaCl; and sodium hydrogen phosphate.

[0261] 36. A pharmaceutical composition comprising SEQ ID NO:3 or a pharmaceutically acceptable salt thereof; wherein the compound concentration of SEQ ID NO:3 is selected from about 2.5 mg / mL, about 40 mg / mL, and about 50 mg / mL; NaCl; and sodium phosphate dibasic.

[0262] 37. The pharmaceutical composition of embodiment 35, wherein the concentration of the compound of SEQ ID NO: 3 or a pharmaceutically acceptable salt thereof is about 40 mg / mL or about 50 mg / mL.

[0263] 38. The pharmaceutical composition of embodiment 35, wherein the concentration of the compound of SEQ ID NO: 3 or a pharmaceutically acceptable salt thereof is about 2.5 mg / mL.

[0264] 39. The pharmaceutical composition of any one of embodiments 35-38, wherein the concentration of sodium phosphate dibasic is about 0.7 mg / mL to about 1.5 mg / mL.

[0265] 40. The pharmaceutical composition of embodiment 39, wherein the concentration of sodium phosphate dibasic is about 1.34 mg / mL.

[0266] 41. The pharmaceutical composition of embodiment 40, wherein the concentration of the compound of SEQ ID NO: 3 or a pharmaceutically acceptable salt thereof is selected from about 2.5 mg / mL, about 40 mg / mL and about 50 mg / mL.

[0267] 42. The pharmaceutical composition as illustrated in embodiment 41, wherein the concentration of the compound of SEQ ID NO: 3 or a pharmaceutically acceptable salt thereof is selected from 40 and 50 mg / mL.

[0268] 43. The pharmaceutical composition of embodiment 41, wherein the NaCl concentration is about 7 mg / mL to about 9 mg / mL.

[0269] 44. The pharmaceutical composition of embodiment 43, wherein the NaCl concentration is about 7.4 mg / mL to about 9.0 mg / mL.

[0270] 45. The pharmaceutical composition of embodiment 44, wherein the NaCl concentration is about 8.2 mg / mL.

[0271] 46. ​​The pharmaceutical composition of embodiment 34, wherein the concentration of the compound of SEQ ID NO: 3 or a pharmaceutically acceptable salt thereof is selected from 2.5, 40 and 50 mg / mL; the concentration of sodium hydrogen phosphate is about 0.7 mg / mL to about 1.5 mg / mL; and the concentration of NaCl is about 7 mg / mL to about 9 mg / mL.

[0272] 47. The pharmaceutical composition of embodiment 46, wherein the concentration of the compound of SEQ ID NO: 3 or a pharmaceutically acceptable salt thereof is selected from 2.5, 40 and 50 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.

[0273] 48. The pharmaceutical composition of embodiment 47, wherein the composition is provided in an automatic injection device.

[0274] 49. The pharmaceutical composition of embodiment 47, wherein the pH of the composition is about 6.5 to about 7.5.

[0275] 50. The pharmaceutical composition of embodiment 49, wherein the pH is from about 6.7 to about 7.3.

[0276] 51. The pharmaceutical composition of embodiment 50, further comprising one or more preservatives.

[0277] 52. The pharmaceutical composition of embodiment 51, wherein the composition further comprises a preservative selected from the group consisting of m-cresol and phenol.

[0278] 53. The pharmaceutical composition of embodiment 35, wherein the concentration of the compound of SEQ ID NO: 3 or a pharmaceutically acceptable salt thereof is selected from about 2.5 mg / mL, 40 mg / mL and 50 mg / mL; sodium hydrogen phosphate is about 0.7 to about 1.5 mg / mL; and NaCl is about 7 mg / mL to about 9 mg / mL.

[0279] 54. The pharmaceutical composition of embodiment 53, wherein the dosage of the composition is about 0.5 mL.

[0280] 55. The pharmaceutical composition of embodiment 53, wherein the composition is administered using an automatic injection device.

[0281] 56. The pharmaceutical composition of any one of embodiments 35-55, wherein the compound is SEQ ID NO: 3.

[0282] 57. A method for treating diabetes, comprising administering an effective dose of the pharmaceutical composition exemplified in embodiment 35 to a person in need thereof.

[0283] 58. The method for treating diabetes as exemplified in embodiment 57, wherein the dose is administered once a week.

[0284] 59. A method for treating obesity, comprising administering an effective dose of the pharmaceutical composition exemplified in embodiment 50 to a person in need thereof.

[0285] 60. The method for treating obesity as exemplified in embodiment 59, wherein the dose is administered using an automatic injection device.

[0286] 61. The method for treating obesity as exemplified in embodiment 59, wherein the dose is administered once a week.

[0287] 62. The pharmaceutical composition as exemplified in embodiment 53, for use in treating T2D.

[0288] 63. The pharmaceutical composition as exemplified in embodiment 53, which is used for treating obesity.

[0289] 64. A method for long-term management of a subject who is obese and requires additional weight management, comprising:

[0290] Identify subjects who have obesity and require additional weight management;

[0291] administering to the subject a dose of at least 15 mg of a compound of SEQ ID NO: 3 once a week for a minimum of 4 weeks; and

[0292] After administering a once-weekly dose of 15 mg of SEQ ID NO: 3 for at least 4 weeks, a once-weekly dose of SEQ ID NO: 3 selected from 20 mg and 25 mg is administered.

[0293] 65. The method of long-term weight management as exemplified in embodiment 64, wherein the once weekly dose of SEQ ID NO: 3 is 20 mg.

[0294] 66. The method for long-term weight management as exemplified in embodiment 64, comprising:

[0295] administering to the subject a dose of 20 mg of the compound of SEQ ID NO: 3 once a week for a minimum of 4 weeks; and

[0296] After administering a 20 mg once weekly dose of SEQ ID NO: 3 for at least 4 weeks, a once weekly dose of SEQ ID NO: 3 of 25 mg was administered.

[0297] 67. Methods for long-term weight management in subjects requiring additional weight management, comprising:

[0298] Identify subjects who require additional weight management;

[0299] administering to the subject a dose of 15 mg of the compound of SEQ ID NO: 3 once a week; and

[0300] At least 1 week later, administering to the subject a weekly dose of SEQ ID NO: 3 of 20 mg for at least 2 weeks; and

[0301] At least 2 weeks later, the subject is administered a once-weekly dose of SEQ ID NO: 3, which is 25 mg.

[0302] 68. The pharmaceutical composition of embodiment 35, wherein the concentration of the compound of SEQ ID NO: 3 or a pharmaceutically acceptable salt thereof is selected from 2.5, 40 and 50 mg / mL; the concentration of sodium hydrogen phosphate is about 0.7 mg / mL to about 1.5 mg / mL; and the concentration of NaCl is about 7 mg / mL to about 9 mg / mL.

[0303] 69. The pharmaceutical composition of embodiment 46, wherein the concentration of the compound of SEQ ID NO: 3 or a pharmaceutically acceptable salt thereof is selected from 2.5, 40 and 50 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.

[0304] 70. The pharmaceutical composition of embodiment 69, wherein the composition is provided in an automatic injection device.

[0305] 71. The pharmaceutical composition of embodiment 35, wherein the pH of the composition is about 6.5 to about 7.5.

[0306] 72. The pharmaceutical composition of embodiment 71, wherein the pH is from about 6.7 to about 7.3.

[0307] 73. A pharmaceutical composition comprising SEQ ID NO:4 or a pharmaceutically acceptable salt thereof; wherein the compound concentration of SEQ ID NO:4 is selected from about 2.5 mg / mL, about 40 mg / mL, about 50 mg / mL and about 60 mg / mL; NaCl; and sodium hydrogen phosphate.

[0308] 74. A pharmaceutical composition comprising SEQ ID NO:4 or a pharmaceutically acceptable salt thereof; wherein the concentration of compound SEQ ID NO:4 is selected from about 2.5 mg / mL, about 40 mg / mL and about 50 mg / mL; NaCl; and sodium hydrogen phosphate.

[0309] 75. The pharmaceutical composition of embodiment 73, wherein the concentration of the compound of SEQ ID NO: 4 or a pharmaceutically acceptable salt thereof is about 40 mg / mL or about 50 mg / mL.

[0310] 76. The pharmaceutical composition of embodiment 73, wherein the concentration of the compound of SEQ ID NO: 4 or a pharmaceutically acceptable salt thereof is about 2.5 mg / mL.

[0311] 77. The pharmaceutical composition of any one of embodiments 73-76, wherein the concentration of sodium phosphate dibasic is about 0.7 mg / mL to about 1.5 mg / mL.

[0312] 78. The pharmaceutical composition of embodiment 77, wherein the concentration of sodium phosphate dibasic is about 1.34 mg / mL.

[0313] 79. The pharmaceutical composition of embodiment 78, wherein the concentration of the compound of SEQ ID NO: 4 or a pharmaceutically acceptable salt thereof is selected from about 2.5 mg / mL, about 40 mg / mL and about 50 mg / mL.

[0314] 80. The pharmaceutical composition of embodiment 79, wherein the concentration of the compound of SEQ ID NO: 4 or a pharmaceutically acceptable salt thereof is selected from 40 and 50 mg / mL.

[0315] 81. The pharmaceutical composition of embodiment 79, wherein the NaCl concentration is about 7 mg / mL to about 9 mg / mL.

[0316] 82. The pharmaceutical composition of embodiment 81, wherein the NaCl concentration is about 7.4 mg / mL to about 9.0 mg / mL.

[0317] 83. The pharmaceutical composition of embodiment 82, wherein the NaCl concentration is about 8.2 mg / mL.

[0318] 84. The pharmaceutical composition of embodiment 73, wherein the concentration of the compound of SEQ ID NO:4 or a pharmaceutically acceptable salt thereof is selected from 2.5, 40 and 50 mg / mL; the concentration of disodium hydrogen phosphate is about 0.7 mg / mL to about 1.5 mg / mL; and the concentration of NaCl is about 7 mg / mL to about 9 mg / mL.

[0319] 85. The pharmaceutical composition of embodiment 84, wherein the concentration of the compound of SEQ ID NO: 4 or a pharmaceutically acceptable salt thereof is selected from 2.5, 40 and 50 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.

[0320] 86. The pharmaceutical composition of embodiment 85, wherein the composition is provided in an automatic injection device.

[0321] 87. The pharmaceutical composition of embodiment 84, wherein the pH of the composition is about 6.5 to about 7.5.

[0322] 88. The pharmaceutical composition of embodiment 87, wherein the pH is from about 6.7 to about 7.3.

[0323] 89. The pharmaceutical composition of embodiment 85, further comprising one or more preservatives.

[0324] 90. The pharmaceutical composition of embodiment 89, wherein the composition further comprises a preservative selected from the group consisting of m-cresol and phenol.

[0325] 91. The pharmaceutical composition of embodiment 73, wherein the concentration of the compound of SEQ ID NO:4 or a pharmaceutically acceptable salt thereof is selected from about 2.5 mg / mL, 40 mg / mL and 50 mg / mL; sodium hydrogen phosphate is about 0.7 to about 1.5 mg / mL; and NaCl is about 7 mg / mL to about 9 mg / mL.

[0326] 92. The pharmaceutical composition of embodiment 91, wherein the dosage of the composition is about 0.5 mL.

[0327] 93. The pharmaceutical composition of embodiment 92, wherein the composition is administered using an automatic injection device.

[0328] 94. The pharmaceutical composition of any one of embodiments 73-93, wherein the compound is SEQ ID NO:4.

[0329] 95. A method for treating diabetes, comprising administering an effective dose of the pharmaceutical composition exemplified in embodiment 73 to a person in need thereof.

[0330] 96. The method for treating diabetes as exemplified in embodiment 95, wherein the dose is administered once a week.

[0331] 97. A method for treating obesity, comprising administering an effective dose of the pharmaceutical composition exemplified in embodiment 73 to a person in need thereof.

[0332] 98. The method for treating obesity as described in embodiment 97, wherein the dose is administered using an automatic injection device.

[0333] 99. The method for treating obesity as described in embodiment 97, wherein the dose is administered once a week.

[0334] 100. The pharmaceutical composition as exemplified in embodiment 73, for use in treating T2D.

[0335] 101. The pharmaceutical composition as illustrated in embodiment 73 is used for treating obesity.

[0336] 102. A method for long-term weight management in a subject requiring additional weight management, comprising:

[0337] Identify subjects who have obesity and require additional weight management;

[0338] administering to the subject a dose of at least 15 mg of a compound of SEQ ID NO: 4 once a week for a minimum of 4 weeks; and

[0339] After administering a once-weekly dose of 15 mg of SEQ ID NO: 4 for at least 4 weeks, administer a once-weekly dose of SEQ ID NO: 4 selected from 20 mg and 25 mg.

[0340] 103. The method of long-term weight management as exemplified in embodiment 102, wherein the once weekly dose of SEQ ID NO: 4 is 20 mg.

[0341] 104. The method for long-term weight management as exemplified in embodiment 102, comprising:

[0342] administering to the subject a dose of 20 mg of the compound of SEQ ID NO: 4 once a week for a minimum of 4 weeks; and

[0343] After administering a 20 mg dose of SEQ ID NO: 4 once a week for at least 4 weeks, a 25 mg dose of SEQ ID NO: 4 was administered once a week.

[0344] 105. A method for long-term weight management in a subject requiring additional weight management, comprising:

[0345] Identify subjects who require additional weight management;

[0346] administering to the subject a dose of 15 mg of the compound of SEQ ID NO: 4 once a week; and

[0347] At least 1 week later, administering to the subject a weekly dose of SEQ ID NO: 4 of 20 mg for at least 2 weeks; and

[0348] At least 2 weeks later, the subject is administered a once-weekly dose of SEQ ID NO: 4, which is 25 mg.

[0349] 106. The pharmaceutical composition of embodiment 73, wherein the concentration of the compound of SEQ ID NO:4 or a pharmaceutically acceptable salt thereof is selected from 2.5, 40 and 50 mg / mL; the concentration of disodium hydrogen phosphate is about 0.7 mg / mL to about 1.5 mg / mL; and the concentration of NaCl is about 7 mg / mL to about 9 mg / mL.

[0350] 107. The pharmaceutical composition of embodiment 106, wherein the concentration of the compound of SEQ ID NO: 4 or a pharmaceutically acceptable salt thereof is selected from 2.5, 40 and 50 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.

[0351] 108. The pharmaceutical composition of embodiment 107, wherein the composition is provided in an automatic injection device.

[0352] 109. The pharmaceutical composition of embodiment 73, wherein the pH of the composition is about 6.5 to about 7.5.

[0353] 110. The pharmaceutical composition of embodiment 109, wherein the pH is from about 6.7 to about 7.3.

[0354] sequence

[0355] SEQ ID NO: 1 Telportide

[0356] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS

[0357] wherein X1 is Aib; X2 is Aib; K at position 20 is obtained by using (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2) 18 -CO2H is conjugated to the ε-amino group of the K side chain for chemical modification;

[0358] And the C-terminal amino acid is amidated to a C-terminal primary amide.

[0359] SEQ ID NO:2

[0360] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS

[0361] wherein X1 is Aib; X2 is Aib; K at position 20 is chemically modified by conjugating a C16-C20 fatty acid or a derivative thereof to the ε-amino group of the K side chain; and the C-terminal amino acid is optionally amidated to a C-terminal primary amide.

[0362] SEQ ID NO:3

[0363] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS (SEQ ID NO: 3), wherein X1 is Aib; X2 is Aib; and K at position 20 is chemically modified by conjugating to the ε-amino group of the K side chain with a fatty acid selected from the following:

[0364]

[0365] and the C-terminal amino acid is optionally amidated to a C-terminal primary amide; or a pharmaceutically acceptable salt thereof.

[0366] SEQ ID NO:4

[0367]

Claims

1. A pharmaceutical composition comprising telpotide or a pharmaceutically acceptable salt thereof; NaCl; and sodium phosphate; wherein the concentration of telpotide or a pharmaceutically acceptable salt thereof is about 40 mg / mL to about 60 mg / mL.

2. The pharmaceutical composition as claimed in claim 1, wherein the sodium phosphate is disodium hydrogen phosphate.

3. A pharmaceutical composition as claimed in any one of claims 1-2, wherein the pH of the composition is from about 6.5 to about 7.

5.

4. A pharmaceutical composition as claimed in any one of claims 1 to 3, wherein the pH of the composition is from about 6.7 to about 7.

3.

5. The pharmaceutical composition as claimed in any one of claims 1 to 4, wherein the concentration of teilpotide or a pharmaceutically acceptable salt thereof is from about 40 mg / mL to about 50 mg / mL.

6. A pharmaceutical composition as claimed in any one of claims 1 to 5, wherein tepoltide is a free base.

7. A pharmaceutical composition as claimed in any one of claims 2 to 6, wherein the concentration of sodium hydrogen phosphate is from about 0.7 mg / mL to about 1.5 mg / mL.

8. A pharmaceutical composition as claimed in any one of claims 2 to 7, wherein the concentration of disodium hydrogen phosphate is about 1.34 mg / mL.

9. The pharmaceutical composition as claimed in any one of claims 1 to 8, wherein the NaCl concentration is from about 7 mg / mL to about 9 mg / mL.

10. The pharmaceutical composition as claimed in any one of claims 1 to 9, wherein the NaCl concentration is from about 7.4 mg / mL to about 9.0 mg / mL.

11. A pharmaceutical composition as claimed in any one of claims 1 to 10, wherein the NaCl concentration is about 8.2 mg / mL.

12. A pharmaceutical composition as claimed in any one of claims 1 to 11, wherein the composition has a shelf-life stability of at least about 6 months.

13. A pharmaceutical composition as claimed in any one of claims 1 to 12, wherein the composition has a shelf-life stability of at least about 2 years.

14. A pharmaceutical composition as claimed in any one of claims 1 to 11, wherein the composition has a stability in use for at least about 3 months.

15. A pharmaceutical composition as claimed in any one of claims 1 to 11, wherein the composition has a stability in use for at least about 6 months.

16. A pharmaceutical composition comprising telpotide or a pharmaceutically acceptable salt thereof; NaCl; and sodium phosphate dibasic; wherein the telpotide concentration is selected from about 2.5 mg / mL, about 40 mg / mL, about 50 mg / mL, and about 60 mg / mL.

17. A pharmaceutical composition as claimed in claim 16, wherein the composition has a shelf-life stability of at least about 3 months.

18. A pharmaceutical composition as claimed in any one of claims 16 and 17, wherein the composition has a shelf-life stability of at least about 6 months.

19. A pharmaceutical composition as claimed in any one of claims 16 to 18, wherein the composition has a shelf-life stability of at least about 2 years.

20. The pharmaceutical composition as claimed in any one of claims 16 to 19, wherein the concentration of teilpotide or a pharmaceutically acceptable salt thereof is selected from about 2.5 mg / mL, about 40 mg / mL and about 50 mg / mL.

21. A pharmaceutical composition as claimed in any one of claims 16 to 20, wherein the concentration of teilpotide or a pharmaceutically acceptable salt thereof is about 40 mg / mL or about 50 mg / mL.

22. A pharmaceutical composition as claimed in any one of claims 16 to 20, wherein the concentration of teilpotide or a pharmaceutically acceptable salt thereof is about 2.5 mg / mL.

23. A pharmaceutical composition as claimed in any one of claims 16 to 22, wherein the concentration of sodium hydrogen phosphate is from about 0.7 mg / mL to about 1.5 mg / mL.

24. A pharmaceutical composition as claimed in any one of claims 16 to 23, wherein the concentration of disodium hydrogen phosphate is about 1.34 mg / mL.

25. A pharmaceutical composition as claimed in any one of claims 16 to 24, wherein the NaCl concentration is from about 7 mg / mL to about 9 mg / mL.

26. The pharmaceutical composition as claimed in any one of claims 16 to 25, wherein the NaCl concentration is from about 7.4 mg / mL to about 9.0 mg / mL.

27. A pharmaceutical composition as claimed in any one of claims 16 to 26, wherein the NaCl concentration is about 8.2 mg / mL.

28. The pharmaceutical composition as claimed in any one of claims 16 to 22, wherein the concentration of teilpotide or a pharmaceutically acceptable salt thereof is selected from 2.5, 40 and 50 mg / mL; the concentration of disodium hydrogen phosphate is from about 0.7 mg / mL to about 1.5 mg / mL; and the concentration of NaCl is from about 7 mg / mL to about 9 mg / mL.

29. The pharmaceutical composition as claimed in any one of claims 16 to 22 or claim 28, wherein the concentration of teilpotide or a pharmaceutically acceptable salt thereof is selected from 2.5 mg / mL, 40 mg / mL and 50 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.

30. A pharmaceutical composition as claimed in any one of claims 16 to 29, wherein the composition is provided in an automatic injection device.

31. A pharmaceutical composition as claimed in any one of claims 16 to 30, wherein the pH of the composition is from about 6.5 to about 7.

5.

32. A pharmaceutical composition as claimed in any one of claims 16 to 31 wherein the pH is from about 6.7 to about 7.

3.

33. A pharmaceutical composition as claimed in any one of claims 16 to 32, further comprising one or more preservatives.

34. A pharmaceutical composition as claimed in any one of claims 16 to 33; wherein the composition further comprises a preservative selected from the group consisting of m-cresol and phenol.

35. The pharmaceutical composition as claimed in any one of claims 16 to 22, wherein the concentration of teilpoitide or a pharmaceutically acceptable salt thereof is selected from 2.5 mg / mL, 40 mg / mL and 50 mg / mL; the sodium hydrogen phosphate is from 0.7 mg / mL to about 1.5 mg / mL; and the NaCl concentration is from 7 mg / mL to 9 mg / mL.

36. A pharmaceutical composition as claimed in any one of claims 19 to 35, wherein teilpotide is a free base.

37. A pharmaceutical composition as claimed in any one of claims 19 to 36, wherein the dosage of the composition is about 0.5 mL.

38. A pharmaceutical composition as claimed in any one of claims 19 to 37, wherein the composition is administered using an automatic injection device.

39. A pharmaceutical composition comprising telpotide or a pharmaceutically acceptable salt thereof; wherein the concentration of telpotide is about 40 mg / mL to about 60 mg / mL; wherein the pH of the composition is about 6.7 to about 7.

3.

40. A pharmaceutical composition as claimed in claim 39, wherein teilpotide is a free base.

41. The pharmaceutical composition as claimed in any one of claims 39-40, wherein the concentration of teilpoxetine is about 40 mg / mL to about 50 mg / mL.

42. A pharmaceutical composition as claimed in any one of claims 39 to 41, wherein the concentration of teilpoxetine is selected from about 40 mg / mL and about 50 mg / mL.

43. A pharmaceutical composition as claimed in any one of claims 39 to 42, wherein the concentration of teilpoxetine is selected from 40 mg / mL and 50 mg / mL.

44. A pharmaceutical composition comprising telpotide or a pharmaceutically acceptable salt thereof; wherein the concentration of telpotide is selected from about 2.5 mg / mL, about 40 mg / mL and about 50 mg / mL; wherein the pH of the composition is about 6.7 to about 7.

3.

45. A pharmaceutical composition as claimed in any one of claims 1 to 44, wherein tepoltide consists of SEQ ID NO:

1.

46. ​​A pharmaceutical composition as claimed in any one of claims 1 to 45 for use in the treatment of T2D.

47. A pharmaceutical composition as claimed in any one of claims 1 to 45 for use in the treatment of obesity.

48. A method for treating diabetes comprising administering to a person in need thereof an effective amount of a pharmaceutical composition as claimed in any one of claims 1 to 45.

49. A method for treating diabetes as claimed in claim 48, wherein the effective amount is administered as a once-weekly dose.

50. A method for treating obesity, comprising administering to a person in need thereof an effective amount of the pharmaceutical composition as claimed in any one of claims 1 to 45.

51. A method for treating obesity as claimed in claim 50, wherein the effective amount is administered using an automatic injection device.

52. A method for treating obesity as claimed in claim 50 or 51, wherein the effective amount is administered as a once-weekly dose.

53. A pharmaceutical composition as claimed in any one of claims 1 to 45 for the treatment of T2D.

54. A pharmaceutical composition as claimed in any one of claims 1 to 45 for use in the treatment of obesity.

55. Methods for long-term weight management in subjects requiring additional weight management; Wherein the subject suffers from obesity, the method comprises: Identify subjects with obesity who require additional weight management; administering to the subject a weekly dose of at least 15 mg of telpotide or a pharmaceutically acceptable salt thereof for a minimum of 4 weeks; and After at least 4 weeks of administration of at least 15 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly, administering a once weekly dose of telpotide or a pharmaceutically acceptable salt thereof that is 5 mg greater than the last dose; wherein the maximum once weekly dose of telpotide or a pharmaceutically acceptable salt thereof once weekly is 25 mg.

56. A method for long-term weight management as claimed in claim 55, wherein the once weekly dose of at least one of telpotide or a pharmaceutically acceptable salt thereof is 20 mg.

57. A method for long-term weight management as claimed in any one of claims 55 or 56, comprising: administering to the subject a dose of 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week for a minimum of 4 weeks; and After at least 4 weeks of administration of 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week, a once-weekly dose of telpotide or a pharmaceutically acceptable salt thereof of 25 mg is administered.

58. A method as claimed in any one of claims 55 to 57 wherein teilpotide is a free base.

59. Methods for long-term weight management for subjects requiring additional weight management, including: Identify subjects who require additional weight management; administering 15 mg of telpotide or a pharmaceutically acceptable salt thereof once a week to the subject; and At least 1 week later, administering 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week to the subject for at least 2 weeks; and At least 2 weeks later, administering 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week; 25 mg of telpotide or a pharmaceutically acceptable salt thereof was administered once a week.

60. A method as claimed in claim 59, wherein 20 mg of telpotide or a pharmaceutically acceptable salt thereof is administered once a week for at least 4 weeks.

61. A method as claimed in any one of claims 59 or 60 wherein 15 mg of tepotide is administered once weekly for at least 4 weeks.

62. A method as claimed in any one of claims 59 to 61 wherein teilpotide is a free base.

63. Methods for long-term weight management in subjects requiring additional weight management, comprising: Identify subjects who require additional weight management; administering 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week to the subject for at least 2 weeks; and After at least 2 weeks of administration of 20 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly, the subject is administered 25 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly.

64. A method as claimed in claim 63, wherein 20 mg of telpotide or a pharmaceutically acceptable salt thereof is administered once weekly without prior administration of a once weekly dose of 17.5 mg of telpotide.

65. A method as claimed in any one of claims 63 or 64, wherein 25 mg of telpotide or a pharmaceutically acceptable salt thereof is administered once weekly without prior administration of a once weekly dose of 22.5 mg of telpotide.

66. A method as claimed in any one of claims 63 to 65, wherein 20 mg of telpotide or a pharmaceutically acceptable salt thereof is administered once a week for at least 4 weeks.

67. A method of long-term weight management in a subject in need thereof, comprising administering telpotide or a pharmaceutically acceptable salt thereof as a once weekly subcutaneous dose selected from 20 mg and 25 mg of telpotide or a pharmaceutically acceptable salt thereof.

68. A method of long-term weight management in a pediatric patient in need of long-term weight management comprising administering 1.25 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly for at least 4 weeks.

69. For patients with an initial body mass index (BMI) less than or equal to 27 kg / m 2 A method for long-term weight management in a subject having at least one weight-related comorbidity, the method comprising administering once weekly telpotide selected from 20 mg telpotide or a pharmaceutically acceptable salt thereof and 25 mg telpotide or a pharmaceutically acceptable salt thereof.

70. A method as claimed in claim 69, wherein 20 mg of telpotide or a pharmaceutically acceptable salt thereof is administered once a week.

71. A method as claimed in any one of claims 69 and 70, wherein 25 mg of telpotide or a pharmaceutically acceptable salt thereof is administered once a week.

72. A method as claimed in any one of claims 69 to 71 wherein telpotide or a pharmaceutically acceptable salt thereof is administered subcutaneously.

73. A method as claimed in any one of claims 69 to 72 wherein teilpotide is a free base.

74. A method of treating obesity in a subject in need thereof, wherein the subject in need of treatment is a pediatric subject, the method comprising administering to the subject 1.25 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly for a minimum of 4 weeks.

75. A method of treating type 2 diabetes in a subject in need thereof, wherein the subject in need of treatment is a pediatric subject; the method comprising administering to the subject 1.25 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly for a minimum of 4 weeks.

76. A method for providing additional weight management to a subject in need thereof, wherein the subject has a BMI of > 27kg / m 2 and at least one weight-related comorbidity; the method comprising: administering to the subject a dose of 2.5 mg of telpotide once weekly; or a pharmaceutically acceptable salt thereof, for at least 4 weeks; After 4 weeks, increase the weekly dose of telportolide or a pharmaceutically acceptable salt thereof to 5 mg; After at least 4 weeks at the current dose, increase that dose in 2.5 mg increments; If additional weight management is required after at least 4 weeks of 15 mg once weekly telpotide or a pharmaceutically acceptable salt thereof; After at least 4 weeks at the current dose, increase that dose in 5.0 mg increments; and The maximum dose is 25 mg subcutaneously once weekly of telpotide or a pharmaceutically acceptable salt thereof.

77. A method as claimed in claim 76, wherein the maximum dose required for weight management is 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week.

78. The method as claimed in any one of claims 76 and 77, wherein administration of 20 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly results in greater weight loss than administration of 15 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly.

79. A method as claimed in any one of claims 76 to 78, wherein the maximum dose required for weight management is 25 mg of telpotide or a pharmaceutically acceptable salt thereof once a week.

80. The method as claimed in any one of claims 76 to 79, wherein administration of 25 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly results in greater weight loss than administration of 15 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly.

81. The method as claimed in any one of claims 76 to 80, wherein the administration of incremental increases of 5.0 mg after 4 weeks of the current dose of telpotide or a pharmaceutically acceptable salt thereof is repeated when additional weight loss is desired.

82. The method as claimed in any one of claims 76 to 81, wherein incremental increases of 5.0 mg are administered after 4 weeks of the current dose or telpotide or a pharmaceutically acceptable salt thereof, are repeated as the subject requires additional glycemic control.

83. A method as claimed in any one of claims 76 to 82 wherein teilpotide is a free base.

84. A method of providing additional weight management to a subject in need thereof, wherein the subject suffers from obesity, the method comprising: administering to the subject a dose of 2.5 mg of telpotide once weekly; or a pharmaceutically acceptable salt thereof, for at least 4 weeks; After 4 weeks, increase the weekly dose of telportolide or a pharmaceutically acceptable salt thereof to 5 mg; After at least 4 weeks at the current dose, increase that dose in 2.5 mg increments; If additional weight management is required after at least 4 weeks of 15 mg once weekly telpotide or a pharmaceutically acceptable salt thereof; After at least 4 weeks at the current dose, increase that dose in 5.0 mg increments; and The maximum dose is 25 mg subcutaneously once weekly of telpotide or a pharmaceutically acceptable salt thereof.

85. A method as claimed in claim 84, wherein the maximum dose required for weight management is 20 mg of telpotide or a pharmaceutically acceptable salt thereof once a week.

86. A method as claimed in any one of claim 84 or claim 85, wherein administration of 20 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly results in greater weight loss than administration of 15 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly.

87. A method as claimed in any one of claims 84 to 86, wherein the maximum dose required for long-term weight management is 25 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly.

88. A method as claimed in any one of claims 84 to 87, wherein administration of 25 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly results in greater weight loss than administration of 15 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly.

89. The method as claimed in any one of claims 84 to 88, wherein the administration of incremental increases of 5.0 mg after 4 weeks of the current dose of telpotide or a pharmaceutically acceptable salt thereof is repeated when additional weight loss is desired.

90. The method as claimed in any one of claims 84 to 89, wherein incremental increases of 5.0 mg are administered after 4 weeks of the current dose or telpotide or a pharmaceutically acceptable salt thereof, are repeated as the subject requires additional glycemic control.

91. A method as claimed in any one of claims 84 to 90 wherein teilpotide is a free base.

92. A method for providing additional glycemic control to a subject in need thereof, wherein the subject suffers from type 2 diabetes, the method comprising: administering to the subject a dose of 2.5 mg of telpotide; or a pharmaceutically acceptable salt thereof, once a week for at least 4 weeks; After 4 weeks, increase the weekly dose of telportolide or a pharmaceutically acceptable salt thereof to 5 mg; After at least 4 weeks at the current dose, increase that dose in 2.5 mg increments; If additional glycemic control is required after 4 weeks of 15 mg once weekly telpotide or a pharmaceutically acceptable salt thereof; After at least 4 weeks at the current dose, increase that dose in 5.0 mg increments; and The maximum dose is 25 mg subcutaneously once weekly of telpotide or a pharmaceutically acceptable salt thereof.

93. A method as claimed in claim 92 wherein the maximum dose required for additional glycemic control is 20 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly.

94. A method as claimed in any one of claim 92 or claim 93, wherein administration of 20 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly results in greater glycemic control than administration of 15 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly.

95. A method as claimed in any one of claims 92 to 94, wherein the maximum dose required for glycemic control is 25 mg of telpotide or a pharmaceutically acceptable salt thereof once weekly.

96. The method as claimed in any one of claims 92 to 95, wherein the administration of incremental increases of 5.0 mg after 4 weeks of the current dose of teilpotide or a pharmaceutically acceptable salt thereof is repeated when the subject requires additional weight loss.

97. The method as claimed in any one of claims 92 to 96, wherein incremental increases of 5.0 mg are administered after 4 weeks of the current dose or telpotide or a pharmaceutically acceptable salt thereof, as the subject requires additional glycemic control.

98. A method as claimed in any one of claims 92 to 97 wherein teilpotide is a free base.

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