MÉTODOS E USOS PARA TRATAR NÁUSEAS E ÊMESES

Abstract

GIP receptor agonists of the present disclosure have anti-emetic properties and therefore can be used to reduce or inhibit the frequency or severity of episodes of nausea or emesis in a patient in need thereof.

Description

[0001] This application claims the benefit of and priority of U.S. Provisional Application No. 63 / 493,384, filed March 31, 2023, and U.S. Provisional Application No. 63 / 585,493, filed September 26, 2023, the contents of which are incorporated herein by reference in their entirety. INCORPORATION FOR REFERENCE PURPOSES OF A LISTING OF SEQUENCES

[0002] A Sequence Listing is provided in this document as a Sequence Listing XML, 30286_WO, created on February 15, 2024, and with a size of 25 KB. The contents of the Sequence Listing XML are incorporated into this document in their entirety by reference. FIELD

[0003] The present invention relates to compositions, particularly long-acting peptide compounds with activity at the human glucose-dependent insulinotropic polypeptide receptor (GIP-R), and methods of use for treating and preventing nausea and vomiting in a patient or a symptom or condition associated with nausea and vomiting. BACKGROUND

[0004] Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are two of the main incretin peptide hormones secreted by the intestine upon ingestion of glucose or nutrients to stimulate insulin secretion by pancreatic β cells. GIP and GLP-1 exert their effects by binding to their specific receptors, the GIP receptor (GIP-R) and the GLP-1 receptor (GLP-1R), which belong to the family of G protein-coupled receptors. Although GIP is the main incretin peptide hormone for improving glycemic control, other therapies that Petition 870250085428, dated 09 / 22 / 2025, p. 10 / 79 2 / 45 focusing on GLP-1 receptor agonism (e.g., liraglutide, semaglutide, and dulaglutide) are effective in glucose control as well as weight reduction, making them an ideal treatment for type 2 diabetes mellitus or obesity. However, a major concern is that these GLP-1 receptor peptide agonists may be associated with adverse side effects, such as nausea and vomiting.

[0005] Similarly, nausea and vomiting are common adverse side effects in patients receiving chemotherapy for cancer treatment. These include the administration of high- and moderate-emetic-risk chemotherapies, which result in chemotherapy-induced nausea and vomiting (CINV). The need for new therapies to prevent and treat nausea and vomiting in patients is a high priority, especially in patients receiving therapies for type 2 diabetes mellitus, obesity, and cancer.In the various aspects and embodiments of the present invention, compositions and methods are presented for preventing and treating nausea and vomiting. SUMMARY

[0006] In some embodiments, the present invention provides a method for treating or preventing nausea or vomiting in a patient, the method comprising administering a therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof.

[0007] In some embodiments, the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is from about 0.3 mg to 30 mg.

[0008] In some modalities, the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID Petition 870250085428, dated 09 / 22 / 2025, p. 11 / 79 3 / 45 NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is approximately 5 mg to 30 mg.

[0009] In some embodiments, the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is 7.5 mg.

[0010] In some embodiments, the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is 20 mg.

[0011] In some embodiments, the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is 25 mg.

[0012] In some embodiments, the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is formulated into a medicament.

[0013] In some modalities, the treatment of nausea or vomiting involves the patient taking medication to treat a metabolic syndrome disorder.

[0014] In some forms, metabolic syndrome disorder is type 2 diabetes mellitus or obesity.

[0015] In some embodiments, the medication to treat metabolic syndrome disorder is selected from the group consisting of a GLP-1 receptor agonist peptide, a dual GLP-1 and glucagon (GCG) receptor agonist peptide, a long-acting amylin receptor agonist peptide, a dual amylin and calcitonin receptor agonist peptide, a monoclonal antibody targeting the leptin receptor, a urocortin peptide, or a Petition 870250085428, dated 09 / 22 / 2025, page 12 / 79 4 / 45 tyrosine-tyrosine peptide analog (PYY) for the patient.

[0016] In some embodiments, the medication to treat metabolic syndrome disorder is selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, or a pharmaceutically acceptable salt thereof.

[0017] In some modalities, the patient's tolerance to nausea- or vomiting-inducing treatment for metabolic syndrome disorder is improved.

[0018] In some modalities, the medication to treat metabolic syndrome disorder is administered without titration.

[0019] In some modalities, the treatment of nausea or vomiting consists of the patient taking a chemotherapeutic agent.

[0020] In some modalities, the chemotherapeutic agent is selected from the group consisting of anthracycline, cyclophosphamide, carboplatin, carmustine, cisplatin, cyclophosphamide, dacarbazine, doxorubicin, epirubicin, fam-trastuzumab deruxtecan-nxki, ifosfamide, mechlorethamine, melphalan, sacituzumab govitecan-hzly and streptozocin.

[0021] In some embodiments, the chemotherapeutic agent is selected from the group consisting of aldesleukin, amifostine, bendamustine, busulfan, carboplatin, carmustine, clofarabine, cyclophosphamide, cytarabine, dactinomycin, daunorubicin, dinutuximab, doxorubicin, liposomal encapsulation of cytarabine and daunorubicin, epirubicin, idarubicin, ifosfamide, irinotecan, irinotecan (liposomal), lurbinectin, melphalan, methotrexate, mirvetuximab soratansin-gynx, naxitamab-gqgk, oxaliplatin, romidepsin, temozolomide, and trabectedin.

[0022] In some modalities, the chemotherapeutic agent is cisplatin. Petition 870250085428, dated 09 / 22 / 2025, page 13 / 79 5 / 45

[0023] In some modalities, the chemotherapeutic agent is a combination of cyclophosphamide and an anthracycline.

[0024] In some forms, anthracycline is selected from the group consisting of doxorubicin, daunorubicin and idarubicin.

[0025] In some modalities, the patient's tolerance to nausea- or vomiting-inducing treatment with the chemotherapeutic agent is improved.

[0026] In some modalities, the chemotherapeutic agent is administered without titration.

[0027] In some embodiments, the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered via subcutaneous, intravenous, intramuscular, intraperitoneal, oral or inhalation routes.

[0028] In some embodiments, the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered to the patient once, once a week, twice a month, once every three weeks, once a month, or once a year.

[0029] In some embodiments, the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered subcutaneously to the patient once a week.

[0030] In some embodiments, the use of a pharmaceutical composition comprising a compound of SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is provided to treat or prevent nausea or vomiting in a patient. Petition 870250085428, dated 09 / 22 / 2025, p. 14 / 79 6 / 45

[0031] In some embodiments, the use of the compound comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is provided in the manufacture of a medicament for the treatment or prevention of nausea or vomiting in a patient.

[0032] In some embodiments, a pharmaceutical composition is provided comprising the compound of SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of nausea or vomiting in a patient. DETAILED DESCRIPTION

[0033] In various aspects and embodiments, the present invention provides compositions and methods for treating or preventing nausea or vomiting. According to some aspects of the invention, the compositions comprise long-acting GIP receptor agonist peptides that target the GIP-R. In some embodiments, the long-acting GIP receptor agonist peptides comprise SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof. In some embodiments, long-acting GIP receptor agonist peptides comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, are effective in treating nausea or vomiting.

[0034] In addition, the present invention also provides methods for clinically controlling (e.g., treating, preventing and / or reducing the incidence of) nausea or vomiting resulting from the administration of therapeutic agents that cause nausea and vomiting (e.g., GLP-1 receptor agonist peptides and chemotherapeutic drugs). The compositions and methods described herein, which comprise SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, have been shown to treat, prevent and / or reduce the incidence of negative side effects of nausea and vomiting. Petition 870250085428, dated 09 / 22 / 2025, p. 15 / 79 7 / 45 and improve the tolerability of nausea-inducing therapies. The improved tolerability of nausea-inducing therapies in a patient described in this document, particularly in the Examples, is measured by counting the number of emetic episodes in a patient receiving a long-acting GLP receptor agonist peptide, for example, SEQ ID NO: 1 or SEQ ID NO: 2, as a treatment for cancer (e.g., chemotherapy) or treatment for type 2 diabetes mellitus or obesity (e.g., a GLP-1 agonist peptide) and is characterized by strong rhythmic abdominal contractions associated with oral expulsion from the gastrointestinal tract (e.g., vomiting) or without the passage of material (e.g., retching).

[0035] In some embodiments, the present invention provides a method for treating or preventing nausea or vomiting in a patient, the method comprising administering a therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof.

[0036] In one embodiment, the present invention provides a GIP receptor agonist peptide comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of nausea or vomiting. In another embodiment, the present invention provides a GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of nausea or vomiting.

[0037] In one embodiment, the present invention provides a GIP receptor agonist peptide comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof, for use in the treatment of nausea or vomiting, wherein the GIP receptor agonist peptide comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof, is administered in at least one dose of about 0.3 mg a Petition 870250085428, dated 09 / 22 / 2025, page 16 / 79 8 / 45 mg. In another embodiment, the present invention provides a GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, for use in the treatment of nausea or vomiting, wherein the GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered in at least one dose of about 0.3 mg to 30 mg.

[0038] In one embodiment, the present invention provides a GIP receptor agonist peptide comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof, for use in the treatment of nausea or vomiting, wherein the compound comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof, is administered once weekly at a dose of about 0.3 mg to 30 mg. In another embodiment, the present invention provides a GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, for use in the treatment of nausea or vomiting, wherein the GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered once weekly at a dose of about 0.3 mg to 30 mg.

[0039] In one embodiment, the present invention provides the use of a pharmaceutical composition comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, to treat or prevent nausea or vomiting in a patient.

[0040] In some embodiments, the present invention provides the use of the compound comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment or prevention of nausea or vomiting in a patient.

[0041] In some embodiments, the present invention provides a pharmaceutical composition comprising the compound of SEQ ID NO: Petition 870250085428, dated 09 / 22 / 2025, p. 17 / 79 9 / 45 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of nausea or vomiting in a patient.

[0042] In some embodiments described in this document, the GIP receptor agonist peptide comprises SEQ ID NO: 1. The chemical structure of SEQ ID NO: 1 is described using the standard single-letter amino acid codes, except for residues Aib2, aMeL13, Orn16, Aib20, K26, and Ser39, where the amino acid residue structures have been expanded: SEQ ID NO: 1

[0043] The chemical structure of SEQ ID NO: 2 is described using the standard single-letter amino acids, except for residues Aib2, aMeL13, K17, Aib20, 4-Pal25 and Ser39, where the structures of these amino acid residues have been expanded: SEQ ID NO: 2

[0044] In some embodiments, a therapeutically effective amount of a GIP receptor agonist peptide to prevent or treat nausea or vomiting in a patient who needs it may range from about 0.3 to 30 mg or about 5.0 to 50 mg.

[0045] In some embodiments, the present invention provides a method for treating or preventing nausea or vomiting in a patient who Petition 870250085428, dated 09 / 22 / 2025, p. 18 / 79 10 / 45 requires the same, which involves administering a therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 1 is about 0.3 mg to 30 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 1 is 7.5 mg. In other embodiments, the therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 1 is 20 mg. In other embodiments, the therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 1 is 25 mg.

[0046] In some embodiments, the present invention provides a method for treating or preventing nausea or vomiting in a patient in need thereof, comprising administering a therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 2 is from about 0.3 mg to 30 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 2 is 7.5 mg. In other embodiments, the therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 2 is 20 mg. In other embodiments, the therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 2 is 25 mg.

[0047] In some embodiments, the present invention provides a method for treating or preventing nausea or vomiting in a patient who Petition 870250085428, dated 09 / 22 / 2025, p. 19 / 79 11 / 45 requires the same, which involves administering a therapeutically effective amount of a GIP receptor agonist peptide consisting of SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting of SEQ ID NO: 1 is about 0.3 mg to 30 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting of SEQ ID NO: 1 is 7.5 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting of SEQ ID NO: 1 is 25 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting of SEQ ID NO: 1 is 25 mg.

[0048] In some embodiments, the present invention provides a method for treating or preventing nausea or vomiting in a patient in need thereof, comprising administering a therapeutically effective amount of a GIP receptor agonist peptide consisting of SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting of SEQ ID NO: 2 is from about 0.3 mg to 30 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting of SEQ ID NO: 2 is 7.5 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting of SEQ ID NO: 2 is 20 mg. In some modalities, the therapeutically effective amount of a GIP receptor agonist peptide consisting of SEQ ID NO: 2 is 25 mg.

[0049] In some embodiments, the present invention provides a method for treating or preventing nausea or vomiting in a patient who Petition 870250085428, dated 09 / 22 / 2025, p. 20 / 79 12 / 45 requires the same, which involves administering a therapeutically effective amount of a GIP receptor agonist peptide consisting essentially of SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting essentially of SEQ ID NO: 1 is about 0.3 mg to 30 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting essentially of SEQ ID NO: 1 is 7.5 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting essentially of SEQ ID NO: 1 is 20 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting essentially of SEQ ID NO: 1 is 25 mg.

[0050] In some embodiments, the present invention provides a method for treating or preventing nausea or vomiting in a patient in need thereof, comprising administering a therapeutically effective amount of a GIP receptor agonist peptide consisting essentially of SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting essentially of SEQ ID NO: 2 is from about 0.3 mg to 30 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting essentially of SEQ ID NO: 2 is 7.5 mg. In some embodiments, the therapeutically effective amount of a GIP receptor agonist peptide consisting essentially of SEQ ID NO: 2 is 20 mg. In some modalities, the therapeutically effective amount of a GIP receptor agonist peptide consisting essentially of SEQ ID NO: 2 is 25 mg. Petition 870250085428, dated 09 / 22 / 2025, p. 21 / 79 13 / 45

[0051] In some modalities, the receptor agonist peptide The GIP of the present invention comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is formulated into a medicament.

[0052] In some modalities, the receptor agonist peptide The GIP receptor agonist peptide of the present invention, comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered as monotherapy to treat or prevent nausea or vomiting in a patient. In some cases, the GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2, may be administered, for example, weekly, twice a week, every two weeks, every 3 weeks, monthly, every 2 months, every 3 months, every 4 months, every 5 months, or every 6 months. In some embodiments, the GIP receptor agonist peptide of the present invention may be administered to the patient once a week for 1 to 5 weeks, 1 to 5 months, or 1 to 5 years.In some embodiments, the GIP receptor agonist peptide of the present invention comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered to treat nausea or vomiting in a patient without concomitant, subsequent or prior administration of a GLP-1 receptor agonist.

[0053] In some modalities, the receptor agonist peptide The GIP of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2, can be administered to a patient who needs the same, for example, in combination with another medication that does not adversely affect the GIP receptor agonist peptide of the present invention for the purpose, for example, of promoting the action (antiemetic action) of the GIP receptor agonist peptide of the present invention, reducing the dose of the GIP receptor agonist peptide of the present invention, and the like. Petition 870250085428, dated 09 / 22 / 2025, page 22 / 79 14 / 45

[0054] In some embodiments, the patient in need receives a GIP receptor agonist peptide with a concomitant dose of another medication used to treat a metabolic syndrome disorder. In other embodiments, the patient in need receives a GIP receptor agonist peptide with a subsequent dose of another medication used to treat a metabolic syndrome disorder. In yet another embodiment, the patient in need receives a GIP receptor agonist peptide with a prior dose of another medication used to treat a metabolic syndrome disorder. In another embodiment, the patient in need receives a sequential, simultaneous, or separate combination of a GIP receptor agonist with another medication used to treat a metabolic syndrome disorder.

[0055] In some forms, metabolic syndrome disorder is type 2 diabetes mellitus or obesity.

[0056] Examples of therapeutic agents with which it is possible to additionally administer a second therapeutic agent in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2 (hereinafter sometimes abbreviated as a concomitant drug), and includes anti-obesity agents, therapeutic agents for diabetes, therapeutic agents for diabetic complications, therapeutic agents for hyperlipidemia, antihypertensive agents, diuretics and chemotherapeutic agents.

[0057] In some modalities, the receptor agonist peptide The GIP of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2, is administered prior to the administration of an anti-obesity agent, a therapeutic agent for diabetes, a therapeutic agent for diabetic complications, a therapeutic agent for hyperlipidemia, an antihypertensive agent, a diuretic, and chemotherapy. Petition 870250085428, dated 09 / 22 / 2025, page 23 / 79 15 / 45

[0058] In some embodiments of the present invention, a patient who needs the same also receives a second therapeutic agent selected from the group consisting of a GLP-1 receptor agonist peptide (SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5), a dual agonist peptide of GLP-1 and glucagon (GCG) receptors (SEQ ID NO: 6), a long-acting amylin receptor agonist peptide (SEQ ID NO: 7), a dual agonist peptide of amylin and calcitonin receptors (SEQ ID NO: 8), a monoclonal antibody targeting the leptin receptor, a urocortin peptide or a tyrosine-tyrosine (PYY) peptide analog (SEQ ID NO: 9).

[0059] In some embodiments of the present invention, a patient who needs it also receives a second therapeutic agent selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, or a pharmaceutically acceptable salt thereof.

[0060] In some embodiments, a GLP-1 receptor agonist peptide comprising SEQ ID NO: 3 is administered in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the patient requiring the peptide receives a sequential, simultaneous or separate therapeutic regimen of SEQ ID NO: 3 in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2, for the treatment of nausea or vomiting. In some embodiments, a GLP-1 receptor agonist peptide comprising SEQ ID NO: 4 is administered in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the patient in need receives a sequential, simultaneous, or separate therapeutic regimen of SEQ ID NO: 4 in combination with a GIP receptor agonist peptide of the present invention. Petition 870250085428, dated 09 / 22 / 2025, p. 24 / 79 16 / 45 present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2, for the treatment of nausea or vomiting. In some embodiments, a GLP-1 receptor agonist peptide comprising SEQ ID NO: 5 is administered in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the patient in need receives a sequential, simultaneous or separate therapeutic regimen of SEQ ID NO: 5 in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2, for the treatment of nausea or vomiting. In some embodiments, a dual agonist peptide of GLP-1 and glucagon (GCG) receptors, comprising SEQ ID NO: 6, is administered in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2.In some embodiments, the patient requiring the peptide receives a sequential, simultaneous, or separate therapeutic regimen of SEQ ID NO: 6 in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2, for the treatment of nausea or vomiting. In some embodiments, a long-acting amylin receptor agonist peptide comprising SEQ ID NO: 7 is administered in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the patient requiring the peptide receives a sequential, simultaneous, or separate therapeutic regimen of SEQ ID NO: 7 in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2, for the treatment of nausea or vomiting.In some embodiments, a dual amylin and calcitonin receptor agonist peptide comprising SEQ ID NO: 8 is administered in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO:. Petition 870250085428, dated 09 / 22 / 2025, page 25 / 79 17 / 45 2. In some embodiments, the patient in need receives a sequential, simultaneous, or separate therapeutic regimen of SEQ ID NO: 8 in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2, for the treatment of nausea or vomiting. In some embodiments, a tyrosine-tyrosine peptide analog (PYY) comprising SEQ ID NO: 9 is administered in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the patient in need receives a sequential, simultaneous, or separate therapeutic regimen of SEQ ID NO: 9 in combination with a GIP receptor agonist peptide of the present invention, for example, SEQ ID NO: 1 or SEQ ID NO: 2, for the treatment of nausea or vomiting.

[0061] In some embodiments of the present invention, a patient who needs it also receives a second therapeutic agent, wherein the second therapeutic agent is a chemotherapeutic agent.

[0062] In some embodiments of the present invention, the chemotherapeutic agent is selected from the group consisting of altretamine, bendamustine, busulfan, carboplatin, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, ifosfamide, mechlorethamine, melphalan, oxaliplatin, procarbazine, temozolomide, thiotepta, trabectedine, carmustine, lomustine, streptozocin, 5-fluorouracil, 6-mercaptopurine, azacitidine, capecitabine, cladribine, clofarabine, cytarabine, decitabine, floxuridine, fludarabine, gemcitabine, hydroxyurea, methotrexate, nelarabine, pemetrexed, pentostatin, pralatrexate, thioguanine, triflurdine / tipiricail combination, etoposide, irinotecan, liposomal irinotecan, mitoxantrone, teniposide, topotecan, cabazitaxel, docetael, nab-paclitaxel, paclitaxel, vinblastine, vincristine, liposomal vincristine, vinorelbine, daunorubicin, doxorubicin, liposomal doxorubicin, epirubicin Petition 870250085428, dated 09 / 22 / 2025, page 26 / 79 18 / 45 idarubicin, mitoxantrone, valrubicin, bleomycin, dactinomycin, mitomycin-C, all-trans-retinoic acid, arsenic trioxide, asparaginase, eribulin, ixabeplone, mitotane, omacetaxine, pegaspargase, procarbazine, romidepsin, vorinostat, or any combination thereof.

[0063] In some modalities, the chemotherapeutic agent is a chemotherapeutic agent with a high emetic risk (e.g., vomiting frequency > 90%) selected from the group consisting of anthracycline, cyclophosphamide, carboplatin, carmustine, cisplatin, cyclophosphamide, dacarbazine, doxorubicin, epirubicin, fam-trastuzumab, deruxtecan-nxki, ifosfamide, mechlorethamine, melphalan, sacituzumab govitecan-hzly, and streptozocin.

[0064] In some other embodiments, the chemotherapeutic agent is a chemotherapeutic agent with a moderate emetic risk (e.g., vomiting frequency > 30%-90%) selected from the group consisting of aldesleukin, amifostine, bendamustine, busulfan, carboplatin, carmustine, clofarabine, cyclophosphamide, cytarabine, dactinomycin, daunorubicin, dinutuximab, doxorubicin, liposomal encapsulation of cytarabine and daunorubicin, epirubicin, idarubicin, ifosfamide, irinotecan, irinotecan (liposomal), lurbinectin, melphalan, methotrexate, mirvetuximab soratansin-gynx, naxitamab-gqgk, oxaliplatin, romidepsin, temozolomide, and trabectedin.

[0065] In some modalities, the chemotherapeutic agent is cisplatin.

[0066] In some other modalities, the chemotherapeutic agent is a combination of cyclophosphamide and an anthracycline.

[0067] In some forms, anthracycline is selected from the group consisting of doxorubicin, daunorubicin and idarubicin.

[0068] In some modalities, the patient receives a sequential, simultaneous, or separate therapeutic regimen of a peptide. Petition 870250085428, dated 09 / 22 / 2025, page 27 / 79 19 / 45 GIP receptor agonist in combination with a chemotherapeutic agent for the treatment of nausea or vomiting.

[0069] In some embodiments, the present invention provides a method whereby patient tolerance to treatment with a second therapeutic agent is improved. In another embodiment, patient tolerance to treatment with a chemotherapeutic agent is improved. In yet another embodiment, the present invention provides a method whereby patient tolerance to treatment with a second therapeutic agent administered to treat a metabolic syndrome disorder is improved.In one embodiment, the present invention provides a method whereby patient tolerance to treatment with a second therapeutic agent selected from the group consisting of a GLP-1 receptor agonist peptide (SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5), a dual agonist peptide of GLP-1 and glucagon (GCG) receptors (SEQ ID NO: 6), a long-acting amylin receptor agonist peptide (SEQ ID NO: 7), a dual agonist peptide of amylin and calcitonin receptors (SEQ ID NO: 8), a monoclonal antibody targeting the leptin receptor, a urocortin peptide or a tyrosine-tyrosine peptide analog (PYY) (SEQ ID NO: 9) is improved.

[0070] In one embodiment, the present invention provides a method in which the second therapeutic agent is administered without titration. In one embodiment, the present invention provides a method in which the chemotherapeutic agent is administered without titration. In one embodiment, the present invention provides a method in which the second therapeutic agent is administered to treat a metabolic syndrome disorder without titration. In one embodiment, the present invention provides a method in which the second therapeutic agent is selected from the group consisting of a re-agonist peptide. Petition 870250085428, dated 09 / 22 / 2025, page 28 / 79 20 / 45 GLP-1 receptor (SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5), a dual agonist peptide of GLP-1 and glucagon (GCG) receptors (SEQ ID NO: 6), a long-acting agonist peptide of the amylin receptor (SEQ ID NO: 7), a dual agonist peptide of the amylin and calcitonin receptor (SEQ ID NO: 8), a monoclonal antibody targeting the leptin receptor, a urocortin peptide or a peptide tyrosine-tyrosine analog (PYY) (SEQ ID NO: 9), is administered without titration.

[0071] In a more specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof, is administered in at least one dose of 7.5 mg. In a more specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered in at least one dose of 7.5 mg.

[0072] In a more specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof, is administered in at least one 20 mg dose. In a more specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered in at least one 20 mg dose.

[0073] In a more specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof, is administered in at least one 25 mg dose. In a more specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered in at least one 25 mg dose. Petition 870250085428, dated 09 / 22 / 2025, page 29 / 79 21 / 45

[0074] In another specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof, is administered at a weekly dose of 7.5 mg. In another specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered at a weekly dose of 7.5 mg.

[0075] In another specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof, is administered at a weekly dose of 20 mg.

[0076] In another specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered at a weekly dose of 20 mg.

[0077] In another specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 1, or a pharmaceutically acceptable salt thereof, is administered at a weekly dose of 25 mg.

[0078] In another specific embodiment, the GIP receptor agonist peptide comprising SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered at a weekly dose of 25 mg.

[0079] In one embodiment, the present invention provides the use of a GIP receptor agonist peptide comprising SEQ ID NO: 1 in the manufacture of a medicament for the treatment of nausea or vomiting. In another embodiment, the present invention provides the use of a GIP receptor agonist peptide comprising SEQ ID NO: 1 in the manufacture of a medicament for the exclusive treatment of nausea. In another embodiment, the present invention provides the use of a peptide Petition 870250085428, dated 09 / 22 / 2025, page 30 / 79 22 / 45 deo GIP receptor agonist comprising SEQ ID NO: 1 in the manufacture of a medicament for the exclusive treatment of emesis.

[0080] In one embodiment, the present invention provides the use of a GIP receptor agonist peptide comprising SEQ ID NO: 2 in the manufacture of a medicament for the treatment of nausea or vomiting. In another embodiment, the present invention provides the use of a GIP receptor agonist peptide comprising SEQ ID NO: 2 in the manufacture of a medicament for the exclusive treatment of nausea. In one embodiment, the present invention provides the use of a GIP receptor agonist peptide comprising SEQ ID NO: 2 in the manufacture of a medicament for the exclusive treatment of vomiting.

[0081] In some modalities described in this document, nausea or vomiting is acute. In other modalities described in this document, nausea or vomiting is chronic. In other modalities described in this document, nausea or vomiting is anticipatory.

[0082] In the embodiments described in this document, the GIP receptor agonist peptide, for example, SEQ ID NO: 1 or SEQ ID NO: 2, is administered once. In other embodiments described in this document, the GIP receptor agonist peptide is administered once a week. In other embodiments described in this document, the GIP receptor agonist peptide is administered twice a month. In other embodiments described in this document, the GIP receptor agonist peptide is administered once every three weeks. In other embodiments described in this document, the GIP receptor agonist peptide is administered once a month. In other embodiments described in this document, the GIP receptor agonist peptide is administered once a year.

[0083] In the modalities described in this document, the Petition 870250085428, dated 09 / 22 / 2025, p. 31 / 79 23 / 45 A therapeutically effective amount of the GIP receptor agonist peptide, for example, SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered subcutaneously to the patient once a week.

[0084] In certain modalities described in this document, the patient requiring treatment is affected by one or more conditions selected from the group consisting of: (1) pregnancy; (2) cyclic vomiting syndrome; (3) infection; (4) ingestion of toxic substances; (5) motion sickness; and (6) chemotherapy-induced nausea and vomiting (CINV). In one specific modality described in this document, the nausea or vomiting is caused by hyperemesis gravidarum of pregnancy.

[0085] Referring to an element using the indefinite article a or an does not exclude the possibility that more than one element is present, unless the context clearly requires that there be only one element. The indefinite article a or an, therefore, generally means at least one.

[0086] As described in this document, administration means the practice of providing a patient with a substance intended for the diagnosis, treatment, or prevention of a disease or medical condition. As used in this document, the administration of GIP receptor agonist peptides comprising SEQ ID NO: 1 or SEQ ID NO: 2 may be administered concomitantly with, before, or after a second therapeutic agent. The timing of administration may also be concomitantly with, before, or after the onset of nausea or vomiting.

[0087] As described in this document, the term amino acid means both naturally occurring and unnatural amino acids. Amino acids are typically represented by standard one-letter codes (e.g., L = Petition 870250085428, dated 09 / 22 / 2025, p. 32 / 79 24 / 45 leucine), as well as substituted alpha-methyl residues of natural amino acids (e.g., α-methyl leucine, or α-MeL, and α-methyl phenylalanine, or α-MeF) and some other non-natural amino acids, such as alpha-aminoisobutyric acid, or Aib, 4-Pal, Orn, and the like. The structures of these amino acids are shown below: aMeL Aib

[0088] As described herein, Orn stands for Lornitine. As described herein, 4Pal stands for 3(4-pyridyl)-L-alanine. As described herein, MeF (2F) stands for alpha-methyl 2-fluoro-L-phenylalanine. As described herein, aMeY and MeL stand for alpha-methyl-L-tyrosine and alpha-methyl-L-leucine, respectively. As described herein, ee D-Glu stands for D-glutamic acid. As described herein, D-Tyr and y stand for D-tyrosine. As described herein, D-Ala and a stand for D-alanine. As described herein, MeF stands for alpha-methyl-F and alpha-methyl-Phe. As described herein, Iva stands for L-isovaline. Petition 870250085428, dated 09 / 22 / 2025, page 33 / 79 25 / 45

[0089] The term chemotherapeutic agent, as described in this document, refers to a drug used to treat cancer by eliminating or preventing the growth of malignant cells.

[0090] Chemotherapeutic agents are toxic to cells with high proliferation rates and can cause side effects such as nausea and vomiting. Doctors classify chemotherapy drugs according to their emetogenic potential (i.e., the likelihood of the drug causing nausea or vomiting) as high emetic risk, moderate emetic risk, low emetic risk, or minimal emetic risk.

[0091] Non-limiting examples of chemotherapeutic agents include altretamine, bendamustine, busulfan, carboplatin, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, ifosfamide, mechlorethamine, melphalan, oxaliplatin, procarbazine, temozolomide, thiotepta, trabectedine, carmustine, lomustine, streptozocin, 5-fluorouracil, 6-mercaptopurine, azacitidine, capecitabine, cladribine, clofarabine, cytarabine, decitabine, floxuridine, fludarabine, gemcitabine, hydroxyurea, methotrexate, nelarabine, pemetrexed, pentostatin, pralatrexate, thioguanine, triflurdine / tipiricail combination, etoposide, irinotecan, liposomal irinotecan, mitoxantrone, teniposide, topotecan, cabazitaxel, docetael, nab-paclitaxel, paclitaxel, vinblastine, vincristine, liposomal vincristine, vinorelbine, daunorubicin, doxorubicin, liposomal doxorubicin, epirubicin, idarubicin, mitoxantrone, valrubicin, bleomycin, dactinomycin, mitomycin-C, all-trans-retinoic acid, arsenic trioxide,asparaginase, eribulin, ixabeplone, mitotane, omacetaxine, pegaspargase, procarbazine, romidepsin, vorinostat, or any combination thereof.

[0092] Non-limiting examples of chemotherapeutic agents with a high emetic risk (> 90% frequency of vomiting) are anthracycline, ci Petition 870250085428, dated 09 / 22 / 2025, page 34 / 79 26 / 45 clofosfamide, carboplatin, carmustine (> 250 mg / m2), cisplatin, cyclophosphamide (> 1500 mg / m2), dacarbazine, doxorubicin (> 60 mg / m2), epirubicin (> 90 mg / m2), fam-trastuzumab deruxtecan-nxki, ifosfamide (> 2 g / m2 per dose), mechlorethamine, melphalan (> 140 mg / m2), sacituzumab govitecan-hzly, streptozocin or any combination thereof.

[0093] Non-limiting examples of chemotherapeutic agents with a moderate emetic risk (> 30%-90% frequency of emesis) are aldesleukin (> 12-15 million IU / m2), amifostine (> 300 mg / m2), bendamustine, busulfan, carboplatin (AUC < 4), carmustine (< 250 mg / m2), clofarabine, cyclophosphamide (< 1500 mg / m2), cytarabine (> 200 mg / m2), dactinomycin, daunorubicin, dinutuximab, doxorubicin, liposomal encapsulation of cytarabine and daunorubicin, epirubicin (< 90 mg / m2), idarubicin, ifosfamide (< 2 g / m2 per dose), irinotecan, irinotecan (liposomal), lurbinectedine, melphalan (< 140 mg / m2), methotrexate (> 250 mg / m2), mirvetuximab soratansin-gynx, naxitamab-gqgk, oxaliplatin, romidepsin, temozolomide, trabectedin, or any combination thereof.

[0094] The term chemotherapy-induced nausea and vomiting or CINV refers to a side effect of cancer treatment. CINV can be classified as acute, anticipatory, recurrent, late, or refractory.

[0095] The term cyclic vomiting syndrome, as described in this document, refers to a syndrome characterized by episodes of intense vomiting without apparent cause. Episodes of cyclic vomiting can last for hours or days and may alternate with asymptomatic periods.

[0096] The term dose, as described in this document, refers to a quantity (e.g., a concentration) of a medicine taken or recommended to be taken. Petition 870250085428, dated 09 / 22 / 2025, page 35 / 79 27 / 45

[0097] The term emesis or emetic episodes, as described in this document, refers to strong rhythmic abdominal contractions associated with oral expulsion from the gastrointestinal tract (i.e., vomiting) or the absence of passage of material (i.e., retching). Emesis may be caused by a medication, such as chemotherapy, for example, cisplatin. In some modalities, nausea and vomiting may be caused by an underlying condition, such as hyperemesis gravidarum of pregnancy, cyclic vomiting syndrome, or an infection. In some modalities, nausea and vomiting may be caused by opioid analgesics, ingestion of poisonous substances, motion sickness, or concomitant treatment with medications that induce or have the potential to induce nausea or vomiting, such as medications used to treat metabolic syndromes.

[0098] As described in this document, a fatty acid consists of a linear chain of an even number of carbon atoms, with hydrogen atoms along the chain and, at one end (monoacid) or at both ends (diacid) of the chain, a carboxyl group (-COOH). In a preferred embodiment, the fatty acid portion is a C20 diacid.

[0099] As described in this document, hyperemesis gravidarum refers to the most severe form of nausea and vomiting during pregnancy. Hyperemesis gravidarum is a condition characterized by intense nausea and vomiting, weight loss, and electrolyte disturbances.

[0100] As described herein, long-acting means that the binding affinity and activity of a composition described herein continue for a longer period of time than that of the native peptide or protein. Dosage and administration regimens may vary depending on the patient's condition and the chemical composition of the long-acting GIP agonist peptides, for example, SEQ ID NO: 1 and SEQ ID NO: 2. Petition 870250085428, dated 09 / 22 / 2025, page 36 / 79 28 / 45 In various modalities, long-acting GIP agonist peptides are administered weekly, bimonthly (i.e., every two weeks), monthly, quarterly, or annually. Dosage and administration regimens may also include variations in dosage and frequency of administration based on patient response.

[0101] As described in this document, metabolic syndrome disorder refers to any one of a set of conditions that frequently occur together and increase a person's risk of developing heart disease, stroke, and type 2 diabetes mellitus. These conditions may include elevated blood sugar, high blood pressure, low HDL cholesterol levels, high blood triglyceride levels, and a large waist circumference. Non-limiting examples of medications used to treat metabolic syndromes include GLP-1 receptor agonist peptides, such as liraglutide, semaglutide, or dulaglutide; dual GLP-1 and GCG receptor agonists; amylin receptor agonist peptides; dual amylin and calcitonin receptor agonists; monoclonal antibodies targeting the leptin receptor; peptide tyrosine-tyrosine (PYY) analogs; or urocortin peptides.

[0102] As described in this document, motion sickness refers to a feeling of nausea induced by movement. Motion sickness refers, for example, to repetitive movements during a trip, such as going over speed bumps in a car or rocking in a boat.

[0103] As described in this document, the term nausea refers to the unpleasant sensation of wanting to vomit. Nausea is a subjective unpleasant sensation in the throat and stomach that can lead to vomiting. There are many words that describe nausea, including, but not limited to, motion sickness, heartburn, or stomach ache. Nausea can Petition 870250085428, dated 09 / 22 / 2025, page 37 / 79 29 / 45 may present other concomitant symptoms, such as increased salivation (spitting), dizziness, vertigo, difficulty swallowing, changes in skin temperature, and accelerated heart rate.

[0104] The term patient, as described in this document, refers to a human being or an animal. In a preferred embodiment, the patient is a human being. In a particular embodiment, the patient is further characterized by having nausea or vomiting or being at risk of developing nausea or vomiting. In other embodiments, said patient would benefit from the therapeutic effects of long-acting GIP agonism, which would treat or prevent said nausea or vomiting.

[0105] By the terms reduce or inhibit, understand the ability to cause an overall reduction of 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95% or more. In some embodiments, reduce or inhibit may refer to a relative reduction compared to a reference (e.g., reference level of biological activity (e.g., the number of episodes of nausea and / or vomiting after administration to a patient of a prescribed amount of chemotherapy, e.g., a prescribed dose of a chemotherapeutic agent that is known to cause nausea or vomiting). In some embodiments, reduce or inhibit may refer to the relative reduction of a side effect (e.g., nausea and / or vomiting) associated with a treatment for a condition or disease.

[0106] As used in this document, the terms prevention, prevent and / or preventing are used interchangeably and refer to all processes, including but not limited to pre-treatment, that prevent something from happening or arising, or that prevent an event, such as vomiting or nausea, from occurring. As used in this document, prevention is not necessarily intended to indicate complete prevention of all symptoms of the disorder. Petition 870250085428, dated 09 / 22 / 2025, page 38 / 79 30 / 45

[0107] The term vomiting, as used in this document, refers to the contraction of the abdominal muscles or diaphragm to trigger the expulsion of stomach contents. Vomiting is also described as throwing up. When vomiting occurs, the abdominal muscles contract (compress) and expel the stomach contents through the mouth. The person may or may not feel nauseous.

[0108] The term nausea, as used in this document, refers to emetic episodes without the passage of substances, for example, the reverse movement of the stomach and esophagus without vomiting. The term nausea, as used in this document, also refers to the sensation of choking without actually producing vomiting.

[0109] As used in this document, therapeutically effective amount refers to the amount of a compound that, when administered to a patient who needs it, for example, for the treatment of nausea and / or vomiting, is sufficient to treat said condition.

[0110] As used in this document, titration refers to a drug that is started at a low dose. The dose is gradually increased until the desired maximum dose is reached.

[0111] As used in this document, tolerance refers to the ability to comfortably endure treatment with a medication.

[0112] As used in this document, treat or treatment means to alleviate, restrict, reverse, slow, or halt the progression or severity of an existing condition, disease, disorder, or symptom.

[0113] As used in this document, the term about, unless the context requires otherwise, means ± an associated value.

[0114] Other aspects and embodiments of the present invention will be Petition 870250085428, dated 09 / 22 / 2025, page 39 / 79 31 / 45 evident in the following examples. EXAMPLES Example 1: A study of the emetic potential of Peptide A (SEQ ID NO: 1), cisplatin, and Aprepitant after a single oral, subcutaneous, or intraperitoneal dose in male ferrets. Methods

[0115] During the experimental period, adult male ferrets (> Animals aged 16 weeks (n = 5 / group (0.9-1.8 kg), Marshall Farms) were housed individually in a temperature-controlled environment (20-26 °C), with a relative humidity of 50 ± 20% and a 12-hour light / 12-hour dark cycle. Animals were pre-treated with vehicle (TrisHCl / PS-80 at 0.02%) or Peptide A (SEQ ID NO: 1) (at doses of 0.012 mg / kg, 0.125 mg / kg, and 0.497 mg / kg, subcutaneously (SC)), 16 hours before administration of cisplatin (at a dose of 10 mg / kg, IP) or a therapeutic antiemetic, Aprepitant (CAS170729-80-3) (at a dose of 2 mg / kg) or saline injection. The analysis of emetic episodes was measured by an observer blinded to the treatment groups. Emetic episodes are characterized by strong rhythmic abdominal contractions associated with oral expulsion from the gastrointestinal tract (i.e., vomiting) or the absence of passage of material (i.e., retching).The latency until the first emetic episode and the total number of emetic episodes (with and without oral expulsion) are quantified. Table 1. Emetic behavior in adult male ferrets. Treatment Nausea (counts) Vomiting (counts) Emetic episodes (counts) Vehicle (Control) 0.40 ± 0.40 0.00 ± 0.00 0.00 ± 0.00 Cisplatin 51.20 ± 17.07* 5.00 ± 1.52* 56.20 ± 17.62* Peptide A (high dose) 4.20 ± 2.56 0.20 ± 1.52 4.40 ± 2.73 Cisplatin + Peptide A (0.012 mg / kg) 22.60 ± 12.01 3.00 ± 1.30 25.60 ± 12.99 Petition 870250085428, dated 09 / 22 / 2025, page 40 / 79 32 / 45 Cisplatin + Peptide A (0.125 mg / kg) 0.40 0.40# ± 0.00 ± 0.00# 0.40 ± 0.40# Cisplatin + Peptide A (0.491 mg / kg) 1.00 1.00# ± 0.00 ± 0.00# 1.00 ± 1.00# Cisplatin + Aprepitant 6.00 4.39# ± 1.40 ± 0.75# 7.40 ± 5.11#

[0116] Ferrets were treated with cisplatin alone or cisplatin in combination with Peptide A or cisplatin in combination with Aprepitant, a known therapeutic antiemetic. Adult male ferrets were pre-dosed with Peptide A at Low (0.012 mg / kg), Medium (0.125 mg / kg) and High (0.491 mg / kg) doses 16 hours before administration of cisplatin (10 mg / kg) or Aprepitant (n = 5 per group). Data are presented as Mean ± SEM. Statistical analysis was performed using a Student's t-test. P < 0.05 vs Vehicle* or Cisplatin#.

[0117] Data indicate that Peptide A (SEQ ID NO: 1) does not cause emesis when administered alone, but pretreatment with Peptide A attenuated emesis and nausea induced by the known emetic agent cisplatin in adult male ferrets. Example 2: A study to investigate the safety and tolerability of Peptide A (SEQ ID NO: 1) when combined with a GLP-1 receptor agonist (GLP-1R) in healthy participants.

[0118] A Phase 1, randomized, placebo-controlled, double-blind study investigated the safety and tolerability of a single dose (25 mg) of Peptide A (SEQ ID NO: 1) or placebo in combination with a GLP-1 receptor agonist, liraglutide, in healthy participants. It was hypothesized that pretreatment with Peptide A (SEQ ID NO: 1) may reduce adverse gastrointestinal (GI) events associated with the administration of a GLP-1 receptor agonist.

[0119] Study Inclusion Criteria. Participants were healthy and between 11 and 60 years of age, inclusive, with a weight Petition 870250085428, dated 09 / 22 / 2025, page 41 / 79 33 / 45 body weight of at least 55 kg and BMI between 23 and 40 kg / m2, inclusive. Female participants should not be of childbearing potential and male participants should use adequate contraceptive methods.

[0120] Study Exclusion Criteria. Participants were excluded if they had a significant history of medical problems, including malignancy, HIV infection and / or positive antibodies to human immunodeficiency virus, evidence of hepatitis C and / or positive antibodies to hepatitis C, or had a known personal or family history of multiple endocrine neoplasia Type 2A or 2B, thyroid C-cell hyperplasia, or medullary thyroid carcinoma. Participants were also excluded if they had undergone any form of bariatric surgery.Participants were also excluded if they had received any systemic or inhaled glucocorticoid therapy (excluding topical, intra-articular, and intraocular preparations) for more than 14 consecutive days within 2 weeks prior to screening, or if they intended to use over-the-counter or prescription medications 7 days prior to the planned dosing, in addition to vitamin / mineral supplements and paracetamol. Participants were also excluded if they had any known allergy to liraglutide, Peptide A (SEQ ID NO: 1), or any GIP or GLP-1R agonists, related compounds, or any formulated components of the study, or a history of significant atopy.Participants were excluded if they were currently enrolled in another clinical trial incompatible with the current trial, if they had participated in another clinical trial within 30 days of screening (or longer if the study drug had a half-life greater than 30 days), or if they had previously completed or withdrawn from this trial. Participants were also excluded if they had abnormalities on a 12-lead ECG that increased the risks associated with the trial. Petition 870250085428, dated 09 / 22 / 2025, p. 42 / 79 Participants 34 / 45 were excluded from the study if they had serum AST or ALT more than 2x the ULN or TBL more than 1.5 ULN, if they had a serum triglyceride level of at least 5 mmol / L (442.5 mg / dL), if they had amylase or lipase levels more than 2.5x the ULN; or if they had a calcitonin level at screening greater than 20 pg / mL. Participants were excluded if they had donated blood in the last month or more than 450 mL of blood in the last 3 months. Participants were excluded if they had consumed alcohol in amounts greater than 21 units per week (men) or 14 units per week (women) or if they were unwilling to stop alcohol consumption 24 hours before dosing until discharge from the research center.

[0121] Study Design. The study was conducted in two parts. Part A evaluated the tolerability of daily administered liraglutide (with dose escalation within the cohort every 2 days), followed by liraglutide in combination with a 25 mg dose of Peptide A (SEQ ID NO: 1) or placebo in a parallel design, in a population of previously untreated healthy participants.

[0122] An accelerated dose escalation regimen was used to increase the liraglutide dose every 2 days for each participant, from an initial dose of 0.6 mg to a final dose of 2.4 mg reached on Day 8, followed by a 2-week interruption period (Part A, Period 1). This accelerated regimen was designed to increase the frequency of gastrointestinal events, thus allowing the potential demonstration of a reduction in gastrointestinal events with Peptide A pretreatment (SEQ ID NO: 1). After the interruption, participants were readmitted the day before dosing and randomly assigned to pretreatment with a 25 mg dose of Peptide A (SEQ ID NO: 1) or placebo on Day 1. The following day, participants began liraglutide dosing (daily) for 8 days, similar to the first treatment period. An accelerated dosing regimen was Petition 870250085428, dated 09 / 22 / 2025, page 43 / 79 35 / 45 used to increase the liraglutide dose every 2 days for each participant (Part A, Period 2).

[0123] Part B evaluated the tolerability of liraglutide administered daily to a population of previously untreated healthy participants with a dose of 25 mg of Peptide A (SEQ ID NO: 1) or placebo as pretreatment in a crossover design, which provided repeated within-patient measurements, avoiding sequence biases.

[0124] Participants were randomly assigned to pretreatment with a 25 mg dose of Peptide A (SEQ ID NO: 1) or placebo on Day 1. The following day, participants began daily administration of liraglutide for 8 days. Part B used an accelerated dosing regimen. The liraglutide dose was increased daily for each participant, followed by an 8-week discontinuation period. After discontinuation, participants switched to the alternative pretreatment, with a 25 mg dose of Peptide A (SEQ ID NO: 1) or placebo, identical to that of the first treatment period.

[0125] The incretin response to a 25 mg dose of Peptide A (SEQ The effect of the placebo incretin, the 25 mg dose of Peptide A (SEQ ID NO: 1), alone or in combination with liraglutide, was evaluated by graded glucose infusion (GGI) in Parts A and B. Intravenous glucose was used to induce hyperglycemia, which stimulated endogenous insulin secretion. By performing this procedure on different days during the dose escalation regimen, the effect of the placebo incretin, the 25 mg dose of Peptide A (SEQ ID NO: 1), the 1.8 mg dose of liraglutide (Part A), the 2.4 mg dose of liraglutide (Part B), and Peptide A + liraglutide could be measured. GGI was performed in Part A, Period 2, and in both treatment periods of Part B. GGI was performed on Day 2, before the first dose of liraglutide (measuring the response of Peptide A (SEQ ID NO: 1) or placebo). Petition 870250085428, dated 09 / 22 / 2025, p. 44 / 79 36 / 45 cebo) and again on Day 6 (measuring the response to liraglutide or liraglutide + Peptide A (SEQ ID NO: 1)).

[0126] Participants. Forty-four (44) participants were randomly assigned to the study intervention, with 12 participants completing Part A and 32 participants completing Part B. Table 2. Summary of the number of events within each treatment group based on the preferred term. The numbers in parentheses represent the average number of events per participant in each group. Adverse Event (AE) Category Preferred Term Placebo (N = 32) 25 mg SEQ ID NO: 1 (N = 32) P* Abdominal discomfort 1 (0.03) 0 (0.00) - Abdominal distension 11 (0.34) 7 (0.22) 0.238 Constipation 2 (0.06) 1 (0.03) 0.310 Diarrhea 12 (0.38) 12 (0.38) 1.00 Gastrointestinal disorders Dyspepsia 3 (0.09) 0 (0.00) - Belching 2 (0.06) 1 (0.03) 0.654 Flatulence 1 (0.03) 0 (0.00) - Gastroesophageal reflux disease 14 (0.44) 5 (0.16) 0.005 Nausea 11 6 (0.19) 0.185 Petition 870250085428, dated 09 / 22 / 2025, page 45 / 79 37 / 45 (0.34) Vomiting 16 (0.50) 9 (0.28) 0.338 All GI 73 (2.28) 41 (1.28) 0.022 General disorders Satiety 5 (0.16) 8 (0.25) 0.510 Metabolism and nutrition disorders Decreased appetite 21 (0.66) 15 (0.47) 0.095 * The p-values ​​are from a generalized linear model that assumes a negative binomial distribution comparing the mean of events by Patient in the Placebo vs. Protein A groups (SEQ ID NO: 1), after considering repeated measurements in the same patient. Some p-values ​​are not available due to low event counts. Table 3. Frequency (%) of participants with > 1 Treatment-Emergent Adverse Event (TEAE) based on the preferred term. Category of AE Preferred Term Placebo (N = 32) 25 mg of SEQ ID NO: 1 (N = 32) Pt Abdominal discomfort 1 (3.1%) 0 (0.0%) 0.317 Abdominal distension 9 (28.1%) 6 (18.8%) 0.257 Constipation 2 (6.3%) 1 (3.1%) 0.317 Gastrointestinal disorders Diarrhea 3 (9.4%) 5 (15.6%) 0.317 Dyspepsia 3 (9.4%) 0 (0.0%) Eructation 1 (3.1%) 1 (3.1%) 1.00 Flatulence 1 (3.1%) 0 (0.0%) Gastroesophageal reflux disease 11 (34.4%) 3 (9.4%) 0.011 Petition 870250085428, dated 09 / 22 / 2025, page 46 / 79 38 / 45 Nausea 10 (31.3%) 5 (15.6%) 0.132 Vomiting 5 (15.6%) 3 (9.4%) 0.317 All GI 23 (71.9%) 16 (50.0%) 0.089 General disorders Satiety Pre- 5 (15.6%) 5 (15.6%) 1.00 Metabolism and nutrition disorders Decreased appetite 19 (59.4%) 14 (43.8%) 0.132 The p-values ​​are derived from a McNemar test comparing paired binary data between groups that received Protein A (SEQ ID NO: 1) and Placebo. Some p-values ​​are not available due to low event counts.

[0127] Results. Thirty-two healthy participants received the dose and 31 completed both study periods. All 32 patients were included for safety data analysis. In the placebo-treated phase of the study, the total number of gastrointestinal adverse events was 73 (2.28 events per participant on average); 23 / 32 (72%) participants experienced gastrointestinal adverse events. With pretreatment with the GIP receptor agonist, the frequency of gastrointestinal adverse events was 41 (1.28 events per participant on average); 17 / 32 (53%) participants experienced gastrointestinal adverse events (p = 0.02 comparing total event rates with Peptide A vs. placebo; no evidence of a sequence effect).

[0128] The number of participants affected by the three most common gastrointestinal events (nausea, vomiting, and gastroesophageal reflux) decreased by approximately 20-65%. The total number of the three events Petition 870250085428, dated 09 / 22 / 2025, page 47 / 79 39 / 45 of the most common gastrointestinal symptoms (nausea, vomiting, and gastroesophageal reflux) also decreased by approximately 45-65%. Example 3: A Phase 1b, 2-part, double-blind, multiple ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of Peptide B (SEQ ID NO: 2) in participants with Type 2 Diabetes Mellitus (T2DM)

[0129] A Phase 1b, randomized, single-center, double-blind, multiple ascending dose (MAD) 2-part Peptide B (SEQ ID NO: 2) study was conducted in participants with T2DM. The study consisted of a screening period, an induction period, a treatment period, and a follow-up period. Part A of the study consisted of 2 cohorts (7.5 mg once weekly (QW) and 20 mg QW), with approximately 9 participants in each cohort randomized to Peptide B (SEQ ID NO: 2) or placebo in a 6:3 manner, and a 1.5 mg dose of dulaglutide (QW) was added to the treatment regimen at week nine for all participants.

[0130] Part B of the study consisted of 3 cohorts with participants randomized in a 2:2:1 manner to receive a dose of 1.5 mg dulaglutide (QW) + placebo matching B-peptide, a dose of 20 mg B-peptide (SEQ ID NO: 2) (QW) + a dose of 1.5 mg dulaglutide QW (24 participants) or B-peptide 20 mg QW + placebo matching dulaglutide (12 participants).

[0131] Inclusion Criteria. To be considered for inclusion in the study, participants had to be healthy and between 18 and 70 years of age, weigh up to 150 kg and have a BMI between 23 and 45 kg / m2, inclusive. Female participants could not be of childbearing potential and male participants agreed to use highly effective / efficient contraceptive methods.

[0132] Study Design. The study was conducted in two parts. Petition 870250085428, dated 09 / 22 / 2025, page 48 / 79 40 / 45 Part A consisted of 2 cohorts (7.5 mg QW and 20 mg QW) with approximately 9 participants in each cohort randomized to B-peptide or placebo in a 6:3 manner, and 1.5 mg of dulaglutide QW was added to the treatment regimen from week nine for all participants. Part B consisted of 3 cohorts with participants randomized in a 2:2:1 manner to receive 1.5 mg of dulaglutide QW + placebo (24 participants), 20 mg of B-peptide QW + 1.5 mg of dulaglutide QW (24 participants), or 20 mg of B-peptide QW + placebo (12 participants), respectively.

[0133] Part A. Eligible participants were randomized in a 6:3 ratio to receive subcutaneous injections of Peptide B or placebo once daily. The doses for Part A were: Cohort 1: 7.5 mg and Cohort 2: 20 mg. The treatment period was 12 weeks. All participants received 1.5 mg of dulaglutide once daily starting in week nine.

[0134] The primary objective of Part A was to investigate the safety and tolerability following SC administration of multiple QW doses of B-peptide versus placebo with and without dulaglutide in participants with T2DM. The endpoints were treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). The secondary objectives of Part A were to characterize the pharmacokinetic profile following multiple QW doses and to characterize the effects on glucose control and glucagon secretion. The endpoints were Cmax and AUC, changes from baseline in fasting and postprandial glucose during sMMTT (total and incremental 240-min AUC), changes from baseline in HbA1c, changes from baseline in fasting and postprandial glucagon concentration during sMMTT (total and incremental 240-min AUC). Exploratory objectives included: characterizing the effects on body weight and lipid parameters following multiple QW doses; characterizing the Petition 870250085428, dated 09 / 22 / 2025, page 49 / 79 41 / 45 effect on appetite and food intake; characterize the immunogenicity of B-peptide after multiple QW doses; characterize the effects of B-peptide on blood markers of target coupling. Exploratory parameters included: changes in baseline body weight, waist circumference, body composition (BIA), and lipid parameters; changes in fasting appetite (VAS); changes in appetite score (VAS) during sMMTT; incidence of treatment-emergent ADAs; CTX-1 and pancreatic polypeptide levels.

[0135] Part B. Eligible participants were randomized in a 2:2:1 ratio to receive subcutaneous injections of 1.5 mg dulaglutide + placebo, B-peptide + 1.5 mg dulaglutide QW, or B-peptide + placebo, respectively. The treatment period was 12 weeks.

[0136] The main objective of Part B was to characterize the effects of Peptide B on insulin secretion and the combined parameter of insulin sensitivity. The primary parameter of Part B was the change in the total clamp disposition index (cDI).

[0137] The secondary objectives of Part B included: investigating the safety and tolerability after subcutaneous administration of multiple doses of B-peptide, dulaglutide, or B-peptide + dulaglutide in participants with T2DM; characterizing the effects on insulin secretion, insulin sensitivity, glycemic control, and glucagon secretion. The secondary parameters of Part B included the frequency of TEAs and SAEs, changes from baseline in ISR and β-cell glucose sensitivity (GS) after a hyperglycemic clamp, changes from baseline in hyperinsulinemia value after a euglycemic clamp; change from baseline in fasting and postprandial glucose during sMTT (total and incremental AUC240 min); change from baseline in Petition 870250085428, dated 09 / 22 / 2025, page 50 / 79 42 / 45 HbA1c; change from baseline in fasting and postprandial glucagon concentration during sMMTT (total and incremental AUC0-240 min).

[0138] The exploratory objectives of Part B were to characterize the effects on body weight and lipid parameters after multiple doses of QW; to characterize the effect on appetite and food intake; to characterize the immunogenicity of Peptide B after multiple doses of QW; to characterize the effects on insulin secretion. The exploratory parameters of Part B include: changes from baseline in body weight, waist circumference, body composition (BIA), lipid parameters; changes in fasting appetite (VAS); changes in appetite score (VAS) during sMMTT; incidences of treatment-emergent ADAs; changes from baseline in insulin response to arginine (incremental AUC0-10 min for arginine and incremental AUC0-30 min for arginine) after hyperglycemic clamp; changes in β-cell GS during sMMT; changes from baseline in ISRg during sMMTT; CTX-1, pancreatic polypeptide levels.

[0139] Results. In Part A, very few adverse events of nausea (n = 1) and vomiting (n = 0) occurred after a treatment regimen with dulaglutide and Peptide B. In Part B, there were numerically fewer nausea and vomiting events in participants treated with dulaglutide and Peptide B than in participants treated with dulaglutide and placebo. Table 4. Summary of the number of events within each treatment group based on the preferred term - Part A Results Adverse Effects (AE) Preferred Term Placebo (n = 6) 7.5 mg B-peptide (n = 6) 20 mg B-peptide (n = 6) Petition 870250085428, dated 09 / 22 / 2025, page 51 / 79 43 / 45 Total gastrointestinal disorders 6 (100%) 3 (50.0%) 4 (66.7%) Nausea 0 (0.0%) 1 (16.7%) 0 (0.0%) Vomiting 0 (0.0%) 0 (0.0%) 0 (0.0%) Table 5. Summary of the number of events within each treatment group based on the preferred term - Part B Results Adverse Effects (AE) Preferred Term Placebo + 1.5 mg dulaglutide (n = 29) 20 mg B-peptide + Placebo (n = 15) 20 mg B-peptide + 1.5 mg dulaglutide (n = 28) Total gastrointestinal disorders 16 (55.2%) 5 (33.3%) 17 (60.7%) Nausea 5 (17.2%) 1 (6.7%) 3 (10.7%) Vomiting 4 (13.8%) 0 (0.0%) 2 (7.1%) Sequence Listing Peptide A (SEQ ID NO:1) Y-Aib-EGTFISDYSI-aMeL-LD-Orn-IHQ-Aib-DFVEYK((2-[2-(2-Aminoethoxy)-ethoxy]-acetyl)2-(Y-Glu)-CO-(CH2)18-CO2H)LEGGPSSGAPPPSNH2 Peptide B (SEQ ID NO:2) Y-Aib-EGTFISDYSI-aMeL-LDKK((2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2(Y-Glu)-CO-(CH2)18-CO2H)HQ-Aib-DFVE-4-Pal-LLEAGPSSGAPPPSNH2 Semaglutide (SEQ ID NO:3) H-Aib-EGTFTSDVSSYLEGQAAK((2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2(YGlu)-CO-(CH2)16-CO2H)EFIAWLVRGRG Liraglutide (CAS Registration Number: 204656-20-2) (SEQ ID NO:4) HAEGTFTSDVSSYLEGQAAK(yGIu-CO-(CH2)i4-CH3)EFIAWLVRGRG Dulaglutide (SEQ ID NO:5) Petition 870250085428, dated 09 / 22 / 2025, p. 52 / 79 44 / 45 Dulaglutide is a human GLP-1 receptor agonist comprising a dimer of a GLP-1 analog fused at its C-terminus via a peptide linker to the N-terminus of an Fc portion analog of an immunoglobulin and is identified by CAS Registry Number 923950-08-7, which gives the following chemical name: glucagon-like peptide fusion protein I [8-glycine, 22-glutamic, 36-glycine] (synthetic human) with immunoglobulin G4 peptide fusion protein (synthetic 16 amino acid linker) (synthetic human Fc fragment), dimer. Each dulaglutide monomer has the amino acid sequence shown in SEQ ID NO: 13: HGEGTFTSDVSSYLEEQAAKEFIAWLVKGGGGGGGSGGGGSGGGGSAESKYGPPCPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG Mazdutida (SEQ ID NO: 6) H-Aib-QGTFTSDYSKYLDEKKAK((2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2(YGlu)-CO-(CH2)18-CO2H)EFVEWLLEGGPSSG-NH2 Long-Acting Amylin Receptor Agonist (SEQ ID NO:7) γE-CNTATCATG-Orn-LAE-aMeF-LVRSSN-NMeN-FGPKLPPTEVGSNTY-NH2 wherein there is a thioacetal bridge between the cysteines at positions 2 and 7; and wherein the lysine at position 26 is linked to a fatty acid-binding moiety according to the formula (yE)2-CO-(CH2)is-CO2H Dual agonist of calcitonin and amylin receptors (SEQ ID NO: 8) Petition 870250085428, dated 09 / 22 / 2025, p. 53 / 79 45 / 45 Acetyl-ASHLSTAVLGK((2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(Y-Glu)-CO(CH2)i8-CO2H)LS-Aib-ELHKLEDYPRTDVGAESP-NH2 Tyrosine-tyrosine (PYY) peptide analog (SEQ ID NO: 9) OH HN O° Olympus HN Ρ K Ρ E N H PGEDASPE EWQR ΥΥ ΑΕ L RHYLNWL Τ RQ R Υ—ΝΗ2Ο

Claims

1. A method for treating or preventing nausea or vomiting in a patient, characterized in that it comprises administering a therapeutically effective amount of a GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof.

2. Method according to claim 1, characterized in that the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is from about 0.3 to 30 mg.

3. Method according to claim 1, characterized in that the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is about 5.0 to 30 mg.

4. Method, according to any one of claims 1 to 3, characterized in that the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is 7.5 mg.

5. Method, according to any one of claims 1 to 3, characterized in that the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is 20 mg.

6. Method, according to any one of claims 1 to 3, characterized in that the therapeutically effective amount of the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is 25 mg.

7. A method, according to any one of claims 1 to 3, characterized in that the treatment of nausea or vomiting consists of the patient taking a medication to treat a metabolic syndrome disorder.

8. Method, according to claim 7, characterized in that the metabolic syndrome disorder is type 2 diabetes mellitus or obesity.

9. Method according to claim 7, characterized in that the drug for treating metabolic syndrome disorder is selected from the group consisting of a GLP-1 receptor agonist peptide, a dual agonist peptide of GLP-1 and glucagon (GCG) receptors, a long-acting amylin receptor agonist peptide, a dual agonist peptide of amylin and calcitonin receptors, a monoclonal antibody targeting the leptin receptor, a urocortin peptide, or a tyrosine-tyrosine peptide analog (PYY).

10. Method according to claim 9, characterized in that the medicament for treating metabolic syndrome disorder is selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, or a pharmaceutically acceptable salt thereof.

11. Method, according to claim 9, characterized in that the patient's tolerance to nausea or vomiting-inducing treatment for metabolic syndrome disorder is improved.

12. Method according to claim 9, characterized in that the medication for treating metabolic syndrome disorder is administered without titration.

13. Method, according to any of the claims Petition 870250085428, dated 09 / 22 / 2025, pp. 76 / 79 3 / 4 1 to 3, characterized in that the treatment of nausea or vomiting occurs when the patient takes a chemotherapeutic agent.

14. Method according to claim 13, characterized in that the chemotherapeutic agent is selected from the group consisting of anthracycline, cyclophosphamide, carboplatin, carmustine, cisplatin, cyclophosphamide, dacarbazine, doxorubicin, epirubicin, famtrastuzumab, deruxtecan-nxki, ifosfamide, mechlorethamine, melphalan, sacituzumab govitecan-hzly and streptozocin.

15. Method according to claim 13, characterized in that the chemotherapeutic agent is selected from the group consisting of aldesleucine, amifostine, bendamustine, busulfan, carboplatin, carmustine, clofarabine, cyclophosphamide, cytarabine, dactinomycin, daunorubicin, dinutuximab, doxorubicin, liposomal encapsulation of cytarabine and daunorubicin double drug, epirubicin, idarubicin, ifosfamide, irinotecan, irinotecan (liposomal), lurbinectin, melphalan, methotrexate, mirvetuximab, soratansinagynx, naxitamab-gqgk, oxaliplatin, romidepsin, temozolomide and trabectedin.

16. Method according to claim 14, characterized in that the chemotherapeutic agent is cisplatin.

17. Method according to claim 14, characterized in that the chemotherapeutic agent is a combination of cyclophosphamide and an anthracycline.

18. Method according to claim 17, characterized in that the anthracycline is selected from the group consisting of doxorubicin, daunorubicin and idarubicin.

19. Method according to claim 13, characterized in that the patient's tolerance to nausea or vomiting-inducing treatment with the chemotherapeutic agent is improved.

20. Method, according to claim 13, characterized by the fact that the chemotherapeutic agent is administered without titration.

21. A method according to any one of claims 1 to 3, characterized in that the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered via subcutaneous, intravenous, intramuscular, intraperitoneal, oral, or inhalation routes.

22. A method according to any one of claims 1 to 3, characterized in that the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered to the patient once, once a week, twice a month, once every three weeks, once a month, or once a year.

23. Method according to claim 22, characterized in that the GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, is administered subcutaneously to the patient once a week.

24. Use of a GIP receptor agonist peptide comprising SEQ ID NO: 1 or SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof, characterized in that it is for the manufacture of a medicament for use in therapy.