Monomeric peptide multi-agonist targeting the GLP1 receptor and NPY receptors
Inventors
Doyle, Robert P. • Milliken, Brandon
Assignees
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Publication Number
US-12384825-B2
Publication Date
2025-08-12
Expiration Date
Abstract
A series of chimeric peptides that provide a mechanism for obesity treatment concomitant with T2DM in the form of dual agonism of the anorectic neuropeptide Y-receptor (Y2-R) and the glucoregulatory receptor GLP1-R. Preliminary results show that, dependent on the selected peptide, once-daily administration suppress FI in male and female rats can be reduced to 12-65% compared to baseline conditions before treatment, dependent on dose and age of animals, and glucose tolerance can be improved as well. Peptides also demonstrated Y1-receptor agonism, conferring protection on beta-islet cells against inflammatory damage. The peptides were designed by targeting serial anorectic pathways simultaneously and are promising candidates for modulating FI and glucoregulation in an efficacious and safe way.
Core Innovation
The invention relates to chimeric monomeric multi-agonist peptides, exemplified by a chimeric peptide having the amino acid sequence comprising SEQ ID NO: 11. The peptides are designed for dual agonism at GLP-1R and NPY receptors, with potent Y2-R activity, partial Y1-R activity, and Y2-R antagonism while enabling GLP-1R signaling.
The problem addressed is obesity and Type II diabetes, including the challenge of reducing food intake and improving glucose tolerance without nausea. The background narrative emphasizes that GLP-1R-related approaches can be limited by adverse effects such as nausea, motivating peptide designs that provide the desired metabolic and appetite effects while aiming to reduce such nausea-associated outcomes.
The documented results describe that the peptides show dose- and age-dependent suppression of food intake in in vivo studies and improved glucose tolerance, along with in vitro activities that stimulate cAMP and insulin secretion in islets. The peptide actions are further reported to mitigate cytokine-induced β-cell injury via Y1-R.
The document also reports observations intended to support reduced emesis, including mammalian observations where shrews show little or no vomiting and reduced fentanyl-drive. The overall disclosed approach combines the specified dual receptor targeting with measured functional outcomes to support treatment of obesity and Type II diabetes while aiming to limit nausea-related side effects.
Claims Coverage
The independent claim is directed to a chimeric peptide with the amino acid sequence comprising SEQ ID NO: 11, and the claim set includes dependent refinements and therapeutic-use limitations. The inventive coverage therefore includes the sequence-defined peptide, specific structural features, and use contexts relating to obesity, nausea, and opioid addiction.
Chimeric peptide comprising SEQ ID NO: 11
A chimeric peptide comprising an amino acid sequence comprising SEQ ID NO: 11.
Chimeric peptide with K12-azido modification
A chimeric peptide according to the peptide of claim 1, wherein the chimeric peptide comprises a K12-azido modification.
Chimeric peptide with D-isomer serine at the second position
A chimeric peptide according to the peptide of claim 1, wherein the serine at the second position of SEQ ID NO: 11 is a D-isomer of serine.
Method for treating obesity in a human patient
A method of treating obesity in a human patient comprising administering a therapeutic amount of a chimeric peptide of claim 1.
Reducing food intake and weight gain without nausea
Administering a therapeutic amount of a chimeric peptide of claim 1 to a human patient to reduce food intake and weight gain without causing nausea.
Opioid addiction treatment using fentanyl as the opioid
The method wherein the opioid used is fentanyl.
The claim coverage is centered on the SEQ ID NO: 11-defined chimeric peptide, with dependent claims narrowing the peptide via specific chemical and stereochemical features. The therapeutic coverage emphasizes treating obesity and reducing food intake and weight gain without nausea, and it also includes an opioid-addiction treatment context where the opioid is fentanyl.
Stated Advantages
Suppression of food intake.
Improved glucose tolerance.
Stimulating cAMP and insulin secretion in islets.
Mitigation of cytokine-induced β-cell injury via Y1-R.
Reduced nausea, including reduced emesis observations (e.g., little or no vomiting in shrews).
Documented Applications
Treatment of obesity in a human patient by administering a therapeutic amount of a chimeric peptide of claim 1.
Reducing food intake and weight gain without causing nausea in a human patient via administration of a therapeutic amount of a chimeric peptide of claim 1.
Type II diabetes treatment.
Opioid addiction treatment, including methods where the opioid used is fentanyl.
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