Method of treating melanocortin-4 receptor-associated disorders in heterozygous carriers
Inventors
Tartaglia, Louis Anthony • Henderson, Bart • Van Der Ploeg, Leonardus H. T.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11702448-B2
Publication Date
2023-07-18
Expiration Date
Abstract
A method of treating a disorder in a subject. The method comprises administering to said subject an effective amount of an agonist of the melanocortin-4 receptor (MC4R). The subject is a heterozygous carrier of an MC4R mutation, and the disorder results from an attenuated response of MC4R to α-melanocortin stimulating hormone (α-MSH).
Core Innovation
The invention relates to a method of treating a disorder in a subject who is a heterozygous carrier of an MC4R mutation by administering an effective amount of an agonist of the melanocortin-4 receptor (MC4R). The MC4R agonist restores MC4R-mediated signaling, including adenylate cyclase and cAMP signaling, and the subject is described as having an attenuated alpha-MSH response.
The disclosed disorders include obesity and metabolic syndrome, as well as related obesity-associated comorbidities. The document provides sequence-defined peptide and chemical shorthand and structural conventions for MC4R agonist compounds, including terminal variants such as amidated C-terminus (-NH2), cyclic and cys-dimer notations, hydantoin-containing motifs, and pharmaceutically acceptable salts.
The disclosure includes extensive peptide MC4R agonists with SEQ ID NOs and terminal variants, together with illustrative structures such as D-Phe-Arg-Trp and hydantoin-containing compounds. Representative explicit compounds include Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ ID NO: 500), and related sequence-defined peptide MC4R agonists.
Claims Coverage
The provided material includes one independent claim for a method of treating a disorder by administering an MC4R agonist to a subject who is a heterozygous carrier of an MC4R mutation. The independent claim is refined by dependent claims covering obesity, metabolic syndrome, exclusion of ACTH, and selection of specific peptide MC4R agonists including hydantoin-containing variants and sequence-defined peptide sets.
Treatment in an MC4R heterozygous carrier
Administering to a subject an effective amount of an agonist of the melanocortin-4 receptor (MC4R), wherein the subject is a heterozygous carrier of an MC4R mutation.
Obesity treatment
The method is for treating a disorder that is obesity.
Metabolic syndrome treatment
The method is applied to treating a metabolic syndrome disorder.
Non-ACTH MC4R agonist limitation
The MC4R agonist is not an adrenocorticotropic hormone (ACTH).
Hydantoin MC4R agonist
The method uses Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ ID NO: 500) or a pharmaceutically acceptable salt thereof.
Sequence-defined peptide MC4R agonist set
The MC4R agonist is chosen from a specified set of peptide sequences listed by SEQ ID NOs, including terminal variants and pharmaceutically acceptable salts thereof.
Overall claim coverage centers on treating an MC4R mutation-associated disorder in an MC4R heterozygous carrier by administering an MC4R agonist, with refinements to obesity and metabolic syndrome, exclusion of ACTH, and selection of hydantoin-containing peptides and other sequence-defined peptide MC4R agonists.
Stated Advantages
Sustained weight loss.
Potential improvements in hyperinsulinemia.
Potential improvements in glucose control.
Potential improvements in hyperphagia.
Potential improvements in multiple obesity-related comorbidities.
Documented Applications
Treating a disorder in a subject in need thereof who is a heterozygous carrier of an MC4R mutation by administering an effective amount of an MC4R agonist.
Treating obesity in subjects with MC4R mutations who are heterozygous carriers.
Treating metabolic syndrome in subjects with MC4R mutations who are heterozygous carriers.
Proposed animal model for MC4R+/- responsiveness to a specific peptide (SEQ ID NO:140).
Human safety/efficacy studies in obese subjects, including cohorts with heterozygous MC4R mutation, with endpoints such as weight loss and exploratory metabolic measures.
Interested in licensing this patent?