Compositions for colon cleansing and the treatment of gastrointestinal disorders
Inventors
Currie, Mark G. • Solinga, Robert • Leitheiser, Christopher
Assignees
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Publication Number
US-10618938-B2
Publication Date
2020-04-14
Expiration Date
Abstract
The present invention provides peptides and compositions that are useful for the treatment of gastrointestinal disorders or for colon cleansing. The present invention also provides compositions and methods of treating gastrointestinal disorders and pharmaceutical compositions for accomplishing the same. In some embodiments, these pharmaceutical compositions include oral dosage forms.
Core Innovation
The invention is directed to GC-C agonist peptides defined by an amino acid sequence framework identified as SEQ ID NO: 1 and containing specific covalent bond patterns between residues Xaa7 and Xaa12, Xaa8 and Xaa16, and Xaa11 and Xaa19. The peptides are provided as a peptide or a pharmaceutically acceptable salt thereof, and the framework includes position-specific constraints in which multiple Xaa positions are absent while other positions are restricted to defined residues.
Allowed residue options include Ag, Cys, Cth, penicillamine (Pen), Glu, Leu, Asn, Val, Pro, Tyr, and Thr as recited. The disclosure also includes explicitly enumerated peptide sequences as SEQ ID NOs and specifies terminal forms for those variants.
The disclosed formulations include pharmaceutical compositions comprising the GC-C agonist peptides or pharmaceutically acceptable salts thereof, including solid oral dosage formulations described as oral solid dosage formulations. The partial content also describes formulation and stability strategies involving cations and sterically hindered primary amines, and relates these strategies to enhanced stability of the peptide components.
Claims Coverage
The partial content contains three independent claim categories: a peptide defined by a 21-position sequence framework with specified absent/allowed residues and three covalent bond requirements; a peptide defined by enumerated full sequences with N- and C-terminal forms; and a pharmaceutical composition comprising such a peptide, including solid oral dosage formulations. Across these independent claims, the key inventive features are sequence constraints and covalent bonding patterns, followed by specific enumerated sequence variants, and then formulation/solid dosage inclusion.
Covalently linked GC-C agonist peptide framework with absent/allowed residues
A peptide or a pharmaceutically acceptable salt thereof comprising the amino acid sequence (SEQ ID NO: 1) in which Xaa1–Xaa6, Xaa20, and Xaa21 are absent and remaining positions are restricted as recited; wherein the peptide contains covalent bonds between Xaa7 and Xaa12, Xaa8 and Xaa16, and Xaa11 and Xaa19.
Enumerated GC-C agonist peptide sequences with terminal capping
A peptide or a pharmaceutically acceptable salt thereof comprising the amino acid sequences recited as SEQ ID NOs 2 through 92, with specific N- and C-terminal forms as recited.
Pharmaceutical composition comprising enumerated GC-C agonist peptides as solid oral dosage
A pharmaceutical composition comprising a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide or pharmaceutically acceptable salt thereof comprises the amino acid sequence of one of SEQ ID NOs 2 through 44, as recited, and further wherein the composition includes a solid oral dosage formulation.
Claim coverage centers on GC-C agonist peptides defined by a constrained SEQ ID NO: 1 framework with specified absent/allowed residues and covalent bonds between Xaa7–Xaa12, Xaa8–Xaa16, and Xaa11–Xaa19; peptides comprising enumerated SEQ ID NO variants with N- and C-terminal forms; and pharmaceutical compositions containing the specified peptides, including solid oral dosage formulations.
Stated Advantages
Enhanced stability of the peptide components by suppressing oxidation and formaldehyde-imine adduct formation.
Improved formulation stability via cation excipients and sterically hindered primary amines.
Documented Applications
Colon cleansing / colonoscopy preparation, including pre-colonoscopy administration.
Treatment indications described as broad gastrointestinal and visceral disorder indications, including visceral pain.
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