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Publication Number
US-11708392-B2
Publication Date
2023-07-25
Expiration Date
Abstract
Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.
Core Innovation
The invention relates to peptide antagonist concepts for selectively disrupting ligand-receptor signaling interactions involving cytokines. It focuses on inhibiting an activity of at least two cytokines selected from a family of cytokines that bind to a common receptor, while avoiding broad blockade. The approach emphasizes targeting conserved receptor-binding interface regions within cytokine families to achieve selective inhibition across subsets of cytokines binding a shared receptor.
The therapeutic constructs include a therapeutic composite peptide conjugated to a moiety. The therapeutic composite peptide comprises a region of 1-20 amino acids in length that aligns with a corresponding region of a single target ligand or receptor, with the single target ligand or receptor specified by a set of SEQ ID NOs. Composite and cross-family antagonist peptide construction is described via linking single-family inhibitory motifs, including PEG-linked dual antagonists and related composite configurations.
The disclosed peptide antagonist concepts are associated with inhibition outcomes and downstream signaling effects for defined cytokines. The document reports inhibition of specific γc-cytokines, with limited effects described for other cytokines, and includes blockade of downstream signaling such as STAT5 phosphorylation. The document further describes therapeutic and cosmeceutical application areas and pharmaceutical composition elements such as a pharmaceutical acceptable carrier, pharmaceutically acceptable carriers/excipients, and moieties such as BSA/albumin and Fc-region-containing entities.
Claims Coverage
The document includes two independent claims covering a therapeutic composite peptide conjugate encoded by a nucleotide sequence and a pharmaceutical composition containing that conjugate. Across the independent claims, the coverage includes inhibition of at least two common-receptor cytokines, conjugation to a moiety, a 1-20 amino-acid aligned region, and restriction of the single target ligand or receptor to a specified set of SEQ ID NOs.
Therapeutic composite peptide conjugate inhibition of common-receptor cytokines
A nucleotide sequence encoding a therapeutic composite peptide conjugate that inhibits an activity of at least two cytokines selected from a family of cytokines that bind to a common receptor.
Composite peptide region aligned to a corresponding receptor or ligand region
The therapeutic composite peptide comprises a region 1-20 amino acids in length that aligns with a corresponding region of a single target ligand or receptor.
Moiety-conjugated therapeutic composite peptide
The therapeutic composite peptide is conjugated to a moiety.
Single target ligand or receptor restricted to specified SEQ IDs
The single target ligand or receptor is any one of SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, and SEQ ID NO:161.
Pharmaceutical composition containing the nucleotide-encoded conjugate
A pharmaceutical composition comprising a nucleotide sequence encoding a therapeutic composite peptide conjugate and a pharmaceutical acceptable carrier, diluent, excipient, or combination thereof.
Both independent claims require a moiety-conjugated therapeutic composite peptide encoded by a nucleotide sequence that inhibits at least two cytokines binding a common receptor. In each claim, the composite peptide includes a 1-20 amino-acid aligned region against a single target ligand or receptor, and that receptor is limited to a defined set of SEQ ID NOs. The second independent claim further wraps the nucleotide sequence into a pharmaceutical composition with a pharmaceutical acceptable carrier, diluent, or excipient.
Stated Advantages
Selective inhibition across subsets of cytokines binding a shared receptor, while avoiding broad blockade.
Limited effects are described for other cytokines.
Blockade of downstream signaling such as STAT5 phosphorylation.
Documented Applications
Therapeutic application areas.
Cosmeceutical application areas.
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