Modified peptide fragments of CAV-1 protein and the use thereof in the treatment of fibrosis
Inventors
Christensen, Dale • Koleng, John J.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11787838-B2
Publication Date
2023-10-17
Expiration Date
Abstract
Provided herein are compositions comprising modified caveolin-1 (Cav-1) peptides. Further provided are methods of using the modified Cav-1 peptides for the treatment of lung infections or acute or chronic lung injury, particularly lung fibrosis.
Core Innovation
The invention provides modified caveolin-1 (Cav-1) peptide fragments, including Ac-aaEGKASFTTFTVTKGSaa-NH2 (SEQ ID NO: 8), with at least one N- or C-terminal addition or modification. The modifications include D-amino acids, non-standard amino acids, and terminal amidation and/or acylation, including forms such as Ac-aaEGKASFTTFTVTKGSaa-NH2. The peptides are optionally provided as multimers, peptidomimetics, cell penetrating peptide (CPP)-containing constructs, and/or PEGylated or fusion protein forms.
The invention relates to using these modified Cav-1 peptide compositions to address injury-associated and fibrotic lung conditions, including acute lung injury and pulmonary fibrotic conditions such as idiopathic pulmonary fibrosis (IPF). The disclosed use includes pharmaceutical formulations for lung delivery, including aerosol and nebulized solutions, and lung delivery approaches described as nebulizing devices for administration to a subject.
Mechanistic background in the document links Cav-1 to uPA, uPAR, PAI-1, p53, and β1-integrin, including injury-induced changes affecting these pathways. The document further describes cellular outcomes in fibrotic settings, including increased smooth muscle actin (SMA) expression in IPF cells after Cav-1 peptide treatment and increased AEC2 viability in precision cut lung slices from NSIP and end-stage IPF biopsies using Cav-1 peptide APi2355 (SEQ ID NO: 8).
Claims Coverage
The independent claim covers treating fibrosis by administering a specific modified Cav-1 peptide (Ac-aaEGKASFTTFTVTKGSaa-NH2; SEQ ID NO: 8) as a pharmaceutical composition characterized as not a dry powder. The dependent claims further define route/device and dosing constraints, and fibrosis type and biomarker modulation endpoints.
Treating fibrosis with a specified non-dry-powder Cav-1 peptide composition
A method of treating fibrosis in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition comprising a peptide consisting of Ac-aaEGKASFTTFTVTKGSaa-NH2 (SEQ ID NO: 8), wherein the pharmaceutical composition is not a dry powder.
Specific mg/kg dose range for the method
Administering the pharmaceutical composition at a dose ranging from 0.01 mg/kg to 500 mg/kg.
Multiple-dose frequency options
Administering the pharmaceutical composition in multiple doses at a specified dosing frequency selected from once daily, once every two days, once weekly, once every two weeks, or once monthly.
Nebulizer type for administration
Administering the pharmaceutical composition using a vibrating mesh nebulizer, a jet nebulizer, or an ultrasonic nebulizer.
Fibrosis limited to specified organs
The fibrosis is kidney fibrosis, liver fibrosis, heart fibrosis, or pulmonary fibrosis.
Smooth muscle actin modulation endpoint
Further administering a pharmaceutical composition that modulates expression of smooth muscle actin in a subject.
Overall, the claims center on administering an effective amount of Ac-aaEGKASFTTFTVTKGSaa-NH2 (SEQ ID NO: 8) as a not-a-dry-powder pharmaceutical composition to treat fibrosis, with dependent claim refinements covering dose, dosing frequency, nebulizer delivery devices, specified organ fibrosis types, and modulation of smooth muscle actin expression.
Stated Advantages
Documented Applications
No documented applications found
Interested in licensing this patent?