Orally active, cell-penetrating homing peptide and methods of using same

Inventors

Mann, David M.

Abstract

Disclosed are compositions and methods useful for oral delivery of targeted therapies for pulmonary diseases, fibrotic disorders and cancer. The compositions and methods are based on peptide sequences that selectively bind to and home to diseased tissue and enable targeted therapies to affect a beneficial therapeutic result. The disclosed targeting is useful for oral delivery of therapeutic and detectable agents to diseased tissue in an animal.

Core Innovation

The invention relates to an orally active targeting peptide comprising a sequence consisting of at least one member selected from SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, together with at least one therapeutic compound that conveys a measureable therapeutic benefit to an individual suffering from a disease. The peptide is described as a CAR-based targeting/cell-penetrating homing peptide, including CARSKNKDC (SEQ ID NO: 1) and related linear and cyclic variants, including SKNKDCCAR (SEQ ID NO: 5), for targeting diseased pulmonary vasculature and fibrotic or injured tissues.

The invention addresses the need for orally active targeting and homing peptides suitable for targeted delivery in disease settings, with a focus on overcoming oral delivery barriers while maintaining stability and selective benefit. The document provides prior art rationale that CAR binding to heparan sulfate proteoglycans supports targeting, and it frames oral bioavailability as a key limitation to be addressed for achieving disease-relevant therapeutic outcomes.

The invention further emphasizes co-administration and the bystander effect, in which systemic therapeutics are administered together with the orally active targeting peptide to achieve selective pulmonary benefit with reduced systemic effects. Experimental support described includes oral CAR that selectively enhances imatinib-induced pulmonary hypotension in PAH rat models, and a trypsin-digestion time course indicating cyclic CAR stability with a predominant resistant SKNKDCCAR (SEQ ID NO: 5) fragment, supporting oral availability.

Claims Coverage

The independent claim covers an orally active composition comprising a targeting peptide limited to specific SEQ ID NO sequences and at least one therapeutic compound that provides a measureable therapeutic benefit to an individual suffering from a disease. The dependent claims further refine peptide sourcing and expand or narrow the disease indications and matching between the therapeutic compound and the disease.

Overall, the claim set centers on an orally active, sequence-restricted targeting peptide used in combination with at least one therapeutic compound that provides a measurable therapeutic benefit, with dependent claims refining targeting peptide source, expanding disease indications, and in some instances narrowing to pulmonary hypertension and requiring disease-specific therapeutic compounds.

Stated Advantages

Documented Applications