CAR peptide for homing, diagnosis and targeted therapy for pulmonary and fibrotic disorders
Inventors
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Assignees
Sanford Burnham Prebys Medical Discovery Institute • Vascular Biosciences Inc
Member
Vascular BioSciencesVascular BioSciences is a biopharmaceutical and medical device company focused on developing targeted therapeutics, minimally invasive interventional devices, and advanced molecular diagnostics for cardiovascular, pulmonary, and inflammatory diseases. The company leverages targeted peptide drug delivery, endovascular tissue sampling, molecular profiling, and bioinformatics to advance personalized medicine for difficult-to-treat diseases. Its operations span California and North Carolina with expertise in biologics, device engineering, and translational research.
Vascular BioSciences is a biopharmaceutical and medical device company focused on developing targeted therapeutics, minimally invasive interventional devices, and advanced molecular diagnostics for cardiovascular, pulmonary, and inflammatory diseases. The company leverages targeted peptide drug delivery, endovascular tissue sampling, molecular profiling, and bioinformatics to advance personalized medicine for difficult-to-treat diseases. Its operations span California and North Carolina with expertise in biologics, device engineering, and translational research.
Publication Number
US-9180161-B2
Publication Date
2015-11-10
Expiration Date
Abstract
Disclosed are compositions and methods useful for delivering 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 effect a beneficial therapeutic result. The disclosed targeting is useful for delivering therapeutic and detectable agents to diseased tissue in an animal.
Core Innovation
The disclosed invention relates to CAR (CARSKNKDC; SEQ ID NO:1) and truncated CARK (CARSKNK; SEQ ID NO:2) peptides that selectively home to diseased pulmonary/fibrotic tissue. The peptides bind to heparan sulfate proteoglycans, thereby enabling tissue targeting via heparan sulfate/GAG biology and HSPG-linked targeting.
The invention provides compositions and use of these targeting peptides with bioactive agents for targeted treatment. The disclosed use includes co-administration (within 1 hour) or conjugation with therapeutic or detectable bioactive agents to achieve targeting of diseases described in the disclosure, including pulmonary hypertension, ALI/ARDS, and pulmonary fibrosis.
Mechanistic and biological support is provided through described tissue localization and enhanced vasodilator effects, including CAR+fasudil and CAR/CARK+imatinib. The disclosure also describes sustained pulmonary-specific hemodynamic effects after peptide infusion and altered expression of heparan sulfate biosynthesis enzymes in a PAH model.
Claims Coverage
The document includes one independent claim. It is directed to a composition defined by a targeting peptide with the amino acid sequence of SEQ ID NO: 1, combined with a vasodilator bioactive agent, with a key requirement that the targeting peptide is not directly or indirectly conjugated to the bioactive agent.
Targeting peptide with SEQ ID NO: 1
A targeting peptide comprising the amino acid sequence of SEQ ID NO: 1.
Vasodilator bioactive agent providing therapeutic benefit
At least one bioactive agent which conveys a therapeutic benefit to a disease, wherein the at least one bioactive agent is a vasodilator.
No direct or indirect conjugation between targeting peptide and bioactive agent
The targeting peptide is not directly or indirectly conjugated to the at least one bioactive agent.
Across the independent claim, the inventive concept centers on using a SEQ ID NO: 1 targeting peptide together with a vasodilator bioactive agent for therapeutic benefit, while maintaining a non-conjugated relationship between the peptide and the bioactive agent.
Stated Advantages
Selective homing to diseased pulmonary/fibrotic tissue.
Enhanced pharmacologic effects in diseased pulmonary contexts.
Targeting of therapeutic or detectable bioactive agents to disease sites.
Sustained pulmonary-specific hemodynamic effects after peptide infusion.
Altered expression of heparan sulfate biosynthesis enzymes in a PAH model.
Documented Applications
Targeted treatment of pulmonary hypertension.
Targeted treatment of ALI/ARDS (acute lung injury/acute respiratory distress syndrome).
Targeted treatment of pulmonary fibrosis.
Diagnostic imaging involving detectable bioactive agents.
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