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 (VBS) is an innovative biomedical company developing breakthrough solutions to critical military and civilian medical challenges including: Military Infectious Diseases, Sepsis, Combat Casualty Care, Acute High Altitude Pulmonary Edema, and CBRN medical countermeasures. Our inflammation homing peptide, CARSKNKDC (CAR), enables increased localized concentrations of drugs to dramatically improve therapeutic outcomes with reduced side-effects. CAR converts systemically administered drugs into precision medicines. CAR peptide, by itself, also dramatically speeds up wound healing.
Vascular Biosciences (VBS) is an innovative biomedical company developing breakthrough solutions to critical military and civilian medical challenges including: Military Infectious Diseases, Sepsis, Combat Casualty Care, Acute High Altitude Pulmonary Edema, and CBRN medical countermeasures. Our inflammation homing peptide, CARSKNKDC (CAR), enables increased localized concentrations of drugs to dramatically improve therapeutic outcomes with reduced side-effects. CAR converts systemically administered drugs into precision medicines. CAR peptide, by itself, also dramatically speeds up wound healing.
Publication Number
US-10039838-B2
Publication Date
2018-08-07
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 invention provides a CAR (SEQ ID NO:1) and a truncated CAR variant CARK (SEQ ID NO:2) as targeting/homing peptides that bind heparan sulfate proteoglycans in diseased pulmonary, fibrotic, and angiogenic/cancer-associated tissues. The targeting peptide is described for use in a composition with at least one bioactive agent to convey a therapeutic benefit to a disease, including tissue-selective delivery and pulmonary-selective delivery to diseased tissues expressing heparan sulfate proteoglycans.
The problem addressed is the need for targeting peptide binding to diseased tissues and delivering therapeutic bioactive agents to those tissues while minimizing systemic side effects. The patent links targeting to heparan sulfate and describes altered heparan sulfate biosynthetic gene expression, including HS2ST1, EXT1, GLT8D2, NDST1, and OGT. The document further describes that targeting peptides can be provided as variants and in multivalent dendrimer constructs to support binding/targeting.
A composition aspect is also described that includes co-administration of the targeting peptide with therapeutic bioactive agents, including cases where the bioactive agent is optionally bound to the peptide, to achieve enhanced efficacy in diseased conditions. The disclosed therapeutic settings include pulmonary hypertension and bleomycin-induced lung injury/fibrosis models, with analysis of heparan-sulfate-pathway gene upregulation in a porcine PAH surgical shunt model. The document also discloses detection/diagnosis approaches based on CAR conjugation or co-administration with imaging agents.
Claims Coverage
Independent claim clm-00001 is directed to a composition with two main inventive features: (i) a specific targeting peptide defined by SEQ ID NO:2, and (ii) at least one bioactive agent selected from a specified group, wherein the targeting peptide and bioactive agent are bound and convey a therapeutic benefit to a disease. No other independent claims are provided in the received partial content.
Targeting peptide consisting of SEQ ID NO:2
A targeting peptide consisting of the amino acid sequence of SEQ ID NO:2.
Bound bioactive agent conveys therapeutic benefit
At least one bioactive agent conveying a therapeutic benefit to a disease, selected from the group consisting of antiallergics, bronchodilators, antifibrotics, antihypertensive agents, bronchoconstrictors, pulmonary lung surfactants, analgesics, antibiotics, leukotriene inhibitors or antagonists, anticholinergics, mast cell inhibitors, anti-neoplastics, prostacyclins, anesthetics, anti-tuberculars, imaging agents, cardiovascular agents, enzymes, steroids, viral vectors, antisense agents, small molecule drugs, proteins, and peptides, wherein the targeting peptide and the at least one bioactive agent are bound.
The claim coverage centers on a composition combining the SEQ ID NO:2 targeting peptide with a disease-appropriate bioactive agent selected from an enumerated therapeutic-agent group, with the defining requirement that the targeting peptide and the bioactive agent are bound to convey a therapeutic benefit.
Stated Advantages
Tissue-selective delivery and enhanced efficacy while minimizing systemic side effects.
Documented Applications
Therapeutic use in diseased pulmonary conditions and fibrotic disorders, including pulmonary hypertension and bleomycin-induced lung injury/pulmonary fibrosis models.
Therapeutic benefit in diseases enumerated in dependent claim refinements, including acute respiratory distress syndrome (ARDS), sepsis, septic shock, and wound healing (as part of a listed set of diseases).
Detection/diagnosis using CAR conjugation or co-administration with imaging agents.
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