Description:
Summary
Non-healing wounds can pose significant problems for cancer patients (e.g., in cases where multiple operations are required for local recurrence, when large wounds are slow to close, and especially when patients receive radiation at sites requiring surgery). In addition, the effects of chemotherapy, nutritional deficits along with co-morbidities (e.g., diabetes), and infections can complicate wound healing. Therefore, the cancer patient population has the potential for non-healing wounds due to the nature and effects of the oncologic disease process and its treatments (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2206003/). Improved methods are thus needed for treating non-healing wounds that often result in lengthy hospital stays, application of multiple types of dressings and ointments, and hyperbaric methods.
Nitric oxide (NO) is an important bio-signaling molecule whose role has been extensively recognized in the body’s endogenous immune, inflammatory, and tissue regenerative responses. Therapeutic application of exogenous topical NO-generating agents has been shown to provide powerful, broad-spectrum antimicrobial action, and NO is capable of providing numerous wound-healing benefits if delivered at the proper concentrations. However, since NO is an easily oxidized gas, controlled topical delivery of NO to a desired area is difficult. The National Cancer Institute (NCI) has developed a family of polymers based on poly(acrylonitrile) that are capable of storing NO bound in a stable chemical functionality, called a diazeniumdiolate group, and releasing NO under aqueous conditions. The next logical step in the utilization of these materials for biomedical applications is the incorporation of these NO-releasing poly(acrylonitrile)-based compositions into suitable, biocompatible dressings for application to wounds to fight infection, modulate inflammation, and promote angiogenesis and collagen synthesis in order to accelerate wound closure and/or otherwise improve functional outcomes.
This invention is the subject of issued patents US 7,968,664 and US 8,093,343, and HHS Reference Number E-188-2004.
Project Goals
The ultimate goal of this effort is to develop a commercially viable wound-healing dressing, utilizing this NCI-developed technology, to alleviate the suffering and costs caused by non-healing wounds, thereby establishing a precedent for supportive care for cancer while quickly creating a product of merit. The short-term goal of this project is to develop a prototype of such a dressing and to provide data that clearly demonstrate the potential of this stable NO-releasing material/formulation. The work scope may include design and fabrication of the material with in vitro evaluation (e.g., product stability testing) and preliminary in vivo assessment of its efficacy and final prototype development. These data will support the continued development of the experimental medical device to the point of filing an Investigational Device Exemption (IDE). The long-term goal of this topic is to enable a small business to bring a fully developed product incorporating NCI’s NO-releasing polymer technology to the clinic and the market.
The dressing to be developed under this contract should demonstrate the ability to maintain the stability of the diazeniumdiolate group during storage and sterilization, and to release NO when triggered by any mechanism related to wound contact (e.g., thermal or aqueous stimuli, biochemical interaction, etc.), or triggered by the health care provider (e.g., light source, chemical mixing, etc.). Since one of the major potential benefits of sustained and controlled release of therapeutic NO is the reduced frequency with which the care provider must contact the wounded skin to apply therapeutics and change the dressing, any stable, NO-releasing formulation will be considered including, but not limited to, fabric-based “traditional” dressings incorporating poly(acrylonitrile) as one of the textile components, hydrogels, creams, gels, nanomaterials, meshes, films, coatings, etc.
This is an NIH TT (Technology Transfer) contract topic from the NCI. This is a program whereby inventions from the NCI Intramural Research Program (Center for Cancer Research, CCR) are licensed to qualified small businesses with the intent that those businesses develop these inventions into commercial products that benefit the public. The contractor funded under this contract topic shall work closely with the NCI CCR inventors of this technology. The inventors will provide assistance in a collaborative manner with reagents and discussions during the entire award period. Between the time this contract topic is published and the time an offeror submits a contract proposal for this topic, no contact will be allowed between the offeror and the NCI CCR inventors. However, a pre-submission public briefing and/or webinar will be given by NCI staff to explain in greater detail the technical and licensing aspects of this program (for further information, see http://sbir.cancer.gov/news/upcoming/). In addition, a list of relevant technical, invention, and licensing-related questions and answers (including those from the public briefing) will be posted, maintained, and updated online (http://sbir.cancer.gov/news/upcoming/) during this time period.
The awarded contractor will automatically be granted a royalty-free, non-exclusive license to use NIH-owned and patented background inventions only within the scope and term of the award. However, an SBIR offeror or SBIR contractor can apply for an exclusive or non-exclusive commercialization license to make, use, and sell products or services incorporating the NIH background invention. Offerors submitting an SBIR contract proposal in response to this topic are strongly encouraged to submit concurrently an application for a commercialization license to such background inventions. Under the NIH NCI TT program, the SBIR contract award process will be conducted in parallel with, but distinct from, the review of any applications for a commercialization license.
To apply for a commercialization license to develop this NIH invention, an SBIR offeror or contractor must submit a license application to the NIH Licensing and Patenting Manager: Betty Tong Ph.D., tongb@mail.nih.gov or 301-594-6565. A license application and model license agreements are available at http://www.ott.nih.gov/pdfs/LicApp.pdf and http://www.ott.nih.gov/forms_model_agreements/forms_model_agreements.aspx#LAP.
This license application provides NIH with information about the potential licensee, some of the terms desired, and the potential licensee's plans for development and/or commercialization of the invention. License applications will be treated in accordance with Federal patent licensing regulations as provided in 37 CFR Part 404. A further description of the NIH licensing process is available at http://www.ott.nih.gov/licensing_royalties/intra_techlic.aspx. NIH will notify an SBIR offeror who has submitted an application for an exclusive commercialization license if another application for an exclusive license to the background invention is received at any time before such a license is granted.
Any invention developed by the contractor during the course of the NIH TT contract period of performance will be owned by the contractor subject to the terms of Section 8.5.
Phase I Activities and Expected Deliverables
• Prepare one or more dressings or other formulations incorporating NO-releasing poly(acrylonitrile) materials
• Produce a prototype product meeting minimum essential characteristics o Quantifiable NO release durations should range from acute time periods (minutes) to 24 hours or longer to support an adequate therapeutic window
o NO storage and release should be quantified via standard electrochemical or chemiluminescent assays routinely used in characterizing NO-based materials
• Characterize the material’s:
o total NO release potential
o triggered NO release kinetics
• Conduct proof of concept in vitro studies in the appropriate models and environments
• Conduct in vivo efficacy studies to demonstrate potential therapeutic benefit of the lead candidate NO-releasing preparation in an appropriate model
Phase II Activities and Expected Deliverables
• All studies in Phase II shall be conducted with the ultimate aim of producing a product acceptable to the FDA, and shall thus follow the recommendations contained in the FDA document “Guidance for Industry: Chronic Cutaneous Ulcer and Burn Wounds-Developing Products for Treatment” published June 2006 and available for download from the FDA website: (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071324.pdf)
• Conduct appropriate stability studies, including thermal stability at sterilization temperatures and shelf life characterization
• Provide quantitative evidence of improved wound healing over the current standard-of-care
• Demonstrate capability for commercial production of the product
• Demonstrate capability to manufacture and sterilize the lead candidate in an industrial setting
• Prototype should demonstrate the ability to provide medical benefit, robust stability, and commercial potential
