Agenta Biotechnologies, Inc. | Date: 2011-07-14
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.09M | Year: 2009
DESCRIPTION (provided by applicant): Barrier membranes are an important adjunct to regeneration therapy aimed at restoring the form and function of the mouth. Commercially available barrier membranes are used in dental surgeries to help retain bone grafting materials, to help exclude epithelium and connective tissue from entering into sites of desired bone and ligament regeneration, or for the combination of these reasons. Whether restoring lost bone around teeth or implants, or in larger areas of the jaws affected by trauma or disease, too often there is inadequate gum tissue to cover the membranes which can lead to membrane exposure, extensive membrane contamination, and procedural failure which is unacceptable. Our data suggests that biologically activating membranes made of chitosan (a versatile, biocompatible, resorbable material used in wound bandages) with our proprietary biologic - a small and soluble heparan sulfate-rich co-activator of growth factors - hastens gingival healing over exposed membranes in the mouth. RandD for this project is directed at development of a bioactivated chitosan regenerative membrane that is highly effective in maintaining gingival health and integrity where membranes are unavoidably exposed to the oral environment after placement, thereby promoting more predictable outcomes for a wider range of regenerative procedures in the mouth. RandD for this project falls along three lines: biologic development, membrane development, and in vivo testing. More specifically, we will 1) advance the prototype biologic used in phase 1 studies, 2) advance our chitosan membrane formulations to incorporate bioactivation with the most clinically appropriate handling characteristics, and 3) test the product candidates in animal models for efficacy. Toxicology and safety testing will be performed with the goal of having product candidate(s) ready for human clinical trials by the end of this phase 2 project. We expect this technology to improve success rates of oral bone regenerative procedures to treat periodontal disease, to place dental implants, and in cases where maxillofacial reconstruction is needed, therefore meeting patient needs and commercial needs in a large market. There is an absence in today's standard of care for bioactivated regenerative membranes and this proposed technology addresses that need with a rationally designed RandD plan with an understanding of the existing market, competitors, or potential partners. PUBLIC HEALTH RELEVANCE: Agenta is developing biologically enhanced regenerative membranes that are used in surgical procedures such as bone grafting. Bone regeneration is often necessary and critical to successful restoration of form and function in the mouth, and procedures called guided tissue regeneration using barrier membranes are essential to achieving optimal results. Whether restoring lost bone around teeth or implants, or in larger areas of the jaws affected by trauma or disease, too often there is inadequate gum tissue to cover the membranes and the graft sites which can lead to membrane exposure and procedural failure. Our data suggests that augmenting membranes made of chitosan (an excellent biodegradable material used in wound bandages) with our proprietary biologic improves gingival healing over exposed membranes in the mouth. Chitosan is a versatile, biocompatible, resorbable matrix with hemostatic and antimicrobial properties. Our goal is to provide chitosan with the additional biological advantage of enhancing wound closure with our proposed technology. We expect this technology to improve success rates of oral bone regenerative procedures to treat periodontal disease, to place dental implants, and in cases where maxillofacial reconstruction is needed, therefore meeting patient needs and commercial needs in a large market. There is an absence in today's standard of care for bioactivated regenerative membranes and this proposed technology addresses that need with a rationally designed RandD plan with an understanding of the existing market, competitors, or potential partners.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 421.26K | Year: 2007
DESCRIPTION (provided by applicant): The role of proteoglycans and carbohydrate polymers such as heparan sulfate in biological processes are becoming better understood, but this new frontier has only begun to be explored. Tissue regeneration is also an emerging frontier. This proposed research, when completed, will make an important contribution to both the proteoglycan and tissue regenerative fields, with a specific, clinical impact on periodontal regeneration. The objectives of this project are both scientific and developmental in nature. Scientific advancements in the structural and functional understanding of proteoglycans, such as Perlecan, are proposed, along with innovative studies investigating their role as therapeutics in bone healing. Site-directed mutagenesis to the Perlecan core will establish a valuable precedent. One of the major innovations of this technology is the ability to deliver DNA, not protein, to generate natural, endogenous Perlecan expression in the wounds or surgical sites. With this patented technology, a host-glycosylated Perlecan core will be generated in vivo, intended to promote vascularity, proliferation, and differentiation for enhanced healing. In addition to being highly cost-effective, this technology offers a low-cost alternative to the costly recombinant biologic adjuncts already in the marketplace. The development of a safe, effective, and useful product for periodontal bone regeneration is another important objective. Phase I support for this project enabled the creation of a prototype Perlecan expression construct for delivery of sequences encoding domain 1 (D1) of the core protein. In situ heparan sulfate glycosylation of the expressed core was validated, and new bone formation appeared to be enhanced by delivery of the Perlecan D1 expression construct in vivo. This Phase II project proposes to develop important modifications to the prototype Perlecan D1 expression construct, to identify other effective bone graft materials for co-delivery with the Perlecan D1 expression construct, and to test the Perlecan D1 expression construct in guided tissue regeneration. Structural modeling has allowed rational design for site-directed mutagenesis of the Perlecan D1 core sequence to increase glycosylation and enhance growth factor binding, while addition of a COOH-terminal tag on the prototype transgene will enhance development and characterization. Effective bone graft materials for co-delivery with the replication-defective adenovirus system, or with plasmid DNA in liposomes, will be identified from common bone graft materials or by copolymerization with resorbable poly D-lactide microparticles through an industry partnership. Periodontal regeneration in vivo will be assessed by radiographic and volumetric magnetic resonance imaging in a university collaboration, by histomorphometric analysis of new bone, new periodontal ligament, new cementum, and immunohistochemical measurement of osteocalcin at a 3 week and 12 week post-surgical time point. Expression of the Perlecan D1 transgene will be assessed locally and systemically while safety and toxicity of molecular Perlecan and heparan sulfate delivery is investigated.
Agenta Biotechnologies, Inc. | Date: 2011-12-22
A composition of exceptionally dense chitosan and a novel method for producing the dense chitosan structure have been described. The novel production method employs coincident compression and vacuum on a neutralized chitosan polymer that results in an exceptionally dense chitosan film or membrane material. The dense chitosan film or membrane composition possesses multiple physical and clinically appealing qualities for a variety of medical applications on or in animals, mammals, or humans.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 121.98K | Year: 2006
DESCRIPTION (provided by applicant): The project proposed by Agenta Biotechnologies, Inc. will produce diagnostic molecular tools to identify where destructive changes in skin, kidney, heart, eyes, bones, and other organs have occurred. These molecular probes do not exist and would be useful in several medical disciplines. The designed molecular probes may also have potential therapeutic value.