002 Australian Taipan Snake Venom to Synthetic Oxynor for Wound Healing

At Ophidia Products, Inc. we have discovered Oxynor a synthetic therapeutic from snake venom for wound healing. The venom of Australian taipan snake ( Oxyuranus s. scutellatus ) is extremely potent due to the presence of taipoxin. The intact complex molecule of taipoxin having molecular weight 45.6 kDa is composed of three subunits α, β and γ. Fractionation of crude venom by High pressure chromatography (HPLC) using ion exchange column permits separation of the subunits. The mitogenic activity was revealed in non toxic β taipoxin. Non toxic β taipoxin showed mitogenic activity on variety of eukaryotic cells. Its activity as a mitogen extended to wound healing in experimental animals. We identified the active domain for wound healing in β taipoxin. after trypsin digestion were separated on HPLC, resolved into 11 different fragments. Each fragment was tested on PC12 cells to test mitogenic/neurotrophic activity. The fragment which showed the highest activity consisted of 21 amino acids. A synthetic peptide consisting of ten amino acids, from the N‐terminal –– was named Oxynor . Oxynor mimics the biological properties of natural β taipoxin when tested in vitro and in vivo systems. The biological results showed that Oxynor was not toxic at the concentration of 100 μg/ml for PC12 cells and 500 μg/adult mouse. Oxynor was mitogenic to various eukaryotic cells. Oxynor is neurotrophic showing neurite outgrowth on PC12 cells. Growth of human skin fibroblast cells indicates that Oxynor has keratinous activity. Experimentally produced 4 mm punched wounds on the back of mice were treated with β taipoxin 100 μg/mouse or Oxynor at 500 μg/mouse for seven consecutive days. The results showed complete closure of the wounds after six days while the wounds of control treated with PBS were open. Histology examination of the skin around the wounds revealed that treated mice showed re‐epithelization of the epidermis, which looked close to the normal mouse skin biopsy. Whereas the controls showed distortion of epithelium. β taipoxin and Oxynor were tested for in vivo at the concentration of 100 μg/ml in hydrogel vehicle applied once daily to help heal 6 mm ischemic skin wounds in rats. At days 7 and 14 wound treated with β taipoxin were about 15% smaller than the wounds treated with Oxynor. This shows that synthetic Oxynor is as efficacious as natural β taipoxin under the conditions of the test. On increasing the concentration of Oxynor to 500 μg/ml should give equivalent wound closure to 100 μg/ml of β taipoxin. In 1997 the US FDA approved for sale the first recombinant human platelet‐derived growth factor (rhPDGF) for treatment of human non‐healing wounds. Oxynor will be next therapeutic for wound healing Currently, Oxynor is in clinical trials, it has passed toxicity tests.