Executive Summary : | Objective: Making intravenous injectable proteins required lot of detailed and careful work-up, followed by prolonged regulatory body clearance. Unless these milestones are addressed, it is difficult to find serious partners for such technologies, especially if these are non-generic and novel. Keeping these things in mind following objectives have planned. Establishing Consistency in Process development and high grade purity optimization for animal toxicological studies.; Detailed physico chemical evaluation and stability studies for high grade protein preparation for animal models of toxicology and efficacy.; Efficacy evaluation of toxicological grade ACSSK in non-human primate model of MI and ischemic stroke by outsourcing the activity to obtain data to be submitted for regulatory clearances paving way for clinical trials/IND application to agencies such as DCGI, India/ EC/ USFDA. Summary: In myocardial infarction (heart attack) and particularly strokes, generally, thrombolytic proteins such as TPA are given for the clearance of artery blockages but, after therapy, reformation of clot at the same site is a major complication. Another common associated problem with FDA approved thrombus lysing agents is hemorrhage. To combat these clinically challenging problems novel EGF 4,5,6-streptokinase fusion construct was designed and expressed in yeast. Detailed scientific studies of recombinant protein suggest that it not only prevents in vitro/ex vivo re-occlusion but was also found safer in dose dependent fibrinogen protection assays clearly indicating a high order of fibrin specificity (see attached reprints/preprints). These properties address a clinically challenging problem, namely lack of clot specificity in streptokinase (both natural and recombinant), and the generation of serious blood brain barrier pathologies by TPA unless given in a very short (~2 h) window after ischemic stroke. A large scale high cell density fermentation for obtaining toxicological grade drug product, also suitable for human intravenous injection, which will help to treat the patients clinically, has already been standardized in the previous leg of this project under the FTC Program. |
