The ideal attributes of a drug delivery system for biologics would combine the ability to effectively provide therapeutic doses of unmodified proteins with safety. There are multiple requirements for use in all organs. The biologics must have:
- The ability to be fully resorbable
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No acid burst or other unsafe excipients or byproducts
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Concentration equivalence of over 100 mg/ml
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pH to be physiological (7.0 to 7.8 pH)
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280 to 360 mOsmol/l
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Release kinetics controlled for up to 6 months
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The ability to provide an initial bolus or fully linear release
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The ability to be injected as a clear or colored gel
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The ability to be injected as a pellet or rod
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The capability to work with all classes of large molecule biologics
TheraKine has successfully demonstrated a system with all of the attributes listed above using monoclonal antibodies selected for the OptiKine™ project. OptiKine™’s system packages and stabilizes the antibodies with an effective concentration in excess of 200 mg/ml, and TheraKine has demonstrated the ability to adjust the release kinetics from 24 hours to multiple months.
This microscope image shows microspheres of monoclonal antibody at 227 mg/ml concentration, ready for delivery. The system is cryo safe and process methods are robust.
Bioavailability after resuspension of the cryopreserved drug has been shown in a biologic assay test. In December 2008, Bioavailability Testing for OptiKine™ was completed. The OptiKine™ formulation was compared with the commercial antibody used for the demonstration, with results showing equivalent bioavailability. This project is now moving into final pre-clinical development with first human use for inflammatory eye diseases set to take place in 2010.
To our knowledge, TheraKine is the first Biotech company to:
- Achieve biopolymerisation of complex proteins and antibodies, and concentrate them to high levels.
- Cryoprecipitate (freeze dry) the resulting complex, rendering them suitable for long-term storage, while maintaining a high bioavailability. This is critical for any future clinical application.
- Demonstrate that the rehydrated complexes release the antibodies over time with full bioavailability.
- Achieve al this without any chemical or structural changes needed for, or resulting from, complexation. During this process, the monoclonal antibody remains unchanged.