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GO pioneered the vision that natural evolution may have lead to the generation in the current population of unpredictable mutations that confer superior or novel therapeutic status to known human therapeutic proteins. In order to implement this vision, the company assembled a fully integrated functional genomics platform and proceeded to an extensive screening of the genomes of 278 individuals accounting altogether for 85% of the ethnic diversity of the human population. These genomes were screened for naturally occurring “functionally relevant” protein mutants in 115 genes coding for cytokines, growth factors, receptors and tyrosine kinases. Most inventive functionally relevant protein mutants were identified using a stringent screening procedure based on sophisticated bio-informatics including functional annotations, molecular modeling calculations, and prediction of mutations impact on host protein structure. |
In particular, significant changes in the 3-dimensional structure and in electrostatic isopotentials at the receptor binding surface of lead interferon alpha variants were identified. Expression and GLP production of selected protein variants were performed within the company, followed by extensive evaluation of their pharmacological properties by independent expert academic laboratories. Direct comparison was made between GO’s therapeutics and the reference “wild-type” proteins on the market in models of human infectious diseases and cancer diseases. A pipeline of 2 lead interferon alpha variants ready for progression to clinical trials plus 1 early lead erythropoietin alpha variant, has been generated for applications in respectively, immunotherapy, virology and anemia. GenOdyssee’s technology is protected by the international patent applications PCT/EP03/13695, EU 03 785 733, US 10/315,493, US 10/ 534,098. |
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GO assembled a genomic DNA bank representative of the human population that is screened for natural genetic variants of therapeutic proteins with superior therapeutic indices than the marketed versions of the same therapeutic proteins. The database, GenOdyBaseTM, contains 290 cytokine & growth factor protein variants from which 80+ lead candidates have been identified, 2 leads and one early lead have been selected for respectively, IND-enabling studies and further pre clinical testing.
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