Boston Strategics Tapboost


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Enhanced Protein Production

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Boston Strategics Tapboost

  1. 1. Enhanced Protein Production TAPTAPBOOSTBOOST TM
  2. 2. Degradation RNA Gene Misfolding folding polypeptide Functional Aggregation Abnormal Function Unfolding Protein Response Secretion · Translation · Expression of Chaperones · Apoptosis Recombinant Proteins Protein Secretion Stability Functional Recombinant Proteins Immunogenicity Alzheimer's disease Parkinson's disease Huntington's disease etc. Impact of Protein Folding Conformational Diseases Protein Folding regulates many events in protein production
  3. 3. TAPBOOSTTM (Targeted Protein Boosting Technology) Proprietary sequence that facilitates protein production Binding domain specific for targeted protein BSC2 TAPBOOSTERTM BSC1 TAPBOOSTTM Technology TAPBOOSTERTM ER Targeted Protein Golgi
  4. 4. Insolubility of expressed proteins is, however, one of the biggest problems of Bacterial expression platforms TAPBOOOSTTM Technology significantly enhances solubility of expressed proteins. Bacterial Expression Platform Difficult-to-Express Protein Platform TAPBOOOSTTM Technology enhances active antibody production in mammalian expression platform. Market for therapeutic recombinant protein is huge (>$100 billions) with tremendous growth potential. However, difficulties in the production of therapeutic recombinant proteins make protein-based therapies the most expensive treatment in the world. Antibody Expression Platform TAPBOOSTTM Technology Bacterial Expression Antibody Expression Tough Protein Expression TAPBOOSTTM Technology (Targeted Protein Boosting Technology) TAPBOOSTTM Technology
  5. 5. Model Protein; IL-13 receptor α2 (IL13Rα2)-Fc fusion protein The expression levels of IL13Rα2 are poor, and the protein is prone to misfolding and aggregation. Cell IL13Rα2-Fc ERNu • The receptor of IL-13, a key mediator of allergic inflammation Aggregation of IL13Rα2-Fc Only properly folded IL13Rα2-Fc secrets • Fc fusion protein with sIL13Rα2 (sIL13Rα2-Fc) has been developed for the treatment of asthma • Production of sIL13Rα2-Fc using human cells is inefficient due to its instability • Soluble IL13Rα2 (sIL13Rα2) blocks the signal from IL-13 as a decoy receptor Difficult-to-Express Protein Expression Platform
  6. 6. Secreted IL13Rα2-Fc mock IL13Rα2-Fc Inside Cells mock TAPBOOSTTM enhances the production of IL13Rα2-Fc drastically Cell IL13Rα2-Fc ERNu Aggregation of IL13Rα2-Fc Cell TAPBOOSTTM Technology ERNu Secreted IL13Rα2-Fc IL13Rα2-Fc TAPBOOSTERTM Difficult-to-Express Protein Expression Platform mock TAPBOOSTTM >20x TAPBOOSTTM
  7. 7. Target Specificity of TAPBOOSTTM TAPBOOSTTM Technology TAPBOOSTERTM ER Targeted Protein Target Protein (A or B) A A A B B B B BTarget Protein
  8. 8. Model Protein; Factor VIII-Fc fusion protein • Factor VIII is the responsible protein for hemophilia A, disorder that causes serious bleeds and can lead to degenerative joint disease. • The primary treatment for hemophilia A is replacement therapy utilizing infusions of clotting factors, mainly Factor VIII. •Manufacture of Factor VIII is extremely difficult due to protein folding problem. Therefore, yields are low and often inconsistent. • The average annual cost for hemophilia treatment in 2008 was estimated at $155,000, with clotting factor concentrates accounting for 70-82% of total costs. Difficult-to-Express Protein Expression Platform
  9. 9. Target Protein; Factor VIII-Fc fusion protein TAPBOOSTTM enhances the production of Factor VIII-Fc drastically Difficult-to-Express Protein Expression Platform Foldinduction FVIII Production 0 2 4 6 8 10 12 14 16 18 20 FVIII-Fc TAPBOOSTTM Foldinduction FVIII Activity 0 2 4 6 8 10 12 14 16 18 20 22 24 FVIII-Fc TAPBOOSTTM
  10. 10. Antibody Expression Platform • Monoclonal antibodies are composed of heavy and light polypeptide chains bridged through disulfide bonds. Due to nature of this structural complexity, monoclonal antibodies are expressed in mammalian expression systems that could benefit from an increase in the yield of fully active antibodies • The combined sales of 25 actively marketed mAb therapeutics in 2010 was $43 billion. Brand Sales ($m) Market (%) Avastin 6973 16.02 Rituxan 6859 15.76 Humira 6548 15.04 Remicade 6520 14.98 Herceptin 5859 13.46 Lucentis 3106 7.14 Erbitux 1791 4.12 Tysabri 1230 2.83 Synagis 1038 2.38 Xolair 750 1.72 Sales of 10 actively marketed monoclonal antibody therapeutics in 2010 International Journal of Pharmaceutics (2013)
  11. 11. Antibody Expression Platform anti-IL8 Ab (DP12) TAPBOOSTTM enhances the production of all three tested antibodies 1 2 3 anti-VEGF Ab (Avastin) No antibody expressed antibody without TAPBOOSTTM 1 2 3 anti-TNFα Ab (Humira) 1 2 3 antibody with TAPBOOSTTM
  12. 12. Antibody Expression Platform anti-TNFα Ab (Humira) anti-VEGF Ab (Avastin) anti-IL8 Ab (DP12) 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8 Antibodies produced by TAPBOOSTTM hold the activity Foldinduction Avastin TAPBOOSTTM Foldinduction Foldinduction Humira TAPBOOSTTM DP12 TAPBOOSTTM
  13. 13. Bacterial Expression Platform Pharma Manufacturing (2012) Bacterial Expression Platforms Expression Systems used for Manufacture of Approved Drugs Major problem in Bacterial Expression System Soluble protein bacteria Bacterial Genome plasmid <Example of Insoluble Protein> Soluble Fraction Insoluble Fraction Expressed protein Mammalian E.coli S. cerevisiae (yeast) Direct synthesis in transgenic animals Other inclusion body
  14. 14. Bacterial Expression Platform Soluble protein (SP) Inclusion Body (IB) bacteria Bacterial Genome plasmid We customized TAPBOOSTTM technology for bacterial expression system by using a proprietary algorithms and intensive search for specific amino acid sequences involved in protein folding. SP IB TAPBOOSTTM Technology SP IB Test Protein A Test Protein B Test Protein C
  15. 15. Summary • Any kind of protein can be expressed by TAPBOOSTTM technology • Easy implementation into your current bioprocess • Combine TAPBOOSTTM with any other technology for synergistic effect Advantages of TAPBOOSTTM Increased Productivity by TAPBOOSTTM (%)Target proteins TNFRI-Fc (Enbrel) 600% Factor IX-Fc 320% Factor FVII-Fc 1000% IL13Rα2-Fc protein 2000% Factor VIII-Fc 2100% Humira (anti-TNFα antibody) Avastin (anti-VEGFa antibody) DP12 (anti-IL8 antibody) 600% 420% 730%