The “Hellstrom” Paradox”, Natur e, 1968; ? Anti-tumor T cells destroy tumor cells in vitro : The “Hellstrom-Schreiber” Paradox: -“ Equilibrium lesions ”(Nature, 2007) The Motivation: 1974, Moscow University In vivo tumor seems to be protected :
Some of the promising opportunities for Skolkovo Specific Examples…
S22-Fc - a multi-specific binder to EGFR, Her3 and Her2/neu Binding to T6-17 (Her2) and NE91(EGFR) cells by S22-Fc MCF7 NE91 T6-17 S22-Fc S22 Fc
“ Creation of a trivalent antibody like molecule with picomolar activity against EGFr, HER2/neu and HER3” The molecule is already fully “human” …; Has potential to help all HER+ breast cancer patients as compared with 25% for original herceptin Ab… as compared with Zero with no “old” herceptin. Is not it something that “ everybody wants and nobody has ”?
Generation of the BSI mAb library against native human plasma proteins using mAb proteomics (patent pending) Patent pending proteome normalization (10,000 mABs / experiment) No translation bottleneck Record speed form bench to market
Molecular Weight hGH ~ 3000 atoms Factor VIII ~ 55,000 atoms Need for Trials Biosimilars – Complexity leads to unknowns - If you don’t run trials – you won’t know the safety or efficacy Aspirin 21 atoms Complexity of biotech products IgG Antibody ~ 25,000 atoms 0 200,000 350,000 250,000 50,000 150,000 100,000 300,000 COOH OCOCH 3
Drug Discovery from Uncultur-able before Microorganisms ● 99% of all species of microorganisms on the planet do not grow in the lab ● Millions of new species, an enormous untapped resource for drug discovery ● A general method to grow uncultured microorganisms developed based on cultivation in situ in diffusion chamber and subsequent “domestication” for growth in the lab ● Growth factors for many uncultured species identified, an additional tool for growing them in the lab Patent: US 7,011,957 Kaeberlein et al., Science 296:1127-1129. Schumacher et al., 2009. Science 323:396-401. Dörr et al., PLoS Biol 8(2): e1000317. Lewis, K. 2007. Nature Rev. Microbiol. 5:48-56. D’Onofrio et al., 2010. Chem. & Biol. 17: 254–264.
Generation of the BSI mAb library against native human plasma proteins using mAb proteomics (patent pending) Plasma Normalization Patent pending Shotgun Immunization Library characterization screening mAb Production mAb microarray Production QuantiPlasma™ PlasmaScan™ Microarray Libraries >600 mABs “ 10 000 mABs” Plasma Collection Nascent library generation HT Hybridoma Cloning mAb validation ELISA Characterization mAb/epitope/protein ID
An Open Forum on the Scientific and Regulatory Issues of Biosimilars and Follow-on Biologics Boston, MA USA Copley Marriott Hotel Address by: Senator Edward Kennedy Chairman of the Senate Health, Education, Labor and Pensions Committee Plenary by: Dr. Randall Lutter Acting Deputy Commissioner for Policy, US FDA Organizing Chair: Prof. Barry Karger Director, Barnett Institute, and James L. Waters Chair, Northeastern University Hosted by: A high level meeting of the international biotechnology and generics industries, together with government regulators and academic laboratories, for an open forum and collegial debate on the scientific and regulatory issues in the introduction of generic complex biological drugs. www.barnett.neu.edu/biogenerics/ For additional information or to receive updates, email Biogenerics2008@neu.edu BIOGENERICS March 2-4, 2008