1. Patent issue

3. Discovery of a new aspect of TNF-α-related signaling • Currently known to causes apoptotic cell death, cellular proliferation, differentiation, inflammation, and viral replication promoting various aspects of immunity and inflammation • High level of TNF-α induces the inflammatory response, which in turn causes many of the clinical problems associated with autoimmune disorders such as rheumatoid arthritis • Reduction in the level of TNF-α new therapeutics to treat autoimmune disease like rheumatoid arthritis

4. Neutralizing the biological effects of TNF-α in situations where over-expression of TNF-α causes negative clinical effects • Soluble forms of TNF receptor : trapping TNF-α in blood  Reduce the severity of many diseases caused by high level of TNF-α • Enbrel : TNF-α blocker approved for medical use - Developed by Immunex and approved by FDA in 1998 - Amgen acquired Immunex in 2002 - Engineered hybrid protein consisting of the extracellular domain of the TNF-α-R75 fused directly to the Fc region of human IgG - Dimeric soluble protein TNF-Receptor Fc

5. Most widely used for treatment of disorders caused by excess TNF-α - Rheumatoid arthritis, psoriasis, ankylosing spondylitis, psoriatic arthritis, and juvenile rheumatoid arthritis. - Administered as a twice weekly via subcutaneous injection (25 in WFI) - Annual sale : $ 4.5 billion in 2010 • Competitors : Humira, Remicade (Monoclonal Ab) • Development of new version with greater potency - Protein engineering : structure-based rational design - Increased affinity /specificity - Stability in blood