Download Patent issue Currently known to causes apoptotic cell death, cellular

Patent issue
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
 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
 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