Antibody Engineering & Therapeutics 2013: Monday's Recap

We began our day off with the presentation 10 A Systems Approach to Studying Disease Enabled by Emerging Technologies from Leroy Hood, M.D., Ph.D., President, Institute for Systems Biology.  He shared that the four challenges of drug discovery are :

• -diagnosis of disease
• -stratification of disease
• -identification of drug targets and
• -making the drug

He also shared that he views systems medicine as the ability to Transform data into useful insights by creating a network of networks. In disease – it alters the system of systems. If it can be captured – there can be new approaches to identifying the disease.

Some of his key strategies for systems medicines are:

• -A systems driven approach to blood diagnostics – making a blood window to health and disease
• -Development to induced pluripotent system cells
• -Systems strategies for disease stratification

Organ specific proteins can reflect what’s happening within an organ. Different combinations have different amounts of proteins. There are 200 proteins that are mapped back to the disease states.

When looking to the future, next generation strategy for diagnostics: assessment will begin with looking at whether a person is well or sick? If a person is sick, what organ is affected? Then identify the disease affecting the organ.  Finally, identify the level the disease has progressed to.  Disease stratification is key for successful disease detection.  The futuristic approach is to focus on wellness.  This opens up opportunity for advanced physiology.

Systems medicine has reached a tipping point and will change the practice of healthcare.

David Baker, Ph.D., Professor of Biochemistry, University of Washington was also on of our keynotes this morning.  He presented Towards Computer Based Design of Smart Protein Therapeutics.  Protein sequence design model can predict the structure. They have a program were volunteers help test sequence design. Scientists can then see if the desired target structure is actually what they want. Structures can be designed accurately with this approach. The program is called Fold it Symmetric Design – and it's where a global collection of intellect for people around the world to design the proteins.

During the keynote presentation Epitope-focused Immunogen Design, William Schief, Ph.D of the The Scripps Research Institute looked at the current licensed vaccines that made up the United States of classical vaccine strategies.  These include live viruses, live-attenuated viruses, whole inactive viruses and sub-unit vaccines. There are also bacterial vaccines. Diseases that are potential vaccine protected cause 18.5% of all human deaths.

Now, we look specifically at HIV and the need to develop a vaccine.   The goal of a vaccine is to get the body to produce antibodies that neutralize viruses in the body. One of the challenges for vaccines is for the immune system to stay ahead of the virus.

Classical strategies for vaccine design won’t work for HIV or a universal flu vaccine. If you have an infectious disease already hosted in individuals, you can get the protective antibodies from those infected individuals. Then that information can be used to develop immunogens that will make a vaccine that works. One of the keys to success is to start with antibodies that human systems can actually make.

One of the key takeaways from the Site Specific ADC Generation Using SMARTAG™ Technology session from David Rabuka, Ph.D., Chief Scoience Officer, Redwood Bioscience was his identificaiton of Limitations of Conventional ADC Technology:

1. 1) Toxicity – aggregation and first pass metabolism in liver
2. 2) Variable potency – uncontrolled payload loading, PK liability
3. 3) Manufacturing -- Lack of lot to lot reproducibility, complex manufacturing, challenging analytics

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