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Antigen and Antibody: Thirty Years of Basic Research Supported by Pharmaceutical Industry

Antigen and Antibody: Thirty Years of Basic Research Supported by Pharmaceutical Industry. Učená společnost ČR 20. May 2013 Ivan Lefkovits University Hospital Basel. This lecture will be about. a pharmaceutical company of 20 th century a research institute self non-self discrimination

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Antigen and Antibody: Thirty Years of Basic Research Supported by Pharmaceutical Industry

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  1. Antigen and Antibody: Thirty Years of Basic Research Supported by Pharmaceutical Industry Učená společnost ČR 20. May 2013 Ivan Lefkovits University Hospital Basel

  2. This lecture will be about • a pharmaceutical company of 20th century • a research institute • self non-self discrimination • monoclonal antibody • fame, success, Nobel prizes • a pharmaceutical company of 21st century • costs of developing a drug • new forms of supporting research

  3. Aim Knowledge Science Research & Development Support State (society, tax payers) Private institutions (industry) What is science? What is basic & applied research? What is research & development?

  4. Hoffmann-La Roche, Basel establishes the Basel Institute for Immunology Foundation stone April 1969 Opening of the Institute first part: October 1970 second half: April 1971

  5. Official communiqué from the President of Roche, Dr Adolf Jann (1969).

  6. the company is of the opinion that its significant position in the field of medical and biological research carries the obligation to further basic research correspondingly the company hopes to profit from the possibility that the presence of a highly qualified research group conducting fundamental research in academic freedom will provide new knowledge and stimulation to industrial research

  7. The Immune System Antibody Antigen

  8. ----------antibody & lymphocyte

  9. Human body 1012 1012 cells = 1 kg immune system

  10. Interaction of antibody with antigen antigen (key) antibody (lock)

  11. Antibody Antigen Repertoire Spectrum hundreds of millions hundreds of millions different specificities different bacteria, viruses, allergens, chemicals

  12. Antibody-forming plaque

  13. Self and non-self • Specificities that are against own body constituents • Specificities that are against pathogens, allergens and also against modified-self (cancer cells) during ontogeny the entire repertoire of specificities is created ANTI-SELF ANTI-FOREIGN

  14. Two most complex biological systems • Human brain 1kg • Immune system 1 kg • 1012 cells ---------------------------------------------- Common features: learning & memory

  15. Brain 1kg 1012 neurons and synapses Immune system 1kg 1012 lymphocytes and macrophages Two organs of learning and memory

  16. cell fusion (immortalization) • A cell producing specific antibody • Tumor cell with the ability to duplicate indefinitely + Sendai virus +

  17. cell fusion (immortalization) Result: hybridoma hybridoma cell line produces monoclonal antibody

  18. Monoclonal antibody (Georges Köhler)Generation of diversity(Susumu Tonegawa)

  19. Monoclonal antibody (mab) • Fusion of antibody forming cell with an “immortal” cancer cell • mouse mab • chimeric mab • “humanized” mab • human mab Fusion agent: Sendai virus, later PEG

  20. Success story? • Pharmaceutical company starts an Institute • Basic knowledge is acquired • 30 years of successful work • Fame, success, Nobel prizes • Side product: monoclonal antibody (mab) • At present the main revenue from mab

  21. Do we remember Roche products of the seventies? • Valium • Librium • Lexotanil • Marcoumar • Vitamin C • 5-fluorouracil These products are either not produced anymore, or were sold to other companies; whatever the case, they do not play any role in the main revenue of the company

  22. Roche in 21st century • is a leader in research-focused healthcare in pharmaceuticals and diagnostics. • is the world’s largest biotech company (oncology, infectious diseases, inflammation, metabolism and neuroscience). • is involved in in vitro diagnostics and tissue-based cancer diagnostics, and in diabetes management. • with personalised healthcare strategy aims at providing medicines and diagnostic tools for improvements in the health, quality of life and survival of patients.

  23. Roche, Genentech, Chugai • Roche has over 82,000 employees world-wide and invests over 8 billion CHF in R&D / year. • Sales of 45.5 billion CHF / year

  24. Roche • Herceptin • Kadcyla • Avastin • Perjeta • MabThera

  25. mab = monoclonal antibody • Herceptin (trastuzumab) • Kadcyla (trastuzumabemtansine) • Avastin (bevacizumab) • Perjeta (pertuzumab) • MabThera (rituximab) • GA101 (obinutuzumab) progression-free survival in patients with chronic lymphocytic leukemia (CLL)

  26. Jan Vilček (not Roche)mentioned here because of mab • Remicade: • rheumatoid arthritis, Crohn’s disease, ulceritive colitis, ankylosing spondylitis • Adalimumab • Golimumab

  27. The path from basics to a mab If you know the biochemical pathway you might identify the biomarker If you know the biomarker you might have a target If you have a target you might be successful in making monoclonal antibody

  28. Patent protection lasts 20 years • Original drug • Generic drug • Biosimilar (monoclonal antibodies) • Orphan drugs (7 years) • 1 drug in 5000 reaches the consumer

  29. 10,000 : 1

  30. Roche HER2-positive metastatic breast cancer • Breast cancer is the most common cancer among women worldwide. Each year about 1.4 million new cases are diagnosed, and over 450,000 women die of the disease annually. • When increased quantities of the human epidermal growth factor receptor 2 (HER2) are present on the surface of the tumour cells, one speaks about “HER2 positivity”. • HER2-positive cancer is a particularly aggressive form of breast cancer

  31. costs of developing a modern drug • 1,000.000.000 CHF • Yearly profit of 100.000.000 CHF has to be generated over a period of 10 years to get even

  32. 1,000.000.000 1,000.000.000 1,000.000.000 CHF CHF CHF costs for running BII for 30 years fine from a court (e.g. punishment for illegal price agreements) …..vitamins…. costs for developing a modern drug ….. mab …..

  33. Strategy of Roche

  34. New forms emerge (a) Pharmaceutical company supports university projects University research group with interesting “not-yet-products” form spin-off companies Venture capital invests in the small companies Pharma companies pick the “pearls”, buy them and continue with D

  35. New forms emerge (b) There is very little commitment towards direct support of institutes like BII R&D becomes very expensive (too small proportion enters into the product pipeline) Main emphasis on D Watching small companies and acquiring those with a promising product

  36. Acknowledgment to Hoffmann-La Roche, Basel for 30 years of unlimited support to 500 former members of BII throughout the existence of BII

  37. First class scientists attract first class scientistsSecond class scientists attract third class scientists

  38. Achievements of BII • Opportunity of doing science at highest level for some 500 scientist • Transfer of ideas and knowledge to over 300 institutions • Thousands of publications in high impact journals • Network of scientists persisting until these days

  39. Instruments from BII to AV

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