INSTITUTO BUTANTAN m 2

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1 NIT do

2 INSTITUTO BUTANTAN 1901 Established to produce serum against the bubonic plague Vital Brazil, first director, investigated antivenoms against snake bites m 2

3 INSTITUTO BUTANTAN 23 scientific labs - Scientific Development Division [16 Labs] - Biotechnology Center [3 labs] - Applied Toxinology Special Lab LETA [4 labs] Hospital Vital Brazil [10 beds] Central Animal Facility 180 PhD researchers 500 graduated students more than 200 published articles citations in 2013 Programs of Scientific Initiation Training Programs University Extension Courses Graduated studies in Toxinology MBA in Innovation Graduated inter-unities studies in Biotechnology [University of São Paulo, Institute for Technological Research, Instituto Butantan] Source: Instituto Butantan; ISI web of science

4 INSTITUTO BUTANTAN 7 plants Anaerobic vaccines - Tetanus and Botulism Bacterial Purification Center Aerobic Vaccines - Diphtheria and Pertussis Hepatitis Influenza Rabies Serums 1 Formulation and Filling Center 6 pilot plants Dengue Rotavirus Recombinant BCG Monoclonal antibodies Influenza - H5N1 Blood products

5 PORTFOLIO OF SERUM 13 immunoglobulins 400,000 vials/year 5 snake antivenoms Diphtheria antitoxin Spider antivenom Tetanus antitoxin Botulism AB antitoxin Scorpion antivenom Botulism E antitoxin Caterpillar antivenom Rabies immunoglobulin

6 PORTFOLIO OF VACCINES 6 vaccines of the national calendar 150 million doses per year DTP Diphtheria-Tetanus-Pertussis (celular) dt Diphtheria-Tetanus (for adults) DT Diphtheria-Tetanus (for children) Rabies Hepatitis B Influenza

7 PARTNERSHIPS Harvar d

8 TTO Instituto Butantan s TTO was established in Pertussis low 1 patent Classification Number vaccine 12 serum 3 immunotherapy 3 coagulant 2 analgesic 2 peptide 2 tissue regeneration 2 anti cancer 1 antibodies 2 other* 11 total 40 * other includes: proteins from Leptospira, spider proteins, DNA of S. mansoni, crotamine, kit and composition, recombinant protein for diagnosis, etc. Lopap 4 patents Biolab Sílica (SBA-15) 1 patent Cristália Amblyomin-X 1 patent União Química Ind. Farmacêutica

9 SOME TECHNOLOGIES

10 TETRAVALENT VACCINE: DTP+PNEUMONIAE Priority application number: PI ; Priority data: 28 september 2010; Title: Synergistic immunogenic compositions based on protein antigens combined with pertussis cell antigen and inactivated toxins; Geographical coverage: Brazil and United States of America; Abstract: Pneumococcal surface protein A (PSPA) is an antigen for the composition of protein-based vaccines against Streptococcus pneumoniae. The successfully addition of pneumococcal protein in to pertussis whole cell vaccine was demonstrated. We propose a tetravalent vaccine DTP + PSPA. We are developing pnemococcal antigens for the conjugation. More info: nit@butantan.gov.br

11 BCG RECOMBIANT VACCINE Priority application number: BR ; Priority data: 17 february 2012; Title: Recombinant mycobacterium bovis bacillus calmette guerin (BCG) strain, immunogenic composition and use; Geographical coverage: Brazil, United States of America, Europe, China, India and South Africa; Abstract: Production of a recombinant vaccine for prevention against tuberculosis and infections caused by Mycobacterium. Results have demonstrated that the protection is enhanced three times. We have already done concept proofs. More info: nit@butantan.gov.br

12 ANTI-DIGOXIN MONOCLONAL ANTIBODY Priority application number: BR ; Priority data: 15 june 2012; Title: Method for producing and obtaining variable domains of anti-digoxin monoclonal antibody FAB fragment using the molecular biology cloning technique; Geographical coverage: Brazil and PCT Abstract:Monoclonal antibody produced by phage display technology that works as an antidote and is used in the treatment of patients with lifethreatening or potentially life-threatening digoxin toxicity or overdose. This antibody is not produced in animals. It is in scaling up process of development. More info:

13 THANK YOU! Luciana Akissue de C. Teixeira Coordinator of Instituto Butantan s TTO 55 (11) luciana.teixeira@butantan.gov.br