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O modelo de inovação do Instituto
Butantan
22 a 24 de outubro de 2012
Inovação Tecnológica em Saúde
Dr. Marcelo de Franco – Diretor Substituto
Instituto Butantan |
 Em 1901 o Butantan foi fundado para produzir soros contra a peste bubônica
 Vital Brazil, primeiro diretor, desenvolveu estudos e pesquisas contra picadas de
cobras e antivenenos
 O Butantan é um dos principais produtores público de vacinas, antivenenos e
antitoxinas da América Latina
 Totalmente dedicado a desenvolver pesquisas científicas e a produção de produtos
biológicos de valor agregado para a saúde pública
BUTANTAN – UMA INSTITUIÇÃO PÚBLICA DO GOVERNO DE ESTADO DE SÃO PAULO
1
Instituto Butantan |
MACRO ESTRUTURA ORGANIZACIONAL
AREAS FINS DO INSTITUTO BUTANTAN
2
 ~ 1.700 Funcionários diretos
 Funcionários Públicos ~770 (45%)
 Funcionários Fundacionais ~932 (55%)
 ~ 100 funcionários terceirizados
Instituto Butantan
Diretoria
Produção
(Vacinas e Soros)
Demais
Áreas
Desenvolvimento
Científico &
Pesquisa
Centro Cultural
Áreas fins
Fundação Butantan
Apoio
Fonte: Butantan, Junho, 2012
Instituto Butantan |
COMPLEXO INDUSTRIAL
3
 7 Grandes Fábricas (Prédios)
 Vacinas anaeróbicas (tétano, botulínico
e Purificação)
 Vacinas aeróbicas (Difteria e Pertussis)
 Hepatite
 Influenza
 Raiva
 Hemoderivados
 Controle, Soros e Formulação & Envase
 6 Plantas Pilotos
 Dengue / Rotavírus (Em Construção)
 Recombinantes (BCG)
 Monoclonais
 Influenza
 Hemoderivados
Instituto Butantan |
MUSEU HISTÓRICO
MUSEU DE MICROBIOLOGIA
MUSEU BIOLÓGICO
TRANSFERÊNCIA DE CONHECIMENTO PARA A SOCIEDADE
4
 4 MUSEUS
 ~300 K visitantes/ano
 Parque com 80 hectares
 Área verde preservada
Instituto Butantan |
LABORATÓRIOS DE PESQUISA & DESENVOLVIMENTO
5
 ~21 laboratórios científicos
 ~180 Pesquisadores
 85% são doutores
 1 Centro de Biotecnologia
 Vários laboratórios
 1 Hospital (10 leitos)
 1 Biotério Central
 Programas de estágio (PAP)
 Pós-graduação em Toxinologia
 Mestrado e doutorado
Instituto Butantan |
0
50
100
150
200
250
0
500
1000
1500
2000
2500
1980 1985 1990 1995 2000 2005 2010
sum of times cited (TOTAL)
Papers Published
Polinômio (sum of times cited (TOTAL))
Exponencial (Papers Published)
PUBLICAÇÕES CIENTÍFICAS INDEXADAS
Publicações e Citações
6
Instituto Butantan |
 ANALGÉSICOS
 ANTI-INFLAMATORIOS
 ANTIMICROBIOLOGICOS
 ANTICOAGULANTES
 ANTITUMORAIS
 AÇÃO NO SISTEMA NERVOSO
 ANTIVENENOS
 ANTIHIPERTENSIVOS
Composição de Venenos
(Transcriptomics and Proteomics)
Atividades Farmacológicas
TRIAGEM DE COMPONENTES BIOATIVOS DE ANIMAIS VENENOSOS
7
Instituto Butantan | 8
Projects - Butantan (2012)
Nº Project Description Phase Partnership Patent
1
Hemoderivatives
Production of IgG, factor VIII, IX, Albumine
and other proteins
construction of the facility GE
2 Dengue vaccine
Tetravalent (sorotypes DEN1, DEN2, DEN3,
DEN4) with attenuated virus
phase II NIH/DVI/BNDE
S/FAPESP
3
Rotavirus
vaccine
Pentavalent (sorotypes G1, G2, G3, G4, G9)
with attenuated virus
phase II NIH/PATH/BND
ES
4
Pertussis low
vaccine
B. pertussis whole cell with lower content of
LPS
phase I NIV PI0402630-6 (2004)
5
Adjuvant
BpMPLA
BpMPLA derived from LPS of B.pertussis
and utilization as adjuvant in influenza
vaccine
scale up PI0721393-0 (2007)
6
Recombinant
BCG-Pertussis
Vaccine for neonates and for bladder cancer
treatment
GMP production
Hospital
Oswaldo Cruz
PI0904468-0 (2009)
7
BCG-Pertussis
+ Hep B
Vaccine for neonates associated with
Hepatitis B
GMP production
8
Monoclonal
Antibodies
Anti-human CD3 pilot production InCor
Principais Projetos Instituto Butantan
Instituto Butantan | 9
Projects - Butantan (2012)
Nº Project Description Phase Partnership Patent
9
DTPlow-HepB-
Hib (Pentavalent
vaccine)
Pentavalent vaccine for the MoH
Scale up of conjugation
process for Hib
Biomanguinhos
10
DTPlow-HepB-
Hib-IPV-MenC
Heptavalent vaccine for the MoH análise de conjugação Biomanguinhos
11 Hepatitis B
Hepatitis B vaccine for > 50 years old and
imunodefficience people
phase IV
12
Leptospira
vaccine
Purified recombinant protein of Leptospira
expressed in Escherichia coli strain
Identification of antigen USPTO 60/360,566 (2002)
13 Lung surfactant Industrial production of the surfactant
Licensed in Brazil
(2009)
BR Foods
14 Silica (SBA-15)
Immunogenic complex formed by vaccinal
antigens encapsulated by nanostructured
mesoporous silica (Adjuvant and vaccinal
antigens)
Pre-clinical studies FAPESP/Labora
tórios Cristália
PI0503817-0(2005)
15 Amblyomin-X Anti-cancer from Amblyomma cajennense Scale up
FAPESP/União
Química/BNDES
PI0406057-
1(2004)/PCT/BR2008/000078
16 Crotalphine
Potent analgesic drugs from animal
venoms and toxins. Long-lasting analgesic
action (2-5 days)
Research
FAPESP/
Biosintética
Farmacêutica
PCT/BR 2005/000073
Principais Projetos Instituto Butantan
Instituto Butantan | 10
Nº Project Description Phase Partnership Patent
Soluble proteins from Lonomia obliqua:
Prothombin Activator Research PI0200269-8 (2002)
Recombinant molecule and its use as
defibrinogenating/antithrombotic agent
Research PCT/BR2005/000171
Anti-apoptotic activity and pharmaceutical
formulations
Research
FAPESP/Biolab
Sanus
Farmacêutica
PI0504199-6 (2005)
Peptides capable of stimulating production
of extracellular matrix (ECM) proteins in
cells (e.g., fibroblasts), and hence can be
utilized as a generating agent for tissue and
skin, as well as utilized as a cosmetic.
Research
FAPESP/Biolab
Sanus
Farmacêutica
USPTO61/022,747 (2008)
18
Haemophilus
influenzae b
Innovative conjugation method for the
polysacharide antigen and the carrier protein
resulting in higher yield.
Research Butantan
19 Crotamine
Treatment of dysfunctions based on its
property of interaction with genetic materials,
such as DNA and RNA, and its celular
selectivity
Research Butantan PI0501037-3 (2005)
20 Pneumococcal
Inactivated non-encapsulated pneumococcal
whole cell
phase I Harvard/PATH
21
Necator
Schistossoma
Cloning, expression and purification of
recombinant proteins from E.coli and Yeast
Research
Sabin
Vaccine/George
Washington
University
22
Bee's
antivenom
Bee's antivenom Research PI0804652-2 (2008)
23
Canine's
Leishimaniose
Vaccine against leishimaniose for use in
dogs
pilot production UFMG
Projects - Butantan (2012)
Lopap
17
Principais Projetos Instituto Butantan
Instituto Butantan |
Modelo Inovação Instituto Butantan
11
Fonte: Chesbrough, Henry. Open Innovation Models
O ponto forte
do IB!
• Incorporação
cultura
pesquisa
aplicada
Instituto Butantan |
Modelo Inovação Instituto Butantan
12
Fonte: Chesbrough, Henry. Open Innovation Models
Estabelecer
parcerias (públicas,
privadas, fomento),
para viabilizar os
projetos e cumprir
missão IB:
Instituto Butantan | 13
Missão IB
Desenvolver pesquisas e produtos que
contribuam para o acesso à saúde,
compartilhando conhecimento com a sociedade
Instituto Butantan |
Modelo Inovação Instituto Butantan
14
Fonte: Chesbrough, Henry. Open Innovation Models
Estabelecer
parcerias (públicas,
privadas, fomento),
para viabilizar os
projetos e cumprir
missão IB:
• Incorporação
tecnologia
(Influenza –
Sanoffi Pasteur),
com proposta
melhoria (MPLA);
• Licenciamento
tecnologias (em
andamento).
Instituto Butantan | 15
Implantação NIT IB
•Importância implantação NIT, publicação Resolução SS-53, de 10/05/12;
•Órgão que fará a gestão da inovação da Instituição;
•Garantirá que estes processos aconteçam.
Instituto Butantan | 16
Patents
PATENTS BY SUBJECT
SUBJECT Nº
VACCINES 12
SERUMS 3
AMBLYOMMA CAJENNENSE 2
LOPAP 3
CROTAMINE 1
MAB 1
LEPTOSPIRA 10
ANALGESIC COMPOUNDS 1
ANTIBACTERIAL AS ANTI-CONVULSIVANT 1
IMMUNOTHERAPEUTIC 2
PEPTIDES 4
STEM CELLS 2
OTHERS 10
TOTAL 52
Instituto Butantan |
IMMUNOGENIC COMPLEX FORMED BY VACCINAL ANTIGENS ENCAPSULATED BY
NANOSTRUCTURED MESOPOROUS SILICA
PI 0503817-0, 12/09/2005
PATENTS
17
• Adjuvant (solid particles of highly ordered nanostructured mesoporous
silica) and vaccinal antigens;
• Presentation of the antigens in a safe, gradual and prolonged manner;
• Immunological memory more efficient;
• Increase of the immunogenicity of the antigen;
• Improvement in antibody production;
• Immune protection efficiently with lower amounts of antigens or less
repeats;
Instituto Butantan | 18
PATENTS
PROCESS FOR OBTENTION OF NEW CELLULAR PERTUSSIS VACCINE
• Less toxic;
• As potent as
B. pertussis
fermentation Tangential
Filtration or Molecular
ultrafiltration?
WCP
Organic
extraction
WCPLow
PI 0402630-6, 05/07/2004
WO/2006/002502, 12/01/2006
MPLA
Adjuvant
PI 0721393-0, 22/03/2007
WO/2008/134830, 13/11/2008
Clinical Trials
2007
Infants
Acellular
Pertussis
Vaccine
PI 0202458-6, 13/06/2002
Adolescents
Recombinant BCG-Pertussis
Immunization at birth
Under GMP production
Clinical Trials
Neonates
Patent
Instituto Butantan |
RECOMBINANT PROTEASE PROTHROMBIN ACTIVATOR (LOPAP)
PI 0200269-8, 31/01/2002
PI 0403882-7, 24/08/2004
PI 0504199-6, 08/09/2005
• Prothrombin activator;
• Defibrinogenating/antithrombotic agent;
• Kit for diagnosis of dysprothrombinemias;
• Anti-apoptotic activity.
Lonomia obliqua
19
PATENTS
FAPESP, BIOLAB SANUS FARMACÊUTICA
Instituto Butantan |
KUNITZ-TYPE RECOMBINANT INHIBITOR, AMBLYOMIN – X, OBTAINED FROM
SALIVARY GLANDS OF THE AMBLYOMMA CAJENNENSE
PI 0406057-1, 15/09/2004
WO/2008/109976, 18/09/2008
• Anticoagulant activity;
• Apoptotic activity in tumor cells;
• Anti-metastatic activity of melanoma tumor;
• Anti-cancer activity;
• Utilization of the recombinant in different hemostatic mechanisms.
Amblyomma cajennense
20
PATENTS
FAPESP, UNIÃO QUÍMICA FARMACÊUTICA
Instituto Butantan |
Crotalphine
Potent analgesic drugs from animal venoms and toxins
21
Venom of
Potent analgesic
long-lasting analgesic action
(2-5 days)
Crotalphine
Molecular mechanisms involved in
the analgesic action
release of
endogenous
opioids
Activation of peripheral  and 
opioid receptors
intracellular
signaling
pathways
activation
Activation of NO-cGMP-PKG
and opening of potassium
channels
Recent studies show involvement of PKC
which activates MAPKs
(Mechanism that may contribute to its long-lasting
analgesic action)
Activation of CB2 cannabinoid
receptors
Crotalus
PATENTS
Instituto Butantan | 22
PATENTS
USE OF CROTAMINE, KIT AND COMPOSITION
PI 0501037-3, 18/03/2005
WO/2006/096953, 21/09/2006
• Interaction with genetic material;
• Transport of molecules to the surface, cytoplasm or cell nucleous;
• Selective cell penetration;
• Use for the treatment of diseases and dysfunctions.
Instituto Butantan | 23
Av. Vital Brasil, 1500 - Butantã
São Paulo – SP
CEP - 05503-900
(11) 3726.7222
www.butantan.gov.br
OBRIGADO!

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Dr. marcelo de_franco

  • 1. O modelo de inovação do Instituto Butantan 22 a 24 de outubro de 2012 Inovação Tecnológica em Saúde Dr. Marcelo de Franco – Diretor Substituto
  • 2. Instituto Butantan |  Em 1901 o Butantan foi fundado para produzir soros contra a peste bubônica  Vital Brazil, primeiro diretor, desenvolveu estudos e pesquisas contra picadas de cobras e antivenenos  O Butantan é um dos principais produtores público de vacinas, antivenenos e antitoxinas da América Latina  Totalmente dedicado a desenvolver pesquisas científicas e a produção de produtos biológicos de valor agregado para a saúde pública BUTANTAN – UMA INSTITUIÇÃO PÚBLICA DO GOVERNO DE ESTADO DE SÃO PAULO 1
  • 3. Instituto Butantan | MACRO ESTRUTURA ORGANIZACIONAL AREAS FINS DO INSTITUTO BUTANTAN 2  ~ 1.700 Funcionários diretos  Funcionários Públicos ~770 (45%)  Funcionários Fundacionais ~932 (55%)  ~ 100 funcionários terceirizados Instituto Butantan Diretoria Produção (Vacinas e Soros) Demais Áreas Desenvolvimento Científico & Pesquisa Centro Cultural Áreas fins Fundação Butantan Apoio Fonte: Butantan, Junho, 2012
  • 4. Instituto Butantan | COMPLEXO INDUSTRIAL 3  7 Grandes Fábricas (Prédios)  Vacinas anaeróbicas (tétano, botulínico e Purificação)  Vacinas aeróbicas (Difteria e Pertussis)  Hepatite  Influenza  Raiva  Hemoderivados  Controle, Soros e Formulação & Envase  6 Plantas Pilotos  Dengue / Rotavírus (Em Construção)  Recombinantes (BCG)  Monoclonais  Influenza  Hemoderivados
  • 5. Instituto Butantan | MUSEU HISTÓRICO MUSEU DE MICROBIOLOGIA MUSEU BIOLÓGICO TRANSFERÊNCIA DE CONHECIMENTO PARA A SOCIEDADE 4  4 MUSEUS  ~300 K visitantes/ano  Parque com 80 hectares  Área verde preservada
  • 6. Instituto Butantan | LABORATÓRIOS DE PESQUISA & DESENVOLVIMENTO 5  ~21 laboratórios científicos  ~180 Pesquisadores  85% são doutores  1 Centro de Biotecnologia  Vários laboratórios  1 Hospital (10 leitos)  1 Biotério Central  Programas de estágio (PAP)  Pós-graduação em Toxinologia  Mestrado e doutorado
  • 7. Instituto Butantan | 0 50 100 150 200 250 0 500 1000 1500 2000 2500 1980 1985 1990 1995 2000 2005 2010 sum of times cited (TOTAL) Papers Published Polinômio (sum of times cited (TOTAL)) Exponencial (Papers Published) PUBLICAÇÕES CIENTÍFICAS INDEXADAS Publicações e Citações 6
  • 8. Instituto Butantan |  ANALGÉSICOS  ANTI-INFLAMATORIOS  ANTIMICROBIOLOGICOS  ANTICOAGULANTES  ANTITUMORAIS  AÇÃO NO SISTEMA NERVOSO  ANTIVENENOS  ANTIHIPERTENSIVOS Composição de Venenos (Transcriptomics and Proteomics) Atividades Farmacológicas TRIAGEM DE COMPONENTES BIOATIVOS DE ANIMAIS VENENOSOS 7
  • 9. Instituto Butantan | 8 Projects - Butantan (2012) Nº Project Description Phase Partnership Patent 1 Hemoderivatives Production of IgG, factor VIII, IX, Albumine and other proteins construction of the facility GE 2 Dengue vaccine Tetravalent (sorotypes DEN1, DEN2, DEN3, DEN4) with attenuated virus phase II NIH/DVI/BNDE S/FAPESP 3 Rotavirus vaccine Pentavalent (sorotypes G1, G2, G3, G4, G9) with attenuated virus phase II NIH/PATH/BND ES 4 Pertussis low vaccine B. pertussis whole cell with lower content of LPS phase I NIV PI0402630-6 (2004) 5 Adjuvant BpMPLA BpMPLA derived from LPS of B.pertussis and utilization as adjuvant in influenza vaccine scale up PI0721393-0 (2007) 6 Recombinant BCG-Pertussis Vaccine for neonates and for bladder cancer treatment GMP production Hospital Oswaldo Cruz PI0904468-0 (2009) 7 BCG-Pertussis + Hep B Vaccine for neonates associated with Hepatitis B GMP production 8 Monoclonal Antibodies Anti-human CD3 pilot production InCor Principais Projetos Instituto Butantan
  • 10. Instituto Butantan | 9 Projects - Butantan (2012) Nº Project Description Phase Partnership Patent 9 DTPlow-HepB- Hib (Pentavalent vaccine) Pentavalent vaccine for the MoH Scale up of conjugation process for Hib Biomanguinhos 10 DTPlow-HepB- Hib-IPV-MenC Heptavalent vaccine for the MoH análise de conjugação Biomanguinhos 11 Hepatitis B Hepatitis B vaccine for > 50 years old and imunodefficience people phase IV 12 Leptospira vaccine Purified recombinant protein of Leptospira expressed in Escherichia coli strain Identification of antigen USPTO 60/360,566 (2002) 13 Lung surfactant Industrial production of the surfactant Licensed in Brazil (2009) BR Foods 14 Silica (SBA-15) Immunogenic complex formed by vaccinal antigens encapsulated by nanostructured mesoporous silica (Adjuvant and vaccinal antigens) Pre-clinical studies FAPESP/Labora tórios Cristália PI0503817-0(2005) 15 Amblyomin-X Anti-cancer from Amblyomma cajennense Scale up FAPESP/União Química/BNDES PI0406057- 1(2004)/PCT/BR2008/000078 16 Crotalphine Potent analgesic drugs from animal venoms and toxins. Long-lasting analgesic action (2-5 days) Research FAPESP/ Biosintética Farmacêutica PCT/BR 2005/000073 Principais Projetos Instituto Butantan
  • 11. Instituto Butantan | 10 Nº Project Description Phase Partnership Patent Soluble proteins from Lonomia obliqua: Prothombin Activator Research PI0200269-8 (2002) Recombinant molecule and its use as defibrinogenating/antithrombotic agent Research PCT/BR2005/000171 Anti-apoptotic activity and pharmaceutical formulations Research FAPESP/Biolab Sanus Farmacêutica PI0504199-6 (2005) Peptides capable of stimulating production of extracellular matrix (ECM) proteins in cells (e.g., fibroblasts), and hence can be utilized as a generating agent for tissue and skin, as well as utilized as a cosmetic. Research FAPESP/Biolab Sanus Farmacêutica USPTO61/022,747 (2008) 18 Haemophilus influenzae b Innovative conjugation method for the polysacharide antigen and the carrier protein resulting in higher yield. Research Butantan 19 Crotamine Treatment of dysfunctions based on its property of interaction with genetic materials, such as DNA and RNA, and its celular selectivity Research Butantan PI0501037-3 (2005) 20 Pneumococcal Inactivated non-encapsulated pneumococcal whole cell phase I Harvard/PATH 21 Necator Schistossoma Cloning, expression and purification of recombinant proteins from E.coli and Yeast Research Sabin Vaccine/George Washington University 22 Bee's antivenom Bee's antivenom Research PI0804652-2 (2008) 23 Canine's Leishimaniose Vaccine against leishimaniose for use in dogs pilot production UFMG Projects - Butantan (2012) Lopap 17 Principais Projetos Instituto Butantan
  • 12. Instituto Butantan | Modelo Inovação Instituto Butantan 11 Fonte: Chesbrough, Henry. Open Innovation Models O ponto forte do IB! • Incorporação cultura pesquisa aplicada
  • 13. Instituto Butantan | Modelo Inovação Instituto Butantan 12 Fonte: Chesbrough, Henry. Open Innovation Models Estabelecer parcerias (públicas, privadas, fomento), para viabilizar os projetos e cumprir missão IB:
  • 14. Instituto Butantan | 13 Missão IB Desenvolver pesquisas e produtos que contribuam para o acesso à saúde, compartilhando conhecimento com a sociedade
  • 15. Instituto Butantan | Modelo Inovação Instituto Butantan 14 Fonte: Chesbrough, Henry. Open Innovation Models Estabelecer parcerias (públicas, privadas, fomento), para viabilizar os projetos e cumprir missão IB: • Incorporação tecnologia (Influenza – Sanoffi Pasteur), com proposta melhoria (MPLA); • Licenciamento tecnologias (em andamento).
  • 16. Instituto Butantan | 15 Implantação NIT IB •Importância implantação NIT, publicação Resolução SS-53, de 10/05/12; •Órgão que fará a gestão da inovação da Instituição; •Garantirá que estes processos aconteçam.
  • 17. Instituto Butantan | 16 Patents PATENTS BY SUBJECT SUBJECT Nº VACCINES 12 SERUMS 3 AMBLYOMMA CAJENNENSE 2 LOPAP 3 CROTAMINE 1 MAB 1 LEPTOSPIRA 10 ANALGESIC COMPOUNDS 1 ANTIBACTERIAL AS ANTI-CONVULSIVANT 1 IMMUNOTHERAPEUTIC 2 PEPTIDES 4 STEM CELLS 2 OTHERS 10 TOTAL 52
  • 18. Instituto Butantan | IMMUNOGENIC COMPLEX FORMED BY VACCINAL ANTIGENS ENCAPSULATED BY NANOSTRUCTURED MESOPOROUS SILICA PI 0503817-0, 12/09/2005 PATENTS 17 • Adjuvant (solid particles of highly ordered nanostructured mesoporous silica) and vaccinal antigens; • Presentation of the antigens in a safe, gradual and prolonged manner; • Immunological memory more efficient; • Increase of the immunogenicity of the antigen; • Improvement in antibody production; • Immune protection efficiently with lower amounts of antigens or less repeats;
  • 19. Instituto Butantan | 18 PATENTS PROCESS FOR OBTENTION OF NEW CELLULAR PERTUSSIS VACCINE • Less toxic; • As potent as B. pertussis fermentation Tangential Filtration or Molecular ultrafiltration? WCP Organic extraction WCPLow PI 0402630-6, 05/07/2004 WO/2006/002502, 12/01/2006 MPLA Adjuvant PI 0721393-0, 22/03/2007 WO/2008/134830, 13/11/2008 Clinical Trials 2007 Infants Acellular Pertussis Vaccine PI 0202458-6, 13/06/2002 Adolescents Recombinant BCG-Pertussis Immunization at birth Under GMP production Clinical Trials Neonates Patent
  • 20. Instituto Butantan | RECOMBINANT PROTEASE PROTHROMBIN ACTIVATOR (LOPAP) PI 0200269-8, 31/01/2002 PI 0403882-7, 24/08/2004 PI 0504199-6, 08/09/2005 • Prothrombin activator; • Defibrinogenating/antithrombotic agent; • Kit for diagnosis of dysprothrombinemias; • Anti-apoptotic activity. Lonomia obliqua 19 PATENTS FAPESP, BIOLAB SANUS FARMACÊUTICA
  • 21. Instituto Butantan | KUNITZ-TYPE RECOMBINANT INHIBITOR, AMBLYOMIN – X, OBTAINED FROM SALIVARY GLANDS OF THE AMBLYOMMA CAJENNENSE PI 0406057-1, 15/09/2004 WO/2008/109976, 18/09/2008 • Anticoagulant activity; • Apoptotic activity in tumor cells; • Anti-metastatic activity of melanoma tumor; • Anti-cancer activity; • Utilization of the recombinant in different hemostatic mechanisms. Amblyomma cajennense 20 PATENTS FAPESP, UNIÃO QUÍMICA FARMACÊUTICA
  • 22. Instituto Butantan | Crotalphine Potent analgesic drugs from animal venoms and toxins 21 Venom of Potent analgesic long-lasting analgesic action (2-5 days) Crotalphine Molecular mechanisms involved in the analgesic action release of endogenous opioids Activation of peripheral  and  opioid receptors intracellular signaling pathways activation Activation of NO-cGMP-PKG and opening of potassium channels Recent studies show involvement of PKC which activates MAPKs (Mechanism that may contribute to its long-lasting analgesic action) Activation of CB2 cannabinoid receptors Crotalus PATENTS
  • 23. Instituto Butantan | 22 PATENTS USE OF CROTAMINE, KIT AND COMPOSITION PI 0501037-3, 18/03/2005 WO/2006/096953, 21/09/2006 • Interaction with genetic material; • Transport of molecules to the surface, cytoplasm or cell nucleous; • Selective cell penetration; • Use for the treatment of diseases and dysfunctions.
  • 24. Instituto Butantan | 23 Av. Vital Brasil, 1500 - Butantã São Paulo – SP CEP - 05503-900 (11) 3726.7222 www.butantan.gov.br OBRIGADO!