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Fernando Goldbaum
II ENCUENTRO DE GESTORES TECNOLOGICOS
San Luis, 30 y 31 de octubre de 2014
El modelo del triángulo de Sábato en la Argentina de hoy: mi experiencia como investigador,
emprendedor y funcionario
Faculty position at Institute Leloir since 2000Laboratory of Structural and Molecular Immunology
(More than 90 papers published in basic research)
PhD Thesis 1987-1992mAbs to detect Brucella antigens that differenciate active brucellosis
Postdoc at USA 1993-1997Structure and engineering of abs using Xray and biophysical techniques
Antibodies Antigens
Biotechnological applications
Competitive niche
Feasibility
Start Up company
From an academic career to enterpreneurship
VISION CONCEPTUAL
Nuestro laboratorio cambió el área de investigación desde la Inmunología a la Microbiología Molecular.
Temas inmunológicos (inmunogenicidad de antígenos e ingeniería de anticuerpos) transferidos a Start Up Inmunova
Tema principal:
Adaptación Brucella a condiciones de falta de nutrientesRol de flavinas y flavoproteínas en dicha adaptación
Mecanismos adaptativos de Brucella para cambiar su metabolismo en el nicho replicativo.
- El rol de la biosíntesis de flavinas en dicha adaptación
- El rol de hemo y flavoproteinas en el sensado de señales externas: luz, oxígeno y otras
- La descripción de una nueva vía de señalización disparada por la luz azul.
Brucella (un patógeno intracelular de mamíferos) y Rhizobium (simbionte de plantas)
Nodo Cristalografía de Proteínas
Fundación Instituto Leloir
Diciembre 2013
Plataforma Argentina de Biología
Estructural y Metabolómica “PLABEM”
Inventors
Inmunova
Start Up
2008 1st round Investment
2012 2nd round Investment
2007-2013 Grant money from Government
BLS presents a compact and very stable decameric structure
% S
ec
on
dary
str
uctu
re
Temperature (ºC)
BLS structure resists to
high urea concentration
and temperature
JBC: Vol. 279, 9, 8093–8101, 2004
DESCRIPTION OF THE CORE TECHNOLOGY
• Patent protected technology
• Innovative and powerful vaccine delivery system
• Optimal antigen presentation to the immune system
• Intrinsic adjuvant properties
BLS can be decorated at ten uniformly distributed positions
The BLS technology is an innovative and versatile vaccine platform endowed
with intrinsic adjuvant properties, which will offer a valuable tool for the
vaccine marketplace, both in the field of prophylactic and therapeutic
medicine.
Full Proteins Protein
Domains
Peptides Polysaccharides
Carrier BLS
Proyects under development
Bovine Brucellosis (Biogénesis
Bagó)
Cisticercosis
(Oral; UNAM)
Foot and mouth disease
(Biogénesis Bagó)
Hemolytic Uremic
Syndrome
(Acad. Nac. de Medicina)
Sugar vaccines
Hepatitis C
(CIGB- Cuba)
Hepatitis B
(therapeutic)
Anti-angiogenic
therapeutic cancer
BLS-VEGF
(CIGB- Cuba)
Ovine Brucellosis
Hemolytic Uremic SyndromeShigaToxin
A Subunit (catalytic)
N-glicosidase, inhibits protein synthesis
toxic
B Subunit (attachment)
pentameric
binds gangliosides
unstable
In Argentina HUS is endemic and represents a serious health problem,
with high incidence of afected children and high values of morbility and
mortality.
25 50 75 100
-2.5
-2.0
-1.5
-1.0
-0.5
BLS-Stx2B L5
BLS wt
Stx2B
BLS-Stx2B L10
BLS-Stx2B L15
Temperature (ºC)
[]
10
-6 (.c
m2.d
mo
l pro
t-1)
AB5 toxins
V.cholerae
S.dysenteriae
E.coli
BLS-StxB
A
0 15 30 45 60 750
2000
4000
6000
8000
10000
50000100000150000200000
BLS-Stx2B + FA
BLS-Stx2B + AH
BLS-Stx2B N/A
Prime Boost
**
** ** **
Protein immunization
Days
Prime boost
***
*Stx
2B
-sp
ecif
ic Ig
G t
ite
rs
0 15 30 45 60 750
500
1000
1500
2000
50000100000150000200000
BLS-Stx2B
Stx2B
** ** ** **
Protein immunization
Days
Stx
2B
-sp
ecif
ic Ig
G t
ite
rs
B
BLS StxB elicits high titles of
high affinity neutralizing Abs
against STX2B
J Immunol. 2013 Sep 1;191(5):2403-11
BLS-StxB: induces a 100 % protection against Shiga toxin in
the murine model
• Vaccines
• Therapeutic antibodies
against HUS
nanobody anti STX2B
Nanobodies
These Abs combine the benefits of conventional antibodies with important advantages of small molecule drugs, allowing the generation of antibodies for new applications inaccessible to conventional antibodies.
Academic achievements
Brucella lumazine
synthase
T. cruzi
trans-sialidase
Enzymeinhibitors
PLoS ONE 3(10): e3524, 2008.
Molecular mimicry
anti-idiotypic antibodies
Journal of Molecular Biology, 2005.
Diagnosticreagents
Nanobodies resistant to
denaturant conditions
J. Agr. Food Chem. 58(2):918-926, 2010.
Therapeuticintrabodies
Immunemodulators
Inhibiting anti-bacterial
toxin nanobody
FASEB Journal, 25(2):526-34, 2011.
Inhibiting anti-ectoenzyme
ARTs immune regulators
FASEB Journal, 21(13):3490-98, 2007.
VHH purification
Vero Cells Neutralization
Identificación de una familia de clones con capacidad inhibitoria
IN VIVO PROTECTION : MODEL WITH INCREMENTAL DOSES OF STX2
The trivalent molecule was able to protect 100% evenwhen it was administered after two doses of toxinand simultaneously to the third.
Therapeutic window
Application of anti STX
- Primer bioterapéutico original totalmente desarrollado en Argentina que entraría en ensayos clínicos- Mercado chico pero importante a nivel mundial (15 M USD Argentina- 200 M USD mundial anuales)
con potencial posición dominante
Fundación Instituto Leloir2001-2007 Secretario y VicePresidente2008-2011 Director2012-2013 Director IIBBA-CONICET
Polo Científico y Tecnológico - Godoy Cruz 2370 4to piso, CABA
[email protected] - Tel.: 0054 11 4899 5300, int.: 8002
www.agencia.mincyt.gob.ar