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THE TECHNOLOGICAL PARTNERTHE TECHNOLOGICAL PARTNER
Life Sciences R&D at LeitatO t iti f b i d li d h ll b tiOpportunities for basic and applied research collaborations
Biomed Division
What is Leitat?
Recognized by
Generalitat de CatalunyaWhat is Leitat?
Leitat is brand of the non‐for‐profit private association Acondicionamiento Tarrasense
Spanish Ministry of Science and Innovation
An internationally recognised Institute
+100 years of experience (1906) +100 years of experience (1906)
250 collaborators
More than 200 annual projects
IP (patents fully owned & with companies)
Spin‐Off companies
MISSION: Create value through research and technological processes
VISION: To be a reference technological partner for companies and institutions,
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creating a corporate culture that allows sustained growth and efficiency.
Multisector foucs Technological Center I+D+2iMultisector foucs Technological Center I D 2i
• Safety & Sustainability• Advanced materials• Biomed• Devices, Design & Engineering• E i t l & Bi• Environmental & Bio
Technologies• Fast Moving Consumer Goods• Scientific & Technical Services• Scientific & Technical Services
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How do we work?How do we work?
Contract Research Collaborations Internal R&D
We help public & private institutions hospital groups universityWe help public & private institutions, hospital groups, universitydepartments, biotechs and pharma companies.
We jointly generate projects and present them to regional, national& European calls.
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OPEN INNOVATION ‐ OPEN COLLABORATION
Pharmaceutical companies
Biotech companiescompanies p
VeterinaryHospitals
Veterinarycompanies
CROsFood companies
Academia & University
Research Centers
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University Centers
Biomed Division backgroundBiomed Division background
Team members come from the Merck‐Serono Laboratory of BioInvestigation (LBI), keeping a remarkable pharmaceutical experience for more than 15 years of biomed research in the preclinical oncology field.
Some of the targets and drug candidates previously developed by our scientists are currently in phase III, II, p y y p , ,and I oncologic clinical trials.
Project Managers: 4 PhD in Biology, 4 Biologists, 4 Laboratory Technicians
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Emergent group label: AGAUR project. SGR 2009
Biomed Division ExpertiseBiomed Division Expertise
Cancer therapy: targets, drug generation & characterization, targeting and drug delivery. Analysis of the therapeutic efficacy of new compounds Other indications:efficacy of new compounds. Other indications: inflammation, autoimmune diseases.
Diagnosis, prognosis and monitorization: biomarkers, reagents, tools, devices (monoclonal antibodies, LFD, biosensors ) Industrial sectors:biosensors…). Industrial sectors:• Pharma, Biotech & Veterinary (diseases, infections, vaccines))
• Food (contaminants, allergies, intolerances, quality)• Environment, etc
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Drug reprofiling: identification of new indicationsfor well‐known and phase‐III drugs.
Biomed Division Technological platformsg p
Generation of monoclonal antibodies (mAb) for basic research, diagnosis and therapy.Recombinant proteins, Immunization, Serum title, Mouse polyclonals, Fusion, Screening, Cloning, Hybridomas Isotyping Production & Purification F(ab’)2 Fab scFv Conjugation ELISA WB FACSHybridomas, Isotyping, Production & Purification, F(ab )2, Fab, scFv, Conjugation, ELISA, WB, FACS, IHC, Diagnosis, Biosensors
mAb engineering: chimerization, humanization & biosimilarsSequencing, Cloning, Chimeric mAbs, Humanized mAbs, scFv fragments, Fusion proteins Modeling, Transient expression, Stable clones, Nanobodies, Bispecifics, ADCs, Production, Biosimilars
Biogenomics BiogenomicsTarget validation by siRNA, PPRH (DNA hairpins), arrays (expression, farmacogenomics, toxicology), cell transfection.
I it ll d l In vitro cell modelsProliferation, Viability, Apoptosis, Nanotox, Migration, Adhesion, Angiogenesis, Tumorspheres (CSC), ADCC, CDC...
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In vivo animal modelsSyngenic & xenogenic, Subcutaneous & orthotopic, Experimental & spontaneous metastasis PDX (avatar), Angiogenesis in Matrigel plugs, Tumor angiogenesis, Non-invasive imaging…
Monoclonal antibody platformMonoclonal antibody platform
Antibody EngineeringGeneration & Characterization Antibody Engineering
• Sequencing• Cloning
Generation & Characterization
• Recombinant proteins• Overexpression & gene silencing • Cloning
• Chimeric Mabs• Humanized Mabs
F f t
• Overexpression & gene silencing• Ag & cell immunization• Serum titlesP l l l • scFv fragments
• Nanobodies• ADCs
• Polyclonals• Fusion, Screening, Cloning• Hybridomas
• Fusion proteins• Bispecifics
• Transient expression
• Isotyping• Production & Purification• F(ab’)2, Fab, scFv p
• Stable clones• Production & Purification
• Therapy
• Conjugation & labeling• ELISA, WB, FACS, IHC• Diagnosis
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Therapy• Biosimilars
g• Biosensors
Cellular modelsIndication Cell lines
Colon
HCT‐116 KM12‐L4aHT‐29 LoVoCellular models
(some examples)Colon
Colo 205 LS174T CT‐26
BreastMDA‐MB‐231 BT‐474 MDA‐MB‐468 SKBR‐3
• Proliferation
MCF‐7 T47‐D
PancreasBxPC3 Mia Paca 2 RPWI NP‐18 Panc 1
• Viability• Apoptosis• Pre tox
Prostate PC3 DU 145 LnCap
LungA549 NCI‐H358 LL2 HI‐1650 • Pre‐tox
• Migration• Wound healing
gNCI‐H1975
Melanoma Sk Mel 28 M21 B16‐F1 MDA‐MB‐435
Ovarian Ovcar 3 SKOV‐3Wound healing• Adhesion• Angiogenesis
Ovcar 3 SKOV 3
CNS DAOY U‐373MG Sh Sy5y U‐87MG Ramos TF‐1 K562 CCRF‐CEM
• Tumorspheres(Cancer Stem Cells: CSC)
Haematologic K562 CCRF CEM Jurkat U937 THP‐1
Renal 786‐0 Fibrosarcoma HT‐1080
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Efficacy assessment, Mechanism of action, Drug reprofiling, Preclinical studies
Fibrosarcoma HT 1080 Endometrium An3Ca Epithelium A‐431 Endothelium HUVEC
Animal modelsIndication Line Subcutaneous
ModelsOrthotopicModelsAnimal models
(some examples)Colon
HCT 116 X XHT 29 X X
Colo 205 X X
BreastMDA‐MB‐231 X XMDA‐MB‐468 X X
MCF‐7 X XBxPC3 X X
• Syngenic & xenogenic• Subcutaneous & orthotopic
PancreasBxPC3 X XPanc‐1 X X
Mia Paca‐2 X XPC3 X X
• Metastasis (exper. & spont.)• Patient Derived Xenografts (PDX)A i i i M t i l l
ProstatePC3 X XLnCap X XDU145 X X
Lung A549 X X
• Angiogenesis in Matrigel plugs• Tumor angiogenesis• Non‐invasive imaging Lung LewisLC X X
Melanoma SkMel28 X XOvary Ovcar‐3 X XCNS DAOY X X
Non invasive imaging
CNS DAOY X X
HematologicRamos XK 562 XJurkat X
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Efficacy assessment, Drug reprofiling, Pre‐Tox (MTD), Pre‐PK, Biodistribution
Jurkat XRenal 786‐0 X X
Fibrosarcoma HT 1080 X
Some examples
More predictive models (Patient Derived Xenograft (PDX), Tumorgrafts or Avatar models)))
So e e a p es
)
• Collaborations with Hospitals ongoing
• Tumor fragments implanted orthotopically
• Colon, breast, pancreas
• CSC identification & expansion
• Personalized therapy
• Useful material for basic translational & clínicalresearch
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research
Adapted from: Richmond & Su, Dis Model Mech. 2008, 2
Some examples
Metastasis models
So e e a p es
Indication Line inocule placement Target organ Assay duration (days) MeasurementMiaPaca tissue pancreas liver, lung, peritoneal 60 surface spotBxPC3 luc tissue pancreas liver 60 surface spot/photon count
PancreasHUMAN
Metastasis Models
Colon KM12L4‐Luc cells intraspleen liver 20 surface spot/photon countLL2 cells iv lungs 25 surface spot
cells sc lungs 25 surface spot Colon CT26 cells intraspleen liver 20 surface spot
4T1 cells mammary fad pad lungs 20 surface spot
Lung
MOUSE
B 4T1 cells mammary fad pad lungs 20 surface spotMHC‐02‐10 cells mammary fad pad lungs 40 surface spot
Breast
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Some examplesSome examples
VACMON: Biosensor for fast vaccine monitoring• Main objective: development of portable biosensors for PoC based on hybrid nanoparticle‐
biomolecules to assess the functional immune response to therapeutic and prophylacticvaccines (cervical cancer, Gardasil™ against human papillomavirus‐HPV) .
i h d f i i i i h ill i ill ll d• Knowing the degree of immunization against human papilloma virus will allow to adaptvaccination schedules to the real immunity status of each patient.
• The biosensor integrates technologies from particular areas: microelectronics,t h l bi di i tib dinanotechnology, biomedicine, antibodies.
• The biosensor platform can be used in many other vaccine programs.
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Some examplesp
IVAGINTEST: Multidiagnostic kit for vaginal diseases
Gardnerella vaginalis, Candida albicans and Tricomonas vaginalis
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Igen Biotech, UCM, Leitat
Some project examplesSome project examples
6 Patents: 3 different therapeutic Mabs/targets, therapeutic+targeting peptide, DNA‐based disruptive technology, new therapeutic peptide against differential target.
RETOS COLLABORATION PROJECTS:RETOS-COLLABORATION PROJECTS: TERET: Treatments for retinal degenerative diseases. TOXAB: Innovative Antibody Drug Conjugates (ADC) for cancer treatment. NUEVAS DIANAS N t t t f th b d th d l ti f i ti NUEVAS DIANAS: New treatments for cancer therapy based on the modulation of epigenetic
targets and adenosine receptors. MICROALMABS: Validation of a new platform for the production of therapeutic microalgae
MabsMabs. ZITOMAB: Development of anti-tumor second generation immunotherapies : Nanobodies and
Antibodies specifically toxin conjugated by inteins –ZIP.
ONCOGALFARMA: Development of new therapies for the treatment of oncologic diseases. CONNECTA PYME project.
ONCOSLIDE: INNPACTO project. ANGIOGENESIS: Peritoneal infection and recurrence of colorectal cancer FIS project MICINN
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ANGIOGENESIS: Peritoneal infection and recurrence of colorectal cancer. FIS project. MICINN
SIMBIO: Platform for the generation and characterization of Biosimilars. INNPACTO project. IVAGINTEST: Development of a Multidiagnostic kit for vaginal diseases. INNPACTO project
Some project examplesSome project examples
EUROPEAN PROJECTS:
LIFE: Comprehensive challenge to breast cancer. CENIT project ‐ 2011
GLAM: Glass Laser Multiplexed Biosensor, H2020: PHC‐10, 2015‐2019
BATCURE: New therapies for Batten’s disease and related lysosomal diseases, H2020: Therapies for rare diseases, 2015‐2019
NANOPOLYTOX: Toxicological impact of nanomaterials derived from processing, weathering and recycling of polymer nanocomposites used in various industrial applications, FP7: NMP‐2009‐1.3‐1
NANOTHER: Integration of novel nanoparticle based technology for therapeutics and diagnosis of different types of cancer, FP7: NMP‐2007
NOBITAN: Novel biofocused targeting of nucleoside analogues with cyclic RGD peptides as enhanced anticancer th E t bi 2011therapy, Eurotransbio‐2011
BIOXPLORE: Bioexploration – novel methodology for the identification of valuable natural products derived from mediterranean flora. EU project funded by ENPI‐CBCMED.
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Main Collaborators ‐ Ia Co abo ato s
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Main Collaborators ‐ IIa Co abo ato s
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