physiologically relevant tools & personalized support for drug discovery research
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1 10/19/2011 | Life Technologies™ Proprietary and confidential
Physiologically Relevant Tools and Personalized Support for Your Drug Discovery ResearchMark FedericiManager- Strategic AlliancesPSCS-Drug Discovery Assay and Services
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Life Technologies brands
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Tools for drug discovery & development research
Ste
• Stem cells
• Neurobiology
• Primary cells & matricies
• Cell Therapy Systems (CTS™)
• Target-based proteins and HTS assays
• Kinases• GPCRs• Pathways• Nuclear receptors• Ion channels
• SelectScreen® screening and profiling services
• Custom assay development and cell engineering
• Fresh hepatocytes
• Cryopreserved hepatocytes
•Microsomes
• Transporter products
Cellular Models Target & Lead Discovery ADME/Tox
Our focus today
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Technologies & Assays
Screening & Profiling Services
Strategic Alliance Partnerships
• Broad panels of biochemical and cell-based assays
• Primary screening Comprehensive profiling
• Robust Biology Multiple target classes
• Biochemical / Cellular Assays, Primary / Stem Cells
• Customized programs of research (Gene to Screen)
• Dedicated project management
Personalized support for your research
Specialized Technical Support
• Ph.D. level drug discovery focused technical support
• Pre- and post-purchase support
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Our team helps our clients develop customized solutions and navigate the full breadth of Life Technologies capabilities
Drug targetprofiling & screening
services
Cell-based assay development
Biochemical assaydevelopment
Biochemical and cell-based ADME assays
Imaging, flow cytometry &cell pathway analysis
Discovery & Target ID
LeadOptimization
SafetyTox
Validation& Lead ID
Preclinical & Clinical Trials
Target-based proteins, assays & services
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Leveraged Content and Technologies in Professional Services Portfolio
> 1,000 kinase assays –biochemical
> 400 GPCR cellular assays –reporter gene, b-arrestin and second messenger
> 70 Nuclear receptor assays –biochemical and cellular
Multiple Ion Channel technologies and first commercially available Fluorescent hERG assay
> 100 Pathway assays (CellSensor®
and LanthaScreen® GFP)Custom assay development and screening collaborations
Developed the Broadest Target Class Content in the Industry
Integrating products and services
SelectScreen® Services Platform
Library screeningBiochemical & cell-based profiling
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Screening, profiling and custom services
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From target to preclinical testing: A comprehensive service provider
Targetidentification and validation
Assaydevelopment
Preclinical and clinical
trialsScreening Lead
optimization
Assay Development
Biochemical Assay Development
Cellular Assay Development
Lead Optimization
Molecular and Cellular Profiling
Drug Metabolism CYP450 Profiling
Safety Testing hERG Screening Service
Choose single projects or an entire program
Screening
Bulk Screening Assays/Reagents
Assay Ready Cryo-preserved Cells
Primary and Secondary Screening
Services
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Dedicated project management
Single point of contact through dedicated Project Manager with all teams supporting SelectScreen® and Custom Services
R&D
MFG Operations
Dedicated Project Manager
Customer Inquiry
SelectScreen®
Team
MFG Sciences
Custom Biology Team
R&D Custom Assay Team
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SelectScreen® platform: A complete solution
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Why SelectScreen® services?• Proven track record of rapid, on-time assay development
and screening execution
• Conducted more than 7,600 screening projects on over 400 targets, including library screens with assay development
− Average cycle times:
− 6 days, biochemical profiling
− 8 days, cellular profiling
• Supportive research environment
− Open and frequent communication between the client and Life Technologies dedicated project manager
− Proactive interactions with client based on results obtained
• All of the reagents and assays are developed, manufactured and QC’d on site
• Over 15 years of experience in high quality protein and reagent production, molecular and cellular HTS assay development
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Custom service capabilities
Service type Target/functional area
Biochemical assay development Kinases, nuclear receptors, proteases
Cellular assay development Kinases, nuclear receptors, GPCRs, ion channels, epigenetics, pathways
Tb/Eu antibody labeling Kinases, post-translational modifications
BacMam generation Targets and reporters
Stem cells Adaptation, expansion, differentiation
TaqMan® assay development mRNA or proteins
siRNA profiling RNA and functional readouts
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Assay platform capabilitiesAssay platform Target area Custom SelectScreen®
service
Z’-LYTE® (FRET) Kinase activity, protease activity √ √
Adapta® (TR-FRET) Kinase activity √ √
LanthaScreen® kinase binding assay (TR-FRET)
Kinase binding √ √
LanthaScreen® biochemical (TR-FRET) Kinase, PTMs, NRs √ √
LanthaScreen® cellular (TR-FRET) Kinase, PTMs √ √
Fluo-4 GPCRs, ion channels √ √
FluxOR™ Ion channels, others √ √
Beta-lactamase/CellSensor™/Tango™ Pathways, GPCRs, NRs √ √
Beta-galactosidase/Luciferase Pathways, GPCRs √ √
TaqMan® assay mRNA √
TaqMan® protein assay Protein: qty, TPM, ix √
Vivid® P450’s and hERG Predictor™ Safety: CYPs, hERG √
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Small-molecule vs. siRNA profiling
Feature Small-molecule siRNA
Availability Not available for all targets Synthesize for any target
Mechanism Inhibition of protein function Depletion of protein expression
Timing Rapid, potentially reversible Gradual, sustained duration
Specificity Non-specific effects possible Off-target effects possible
siRNA profiling addresses a broader number of targets and achieves specificity through target-specific knockdown
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How can siRNA profiling be used?
1. Dilute oligo
2. Add RNAiMAX
Reverse transfection
ScreeningAssay
3. Add cells
siRNA Library
Gene Expression Analysis TaqMan® assay
Protein ModificationLanthaScreen® cellular assay or
immuno-cytochemistry
Reporter Gene AssayCellSensor® beta-lactamase
Cell proliferationCyQuant® Cell Proliferation assay
or PrestoBlue™
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TaqMan® protein assaysProtein Detection from lysates of engineered, normal or primary cells as well as tissues (fresh, frozen or FFPE)
Combines protein detection using Antibodies with robust, sensitive real-time PCR
Relative quantification of proteins in cell and tissue lysates
− No purification of proteins required!
> Just lyse and dilute
Enables very small sample protein analysis
Typical Sample Input
10-500 cells 1-1000 ng protein from tissues
Compatible with StepOnePlusTM, 7500, 7500 Fast, 7900 HT, & ViiATM 7 Real-Time PCR Systems
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TaqMan® protein assay features
• Provides all the amplification benefits of nucleic acid based qPCR, but for the analysis of proteins
• Vastly improved sensitivity compared to ELISA and other immunodetection methods, in some cases up to 1000xmore sensitive
• Wide range of exciting new applications:
• Detection of post-translational modifications
• Analysis of both endogenous and exogenous proteins with high sensitivity
• Detection of biomarkers and pluripotency factors
• Detection of protein-protein interactions
• Direct follow-up of mRNA expression with analysis of corresponding proteins levels
p53P
BBB
GFP
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Target-based proteins & assays
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Comprehensive pathway biology approach
Assay Classes
• GPCR Assays
• Kinase Assays
• Ion Channel Assays
• NR Assays
• Post-translational
modifications
The Integration of Biological Capabilities Into Customer Solutions
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Cell engineering tools
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What is BacMam?
BacMam uses baculovirus to deliver and
transiently express genes in mammalian cells
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How do I use BacMam?
Actin RFP + Tubulin GFP
Clones
TransientTransfections
BacMam
Stable Pools
Workflow
/Assay Tim
e
4-8 Weeks
Fixed Assay
Portable Assay
3-4 Weeks
days
1-2 days
Why should I use BacMam?
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BacMam benefits
• Convenient and Fast: just add virus to cells
• Efficient: High expression level
• Flexible: Allows expression of multiple subunits
• Titratable: Control level of expression
• Safe: Non-toxic to cells
• Portable: Works efficiently with most cell types (including primary and stem cells)
BacMam allows you to run the assays you need
in relevant cellular models quickly with high quality results.
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Flexibility of BacMam-enabled cellular assays
Bacmam-enabled Cellular Assays enable interrogation of multiple enzymatic activities responsible for posttranslational modifications, including challenging targets like histones.
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What is Jump-In?
Jump-In™cell line
Isogenic Jump-In™ Cell Pool
+
AntibioticSelection
R4 Integrase
Gene of Interest
4 weeks
Transfection
For Research Use Only. Not intended for animal or human therapeutic or diagnostic use
Genomic Integration of Genetic Material via Homologous Recombination
The Ideal Solution For:• Building and developing a panel of targets
- All Targets integrated at the same, single genomic site
• Rapid Assessment of Target Biology
Foundational tools:• Jump-In™ platform cell line• Gateway® targetable vector• Integrase vector
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Jump-In™ cell engineering technology
Jump-InTM Fast Gateway®
System
Jump-In™ TI™ Gateway®
System
Jump-InTM
Parental Cell Line Kits (New!)
Jump-InTM
Custom Services
Saves time and effort compared to traditional cell engineering methods
Yes Yes Yes Yes
Engineered cell line is isogenic
No Yes Yes Choice
Can use your preferred cell background
Yes Yes Limited to parental cell lines in catalog
Choice
Requires generation of platform/parental cell line (with R4 sites)
No Yes No Choice
Requires Clonal Selection Optional Yes Optional Choice
Ideal when you need… Faster stable cell lines in your preferred cell background
Isogenic cell lines in your preferred cell background
Isogenic cell lines created with less hands-on time
Experts who can meet your project specs and timelines
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CHO-K
GripTite™
T-Rex™ CHO
T-Rex™ 293
Jump-In™ cell line portfolio
Currently available through
Discovery Services
HeLa
K562
786-O
HEK293 (2x)
JurkatU2OS
HCT116
TANGO-U2OS
H9
NCI 60
Hemato-poeitic
“Workhorse”
Assay enabled
StemCells
A549
BG01vHEK293
R4
For Research Use Only. Not intended for animal or human therapeutic or diagnostic use
The Jump-InTM cell lines are not catalog products. For more information on how to gain access to this technology, please contact us at discoveryservices@lifetech.com
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Non-excisable integration of construct
Accepts large multigene inserts (up to 20 kb)
Streamlined workflow for cell line generation possible
Stable pools/cell lines easy to maintain
Ideal solution for studying mutants/orthologues:
– Gene of interest expressed from same locus in cells
– Stable pools can be quickly generated
Jump-In™ benefits
Jump-In CCKAR Pool vs. Traditional Clone
-12 -11 -10 -9 -8 -70
500
1000
1500
2000Jump-In 293 CCKAR pool
Traditional CCKAR clone
log10[CCK-8-S] (M)
RFU
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Resources & support
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Personalized support
Collaboration in action: video portal www.invitrogen.com/collaborate
Drug discovery technical supportdrugdiscoverytech@lifetech.com
SelectScreen® and custom services inquiriesdiscoveryservices@lifetech.com
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Personalized support
Virtual visits program Sign up at: find.lifetechnologies.com/visits
Free personalized webinars for drug discovery researchers
− Private, 1:1 webinar with Life Technologies R&D experts
− 30 minutes
− Six topics to select from:
> Cellular methods for kinase analysis
> Assay development for primary cells
> Stem cell culture and modification
> Cell engineering
> Assays for drug metabolism
> Research partnerships and services
Thank you!
Mark Federicimark.federici@lifetech.comTel 908 752 4864
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