This document describes ProteoCell Biotechnologies Inc., a company that offers an integrated cell line engineering and bioprocess development platform called ProteoCell SSI. The platform includes molecular engineering to design high producing cell lines, preliminary bioprocess development overlapping with clonal selection, and GMP cell banking and process development. ProteoCell's services cover molecular engineering, cell culture, purification, and bioprocess consulting. The ProteoCell SSI platform aims to rapidly generate stable high producing cell lines and test clones in bioreactors to simulate production conditions before cell banking.

1. www.proteocell.com
PROTEOCELL BIOTECHNOLOGIES INC.
a bioprocess specialty company
Montreal, Canada
ProteoCell SSI– ProteoCell’s INTEGRATED Cell
Line Engineering and Bioprocess Development
Platform

2. www.proteocell.com
BIOPROCESS AT PROTEOCELL
Molecular
Engineering
Process
Engineering
Facility
Engineering

3. www.proteocell.com
Molecular
Engineering
Expression plasmid design
and generation
(Mammalian, Yeast, and E.
Coli cell systems)
Sequence Analysis,
construct design, and
molecular optimization
Upstream Process
(Cell Culture)
Downstream Process
(Purification)
Transient transfection
Clonal selection
Generation of optimal stable cell line
Creation of Master and Working Cell
banks
Small & Medium scale cell culture
(Mammalian, Yeast, & E. Coli)
Molecular engineering
expertise & consulting
Bioprocess Scale-up expertise & consulting
Purification expertise &
consulting
GLP & GMP Material Production
Bioprocess Analytics suite—process and auxiliary bio-analytics services
Small & Medium scale
Purification
Viral Clearance
Ultrafiltration/Dialfiltration/Concentration
Purified end-products
Non-purified end products (clarified harvest)
Small-scale bioprocess development & optimization (Cell
Culture & Purification)
Cell Culture & fermentation
expertise & consulting
PROTEOCELL BIOTECHNOLOGIES’ SPECTRUM OF SERVICES

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3 KEYS TO EFFECTIVE BIOPROCESS FOR BIOPHARMA MANUFACTURING
1) Superior cell line and cell line technology used;
2) Efficient and effective bioprocess development;
3) A-Z adequate regulatory compliance.

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BIOPROCESS INTEGRATION STRATEGY OF PROTEOCELL SSI
1) Cell Line Engineering:
•Using the latest in Ab molecular engineering methods to design a DNA expression vector
system that is stable and high producing, and scalable to a production system (bioreactor
scale)
2) Process Development:
• Preliminary bioprocess work that ProteoCell has successfully incorporated into its cell line
engineering strategy by overlapping clonal selection concepts with Process Development
concepts;
• It includes the preliminary expression of the designed Ab clones in a quasi-production/full
production setting to test for product homogeneity and stability—before final clonal selection
and cell banking;
• This includes production in a bioreactor, simulating production batch conditions, including
chemically defined media and other regulatory compliant bioprocess conditions.

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MOLECULAR ENGINEERING HIGHLIGHTS OF PROTEOCELL SSI SYSTEM
1) Alternate “tagging-targeting vector” mechanism for rapid generation
of stable genomic integration of target gene sequence;
2) Strong CMV promoter drives LC or HC expression;
3) Weaker promoter or IRES drives selectable marker to ensure that
MAb expression is dominant;
4) Single or double fluorescence tagging of protein sequence depending
on experimental design strategy.

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PROTEOCELL SSI = SPEED; CLONAL SELECTION IN RECORD TIME!!
Targeting vector
Culture of appropriate
tagged cell line
Weeks 1,2 Weeks 2,3 Weeks 4,5
Clonal selection and expressionTransfection

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PRELIMINARY PROCESS DEV. OF A CELL LINE USING PROTEOCELL SSI PLATFORM
•Initial Process Development in Flask (Batch and Fed Batch mode) and further optimization
in Bioreactor culture.
•Multiple tracks are then undertaken for optimizing clonal conditions in both flasks and
bioreactor culture (before MCB is produced to confirm scale-up capability of selective
clone)
Media/Culture Parameters
Cell
Growth
Cell
Viability
Cultivation
Time
0
1
2
3
4
5
6
7
Productivity(FoldIncrease)
Preliminary Process Dev. Projection
Flask Process Dev.
Months 1 2 3 4
Flask /Bioreactor Process Dev.

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INCREASED ANTIBODY YIELD IN CHO CELLS WITH PROTEOCELL SSI PLATFORM
0
1
2
3
4
5
6
IgGTiter(g/L)
Cell Line Engineering 30-60 days
Preliminary Process Dev. 30-75 days
Advanced Process Dev. 45-75 days

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PROJECTING INTO PROCESS DEVELOPMENT AND BEYOND....
Completion of Cell line engineering and Preliminary Process Development
GMP Cell Banking and Process Development
Process Scale-up
Pilot scale cGMP process development at ProteoCell (Engineering runs)
Tech transfer to commercial manufacturing facility

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THE PROTEOCELL SSI MFG. PROCESS STAGES OF DEVELOPMENT OUTLINE
Stage 2: Process Scale-up to
50-100L scale
Stage 1: GMP Cell Line and
Process Development
Stage 3: GMP Pilot scale
process production
Stage 4: Technology Transfer
to Commercial Mfg. site
3 90 6 12 15 18 21 24
(months)