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PROTEOCELL BIOTECHNOLOGIES INC.a bioprocess specialty company

Montreal, Canada

ProteoCell SSI– ProteoCell’s INTEGRATED Cell Line Engineering and Bioprocess Development

Platform

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BIOPROCESS AT PROTEOCELL

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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)

Flask /Bioreactor Process Dev.

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INCREASED ANTIBODY YIELD IN CHO CELLS WITH PROTEOCELL SSI PLATFORM

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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)