Oligo PRO ™ System: Competing Technologies

1. Oligo PRO™ System: Competing Technologies

2. Competing Technologies for Oligonucleotide Analysis • Slab Gel Electrophoresis • Single column capillary electrophoresis-UV detection • HPLC (Reversed-phase and Ion Exchange) • Mass Spectrometry (MALDI-MS and LC-ESI-MS) CONFIDENTIAL

3. Slab Gel Electrophoresis • Multiple sample analysis capabilities • Good resolution • Manual, very labor intensive • Semi-Quantification • Poor data storage capabilities • Long separation time • Oligo PRO™system provides: • Increased automation • Higher resolution • Better quantification • Digital data storage • Customized report generation • Much greater ease of use • More efficient use of labor resources Slab gel results CONFIDENTIAL

4. Single Column Capillary Electrophoresis • Similar resolution to the Oligo PRO™ • Slightly better sensitivity and reproducibility • Low sample throughput (20–40 samples/day) • High operational costs: • Uses expensive, permanently coated capillary • Customer must prepare gel matrix manually • High cost of consumables • No application specific software available • Estimated system cost: ~$60,000 US Beckman P/ACE™ MDQ DNA System • Oligo PRO™system provides: • Greatly increased sample throughput • Lower cost per sample • Longer capillary lifetime • Lower cost of operation/ownership • Dedicated software for oligonucleotide analysis • Ready-to-use reagents • Predefined methods for greater ease-of-use CONFIDENTIAL

5. HPLC (Ion Exchange, Reversed-Phase Chromatography) Waters, Dionex • Slightly better detection sensitivity • Can perform prep scale as well as analytical scale • Low sample throughput (serial analysis) • Resolution highly dependent upon length and sequence • Separation not completely based on size • Limited length of n-1 resolution (max varies from 40-mer to 60-mer?) • Many factors affect resolution and performance (pH, T, column material, mobile phase, flow rate) = complex method development • Higher cost of ownership (higher maintenance, greater waste volume generated) • Oligo PRO™system provides: • Greatly increased sample throughput • Much higher sizing range (to 150-mer) • Increased resolution strictly based upon oligo length • Lower cost of operation/ownership • Dedicated software for oligonucleotide analysis • Predefined, optimized methods for greater ease-of-use CONFIDENTIAL

6. MALDI Mass Spectrometry Sequenom • Matrix Assisted Laser Desorption Ionization (MALDI) • MS provides accurate measurement of MW (identity) • High throughput (1000s/day) • Limited sizing range (< 50-mer) • Extremely sensitive to salt in sample • Variation in response with spot size and laser position • Different length and sequence of oligo give different responses • No comparability of n-1 impurities with CGE (MS NOT quantitative) • High system cost (>$150,000?) • Oligo PRO™system provides: • More quantitative assessment of oligo impurities (purity QC) • Much higher sizing range (to 150-mer) • Separation with uniform, UV absorbance-based detection • Greater ease-of-use • Lower cost of operation/ownership CGE is often considered a complementary QC method to MS! CONFIDENTIAL

7. HPLC-ESI Mass Spectrometry Novatia • ElectroSpray Ionization (ESI) • MS provides accurate measurement of MW (identity) • High throughput (1000/day, ID only no purity info) • Good sizing range (to 120-mer) • Extremely sensitive to salt in sample (need HPLC to desalt) • Different length and sequence of oligo give different ionization response • No comparability of n-1 impurities with CGE (MS NOT quantitative) • Better purity info if perform LC separation first; throughput reduced to 10 min/sample • High system cost ($250,000?) and cost of ownership • Oligo PRO™system provides: • More quantitative assessment of oligo impurities • Higher sizing range (to 150-mer) • Higher sample throughput for purity analysis • Uniform, UV absorbance-based detection • Greater ease-of-use • Lower cost of system/ownership CGE is often considered a complementary QC method to MS! CONFIDENTIAL