CELLTHEON SERVICES: FROM cDNA TO SCALE UP
Celltheon Corporation uses novel genetic and process technologies to produce high quality cell lines and research level quantities of protein material for the easiest and most difficult to express proteins including bi/tri-specififc, DARPins, enzymes, growth factors, membrane proteins and antibody fragments/fusions. The CELLTHEON SMART™ Platform ensures high quality and high titer through newly developed, yet highly robust technologies such as Celltheon SUPERCELL™, suPRE™, and CT STABILIZER™. All of which have been seamlessly integrated into the CELLTHEON SMART™ Platform for fast and worry-free protein production.
Immediate benefits of the CELLTHEON SMART™ Platform and Celltheon Services include:
Celltheon is a one stop shop for all protein production needs. Services are offered from an early R&D phase to pre-GMP development. Our services are highly collaborative, well-documented and timely, giving you control over the entire process.
Celltheon Services include:
Immediate benefits of the CELLTHEON SMART™ Platform and Celltheon Services include:
- Rapid timelines
- Increased efficiency
- Cost savings at all production scales
- Higher quality protein for safer therapeutics
- Consistent CQA’s from thoroughly defined, QbD based processes
Celltheon is a one stop shop for all protein production needs. Services are offered from an early R&D phase to pre-GMP development. Our services are highly collaborative, well-documented and timely, giving you control over the entire process.
Celltheon Services include:
- Transient transfections/production
- Stable cell line development
- Cell culture process optimization
- Protein purification process development
- Assay development
- 3L, 5L, 10L, 20L, 50L, and 200L production of GLP tox material/research material
TRANSIENT TRANSFECTIONS
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Celltheon offers high titer transient production to streamline early drug development and lead candidate validation. Implementation of the Celltheon suPRE™ and CELLTHEON SMART™ Platform results in a 10x increase in transient titers over comparable competing platforms. Within 10-12 days, Celltheon can generate your early stage material to:
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CELL LINE DEVELOPMENT
The CELLTHEON SMART™ Platform for cell line development employs highly reproducible and novel production technologies to give your drug development program a head start. The Celltheon SMART™ Platform implements a Quality by Design (QbD) approach during clone selection to achieve a final RCB that is not only stable and high expressing, but also has optimal product quality attributes for ensured success in clinical trials. End results include stable pools titers of 1.5-2.5 g/L, clone titers of 4-8g/L, and >97% monomeric protein in both cases.
Celltheon’s homogenous high titer clone development platform allows for minimal clone screening with the following characteristics achieved consistently through screening only 500 clones:
The majority of Celltheon's clones are highly stable and productive with:
Celltheon’s homogenous high titer clone development platform allows for minimal clone screening with the following characteristics achieved consistently through screening only 500 clones:
- RCB within 12-14 weeks: 4-6g/L clones
- Highly stable clones for >120 generations
- High Specific Productivity (Qp): 60-120pg/cell/day
- >97% Monomeric protein
- Optimal Product Quality
- Documentation of monoclonality
The majority of Celltheon's clones are highly stable and productive with:
- No gene amplification
- No added pool enrichment
- No automated colony picking / HTS equipment required
- No issues regarding clonality: full documentation with imaging
- No need for screening 100,000's of clones and looking for a "needle in a haystack"
- No CQA issues due to QbD based processes
- No animal origin or non-chemically defined media and feed supplements
- No clumping issues or high ammonia levels that can lead to challenges at scale up in bioreactor
Celltheon Handles Difficult to Express Proteins by Design
State of the art production cell lines express complex/large glycoproteins, non-natural proteins, and protein fragments at significantly lower titers than the model antibodies titers are commonly reported for. Celltheon’s SUPERCELLs™ have been optimized to streamline production of difficult proteins through the engineering of protein folding, secretion, and aggregation related pathways. These cells in combination with CT STABILIZER™ improve product quality and expression of difficult to express proteins significantly and consistently.
The following data compares expression of several different proteins from Celltheon's SMART™ Stable Pools, generated within 3 weeks:
The following data compares expression of several different proteins from Celltheon's SMART™ Stable Pools, generated within 3 weeks:
Cell Line Development Timeline
Celltheon's SMART™ Technology Platform provides highly Optimized workflows and accelerates the timeline from cDNA to RCB:
- 2-3 weeks to select high expressing stable pools
- 12-14 weeks from transfection to RCB
- 6 weeks for 60 generation stability assessment
- No additional PD needed with Celltheon's high titer fed-batch platform
The Celltheon Workflow is simple resulting in robust repeatability when scaled up for production:
PROCESS DEVELOPMENT & OPTIMIZATION
The CELLTHEON SMART™ platform for process optimization reduces timelines to improve expression through the usage of defined media additive libraries. Within 1-2 months titers have been shown to increase 6 to 25-fold, with further improvements achieved after purification process optimization.
With our expertise, we help clients reach their goals of:
With our expertise, we help clients reach their goals of:
- Increasing productivity
- Improving product quality
- Reduced timelines
- Reduced manufacturing costs
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Upstream Process Optimization
Our Process Development Scientists have several years of experience in upstream process optimization. Up to 10 3L bioreactors may be run in parallel to quickly and efficiently determine and deliver a defined, scalable, and production ready process. Pilot-scale Single Use Bioreactors (50L and 200L) can additionally be used to ensure process scalability prior to GMP tech transfer. Celltheon understands the complexity associated with process scale-up and strives to reduce tech transfer and scale-up timelines. Celltheon process development goals include:
Downstream Purification Development Celltheon’s expert scientists routinely replicate or develop new purification processes, improve and trouble-shoot existing purification steps, and systematically evaluate process parameters to improve purification efficiency and recovery rates. These purification processes are developed using industry standard, commercially available purification equipment and platforms. Through working closely with the customer, we ensure successful realization of desired process goals such as:
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BIOPRODUCTION (NON-GMP)
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Celltheon has many Single Use Bioreactors (SUBs) for small-to-mid-scale, non-GMP production. Following process development, Celltheon can scale up processes and perform multi-column chromatography to deliver purified, low-endotoxin protein for in vivo studies. Celltheon has already delivered several-hundreds of grams of purified protein for tox studies to clients. Bioproduction offerings include:
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ANALYTICS
At Celltheon, quality by design (QBD) is built into our cell line development workflows and clone selection procedure. With a suite of optimized assays, we routinely screen clones in a high throughput fashion to achieve high quality production cell lines with minimal time and cost investments. Services include:
- Quantitative ELISA
- Octet- Protein Quantification and Affinity
- HPLC (CEX/SEC/RP assays)
- SDS-PAGE
- Cell based assays
- LAL Endotoxin
- Host Cell Protein Assay
- FACS assays
- Binding assays
- High throughput N-Glycan (CE-based assay)
- Other assays are outsourced to our preferred vendors/ partners
