Recombinant proteins/mABs

YURiA-PHARM performs full-cycle development of recombinant protein-based therapeutics.

We integrate and have full control of all development activities for biopharmaceutics: from discovery to pilot production. That includes:

  • Expression vector architecture design;
  • Product-specific expression library screening;
  • Stable cell pools generation;
  • Stable clonal cell lines generation;
  • Product CQA-guided clonal cell lines screening;
  • Upstream process development (including high-density intensified and continuous processes);
  • Purification process development (including batch and continuous operation modes);
    Process scale-up and pilot manufacturing;

All activities are supported by state-of-the-art analytical technologies with in-house Quality-by-Design- developed analytical procedures.

Our expertise is based on diverse experience in engineering and expression of recombinant protein therapeutics such as mABs (produced in CHO and SP2/0 as well), fusion proteins, including such difficult-to-express proteins like TGF-b-family growth factors etc.

We don’t just utilize state-of-the art methodology during discovery and process development , but also create proprietary solutions, aimed at increasing efficacy, reducing time-to-market and develop approaches tailored to every product.

See our key proprietary bioprocessing solutions in action

  • CHO DG44-based production cell line
    • Cell line specifically adapted for high-cell density cultivation
    • Specifically designed DHFR selection system for low-concentration MTX, with no amplification step, high-producing stable pool selection
    • Demonstrated engineering of cell lines for specific CQAs optimization (glycosylation modification, cotranslational protein processing) allows de-risking of biosimilar development projects
    • Optimized high-yield FACS-based cloning strategy with flow cytometry-based single-cell productivity assessment
  • PUZZLEX Expression Vector Platform
    • Modular assembly vector platform allows seamless generation of barcoded vector libraries for stable pool transfection
    • Hundreds of experimentally validated modules (promoters, UTRs, signal peptides, polyadenylation signals etc.) ready to be cloned into expression vectors
    • Solid-based vector assembly allows generation of multicistronic vectors (up to four cistrons experimentally verified) in 384-plate format
    • Fully automated hands-free assembly, operated by automatic liquid handling system
  • COMPREHENSIVE clonal cell line profiling platform (low-flow-based)
    • Critical quality attributes assessment platform at nanogram product scale
    • Primary sequence confirmation, identification and quantification of glycoforms, clipping, oxidation/deamidation profiling, and assessment of other important analytical characteristics
    • Ability to perform CQA profiling early during the mini-pools/clones scaling process
  • Perfusion and continuous capture manufacturing process
    • Established and experimentally validated state-of-the-art scale-down perfusion process models (SpinTubes, ambr15 microbioreactors, 3L TFF/ATF perfusion system)
    • Perfusion process optimization guided by design-of-experiment methodology
    • Comprehensive metabolomic profiling of culture media and producer cell lines to guide media and process optimization
    • 2 column-continuous product capture technology allows most efficient utilization of affinity capture media, while minimizing hold and processing times, CAPEX/OPEX and facility footprint

Analytical development

YURiA-PHARM has developed and qualified a comprehensive set of platform analytical methodologies, capable of providing maximum information on the recombinant protein product quality that may be necessary for future development:

  • UHPLC – Intact mass-spectrometry (reduced, nonreduced, after fragmentation (papain, IdeS));
  • Peptide mapping with UPLC-MS/MS or CE-MS/MS separation, reduced, non-reduced;
  • CZE, cIEF, CE-SDS;
  • HILIC-UPLC, CE, PGC-CHIP-based glycoprofiling;
  • DSF (high-order structure profiling)
  • FcRs, C1q, other binding kinetics profiling;
  • Etc.

YURiA-PHARM has also developed a unique analytical solution, based on low-flow chromatography system for comprehensive characterization of CQAs for a target product utilizing multiple-attribute method (MAM) approach at the earliest stages of pools and clones selection (COMPREHENSIVE platform) to perform data-driven decision on producer cell line selection for research and masteer cell banks. Apart from the internal projects, our analytical platform can perform stand-along analytical tasks to support your project needs.

Discovery solutions

YURiA-PHARM is developing a unique two-stage phage display platform for antibody affinity selection.

YPhAGE platform allows screening of binders in a full-size format early in a discovery campaign without losing the diversity advantage of phage libraries.

All risks and additional time/cost, associated with humanization, are eliminated by direct utilization of the human IgG framework.

Our facilities allow us to sample diversity libraries of 10^11 and support further BLI-based high-throughput epitope binning. With that we are able to select pools of the most optimal binders while substantially reducing the risk of process development issues due to the full-size IgG format.

Each selected candidate is fully profiled according to:

  • binding kinetics and specificity (BLI, flow cytometry, bioassays);
  • activity (FcRs, C1q binding, ADCC, CDC);
  • manufacturability assays (SEC-HPLC-TDA, DSF, Intact MS etc.)

The workflow allows seamless generation of stable cell pools for large-scale production of selected antibody candidates.

Currently, platform-demonstration studies on selected antigens are under execution.

We are looking for collaboration on your target to exploit the advantages of the YPhAGE workflow.