Professors Stefano Menegatti and Ruben Carbonell have received $60,000 from the Chancellor’s Innovation Fund (CIF) to develop and commercialize a novel technology for the purification of therapeutic monoclonal antibodies (mAbs). Established by Chancellor Woodson in 2010, the CIF mission is to support campus researchers as they turn their discoveries into market-ready solutions.
The technology, developed for commercialization as LigaGuardTM in partnership with LigaTrap Technologies LLC, has the potential to substantially reduce the manufacturing costs of therapeutic mAbs, which are currently the main weapon in the fight against cancer, autoimmune diseases (e.g., rheumatoid arthritis), and degenerative disorders (e.g., Alzheimer’s).
Since the first mAb was commercialized in 1986, this class of therapeutics has grown to nearly 80 products approved in the US and Europe, producing combined sales > $200 billion. In human terms, a team of researchers at the University of Pittsburg estimates the median cost of one year of oncology or hematology treatments with various mAbs combinations is $142,833.
Current industrial production of mAbs relies on expression in engineered Chinese Hamster Ovary (CHO) cells. Following expression, mAbs are purified using a series of up to five “downstream” purification steps. Those operations clear a number of contaminants, including “host cells proteins” (HCPs) and DNA, which must be stringently removed (> 99.99%) to avoid adverse effects in patients.
Current downstream purification processes rely on a series of batch operations, each featuring steps of adsorption, washing, and release of the mAb product. These processes enable the production of large-scale quantities of therapeutic mAbs and have ensured a steady supply to clinics worldwide for decades. On the other hand, they are characterized by long production times, large footprint, and high capital and operational costs. The latter in particular come from the use of expensive adsorbents for mAb purification.
LigaGuard is unique in at least three important ways. First, it enables continuous processing in lieu of batch operation, as the liquid harvest from the cell reactor is continuously flowed through a unit packed with the LigaGuard adsorbent, which captures the impurities while letting the mAb product flow through unbound. Second, LigaGuard is capable of efficiently removing groups of high-risk protein impurities (HRPs) that current purification systems struggle to remove. HRPs are a major threat to patient health as they are highly toxic or can degrade the mAb product during storage. Third, LigaGuard is inexpensive and can be employed as single use technology, thereby simplifying process validation.
The key to LigaGuard’s purification activity is its chemical design. It comprises a collection of chemical binders tailored for the task by Profs. Carbonell and Menegatti. Ruben and Stefano are masters of the art.
The request-for-funding application they submitted to the CIF included letters of support from several corporate sponsors of the research. One corporate author wrote that “[LigaGuard] could be a critical component of a purification toolbox that ultimately enables an all-flowthrough polishing solution. A second author describes LigaGuard as having “the potential to revolutionize the landscape of purification tools for bioprocessing and become adopted by the major biopharma players worldwide.” A third author wrote “[…] the PepMix technology has all the characteristics to become a game changer in the downstream segment of biomanufacturing” (PepMix was the original name for LigaGuard).
The initial work on LigaGuard technology has been published in two articles: “Targeted Capture of Chinese Hamster Ovary Host Cell Proteins: Peptide Ligand Discovery” and “Targeted capture of Chinese hamster ovary host cell proteins: Peptide ligand binding by proteomic analysis.” A third publication demonstrating this technology in a flow process is forthcoming. Several of Ruben and Stefano’s patents involving chromatographic separation resins are already licensed.
Congratulations and Good Luck to Stefano and Ruben on this groundbreaking venture!