THE SPARX SAILINGTM MULTI-SPECIFIC ANTIBODY DISCOVERY
Big Data-Aided Target Mining
Target validation remains a bottleneck for the development of innovative medicines, primarily due to the complexity of the biology and pathology of a given disease. The true link between a disease and a molecular target is still largely established in late stage clinical trials. Therefore, data mining in patients without large and expensive clinical trials would be a cost-effective approach to obtain early but potentially true therapeutic signals on previously unexploited molecular targets. Data-driven innovation requires data mining from the massive volume of multi-dimensional and complex datasets out of press releases, journals or web articles, scientific reports, and Twitter feeds. At Sparx Therapeutics, we utilize big data analytical techniques, such as machine learning algorithms, to integrate the massive amount of potentially useful data in drug discovery. Multiple in-depth processing layers in the data-driven learning methods followed by the commonly used natural language processing (NLP) models is employed for target mining and prompt development of drug candidates.
Antibody Phage Display
Developed by GP Smith (2018 Nobel Laureate in Chemistry), phage display technique has been widely used in peptide, protein, as well as antibody engineering. Encapsulating the ssDNA gene, phage particles display the protein encoded by the gene on the surface, providing a physical linkage between phenotype and genotype. A large pool of phage particles can be incubated with target antigens on a solid support, washed, eluted and re-amplified by bacteria for additional round of selection to enrich positive clones to identify therapeutic leads. Sparx utilizes proprietary antibody phage display libraries to discover and develop therapeutic antibodies. Sparx’s antibody phage libraries include both human antibody libraries from human blood donors as well as synthetic antibody libraries from a human antibody framework. These large and effective antibody libraries are coupled with streamlined and robust phage display selection techniques to identify high-affinity and high-specificity human antibodies that bind to Sparx’s valuable and promising therapeutic targets.
Hybridoma Antibody Discovery
The hybridoma technology is a traditional but still widely used method to produce monoclonal antibodies. The B lymphocytes secrete monoclonal antibodies but cannot replicate themselves in culture. On the other hand, the myeloma cells do not produce antibody but can replicate in culture easily. The hybridoma, a fusion of the B lymphocyte and the myeloma cell, inherits features of both B cells’ antibody secretion and myeloma cells’ replicative abilities, and therefore has the capability to produce large quantity of monoclonal antibodies continuously. At Sparx, mice are immunized with variety of antigens, including DNAs (encoding protein antigens) peptides, proteins as well as antigenic proteins over-expressed on the surface of cells or incorporated in nanoparticles. After nine days of one-time immunization (quick protocol), or after weekly repeated immunizations for 3-4 times followed by a booster immunization (regular protocol), the mice are sacrificed and the B lymphocytes from their spleens are fused with myeloma cells. The fused hybridoma cells that can survive in HAT medium are further screened, and the clones secreting the desired antibody are selected for antibody production.
Sparx Multi-Component Nanotechnology Platform – SPARX MULCOMTM – is an advanced drug delivery polymer-lipid hybrid technology designed to deliver multiple drugs and biologics for combination therapy. With our SPARX MULCOMTM, stable nanoparticles encapsulating molecules with multiple properties within the same particle via self-assembly processes are formed. Hydrophobic drug to hydrophobic polymer/lipid tail interaction allows for their efficient entrapment within a dense polymer matrix or lipid bilayer. Hydrophilic compounds/biologics are first pre-formulated via nano-coordination chemistry and/or reverse-micelle strategy to obtain suitable surface coating for enhanced drug encapsulation. Nanoparticles are well protected with a dense poly (ethylene glycol) (PEG) layer that provides steric stability and can be further tuned to for targeted drug delivery via attachment of targeting ligands and/or antibodies.
LEMMAbTM (Linker Enhanced Mono-chained Multi-specific Antibody) is our proprietary technology platform that uses natural IgG with Fc in constructing bispecific or multi-specific antibody for cutting-edge biomedical research and development. Owing to the single chain and symmetrical nature, LEMMAbTM antibodies resulting from this technology are free of mismatches, more soluble, less prone to aggregate, simpler to purify, and expressed in higher yield. These types of antibodies tend to have decreased immunogenicity and improved binding affinity, safety profiles, and developability.
SMARTOPTM (Symmetric Multispecific Antibodies with Relative-affinities fine-Tuned by phage Off-rate and PH-selections) is another proprietary technology platform that constructs novel bispecific or multi-specific antibodies for biotech and pharmaceutical research and development. SMARTOP™ antibodies shares several features with LEMMAb™ antibodies as this type of antibodies are also symmetrical and free of mismatches, more soluble, less prone to aggregate, simpler to purify, and expressed in higher yield. In addition, SMARTOPTM antibodies are selected by slower off-rate and better tolerance for the lower pH values in tumor microenvironment. As a result, SMARTOP™ antibodies tend to have improved tumor retention and more tailored target engaging kinetics. They also enjoy decreased immunogenicity and improved binding affinity, safety profiles, and developability.