Pronectins™ are an emerging, proprietary, protein therapeutic class that can be developed to address a broad range of diseases, including cancer, inflammatory and degenerative diseases. Pronectins™ are based on the fourteenth fibronectin type-III scaffold of Human Fibronectin (14Fn3). The well-characterized fibronectin protein is prevalent throughout the human body. Human fibronectin, an extracellular protein, is naturally abundant in human serum. Intelligent loop-diversity has been designed to closely mimic the natural human repertoire and avoid sequence immunogenicity. The intrinsic properties of a Pronectins™ align with the pharmacological properties needed to make it a successful drug, including high potency, specificity, stability, favorable small size, and high-yield production in E.coli and yeast.
Pronectins™ are designed using Protelica’s patented protein design and optimization engine, to achieve high potency and specificity for a therapeutic target while simultaneously selecting for ideal pharmaceutical product characteristics. Protelica is able to screen billions of unique Pronectin™ loop sequences for each drug discovery program and redirect a laboratory designed human fibronectin analog to act as a protein proprietary ligand against a specific therapeutic target. The power of our Pronectin™ platform is distinguished by the synergistic benefit of our universal fibronection type III library design, derived from a bioinformatics analysis of more than 3000 FN3 loop sequences, combined with our patented mutagenesis technologies to create meaningful loop diversity and expand the human repertoire from few thousand to 25 billion new sequences.
Loop diversity is solely generated by the combinatorial effect of a set of naturally/ human occurring amino acids. When combined with the use of statistically preferred loop lengths in Nature, this results in a higher percentage of stable, non immunogenic functional variants. With regard to potential immunogenicity of artificially created loop sequences, we believe our approach has the least risk. Protelica “evolutionary” approach maximizes the use of amino acids selected by nature over the course of millions of years. In addition, since we isolate families of high affinity binders with similar sequences from our library, we can further screen these ligands for lack of potential immunogenicity using in silico, in vitro, and in vivo methods.