StableBody Technologies

Technology — StableBody Technologies, LLC

TECHNOLOGY | Meeting the Unmet Need in Protein Engineering | Molecular or protein engineering of antibodies is employed to improve the biochemical and biophysical properties of the antibodies of interest. Two strategies to achieve protein optimization are: | 1.    Rational methods are based on structural knowledge derived from X-ray crystallography, Nuclear Magnetic Resonance (NMR) spectroscopy, and in silico modeling, yielding the generation of a small set of variants. However, despite the development in algorithms and computer power, the quality of antibody structure prediction, particularly regarding CDR-H3, remains inadequate, and the results of antibody–antigen docking are also disappointing. |  2.    Empirical methods are based on generating large libraries using phage, ribosome, or yeast display, relying on screening to select the desired variants. Despite great progress in the expensive rational method strategy, new approaches are in high demand. One of the major remaining goals is to improve the accuracy of computational methods, which will allow for the prediction of point mutations that improve the affinity, stability, and other properties of interest. A new approach by StableBody Technologies, LLC is continually being developed to create antibody-based molecules that are superior in their potency, specificity, localization, and safety. | Stablebody Technologies, LLC has developed an elegantly simple, rapid, and cost- effective method to design, engineer, and produce large numbers of structurally and functionally improved proteins. This is not a high throughput screening approach but a rational, focused, and computational approach producing calculable, rapid and robust improvements. These novel, proprietary bioinformatic algorithms are making huge improvements in the protein engineering field. | Through earlier StableBody Technologies, LLC research on thermodynamic parameters of antibody structure/function variations we uncovered compensatory mechanisms that stabilized suboptimal residues in antibodies caused by both variable region rearrangements and hypervariable mutations.  StableBody Technologies, LLC identified the underlying destabilizing alterations and replaced suboptimal amino acid residues with evolutionarily- selected stabilizing residues.   While these alterations can be determined though brute force approaches, this path is highly inefficient.  StableBody Technologies, LLC has cataloged a number of alterations that greatly enrich for beneficial/stabilizing substitutions, thus requiring far less effort to achieve improvements in thermal stability.  | A simplified screen involves scoring amino acid positions in the target scFv, giving highest priority for mutational analysis to sites at which a limited repertoire of amino acids is observed in our database.  Low priority is given to invariant sites and sites with the lowest variability.  By restricting our screening of amino acid alterations to changes documented in functional antibodies, as well as other considerations of protein structure such as the location and size of each residue, we have demonstrated dramatic stabilization using minimal R&D effort compared to randomized or combinatorial approaches. | AffiBio-UIA™ affords a proprietary set of parameters for the routine and facile production of recombinant antibody fragments with improved stability and affinity profiles. Efficient means of providing improvements in protein function and structure offer many competitive advantages over other recently developed methods.  Such an efficient method reduces prohibitive R&D costs, decreases the probability of product failure, shortens lengthy development times and increases production scale-up; all with the goal of optimizing product commercialization. | Challenges AffiBio-UIA™ addresses: | Performance: The AffiBio-UIA™ designs and confers better specificity and performance to less optimal antibodies. | Thermal and Chemical Stability: The AffiBio-UIA™ analyzes amino acid sequence alignments and identifies key amino acid sequence changes for conferring thermal stability to less stable antibodies. | Variability: AffiBio-UIA™ makes protein reagents that are consistent lot to lot and reproducible. | Development Timelines: AffiBio-UIA™ significantly reduces the development time using rational protein design through computational biology protein engineering. | Production Timeline and Cost: AffiBio-UIA™ makes proteins that are easier to isolate and purify, producing larger yields. | Product Applications – The versatile AffiBio-UIA™ allows a single antibody fragment to be used in various applications. | The StableBody core technology introduces major cost savings while greatly expanding revenue opportunities for any product candidate!