LassoGraft Technology® “doi.org/10.1038/s41467-021-21875-0”
We possess two technologies, the RaPID selection technology, and LassoGraft Technology® , to discover high-potential Therapeutic Biopharmaceuticals.
Using the mRNA-display in combination with genetic code reprogramming, the RaPID (Random non-standard Peptides Integrated Discovery) system provides many de novo target-specific high-affinity macrocyclic peptides from a pool of random sequences consisting of more than 1012 members.
Such peptides generally exhibit exquisite binding specificity and high affinity toward the target. They have proven to be highly useful in applications such as receptor antagonist or agonist, crystallization chaperone, and imaging/detection tool. Even though the method offers an extraordinary speed to identify potent species, the macrocyclic peptides are not necessarily ready for drug use because they often suffer from unpredictable pharmacokinetics and bioavailability.
We solved this limitation by copying a “pharmacophore(s)” of macrocyclic peptides and making it (or them) an integral part of a natural human protein resulted in making a more reliable drug format bearing the merit of both macrocycles and proteins. This does not demand any special protein engineering efforts and can be achieved by simply taking the internal sequence of a RaPID peptide and simply inserting it into surface-exposed loops of a wide range of proteins. This technology is named LassoGraft Technology®. By applying this technology, many different proteins, including IgG and serum albumin, could be endowed with binding capability toward various receptors, allowing us to quickly formulate bi-, tri-, and even tetra-specific binder molecules.
Technological benefits of the LassoGraft Technology® are its speed, diversity, affinity maturation, and “Plug and Play” capability. Our technology eclipses existing ones like conventional hybridoma and synthetic library method of Phase display.
Our company entered into an exclusive licensing agreement with applicants’ the University of Tokyo and Osaka University at the end of August 2018 for two patent applications that are the basic technologies of this LassoGraft Technology®. Subsequently, our company has a sublicense agreement with PeptiDream Inc. (TSE First Section: Securities Code 4587) concerning a part of the patent of the drug discovery platform system: PDPS (Peptide Discovery Platform System) technology.
We can apply our technology to any proteins (scaffolds) of your choice, including albumin. However, one of our main application targets is the antibody molecule. Antibodies, including bi-specific and tri-specific ones, are in the center of biopharmaceutical products and development. They inherit many good features as a drug, i.e., solubility, low immunogenicity, pharmacokinetics, immunologic characters (ADCC, CDC), etc.
The Fc portion of the immune-globulin molecule is an interesting scaffold for the application. You can design grafting sites so that it still maintains many of the antibody features. We call the grafted Fc portion Mirabody®. Mirabody’s molecular weight is about one-third of the original antibody, which benefits productivity and therefore the cost of goods. There are eight grafting sites in the Fc portion molecule.
We can also utilize a whole antibody as a scaffold still keeping the original CDR binding activity. We have created bi-specific, tri-specific, or even quadruple-specific antibodies. We named them Addbody®. Similar to Mirabody®, Addbody® possesses many features of the original antibody. There are more than 30 sites for grafting in an antibody.
We welcome your proposal for collaboration in biopharmaceutical product discovery. Our therapeutic target area has no restriction as long as you have (cellular membrane) protein targets.
- Mirabody® uses only the Fc portion of antibody as its structure, and similarly to Addbody® is generated by grafting Lasso peptide sequences with strong target-binding affinities to the Fc structure.
- Addbody® is a novel molecule generated by grafting Lasso peptide sequences with strong target-binding affinities to a part of existing antibody.This is particularly useful when you want to add a second or third functionality to an antibody, or other leading candidate compounds already owned by other pharmaceutical companies.