Toray Industries, Inc., which was celebrating the 90th anniversary of its founding last year, is a diversified chemicals manufacturer. Our aim is to lead the world in advanced materials for contributing to society through the creation of new value based on chemistry. The pharmaceutical business is expected to be an important part of our Life Innovation project, which is prioritized as a growth business area in our management plan. The driving force behind this project is in the DNA of Toray as a manufacturer. Through our fundamental, distinctive, and persistent efforts, we have achieved world firsts in synthetic organic chemistry and bioprocess engineering (Beraprost Sodium, Nalfurafine Hydrochloride, natural Interferonbeta). Toray will continue to strive to overcome intractable diseases that have been left behind, including neurological, autoimmune, and renal diseases, by integrating our acquired understanding of these disease areas and our accumulated drug discovery technologies.

Many self-assembling molecules have been developed as surfactants and gelators. On the other hand, a new class of self-assembling molecules has been emerging as biologically active molecules. These “self-assembling bioactive molecules” are classified into two categories: designer molecules that exert biological activities through self-assembly, and bioactive molecules whose mechanism of action turned out to be self-assembly. In the present review, we summarize these two classes of self-assembling bioactive molecules.

For pharmaceutical companies focusing on to deliver new chemical entities, the circumstance around the pharmaceutical industries becomes more severe in these years. From the point of view of reducing cost and improving speed, many companies try to introduce open innovation as a crucial idea for departing from “go it alone”. Using this opportunity, I introduce how we apply open innovation at the stage of lead generation as a key item of compound library for HTS. For improving diversity of chemical library, we have joined Japanese Compound Library Consortium (J-CLIC) for group purchasing compounds and shared compound libraries with Astellas. For adding value and making full use of potential of our library, we have joined Drug Discovery Innovation and Screening Consortium (DISC) supported by Japan Agency for Medical Research and Development (AMED). And we have initiated screening activities against anti-malaria supported by the Global Health Innovative Technology Fund (GHIT Fund).

Antibody based-technologies are well known as the established format for the drug discovery and development. Antibody based-technologies are composed of multiple technologies. In early stage of antibody-drug history, immunogenicity of antibody obtained from rodent was a big issue. However, it has been overcome by chimeric antibody technology, humanized antibody technology, followed by phage display technology and human antibody generating transgenic mice technology. At present, drug targets applied to normal antibody technology seemed to be nearly exhausted. For further success of antibody-based biologics, expectations towards small molecular antibody technology are getting larger because of possible better penetration profile to tissues and organs, easy production, capability of combination with other drug formats, and unique bonding characteristics.

Advance in library approach and accumulation of conformational information of proteins are causing drastic changes of protein engineering. Flexible design for the combination of amino acids appearing in library and easy access to conformational information enable us to draw up effective and dense libraries to express a new function on non-functional protein. Here, we show the creation of a protein with a new function, especially molecular recognition, by means of library approach and conformational information of proteins.

Antibodies are indisputably the most successful reagents in molecular-targeting therapy. However, use of antibodies has been limited due to the biophysical properties and the cost to manufacture. To enable new applications where antibodies show some limitations, we have developed an alternative-binding molecule with non-immunoglobulin domain. The molecule is a helix-loop-helix peptide, which is stable against enzyme degradations in vivo and is too small to be non-immunogenic. Here, we introduce the molecular-targeting peptides termed “microantibodes” that show antibody-like functions, high affinity and high specificity for the targeted proteins. Since the helix-loop-helix peptide folds by virtue of the interactions between the amino acid residues positioned inside the molecule, the outside solvent-exposed residues are possible to be mutated with a variety of amino acids to give a library of the helix-loop-helix peptides. Based on our technology of phage-displayed libraries for antibodies, we constructed a phage-displayed library of “microantibodes”. The library was screened against granulocyte colony stimulating factor (G-CSF) receptor, and the screened peptide was cyclized by a thioether linkage into the N- and C-termini. The cyclic peptide showed a strong binding affinity (Kd of 4 nM) to the receptor and a long half-life (>2 weeks) in mouse sera, proving an enzyme-resistant property. Furthermore, immunization of the peptide to mice showed no induction of the antibody titer (non-immunogenic). We have applied our peptide libraries for VEGF, hIgG/Fc, interleukins, and kinases to obtain their molecular-targeting peptides “microAntibodies”.

VHH domain therapeutics derived from heavy chain antibodies of Camelidae are currently being developed as novel antibody therapeutics. Advantageous properties of this VHH include high stability, efficient bacterial expression, and ease of antibody engineering; however, it has a short blood half-life. Through examples from previous clinical studies, we would like to consider the issues and the prospects of the development of VHH therapeutics. Furthermore, we describe a new method of VHH development by combining a phage display library and high-throughput sequencing, and introduce the IgG-VHH conjugate as a novel antibody therapeutic prepared by antibody-specific modifications (CCAP: Chemical conjugation by affinity peptide).