July 24, 2017
The University of Tokyo
BrightPath Biotherapeutics Co., Ltd.

Patent for rejuvenated antigen-specific T lymphocytes using iPS cells*1Tokyo, July 24, 2017 – The University of Tokyo and BrightPath Biotherapeutics Co., Ltd., (TSEMothers: 4594) jointly announced the issuance of a patent (P6164746, dated July 19th 2017) forgenerating rejuvenated antigen-specific T lymphocytes using iPS cells*1. This breakthrough wasachieved in the laboratory of Professor Hiromitsu Nakauchi, at the Institute of Medical Science,
University of Tokyo. This patent has been exclusively licensed to Advanced Immunotherapy Co.,Ltd (a subsidiary of BrightPath Biotherapeutics) and is being co-developed for future use.
1. Summary of Patent
Patent No.

P6164746

Title of the Invention

Method for producing antigen-specific T cells

Patentee

The University of Tokyo

LicenseeAdvanced Immunotherapy Co., Ltd.

2. Patent Description
T lymphocytes play an important role in acquired immunity by protecting us against pathogens
and cancer. Cytotoxic T lymphocytes (CTLs), in particular, recognize various pathogenic antigens
and specifically eliminate the cells that display these antigens. Numerous attempts to develop T
lymphocyte therapieRs for treating viral infections and cancer have been made, albeit with lesssuccess. This is primarily due to the exhaustion of T lymphocytes. Moreover, these T lymphocytes
are often rendered non-functional when collected from peripheral blood or processed outside thebody, especially using the techniques which are available today.
The invention in the patent (P6164746) achieves the technical breakthrough by specifically
producing antigen-specific CD8*2 or CD4*2 single-positive cells from iPS cells generated fromhuman T lymphocytes. The iPS cells are generated from the T lymphocytes and then rejuvenated Tlymphocytes are derived from these iPS cells. This process significantly increases the frequency ofT lymphocytes with the same TCR gene*3 rearrangement pattern, similar to the donor’s
T lymphocytes. These rejuvenated T lymphocytes possess potent killing activity and can belimitlessly derived from the parent iPS cells.
Similar approaches have been tested previously but primarily resulted in the inefficientdifferentiation of active T-cells from iPS cells*1 and hit a dead end because they didn’t use a specificmethod for generating CD8*2 or CD4*2 single-positive cells from iPS cells. The method allows us tomass-produce biologically rejuvenated T lymphocytes that maintain their antigen specificity, andmarkedly increases efficiency of T-lymphocyte therapy. Thus, this invention provides atechnological breakthrough by overcoming the aforementioned issue and we ultimately envision
establishing a viable commercial platform for effective cancer immune therapies.

1Definitions of Terminology*1 iPS (induced pluripotent stem) cells: Pluripotent stem cells induced by introducing certaingenes (initially, the 4 transcription factors Oct3/4, Sox2, Klf4, and c-Myc were used) into
somatic cells. Dr. Shinya Yamanaka and colleagues at Kyoto University established iPS cells
from mice in 2006 and from humans in 2007.
*2 CD8/CD4 cells: T lymphocytes are broadly divided according to the CD8 and CD4 molecules
they express during differentiation. Cells do not express CD4 or CD8 during early
differentiation, a process termed as the double-negative (DN) stage. Cells then express bothmolecules in the double-positive (DP) stage, before maturing into cells that express either CD4or CD8 in the single-positive (SP) stage. CD4 SP cells are T helper cells, and CD8 SP cells arecytotoxic T lymphocytes.
*3 TCR (T-cell receptor) gene: Expressed on the cell membrane of T lymphocytes, the T-cell
receptor recognizes and binds to antigens. T lymphocytes form a great variety of TCR genes
by rearranging the gene fragments by the process of recombination. This allows recognition ofendless antigens presented on the surface of cancer cells, bacteria, and viruses.
For inquiries, please contact:
Division of Stem Cell Therapy, Institute of Medical Science, University of Tokyo
Hiromitsu Nakauchi, IMSUT Distinguished Professor
Phone: 03-5449-5330, E-mail: nakauchi@ims.u-tokyo.ac.jp
Motoo Watanabe, Senior Research Advisor
Phone: 03-5449-5333, E-mail: mwatanab@ims.u-tokyo.ac.jp
BrightPath Biotherapeutics Co., Ltd.
Teruhiko Sakai, Director/CFO
Phone: 03-5840-7697, E-mail: sakai_t@brightpathbio.com

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