Cellular Dynamics Awarded Patents Covering Derivation of Pluripotent Stem Cells from Fresh or Banked Human Blood Samples

Patents Secure CDI’s Position as Leading Manufacturer of Human Cells from Most Common, Easily Accessible Donor Source for Research, Drug Discovery and Regenerative Medicine

Cellular Dynamics International, Inc. (CDI; Nasdaq: ICEL), recently announced that the U.S. Patent and Trademark Office (PTO) awarded the company three patents on the reprogramming of human cells into pluripotent stem cells from human blood. Joining an IP portfolio of over 800 patents awarded to or in-licensed by CDI, these patents position the company as the leading supplier of choice for a reliable, high quality supply of human cells for research, stem cell banking, and cellular therapy development.

Key points:

• Blood is the preferred tissue for the creation of human induced pluripotent stem cells (iPSCs) because of the standardized and relatively non-invasive nature of blood collection.
• The patents cover reprogramming using freshly collected blood as well as samples stored in blood banks.
• US Patent 8,691,574, issued April 8, 2014, covers the reprogramming of hematopoietic progenitor cells from blood into iPSCs using episomal vectors and under feeder-free conditions.
  - An advantage of CDI’s method is that it requires only small volumes of blood, consistent with a standard doctor’s office blood draw.
  - The original method of iPS cell reprogramming uses viral vectors to insert four genes into the adult tissue cell's DNA. These genes integrate directly into the cell's genome. Concerns have arisen over the potential risks associated with this insertion of foreign DNA into the cell's genome, including insertion defects and errors that could lead to tumors.
  - CDI owns the patent covering iPSC episomal reprogramming, whereby episomal vectors drive adult tissue cells back to a stem cell state before exiting the cell. This non-integrating methodology alleviates major safety concerns over the potential use of iPS-derived cells as therapeutics and removes a significant barrier for applying the technology in a clinical setting. Episomal reprogramming already has been performed to Good Manufacturing Practice (GMP) standards, a prerequisite for use of these cells in clinical applications.
• US Patent 8,741,648, issued June 3, 2014, covers the reprogramming of CD34+ hematopoietic blood cells isolated from fresh blood samples into iPSCs.
  - Other reprogramming methods utilize epidermal cells obtained from skin punch biopsies, which are often painful, typically require local anesthetic and may leave scars.
  - Collection of blood is much less invasive.
• US Patent 8,765,470, issued July 1, 2014 covers the production of iPSCs from B cells collected from a banked blood sample and immortalized by introducing elements from the Epstein-Barr virus (EBV).
  - CDI was the first to publish on the methodology to reprogram EBV-transformed cells into iPSCs, in June 2011.
  - Blood samples are often banked as reference material from the study of various diseases, rare genetic disorders and genome wide association studies (GWAS). Banked blood from these repositories can serve as a valuable resource for studying human disease.
  - Banked blood has been modified through the introduction of Epstein-Barr virus (EBV) to enable cells to be frozen, thawed and proliferate indefinitely, known as "immortalization." This patent covers the ability to take small volumes of EBV-transformed blood and create iPSCs, as well as terminally differentiated cells, that do not contain the EBV genetic elements or the episomal reprogramming vectors.
• CDI uses the technology covered in these patents to manufacture its iCell® and MyCell® products.
• CDI’s iCell and MyCell products are used by biopharmaceutical companies for drug discovery; non-pharmaceutical companies, such as food companies, to develop healthier foods; and academic customers in research as well as in the development of cell-based therapies.
• These patents position CDI as the leading supplier of choice for researchers needing a reliable and high quality supply of human cells for research, stem cell banking, and cellular therapy research and development.
  

Quotes:
Bob Palay, chief executive officer of CDI, said, “These patents are further evidence of CDI’s continued leadership in the pluripotent stem cell field. Derivation of iPSCs from blood has several advantages over other tissues: donors are already familiar with a standard doctor’s office blood draw, where only a small amount of blood is required; blood is easily accessible and not exposed to environmental influences, as skin is; and the hundreds of thousands of previously banked blood samples enable researchers to create human disease models from donors with known genotypic and phenotypic backgrounds. These patents cover the reprogramming of both fresh and banked blood, enabling our customers to access any samples in their research quest to improve healthcare.”