ASCII Startup Industry-Government-Academia Collaboration Aiming for Practical Use of Regenerated Organs Produced with a Bio 3D Printer Listening to How to Refine Japan's Unique Technology
This article is a reprint of an article published on the IP BASE community site on intellectual property and startups of the Patent Office (external link https://ipbase.go.jp/). .
Cyfuse Co., Ltd. is a regenerative medicine startup from Kyushu University that develops bio 3D printers that create tissues and organs using only cells. Currently, we are conducting clinical trials at universities and joint research and development with dozens of companies. Shizuka Akieda, Representative Director of the company, which aims to realize a regenerative medicine platform using its own technology from Japan, and Masahiro Sanjo, Director, CFO and General Manager of Business Management Department. We asked about the intellectual property strategy in
Cyfuse Co., Ltd. Representative Director Shizuka Akieda Graduated from the Department of Agricultural Chemistry, Faculty of Agriculture, Meiji University. After completing graduate school at Kyushu University, she worked as a researcher in the field of gene analysis and regenerative medicine at Kyushu University, and then engaged in the JST project (commercialization of bone and cartilage regeneration) at Kyushu University Hospital. Joined Cyfuse as one of the founding members in 2010, participated in NEDO projects and other projects as a core researcher, and oversaw all internal and external R&D projects related to Cyfuse. From 2016, he will work on the company management of Cyfuse as a director from the top position of research and development.
Manufacturing blood vessels and organs with a bio 3D printer
Cyfuse Co.,Ltd. Founded regenerative medicine startup from Kyushu University. Currently, we have laboratories at Kyushu University and the University of Tokyo. Development and sales of 3D printers "Device business" We are developing three businesses.
https://www.cyfusebio.com/development
The basis of the company's organ fabrication technology is a unique bio-3D printing technology that stacks cell-only clumps called spheroids on fine needles like a flower arrangement. At first glance, it looks very simple, but in fact there are about 200 types of cells in the human body, and various types of know-how are required to produce organs for regenerative medicine products, such as different culture methods depending on the type.
For example, regarding cell-to-cell adhesion, we use the natural aggregation of spheroids (cell aggregation phenomenon). has been acquired and held as the company's basic patent.
The company protects its own products by possessing these basic patents exclusively, while promoting cell development in the field of regenerative medicine and cells in collaboration with joint research partners and joint development partners. Bio 3D printers have already been installed and operated at various research institutes in Japan and the United States, and together with these partners, we are proceeding with research and development aimed at the practical application of the world's first cell products.
https://www.cyfusebio.com/product
There are two types of bio 3D printers to be deployed: "Regenova", which stacks spheroids on a sword mount, and "S-PIKE", a tabletop type that moves needles to arrange and fix cells. Approximately 1 cm of spheroids can be accumulated in about 1 hour. Technically, there are no restrictions on shape or size, and in theory, it is possible to create organs from the whole body. Currently, we are conducting three clinical trials, which are in high demand: blood vessel regeneration, nerve regeneration, and bone and cartilage regeneration.
For example, hemodialysis patients often end up with vascular damage because they need to be punctured with dialysis needles about three times a week. When it is difficult to perform dialysis using the patient's own blood vessel, an artificial blood vessel made of synthetic fibers or the like is used. It is expected that if a patient's own cells are used to create and transplant a blood vessel, it will function in the same way as the patient's own blood vessel. Blood vessels made only from cells are thick and elastic, so they are characterized by their ability to withstand surgical procedures using sutures. Currently, clinical trials are underway, and the company is moving toward early commercialization.
Regenerated blood vessels (Image source: Cyfuse)
As for nerves, conventional artificial nerves such as silicon tubes can only regenerate thin nerves, but nerves made of cellular components are expected to regenerate nerves and restore lost sensory and motor functions. It is We are working on development so that we can regenerate peripheral nerves such as fingertips first, then central nerves and spinal cord nerves.
Regenerated nerves (Image source: Cyfuse)
Collaboration with companies with strengths in various fields for practical application
The company's business is centered on joint research and collaboration with medical institutions and companies. has partnerships with dozens of companies. This is an unusually high number for a medical startup.
"The company name Cyfuse was named with the idea of making things by fusion. It is difficult for us alone to make organs and deliver them to patients. We will deliver them to patients as soon as possible. In order to deliver it, we are focusing on the development of organs, and other parts are being collaborated with doctors and companies who are experts in each field." (Mr. Akieda)
So far, we have developed cell culture and bio 3D printers in the labs of Kyushu University and the University of Tokyo, but for full-scale commercial production, mass production and storage technology, manufacturing facilities, supply chains related to regenerative medicine You will also need the surroundings. Therefore, we are collaborating with Fujimori Industry Co., Ltd. for the development of mass cell culture technology, and with Iwatani Corporation, which has gas and cooling technology, for the development of cell preservation technology. For the manufacturing base, we have partnered with Hitachi Global Life Solutions Co., Ltd. and are using the company's facilities. In addition, a manufacturing base for cell products was established within the facilities of Taiyo Pharma Tech Co., Ltd. in Takatsuki City, Osaka.
"In the near future, for example, we hope to be able to deliver even one necessary organ to each medical field. In the future, regenerative medicine will become one of the treatment options as a matter of course. Yes, and I think it would be good if patients themselves could choose regenerative medicine products and treatment methods according to their disease, just like choosing the specs of a smartphone.”
Intellectual property is the key to making good use of external experts and partner companies
https://www.cyfusebio.com/product/regenova
At Cyfuse, CFO Masahiro Sanjo oversees all legal and intellectual property matters, and in addition to negotiating intellectual property with external universities and applying for intellectual property, is working on the development and operation of the internal intellectual property management system. . As a strategy, with the three patents of the basic technology "3D cell stacking technology", "Kenzan method", and "bio 3D printer device" as the core, we will hold these peripheral patents and hide the parts we want to protect with know-how. ,something like. How to handle patents tends to be an issue for university-launched startups.
“When we were doing research at the university, it was a time when researchers themselves often issued patents on their own, and the handling of intellectual property was immature. We have received an exclusive license from Kyushu University, the holder of the basic patent, and have started research and development as a company.” (Mr. Akieda)
In the medical field, it takes a long time to generate business profits, and during that time, the support from universities such as industry-university joint research is not small. It is also important to dare to take the form of a license rather than a purchase and foster a good relationship for both parties.
"I think that each university and company have their own individual relationships.In our company's case, they have supported the growth of the company's business since its founding, and have been in contact with us with the stance of moving forward together. I feel very blessed by all of them.” (Mr. Sanjo)
Of course, it may take 10 to 20 years for such research and development and technology development to finally become a product. For start-ups that have just been established, it is difficult to talk about specifics at the beginning of joint research, as it is often not possible to discuss intellectual property, let alone the image of commercialization. It is said that there is also a part.
"I feel that the university understands the situation of startups like this. Under such circumstances, for example, when the company succeeds in raising funds, the company hastily buys the intellectual property, We believe that severing a relationship may, in some cases, hinder future corporate growth.
At the time when I applied for the basic patent, the theoretical element of ``making practically living cells three-dimensional'' was large, but it was not until the actual research and development results became visible. A real pleasure for those involved. When I visited Kyushu University to report on the company's research and development progress, they were delighted to see the size of the tissue and organ that could be produced gradually increasing from less than 1 millimeter to 1 centimeter, then several centimeters, and the organ being completed. To be honest, I was really happy.” (Mr. Sanjo)
While more and more startups are appointing dedicated IP officers, Cyfuse has taken a unique approach.
"I think it's generally a reasonable strategy for startups in the growth period to set up an IP department or an IP manager, but in reality, they have to run development recklessly for about five years after their founding. I think it's important to strike a balance between management and strategy during times of crisis.I think it's important for people who have some understanding of development sites and intellectual property practices to act strategically. I think it would be reasonable to ask outside experts such as patent attorneys,” says Mr. Sanjo.
Cyfuse, in particular, has a wide range of technical research to handle, so it uses multiple external experts depending on the content of the intellectual property. Rather than having a single patent attorney understand all technologies, we carefully select and request experts who can understand the words of researchers in the field by dividing them into areas of specialty such as pharmacy and mechanical engineering. It is said that he tried to do it. From within the company, the on-site person in charge acts as a point of contact and communicates with external offices regarding requests for applications and investigations.
“In the startup phase of a company, various obstacles are expected, such as a situation where the intellectual property strategy is not organized, and there is a high turnover of personnel.In such a situation, there is no sufficient internal discussion. If you just set up a full-time intellectual property manager and leave everything from strategy planning to management, you will feel relieved, and as soon as that person leaves the company, there is a risk that there will be no one in the company who understands intellectual property. In the case of our company, as our research and development progresses, our relationships with outside experts have grown longer, and we manage intellectual property with continuity and continuity.” (Mr. Sanjo)
Rather than a full-time intellectual property officer, researchers and engineers who know the field directly interact with external experts to increase understanding of intellectual property. In fact, at Cyfuse, young researchers who have learned intellectual property on the job grow through practical work, and they aim to become an intellectual property manager in the future.
"At a startup with few people, when you have a problem, ask a reliable outside person (experienced person)! This is also a lesson from seniors. By borrowing the help of an experienced outside person, For example, when conducting joint research, we create documents together with the partner's intellectual property department, so we can learn a lot from that. I feel like I'm being nurtured in all aspects.I'm really blessed and grateful to my teammates." (Mr. Akieda)
In order to build a good relationship, it is said that the partners are carefully selected. For example, when selecting an external patent attorney, he emphasized communication skills.
"Our business domain is a new field of medical-engineering collaboration and industry-academia collaboration, so we need a challenging spirit and a new development mindset in every aspect. Dr. In addition to their technical knowledge and expertise, many of them have good personalities and are enthusiastic, so we have been able to build a really good relationship.” (Mr. Akieda)
The company's intellectual property strategy is also utilized in open innovation and partnerships with dozens of business companies. In intellectual property-related due diligence, which is often carried out when collaborating, the content that was considered to be an issue at the beginning of the alliance has changed, and as various clinical trial results and the number of alliances increase, the intellectual property strategy will change. It is said that evaluation from the outside for intellectual property management has also increased. For Cyfuse, it was necessary and important to think about the "evaluated intellectual property strategy" to such a level through trial and error from the early stage of development through continuous discussions both inside and outside the company.
(Image provided by Cyfuse)
Recently, Cyfuse has finally entered the product development stage for commercial production of future regenerative medicine products. Regarding the next business development, Mr. Akieda said, "We are finally seeing the path from the stage of basic research and application development to manufacturing and production. First of all, we have obtained approval for one regenerative medicine product from our current pipeline. We would like to increase the trust and value of the company, and then expand it widely, including overseas.Based on our technology and activities, our people will grow, the company will grow, and in the future, we will develop medical care. We would like to expand our activities not only in this field, but also in other industries and fields such as education and food," he said.