Patenting is surely a big game in Biotech and science generally, as some open-source initiatives have started to question whether such a choice is sustainable and whether they are other productive models for society?
As I was looking for a contact at Cambia.org, I came across Osmat Jefferson LinkedIn profile. At that time we needed to find an open-source technology to develop our product pipeline and Cambia has provided several of these technologies under BiOS (biological innovation based on open society) licenses. Open-source and DIY Biology is part of the DNA of Tiamat Sciences, the project is born in the community lab ReaGent and we strongly believe that science should be accessible to everyone. Osmat has been a principal scientist at Cambia.org for 15 years and although no longer working in a lab, she has considerable experience in open-source biotechnology, and she agreed to be interviewed on the matter of open-source in Biotech.
France-Emmanuelle Adil - Tiamat CEO
Can you introduce yourself?
I am the director of application development at Lens.org. Len.org is a public benefit company that is owned by Cambia, a social enterprise, and Queensland University of technology. The Lens team is building an open platform for innovation cartography. By serving nearly all the global patents as annotated public goods integrated with scholarly and technical information, we strive to expand the demographics of problem solving so that collectively, we can make the innovation system more fair, equitable, transparent and inclusive. The purpose of my role is to lead a Lens team to design and implement applications that would make the scientific and patent knowledge behind the two data corpora and their linkages, and soon other innovation knowledge, open and public to inspire, inform productive partnerships, and help entrepreneurs, citizens and policymakers find their own solutions.
“I believe that science is a public good which means that scientific knowledge is not rivalrous or exclusive.”
What made you work on open-source projects?
For me, openness has been part of the scientific social norms I grew up with. I believe that science is a public good which means that scientific knowledge is not rivalrous or exclusive. In the not distant past, scientists were mainly recognised for their contribution to society. To gain societal trust, they share and open up their scientific methods/findings to objective testing and verification by others to ensure the collective knowledge is advanced, public interest is served, and society benefits from diverse contributions. From that perspective, I feel that right now the
a diverse ecology of innovators that can keep our society in a more balanced state.
I am committed to open-source and open-biology because of its potential to restore a balance and nudge a positive change in our society. I come from that principle of openness.
So, do you think that open-source is good for innovation?
It depends on how you define and use open-source. If openness is the ability to, not only access, but use and re-use in a receptive culture, then yes, I believe that open-source is the best way to induce a collaborative innovative culture that can be more efficient and fair.
You mentioned different meanings for openness, what do you mean? Are there other ways to understand open-source?
There are more than 50 meanings for the word “open” or “openness” and unfortunately there is no common understanding of the concept among the scientific community. Some people think of “open” as “open access” which is just the ability to access and read information, but doesn’t include the ability to share, use, and re-use with a common purpose to solve a collective problem. Open may also mean “open science”, a free exchange of scientific knowledge and at the same time, patenting research outputs, or charging for an added value to a product/service.
You can read more about such meanings here:
What do you think about patents?
A patent is a bargain between a government and an inventor. In exchange of getting a monopoly for a certain limited time, the inventor fully discloses their invention to enable those skilled in the art to reproduce it. So, the government uses the patent as an economic incentive to encourage investment, boost innovation, and serve the public interest. This is the basis of having patents in an economy, as I understand it.
But over time, that concept has changed mainly because of the discovery that patents or intellectual property rights could also be used as a business asset and companies can trade these assets. So, when some governments implemented policies to accelerate innovation, they relaxed some of the patenting requirements and used intellectual property rights in their international trading agreements as well, which as you know, lead to a huge increase in patenting activity across the globe. So, governments can use that tool to make patenting rules more elastic or restrictive based on their economy’s needs. In the life sciences and around the
Moreover, since the early 1990s, the culture of patent offices has begun to change. Patent offices have become user-based funded agencies, which means, unlike any government agency, their funding depends on the number of patents processed per year. So, naturally patent offices’ focus shifted from fully serving the public interest to serving both their clients, whose activities were critical to the office’s financial sustainability, and the public. Serving clients can be different from serving the public interest in terms of ramification to an equitable and transparent innovation system. I believe that the culture shift across various aspects of the innovation system has influenced our current innovative environment and exposed collective challenges for an inclusive and fair society.
Now, patents are more complex to interpret or understand. The complexity of the claim language can be mind boggling and hard to comprehend except by a few highly specialised patent agents and lawyers. It is difficult to navigate the full contextual information around an invention, understand who owns what rights, and until recently, the patent data was not even fully accessible. Full text searching in patents from many jurisdictions is still an issue, and disclosed patent sequences, for example, are not in machine searchable format across many patent offices. (https://www.sciencedirect.com/science/article/pii/S0172219015000848).
“Now, the patenting game is mainly for those companies, organisations or universities that can afford to invest in their acquisition and enforcement.”
When Cambia IP resource and later Patent Lens, the precursor to Lens.org, started in early 2000, Cambia had to buy the patents as image/pdf files and render them text searchable to enable searching and analysis of IP rights in the Biotech field. Then, there was a lot of fighting about Intellectual property rights around genetic work, and Cambia, served the first free patent resource platform enabling people to navigate patenting activities to better understand claimed rights. In addition, Cambia published many landscapes on key biotechnologies including the Agrobacterium-mediated gene transfer collective landscape at https://cambia.org/technology-landscapes/agrobacterium/. And today, despite Cambia’s and other efforts, still, we don’t have a complete picture about claimed IP rights because details on ownership, and licensing information, for example, are not publicly available. This information is not an open knowledge (www.nature.com/articles/nbt.3393).
I see patents as a useful teaching tool, if they are of high quality and used in the purpose they were created for. Granted a limited monopoly but enabling the skilled in the art to fully understand and reproduce the invention. Transparency matters. The public is entitled to view all contextual information around patents.
As discussed earlier, now, the patenting game is mainly for those companies, organisations or universities that can afford to invest in their acquisition and enforcement.
From my perspective, I would like to see a more diverse and richer ecology of inventors able to put the patents to work to make services and products useful to our society, environment, and economy.
Do you know any companies currently working with open-source technology in biotech?
There are several initiatives around the world nowadays. Cambia was kind of unique at the time when it launched the BiOS initiative in 2004.
There are other initiatives like open-society, open-corporates (https://opencorporates.com/), a public benefit company that is developing an open database for the world’s companies, open for all.
In terms of open biotech and Biopharma, here is a link to a few open source projects www.opensourcepharma.net/projects.html and there is a recent initiative by Jenny Molloy at University of Cambridge, who is trying to develop open-source biotech tools for Africa. Here is an interesting article on the six laws for an open-source drug discovery project by Matt Todd that you may find useful. It is open access and available at https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.201900565
In terms of open and free data platforms, you may want to check Lens.org, espacenet, and others.
What is your advice for companies willing to work with open-source technology?
Through my national and international work, I came to experience that science or patents are only a part of the innovative process, and working with open-source technologies allows you to build partnerships based on confidence and trust in that technology. But for these to succeed, the innovation strategy needs to integrate and take into consideration every component, like the technology, the science, intellectual property rights, marketing, manufacturing standards etc..and how they intersect with each other… It’s like a puzzle, as described by Richard Jefferson (www.nature.com/articles/548S8a), all the pieces have to be assembled together in the right place to see the bigger picture in order to make a headway in solving a problem. The global challenges we face as a collective group are enormous for a single group to tackle them alone. We need increased openness, transparency, and a receptive culture to accelerate innovation.
Thank you Osmat for those inspiring answers and considerations, I am sure they will inspire the new generation of innovators, entrepreneurs and researchers! They already opened new doors for us!
What do you think about open-source in Biotech? Share a comment to start the discussion!
A Biotech Talk with Nadège Grabowski, Healthcare team leader at ZAZ ventures
Shortages in raw materials have a big impact on the manufacturing process and unavoidably as well on the end-user, in this case, the patient. Raw materials can be anything used in the process ranging from pipets over bioreactors, as well as organic materials. We interviewed Nadège Grabowski, who worked for several years in cell & gene therapy.
France-Emmanuelle Adil - Tiamat CEO
Do raw material shortages happen often?
I can’t make a statement as to the entire market, but in my experience, in the last 3 years, I had to deal with shortages twice for 2 different raw materials.
How do you react when this happens?
Unfortunately, there is not much you can do when this happens. You can check whether the supplier can procure the materials from a different production site. The best thing you can do is to plan for shortages before they happen because you can’t just start using new materials in your process. Shortages thus imply that manufacturing has to be stopped.
Are any specific raw materials more sensitive to shortages?
Some lab consumables are less critical, for instance, if it is a pipet it can be replaced without any issue. But if it is your bioreactor, for example, it is an issue. These are referenced in IMPD and IND, so they need to be qualified and validated before use.
What does that imply for you and your end-customer, the patient?
If it leads to a change that implies modification to all the batch records, it will require several validations and final approval from quality assurance, so that takes quite some time. The changes have to be analysed, to be sure that the equivalents are understood and managed. For instance, for the pipets, is supplier A the exact same as supplier Z? We need to be sure that it will not impact the end product. If it is the exact same, you still have to modify the batch records, because you have to be sure you take the right reference. You might even ask for the deviation to be validated. If it is something that you cannot change, You can’t do anything, it stops the manufacturing activities.
"If it is something that you cannot change, You can’t do anything, it stops the manufacturing activities."
So, stopping a manufacturing process not only costs you money and time, but it also impacts your end-user, the patient?
To treat patients with an autologous therapy you generally have a little window of time to harvest the starting material (patient apheresis) and manufacturing the product for the injection. If you have to delay the harvesting of two weeks because of a raw material shortage, you are not sure that the patient is still unable to undertake the apheresis procedure because of the advancement of the disease.
What alternatives do you have in case of shortages?
You need to plan for it upfront, if you don’t validate your raw material, if you don’t include them in IND/IMPD you don’t have any alternatives.
Do you usually have backup suppliers?
It is a requirement, but unfortunately, for small companies, it is unusual. It costs a lot of money to validate alternative suppliers, and you have to use them regularly to manufacture clinical/commercial batches. To validate them you have to show that the final product is exactly the same with the two references though complete comparison studies. For raw materials, in vivo studies are required. Then the regulatory dossier should be amended and approved. It takes several months.
What about animal-based raw materials specifically, are they sensitive to shortages?
We don’t have more shortages of animal-based raw materials than others, because mainly the problem is when we have contamination of the manufacturing lines, the animal-based raw materials are not more impacted than the others. Animal-based raw materials are very well checked before usage, the regulations are very strict. This does mean that when we have to replace them we need to go through the validation process again and are delayed significantly.
What do you need that doesn’t exist yet?
We need all backups that give the exact same results as the initial raw materials.
Do you have anything to add?
Raw material shortages are very stressful, especially if you are producing an autologous solution because you can’t treat patients in a high need for treatment.
Raw materials are definitely a critical part of the cell & gene therapy manufacturing. Shortages can be a catastrophe when the deadlines are short, and the patient is always the one who suffers from it.
How do you manage raw material shortages in your field? Share your good practices to avoid critical production delays with us: comment below.
Thank you Nadège for your insights, this talk is intended to explain the complexity of shortages in Cell & Gene therapy industry, quoted words by France-Emmanuelle Adil, Founder & CEO of Tiamat Sciences.