Putting the IP in iPS cells: patent war looming?

war

By Paul Knoepfler

Will intellectual property (IP) wars over patent rights to one of the most exciting new stem cell technologies hold back getting novel therapies to patients?

Unfortunately, it’s very possible.

Induced pluripotent stem (iPS) cells are very cool stem cells made from non-stem cells through a process called cellular reprogramming.

iPS  cells have essentially all of the same properties and powers as embryonic stem (ES) cells, but without the potential ethical complexity of utlizing a human blastocyst for their generation.

Pretty amazing, huh?

iPS cells have huge therapeutic potential both directly via potential cell therapies (e.g. for treatment of macular degeneration) and indirectly as the basis for disease modeling and drug screens.

All of this sounds wonderful and it is, but of course you know there had to be a catch, right?

The huge potential problem here is the issue of intellectual property (IP) rights to iPS cells.

All the talk and the slew of publications about potentially using iPS cells to develop therapies to help patients is exciting in theory, but unfortunately the reality is that it is not entirely clear if most researchers are, from a legal standpoint, even allowed to develop and commercialize iPS cell-based therapies at all.

The patent landscape for iPS cells is complicated to put it mildly. A Google patent search for “induced pluripotent stem cells” produced almost 200,000 results.

A search for “cellular reprogramming produced more than 1,000 results.

I’m not sure all of these results are really separate patents, but still….that’s a big complicated mess.

To me simplistically it seems like Yamanaka and his institution should own the rights, but clearly it’s not so simple.

Can any Dr. Joe Shmoe clearly without IP rights to iPS cells develop a therapy?

So if, for example, my lab wanted to develop an iPS cell-based therapy to treat an important disease, would it be possible to do so?

I don’t know. It sure seems risky to me to develop a therapy based on a technology that someone else owns even if I’m not entirely sure who that someone else is.

What about other companies or researchers? Many are working feverishly to develop iPS cell-based therapies, but to my knowledge almost none of them have any IP rights to iPS cells.

It seems like a recipe for trouble to me if not an outright nightmare.

And also I wonder could some other companies be challenging (directly or indirectly by their actions) the Japanese IP and patents on iPS cells?

For example, the company Advanced Cell Technology (ACT; stock symbol ACTC) is most well-known perhaps for its ES cell-based therapies in clinical trials for macular degeneration, but it has clearly indicated that  it is developing an iPS cell-based platelet product and perhaps other iPS cell-related products.

But does ACTC in fact have the necessary IP rights to do this? Will they have to pay someone else for the right to use iPS cell technology? ACT has indicated that they have some IP rights to iPS cell-like technology, but what exactly does that mean? Will they be sued if they try to commercialize an iPS cell-based product?

I’ve heard that Stanford is also working on an iPS cell-based therapy with every intent to make it into a stem cell-based treatment to be used for patients….but does Stanford have the legal right to do that?

I’m not aware of Stanford have any IP claim to iPS cell technology at all. Have they signed a licensing agreement with another institution that has a patent for iPS cells?

What about all the other universities and researchers working on clinical translation of iPS cells?

It is no exaggeration to say there are likely dozens of institutions around the world wanting to commercialize iPS cell-based products.

Will they all have to pay expensive licensing fees or end up in court?

…or will the patent holders voluntarily and freely allow others to commercialize iPS cell-based medical treatments?

I don’t think so.

This could get really messy.

20 thoughts on “Putting the IP in iPS cells: patent war looming?

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  2. Pingback: Putting the IP in iPS cells: patent war looming?


  3. If ACT (Lanza) uses OCT4 proteins for differentiation versus Yamanaka’s virus delivery method, wouldn’t there be two types of IP involved to end up at the same place?


    • Great question, but I don’t know that there is a clear answer. My understanding is that there are many IP claims to iPS cell-related technologies. I would not be at all confident that ACT has a clear IP path to make iPS cell-based platelets for example without a potentially-expensive licensing agreement with another organization that does have a strong iPS cell IP portfolio. At the same time, there are many groups doing iPS cell pre-clinical work who have NO IP rights to iPS cells at all.


  4. I’m glad to see a serious discussion of this issue. Perhaps an interview with someone who might shed more light on the issue is warranted if they will speak freely about it. I hope to see some follow up by you if possible as I agree that it could well be a nightmare.


  5. Paul, This is an important issue and certainly the companies involved know enough to sort out IP before making major investment. For academic institutions, probably not an issue at pre-clinical stage.

    I am more concerned about your statement that human ES cells have “ethical baggage.” This baggage is almost entirely a fabricated political issue. Essentially all human ES cells come from pre-implantation blastocysts created in IVF clinics and they would be discarded if not used for research and possible therapies. Most couples would rather these blastocysts be used for research and therapies rather then discarded. Therefore, unless you support shutting down all IVF clinics, there is really no “ethical baggage” to human ES cell work. Indeed, just the opposite, this is the ethically correct thing to do.

    I enjoy your posts. This statement seemed to slip through. I think you know better.


    • Good catch, Dan. I have corrected this with the addition of a single word in front of it. Thanks. Paul


      • It’s your blog, but I would just remove any reference to ethics as a strength or weakness of hESCs vs iPSCs.

        iPSCs can also raise ethical issues- can I make iPSCs from dead people? Can I make them from someone without their permission? Oh no- ethical baggage!

        Let’s focus on science, or in this case legal, issues.


        • Thanks for your comment, Dan.
          However, ethics is an important element to discuss and is part of the reality we face.


          • Of course ethics are important. My point is that hESCs should not be singled out if you want to raise “supposed” ethical issues.

            For every study you discuss that use experimental animals, will you mention that this use is ethically controversial? Many people are opposed to animal experiments- so I guess you should mention this whenever discussing animal work.

            iPSCs and hESCs have differing strengths and weaknesses for scientific studies and development of potential therapies. However, I don’t think it is valid to say an advantage of iPSCs is they don’t raise ethical issues.


            • In the discussion of iPS cells, it is often appropriate to discuss their relative strengths and weaknesses compared to hESCs and it is fact that iPS cells are less ethically controversial than hESCs in a general sense. Even Yamanaka has pointed that out.

              A significant segment, perhaps 40% in the US for example, of the population is uncomfortable with hESC research at an ethical level.That’s simply reality.

              You are right that there are many other ethical issues that one could discuss and I do try to include discussions of those when relevant.


  6. I’m sure there are several examples throughout history where cutting edge technology is forsaken in the short-term, only to persist and contribute to medical breakthroughs.

    One example comes to mind. Henrietta Lacks had cervical cancer cells taken without her permission in 1951 and died later that year. The HeLa line is now the oldest and most persistent cell line in the medical field. It was instrumental in the development of the polio vaccine and has been included in about 60,000 scientific papers including, but not limited to, cancer and AIDS research.

    This issue and Mrs. Lacks’s situation was brought up in the Supreme Court of California case of Moore v. Regents of the University of California. The court ruled that a person’s discarded tissue and cells are not their property and can be commercialized.

    The interesting thing from my point of view, is that many of the critics of iPS and hESC studies have directly benefited from the HeLa cell line.


  7. Hi Paul:
    We fear what we don’t understand and feel powerless to change. I just looked back at the seminar I used to give about my practical experience in challenging the WARF patents on human ES cells. At first I knew very little about patents. But I was driven by a sense of outrage that made me want to learn about patent law.
    I would like to send a message to both iPSC researchers and the owners of iPSC technology. Researchers, you are not helpless; you CAN pressure patent holders if the patents impede your work. Patent owners, you should tread carefully; if you gouge researchers, they will fight back.


    • Thank you, Jeanne, for the very helpful and instructive advice to the field. Your experience is so valuable!

      I hope that both iPS cell patent holders and iPS cell researchers w/o iPSC patents will read this and take it to heart. Patients too.

      Part of the reason for my post on such an explosive issue was to get people thinking and talking about this difficult, but extremely important aspect of clinical translation of iPS cell technology to patients. It is not an issue that the field can afford to ignore just because it is unpleasant and hard to understand.


  8. Hi Paul – I see your topic of IP conflict and inevitable war in the nascent stem cell field is getting some attention, go figure!

    I’d like to bring my comment to you over from investorstemcell.com to here as I think it’s worth airing out, given your position statement – plus add some thoughts on the comments posted.

    The ethical baggage of hESC science is old news, it mainly had to do with human cloning. The fact that assisted reproduction, in the form of IVF, exists is not where I think you refer to the ethical baggage. Using donated pre-implanation embryos is problematic for a minority IF it harms the embryo. This minority would prefer scientists pursue their work another way. However in a democracy the majority decide and establishes the Rule of Law and until that freedom to operate is taken away by a majority of the vote science will have the backing of the people, irrespective of the minority voice. Besides as you know a viable and important middle-ground using a non-destructive technology exists in hESC science for therapeutic purposes – which has been conveniently overlooked by the minority in their quest to continue their old arguments against clearly ethical and respectful scientific progress.

    The very nature of opinion is that sometimes individuals and groups see things differently – that is not to say however that the rightful truth in the matter should remain obscured in the background of the debate. It is only here in Europe that the adoption of non-destructive hESC positioning of Govt. bodies is clearly stated and only in a sidebar manner via Patent law. Non-destructive hESC technology is the solution which should be promoted as the middle-ground rather than repeating the old news which fails to address this scientific realty.

    On iPS being the squeaky clean new methodology to have your cake and eat it too – I must remind everyone that making an Egg and a Sperm from skin cells and fertilizing it produces a viable human embryo unless technology is employed to stop growth. What is the moral high ground on that versus a non-destructive hESC process working within the legally established guidelines set down long ago on the cloning of human embryos?? There is no legal basis yet for what a scientist can do with a human skin cell… iPS isn’t morally superior to hESC in any way given this reality – especially when considered against an innocuous non-destructive cell extraction technology for therapeutic purposes.

    You made an important comment on your position when you said “I don’t know that there is a clear answer” when asked about ACTC’s OCT4 Patent Priority, as that is fundamental to your statement about Yamanaka. I don’t think you can rightly state an opinion on Yamanaka’s IP without knowing the legal situation with regard to his Claims and the others, which you haven’t presented. Perhaps it would be worth presenting publicly your research into the matter with regard to the “mess” that is iPS IP, those involved and their Claims…

    The comment that ACTC needs to seek an iPS License for their Platelet program is not clear as of now agreed given the GMP compliance requirement of the FDA and what ACTC is doing to secure an acceptable line… However you make it seem as if that is everything in this program and it certainly isn’t… Getting an iPS cell in a Pluripotent state is the 1st step – the 2nd and more important IP step is to get that Pluripotent cell to do what you want it to do – in this case develop into a MK cell and from there into a Platelet using differentiation technology which ACTC has patent rights to… So please make it clear that their is a difference in the IP involved between deriving an iPS to Pluripotent 1st step and from there differentiating that Pluripotent cell with proprietary IP.

    I realize your piece is meant to stimulate dialogue but in some ways it polarizes the ethical positions rather than bringing the community together IMO – which is what is needed rather than a continuation of the war that has been going on for some time already. Also, as stated, the IP issues are not a quick essay topic and deserve a bit more meat on the bone to explain a position.

    Cheers


    • Thanks for the comment. You make some good points. The iPS cell IP mess assertion is based on a few things: the tons of iPS-related patents out there (in the database at least), the many people/organizations I am aware of who are on a path to development of iPS-related therapeutics, but who have zero existing rights to do so, and scuttlebutt that in the near future there will be actions taken related to possible infringement. I’m no IP expert by any means, but together this sure sounds like a recipe for a mess.

      I do not believe that iPS cells are “squeaky clean”, but I do believe that from an ethical perspective they present fewer issues with the general population. I would stress that I am concerned about iPS cell technology being used to clone people as I have indicated in the past.

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