Suppose you are a (patent) attorney in a pharmaceutical company and want to advise your company how to best protect the results of a clinical trial designed to find out the best possible treatment regimen of a certain known and approved drug X. The researchers of your company have devised and been allowed to conduct a clinical study in humans, involving a number of pretty different treatment regimens. The trial will be lengthy and quite costly; its result is not really predictable. In the end, your company’s trial will (hopefully) provide mankind with valuable new information how to best administer drug X. Your company’s management tells you that they want and need and, in their opinion, deserve patent protection for the new treatment regimen.

Now it’s your turn. You know that a compound for a new use can be patented in principle (Art. 54(4) and (5) EPC) and that a new use may consist, inter alia, of a new treatment regimen (established case law since T 1020/03, a decision back from the good old times when important decisions were still published in the OJ EPO). So far, so good. But now comes the BIG question: Should you file the patent application that your company expects you to file before your company starts the trial, possibly including all treatment regimens included in the trial, or only after your company has received and evaluated the results?

I cannot and will not try to answer this question in this generality. Clinical trials and the circumstances under which they are conducted can be quite different; as can be the common general knowledge and the internal information available to the inventor/applicant when filing the application. But I wonder whether there are certain scenarios where it is truly difficult to get the decision right.

Firstly, filing a patent application directed at a new use of a known compound X without any supporting data may be very risky. The EPO may easily pull out and fire the plausibility gun at you, which may result in problems for your compound-for-use claims either under insufficiency (T 609/02) or under inventive step (T 1329/04) or both. In the end, you are supposed to invent, not to speculate.

Conversely, waiting with your application until the results of the trial have become (internally) known can also be very risky. First and foremost, there is always the risk that somebody else pre-publishes something pertinent. Secondly, there may be certain clinical trials where confidentiality cannot be or is not maintained for one reason or another. The latter scenario is particularly painful: In this case, it is already known that a clinical trial is ongoing and – in the worst case – that certain treatment regimens of drug X are being tested. Naturally, the result of the trials may not yet be known at your priority date. But your generic opponent drily argues (i) that the published information about the trial already anticipates your claim, as it includes the treatment regimen which you have (later) claimed when you knew it worked, and thus all the technical steps necessary and sufficient to anticipate the invention and (ii) even if this information were not to anticipate the invention, it would at least render it obvious.

This brings us to the recent decision T 239/16 brought up by the commendable Just Patent Law Blog, wherein the claimed invention was „Zoledronic acid or a pharmaceutically acceptable salt thereof or any hydrate thereof for use in a method of treating osteoporosis in which the zoledronic acid or the pharmaceutically acceptable salt therefore or the hydrate thereof is administered intravenously and intermittently and in which the period between administrations is about one year.”

The Board first established that the trial information summarized in a document (55) and describing, inter alia, this treatment regimen, was public and then proceeded to examine novelty and inventive step.

With regard to novelty, the Board stated:

In the present case the next step involves analysing whether the effect discussed above would arise with certainty from the treatment as described in document (55), i.e. whether the disclosure of document (55) has to be read as an implicit disclosure of the effective treatment of osteoporosis.

Thus, the Board – in my opinion, rightfully – was apparently not satisfied that all the necessary technical steps sufficient to obtain the claimed effect (successful treatment of osteoporosis) were described in document (55). In other words, the effect was not seen to be inherent in the use as described in document (55). The Board additionally wanted to establish that the trial information (which obviously included no prediction as to the outcome) had to be read as an implicit disclosure of the effective treatment of osteoporosis.

The Board then went on to examine this question by looking at various other documents filed by the opponents. You may perhaps find this odd, but we can put the question whether and when secondary references can inform the skilled person about what was implicit in a primary reference to one side. The Board’s result was that there is no such implicit disclosure in document (55).

But then… you probably guessed it. Document (55) still killed the invention:

6.2 A possible starting point for the assessment of inventive step is document (55). The content of document (55) is discussed in detail in point 5.2 above. The five study arms are presented in the same manner. Each can be seen as a valid starting point. In the present case, the board considers the last study arm pertaining to once-yearly administration as the most promising starting point for the assessment of inventive step.

6.3 As can be seen from the discussion under point 5.2 above, the difference between the disclosure of document (55) and the subject-matter of claims 1 and 2 of the main request lies in the failure of document (55) to directly and unambiguously disclose the effective treatment of osteoporosis.
Consequently, the technical problem to be solved in view of the once-yearly arm as starting point in document (55) is the provision of an effective treatment of osteoporosis.

6.4 As already stated under point 5.2 with regard to the content of document (55) in the context of novelty, a certain doubt remains as to whether the yearly treatment arm leads to an effective treatment of osteoporosis. The question to be answered is thus whether this doubt would diminish the skilled person’s expectation of success for this yearly treatment arm. The board considers that the mere fact that an active agent selected from the group of bisphosphonates is being tested in a clinical study for the treatment of osteoporosis (as disclosed in document (55)) leads to an expectation of success, due to the fact that clinical studies are based on data obtained by pre-clinical testing both in vitro and in animals and require authority approval which takes ethical considerations into account. This means in the present case that the skilled person would expect all study arms to treat osteoporosis effectively, unless he was dissuaded from this by the prior art.

And, perhaps unsurprisingly, the Board did not find the prior art to dissuade the skilled person from believing that each of the tested treatment arms might be effective.

It cannot be said that the patent proprietor did not try what it could to persuade the Board to come to a different conclusion, including properly citing case law such as T 158/06, T 293/07, T 715/03 and T 2506/12. But the Board rejected each of these attempts. When discussing T 2506/12, the Board argued as follows:

The appellant-proprietors argued that, unlike the situation in case T 2506/12, in the present case there was only pre-clinical evidence that the active agent, zoledronic acid, could be effective in the treatment of osteoporosis.

The board refers to point 5.2 above, in which the fact that zoledronic acid has not yet been shown to be effective in humans is exhaustively discussed. The board holds that there remained a residual doubt that the desired treatment would be obtained, which however did not diminish the prospects of success to such an extent that the reasonable expectation turned into a mere “hope to succeed”. Clinical trials in humans are planned scientific investigations. They require authority approval, which is only given after a risk/benefit evaluation. For ethical (but so economic) reasons it has to be ensured that research risks are minimised and are reasonable in relation to any potential benefits. Ethical and economical considerations require that the “benefit” will arise with reasonable certainty and will not only “be hoped for”. This has to be taken into consideration as part of the technical circumstances when assessing the level of confidence of the skilled person in making rational predictions about achieving the envisaged treatment. Consequently, even though the circumstances are different from those of case T 2506/12, that does not automatically mean that an inventive step is to be acknowledged.

So all in all, a sad outcome for the patent proprietor, which is perhaps also a bit unsatisfactory from a more general point of view. Is it possible at all to protect the (valuable) outcome of such (lengthy and costly) clinical trials, particularly if they cannot be conducted under full confidentiality? And if not, what could be done about it?


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9 comments

  1. So, Thorsten, it is all about a known drug for a known disease. The expensive trials are for the purpose of optimising the existing,operational treatment regimes. Should I take a Jumbo Pill once a day or several smaller pills through the day (I’m over-simplifying, aren’t I). Crucially important stuff, sure. At least in the eyes of the pharma firm financing the trials.

    I’m no pharma attorney but I’ve heard of evergreening and I’m not convinced it is always for the public good. I would rather see Big Pharma researching treatments for orphan tropical diseases than how to get a year or two more out of an existing patent portfolio.

    I’m wondering whether the expensive trials, to “optimise” the treatment regime, are done out of the goodness of the hearts of the Big Pharma sponsor, or, rather, to eke out a few more years of monopoly profits.

    To my way of thinking patents are hugely beneficial and important for the public good. The biggest threat to the health of the patent system is allowing too much to be patented, thereby bringing the patent system into disrepute with the public and thereby clearing the way for populist politicians to shake it down. Donald Trump, anybody?.

    As with everything, there needs to be a balance, and finding the balance is a challenge. Debate in a forum like this surely helps. I hope you get more comments.

    Incidentally, have you ever thought that the only trial results that Pharma publishes are trials that deliver the desired result. The ones that deliver evidence of non-efficacy (the ones that are so useful for public health bodies like the National Institute for Clinical Excellence) never see the light of day. Do you know about the Goldacre Alltrials campaign, I wonder? Here two useful Links for you:

    http://www.senseasdata.com/drupal/sites/all/modules/civicrm/extern/url.php?u=6424&qid=3564689

    http://www.alltrials.net/

  2. Congratulation maxdrei on that “balancing” contribution! After almost 30 years in pharma business I fully agree with you, nothing to add.

  3. Also working in the pharma business, I cannot agree with Maxdrei’s views which echo common prejudices but do not reflect reality. If a pharmaceutical company develops a new dosing regimen, which does not bring a true benefit to the patient, patent protection for such new dosing regimen leads you nowhere, as generics/biosimilars could simply market the previous dosing regimen. Also the comment that “Big Pharma” is trying to hide clinical trial results is at least outdated in view of the new transparency regulations implemented around the world and (additionally) self-committed to by most pharmaceutical companies. Certainly, not everything is gold, but where would we stand without “Big Pharma” nowadays?

  4. Thanks for the article. Food for thought even for the non-pharma patent attorneys. Personally, I see a basic law/consitutional issue if documents that an applicant is required by law to submit before “plausibility of a treatment” at the patent office can established via studies are used by the patent office to deny a patent. Basically the legislator says “sure you can have patents (and gives the public patent law) but then again not really (due to the legal disculosure requirements with respect to human experiments)”. Further, I cannot find any requirment for “plausibility” or a similar concept in the EPC and find it strange that the public accepts that the EPO/BoA come up with creative new hurdles that have no legal basis. It is quite telling in this respect that the EPO/BoA have problems to clearly summarize such situations as lack of inventive step or lack of industrial applicability (which are valid reasons to refuse a patent application) and have to create new legal constructs.

  5. I don’t know whether you are being deliberately provocative and obtuse, Peter Parker, or just don’t see the Big Picture, but I will take the bait anyway.

    Many Americans criticise “First to File” because it forces files to file on mere speculation. Patents (20 year monopolies) are a restraint on trade and free competition. They should be handed out sparingly, not dished out like bags of sweets, to anybody who reports his dream in the specification of a patent application and pays the Patent Office its filing fees.

    The UK Patents Act 1949 had about 15 grounds of invalidity. The EPC pruned it down to about four or five. So, inevitably, it would appear to All True Englishmen, that there is too much “shoe-horning” going on, so as to squeeze a ground of invalidity in under one of the only four or five headings of invalidity available.

    Whether a granted patent is a “good thing” rather depends on whether you are the one holding that particular gun at the head of your competitor, or are the competitor with the gun held to your head. This is the great thing about the patents judges in England. Before they became judges, they were patent barristers, helping clients, with all the legal tricks available, to win the litigation. They were acting just as often for the poor accused infringer as for the poor patent owner unable to make the infringer cease and desist. They know all the tricks that litigants play. This experience gives them the wisdom, to decide with justice all complaints of invalidity, and all complaints of infringement.

    And once more, competition in Europe is good for the development of patent law. On Art 52 EPC eligibility, England disparages the EPO approach as “intellectually dishonest” while DG3 dismisses the English approach as impracticable and unhelpful. Over in the USA, they are still unable to decide which of those two intellectual positions they prefer. Sometimes, Europe does it better than the USA.

    You see something as “quite telling”. As you will infer from the above, I disagree.

    1. Dear MaxDrei, please allow me to add my 2 cents to yours.

      Firstly, let me say that I mused for a few minutes whether or not to edit your comment in reply to Peter Parker by removing most of the first two lines, which I found a bit too personal. Let us all be opinionated but argue to the facts, rather than about how provocative, obtuse etc. another commentator IS. Having a “civilized debate” in the good old English style should be our common goal.

      Secondly, it is certainly a matter of debate whether any patent is a “good thing” in a concrete dispute, as you rightly point out. Nevertheless, I hope we all agree that patents in principle are good for the society if and when they are granted according to certain rules and satisfy certain criteria that (ideally) help to stimulate creativity and competition rather than inhibit it.

      I will not want to argue with you whether a Jumbo Pill once a day or several smaller pills through the day should generally be considered an invention or not, but I agree with you that you are a bit over-simplifying. It is a well-known fact that patient compliance is an important factor determining how faithfully patients take their prescribed medication. Not taking your pill at the prescribed moment can have serious consequences for your health and even for your life in some cases. This is one main reason why such trials are conducted. Another is that pharma companies like to have unique selling points for their drugs, particularly when the active ingredient per se is off-patent. However, in such a case, such companies do not monopolize the entire market for this drug – their competitors are still free to sell the drug e.g. in a different formulation or with a package insert that provides for a different administration regimen. Absent any particular and exceptional circumstances, I would not call this “evergreening”, but “improvement inventions” that should be open to pharma industry as well as to other industries. Let us also not forget clinical trials trying to identify new indications, i.e. cures for diseases not yet identified.

      Whether the individual improvement is a patentable invention or not is another matter and must of course be determined by the proper authorities and eventually the great patents judges in England. My article was motivated by the increasing difficulties for a particular group of applicants to obtain patents in a particular technical field, no more, no less.

      Finally, I do not at all share your view that the only trial results that Pharma publishes are trials that deliver the desired result and that the ones that deliver evidence of non-efficacy never see the light of day. I remember only too well one case that went up to the Supreme Court in Germany, where one of the critical prior art references was an article about a clinical trial using the same active substance for the same indication as the patent claimed that I had to defend. However, the article came to the conclusion that my drug did NOT work better than placebo in the patient group tested. The FCJ – rightly in my view – came to the conclusion that this prior art reference did not anticpate the use claims of my patent. Thus, there are clearly responsible scientists who publish the results of trials, even if they had a negative outcome. Viagra for women is just another example of a published, unsuccessful clinical trial.

      I do admit two things though. Firstly, the situation may have been different 10 or 20 years ago, but nowadays the transparency obligations are quite serious and most companies take them seriously. There are still exceptions and there is still work to do, as your links (thank you!) show, but generally speaking I think it is no longer possible to keep the outcome of a large clinical trial under the carpet, if the results are not what they were supposed to be.

  6. Dear Thorsten, quite right. Thank you. From now on, I must remember: the more a contribution provokes me, the cooler must be my response. It might help me, to imagine I’m arguing with the commenter face to face, rather than anonymously, on the internet, and only then choose my words of reply. Sorry about my answer above, Peter Parker, if it bothered you too.

    On the subject of evergreening, yes, sure. If, on the evidence of the application as filed, the claimed subject matter has plausibly solved a technical problem in a non-obvious way, then it is worthy of a patent. I do not argue with you, that patent compliance can be a serious problem. So, increasing compliance is a worthy aim. Ways to achieve this result are to be welcomed. Family members striving to achieve better compliance by a recalcitrant family member reach instinctively for obvious solutions, to achieve better compliance. But if a research team can find a way that isn’t obvious, bravo. Give its employer a patent. I think also that Patent Offices and judges have to be alert against “creep” of patents for solutions to problems that are not technical and mindful that, until there are disputed proceedings they are only getting one side of the story.

    As to much-improved level of transparency of clinical trials, of the results which are the property of those financing the trials, I’m encouraged that you write: “There are still exceptions and there is still work to do….”

    I wonder, what is this “work” you have in mind, and who is going to do it?

    Finally, I do hope that other contributors to this thread will enjoy it, and feel inspired to join in.

  7. I’ve always wondered how difficult it would be to patent a new drug or pharmaceutical, so thanks for sharing this. I can see how it might be difficult to decide if you should patent the application before the trials or after. I agree that it probably depends on the compound and what it’s used for.

  8. As discussed on my blog, Canadian courts are developing an experimental use exception to anticipation which would be applicable in such circumstances. See Hospira Healthcare Corporation v. Kennedy Trust for Rheumatology Research 2018 FC 259; Bayer Inc v Apotex Inc 2016 FC 1013; Bayer Inc v Apotex Inc 2014 FC 436

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