Conducting Clinical Trials Part 1: When Should You File Your Patent Applications?
Clinical trials have found their way into the spotlight of the coronavirus pandemic as multiple pharmaceutical and biotechnology companies race to develop and market vaccines and therapies. As breakthrough technologies are on the rise, so are the risks associated with vaccine and drug development. “Conducting Clinical Trials” is a podcast miniseries featuring Choate attorneys covering a number of topics related to clinical trials, including common mistakes companies make along the way and various strategic choices they face.
What are some important timing considerations when filing patent applications that cover the results of a clinical trial, particularly in situations where the clinical data are not yet available? As the first installment of Choate’s Conducting Clinical Trials series, Bryana McGillycuddy and John Rearick discuss a range of implications associated with the timing of filing, including the validity of the patent and the risk of inadvertent disclosure.
Welcome to Choate’s Life Sciences Insights. A podcast series hosted by our Intellectual Property Litigation and Corporate attorneys covering trending topics at the intersection of science and law.
Bryana McGillycuddy: Hi Everyone, thanks for joining us. In this episode, which is part of a series that addresses a range of important issues which need to be considered when conducting clinical trials, will focus on the question: how long should you wait to file a patent application that covers the results of a clinical trial – when you don't yet have any clinical data to cite in that application.
I am Bryana McGillycuddy and I am a Principal in the Litigation Department at Choate and my practice focuses on IP Litigation.
John Rearick: And I am John Rearick, a Principal in Choate’s Patent and Intellectual Property Group.
BM: So the decision on when to file can have implications on a number of issues, including validity of the patent under Section 112 which requires the claimed invention to be sufficiently described and enabled and Section 103 which requires the claimed invention to be nonobvious. Now, as a litigator, I am usually handling these arguments post hoc, long after the application has been filed. But, there is an opportunity to address these issues earlier – at the drafting stage. It is important to note though that this is a very complex topic with no easy answers. Today we are going to explore various options to have in mind. John, maybe you can walk us through the process from the prosecution perspective.
JR: Sure Bryana. One of the more common scenarios is where a drug in development is being dosed in humans for the first time such as a Phase 1 clinical trial. Phase 1 trials primarily evaluate drug safety and they provide some information on dosing for later phases. However, Phase 1 trials are often testing healthy patients and may not provide much or any information as to the efficacy of the drug which becomes more of a focus in Phase 2. So we might consider filing a patent application prior to starting Phase 1 based on the indication that will ultimately be treated or the dosing regimen to be tested in Phase 1, but the application as filed will obviously lack any human clinical data to support claims to those inventions. And because clinical trial phases often take months or even years to run, we might not have data to include in the application even by the one year convention filing deadline and in the case of a Phase 1 trial like I mentioned, no meaningful data regarding efficacy may arise in any event. So by filing the application prior to conducting the trial presumably to avoid some prior art that might be created in the trial itself, what we could end up with in the end is a patent application based on a clinical trial protocol but is mostly or entirely prophetic because it lacks any efficacy data from the trial. This can lead to some significant challenges when prosecuting these patents as patent examiners may view claims in these situations as not enabled or not sufficiently described by the underlying application. Another risk of early filing is that we may not capture certain unexpected results that may emanate from the clinical trial itself and those results could be the basis of a very valuable invention – for example, dosing or patient stratification aspects. Bryana, have the courts said anything recently on this topic?
BM: Great question John. Of course these decisions need to be made with the applicable case law in mind, and the courts have towed a fine line on this topic. Most recently in the 2019 Nouveau Pharm’s case, the Federal Circuit addressed an extreme example where the asserted patent claimed efficacy but the specification was completely devoid of supportive data or even a theoretical explanation of why the drug would be efficacious. In fact, it stated only that the claimed drug might work. At the same time, the record included arguments that the patentee in support of non-obviousness that a person of skill in the art would not have expected the drug to be effective. In that case the Federal Circuit invalidated the patent for insufficient written description. Now the Federal Circuit was careful to recognize that experimental data demonstrating effectiveness or a theory explaining how the drug will be effective is not an absolute requirement related to efficacy claims, but there must be something more than the claim itself particularly where there is evidence in the record that skilled artisans would not have expected the claimed efficacy. So, one takeaway from Nouveau is that filing efficacy claims before you have some clinical data or other reason to show that the inventors knew the claimed invention would be efficacious does present potential risk under 112 particularly where you also need to argue that a skilled artisan would have had no expectation of success to overcome an obviousness argument. Now, in litigation we are often in the position of creating a delicate balance in arguing that the claimed results would not have been obvious to a person of skill in the art while also needing to point to sufficient support in the specification demonstrating knowledge of the unexpected result. There are, of course, different legal standards for obviousness and 112 issues but quite frankly, it can be difficult to present both arguments to a lay jury and expect that jury to appreciate the difference and not view your arguments as being in conflict. All of that said from the litigator’s perspective, it’s important to be mindful of these potential landmines when you’re prosecuting. The more data you have to show that the inventors in fact achieved the unexpected result, the better position you are in to balance those arguments in litigation but, of course, waiting too long presents other potential challenges. So John with all this in mind, from your perspective what are some of the things to consider when you are deciding when to file?
JR: There are certainly a few aspects to consider Bryana, and I think they generally revolve around this delicate balance of prior art risk versus enablement. There is often some level of uncertainty about the confidentiality of what is being tested in the clinical trial. For example, will there be some inadvertent disclosure on clinicaltrials.gov or a press release or a poster presentation. Even if an inadvertent disclosure does not disclose the full details of the trial, it could still potentially constitute prior art against a later filed patent application. Another motivation to file early could be concern that a competitor might soon file in the same or similar invention and the race to the patent office would, therefore, be lost. The levels of risk for inadvertent disclosures and competitors beating you to the patent office vary depending on a number of factors, but these are the things we are thinking about on the prosecution side as we navigate the timing and content of filings based on clinical trials. I also think it’s important to consider what’s already out there in the prior art including your own art. Is a new filing likely to succeed without unexpected results? If there is already prior art on the composition of matter and the indication, the new filing is likely to be very data-driven anyways. So that would favor waiting until some data are in hand to best tell the invention story in the application. I think many of the cases where things have fallen apart in court with these filings are where the story was pieced together after the fact and the patent was filed too early in the development timeline. Another consideration is based on the state of the prior art. Is the invention something that would not be expected to work by a person of skill in the art? As you said earlier Bryana, if the claimed invention would not be expected by a person skilled in the art and you don’t have data to suggest it would, you are in a very weak position in terms of 112. But again, in terms of when to file, we are always trying to balance these considerations against the question of whether the clinical work itself will somehow create a public disclosure that then creates hurdles to patentability. Bryana, from your perspective, what’s the real risk of such disclosures?
BM: Well as you mentioned John, things you may not consider as typical prior art such as clinical trials and conference posters, can in fact be cited against you down the road. Everything needs to be timed and presented carefully so you’re not creating prior art from your own development work. For example, if a clinical trial proceeds before the patent application is filed, one could argue that the trial itself constitutes an invalidating public use. We’re going to explore this topic in more depth in an upcoming podcast, but I just want to note that clinical trials provide one example of the risk associated with disclosure before a patent application is filed. Now another example would be an inventor promoting early-stage development efforts at conferences or in academic settings before the patent application is filed whether it is to generate funding, update the field or has some other purpose.
JR: Those are all great considerations Bryana. What can be done to help mitigate the risk of creating problematic prior art regarding a clinical trial?
BM: Well, it’s critical John to stay on top of what goes out the door in terms of postings, talks, publications, press releases and the like. Any disclosure should be deliberate and with full awareness of the potential risk. We frequently see conference posters cited as prior art in 103 challenges during litigation. Even though there may be motivation to tout success at the development program, whether it is for financing or another reason, it’s important to be very mindful to not disclose the entire invention or enough details that could lead one to say that based on the disclosures and the poster or press release or whatever it might be, it would have been obvious to reach the entire invention. And this is the case even where certain aspects of the invention, like the dosing regimen, may change over time. The same is true for proceeding with clinical trials and postings on clinicaltrials.gov? Folks may not be aware that those postings may not really need to be as detailed as you’d think. For example, you should consider what is actually required and whether you can disclose only the necessary details. See if Phase 1 postings are required at all or whether you can omit certain critical details. The risk is somewhat reduced when you take the disclosures down to their bare essence, but even with these litigation steps, you still might see the reference phrased in an obviousness rejection or a challenge down the road. Also, it’s important to be mindful that other countries have similar listings like clinicaltrials.gov and those may come into play when trials are being done outside of the U.S. One last point on this topic John is that it’s very important to make sure that others within the company who may not be as involved with the legal side of things are aware of this as well. Now all this begs the question during prosecution is there a middle ground approach that you can take in light of these disclosure risks?
JR: Well as prosecutors we tend to be risk adverse about filing dates when we know something is going out the door. If there is a real concern about a disclosure creating problematic prior art down the road, one option is to file a provisional application before disclosure and without the clinical data and include information about the clinical trial protocol so that you can later supplement the application with data as it is available. We like to call this “I told you so data” where you have said up front what is being tested and why, perhaps even hypothesizing about an effect without being too committal and then presenting later the actual data as a confirmation. When done right, this approach can often withstand 112 scrutiny. Ideally, the data would be added into the actual application though during the priority year so that the prosecuted application contains the data. Another option though is to present what is called post-filing data during prosecution which can be introduced via an inventor or an expert declaration. However, this isn’t a reliable worldwide strategy as many jurisdictions outside of the U.S. will not consider post-filing data. Even in the U.S., such declarations may be used to overcome lack of enablement but can’t really fix a lack of written description. The other thing to keep in mind with these declarations in the U.S. is that with respect to enablement, courts have said that they are only to be used to substantiate statements already made in the application, but not to introduce something completely new. Another middle ground approach that could be considered is whether any pre-clinical data are available that could be included to support the expected outcome of the human clinical trial. Bryana, are there any post-grant considerations that we should keep in mind?
BM: Yes. There definitely are John particularly with pre-litigation IPRs and other post-grant proceedings. It’s important to be mindful to not undermine your future 112 case with one or three arguments that are presented in an IPR or another proceeding that takes place before the litigation. For example, you want to be careful saying the invention is not obvious because no one thought it would work if your 112 argument is going to depend on a skilled artisan’s understanding that the drug would in fact have had the intended effect. It’s important to strike a delicate balance there. Often IPR arguments are made before addressing the substantive issues in litigation and the defendant could try to use those arguments against you down the road. So your IPR arguments should always take future litigation strategy into consideration. A great way to head off these issues is to make sure that your prosecution team, IPR team and litigation team stay in close counsel of course being mindful of any protective order bars. That’s the best way to make sure that all of your strategies are aligned.
JR: Thanks Bryana. That wraps up our discussion for today’s topic. Thank you to our listeners for joining us and stay tuned for additional podcasts in this series on clinical trials.
The information presented in this recording is for educational purposes only. It does not constitute legal advice for a specific situation. If you wish to obtain legal advice, you should retain an attorney and explain the facts of your particular situation.