Legal Commentary

Originators respond with individual strategies

When filing second medical use claims, the companies surveyed by JUVE Patent are satisfied with the European Patent Office. But creativity is called for when it comes to enforcement. Companies are responding to the unclear situation with individual strategies that frequently vary from country to country.

8 June 2021 by Konstanze Konstanze (Journalist)

©ADOBE STOCK

The filing of second medical use claims at national patent offices plays virtually no role at all for pharmaceutical research companies. Most of them go down the validation route via the European Patent Office, usually with a PCT application.

Overall, the companies surveyed by JUVE Patent are satisfied with the EPO’s granting practice and the rulings of the Boards of Appeal. Compared to the situation regarding later enforcement against generic products, the problems are only marginal.

Nevertheless, company representatives would like to see second medical use patents examined and granted more quickly. But companies also criticise the same thing when it comes to active substance patents.

“Now and then, there is more intense debate about inventive step, but that’s simply a part of the process,” says the in-house counsel of a mid-sized pharma company.

Another in-house counsel is critical of the EPO’s high plausibility requirements. He explains that, as early as the filing stage, so much data has to be presented that a problem with inventive step may arise in the end.

The problem is well known. EPO examiners and judges face a fundamental problem with second medical use claims. They must reconcile the functional feature of a therapeutic application with the technical character stipulated under patent law. This requires much more evidence than for active substance patents.

In this context, the issue of plausibility has led to much debate. Conflicting Boards of Appeal decisions are causing confusion among companies.

Two 2017 rulings by the Board of Appeal 3.3.01. against a second medical use claim for the anti-cancer active substance dasatinib from Bristol-Myers Squibb (case ID: T 0488/16), and for the anti-breast-cancer active substance zoledronic from Novartis (case ID: T 0239/16), reflect the range of BoA case law especially well.

“Either companies don’t write any data in the application for the claim, in which case the invention is not plausible, or they include data from clinical trials, in which case they run the risk of the claim being rejected as not novel or inventive,” a former judge explains.

 

Overall, the companies surveyed by JUVE Patent are satisfied with the EPO’s granting practice and the rulings of the Boards of Appeal. ©EPO

But, according to that judge “Some applications are based merely on assumptions and presumptions. When the chambers realise this, the judges rightly get angry.” This then leads to decisions that are correct on the merits of the case – but highly problematic according to legal doctrine.

“A referral to the enlarged Board of Appeal to clarify the plausibility issue would be very desirable,” says Cohausz & Florack partner Natalie Kirchhofer.

But still some companies see a problem in the accusation of “evergreening” and the resulting scepticism at the EPO and in court. EPO examiners often dismiss second medical use claims as being of secondary importance, one in-house counsel complains.

An EPO insider confirms that this impression is indeed widespread in the office. However, the companies themselves are partly to blame, for instance if they provide poor reasoning for the applications or even misuse the system.

“With strong arguments and data, the EPO examiners and judges can also be convinced that a second medical use claim is worthy of protection,” says Arwed Burrichter, partner at Cohausz & Florack.

Wolfgang Kellenter, partner at Hengeler Mueller, says, “The EPO’s generally generous granting practice compared to the German patent office has led to originators being able to enforce second medical use claims for a while, to keep generics off the market – even if the patent is later destroyed.”

Patent infringement battlefield

According to pharmaceutical research companies, what is already apparent at the EPO is continuing in the enforcement of second medical use claims. One in-house counsel says, “Here, too, we see infringement judges with preconceived negative opinions. Companies are simply denied the chance to put inventions to further use.”

The matter of infringement is always a national decision for second medical use patents, too. The biggest problem for holders of second medical use patents is the off-label use of generic products. This is because it is generally very difficult to prove the act of infringement. Moreover, it is often unclear who is committing the act in the first place. It could be the manufacturer of the generic drug, the doctor, the pharmacist – or even the health insurance fund.

In Germany, the health insurance discount system is criticised, so the accusation goes, because it promotes the act of infringement. Company representatives say that the legislator has a duty to change something.

From the companies’ point of view, off-label use is a bigger problem in some jurisdictions than others. Countries such as Denmark, Norway or Switzerland are not critical from the pharmaceutical research companies’ perspective, but rather they are more concerned about the situation in the large sales markets of Germany and the UK.

Pregabalin will have lasting impact on UK disputes

In several respects, Warner-Lambert’s lawsuit against various generic drug companies concerning pregabalin has become the landmark decision for second medical use claims in the UK.

In December 2020, the Supreme Court dismissed Warner-Lambert’s claims of insufficient disclosure, invalidity and infringement against generic pharmaceutical manufacturers Actavis and Mylan. In applying the concepts of plausibility and insufficiency, the Supreme Court set a new precedent for cases concerning generics products in the UK.

Warner-Lambert launched proceedings against generics in 2014. Although patented as a second medical use for neuropathic pain treatment, Actavis and Mylan sought to launch a new generic pregabalin product following the expiration of Warner-Lambert’s first medical use patent for Lyrica. Introduced as a “skinny label” product, Actavis and Mylan’s product focused on the treatment of generalised anxiety disorder (GAD) and epilepsy but excluded the indications of pain treatment.

However, in 2015, Warner-Lambert launched an interim injunction against Actavis to prevent the “skinny label” product sale. But ultimately, the UK Supreme Court refused Warner-Lambert an interim injunction.

Consequently, the generics and the UK’s National Health Service (NHS) are now fighting with Warner-Lambert for damages for the period in which the generic pregabalin products could not be sold. According to sources, the amounts involved are several hundred million British pounds sterling.

The pregabalin case is not a standard UK second medical use dispute. Often, the generic company will label the patent-protected indication in the documentation and the infringement is clear.

However, the Supreme Court judgment will influence case law on the issue of plausibility, which has a high relevance in the UK, but has so far not been adopted in Germany. A London patent lawyer says, “UK courts tend to follow the EPO quite closely on plausibility.”

The intensive involvement of the NHS in the pregabalin litigation is also likely to have consequences. The UK patent courts inform the NHS by default about proceedings concerning second medical use patents. However, it usually stays out of the cases on the issues of infringement and validity. On the issue of damages, however, the authorities behind the NHS are very much involved, according to an insider. But the NHS and the generics have conflicting interests in this. They are in competition with each other on the question of who has the biggest claim.

It is currently unknown when the UK High Court will rule on the generics and NHS damages claims against Warner-Lambert. One observer says that from the originators’ point of view, the pregabalin case raises uncertainties for future second medical use lawsuits in several respects. Regardless of how high the resulting damages are, financially there can be a lot at stake for the NHS in such patent cases.

“Moreover, the Supreme Court judges were far from unanimous in their vote,” explains one patent lawyer. “It’s a tough standard to meet in the future.” Experts agree that general counsels will more often decide against suits based on second medical use patents, unless the initial situation is clear.

Fulvestrant case law

In Germany, two decisions in particular have shaped the legal framework. Both make generic manufacturers more accountable.

As in many other European countries, Warner-Lambert also acted in Germany against various generic manufacturers such as Hexal and Ratiopharm, for the use of Lyrica.

In its 2015 pregabalin decision, Hamburg Regional Court obliged the manufacturers of imitation products of Warner-Lambert’s blockbuster Lyrica to point out in their discount agreements with health insurance funds that their generic product may not be dispensed for the second medical use claim, in this instance use for neuropathic pain.

Then, in 2019, Düsseldorf Higher Regional Court created a new situation with its ruling on the breast cancer drug fulvestrant.

Wolfgang Kellenter says, “The fulvestrant ruling of the Düsseldorf Higher Regional Court has significantly improved the situation for original manufacturers. In Germany they now have far more extensive opportunities to enforce second medical use claims than in other countries.”

 

In 2019, Düsseldorf Higher Regional Court created a new situation regarding second medical use in Germany with its fulvestrant ruling.

However, the Düsseldorf Higher Regional Court did not grant claimant AstraZeneca an injunction, because the basic problem remained. Off-label use is difficult to prove; the burden of proof is on the holder of the second medical use claim. Infringement is particularly difficult to prove if the generic manufacturer is not guilty of any purposeful preparation.

According to Kellenter, however, the quantitative proof of the act of infringement beyond the doctrine of purposeful preparation remains extremely complex and difficult.

One in-house counsel also confirms, “The new case law is good for originators, but it misses the mark somewhat in -practice.”

“Proof can actually only be successfully provided in very obvious situations, such as when a generic may only be sold for very few applications, but the actual revenues from it are disproportionately high,” he adds.

“There is virtually no chance of getting a preliminary injunction from a second medical use patent from a German court at the moment,” says one judge.

According to in-house counsel, this is not least because the Federal Court of Justice is yet to weigh in on the fulvestrant case law. “There is no uniform case law in Germany,” one in-house counsel complains. “We also don’t know what the patent courts in Mannheim and Munich think about fulvestrant.”

Companies therefore seem to be very hesitant to bring infringement actions in Germany. As far as JUVE Patent is aware, there are currently no lawsuits stemming from second medical use patents in Mannheim and Munich. Düsseldorf may be the go-to court for pharma patents, but even here parties have only filed a handful of such suits in recent years.

Lawsuits against the health insurance funds are another way to resolve the situation in Germany. Pfizer has taken this path in the Lyrica dispute. Novartis took it for its leukaemia drug Glivec. These lawsuits tackle the discount agreements and therefore usually end up before social and public procurement chambers. JUVE Patent is aware that the two pharma giants have each reached an agreement with the health insurance funds. Publicly-known judgments are practically non-existent.

“No generics is no option”

Compared to originators, generic manufacturers are in a comfortable position. Representatives from pharmaceutical research companies complain that they can wait and see, taking their time to adjust their strategy.

Moreover, when generic manufacturers attack a patent immediately after it has been filed, this requires a lot of time and effort. But this is not a problem specific to second medical use; it applies just as much to all active substance patents. The most frequent accusation from the generic companies is that second medical uses are not real innovations at all, but rather evergreening patents with which originators are trying to keep the competition out of the market.

“On the other hand, we need the generics industry,” says an in-house counsel from a major drug manufacturer. “Competition encourages new inventions. If patent protection and terms were not limited, originators would rest on their laurels.”

Of course, pharmaceutical research companies look carefully at the costs when launching litigation campaigns. The same applies here as to patent suits overall. In Germany and other continental European countries, litigation costs tend to be moderate. Dorian Immler from Bayer puts the average costs in Germany at around 500,000 euros per dispute.

However, if a patent is enforced in several European countries, the costs from the individual national proceedings quickly add up. In the UK, the pure costs of litigation are far higher. But there are also additional pitfalls in terms of liability. The NHS’s strong involvement in the pregabalin case on the issue of damages has opened everyone’s eyes to how carefully companies must think before enforcing a second medical use claim at the UK High Court.

Harnessing experience when applying for patents

Pharmaceutical research companies frequently use the experience gained in infringement proceedings to improve their -patent applications for new claims.

“We draw conclusions from every patent infringement or nullity suit,” says one in-house counsel. However, current research has usually long overtaken the prior art that the courts are debating. Several in-house counsels emphasise that this makes integration into the new application strategy more difficult.

Dorian Immler says, “Currently, the only way is to separate patent claims into first indication and second medical uses at product level. An originator can thus already carry out its planning in the clinical development of a second medical use in a way that ensures that the product for the second indication is not identical to the first indication.”

“If the first medical use is interpreted too broadly, this leads to problems in protecting the second medical use,” Arnold Ruess partner Bernhard Arnold knows from his litigation experience. Caution is not only advised in the application, but also in descriptions in papers and presentations.

“Research managers should always discuss with their -patent department beforehand what prior art may be communicated to the outside world. This works best where the patent department is directly linked to the R&D department.” But this does not solve the problem of off-label use by any means. (Co-author: Mathieu Klos)

 

Read what originators claim politicians can do to solve the enforcement problem, and the UPC’s unexpected comeback, in part three: Dead end with no way out

Read why originators file SMUCs frequently, despite the low economic importance, in part one: Beloved problem child