Second (and further) Medical Use Patents

Second (and further) medical use refers to the discovery or development of a new therapeutic use for an existing substance or composition. Throughout this article, the term second medical use shall also cover further medical uses.

Patentability of second (and further) medical use claims

Second medical use patents have been debated in Turkey for years which eventually led to the Supreme Court case law on the matter. Before going into the details of this topic, it is worth to provide an overview of Turkish legislation which is relevant to the second medical use patents.

1. Turkey is a party to TRIPS and as a matter of principle TRIPS mentions that patents shall be available and patent rights enjoyable without discrimination as to the field of technology.

2. Turkey was a party to the EPC (1973) and is party to the EPC (2000). The EPO case law issued during the EPC (1973) allowed second medical use claims to be patented. With the introduction of Art. 54/ (4) and (5) in the EPC (2000), it became possible for second medical use claims to be patented.

3. Turkey has enacted an IP Code in 2017. The Turkish IP Code is silent on the patentability of second medical use claims.

• Implementation regarding European patents with filing dates before 12th December 2007

Before the EPC (2000) entered into force for Turkey on 12th December 2007, the Turkish courts issued decisions invalidating second medical use patents having filing dates prior to that date based on Article 52/4 of the EPC (1973), which provided methods of treatment cannot be patented.

During the period the EPC (1973) was in force, the main argument in favor of the patentability of second medical use patents was the G5/83 decision of the EPO Enlarged Board of Appeal. When Turkey became a party to the EPC, the Government’s ratification of the EPC involved both the EPC itself and the G5/83 decision. However, the issue concerning the ratification intention with the existence of the G5/83 decision was an often-disregarded argument.

The 2021 decision of the Civil General Assembly of the Supreme Court put an end to these discussions. The decision was related to the European patent that was granted as per the EPC (1973) decision. The decision briefly states that the second medical use claims could be patentable if drafted in Swiss-type claim format and whether other patentability conditions (novelty, inventive step, industrial applicability) are met and that such patents should be interpreted within the scope of the EPC (1973) and the EPO case law.

• Implementation regarding European patents having filing dates after 12th December 2007

According to Article 54/ (4) and (5) the second medical use claims are explicitly protected in the EPC (2000) provided that said use is novel and inventive which avoided the interpretation concerning the protection of the second medical use patents.

• Implementation regarding the national patents

As mentioned above the Turkish IP Code dated 2017 is silent on patentability of second medical uses. Articles 54/ (4) or (5) of the EPC 2000 was not incorporated in the Turkish IP Code.

The same decision of the Civil General Assembly of the Supreme Court states that “If the "novelty" criterion is interpreted narrowly in a national patent for a second medical use, while the European patent for the second medical use continues to exist validly in Turkey, a situation may arise where the national patent for the second medical use, which is made to have effect only in Turkey, is not protected in Turkey. In addition, the fact that a European patent for a second medical use will be protected in Turkey, while a national invention will not, will lead to legal insecurity.”

Second medical use patents granted by the EPO are indeed validated in Turkey and granted by the Turkish Patent and Trademark Office without an interruption.

Enforcement of second (and further) medical use patents

In addition to patentability challenges, the enforcement of second medical use patents has been observed to be challenging as well. Even though the IP Code is silent with respect to patentability of second medical use claims, these patents are enforceable under the Turkish law.

According to the IP Code, every unauthorized production, sale, distribution, commercialization in any other way, import, storage, use, and offering of a patented second medical use constitute patent infringement.

Particularities of the enforcement of second medical use patents

• Skinny label (carve-out) practice

Where the second medical use patent provides patent protection for the treatment of the same disease, such as a dosage regime or a different patient group, it leads to problems in determining and evidencing the infringement in practice, especially in cases of skinny labelling.

Abridged application for generic pharmaceuticals allows generic pharmaceutical companies to apply for marketing authorization without submitting the results of toxicological and pharmacological tests and clinical studies if data exclusivity period for reference drug expired. In abbreviated applications, generic companies carve out the patent-protected use from the SmPC and PIL of the generic drug whereby the generic drug is approved with a skinny label.

Although in Turkey the medical practice is to prescribe the drug with its commercial name [not with active ingredient or international non-proprietary name (INN)], the fact that doctors and pharmacists can still prescribe/dispense drugs for the patented use has caused the skinny label practice alone to be insufficient in terms of preventing infringement of second medical use patents.

In such case, how could the patentee prove that there is patent infringement despite skinny label? The European courts’ decisions provide guidance in this regard.

In the Fulvestrant case (AstraZeneca v. Hexal), the Dusseldorf Court of Appeal developed several conditions to establish infringement of a second medical use patent. One noteworthy condition is whether there is sufficient extent of use of the generic drug for the patented use. In the Fulvestrant case, the court did not specify an exact interval when a sufficient extent of use can be assumed. This is an issue which shall be reviewed case by case (the court found 7% was insufficient in the said case). Another condition is whether the supplier exploits circumstances that lead to the drug’s use for the patented application. In the instances, where the generic company induces the use of the generic drug such as promoting the generic drug to doctors for patented indication, or where the pharmacies are obliged to substitute drugs for generic versions, or where the generic company participates in public tenders for patented use, can be claimed as exploitation of circumstances that lead to the drug’s use as in the patent.

At this point, it may also be examined whether the generic company has proactive behavior to prevent infringement as in the Pregabalin case (Warner-Lambert v. Teva) before the Paris Court of First Instance whereby Teva had sent thousands of information letters to healthcare professionals urging them not to prescribe or deliver the generic drug for patented indication.

In Zoledronic Acid case (Novartis v. Sun Pharmaceuticals), the Dutch Supreme Court held that a generic company must prove that it has taken sufficient precautions to avoid use of the active substance for the patented indication. The fact that Sun sent an e-mail to wholesalers and pharmacists with the heading “This announcement pertains to formality” or the fact that Sun did not deduce from the volume of its sales that its product was not only being used for the off-patent indication or the fact that Sun did not try to convince the health insurance company to change its tender only to off-patent indication, led the Dutch courts to rule that Sun was liable of patent infringement.

2- The direct and indirect patent infringement issue in second medical use

The main players in the system are the generic company manufacturing the drug, the Social Security Institution reimbursing the generic drug, the wholesaler supplying the drug further to the pharmacists, the pharmacists dispensing the drugs to the patients and the doctor prescribing the drug for a patented use.

At first glance, as it is doctors or pharmacists who perform the off-label use, they would be liable. Even when this liability is determined, it is not common practice for the pharmaceutical companies to sue doctors and pharmacies. It may not be reasonable to expect from doctors, pharmacists, or drug warehouses to know about a patented use. Their responsibility may arise if they prescribe or distribute a drug despite being warned not to use it for patented use. Secondly, there would be countless defendants considering that there are over hundreds of thousands of doctors, tens of thousands of pharmacies, dozens of warehouses in Turkey and this would be neither manageable nor cost-effective for the patentee.

It is not common practice to sue Social Security Institution as well. If the Institution grants reimbursement for a patented use, the Institution would not be held liable because there is no patent linkage system in Turkey which would give rise to the liability of the Institution. But healthcare authorities could take necessary measures. For example, in the Pregabalin cases in the UK, the National Health Service issued directives regarding the prescription and deliverance of pregabalin.

In contrast to first medical use patents, which are infringed by the generic company as soon as the product is manufactured, second medical use is not carried out by the generic company directly when there is skinny labelling. As per the general rules of law, the objective liability of generic company shall arise in these cases. Where the accused generic company cannot demonstrate that it had taken precautions to avoid patent infringement, such a generic company should be held liable for direct patent infringement. Because such a generic company should have known that its generic drug would have been prescribed or distributed for the patented use.

If the evidence does not lead the court to direct infringement, the indirect infringement could be argued. As per the Turkish IP Code, indirect infringement occurs when a party supplies unauthorized parties with the means which are related to an essential part of the invention, and which make it possible implementation of the invention. The supplier must know, or it must be sufficiently obvious from the circumstances, that such means are suitable and intended for the implementation of the invention.

What are the available legal remedies against infringement?

Determination of Evidence: Determination of evidence is an ex-parte court action that upon filing, the court determines the existence of an infringing evidence usually through expert examination, and the case is closed after the submission of the expert report without exchange of petitions. The claimant can request and obtain preliminary injunction (PI) as per the findings of the expert report within the context of this evidential procedure. However, in pharma and biotech cases, since those cases potentially block access of public to a certain medicine, courts prefer to receive defense of the adverse parties and even another expert report before deciding on PI. Therefore, the determination of evidence route may not be effective in this technical field.

Patent infringement action and PI request: As the judges being IP judges without technical background, the established jurisprudence of the Regional Appellate Court obliges the first instance courts to obtain expert report before granting PI in a technical dispute. Therefore, in patent infringement actions, especially in pharma and biotech cases, the expert report is highly important to obtain PI.

It is also possible to ask for actual damages including non-realized income, reputational and moral damages within the context of the main infringement action.

It is important to note that generic companies can file declaratory action for non-infringement before the patentee files the main infringement action. Moreover, the generic companies can also file an invalidity action independently, or as a counter invalidity action against the main infringement action or within the context of the action for declaration of non-infringement.

Conclusion

Second medical use claims are patentable and enforceable in Turkey. However, there is still room for improvement as there has not yet been an established case law as to particularities of the enforcement of second medical use patents concerning the skinny label, direct and/or indirect infringement or the liability of the actors in the system.

* First published by Lexology.