15 October 2019

Eli Lilly v Fresenius Kabi: a Dutch departure from the trend

The UK Supreme Court’s decision in 2017 in Actavis v Lilly has received plenty of comment and analysis. The case concerned Lilly’s dispute with Actavis over sales in Europe of a generic version of Lilly’s anti-cancer Alimta® product.

Lilly’s European patent, EP 1 313 508 B1 (EP’508), covering Alimta® claims pemetrexed disodium in combination with vitamin B12 or a derivative thereof (claim 1) for inhibiting tumour growth.  Actavis, along with other generics companies, developed products in which a different pemetrexed salt was used, assuming that such formulations would not fall within the scope of the claims of Lilly’s patent.

However, the UK Supreme Court found that Actavis’ pemetrexed dipotassium and vitamin B12 product infringes Lilly’s patent. The impact of this decision was significant as it challenged the UK’s long established approach to the assessment of infringement, and saw re-formulation of the approach adopted by the UK Courts to determine the scope of claims and infringement by equivalents.  Further details can be found in our earlier articles:

Since the Supreme Court decision, the multi-jurisdictional battle over this patent has continued across Europe, with the resultant decisions coming at regular intervals.  The question in many of these proceedings has been whether a pemetrexed product with a different salt falls within the scope of Lilly’s patent.  In almost all these proceedings the decision has found in favour of Lilly. However, a recent decision from the Netherlands has bucked this trend.

On 19 June 2019, a decision was issued by the Dutch District Court of The Hague, which has jurisdiction over patent matters in the Netherlands, in Eli Lilly & Company v Fresenius Kabi, regarding Fresenius’ pemetrexed product.  The product ‘Pemetrexed Fresenius’, which is indicated for malignant mesothelioma of the pleura and non-small cell lung carcinoma, contains the tromethamine salt of pemetrexed rather than the disodium salt, but is otherwise identical to Alimta®.

As well as arguing that Pemetrexed Fresenius directly (literally) infringed EP ‘508, Lilly also argued infringement by way of equivalence, on the basis that Pemetrexed Fresenius performs essentially the same function, in essentially the same way, with essentially the same result as the patented product.  Fresenius countered by asserting that the use of Pemetrexed Fresenius in combination with vitamin B12 fell outside the scope of EP 508’s protection.

The Court’s analysis started with consideration of the scope of protection conferred by EP ‘508 under Article 69(1) EPC, and the Protocol on the Interpretation of Article e69 EPC, and stated that Article 1 requires both fair protection to the patentee and a reasonable degree of legal certainty third parties. The Court also stated that Article 2 of the Protocol requires due account to be taken of any element known to the skilled person in the art which is equivalent to an element specified in the claims.

It was noted that the parties agreed on the literal wording of the claims (which only covered pemetrexed disodium), whilst the person skilled in the art would recognise that the idea of the invention behind those words is not so limited.

It was also noted that the novelty and inventive step of the patent was not based on the choice of the salt, but its therapeutic application in combination with vitamin B12.  As the benefits of this combination (reduced toxicity with no adverse affect upon efficacy) are not specific to pemetrexed in the disodium form, a skilled person would see that the benefits could be achieved by applying a different form of pemetrexed.

So, the skilled person would be aware of the concept of the invention, but the question was whether the scope of protection of EP ‘508 went beyond the literal wording of the claims.

The Court determined that in order to decide on this question, the prosecution history from the grant of EP ‘508 was relevant, and the following points were noted:

In response to an objection raised by the European Examiner on the basis of a lack of novelty arising from the prior disclosure of the use of an antifolate (5-fluorouracil and methotrexate) in combination with vitamin B12, claim 1 was limited by the Applicant’s Representative (i.e. the representing patent attorney) to “pemetrexed” and “vitamin B12 or a pharmaceutical derivative thereof”.

The European Examiner responded, raising an added matter objection under Art 123(2) EPC, pointing out that original description referred (in a preferred example) to “pemetrexed disodium”, and that “pemetrexed” was a distinct compound to pemetrexed disodium.

A response was filed by Lilly’s patent attorney, limiting the claim 1 to pemetrexed disodium, amending the description to reflect this limitation and including the statement “the Applicant seeks to draw a distinction between subject matter which is relevant to the invention which is indicated as being that to which “the present invention generally relates” and “the subject matter provided by the invention” which is the subject matter claimed”.  The Court noted that the application proceeded to grant, following acceptance by the Applicant’s Representative of further amendments to the description proposed by the Examiner in order to bring it into line with the subject matter of the claims.

It was further noted by the Court that the same Representative had been involved in the prosecution of another European patent held by Lilly (EP 1 265 612) which included a paragraph in the description which defined the term “pemetrexed” in broad terms, and that such a definition was absent from the original disclosure in EP ‘508.

Following consideration of these points, the Court made a number of comments:

  • The skilled person would have known – as would Lilly – that it was “(childlike) simple” to manufacture pemetrexed in forms other than the acid or disodium salt.
  • There is more reason to assume a broader scope of protection if it is clear that the restriction in the formulation is not based on a conscious choice (i.e. it was unintentional) and for this, the prosecution history of the case is useful.
  • In this case, the skilled person would not have considered limitation of claim 1 to its literal wording to pemetrexed disodum to have been a (clearly) unintended restriction.
  • Lilly did not dispute or probe the nature of the Examiner’s added matter objection in prosecution, or even discuss with the Examiner the intention to obtain protection for multiple forms of antifolate pemetrexed administration, but simply limited the claims to the preferred disodium embodiment, and accepted without question the Examiner’s subsequent limitation of the description to reflect this.Furthermore, the Court noted the comment by the Representative regarding the distinction between subject matter which was considered relevant to the invention in general and the claimed subject matter.
  • Lilly, as a “pharmaceutical superpower” could be attributed the necessary expertise and experience in patent applications, was not under time pressure during the prosecution of the patent application in questions, and had omitted the broad definition of ‘pemetrexed’ included in other cases which they held.

These points led the Court to conclude that Lilly had deliberately limited EP ‘508 to pemetrexed sodium, and that these circumstances stood in the way of protection for more than pemetrexed sodium.

Accordingly, Pemetrexed Fresenius, which comprises pemetrexed tromethamine, was held not to fall within the scope of protection conferred by EP ‘508.

In reaching this conclusion, the Court dismissed Lilly’s submissions concerning the ‘nature of the patent’, ‘intended purpose of the invention’ and ‘advantages of the patented combination therapy’ on the basis that these elements are already been considered as part of the concept of the invention.

The Court concluded the decision with a reference to Justice Arnold’s judgement in the UK Patents Court decision in Actavis v Lilly, in which he stated that patent holders tend to rely on equivalence in three classes of situations:

  • the first, where the specification has been drawn up in a unfortunate manner, for example due to bad instructions from the inventor or bad editing by the attorney or a combination of these things;
  • the second, where, as a result of the progression of the technique, implementation variants were created that were not yet foreseeable on the priority date and therefore have not been claimed; and
  • the third, where the patent proprietor regrets a decision taken during the grant procedure by himself or the Examiner and wishes to avoid the consequences of those choices after grant.

The Dutch Court commented that in the first two situations it may be equitable for equivalent protection to have a corrective effect, but that these situations did not arise here.

Clearly, the District Court of The Hague was not daunted by diverging from the judgements in other jurisdictions regarding the scope of protection conferred by Lilly’s pemetrexed patent.  It will be interesting to see, assuming the decision is appealed, how the case is addressed by the Court of Appeal of The Hague.

In the meantime, this case provides a salutary reminder to applicants and patent practitioners alike of the need for careful drafting of patent applications and the dangers of relying upon the doctrine of equivalents to remedy ambiguities or omission in an application; as well as the need to question and, if needed, contest the opinion of the European Examiner during prosecution, rather than making an amendment which may later be regretted.