DE – Hexal v. Eli Lilly – Pemexetred – Invalidity

Posted: November 22nd, 2018

Hexal AG and Stada Artzneimittel AG v. Eli Lilly and Company, Federal Patent Court, Germany, 17 July 2018, Case no. 3 Ni 23/16 (EP) joined with 3 Ni 19/17 (EP), with thanks to Dr. Michael Best from Lederer & Keller, for providing the decision and an English translation thereof

This blog has covered the pemetrexed cases all over Europe (DenmarkSwitzerland, The Netherlands, ItalyAustriaUnited Kingdom).

Most of these decisions concern the question of infringement of the Eli Lilly patent EP 1 313 508 (EP‘508) which relates to the use of the active ingredient pemetrexed in combination therapy with vitamin B12 and optionally folic acid (formulated as a so-called Swiss-type claim).

Generic competitors and Eli Lilly have fought this battle in many jurisdictions. The discussion has in many cases been focused on the doctrine of equivalence. Also the German Federal Court of Justice (Bundesgerichtshof) has ruled that the generic product is an infringement of EP‘508 (the decision can be found here.) Now the Federal Patent Court in Germany has revoked the German part of EP‘508 in its decision of July 17, 2018.

The Federal Patent Court has decided that EP’508 is not based on an inventive step over the prior art cited in the nullity proceedings. The teaching of EP’508 is therefore obvious in the eyes of the German court. Basis for this conclusion were a combination of previously published articles which served as prior art for the Federal Patent Court. Eli Lilly also filed 9 auxiliary requests in which they further limited the scope of the patent. Each of those requests failed as the Federal Patent Court also deemed them as being obvious over the prior art.

Interestingly the EP’508 had survived opposition proceedings before the EPO. However, the Federal Patent Court explained in its decision that it is not in contradiction with those opposition proceedings as the prior art in the two proceedings differed. The prior art documents which the Federal Patent Court used to argue against inventive step were in that combination not part of the proceedings before the EPO. The Federal Patent Court also explained that it is not in contradiction to the existing German infringement cases which have not stayed the proceedings, as those infringement proceedings based their assumption on the decision of the EPO.

It is almost certain that this decision of the Federal Patent Court will be reviewed in appeal. Such an appeal is handled by the Federal Court of Justice who already had a look at this patent when they decided on the infringement case.

A copy of the decision of the Federal Patent Court (in German) can be found here. A translation of this decision can be found here.

Reported by Alexander Haertel, Kather Augenstein Rechtsanwälte

3 Responses

  1. Andrew Brown says:

    A review of the technical arguments and a comparison with those used in the EPO can be found on my posting on LinkedIn reviewing this case.


    It appears Actavis did Lilly a great favour in seeling a pan-EU non-infringement decision by delaying the invalidity challenges expected on this wobbly patent.

    Andrew Brown EPA RPA (UK)
    Head of IP Juno Pharma

  2. Attentive Observer says:

    The whole hype created by the various pemetrexed decisions in various jurisdictions will die sooner or later, and especially the one from the UK Supreme Court.

    The biggest lesson to be learned from the case is that there should not be a premium for slapdash drafting, allowing the applicant/proprietor to reap profit from an invention he might have broadly thought off in theory, but for which no plausibility was given at filing date.

    It is good that another view on the patent has been given by the German Federal Patent Court (GFPC-DPatG). It is to be seen whether this decision will be upheld by the German Federal Court (GFC-BGH), as it would be surprising that the proprietor would not fight such an outcome. All the efforts put into the claim that other salts of pemetrexed have an equivalent effect of that of pemetrexed disodium would then have been in vain.

    It is interesting to see that to decide on lack of inventive step, the GFPC did not rely exclusively on the documents brought forward by the nullity claimant (NIKn), but also took into consideration documents brought forward by the proprietor (HLNKn).

    Not only was there a promising starting point for the combined use of pemetrexed disodium and vitamin B 12, but also for the longest known antifolate, i.e. methotrexate, albeit in the treatment of rheumatoid arthritis, but in which the deleterious effects of methotrexate exist as well. The GFPC concludes that there was no prejudice against the use of vitamin B12 to treat the serious side effects of pemetrexed treatment.

    In the case before the EPO, the parties were different than before the GFPC, one opponent, TEVA, and one intervener, Actavis, but since the appeal was withdrawn, no decision was given by a Board of Appeal. The angle of attack by the opponent was totally different. Only one of the documents cited in the procedure before the EPO, D27, was used in the action before the GFPC under the name NIK 8. No wonder thus that the conclusion were totally different.

    It is interesting to note that the GFPC considered that it did not need expert advice, as its own members have the technical expertise needed to decide on inventive step. The positive side of the presence of technical judges in patent matters as foreseen by the UPC, should it ever come to life, has to be seen in this light.

    Last but not least, bifurcation has sometimes its good sides….

    That the pemetrexed story will continue, also in countries were non-infringement declarations have been refused is more or less sure. Too much attention has been given to the whole story, to assume that the last word on this topic has been said.

    When attacking alleged infringers, the proprietor might not feel as comfortable as he could have felt after his success in claiming that equivalents also fall under his claim. If the patent is revoked for lack of inventive step, then equivalents will not help much.

    There might sometimes be justice, even in the patent world….

    • Andrew Brown says:

      Your point on drafting is well made! Many of us in pharma have asked ourselves – “why did they limit the claims to di-sodium salt”? It appears that in the UK decisions reference is made to the fact that the patent attorney only had a day to draft and file and was American. I shall let you choose which was the most important factor in the failure to draft an adequate claim.

      Again perversely this error did Lilly a great favour as it opened up the idea of a non-infringing product which Actavis took through the Brussels Regulation to try to enforce in other EU countries.

      I think once you look in depth at the metabolic pathways of folic acid and the central role of vitamin B12 the route to invalidity is clear. It was widely known and admitted that the use of folic acid was known the ameliorate the side effects of pemetrexed and other antifolates it is just that the role of vitamin B12 was not known explicitly. The Phase II study published before the patent shows no correlation with MMA and toxicity. MMA is a marker for vitamin B12. BUT as a marker, it is only an indirect measurement of vitamin B12. Other factors may control MMA levels. The levels of homocysteine were known to correlate to folic acid and vitamin B12. Again as a marker it is an indirect measurement of the levels of both. You have to bridge between homocystein, MMA, folic acid and vitamin B12 and come up with the right background CGK.

      I think the key difference with the EPO are;

      1. The documents cited – as you say
      2. The fact that the EPO technical member(s) are not prepared to bridge a gap as much as the technical members of the German Court.

      As for bifurcation – I have nothing positive to say about it having been the recipients of many PIs where the validity of the patent was still being determined at the EPO. I think DE system needs to think more about their role in shielding the German public from bad monopolies and not wholly serving the rights of the patentee. I have light the touchpaper and now I shall stand back.

      Validity was not in anyway held back in any other jurisdictions it was merely that companies saw that Actavis and others had a non-infringing route to market so why bother? Ultimately that route has now closed and everyone is looking at validity.

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