Thursday, 13 October 2016

Sofosbuvir EP opposition - an update

As I reported in February last year, Gilead's European patent EP2203462B1 to sofosbuvir (Sovaldi) was opposed by various organisations, the first of which was M├ędecins du Monde (MdM). Their main reason for opposing the patent seemed to be that Gilead was charging a high price for the drug, which is effective for treating Hepatitis C. The opposition has recently concluded, following oral proceedings earlier this month. A press release issued on October 5th indicated that MdM's opposition was partially successful, and that "the quality of the patent was weak". Details of how exactly the patent fared as a result of the opposition were, however, missing, except for a mention that "the patent extended beyond the content of the patent application as filed" (suggesting an Article 123(2) issue). Another report from IP Watch did not provide much in the way of further illumination, and as yet there has been no word from Gilead or the EPO on the outcome.

The decision and minutes of the oral proceedings have not yet appeared on the EP register for the case, and are unlikely to do so for some time. It can, however, be inferred from what has already been said, and in particular a document that has appeared on the register, what actually happened.

In their preliminary opinion, issued on January 28, 2016, the opposition division indicated that claim 1, corresponding to the racemate (shown here), had been specifically disclosed in the application as filed. Claims 2 and 3, however, which were directed to the enantiomers (or diastereomers - see the comment below), did not appear to be disclosed. Whether the disclosure was sufficient to disclose the enantiomers was something that was due to be discussed at the oral proceedings.

Gilead filed a large number of auxiliary requests, the first of which had a set of claims that had been amended to define the enantiomers instead in terms of the slow and fast eluting isomers obtainable by a specific method that was disclosed in the application. The clue that this succeeded at oral proceedings is this document, issued shorty after the proceedings, that contains amendments made to the summary of the invention, and indicating that this corresponds to the first auxiliary request. This shows that claims 2 and 3 have been removed from the application, clearly indicating that claim 1 survived, but that the specific claims to the enantiomers did not.

As a result, the patent seems to me to have survived pretty well, and not really limited in any substantial way. It will, of course, be irritating to Gilead that the specific claims to the enantiomers have gone, but the patent as amended would still protect the drug. Reports (such as this one, for example) that suggest generics may be able to enter the market sooner than expected, therefore seem to be a bit wide of the mark.

UPDATE 3/11/16: The grounds for the decision have now appeared on the EP register. As expected, claim 1 to the racemate stands, and the claims to the enantiomers/diastereomers have gone.

12 comments:

  1. It seems indeed that the claim with the structure with the undefined phosphorus stereochemistry has survived. Allow me to clarify that the two possible stereochemistries in the phosphorus atom give rise to a pair of diastereomers and not enantiomers. This is because there are already four stereocenters present at the molecule, which have defined stereochemistry. Diastereomers are not mirror images, unlike enantiomers which form racemates when present as 50-50 mixtures.
    The reason I make this remark is because the patent application (A2 doc of PCT, p. 18) reads "...compounds of the formula I are racemic because the chirality at phosphorous". This is present at the definitions part.
    In view of that, I asked myself the question "what exactly is disclosed by the structure of this compound, with undefined stereochemistry at the phoshporus atom?". Sure, the application points out that there is chirality and all stereoisomers are part of the scope, but what is actually protected under such a claim? Especially when there is a clear statement that the compounds are racemic, which, although an incorrect term, implies a mixture? To put it in another way, if you have three flasks, one with the R isomer, one with the S isomer and one with the R+S isomers, are they all infringing claim 1?

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    1. Thank you for your comment. I am not a practising chemist, so didn't get the point about enantiomers versus diastereomers, but then neither did the opposition division.

      On the question of whether the chemicals in the flasks would infringe, I would say they all will because they all contain a chemical having the formula defined by claim 1. Claim 1 does not state that it has to be a mixture.

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  2. As the OP took place on 05.10.2016, one should expect a decision and minutes of the OP within the next 6 weeks.

    When looking at what has been added into AR1 one reads the word "clause" and not claim. This is strange as clause are allowed in EP practice.

    The last word has not yet been said as it can be pretty sure that Gilead or MdM will appeal the decision of the OD.

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    1. The extra part that was submitted during oral proceedings is a replacement part of the description, not the claims. This was presumably done to conform the description of the patent as amended with the claims of the first auxiliary request.

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  3. Yes, (R), (S) and (R/S) at P would all infringe the claim. It is pretty clear from an infringement analysis, but it has also been subject to a court decision in Pfizer/Ranbaxy re atorvastatin.

    If it is the claims worded as slow and fast eluting isomers that have been granted, these should have been allowed to be claimed under the (R) and (S) designations. But as we know, the opposition believe their role in life is to get everything wrong to create work for the Appeal Boards.

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    1. Sovaldi is a prodrug. Prodrugs, by definition cannot themselves be active, from what I recall. Any argument that one protide (R vs S) is more active than the other is disingenuous, at best.

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  4. I agree that we'll have to await the written decision (or an indication from the patentee or one of the oppoents) to be sure, but I would say that the amendment suggests that auxiliary request 3 is the one that survived the opposition. The upper corner contains AR3, wherein the 3 has been changed to 1. I assume that they withdrew two higher-ranking requests. The amendment also does not contain the wording of the slow and fast elution.

    I'm _assuming_ that the person stating that generics can come to the market faster, is of the opinion that the SPC extension will no longer be granted/valid as the claims don't specify the exact enantiomer/diastereomer underlying the marketing authorization of Sofosbuvir (that would. I consider that a (much) too narrow interpretation of the requirement set forth in the CJEU Medeva decision.

    If this decision stands (I'm assuming that at least one of the opponents will feel the urge to appeal), there doesn't seem to be a real problem for Gilead.

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    1. Good point. Auxiliary request 3 has all claims to the enantiomers/diastereomers deleted, so could be the one the patentee ended up with. I would, however, be surprised if the representative decided on the day to elevate aux3 to aux1, as this would restrict their options on appeal. We will just have to wait and see. It does though still look like the claim to the racemate stands, which is the key.

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  5. There is an interesting discussion here about whether sofosbuvir is still covered by amended claim 1, and it confirms my assumption about how the patent survived opposition.

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  6. The decision and minutes are now online on the European Patent Register. The patent has indeed survived with the claims to the (R) and (S) isomers deleted.

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    1. Thanks. There is an interesting comment from the OD at point 21.2 of the grounds, but I don't think it means what the opponents want it to mean.

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  7. It probably means "not my job to rule on infringement". And I suppose they are right. I just hope we won't see a case where english and german courts take opposite directions. This is an extremely important issue for everyone who is drafting chemistry-oriented patents.

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