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Cardiovascular Disease

Amgen Claims It All

There’s plenty of excitement about PCSK9, the latest LDL-lowering pathway to make it deep into the clinic. You can tell that companies (and investors) have high hopes for it, since it’s heading right into a market that’s dominated by generic statins. The optimism may well be justified – for example, Sanofi and Regeneron recently presented some impressive data comparing their antibody to Zetia in patients who can’t take higher statin doses, and Amgen has shown similar numbers. There are at least five antibodies and one RNAi in development, in a very tight race to the FDA and to the market. To give you an idea, the latest development was Sanofi and Regeneron paying cash to Biomarin for an FDA priority voucher that reduces their review time to six months instead of ten. (No, I didn’t know that you could do that, either).
Amgen, though, appears to be trying to own the whole racetrack. They’re pushing a patent claim to any antibody to PCSK9, not just their own agent. Update: See below for more on this Here’s their press release; they’re quite up front about this strategy. But I have doubts about how well that’s going to work. Over the years, the judicial trend seems to have been to not go for such broad claims in the biomedical field. There are so many potential antibodies to any given protein, and so many ways of modifying them and dosing them, that I find it hard to imagine a straight patent claim on all that space. It’s a lot like claiming “All inhibitors of enzyme X” in small molecules, and we already know that such claims don’t stand up. It wouldn’t surprise me, in fact, if someone had already tried a broad antibody claim like this and had it shot down (does anyone have an example?)
So I don’t think that the PCSK9 struggle is going to be decided by the patent lawyers. It looks to be fought out in the clinic, at the FDA, and especially out there in the real market. And it will be quite something to see.
Update: see the comments section. Amgen doesn’t seem to be claiming every single antibody; just those against a particular epitope (although a very useful epitope, obviously). And patent litigation in such situations is complex, with precedents (none of them necessarily exact) going both ways. So this will be quite something to watch. Perhaps Amgen is hoping to paid a cut to go away?

23 comments on “Amgen Claims It All”

  1. steve says:

    I’ve consulted for biotechs that wanted to try this and advised against it for the same reasons. It would be great to hear from some patent lawyers what their views on this are.

  2. Henry's cat says:

    Perhaps I’m oversimplifying the whole deal here, but there is something extremely distasteful about one company taking something given to them to assist them in their ‘good work’ in their honourable quest to help cure a rare disease and then flogging it to the highest bidder. For the authorities to allow this to happen further salts the broth. For shame. Ugh.

  3. Nicolai says:

    Not to be confused with PKCS #9 🙂

  4. Chris Kuckleburg says:

    A recent example that is still playing out in the courts is the lawsuit between Bristol-Myers Squibb and Ono vs. Merck in the anti-PD-1 space. BMS/Ono have a patent covering the use of any monoclonal antibody to treat any tumor. This patent covers BMS’ antibody (Opdivo) as well as Merck’s (Keytruda), and the antibodies being developed by other groups. Merck challenged the validity of the patent in Europe, but it survived. We still don’t know what the U.S. court will say – but I imagine BMS will bring up the European decision to support its case.

  5. Chris Kuckleburg says:

    A recent example that is still playing out in the courts is the lawsuit between Bristol-Myers Squibb and Ono vs. Merck in the anti-PD-1 space. BMS/Ono have a patent covering the use of any monoclonal antibody to treat any tumor. This patent covers BMS’ antibody (Opdivo) as well as Merck’s (Keytruda), and the antibodies being developed by other groups. Merck challenged the validity of the patent in Europe, but it survived. We still don’t know what the U.S. court will say – but I imagine BMS will bring up the European decision to support its case.

  6. SP says:

    The vouchers are only valuable to rare disease companies in that there’s a market for them to be sold to pharma companies working on blockbusters. Many rare disease companies are one-hit wonders, they don’t really have another compound that they could use for expedited review, and even if they did the value of four more months of exclusivity is much lower for a rare disease than for something with a huge market. So if you want to encourage rare disease research through this mechanism, you need to let them sell the vouchers.

  7. steve says:

    Chris – When you say the patent survived, is this just in the lower courts or was it a final decision? Thanks.

  8. Barry says:

    there are two barriers here. First is what (of the claims in the patent app) the examiner will allow. Second is what a U.S. patent court will affirm. A tiny minority of drug patents ever get litigated, so we rarely get over that second hurdle.
    It seems to me that both the Amgen claim here and the BMS claim will in time be judged over-broad and unenforceable. But the law is whatever the court says it is, whether it make sense to any of us or not.

  9. Cellbio says:

    Not a patent lawyer, but it used to be that if you had the patent on the protein then you had patents on all antibodies to that protein, as antibodies were obvious to those skilled in the art. Has that changed? It was like having all inhibitors to enzyme X. Problem now is what patent for a gene has any life remaining? Perhaps with credits for clinical research Amgen can try to protect the market for a few years yet.

  10. johnnyboy says:

    Hmm, the FDA offers transferable vouchers for expedited review, how nice… How about 2 for 1 deals ? Reconditioned Complete Response Letters ? Gift cards for the Silver Springs Red Lobster ?

  11. Stephan says:

    For those playing along at home:
    The relevant patent appears to be US8563698B2 formerly US2009326202A1: (partial) priority date 2007-08-23, published 2009-12-31, granted 2013-10-22.

  12. Old man says:

    Kind of like Diels and Alder in their 1928 paper, “We explicitly reserve for ourselves the application of the reaction developed by us to the solution of such problems.”

  13. Thoryke says:

    Isn’t this the strategy that Amgen has used to prevent other EPO promoting agents in the US market?

  14. earth23 says:

    Derek –
    Patent attorney here. Small molecules are a different beast when it comes to patenting than antibodies because they are typically easier to define–this helps particularly with written description and enablement.
    But, broad antibody claims are well known in the case law and have been shot down for various reasons: Chiron v. Genetech (Monoclonal antibodies for HER2); Schering v. Amgen (a-interferon); Amgen v. HMR (EPO); and last but not least, BiogenIDEC v. GSK (CD20 antibodies).

  15. Imaging guy says:

    # steve
    I am not a patent lawyer. I think this article may answer your question.
    “Antibody specification beyond the target:
    claiming a later-generation therapeutic antibody
    by its target epitope”
    The following press release from a law firm is about the latest court decision concerning an antibody discussed in the article.
    “GSK Backed By Fed. Circ. In Leukemia Drug Patent Suit”

  16. Chrispy says:

    Derek, you need to look more closely at the patents mentioned in that press release. Amgen is not claiming ANY antibody to PCSK-9, just ones that bind to a particular epitope of PCSK-9. This is a layer of subtlety. The closest case may be the Centocor vs. Abbott saga in the anti-TNF arena. Centocor initially won that case (for >$1.6 billion in damages) only to have the patent tossed for lack of an adequate written description. The devil is clearly in the details.

  17. Anon2 says:

    AHA had PCSK9 everywhere, even my hotel keycard.
    I do wonder though if the race to market matters so much anymore. We are already seeing with Sovaldi and Harvoni payers are very satisfied with placing patients on the sidelines until there are at least two competitors in the market.

  18. Lou says:

    If Chrispy’s comments are correct, Derek’s post should be edited to reflect reality.

  19. PKU me harder says:

    Biomarin is the scumbag company who took tetrahydrobiopterin, an unpatentable natural product discovered by someone else and with no obvious substitutes, got it declared an “orphan drug”, and raised the price to $12,000 a month. Tetrahydrobiopterin is an endogenous folate analog used to treat congenital inability to catabolize phenylalanine. Total market take will be $2 billion, for an investment of a few million dollars in a trial.

    I am not surprised to see Biomarin getting a special dispensation to help dying babies, then immediately auctioning it to help old people who cannot be bothered to exercise their muscles or their self control.

    DELENDA EST BIOMARIN

  20. Featherson says:

    I do not know about all of this patent kerfuffle, but I do know that the answer to cholesterol problems is not the ridiculously expensive and dangerous drugs such as the statins etc. Simple solution which has worked for me-garlic pills-$7.00/month. My doctor was amazed. Cholesterol level improved markedly. Of course I may go down like a stone tomorrow because we don’t know if cholesterol is even relevant-see carbon dioxide/global warming/Buffalo NY 9 feet of snow in two days.

  21. WernerDJuan says:

    Reading the claims to US2014235831 reminds me a lot the Myriad case where the subject of the controversy was if it is allowable to grant a patent to diagnostic methods that find the potentially cancerous mutations of the BRCA genes. In this case the sequence mentioned is the epitope of a protein, a natural sequence of amino acids, no less natural than a DNA sequence.

  22. catize says:

    I agree with Crispy, there are several granted US patents but they all claim specific epitopes with specified amino acids that a binder should bind/block. Indeed, if you combine the scope of the patents it is probably difficult to find an antibody that does not bind within the several epitopes claimed. However, it could be possible (needs to be measured). Amgen tried to get the broad claim but it did not get granted as such (see original first claim from PCT below):
    Claims (WO09026558A1)
    1. An isolated neutralizing antigen binding protein that binds to a PCSK9 protein comprising the amino acid sequence of SEQ ID NO: 1, wherein the neutralizing antigen binding protein decreases the LDLR lowering effect of PCSK9 on LDLR.

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