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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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« Merck: Unfigure-outable | Main | Ariad's Patent Eviscerated »

September 4, 2006

Plavix Plot Twists

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Posted by Derek

The mighty Plavix battle has taken another unexpected twist. In the last installment, Canadian generic company Apotex had snookered (a completely accurate description) Bristol-Meyers Squibb and Sanofi/Aventis into an ill-advised agreement that ended up destroying the drug's patent protection. Apotex had begun gleefully shipping their generic, while the two larger companies sought relief in court from what appears to have been largely a problem of their own making.

To my surprise, that relief has been granted. Last week, a judge issued an injunction against further sales by Apotex in the U.S. until the patent infringement trial is completed. That's not even going to begin until early next year, and you can be sure that BMS and S-A are going to drag it out as much as possible. No legal bills can compare with the hit they've taken over generic Plavix. Sanofi-Aventis, for example, has lowered its profit forecast to a 2% increase over last year, instead of 12%, claiming that Apotex has clogged up all the distribution channels with their generic. I'm a little sceptical of the size of that effect - it's not unheard of for companies to unload other types of bad news under a convenient banner, given the chance - but there's no doubt that it's been a nasty experience.

Apotex may have just had its moment of glory, at least as far as Plavix is concerned. I'm sure that they made money during this adventure, so if they were going to lose the patent case anyway, they're still ahead. No doubt they'd have been even happier to go on selling it, but they'll take what they can get.

Meanwhile, the Federal Trade Commission is making threatening noises about investigating other pay-the-generic-to-go-away deals. The courts have ruled that such deals are legal if they don't push past the patent expiration of the drug, so I'm not sure what the FTC is going to be able to do. But they're clearly unhappy about the situation. For my part, I'd as soon see the generic companies go ahead and challenge the patent-holding ones, as long as the decisions are made in a competent legal venue. By which I mean, not like the one that upheld Ariad's patent. Keeping everyone on their toes is a good thing, as long as it's done fairly.

Comments (10) + TrackBacks (0) | Category: Cardiovascular Disease | Patents and IP


COMMENTS

1. Anonymous BMS Guy on September 5, 2006 5:46 AM writes...

As you can well imagine, all of us at BMS are very much relieved by the preliminary injunction, especially since this judge -- who will be the one hearing the full trial in 2007 -- included in his opinion a fairly detailed dissection of the arguments Apotex has made on the enantiomer issue that makes it quite clear they would need a dramatically stronger and different case to prevail.

We are still quite uncertain about our personal futures with BMS and have zero trust in our top management.

I do think our patent system badly needs reform; as it stands right now I don't think it really serves anybody's interests. I'm not a lawyer so cannot pretend to have any good ideas on how it should be reformed, but that it needs major reform is IMHO beyond dispute.

The full text of Judge Stein's opinion is here:
http://www.nysd.uscourts.gov/courtweb/pdf/D02NYSC/06-03453.PDF

Permalink to Comment

2. JSinger on September 5, 2006 11:38 AM writes...

I don't understand -- isn't the whole point that S-A and BMS waived their patent protection in their agreement with Plavix?

Permalink to Comment

3. Former BMS Guy on September 5, 2006 7:50 PM writes...

Derek

You forget the one key to Apotex's strategy:

Peter Dolan is the CEO of BMS. Until he is no longer CEO, I'd bet on Apotex, every day of the week and twice on Sunday.

Permalink to Comment

4. secret milkshake on September 5, 2006 10:27 PM writes...

BMS-Anonymous: Thank you for the text of ruling, I was reading the judge's expose with a great interest - it is a lucid and detailed writeup on invalidating patents in court.

Permalink to Comment

5. SRC on September 6, 2006 1:33 PM writes...

Former BMS Guy, it looks like you're about to get your wish.

Permalink to Comment

6. Canuck Chemist on September 6, 2006 6:01 PM writes...

I have some problems with Judge Stein's analysis. First of all, it is agreed that Plavix (clopidogrel bisulfate) is covered under the various broad claims of the earlier Sanofi patent, but he contends that the claims are not specific enough to direct one trained in the art to choose and then make clopidogrel bisulfate, even though the racemic version is given as example 1 of this earlier patent, and the first claim of the earlier patent also covers “both enantiomeric forms or their mixture". One would think that these claims in the earlier patent would make Sanofi's later patent (which specifically describes the single-enantiomer compound clopidogrel bisulfate) invalid, but not according to Judge Stein:

“Indeed, Sanofi's experts testified that nothing in the prior literature could have
predicted that a single enantiomer of the racemate PCR 4099 would have more
acceptable pharmaceutical properties than the racemate itself. Thus, a scientist would not
have been motivated to split the enantiomers of 4099 without guidance that the '596
patent did not provide."

I find it rather amazing that a company can have the best of both worlds when making these patent claims. The claims can be sufficiently vague to prevent others from potentially operating within huge swaths of chemical space, yet they can get follow-up patents with no real inventiveness (in my educated opinion) over the original patents. I don't think Judge Stein understands that in fact under most circumstances enantiomers can have substantially different activities, and despite Sanofi's arguments it is routine in medicinal chemistry to synthesize or isolate single enantiomer versions of promising lead compounds.

One would think that if one tries to live by broad claims, one should die by them too (i.e. by not allowing silly follow-up patents).
It'll be interesting to see how the actual trial plays out...

Permalink to Comment

7. Petros on September 7, 2006 2:00 AM writes...

Canuck chemist highlights an intersting point in the judge's coments

"“Indeed, Sanofi's experts testified that nothing in the prior literature could have
predicted that a single enantiomer of the racemate PCR 4099 would have more
acceptable pharmaceutical properties than the racemate itself. Thus, a scientist would not
have been motivated to split the enantiomers of 4099 without guidance that the '596
patent did not provide.""

As he says this clearly questions the judge's competence in matters chemical since it was well known by the time in question that most pharmaceuticallya ctive agents had a eutomer and a distomer and that it would be preferable to develop the eutomer, although as that time it was unclear whether the regulatory authorities would demand the development of a single enantiomer.

I remmember the long discussion we had in resepct of one compound where the two enantiomers had almost identifical potencies.

This also raises the question of the reliability of the evidence given by Sanofi's experts, or their competence.

Permalink to Comment

8. Master P on September 15, 2006 5:32 AM writes...

I'm amazed at how the focus been entirely on BMS and the press is not linking sanofi into this. Plavix is a 50-50 joint venture. No decision is made without both parties agreeing to it. Therefore, Jean-Francois Dehecq as much as Dolan are to blame for this disaster.

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9. Patrick Mullen on September 15, 2006 12:18 PM writes...

Couple of points. BMS just marketed it in the US, not sure how that affects the rest of the world distribution, if any.

Also, BMS may have received the injunction, but that was almost like closing the barn doors after the horses were out. There is probably 7 or so months inventory of the generic out there being sold.

Permalink to Comment

10. Master P on September 18, 2006 5:22 AM writes...

Actually, both sanofi and BMS Market Plavix in the US. All Marketing Strategy and tactics are agreed upon by both companies.

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