I've written before about method-of-treatment patents, and now the subject makes today's front page of the Wall Street Journal. They've picked a pure example of the breed. Hans-Ulrich Demuth at the University of Halle in Germany filed for a patent in 1996 on the use of inhibitors of dipeptidyl peptidase IV in the treatment of diabetes. The patent was granted in the U.S. in late 2001 (as US6303661, and no, for those outside the field, that's not an odd delay at all, for better or worse.)
Like many peptidases, DPP-IV is a wrecking ball of an enzyme. It breaks down (among other things) an important signaling protein called GLP-1 (that stands for glucagon-like-peptide 1, which shows you how fuzzy a lot of biochemical nomenclature can be.) And GLP-1 is important in maintaining glycemic control - type II diabetic patients could sure use more of it than they have. If you could find a GLP-1 mimic, you'd have a very interesting drug. That's an unlikely hope for a small molecule, though, so other bounce-shot approaches have been tried. GLP-1 itself has been tweaked in attempts to make it more stable, and people have tried various smaller proteins as well.
There are more. People have tried to cause more GLP-1 to be secreted, without tremendous amounts of success, and then there's the DPP-IV inhibitor approach, which would cause it not to be broken down so quickly. Whatever works! Several companies have taken a whack at this route, because the inhibition of protease enzymes, while still nowhere near a sure thing, has a reasonably good track record in drug development. Novartis is the company in the lead, with a compound well into clinical trials.
Demuth, naturally enough, wants a piece of the action. His first patent claim is for: "A method for lowering elevated blood glucose levels in mammals resulting from food intake comprising administering at least one oral administration of a therapeutically effective amount of at least one inhibitor of Dipeptidyl Peptidase IV (DP IV) or of DP IV-like enzyme activity."
Well, that covers the bases, you'd think. But there's a Prof. Jens Holst in the picture as well, from the University of Copenhagen. His group published a paper a few months before Delmuth's patent was filed, in which they showed the effect of a DPP-IV inhibitor in vitro, and suggested it as an adjunct therapy for diabetes. That's a complication, because if anyone spells out your idea in print, you can't get a patent on it later. (This applies to your own statements, too, which is another reason why we in the drug industry only publish on projects that either well along in the clinic or already dead.)
But Delmuth's patent issued, Holst or no Holst, and he cited the prior work in it. That makes breaking his patent harder, because (presumably) the patent examiner took Holst's work into account and decided to allow the claim anyway. Anyone who wants to say that the earlier publication is invalidating prior art is going to have to prove that the examiner blew it - which certainly isn't unheard of, but is still a harder path to take.
Merck and J&J have already either paid Delmuth or indicated that they're going to. BMS isn't saying what they'll do. Novartis, on the other hand, has so far flatly refused to pay anything. A spokesman told the Journal that they're considering doing some sort of deal, though. You can bet that it's going to be based strictly on the numbers: on one side, figure out how much the drug is likely to make, and find out what sort of cut Delmuth wants. Then factor in how likely it is that you'll actually get to the market. On the other side, how much would it cost in time and legal fees to break his patent? Factor in how likely you think you'll be to win, and you've got the whole equation.
Now, I haven't studied this closely, but that's not going to stop me from having an opinion. (When, since the dawn of time, has that every stopped anyone?) Holst's paper looks like a reasonable candidate for prior art to me, frankly. (He seems to think so, too - he and Delmuth have had some testy exchanges in print.) You'd want to look over the prosecution history of Delmuth's patent, to see if there was any back-and-forthing about it during the examination period. It seems clear to me that the higher the expectations Novartis has for their inhibitor, the less likely they'll be to settle.
But all this suggests the next question, coming up for discussion here within the next few days: should such patents even be granted? Highly paid people are prepared to argue either side of the issue! Heck, I'm even prepared to take one side of it myself.