As many readers will have recognized, I was speaking yesterday about the suit between Merck KGaA and Integra. This one has been going on for nearly ten years now, and is a bit of a mess, but here comes the short version:
In the early 1980s, researchers at the Burnham Institute in La Jolla discovered the so-called "RGD peptides", named for the single-letter amino acid sequences they share. These bind to cell-surface receptors called integrins, which are important in a variety of processes that involve cell adhesion. Blood clotting, wound healing, bone growth, and the invasiveness of some cancer cells all have integrin components. The Burnham group formed a company, Telios, and licensed their patents to it. (Later on, Integra bought the rights from Telios, which is where they enter the picture.)
Merck (Darmstadt) and several other companies also became interested in integrins. In the mid-1980s, Merck collaborated with a group at Scripps (also, as fate would have it, in La Jolla), who showed the potential of blocking some integrin subtypes as a method for inhibiting angiogenesis in tumors. (Yep, anti-angiogenic therapies have been in the works for that long.)
Burnham sued, claiming that use of three key RGD peptides by Merck and Scripps violated their patents. (Licensing discussions had fallen though.) Merck fought back by claiming that their work came under a "safe harbor" provision of patent law, by which companies can do research needed for FDA approval of a drug even if that work actually infringes other patents. A District Court jury awarded Integra $5 million in 2000, later reduced, and Merck appealed. The Federal Circuit Court didn't buy Merck's reasoning, either, and ruled that the safe harbor language wasn't meant to extend that far back into early drug discovery and lead identification. (A longer discussion of that ruling can be found here.)
Merck appealed again, and the Supreme Court agreed to hear the case. That's unusual; most patent disuputes don't make it past the Federal Circuit. But the court seems to think that the safe harbor language is both ill-defined and important enough to deserve their attention, and I think that they're right. Merck (and several other drug firms who've filed friend-of-the-court briefs) argue that if the safe harbor provision is defined that narrowly, then big swaths of drug research are going to have to either come to a halt while patents are hashed out, or it'll just up and move to some country that doesn't respect the IP.
Meanwhile, Integra (and other companies who've lined up with them) say that if the law were interpreted according to Merck, then there would be no incentive to companies to search for and patent new research tools. After all, if you could claim the FDA exemption for anything that might end up leading to a drug - that is, anything that might lead to someone making some money - then what's the point?
Oral arguments took place on April 20th. I'm going to bet that the decision will split hairs in such a way as to not shake things up too drastically (as the court did in the Festo patent law case), but I'm glad I'm not betting with the kind of money that Merck and Integra are.
1. LNT on May 3, 2005 10:44 AM writes...
Here's a related question for more experienced medicinal chemists out there: Certain reactions are patented (Sharpless epoxidation, various suzuki-type ligands, etc). Certainly medicinal chemists use these patented reactions all the time in the development of drug candidates. What prevents the patent holder from suing pharmaceutical companies for using thier "patented" reactions?
Permalink to Comment2. Derek Lowe on May 3, 2005 11:05 AM writes...
These reactions often aren't used in the real production route of the final drug candidate. When they have to be, then it's worthwhile to talk about licensing. Otherwise, it's more of a research-exemption case, and not worth trying to enforce.
Permalink to Comment3. LNT on May 3, 2005 11:13 AM writes...
True, but the same could be argued for the RGD peptides. In my mind, the use of RGD peptides by Merck for very early stage research is very much like the use of the Sharpless epoxidation in very early stage lead development.
One could easily make the case that use of a patented reaction speeded the lead discovery efforts by many months, which is quite a lot of money in terms of sales.
Ultimately Merck could have probably screened the integrins without violating the Integra patent -- but it would have cost them months or even years of valuable time to work around the patent. Fundimentally, I view the use of a patented reaction and the use of a patented patented biomolecule (or assay) as equivalent. Do you disagree?
Permalink to Comment4. patentobserver on May 3, 2005 1:56 PM writes...
The use of a patented reaction (method) and the use of a patented biomolecule (composition of matter) are different as kinetics and thermodynamics.
Permalink to Comment5. MDL on May 3, 2005 2:35 PM writes...
I think that are two issues here with regard to infringement.
First, does the work performed (e.g., Sharplesss Epoxidation" infringe? Secondly, what income was lost to the patent holder due to this infringement (damages)?
In the case of using a Sharpless Epoxidation to make some compound for exploratory work, yes it does infringe. However, the damages for such activity would not likely pay the legal bills necessary to pursue this level of infringement.
On the other hand, if one goes to a CRO and requests a large scale Sharpless Epoxidation, they will most likely require that you pay the license fees. In the case of some reactions, like the Jacobson epoxide hydrolysis, only certain CRO's have the license to perform this chemistry.
On a different note, I have been curious as to what might happen when one files a composition of matter patent has not only therapeutic claims, but one that reads, "A compound of composition X that is useful for the discovery of new drugs for the treatment of Y?"
Permalink to Comment6. patentobserver on May 3, 2005 4:21 PM writes...
MDL wrote: "I have been curious as to what might happen when one files a composition of matter patent has not only therapeutic claims, but one that reads, "A compound of composition X that is useful for the discovery of new drugs for the treatment of Y?"
Seems to me that such an applicant would have to enable that claim by saying which new drug and defining "Y". Otherwise, an Examiner (let alone a Court) wouldn't know how to interpret that claim term. Would any attorneys care to weigh in here?
Permalink to Comment7. Derek Lowe on May 3, 2005 5:14 PM writes...
That example of MDL's sounds a bit like Rochester's COX-2 patent, where they held the IP to the enzyme and tried to get royalties on the inhibitors. That, of course, got knocked down on the grounds that their patent did not have anything to say about what that eventual chemical matter would be.
Permalink to CommentHow can you claim something that you have no description of, other than its function? I might as well go get a patent covering "stuff that stops the progression of cancer, whatever that might turn out to be" and sit back and watch the money roll in.
8. patentobserver on May 3, 2005 6:54 PM writes...
It's important to remember that that the PTO oversees an important "public vs private" exchange: monopoly rights (technically right-to-exclude others) in exchange for public disclosure. The patent process feeds a dynamic equilibrium which has endured for over 200 years with minor revisions. Trouble ensues when either side (public knowledge or monopolistic greed) gets the upper hand.
Permalink to Comment9. cytokid on May 5, 2005 12:06 PM writes...
So many drugs are cross-labled that the terms might be "this stuff (or any stuff derived therefrom) helps health." Although this level of protection may be impractical, that is reflective of what is going on in the real world.
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