Integra v. Merck: Research Tools Exemption Still Undecided

Integra Lifesciences v. Merck KGaA (Fed. Cir. 2007).

In 2005, this case reached the Supreme Court – who held that the safe harbor created by 35 USC 271(e)(1) “exempted from infringement all uses of patented compounds ‘reasonably related’ to the process of developing information for submission” to the FDA. ‘Reasonably related’ research is determined in a two-part test:

1. Was the research conducted after the biological mechanism and physiological effect of a candidate drug is reasonably recognized; and
2. If the research is successful would it “appropriately be included in a submission to the FDA.”

On remand, the CAFC applied the Supreme Court’s legal ruling to find that Merck’s uses of Integra’s patented RGD peptides was not infringement under the 271(e)(1) safe harbor.  In part one of the test for ‘reasonably related the CAFC found that the accused experiments had all been “conducted after it had been discovered that a RGD peptide shrank tumors in an animal model. ” Part two, is satisfied because of the fact that the experiments “yielded data relating to efficacy, mechanism of action, pharmacology, or pharmacokinetics.”

Applying these criteria, there was no evidence at trial in conflict with the evidence that all of the experiments here at issue were conducted after it had been discovered that a RGD peptide shrank tumors in an animal model; indeed, Integra so conceded to the Court. The primary Integra argument on this remand is that the FDA is interested only in safety data at the IND application stage; although that argument was unambiguously disposed of by the Court. At the jury trial, before the Court, and on this remand, Integra does not dispute that the accused experiments yielded data relating to efficacy, mechanism of action, pharmacology, or pharmacokinetics. At the trial the admissibility of the scientific evidence and its premises were not challenged.

In the process of reversing the lower-court’s infringement decision, the CAFC dismissed a number of argument by Integra. For instance, Integra argued only experiments that are “entirely routine” should be subject to the exemption. The CAFC rejected those arguments in turn.

[T]he [Supreme] Court's explanation of the criteria of '271(e)(1), the safe harbor does not depend on a distinction between "discovery" and "routine," but on whether the threshold biological property and physiological effect had already been recognized as to the candidate drug. The Court recognized that experiments are run in order to learn information, whatever the stage of the research.

Research Tools: The court did not discuss the issue of “research tools” because “the parties emphatically confirmed that research tools were not at issue.” (post-hearing letter).

Judge Rader in dissent to Judge Newman’s opinion:

This decision casts a large shadow over patent protection by its overly expansive interpretation of the 35 U.S.C. § 271(e)(1) exemption. In particular, this court today expands the exemption beyond the Supreme Court’s limits on the provision to eliminate protection for research tool inventions.

Rader would have decided the research-tool issue.

Sadly this court does not even examine the patents at issue in this case. This court, noted for its emphasis on claims as definers of patent scope, ironically does not recite or analyze the claims of these patents in the slightest. Moreover this court speaks in broad terms about the experiments and results without specifying which patented compound or method was in use in the experiments. A careful examination of the patents shows that two of them have no application at all outside of a laboratory. If the patents in this case are not research tools, then of course this court could quickly construe the claims and show that they claim drugs or other products likely to undergo FDA clearance, not simply laboratory methods. Unfortunately even a cursory analysis of the patents (undertaken in this dissent) shows that two of them have no application outside the laboratory.

Comments

[DJF]

I'm not sure that Judge Rader's "the sky is falling dissent" is warranted; we need to wait and see a few more of these research tools cases to see if he's right. I agree that it's bizarre for the panel majority not to analyze the claims in detail. On the other hand, I find it strange that Rader relies on the legislative history in support of his position - compare to Eli Lilly v American Cyanamid, a 1996 case, where he flat-out refused to consider legislative history in interpreting 35 USC 271(g).

The panel majority went out of its way to point out that in this case, the patented methods were being used to determine which compounds out of an already defined subset were suitable for submission to the FDA. So it sounds to me like the door is still open for someone who develops a "research tool" and has a method claim protecting that "research tool" to nail someone else for infringement. Of course, under Bayer v Housey, if they practice that method abroad to identify drug candidates, and then send a list of identified candidate compounds to the USA, the importation isn't infringement; and under the new Integra v Merck decision, once those candidates have been identified, use of the method to collect further information for FDA submission isn't infringement. So although Judge Rader didn't say so, looks like there's now good incentive to use all research tools overseas to ID drug candidates.

[Malcolm Mooney]

compare to Eli Lilly v American Cyanamid, a 1996 case, where he flat-out refused to consider legislative history in interpreting 35 USC 271(g).

I don't remember it quite that way. I think Rader was just shocked at what the majority came up with when it went to the legislative history. "Material change" = no commercially viable alternative for making compound??? Who'd a thunk?

My opinion is that the Supreme's messed this statute up and Congress should fix it, not the CAFC.

[koti]

I want to some new patents of peptide