Of Patents and the Parsing of Words

Makers of FDA-regulated products usually have a lot to keep track of, and the last few weeks are no exception. Recently, the FDA seemed to tell industry, “do as I say, not as I do” in connection with combination product classification, while a federal court breathed new life into a lawsuit that could badly damage a very expensive patent for a cholesterol statin.

FDA; Devices are Drugs, too

Some systems of justice say you are innocent until proven guilty, but the FDA guidance for combination product classification has a different approach, stating that in conceptual terms, “all FDA-regulated medical products meet the definition of a drug.” The passage seems to resurrect industry concerns that the primary mode of action (PMOA) controversy is not over yet after all.

The 21st Century Cures Act purportedly fixed a number of problems with combination products, including the PMOA problem as seen in Section 3038 of the Cures Act. That portion of the legislation stated that the PMOA is “the single mode of action of a combination product expected to make the greatest contribution to the overall intended therapeutic effects of the combination product.”

Granted that this passage is no novelty where the regulation is concerned, but the inclusion of this language in the statute might be seen as putting the FDA’s Office of Combination Products on notice that would get away with no adventurism on the PMOA question. As is widely known, the FDA has locked horns with industry, in and out of the courts, on a number of occasions over the agency’s product classification process, partly because the agency seemed to develop a penchant for seeing any chemical mode of action at all as necessarily categorizing the product as a drug.

This bias toward categorization  of a combo product as a drug was a significant bone of contention with industry in the 2011 draft guidance for determination of product classification. One of the arguments raised by industry at the time was that the text and the legislative history of the Food, Drug and Cosmetic Act suggested that if anything, the bias should be that a medical product is a device, not a drug. However, the final guidance states, “conceptually, all FDA-regulated medical products” meet the definition of  a drug “due to the broader scope of the drug definition.”

For what it’s worth, the agency addressed the chemical action question a bit more forthrightly than it has in the past, vowing that it will not assume that a product with a chemical action in the body is necessarily a drug, but that passage may prove to be of little consolation when the next inevitable close call shows up at OCP’s doorstep.

Patent Scrum Over PCSK9s Not Over Yet

Amgen v. Sanofi is headed back to a district court after the Court of Appeals for the Federal Circuit overturned a couple of determinations by a district court, and upheld a couple of others. The Federal Circuit lifted an injunction the district court placed on one of these cholesterol statins, but the more interesting matter may be how the Federal Circuit ruled on whether evidence developed after the patent priority date can be used to invalidate a patent.

Amgen’s lawsuit against Sanofi and Regeneron alleged infringement of Amgen’s patents for Repatha, the PCSK9 inhibitor that hit the market a couple of years ago with an eye-popping price tag that had payers in an uproar. Prior to the hearing at the Federal Circuit, the case was heard in a district court in Delaware, where U.S. District Judge Sue Robinson affirmed Amgen’s argument that the patent was not obvious, and ordered the defendants to pull Praluent off the market.

Robinson also excluded evidence about the patents for Repatha that was based on data developed after the patent priority date of January 2008. The question here seems to revolve around whether Amgen was required to characterize all the species of antibodies that bind to the PCSK9 enzyme, a bit of biochemistry that is necessary to achieve the cholesterol-lowering effect of this class of drugs.

Amgen is said to have screened 3,000 species of antibodies to arrive at the two that are used in the drug, but Robinson had ruled that Sanofi and Regeneron could not introduce evidence that the written description for Repatha failed to comport with the statute governing patents. The passage in question, Title 35 of the U.S. Code (§112), states that a patent applicant must characterize the patented item in “full, clear, concise and exact terms,” a standard the sponsors of Praluent said Amgen had failed to fulfill.

Robinson’s rationale was that the evidence offered by Sanofi and Regeneron would not have served to “illuminate” the state of the art at the time of the filing of the Repatha patent, but the Federal Circuit saw otherwise, essentially concluding that the question is not whether the evidence was illuminating, but rather whether Amgen’s written description of these antibodies was sufficient to support a patent.

The Federal Circuit also said Robinson’s instructions to the jury led the jurors to believe that a description of a novel antibody would suffice to cover the requirement that a patent describe a correlation between structure and function. The net effect of all this is that the case will head back to the district court, but a date has not been set, and Robinson is said to have left the court. Her absence will likely be felt, given that TC Heartland v. Kraft will soon load the court with a large volume of cases thanks to that decision’s effect on the long-standing forum question and the presence of a huge number of LLCs in the Blue Hen State.

Of Combo Products and High Courts

Tourists to our nation’s capital can always find plenty to do, and the same can be said for those in the life sciences with an ear for crucial policy matters. Following are two items of interest to makers of FDA-regulated products, one of which may have a significant influence over FDA regulation over an increasingly important class of medical products, while the other addresses federal prosecution under the responsible corporate officer doctrine.

Misgivings regarding the FDA’s CPPC

The FDA’s Combination Products Policy Council (CPPC) has a pretty serious lift in front of it, not the least of which is the thorny problem of differences in culture and attitude at the various centers that will be caught up in these combo product applications.

For some time, it has been known that many reviewers at the Center for Drug Evaluation and Research are no fans of the 510(k) program, apparently seeing it as an unforgivably fast track to market. Of course, the notion of substantial equivalence is a stranger in a strange land at CDER, which might explain a lot of the antipathy toward 510(k) devices there.

The agency opened a docket at regulations.gov in January, seeking feedback on topics the CPPC might address, and as might be expected, some of the consternation has to do with the process for determining a combo product’s primary mode of action. One concern in particular is how the agency will go about determining what sort of evidence will be needed to establish a product’s PMOA.

Other concerns relate to procedures for handling inter-center disputes regarding PMOA when the Office of Combination Products seems unable to broker a conflict. On the other hand, some have indicated that the interactive review process at CDER is more cumbersome than at the Center for Devices and Radiological Health, and thus would add time to what already promises to be a difficult review process.

One issue that was not conspicuous in comments to the docket was that of user fees. A sponsor will obviously have to pay more if the product’s PMOA is declared to be that of a drug, but what about fee sharing between centers? Will the lead center share user fees with the other center or centers? That’s not clear, and while reviewers at CDRH might find the drug user fees more than adequate, reviewers at CDER might find the device fee schedule unacceptably miserly.

SCOTUS says no to DeCoster

In one of the more interesting Park doctrine cases of recent vintage, the Supreme Court has opted not to hear arguments in the case of Decoster v. U.S., which allows to stand a three-month jail sentence imposed on the father-son ownership team in the egg business.

Many members of the bar see DeCoster as an outlier in that it entailed a jail sentence for Jack and Peter DeCoster, who are said to have been unaware of the violative behavior going on at their company, but more important is the prospect that this case will serve as a precedent for federal prosecutors who want to imprison those in the food, drug and device industries for problematic products. The high court’s decision to pass on the case means the two men will serve their jail sentences, but it also suggests that the Supreme Court will not hear this case until an appeals court other than U.S. Eight Appeals renders a different verdict in a similar case.

It may be an odd source of comfort to note that federal prosecutors will likely try out this new enforcement tool fairly promptly, which suggests that a different appeals court will have a crack at this question in fairly short order. Understandably, nobody in the food, drug or device business wants to serve as the subject of that case, but industry as a whole might want to see this question resolved as quickly as possible.

There is some question as to whether the current composition of the Supreme Court makes this the ideal time to take up such a case, but it’s difficult to predict which of the justices will be the next to leave the Court. Ruth Bader Ginsberg is a leading candidate for retirement because of her age (84), but Anthony Kennedy is no kid, either, as his 81st birthday is fast approaching. A Trump administration replacement for Ginsburg would seem to guarantee DeCoster will be overturned, but those in search of a predictable legal environment might say sooner is better, regardless of the prospects for churn at 1 First St. NE in our nation’s capital.