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bias toward categorization  of a combo product as a drug was a significant bone of contention with industry in the 2011 draft guidance for determination of product classification.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.

Life Sciences’ September Surprises

The October surprise may be the stuff of electoral legerdemain, but drug and device makers are seeing a few interesting legal twists inside and outside the courtroom in the month of September. In one instance, PMA preemption is back in the news, while another story involves what seems a very generous sale of intellectual property assets forced by multiple patent challenges.

Lassoed Again by the Riata

Despite best intentions, sometimes an old drug or device comes back to haunt its maker. This would appear to be the case with the Riata and Riata ST series of electrophysiology leads made by St. Jude Medical, now a subsidiary of Abbott. While this seems a fairly typical preemption case, Connelly v. St. Jude Medical seems to revive the issue of a litigant’s access to confidential commercial information.

According to documents from the U.S. District Court for the Northern District of California, Richard Connelly received a total of three Riata leads between 2003 and 2015. Connelly’s attorneys argued liability on the basis of manufacturing defects, failure to warn, negligence and negligence per se, and Abbott responded that the first three claims are explicitly preempted while the last is truncated by implied preemption.

Judge Edward Davila rejected the failure to warn claim, albeit with a possible amendment of the claim, the same determination he came to regarding the negligence per se claim. Avila gave the plaintiff until Sept. 8 to amend those claims, which apparently his counsel has done.

However, Avila affirmed the manufacturing defect claim partly because the plaintiff’s attorneys had no access to the entirety of the documentation for the regulatory filing. The basis of the manufacturing defect argument commenced with three pieces of evidence; an FDA inspectional form, the recalls of the Riata series of devices, and an internal root cause analysis undertaken to examine the lead insulation problems.

Avila wrote that California state law does indeed run parallel to federal law on the manufacturing defect issue because the plaintiff had demonstrated “a plausible connection between the alleged manufacturing defect and his injuries.” He based this conclusion in part on a 2014 case in the U.S. District Court for the Northern District of New York, Rosen v. St. Jude, but not much else.

Avila conceded that the Court of Appeals for the Ninth Circuit “has not directly addressed this issue,” but states that a plaintiff’s inability to access confidential commercial information at the time complaint was filed – coupled with factual evidence presumed to be sufficient to demonstrate a causal connection – are all that is needed to sidestep federal preemption and satisfy the requirements of Twombly.

The negligence claim survived on essentially the same set of facts, and the court determined that Abbott is not liable in this instance because its acquisition of St. Jude was not completed until after Connelly was injured. Avila indicated that the plaintiff can amend the complaint on this point as well, however. It seems fairly plausible that this case will end up in Ninth Appeals, regardless of the outcome in this venue.

Allergan’s IP End Run

Most methods for dealing with patent challenges run to the tried and true, but Allergan’s move to insulate its patents for Restasis may have left some members of the patent bar a bit dewy-eyed for not having thought of it themselves.

Allergan has declared it will transfer all patent rights for the treatment for dry eye to the St. Regis Mohawk Tribe, which will confer sovereign immunity on the related patents. This would seem to fend off ongoing challenges via the inter partes review process at the Patent and Trademark Office, but there are suggestions that Allergan has progressively less to lose. While sales of the product exceeded $350 million in the third quarter of 2016, the FDA has yet to decide whether generic versions will have to go through clinical trials in a debate between the agency and the manufacturer that is now in its fourth year.

The company is also fending off a patent challenge in the patent rocket docket in Marshall, Texas, over the production of generics, which some believe will hit the market as early as 2019. The problem for Allergan in this lawsuit, at least in terms of optics, is that the company has already settled with Famy Care Ltd., which will be able to market its generic version no later than 2024 (when the patent expires), and possibly substantially earlier.

Under the terms of the licensing agreement, the St. Regis Mohawk Tribe seems to be doing quite well, indeed, explaining in a Sept. 8 statement that it will receive more than $13 million from Allergan to take ownership of the patents in addition to an expected annual sum of $15 million in royalties.

Cardiaq Sustains Narrow Win Over Neovasc

The patent scrum between Cardiaq Valve Technologies and Neovasc Inc., made it all the way to the Court of Appeals for the Federal Circuit, which has affirmed a district court decision awarding the plaintiff more than $110 million. In Cardiaq Valve Technologies v. Neovasc, Inc., the plaintiff alleged that Neovasc had breached a contract the two companies had signed as part of a development program by Cardiaq toward a transcatheter mitral valve technology, which Neovasc purportedly violated by using some of the intellectual property in an effort to develop its own mitral valve device.

In addition to the initial jury damages of $70 million, Neovasc will have to pay roughly $20 million each for interest and enhanced damages, although neither the district court nor the Federal Circuit agreed to enjoin Neovasc’s development program. While Cardiaq won’t enjoy the kind of exclusivity typically afforded by a patent, it was acquired by Edwards Lifesciences, which has a degree of credibility with cardiologists that Neovasc cannot possibly match in the near term. Thus, while the patent fight seems uncomfortably close to a draw for plaintiff, the physician adoption curve is nearly certain to favor Cardiaq by a wide margin.