Bending Patent System to Head Off Competition Long-Term

 AbbVie’s Humira, an injectable biologic for treating the symptoms of rheumatoid arthritis, is one of the best-selling drugs worldwide with over $20 billion in sales in 2022. Humira also stands out for a different reason: more ancillary patents have been filed for it with the U.S. Patent and Trademark Office (PTO) than for any other drug, according to a recent analysis. Such patents enable companies to keep an exclusive grip on the market for long after their primary patent expires, authors of the analysis say, maintaining the typically high prices of their brand-name drugs.

“The USPTO grants primary patents to incentivize innovation, and [typically grants] twenty years of market exclusivity,” said S. Sean Tu, professor of law at West Virginia University College of Law and the co-author of two November Journal of American Medical Association (JAMA) publications looking at what the authors call patent gamesmanship by Big Pharma. Given their financial interest in preserving the profits garnered by their drugs, biopharma companies find loopholes in the patent system to extend the intellectual property (IP) lifecycle of their drugs and deter competition from entering the market, Tu told BioSpace in an interview.

“Patents should last for a limited time, after that, competitors should enter the market and drive down the price of a drug,” wrote Robin Feldman, a professor of law at University of California Hastings College of Law who did not participate in either of the JAMA studies, in an email to BioSpace. “But that is not what’s happening in the pharmaceutical markets. Companies have become adept at piling new protections onto existing patents.”

Frequently, as the primary patent nears expiration, companies make slight modifications to a drug’s dosage, formulation or mode of delivery to obtain ancillary product patents. “EpiPen is a classic example of misusing [device] patents,” Tu said, with the introduction of a retractable needle extending market exclusivity by 15 years.

Such secondary patents do not have the innovation value of primary patents, which reward the discovery of novel therapeutic agents, and may be of questionable validity, Feldman said. However, it takes time and money to legally challenge patents.

Biologics manufacturers are especially notorious for laying ancillary patents on top of primary patents to extend market exclusivity, Tu said. In many cases, “Ancillary product patents cover critical aspects of the biologic that are important for the efficacious functioning of the drug,” he noted. Such patents cover key biochemical features like glycosylation profiles (carbohydrate molecules attached to the protein) or oxidation profiles (free radical–induced modifications to the protein structure), which influence the structure, stability and biological activity of the therapeutic. Instead of filing such product features in the primary patent, Tu explained, companies often keep them confidential, then file the features as ancillary patents close to the expiration date of the primary patent. “Ancillary product patents were usually filed 18 years after the primary patents were filed and extend [patent protection] by ten to fifteen years,” Tu said.

The Worst Offenders

In the JAMA analysis, Tu and his co-authors name 12 biologics companies involved in litigation against competing biosimilar companies. Of these, four companies had active ancillary patents protecting their biologic from market competition. AbbVie topped the list with 15 ancillary patents on Humira. Regeneron’s Eylea, Johnson & Johnson’s Epogen/Procrit and Genenetch’s Herceptin were similarly protected by ancillary patents that enabled the companies’ suits against their competitors.

The practice of filing ancillary patents to extend the IP lifecycle of a drug is legal. However, in rare cases pharmaceutical companies withhold or misrepresent information presented to the PTO when filing primary or ancillary patents. Such fraudulent practices are known as inequitable conduct and can lead to invalidation of patents, Tu and colleagues noted in their second JAMA article.

In 2014, for example, Belcher Pharmaceuticals LLC filed a patent for an injectable l-epinephrine formulation that the company claimed had a new pH range that improved stability of the product. The previous year, however, Belcher had submitted two published references to the FDA seeking a literature-based new drug application (NDA).

When Hospira Inc. filed an NDA for its l-epinephrine formulation in 2017, Belcher filed a patent infringement suit against Hospira. In a twist of events, it emerged during the trial that Belcher engaged in inequitable conduct by withholding material information at the time it filed the primary patent, and the patent was rendered unenforceable in 2021. “The case demonstrates two of the most common methods employed in such cases: intentional deceit and withholding key reference publications,” Tu said.

According to the JAMA analyses, in every case of biopharma companies accumulating ancillary patents to squeeze out competition, and in every case of inequitable conduct, the FDA had the requisite information to show the patent filing was not justified—information that was not available to the PTO. The FDA could not release such information because it is protected as trade secrets.

Tu and his co-authors on the two JAMA papers concluded that close collaboration and information exchange between the PTO and the FDA may deter pharma and biotech companies from using ancillary patents to extend the IP lifecycle of their drugs, facilitate early market entry of biosimilars, and prevent the approval of invalid patent applications. In a step in that direction, President Joe Biden in 2021 signed an executive order mandating increased correspondence between the FDA and PTO.

“Communications between the FDA and PTO could reduce the number invalid patents,” said Arti Rai, a professor of law at Duke Law School who was not an author of the JAMA analyses but was involved in drafting the executive order. Such collaboration during the patent application process could, experts told BioSpace, help return the patent system to accomplishing its original mandate: incentivizing medical innovations and fostering their equitable distribution to American patients most in need of life-saving treatments.

https://www.biospace.com/article/companies-bend-patent-system-to-head-off-competition-long-term-analysis/