Studies: Drugmakers are gaming the patent system with misrepresentations, ancillary patents

Drugmakers are withholding critical information from the U.S. Patent and Trade Office (USPTO) to protect and extend patents on approved biologics, classifying ancillary product data as trade secrets or, in some cases, misrepresenting or omitting key information on a patent application, according to two related research letters published in JAMA.

The findings point to the need for the USPTO and the US Food and Drug Administration (FDA) to work together to manage pharmaceutical companies’ “patent gamesmanship,” making it easier to bring lower-cost biosimilars to market, according to S. Sean Tu, of the University of West Virginia College of Law, who was a co-author on both analyses, and colleagues.

“Agency coordination could facilitate biosimilar development, reduce market exclusivity periods by promoting earlier patent filings, and ensure that patients have earlier access to lower-cost therapies,” they wrote.

Since both studies extracted their data from court filings, the findings likely do not show the full extent of these patent tactics, the researchers wrote. For example, inequitable conduct – the practice of omitting or falsifying information on patent applications – can only be identified through litigation. “Although inequitable conduct appellate cases have affected few drug patents during the past 15 years, the prevalence … is unknown because not all cases … are identified or litigated,” the researchers wrote.

Similarly, the ancillary ingredient analysis was also limited by focusing exclusively on litigated patents. “[I]t is unknown how many ancillary product patents are filed but not litigated,” Tu and colleagues wrote.

Ancillary product patents

Ancillary products are critical features of the active ingredient that allow it to act on its therapeutic target, such as glycan profiles, oxidation levels or other physiochemical properties, Tu and colleagues explained. Withholding information on them is an under-recognized tactic used to extend patent life.

“Rather than filing ancillary product patents as part of their initial primary patent filing, manufacturers often keep ancillary product features confidential as trade secrets and wait years before obtaining ancillary product patents. The [FDA] possesses ancillary product information but also maintains it as a trade secret. By keeping this information confidential, biologic manufacturers make it more difficult for competitors to access information needed to develop biosimilars. In addition, this strategy may allow biologic manufacturers to extend periods of market exclusivity because later-filed ancillary patents typically expire after the primary patents,” the researchers wrote.

Tu and colleagues identified 271 patents involved in litigation brought by biologics manufacturers against biosimilar-producing firms from 2010, when the biologics approval pathway was established, to mid-2023. Looking at court cases is the only way to examine this issue, he noted, because it forces manufacturers to disclose all patent information.

The cases were brought by 12 biologics manufacturers against 48 biosimilar manufacturers. Of these, 22 (8%) involved ancillary products used in four biologic medications: Johnson and Johnson’s Epogen (epoetin alfa); AbbVie’s Humira (adalimumab); Genentech’s Herceptin (trastuzumab); and Regeneron’s Eylea (aflibercept). Ancillary product patents were filed a median of 18.3 years after the first primary patent was filed and extended the expected exclusivity by a median of 10.4 years.

Epogen was first approved in 1989 with a patent expiration in 2013. However, a single ancillary product patent extended the expiration to 2016, netting an additional 868 days of exclusivity.

Eylea was approved in 2011 with a patent expiration of 2023. However, Regeneron filed four additional ancillary product patents that extended the patent by up to 17 years. These granted product exclusivity until 2040 – an additional 6,273 days.

Herceptin was approved in 1998 with a patent expiration date of 2015. The two ancillary product patents extended that to 2019 for an additional 1,298 days of exclusivity.

Humira, first approved in 2002, had a patent expiration date in 2016. AbbVie filed 15 ancillary product patents that extended that date to 2034, granting an additional 6,527 days of exclusivity.

Although representing only a small proportion of litigated patents, ancillary product patents “pose obstacles for biosimilar entry because, unlike manufacturing and formulation patents, they cannot be designed around, and unlike method-of-treatment patents, they cannot be carved out of the label,” Tu and colleagues wrote. “The FDA and the patent office should work together to ensure that key information on biologics is timely disclosed, either through direct release by the FDA or transmission from the FDA to the patent office during the patent examination process.”

Inequitable conduct

The inequitable conduct study examined cases alleging that manufacturers acquired patents fraudulently or by deceit, by intentionally withholding or misrepresenting material information, the researchers wrote.

They identified 125 inequitable conduct cases from October 2004 to December 2021 at the Court of Appeals for the Federal Circuit, which is the only appellate court to hear such cases.

Of the 125 cases ruled on, 36 (29%) led to the invalidation of 75 patents. Among the 75 invalidated patents, 34 (45%) were for FDA-regulated products, including 15 related to drugs and 10 related to devices. Eight were related to food, and one was a research tool. About half of the drug-related patents (53%) were for drugs listed in the Orange Book. The remainder were related to biologics or covered methods of manufacture.

Most invalidations (88%) were for material omissions in the patent, including omitting printed publications (38%), product sales or public use (35%), negative experiments (35%), other US patents and patent applications (6%) and non-US patents (6%). Almost half (47%) were judged to be active misrepresentations; 15% were prophetic examples passed off as working examples.

Findings of inequitable conduct were more common between 2004 and 2011, with a mean of 2.25 cases per year. However, in 2011, the appellate court “raised the bar to prove inequitable conduct, adopting higher standards for demonstrating intent and materiality,” Tu and colleagues wrote. Since then, one case was upheld in each year from 2012 through 2017. None were upheld in 2019 and 2021, for a median of 0.60 cases upheld per year.

The only way to proactively address this issue, the researchers concluded, is for the USPTO and the FDA to work together.

“Alternatively, Congress could require reexamination of patents on FDA-regulated products after FDA approval. Such reexamination would allow the USPTO to review and determine whether there were any material references, statements, or relevant experiments disclosed to the FDA that were hidden or misrepresented to the USPTO.”

Ancillary product research letter
Inequitable conduct research letter

Studies: Drugmakers are gaming the patent system with misrepresentations, ancillary patents

Related topics

Recommended content

Welcome to the new RAPS Digital Experience