Opinion: Purple Book Patent Listings Are Only a First Step

Stacie Ropka, JD, PhD

Stacie Ropka, JD, PhD, is a partner at Axinn. Her practice focuses on intellectual property litigation, due diligence, and client counseling, with an emphasis on the life sciences. Ropka’s experience includes extensive counseling for product development efforts relating to biologics and reconstructive biomaterials, including products that utilize adult stem cells. Prior to attending law school, she held a faculty position at SUNY Upstate Medical University, and she also spent many years as a research scientist in the fields of neurology, virology, and immunology.

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Ted Mathias, JD

Ted Mathias focuses on trying patent cases. In the last 2 years, he tried 2 cases to judgment and served as lead counsel in a case involving 33 patents that settled favorably on the eve of trial. Mathias has litigated patent cases and handled successful appeals to the Federal Circuit in the areas of medical devices, pharmaceuticals, mechanical devices, e-commerce and software.

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Aaron Z. Savit, PhD

Aaron Z. Savit, PhD, is an intellectal property attorney with Axinn whose practice focuses on patent litigation and counseling, with an emphasis on the life sciences and biotechnology. His experience includes matters before the federal courts and the United States International Trade Commission. Aaron uses his scientific background to assist clients with biosimilars proceedings and litigation under the Hatch-Waxman Act.

Intellectual property attorneys from Axinn discuss the limitations of the Purple Book patent disclosure requirements and the burden these impose on biosimilar developers.

For years, biosimilar developers have lamented the lack of patent transparency around reference biologics. The Purple Book Continuity Act (PBCA), enacted in December 2020 under Title II § 325, directs FDA for the first time to publicly list certain patent information in the “Purple Book,” a database of approved biological products.

The PBCA is a welcome first step, but many in the biosimilar industry argue that Congress needs to do more to illuminate the patent landscapes for approved biologic products. Disclosure of reference product patents comes too late and is too incomplete to meaningfully guide business decisions. Developers of follow-on biologics need greater disclosure in order to make well-informed decisions about which products to pursue, with the ultimate goal of encouraging more development and earlier entry of follow-on biologics.

Pharmaceutical companies seeking to develop small molecule generic drugs have long looked to a different database maintained by the FDA, the “Orange Book,” for patent information. Here, sponsors of small molecule drugs are required by the Hatch-Waxman Act to list patents they own or license that cover those drugs. Generic developers can thus rely on the Orange Book to provide the universe of patents that an originator might assert during prelaunch litigation and thereby gauge their litigation exposure in considering whether to pursue a generic pharmaceutical. This increased certainty allows generic manufacturers to proactively prepare for litigation, thereby increasing their chances of a clear path to launch.

A Measure of Patent Disclosure

Until the PBCA’s enactment, follow-on biologic developers had no such clarity and had to rely on their own due diligence in assessing which patents they might face in litigation. The FDA’s Purple Book listed approved biologics but provided no patent information. The PBCA now provides at least some degree of patent disclosure. Under the new law, a reference product sponsor (RPS) must provide the FDA with a list of the patents and associated expiration dates that it discloses under 42 USC § 262(l)(3)(A) and 262(l)(7) as part of the patent dance, a series of disclosures required under the Biologics Price Competition and Innovation Act (BPCIA).

Although some patent transparency is better than none, many biosimilar companies argue that the PBCA nevertheless falls short in several important respects. First, the PBCA does little for companies seeking to expedite development of follow-on biologics. The RPS must only provide information on its patents to the FDA for listing in the Purple Book after it engages in the patent dance with a follow-on developer. Therefore, rather than encouraging companies to move quickly to develop follow-on products, the PBCA only helps those developers who wait for others to forge ahead without the benefit of patent transparency. Contrast this with the Orange Book, which delivers the patent information to all developers, including first-movers who push to get their products to market faster.

Second, the patent disclosures that an RPS makes pursuant to the patent dance might not include, as the Orange Book does, all of the patents owned or licensed by the RPS that cover its product. Instead, the Purple Book will only list patents that the RPS alleges covers a specific follow-on product. It is entirely possible that the RPS might have a different set of patents that it would assert against another follow-on product. But under the PBCA, that different set of patents would not be listed in the Purple Book, until and unless they are included in another (l)(3)(A) list against a different follow-on developer.

This concern is not merely theoretical. A survey of previous BPCIA litigation shows that RPSs can and do assert different patents against different defendants. For example, the RPS of trastuzumab, Genentech, brought suit against 4 different follow-on developers. Against both Celltrion and Pfizer, Genentech disclosed the same 40 patents. When Amgen filed, Genentech disclosed 37. And when Genentech brought suit against Samsung Bioepis, it disclosed 21 patents. Some of the patents asserted against Amgen and Samsung Bioepis were neither disclosed nor asserted in the Celltrion and Pfizer cases. Thus, which patents get listed in the Purple Book may depend upon which developers file an abbreviated biologics license application (aBLA).

Extensive patent portfolios—sometimes called “patent thickets”—compound this problem. With larger patent portfolios, it is more likely that the RPS will have patents that have not been asserted or disclosed in previous suits. It will thus take more aBLA filings, resulting in more (l)(3)(A) lists, to expose the full extent of larger thickets.

On top of this, more patents qualify for prelaunch litigation under the BPCIA, where RPSs can assert patents covering manufacturing processes. Because manufacturing patents can be asserted prelaunch under the BPCIA but not under Hatch-Waxman, the Purple Book should have comparatively greater patent disclosure requirements than the Orange Book.

Proactive disclosure of manufacturing patents would also give follow-on developers the opportunity to design around patents during the early phases of product development. For example, Humira is the subject of some 154 patents and Rituxan is covered by at least 80.

Greater Need for Disclosure

The large number of patents that tend to cover biologics (relative to small molecule drugs) weighs in favor of more transparency. Yet, even with the passage of the PBCA, the Purple Book will provide less patent information than the Orange Book. And while follow-on developers can depend upon earlier waves of litigation to identify some portion of an RPS’s patent portfolio, a great deal of diligence is often required to identify the universe of relevant patents with reasonable certainty.

The PBCA has also been criticized because, even after an RPS engages with the first follow-on developer to begin the patent dance for a given biologic, that engagement might not yield a patent listing in the Purple Book under the PBCA. The parties could reach a settlement before the RPS provides its Section 262(l)(3)(A) patent list. Or, the FDA may decline to request retroactive disclosure of patents from previous biosimilar litigations.

It is true that these patents—and those to be listed in the Purple Book going forward—can be found by leafing through public court dockets. But asserted patents routinely make up only a subset of the entire portfolio. Whether it be in the Purple Book or in a court filing, those disclosures are insufficient to bring meaningful transparency to follow-on developers.

In any event, the PBCA means that some patents will soon be coming to the Purple Book. Although the FDA is not required to make patent data available in the Purple Book until June, the obligation to communicate lists under Sections 262(l)(3)(A) and (l)(7) to the FDA is already in effect. Thus, the patent disclosures from biosimilars litigation initiated in 2021 may be among the first posted to the Purple Book.

For example, Alvotech announced on November 19, 2020, that the FDA had accepted its application for a biosimilar of Humira. And on April 27, 2021, AbbVie, the RPS, filed suit. Although Alvotech agreed to only 4 patents for prelaunch litigation, AbbVie disclosed 62 patents which it could potentially assert in the Section (l)(3)(A) list. As of December 27, 2020, the PBCA requires that the RPS communicate any list under Sections 262(l)(3)(A) or (l)(7) to the FDA within 30 days of sending it to the aBLA applicant. Presumably these 62 patents will be provided to FDA for inclusion in the Purple Book.

The PBCA will bring some nominal level of transparency and notice for follow-on developers. But many in the biosimilar industry argue that it falls far short of what is needed. The PBCA provides no patent disclosure to the first filer of an aBLA, which must rely on its own diligence to identify patents that may be asserted. Nor does the PBCA require RPSs to proactively identify patents which cover a given biologic, as they must do for small molecule drugs in the Orange Book.

It may be true that numerous manufacturing patents might apply to a given product or its biosimilar depending upon the methods of manufacture. But the same cannot be said of patents which cover the active substance or those which cover a method of use. If proactive disclosure of such patents were compulsory, the Purple Book would begin to provide a level of transparency and utility on par with the Orange Book.

Nevertheless, there is reason for hope for the biosimilar industry: Congress has indicated a willingness to revisit which patents are listed in the Purple Book. The PBCA requires that, in 3 years’ time, the FDA take public comments on the type of patent information that should be included in the Purple Book. The FDA will then report this information to Congress along with its own recommendations.

If and when Congress revisits the issue, it might impose proactive patent disclosure requirements that would facilitate informed decision-making by follow-on developers and thus stimulate the development of more biosimilars for the US market.