Patent Transparency For Biologics & Biosimilars: The Revamped Purple Book

By Jacqueline R. Berman, Jeffrey R. Gargano, Zachary D. Miller, and Maria Kalousi-Tatum; Morgan Lewis

As a result of the Purple Book Continuity Act (PBCA), the FDA updated the “Purple Book”¹ — a database containing information about all licensed biological products — to include, for the first time, patent information relating to biologics as well as FDA regulatory exclusivity information. The revamped database will present new opportunities for those in the industry to identify (i) potential partnerships for licensing of existing intellectual property; (ii) new strategies regarding intellectual property enforcement and protection; and, potentially, (iii) opportunities for the development of new technology.

What Is The Purple Book?

The Purple Book (formally titled the List of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations) was first published in 2014, a year before the 2015 approval of the first biosimilar product. The Purple Book lists FDA-licensed biological products (including biosimilars) and currently provides information on the biologics’ name, application number, approval date, biosimilar information, and, in some cases, the date of first licensure.

The Purple Book was based on a similar FDA publication for small molecule drugs — the Approved Drug Products with Therapeutic Equivalence Evaluations, which is colloquially called the “Orange Book.” However, because the Purple Book is less established than its small molecule older sibling, not all of the foregoing information is regularly populated for every biologic product (e.g., first licensure date is frequently omitted).  It was also only in February 2020 that the Purple Book transitioned from two separate tables (one for the Center for Drug Evaluation and Research and one for the Center for Biologics Evaluation and Research) to a single searchable database. The historical lack of publicly available patent information related to approved biologics can cause challenges to applicants seeking approval for biosimilar products. Although the latest additions to the Purple Book will, no doubt, be useful to those in the biologic industry, these improvements will not provide the same level of information as currently exists for small molecules in the Orange Book.

The Patent Dance

In 2009, Congress enacted the Biologics Price Competition and Innovation Act (BPCIA) to create (i) an abbreviated approval pathway for biosimilars² and (ii) a framework for biosimilar applicants and the reference product sponsors to resolve patent disputes.³ This patent dispute procedure is commonly referred to as the “patent dance.”

To start the patent dance, the biosimilar applicant provides the reference product sponsor with its biosimilar Biologics License Application (BLA) and additional information about its manufacturing process.⁴ Within 60 days of this initial exchange, the reference product sponsor must provide the biosimilar applicant with a list of unexpired patents for which a claim of infringement could reasonably be made.⁵ The biosimilar applicant has 60 days to provide noninfringement and invalidity positions,⁶ after which the reference product sponsor has 60 days to respond with its positions.⁷ The reference product sponsor must update its list with any newly issued patents within 30 days after those patents issue.⁸ Following these initial rounds of disclosures, the parties engage in a series of responses and negotiations, which can culminate with the reference product sponsor bringing a lawsuit for patent infringement in U.S. federal court. Notably, however, in 2017 the Supreme Court found that the patent dance is not mandatory as it is not enforceable via an injunction action.⁹

Having early access to patent information regarding licensed biologic products is not only valuable for biosimilar applicants but also for reference product sponsors. Given the short timing of the patent dance, it is an advantage to a biosimilar applicant to obtain as much information regarding the patents identified by the reference product sponsor before the dance begins. Such information will allow more time for a biosimilar applicant to develop noninfringement and invalidity positions. However, on the other hand, if a reference product sponsor has strong patent coverage for its product, a biosimilar applicant may decide to wait to seek approval until after the reference product sponsor’s patents expire. This would allow the reference product sponsor to avoid the costs of engaging in the patent dance and litigation.

Historically, however, companies have had few strategies to identify potential biologic patent coverage other than traditional patent searching and competitive patent landscaping exercises. Potential applicants can conduct patent searches to identify potential patents, but given the various types of patents involved, such searches are expensive and not guaranteed to be comprehensive. Alternatively, certain patents can be identified after a patent infringement lawsuit is filed — but that information would only include the patents that were eventually asserted, not all patents identified by the reference product sponsor as being reasonably infringed.

With the improvements to the Purple Book, applicants now have a new source for patent information related to biologics, as well as regulatory exclusivity information.

The Revamped Purple Book

On Dec. 27, 2020, the Purple Book Continuity Act (PBCA) was signed into law as part of the Consolidated Appropriations Act.¹⁰ One of the provisions of the Consolidated Appropriations Act, Section 325 of Division BB, is directed to “Biological Product Patent Transparency.”¹¹ This section codifies the Purple Book in its electronic form and establishes new information requirements. There are a number of key provisions that set out different aspects of the Purple Book’s requirements:

• Timing: FDA must begin publication of the new Purple Book information within 180 days of enactment — June 25, 2021.¹²
• Revisions: FDA must update the publication at least every 30 days.¹³
• General Information: The Purple Book must include (i) the nonproprietary or proper name of the biologic, (ii) the date of licensure of the marketing application and the application number, (iii) and the licensure and marketing status.¹⁴
• Patent Information: As part of the statute, any reference product sponsor engaged in a patent dance must provide to FDA a list of patents identified to a biosimilar applicant as part of the patent dance.  The information must be provided within 30 days of the disclosure to the biosimilar applicant and must include patent expiry information.  FDA is then required to include the patent and expiry information in the Purple Book in connection with the biologic.¹⁵
• Exclusivity Information: If the biologic or biosimilar is entitled to exclusivity, the Purple Book must identify certain, but not all, exclusivity periods.¹⁶

Impact Of The Patent Information Requirements

A key difference between the new Purple Book requirements and the information in the existing Purple Book published by FDA is the inclusion of patent information. Previously, information exchanged between a reference product sponsor and a biosimilar applicant during a patent dance was treated as confidential. The publication of patent information in the Purple Book changes the scope and access to information regarding patents that cover approved biological products.

However, there are limitations to the information included in the Purple Book. First, this additional patent information does not affect the first biosimilar to file an application following the implementation of the Purple Book changes. They will still be in the dark as to patents likely to be identified by a reference product sponsor during the patent dance. Indeed, until a biosimilar filing, patent information would not be posted in the FDA database.  Second, the statute leaves open the question of what happens if the biosimilar sponsor decides not to engage in the patent dance.  Finally, unlike the Orange Book, there is no obligation for product sponsors to keep patent information in the Purple Book current outside of the patent dance.  A product sponsor is only required to update information each time it engages in a patent dance with a biosimilar.  Accordingly, subsequent applicants should not solely rely on the Purple Book when trying to identify and understand the potential patent landscape.

Nonetheless, publication of the patent information in the Purple Book will allow subsequent applicants to prepare noninfringement and invalidity positions more easily before the patent dance even starts. This advance notice could be critical to a biosimilar applicant’s legal and business strategies when pursuing a biosimilar filing. In addition, the publication of information may also be useful to reference product sponsors. For example, if a reference product sponsor has strong patent coverage published in the Purple Book, it may dissuade a biosimilar applicant from seeking approval prior to the expiration of the reference product sponsor’s patents.

Impact Of The Exclusivity Information Requirements

Under the new legislation, the Purple Book must identify unexpired reference product and interchangeable product exclusivity periods. Notably, however, under the text of the statute, the listed exclusivity periods are only required to include the 12-year reference product exclusivity and exclusivity granted to interchangeable biosimilar products. While the Purple Book's data download does include information on orphan exclusivity, companies should still refer to FDA’s orphan drug database to confirm whether a product has unexpired orphan exclusivity periods. It is also unclear whether six-month pediatric exclusivity extensions will be added onto the Purple Book exclusivity periods.

Moreover, the statute only requires that exclusivities be posted if FDA has made an exclusivity eligibility determination.  At least with respect to small molecules, FDA frequently does not make official exclusivity determinations until the issue becomes ripe (e.g., through the filing of an abbreviated new drug application or 505(b)(2) New Drug Application). If the Purple Book follows the Orange Book in this regard, exclusivity periods will not necessarily be included for every newly licensed biologic, as FDA may not have made an official exclusivity determination in every case. Notably, the FDA's latest Purple Book data download includes reference product exclusivity periods for some but not all listed products.

Other Ways To Leverage The New Purple Book Requirements

In addition to utilizing the Purple Book patent information in connection with the patent dance, the availability of patent information in the Purple Book will allow companies in the biologics space to identify new business opportunities in a variety of different ways.

First, biologic companies will be able to review the Purple Book’s patent information with their own existing technology in mind. Companies can use the information to identify potential licensing or collaboration opportunities with other reference product sponsors or with a biosimilar applicant. For example, if a reference product sponsor does not have patent protection over a certain part of its manufacturing process, and another company has relevant patent coverage in that area, the reference product sponsor may be interested in licensing or purchasing those patents. This would benefit the reference product sponsor by providing even stronger patent protection for its approved product. Alternatively, if a reference product sponsor has patent coverage in a specific area, and another company has technology that would allow a biosimilar applicant to design around that coverage, potential biosimilar applicants may be interested in collaborating on that technology.

Second, a company can also use the Purple Book’s patent information to commercialize intellectual property that is similar to or overlaps with existing patents. For example, a reference product sponsor may be interested in licensing intellectual property even if the sponsor already has patent coverage in the same area, especially if the intellectual property predates the sponsor’s patents. This could benefit the reference product sponsor by providing even stronger patent protection for its product. On the other hand, a biosimilar applicant may be interested in collaborating in filing a proceeding at the patent office to invalidate a reference product sponsor’s patent using another company’s intellectual property as the basis for invalidation.

Finally, when reviewing the Purple Book’s patent information, a company should consider areas for future technological development. If a company has expertise in a specific technical area, a second company may be able to utilize that expertise to collaborate with a reference product sponsor or biosimilar applicant in developing new technologies.

References

1. Purple Book: Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations, available at https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/purple-book-lists-licensed-biological-products-reference-product-exclusivity-and-biosimilarity-or.
2. 42 U.S.C. § 262 subsection (k), available at https://www.law.cornell.edu/uscode/text/42/262.
3. Id. at subsection (l).
4. Id. at subsection (l)(2).
5. Id. at subsection (l)(3)(A).
6. Id. at subsection (l)(3)(B)(ii).
7. Id. at subsection (l)(3)(C).
8. Id. at subsection (l)(7).
9. Amgen v Sandoz, 137 S. Ct. 1664 (2017).
10. Consolidated Appropriations Act, available at https://rules.house.gov/sites/democrats.rules.house.gov/files/BILLS-116HR133SA-RCP-116-68.pdf.
11. Id. at Division BB, Sec. 325, “Biological Product Patent Transparency.”
12. Id. at Sec. 325(a)(9)(A)(i).
13. Id. at Sec. 325(a)(9)(A)(ii).
14. Id. at Sec. 325(a)(9)(A)(i)(I)–(III).
15. Id. at Sec. 325(a)(9)(A)(iii).
16. Id. at Sec. 325(a)(9)(A)(iv).

About The Authors:

Jacqueline R. Berman is a partner at Morgan Lewis. She advises companies on FDA regulatory, compliance, and enforcement issues, as well as clinical trials and FDA-regulated product development programs. She also counsels clients on the safety, labeling, and reporting requirements for consumer products under the laws enforced by the US Consumer Product Safety Commission (CPSC), the Federal Trade Commission (FTC), and related state enforcement agencies. Jacqueline’s clients include pharmaceutical, device, biologic, dietary supplement, and food/food additive manufacturers. You can contact her at jacqueline.berman@morganlewis.com.

Jeffrey R. Gargano is a partner at Morgan Lewis. He is a seasoned litigator, focusing his practice on disputes involving intellectual property in US federal courts and before the International Trade Commission (ITC). Jeff counsels clients on overall IP strategy and litigation avoidance. He has litigated cases involving myriad IP law issues, including domestic and foreign patents, trademarks, trade secrets, copyrights, false advertising, and unfair competition. Additionally, he helps clients navigate the regulatory, patent, and antitrust issues unique to pharmaceutical litigation arising under the Hatch-Waxman Act. You can contact him at jeffrey.gargano@morganlewis.com.

Zachary D. Miller is an associate at Morgan Lewis. He focuses his practice on intellectual property litigation and has experience practicing in federal district courts, before the International Trade Commission, and before the US Court of Appeals for the Federal Circuit. Zach utilizes his chemical engineering background to provide litigation advice in a wide range of technologies, with an emphasis in pharmaceutical, biologic, and medical device matters. Zach distills these complicated technologies into simple concepts for easy comprehension by judges and juries. You can contact him at zachary.miller@morganlewis.com.

Maria Kalousi-Tatum is an associate at Morgan Lewis. She focuses her practice primarily on FDA approval, compliance, enforcement, and promotion matters related to medical devices and digital health technologies, such as software as a medical device (SaMD), clinical decision support software, wearable devices, artificial intelligence systems, and mobile medical apps. She also assists clients with approval, regulation, and promotion of drugs, dietary supplements, and conventional foods. You can contact her at maria.kalousi-tatum@morganlewis.com.