“Reference biologic drug makers until recently faced no obligation to disclose to the public the patents associated with their licensed biologic products…. This disparity between the Hatch-Waxman and Biologics Price Competition and Innovation Act regimes now has narrowed somewhat.”
Innovator (or “reference”) biologic drug makers and small-molecule drug makers face differing legal obligations with respect to public patent disclosures. Under the Hatch-Waxman Act, reference small-molecule drug makers are required to provide to the U.S. Food and Drug Administration (FDA) a list of the patents covering the active ingredients, compositions, formulations, and methods of treatment for their approved reference drug products, which the FDA in turn is required to publish in its “Orange Book.” 21 U.S.C. § 355(b)(1), (c)(2). The publication of such patents in the FDA Orange Book thus gives all generic drug applicants advance notice of the patents to be asserted by a reference drug maker in future Hatch-Waxman litigation.
By contrast, under the Biologics Price Competition and Innovation Act (BPCIA), reference biologic drug makers (also known as reference product sponsors or RPSs) until recently faced no obligation to disclose to the public the patents associated with their licensed biologic products. The absence in the BPCIA of such public patent disclosure requirements was broadly consistent with the BPCIA’s provisions at 42 U.S.C. 262(l) governing the pre-litigation information exchanges between a particular RPS and a particular biosimilar applicant (collectively known as the “patent dance”). Under those provisions, such exchanges—which encompass not only the RPS’s patents but also manufacturing information about the biosimilar applicant’s product—are voluntary and non-public, and the FDA plays no part in them. Thus, biosimilar makers not currently involved in a patent dance with the RPS could not determine with certainty what patents an RPS might assert in future BPCIA litigation.
This disparity between the Hatch-Waxman and BPCIA regimes now has narrowed somewhat. On June 25, 2021, the Biological Product Patent Transparency (BPPT) amendments to the BPCIA took effect. The BPPT amendments—enacted as part of the Consolidated Appropriations Act, H.R. 133, Pub. L. No. 116-260—require that the FDA publish certain information about biologic products—most significantly, a list of the patents that are owned or licensed exclusively by the RPS and that the RPS previously has identified pursuant to 42 U.S.C. 262(l)(3)(A) or (l)(7) as part of the patent dance. As discussed below, the disclosure of this previously non-public patent information has strategic implications for both RPS and biosimilar applicants.
What the BPPT Amendments Have Changed
Notwithstanding the absence of any prior statutory requirement to do so, the FDA for several years has voluntarily published the “Purple Book,” an electronic reference that sets forth basic information about FDA applications for biologic products, also known as biologic license applications (BLAs). The Purple Book lists the BLA applicant’s name and BLA number, the date on which the biologic product was licensed by the FDA; and whether the product has been determined to be biosimilar to or interchangeable with a reference biologic product. Unlike the Orange Book, however, the Purple Book until now has not included any patents associated with biologic products.
Under the BPPT amendments, FDA publication of the Purple Book is now mandatory, and the Purple Book must now provide the following patent and exclusivity information:
- For each reference biologic, a list of the patents that were included on any (l)(3)(A) or (l)(7) list provided by an RPS to a biosimilar applicant as part of the patent dance. An (l)(3)(A) list sets forth patents that currently are owned or licensed exclusively by the RPS, and for which the RPS “believes a claim of patent infringement could reasonably be asserted” against the particular biosimilar product for which that biosimilar applicant has submitted an abbreviated BLA. An (l)(7) list is a supplemental list that covers later-issued or later-licensed patents within that category. Importantly, unlike Orange Book-listed patents, (l)(3)(A)- or (l)(7)-listed patents (and hence Purple Book-listed patents) can include manufacturing process patents.
- Each reference product exclusivity period and each first interchangeable exclusivity period “for which FDA has determined such biological product to be eligible and for which such period has not concluded.”
42 U.S.C. 262(k)(9)(A)(iii)-(iv).
Although the BPPT amendments require the publication of those two additional categories of information, it is important to understand that the BPPT amendments do not impose any obligation upon biologic makers or the FDA to generate new information specifically for the Purple Book. As to patents, the BPPT amendments require only that an RPS disclose those (l)(3)(A) or (l)(7) lists that the RPS already has provided to a biosimilar applicant during the patent dance—and, as noted above, participation in the patent dance is voluntary. And as to exclusivities, the BPPT amendments do not impose an obligation upon the FDA to determine, prospectively, exclusivity periods for all reference and interchangeable biologic products; rather, the FDA is required to list in the Purple Book only those exclusivity periods for which the FDA “has determined a biological product to be eligible.”
The BPPT amendments require that an RPS provide an (l)(3)(A) or (l)(7) patent list to the FDA no later than 30 days after such a list has been provided by the RPS to a biosimilar applicant. 42 U.S.C. 262(k)(9)(A)(iii). The BPPT amendments do not, however, specify what should happen if an RPS does not provide an (l)(3)(A) or (l)(7) list to the FDA.
As to when patent listings will start appearing in the Purple Book, the FDA indicates that it “will begin publishing patent lists in the Purple Book not later than 180 days after the date of [BPPT] enactment (June 25, 2021), or when FDA has received any such lists from reference product sponsors, whichever is later. FDA subsequently will revise the list on a monthly basis to include any additional initial lists and any updates from subsequent or supplemental lists.” See https://purplebooksearch.fda.gov/faqs#5.
Potential Effects of the BPPT Amendments on the Patent Dance
The fact that patents included on (l)(3)(A) or (l)(7) lists will become public under the BPPT amendments raises a number of strategic implications for both RPSs and biosimilar makers with respect to how they participate in the patent dance.
For RPSs, the BPCIA provides a degree of discretion in terms of which patents to include on (l)(3)(A) or (l)(7) lists: the lists shall include those patents that “could reasonably be asserted” against the specific biosimilar that is the subject of that patent dance. Prior to the BPPT amendments, the BPCIA generally incentivized longer and more inclusive (l)(3)(A) and (l)(7) lists, due primarily to the risk that omitting patents from those lists would limit the availability of certain forms of preliminary injunctive relief in subsequent BPCIA litigation. See 42 U.S.C. 262(l)(8)(B). However, now that the listed patents will be disclosed to the public—including to other biosimilar makers—RPSs face competing incentives to shorten their (l)(3)(A) and (l)(7) lists. For example, the public disclosure in the Purple Book of a broad and comprehensive list of RPS patents may expose those patents to preemptive validity attacks by other biosimilar makers in IPR proceedings, and may encourage future biosimilar makers to “design around” the bounds of the RPS’s patent estate. At a minimum, the public disclosure in the Purple Book of (l)(3)(A)- and (l)(7)-listed patents likely will give future biosimilar applicants advance notice of those RPS patents on which they should focus their defensive efforts. In view of those risks, an RPS may wish to draw its (l)(3)(A) and (l)(7) patent lists more narrowly to match the specific biosimilar at issue.
As for biosimilar makers, the Purple Book patent disclosures may discourage them from participating in the patent dance entirely, for at least three reasons. First, the initial step in the patent dance involves the exchange of the biosimilar applicant’s confidential abbreviated BLA, and its proprietary manufacturing information, for the RPS’s (l)(3)(A) list. See 42 U.S.C. 262(l)(2)(A); (l)(3)(A). Over time, as more and more of an RPS’s (l)(3)(A)- and (l)(7)-listed patents appear in the Purple Book, biosimilar applicants likely will become increasingly unwilling to divulge valuable proprietary information about their biosimilar products to an RPS in exchange for patent information that is, or will become, public knowledge. Second, as explained above, (l)(3)(A) and (l)(7) lists can be narrowly drawn to patents that address a particular biosimilar product. The disclosure of certain (l)(3)(A)-listed patents in the Purple Book (as well as the omission of other RPS patents from the Purple Book) thus raises a risk that the public and competing biosimilar makers will be able to glean otherwise confidential details of a biosimilar applicant’s product. Third, an earlier biosimilar applicant may try to stymie later biosimilar applicants’ efforts to learn about the RPS’s patent estate by electing not to participate in the patent dance, thereby bypassing the (l)(3)(A) and (l)(7) steps of the patent dance and foreclosing the publication of any (l)(3)(A)- and (l)(7)-listed patents in the Purple Book.
Because the BPPT amendments have only recently been passed into law, only time will tell if the amendments will bring a true measure of transparency to biologics patents, and whether the above-mentioned strategic incentives will come into play. In that respect, the BPPT amendments themselves appear to acknowledge the uncertainty surrounding their effects: the BPPT amendments include provisions that require the FDA to solicit public comments regarding the new information required to be published in the Purple Book, and to provide to Congress within three years a recommendation on what types of information should be added or removed.