Surely You Must be Kidding, PTO?!? “No, and Don’t Call Me Shirley!” – The Seemingly Slapstick (But Yet Unfunny) World of Recent Patent Term Extension Decisions (PART 1)

It’s been a while since we last blogged on Patent Term Extension (“PTE”) issues of interest.  And with 2024 (September 24th) being the 40th anniversary of the enactment of the 1984 Hatch-Waxman Amendments—the statute that amended Title 35 of the United States Code to create PTEs for certain FDA-regulated products—and a recent spate of PTE-related items posted on regulations.gov, we thought we would peruse some decisions to see what’s up at the Patent and Trademark Office (“PTO”) PTE-wise.  Well, we found much more than we thought we would.  And some of our finds left us asking if the PTO has taken on the role of Dr. Rumack (Leslie Nielsen) in the 1980 movie “Airplane!”.  But all kidding aside, some of the recent decisions we found are rather distressing.

Our last two PTE-related posts concerned the issues of: (1) multiple PTEs—a topic we blogged on in 2020, but that we have been following since the very early days of the FDA Law Blog in 2008 and 2009 (see our previous posts here, here, and here)—and (2) the Improving Regulatory Transparency for New Medical Therapies Act (“IRTNMTA”)—a topic we blogged on in 2022, and that was enacted to, among other things, address controlled substance scheduling issues that arose with BELVIQ (lorcaserin HCl) Tablets (NDA 022529; approved on June 27, 2012) (see our previous posts here and here) and that ended up raising some PTE issues.

We will start this post—Part 1 of a three-part series over the next several days—with one of the PTE topics we last posted on (i.e., Multiple PTEs), then move on to the second topic (which involves BELVIQ, among other drug products, and that we’ll call “Accelerated Approval Withdrawals and the End of the PTE Road”), and end with a third topic that will surely (or is that Shirley?) leave you scratching your head (we’ll call it “Who’s Buried in Grant’s Tomb?”).

Part 1:  Multiple PTEs

Under the PTE statute at 35 U.S.C. § 156, a patent may be extended only once (even if it would be eligible for extension on more than one occasion because it applies to several FDA-approved products), and only one patent may be extended for each regulatory review period.  To that end, 35 U.S.C. § 156(c)(4) states that “in no event shall more than one patent be extended under subsection (e)(1) for the same regulatory review period for any product” (emphasis added).  This led one commentator—Federal Circuit Judge Alan David Lourie—to speculate shortly after enactment of the Hatch-Waxman Amendments that a second patent could be extended for a second regulatory review period for the same product. See Lourie, Patent Term Restoration: History, Summary, and Appraisal, 40 Food, Drug, and Cosm. L.J. 351, 355-56 (1985).

For years after the enactment of the Hatch-Waxman Amendments the PTO interpreted the PTE statute to permit multiple PTEs, provided there are separate, but not necessarily different, regulatory review periods.  This means that there multiple same-day FDA NDA approvals for the same drug.  For example, the PTO has granted multiple PTEs with respect to pregabalin (LYRICA) (U.S. Patent No. 6,001,876 with respect to NDA 021446 and U.S. Patent No. 6,197,819 with respect to NDA 021723); cefdinir (OMNICEF) (U.S. Patent No. 4,559,334 with respect to NDA 050739 and U.S. Patent No. 4,935,507 with respect to NDA No. 050749); brentuximab vedotin (ADCETRIS) (U.S. Patent No. 7,829,531 with respect to BLA 125399 and U.S. Patent No. 7,090,843 with respect to BLA 125388), and alogliptin (U.S. Patent No. 6,329,404 with respect to NDA 022426 for OSENI (alogliptin and pioglitazone) Tablets, U.S. Patent No. 8,288,539 with respect to NDA 203414 for KAZANO (alogliptin and metformin HCl) Tablets, and U.S. Patent No. 8,173,663 with respect to NDA 022271 for NESINA (alogliptin) Tablets – see our previous post here).

FDA also approved two NDAs on the same first day for micafungin (MYCAMINE)—NDA 021506 for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation, and NDA 021754 for the treatment of esophageal candidiasis.  In that case, the NDA sponsor applied for two PTEs based on these approvals—one for either U.S. Patent Nos. 5,376,634, 6,265,536, or 6,107,458 for NDA  021506, and one for either of these same patents for NDA 021754—but ultimately decided not to elect a second PTE.  A similar decision was made with respect to lacosamide (VIMPAT).  In that case, the NDA sponsor applied for two PTEs based on the same-day approvals of NDA 022253 and NDA 022254 and with respect to U.S. Patent No. RE 38,551 and U.S. Patent No. 5,654,301.  The sponsor ultimately decided not to elect a second PTE. (As an aside, the PTO has also granted multiple interim PTEs under 35 U.S.C. § 156(e)(2), but has denied multiple interim PTEs under 35 U.S.C. § 156(d)(5) (see our prior post here.)

Despite a rather long history of granting multiple PTEs, in 2020, in an about-face, the PTO took the position that multiple PTEs are no longer supported by the statute.  In several letters to applicants, each styled as a REQUIREMENT FOR INFORMATION PURSUANT TO 37 C.F.R. § 1.750, the PTO takes the position that “Section 156 does not allow for multiple extensions of patents beyond the one patent per one approved product.”  See, e.g., Letter from PTO to FDA CDER, Docket No. FDA-2020-E-1840 (July 13, 2020).  These determinations were finalized in 2021.  See, e.g., Letter from PTO  to FDA CDER, Docket No. FDA-2020-E-1840 (Mar. 25, 2021) (“[U]nder the plain statutory language of 35 U.S.C. § 156 and interpretive case law, if an applicant for patent term extension has multiple NDA approvals of a product, PTE applicant can only rely on ‘a’ (single) regulatory review period for a first permitted commercial marketing or use of a product to establish the requirements for patent term extension.  That is, pursuant to § 156, there cannot be more than one ‘first permitted commercial marketing or use’ of the product.”).

The PTO’s not-even-specious-argument, citing what certainly appears to us to be absolutely irrelevant case law, such as Novartis AG v. Ezra Ventures LLC, 909 F.3d 1367 (Fed. Cir. 2018), Arnold Partnership v. Rogan, 246 F. Supp. 2d 460 (E.D. Va. 2003), and Biogen lnt’l v. Banner Life Sciences LLC, 956 F.3d 1351 (Fed. Cir. 2020), has not yet—and to our surprise—ended up in court.  But there are still a couple of possibilities lurking out there!

The first multiple PTE case up-to-bat concerns Gilead Sciences Inc.’s idelalisib (ZYDELIG) tablets, which FDA approved on July 23, 2014 under NDA 205858 (for relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies and relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies) and under NDA 206545 (for relapsed chronic lymphocytic leukemia, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities).  In September 2014—nearly ten years ago!—PTE applications were submitted to FDA for each of U.S. Patent No. RE 44,599 and U.S. Patent No. RE 44,638 and with respect to each NDA approval,  See FDA Docket Nos. FDA-2015-E-2602, FDA-2015-E-2604, FDA-2015-E-2619, and FDA-2015-E-2615.

Earlier this month, the PTO issued a REQUIREMENT FOR INFORMATION PURSUANT TO 37 C.F.R. § 1.750 with respect to the multiple PTE applications for each of U.S. Patent No. RE 44,599 and U.S. Patent No. RE 44,638 (here and here).  The issue, of course, is the legitimacy of multiple PTEs.  Thus, the PTO states:

The issue is whether 3 5 U.S.C. § 156 permits a patent owner who owns more than one patent to obtain more than one patent term extension for the same FDA approved product.  Applicant has filed multiple PTE applications directed to the same product (idelalisib ).  If applicant contends that more than one patent may be extended based on the approval of idelalisib, then applicant is required to provide legal support pursuant to 35 U.S.C. § 156, expressly demonstrating that the statute permits multiple term extensions based on the same product.  Absent a convincing showing, the Office after considering all of Applicant’s argument plans to issue only one PTE directed to ZYDELIG® (idelalisib).

Despite the PTO’s request, the Office makes its position clear later on in the letter, citing to the same cases identified above (and with a footnote addressing past precedent):

Section 156 does not allow for multiple extension of patents beyond the one patent per one approved product. The regulatory review period of ZYDELIG® (idelalisib) can be used as a basis for extension of only one patent.  See 3 5 U.S.C. § l 56(c)(4) and 37  C.F.R. § 1.785(b).  Therefore, the Office plans to limit applicant to extending only one patent for the approved product (idelalisib).

The Office acknowledges that in the past it has permitted more than one extension when multiple forms of administration of the same drug product were applied for and approved by the FDA on the same day. However, the Office believes that the proper interpretation of the statute, especially in light of recent court decisions discussed in this requirement for information mandates that only a single patent be extended for any given drug product, regardless of the number of forms of administration approved by the FDA.

We’ll be keeping out eye out for the applicant’s response to the PTO’s request.

The second multiple PTE case brewing concerns FoldRx’s (a wholly owned subsidiary of Pfizer, Inc.) tafamidis, which FDA approved on May 3, 2019 as VYNDAMAX (tafamidis) Capsules under NDA 212161, and as VYNDAQEL (tafamidis meglumine) Capsules under NDA 211996—both approved for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. Two PTE applications were submitted to FDA (See FDA Docket Nos. FDA-2022-E-3123 and FDA-2022-E-3120) with respect to U.S. Patent Nos. 7,214,695 and 7,214,696.

On February 8, 2024—the same day the PTO requested information with respect to the multiple PTE applications for idelalisib—the FDA sent a letter to the PTO in response to the PTE applications for U.S. Patent Nos. 7,214,695 and 7,214,696 and a PTO request for information as to the first permitted commercial marketing prong of the PTE statute.  According to FDA:

USPTO has requested information about whether the FDA first approved VYNDAMAX (NDA 212161, tafamidis) or VYNDAQEL (NDA 211996, tafamidis meglumine).  Our records indicate that the two NDAs were received for review at the same time and were approved concurrently in the same approval action.  Consequently, because both applications were approved at the same time, both applications represent the first permitted commercial marketing or use of the product or the individual active ingredients, as outlined under 35 U.S.C. sections l56(a)(5) and 156(f)(1).

NDA 212161 and NDA 211996 were approved concurrently on May 3, 2019, at 6:13 pm, which makes the submission of the patent term extension applications on June 27, 2019, timely within the meaning of 35 U.S.C l56(d)(1).

Oh-oh!  Another case of same-day (and same-time) FDA approvals!  It’s another possible set-up to challenge the PTOs 180-degree position change on multiple PTEs.  But before the multiple PTE issue can be addressed, there’s another interesting issue lurking here that needs to be resolved first.

The PTE statute defines the term “product” to mean “drug product,” and the term “drug product” is defined to mean “a new drug, antibiotic drug, or human biological product (as those terms are used in the [FDC Act] and the Public Health Service Act). . . including any salt or ester of the active ingredient, as a single entity or in combination with another active ingredient.”  35 U.S.C. § 156(f)(2).  For several years, the PTO interpreted the term “product” to mean “active moiety” rather than “active ingredient” (i.e., the ion or molecule, excluding salts, esters, etc., responsible for the pharmacological action of a drug, instead of the ion or molecule including salts, esters and other derivatives).  In PhotoCure v. Kappos, 603 F.3d 1372 (Fed. Cir. 2010), however, the U.S. Court of Appeals for the Federal Circuit interpreted the term “product” in the PTE statute to mean active ingredient rather than active moiety.  Post-Photocure, the PTO has framed PTE eligibility as a three-part inquiry: (1) Has the active ingredient been previously approved?; (2) Has a salt of the active ingredient been approved?; and (3) Has an ester of the active ingredient been approved?  A “yes” to any of these questions means that permission does not meet the first permitted commercial marketing prong of the statute.

VYNDAQEL (NDA 211996) contains tafamidis meglumine, an organoammonium salt obtained by combining tafamidis with one molar equivalent of 1-deoxy-1-(methylamino)-D-glucitol, whereas VYNDAMAX (NDA 212161) contains the tafamidis base.  Which approval came first (if any)—a bit of a “Which came first, the chicken or the egg?” issue—could affect PTE eligibility as a foundational issue.  While FDA has confirmed date and time stamps in the past for PTE purposes (for example in the 2020 case of U.S. Patent No. 8,327,844 for XHANCE (fluticasone propionate) (here)), we’ve never seen such determinations come down to seconds on the clock.

. . . . Part 2 (Accelerated Approval Withdrawals and the End of the PTE Road) coming soon . . . .