Cross-Motions for Summary Judgment Filed in PRADAXA Patent Term Extension Dispute

By Kurt R. Karst –

Hatch-Waxman Patent Term Extension (“PTE”) disputes never get old for this blogger.  There’s often some new twist for FDA or the U.S. Patent and Trademark Office (“PTO”) to consider, as shown in a recent PTE denial for a patent concerning the ZILVER PTX Drug Eluting Peripheral Stent (Docket No. FDA-2013-E-0781).  And even when yet another PTE denial based on a product not meeting the first permitted commercial marketing prong of the PTE statute (35 U.S.C. § 156) pops up, as shown in a recent PTE denial for a patent covering ARIDOL (mannitol inhalation powder) (Docket No. FDA-2012-E-0168), this blogger still feels a little giddy before reading the decision.  But what this blogger enjoys most is a good PTE court battle.  That’s what we have in Boehringer Ingelheim Pharma GmbH & Co. KG, et al. v. FDA, et al., Case No. 15-cv-00656-CKK (D.D.C.).  

As we previously reported, in April 2015, Boehringer Ingelheim Pharma GmbH & Co. KG and Boehringer Ingelheim Pharmaceuticals, Inc. (collectively “Boehringer”) filed a Complaint in the U.S. District Court for the District of Columbia alleging that FDA and the PTO unlawfully shorted by about two months a PTE for U.S. Patent No. 6,087,380 (“the ‘380 patent) covering Boehringer’s PRADAXA (dabigatran etexilate) Capsules approved under NDA 022512.  The Complaint was prompted by a December 2014 PTE regulatory review period decision from FDA in which the Agency refused to revise the Agency’s previous determination published in the Federal Register (see our previous post here).   In that May 2012 Notice, FDA commented that:

[Boehringer] claims December 15, 2009, as the date the new drug application (NDA) for PRADAXA (NDA 22-512) was initially submitted.  However, FDA records indicate that NDA 22-512, received December 15, 2009, was incomplete.  FDA refused to file this application and notified the applicant of this fact by letter dated February 12, 2010.  The completed NDA was then submitted on April 19, 2010, which is considered to be the NDA initially submitted date.

Boehringer alleges in its Complaint that FDA violated the Administrative Procedure Act and the Hatch-Waxman Amendments when the Agency unlawfully relied on the NDA “filing” standard instead of an “initially submitted” standard in the Agency’s calculation of PTE for the ‘380 patent. 

Boehringer lays out its case in a Motion for Summary Judgment filed in September.  According to the company:

The agency violated the Hatch-Waxman Act’s plain language that the approval phase begins “on the date the application was initially submitted for the approved product.” 35 U.S.C. § 156(g)(1)(B).  The agency failed to follow its own patent term extension regulation, which makes clear that the approval phase begins when an applicant initially submits an application sufficiently complete to allow review to commence.  And the agency abandoned without reason or explanation the previous position that it had applied to other applicants. [(Emphasis in original)]

Although Boehringer goes through the two-step Chevron analysis in the company’s memorandum, the company says it’s not really necessary, because the inquiry should end at Step One, as the statute is clear:

FDA’s position is fatally inconsistent with the plain text of the Hatch-Waxman Act itself.  The statute does not provide that the approval phase starts when an application is “ready for filing,” “accepted for filing,” “finally submitted,” or “complete.”  The statute mandates that the approval phase commences when an application is “initially submitted.”  35 U.S.C. § 156(g)(1)(B).  “Initial” means “happening or being at the very beginning: FIRST.”  Webster’s II New College Dictionary (1995).  And Congress quite deliberately chose to use the word “submitted” rather than “filed,” making clear that the application need only be submitted by the applicant and need not be cleared for filing by FDA before the review phase starts.  By selecting the words “initially submitted” rather than “ready for filing,” Congress chose to end the testing phase and begin the approval phase based on the action of the sponsor, not the action of the agency.  [(Emphasis in original)]

Moreover, says Boehringer, citing to legislative history (H.R. Rep. No. 98-857, pt. 1 (1984)), Congress directly addressed the issue presented in the dispute during passage of the Hatch-Waxman Amendments:

The term “initially submitted” is used to describe the point in time when the testing phase is considered to be completed and the agency approval phase to have begun.  This term is used instead of the term “file,” because an application is often not considered to be filed, even though agency review has begun, until the agency has determined that no other information is needed and a decision on the application can be made.  For purposes of determining the regulatory review period and its component periods, an application for agency review is considered to be “initially submitted” if the applicant has made a deliberate effort to submit an application containing all information necessary for the agency review to begin.  [(Emphasis added in brief)]

Turning to FDA’s PTE regulations (21 C.F.R. Part 60), Boehringer says that those regulations “make clear that an application need not be ‘ready for filing’ in order to count as ‘initially submitted,’” because those regulation make no reference to “filing.”  “First, the agency has defined the term “marketing application” as an application for human drug products, medical devices, food and color additives, or animal drug products “submitted” under the applicable laws,” and “[s]econd, FDA’s patent term extension regulations define the phrase ‘initially submitted’ as the date upon which a marketing application ‘contains sufficient information to allow FDA to commence review of the application,’” writes Boehringer. 

Boehring also cites a blast from the past as evidence of FDA acting in an arbitrary and capricious manner in this case.  According to Boehringer, there’s a 1985 PTE decision concerning TONOCARD Tablets that does’nt jibe with FDA’s position here concerning PRADAXA:

FDA’s calculation of PRADAXA’s regulatory review period is contrary to the agency’s past precedent with regard to similarly situated applicants.  Previously, FDA has determined that submission of an application starts the approval phase of the regulatory review period even when the agency later determines that the application is not approvable.  See A.R. 5514-16 (Determination of Regulatory Review Period for Purposes of Patent Extension; Tonocard Tablets, 50 Fed. Reg. 19,809, 19,810 (May 9, 1985)).  The facts in that case are strikingly similar to those presented here: The applicant submitted an application on December 19, 1979.  Six months later, FDA declared the initial application to be “nonapprovable.”  The applicant submitted a different application a few years later that was eventually approved.  The agency found that even though the first application had been declared “nonapprovable” and was replaced by a later application, that fact “did not preclude that application’s commencement of the approval phase of the regulatory review period.”  Id.  The agency reasoned that while the December application “was not approvable, it was sufficiently complete to permit agency action to begin.”  Id.  Accordingly, the applicant received day-for-day credit for the intervening months for patent term extension purposes.  Id.

FDA, in the Agency’s Cross-Motion for Summary Judgment (Motion to Dismiss), has a response for each argument proffered by Boehringer.  Citing another court decision on PTEs involving the statute’s “initially submitted” language – Wyeth Holdings Corp. v. Sebelius, 603 F.3d 1291 (Fed. Cir. 2010) (see our previous post here) – FDA paints Boehringer’s case as an attempt by the company to have its cake and eat it too:

Generally, priority review shortens the targeted review time for a drug that may provide a significant improvement over marketed therapies.  Priority review often enables a drug sponsor to market its product sooner than the traditional review process.  But there is a trade-off.  Priority review usually leads to a shorter patent term extension because a shorter approval phase typically reduces the regulatory review period.  Yet here, Boehringer wants it all.  In order to obtain an earlier approval, Boehringer requested and enjoyed the benefits of priority and rolling review (and a shorter approval phase); but in order to obtain a longer patent term extension, Boehringer now seeks a longer approval-phase than the statute provides.  In an earlier lawsuit, similarly challenging FDA’s determination of the date a New Animal Drug Application was “initially submitted” in a case where it had conducted phased review, the Federal Circuit rejected a similar request for an overly generous patent term extension, holding that the statutory term “initial submission” was ambiguous, and that FDA’s interpretation was reasonable.  The same is true here, and this Court should likewise reject Boehringer’s attempt to unduly extend its patent term.  [(Internal citations omitted)]

Because the statute is unclear as to the meaning of “initially submitted,” says FDA citing Wyeth, the Agency’s determination must be considered under Chevron Step Two, where a court determines whther or not an agency interpretation is reasonable.  And FDA says the Agency’s decision is quite reasonable, relying in part on the same House Report relied on by Boehringer:

An “application” for purposes of this provision must be “submitted . . . under”—and thus contain the information required by—the cross-referenced subsection of the FDCA, namely, 21 U.S.C. § 355(b). . . .  An application with inadequate sections that cannot be substantively reviewed is not enough. . . .  In order words, to count as “the application . . . submitted . . . under subsection (b) of section 505 [of the FDCA, codified at 21 U.S.C. § 355(b)],” “the application” must be sufficiently complete and capable of being reviewed. . . .  [A]n “application” is “initially submitted” under 21 U.S.C. § 355(b) when the sponsor has provided FDA with all the elements required by Section 355(b) and the corresponding regulations to make an approval decision.  Indeed, the House Report’s use of the words “all information necessary” rather than “some information necessary” reflects Congress’s intent that the approval phase commence when an application is sufficiently complete to permit FDA’s substantive review of all required components of the application.

FDA continues this line of argument in refuting Boehringer’s interpretation of the PTE statute:

Boehringer wrongly focuses on the words “initially submitted” rather than the phrase “the application . . . for the approved product . . . under . . . [21 U.S.C. § 355(b)]” as the critical statutory language in this case.  The relevant question is what must be “initially submitted.” Determining the date that “the application . . . for the approved product . . . under . . . [21 U.S.C. § 355(b)]” is “initially submitted” requires knowing what constitutes such an “application.”  As explained above, such an “application” must contain the information required by 21 U.S.C. § 355(b) and 21 C.F.R. § 314.50.  Boehringer did not submit clinical data (which is required by FDA regulations) that was sufficiently reviewable until April 19, 2010.  Therefore, Boehringer did not “initially submit[]” a sufficiently complete and reviewable application until April 19, 2010.

Turning to the TONOCARD Tablets PTE precedent cited by Boehringer as evidence of arbitrary and capricious action by FDA, the Agency comes armed with its own precedents beginning in 1994, and says that the Agency’s “position in this case is not new.  On the contrary, the agency has consistently maintained, for over two decades, that the approval phase begins when FDA receives an application that is sufficiently complete to be reviewed.”  The TONOCARD Tablets precedent is “readily distinguishable,” says FDA.  “In the Tonocard Tablet case, the non-approvable decision is not analogous to FDA’s refuse-to-file decision for Pradaxa: the Tonocard application was ‘complete enough’ for FDA to commence review and determine that it was not approvable, while for Pradaxa, the deficient module in the application meant that it was not yet at that stage.”  (Citation omitted)

Responses to the Cross-Motions for Summary Judgment are due by November 24, 2015, and replies are due by December 16, 2015.