A New Orange Book First: FDA Unilaterally Changes a Patent Use Code

By Kurt R. Karst –      

Over the years, we’ve witnessed, learned of, and have even been part of several Orange Book “firsts.” There’s the first listing of patent information covering an old antibiotic drug product (here); the Orange Book note addressing a leap year new chemical entity NDA approval (here); the launch of an electronic Orange Book on October 31, 1997, and then the more recent launch of the Orange Book Express app on November 9, 2015 (here); the first (and apparently the last) listing of a tentatively approved ANDA in the Orange Book (ANDA 071611 for Cyclobenzaprine HCl Tablets, 10 mg [FLEXERIL]; added with Cumulative Supplement No. 2 in 1988); the first patents listed in the Orange Book with a “Patent Delist Request Flag” – U.S. Patent Nos. 6,248,735 and 6,316,443 (on April 18, 2008) – identifying that the NDA holder has withdrawn the patent and submitted a request for removal of the patent information from the Orange Book; and then there’s that crazy guy who summited Mt. Kilimanjaro in Tanzania, Africa with the Orange Book (here). 

For all that we’ve seen, however, we never witnessed FDA unilaterally change a patent use code. . . . until now. And the timing of this first is interesting.  It was just last month that FDA issued final regulations implementing portions of the 2003 Medicare Modernization Act.  A major focus of the rule, which goes into effect on December 5, 2016, is patent use codes.  (And, oh, by the way, the new regulations will result in other new Orange Book firsts as FDA is required to make several changes to the Orange Book, including identifying patents for which a dispute has been submitted by an interested party.)

Within the past week or two, the “Newly Added Patents” search function on FDA’s Electronic Orange Book website showed the following entries buried within a larger list of new patent information:

At first blush, there doesn't seem to be anything out of place here. What’s new?  Well, it’s the U-1276 patent use code listing for U.S. Patent No. 8,536,130 (“the ‘130 patent”) covering Depomed, Inc.’s (“Depomed’s”) NUCYNTA ER (tapentadol) Extended-release Tablets that’s “new” . . . . but only “new” insofar as it’s “new again.”

NUCYNTA ER is approved under NDA 200533 for the management of: (1) pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate; and (2) neuropathic pain associated with diabetic peripheral neuropathy in adults severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. In January 2016, Depomed submitted a Citizen Petition (Docket No. FDA-2016-P-0383) to FDA requesting that the Agency stay final approval of any ANDAs referencing NUCYNTA ER that don’t contain either a Paragraph III or Paragraph IV certification to the ‘130 patent and that instead contain a section viii statement seeking to omit from labeling information reflected by the patent use code.

The ‘130 patent was initially listed in the Orange Book with a U-1276 patent use code, which is defined in an addendum to the Orange Book as “MANAGEMENT OF NEUROPATHIC PAIN ASSOCIATED WITH DIABETIC PERIPHERAL NEUROPATHY.” After Depomed acquired NUCYNTA ER from Johnson & Johnson, Depomed “became aware that the ‘130 patent claims were actually much broader than what was reflected in the use code then on file in the Orange Book.”  As such, in Septemebr 2015, Depomed requested that FDA change the patent use code for the ‘130 patent to “MANAGEMENT OF PAIN SEVERE ENOUGH TO REQUIRE DAILY, AROUND -THE-CLOCK, LONG-TERM OPIOID TREATMENT, INCLUDING NEUROPATHIC PAIN ASSOCIATED WITH DIABETIC PERIPHERAL NEUROPATHY.”  Consistent with FDA’s ministerial role in Orange Book patent matters, the Agency acquiesced and assigned the narrative the number U-1739.  With the patent use code change, “a section viii statement is no longer appropriate, as any carve out will require the removal of both labeled indications for Nucynta ER®, and anything less will overlap the new use code and infringe the patent,” according to Depomed.  “Therefore, ANDA applicants with section viii statements must amend their applications to address the new use code as required by FDA regulations.”

In April 2016, FDA denied Depomed’s Citizen Petition, saying that the U-1739 patent use code is “uninterpretable.” FDA also threatened to unilaterally change the use code for the ‘130 patent from U-1739 back to U-1276. 

FDA denies your Petition at this juncture because the information that you have placed before the Agency makes your patent use code for ‘130 patent uninterpretable . . . . FDA . . . requests that Depomed submit a new patent declaration form (Form FDA 3542) for the ‘130 patent, consistent with this response, within 15 calendar days from the date of this response.  If Depomed fails to submit an interpretable use code on the requested Form FDA 3542 within this timeframe, FDA will revert to the last interpretable patent use code submitted for the ‘130 patent, which is the use code submitted before Depomed’s September 2015 revisions.

Apparently Depomed never responded to FDA, and earlier this month FDA carried through with its threat to revert back to the U-1276 patent use code.

What effect the change in patent use code might have in the long-run remains to be seen. In September 2016, Depomed prevailed in district court patent infringement litigation against three ANDA applicants (see Depomed, Inc. v. Actavis Inc., et al., Case No. 2:13-cv-4507 (D. N.J.)), potentially delaying ANDA approval until late 2025. In an Order issued in that case, the court enjoined the ANDA applicants from launching their generic Tapentadol HCL drug products.  One ANDA applicant has already appealed the ruling to the U.S. Court of Appeals for the Federal Circuit.

One potential short-term effect of the patent use code change, however, might be to moot a counterclaim filed by ANDA applicant Actavis Inc. (“Actavis”). That counterclaim was initially filed by Actavis in a separate patent infringement action (Case No. 15-cv-6797 (D. N.J.)) pursuant to FDC Act §505(j)(5)(C)(ii)(I) seeking “an Order requiring Depomed to immediately request the FDA to correct the Orange Book use code for the ‘130 patent from U-1739 to U-1276.”