One Sponsor’s Failure is Another Sponsor’s Fortune: The Importance of Timely Listing (and Challenging) Orange Book Patents

By Kurt R. Karst –      

“Oddities” are not the sole domain of the world of antiques and other rarities (for those of you who are fans of the television show that focuses on the day-to-day operation of Obscura Antiques & Oddities).  Food and drug law – and in particular Hatch-Waxman – has its own oddities.  Over the years we’ve seen a lot of Hatch-Waxman oddities.  And they’re often discovered in the listings of patent information in FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (“Orange Book”) for various drug products.  For example, perhaps a company neglected to notify FDA of a patent term extension for a particular patent covering a brand-name drug, leaving the drug exposed to premature generic competition.  Or perhaps a company obtained staggered approvals of various drug product strengths and forgot to inform FDA – through the submission of a Form FDA 3542 – that the patents listed for the initial strength also apply to subsequently approved strengths.  What’s the harm of that?  That’s the odd story that’s the topic of today’s post: Two ANDA approvals for generic versions of FOCALIN XR (dexmethylphenidate HCl) Extended-release Capsules, 30 mg, that left a lot of people wondering what happened.

FOCALIN XR is approved under NDA No. 021802 in several strengths: 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, and 40 mg.  The 8 strengths were approved in a staggered fashion, instead of simultaneously:

• May 26, 2005 – The 5 mg, 10 mg, 20 mg strengths were approved
• August 1, 2006 – The 15 mg strength was approved
• October 23, 2009 – The 30 mg strength was approved
• August 11, 2010 – The 40 mg strength was approved 
• April 21, 2011 – The 25 mg and 35 mg strengths were approved

Patent information was added to the Orange Book (as shown in the respective Orange Book Cumulative Supplement) for each of the 8 approved strengths as follows:

• September 2005 Cumulative Supplement –  5 mg, 10 mg, 20 mg strenghts
• February 2007 Cumulative Supplement – 15 mg strength
• November 2010 Cumulative Supplement – 30 mg and 40 mg strengths
• May 2011 Cumulative Supplement – 25 mg and 35 mg strengths

Comparing these two sets of bullet points, one strength in particular stands out as an oddity: the October 23, 2009 approval of the 30 mg strength, for which patent information was shown as added with the November 2010 Orange Book Cumulative Supplement, which was published on FDA’s website around December 20, 2010.  Information on those patents, however, was not timely submitted to FDA for Orange Book listing because more than 30 days had passed since the October 23, 2009 approval of the new strength NDA supplement.  See FDC Act § 505(c)(2).

Just days earlier, on December 15, 2010, one ANDA sponsor (either through amendment or submission of an original ANDA), certified to patents listed in the Orange Book for FOCALIN XR, 30 mg, and became eligible for a period of 180-day exclusivity.  That fact became known with FDA’s February 21, 2011 update of the Agency’s List of Paragraph IV Certifications.  Fast-forward to August 28, 2013 when FDA approved Mylan’s ANDA No. 202580.  As a first applicant, Mylan was eligible for 180-day exclusivity, which would be triggered by the company’s first commercial marketing of the drug product.  According to a press release, that exclusivity was triggered on November 18, 2013.

But something else happened on November 18, 2013 . . . .  FDA approved a second ANDA for generic FOCALIN XR, 30 mg: Intellipharmaceutics’ ANDA No. 078992.  And then a third ANDA was approved just days later on November 21, 2013: Watson’s ANDA No. 079108.  What gives?

There are a few possibilities as to how FDA was able to approve ANDA Nos. 078992 and 079108.  It is possible that Mylan, Intellipharmaceutics, and Watson were serially certifying to patents they anticipated would be listed in the Orange Book for the 30 mg strength and were co-first applicants that would share 180-day exclusivity eligibility.  A second possibility is that Mylan selectively waived 180-day exclusivity in favor of Intellipharmaceutics and Watson.  A third possibility is that Intellipharmaceutics and Watson sought approval of the 30 mg strength before the patents were listed, and because the patents were late listed, the companies decided not to certify to them, while Mylan did decide to (or was otherwise required to) certify to them.  It turns out that this third possibility – or some variation of it – is the case.

Under FDA’s regulation at 21 C.F.R. § 314.94(a)(12)(vi):

If a patent on the listed drug is issued and the holder of the approved application for the listed drug does not submit the required information on the patent within 30 days of issuance of the patent, an applicant who submitted an [ANDA] for that drug that contained an appropriate patent certification before the submission of the patent information is not required to submit an amended certification.  An applicant whose [ANDA] is submitted after a late submission of patent information, or whose pending abbreviated application was previously submitted but did not contain an appropriate patent certification at the time of the patent submission, shall submit a certification under paragraph (a)(12)(i) of this section or a statement under paragraph (a)(12)(iii) of this section as to that patent. [(Emphasis added)]

In other words, a company with a pending ANDA is not required to certify to patent information listed in the Orange Book that was late-listed.  Of course, such an ANDA sponsor may voluntarily certify to late-listed patent information; however, doing so may make that ANDA sponsor subject to another ANDA sponsor’s 180-day exclusivity. 

That’s what happened with Intellipharmaceutics ANDA.  The company voluntarily certified to the late-listed Orange Book patents in early February 2011 and was sued for patent infringement in March 2011 (see here).  Once FDA updated its Paragraph IV Certification List on February 21, 2011 to reflect a December 15, 2010 first filing date for the 30 mg strength, Intellipharmaceutics realized that the company was not a first applicant and would be subject to the first applicant’s 180-day exclusivity unless it reneged on its Paragraph IV certification.  And because Intellipharmaceutics’s Paragraph IV certification was voluntary to a late-listed patent, FDA allowed the company to rescind the certification.  As such, the company would not be subject to the first applicant’s 180-day excluivity.  Of course, had the patents for the 30 mg strength been timely listed, ANDA sponsors would not have had the option to certify to them. Thus, it is possible that the brand-name sponsor would have had only a single generic entrant to contend with instead of three. 

Indeed, that was the somewhat similar scenario that played out earlier this year when a new patent, U.S. Patent No. 8,481,565, came out of the blue and was promptly (and timely) listed in the Orange Book for ARICEPT (donepezil HCl) Tablets, 23 mg, approved under NDA No. 022568.  In that case, the first companies to certify to the patent (likely through serial Paragraph IV certifications) were granted 180-day exclusivity (here and here), while other ANDA sponsors not as quick were left in the starting blocks until 180-day exclusivity expires. 

The Hatch-Waxman morals of these stories: If you are an NDA sponsor, ensure the accuracy of your Orange Book patent listings as soon as possible after approval (and on a continuing basis); and if you are an ANDA sponsor, look for the errors in Orange Book patent listings and be vigilant in monitoring new patent listings on a daily basis.