By Kurt R. Karst –
We don’t like loose ends – especially loose ends in the Hatch-Waxman world! Last June, we posted on FDA’s decisions to require sponsors of ANDAs for generic versions of ADDERALL XR (dextroamphetamine mixed salts of a single-entity amphetamine product) Extended-release Capsules to demonstrate bioequivalence using certain partial AUC metrics (see here), and to approve Actavis’ ANDA No. 077302. As we noted back then, ADDERALL XR is listed in FDA’s Orange Book with four unexpired patents – U.S. Patent Nos. 6,322,819 (“the ‘819 patent), 6,605,300 (“the ‘300 patent”), RE41,148 (“the ‘148 patent”), and RE42,096 (“the ‘096 patent”) – that are all scheduled to expire on October 21, 2018, but that are each subject to a period of pediatric exclusivity that expires on April 21, 2019. The ‘148 patent is a reissue of the ‘300 patent, and the ‘096 patent is a reissue of the ‘819 patent. The lack of any mention of 180-day exclusivity in the approval letter for ANDA No. 077302 perplexed us. We concluded our post with the following comments:
Still unclear is how FDA resolved another round of 180-day generic drug marketing exclusivity for generic ADDERALL XR. 180-day exclusivity for generic ADDERALL XR is governed by the pre-Medicare Modernization Act version of the FDC Act where exclusivity is patent-by-patent and product-by-product. Exclusivity with respect to the ‘819 and the ‘300 patents (for all strengths) was apparently triggered for another ANDA sponsor with the marketing of an authorized generic (see here). In April 2010, Actavis submitted a citizen petition (Docket No. FDA-2010-P-0188) to FDA requesting the Agency’s determination that Actavis is entitled to 180-day exclusivity with respect to the ‘148 patent. We understand that the petition was withdrawn. [(In fact, it was – see here.)] (The ‘096 patent, which issued on February 1, 2011, first appeared in the February 2011 Orange Book Cumulative Supplement, and presumably triggered a certification from sponsors with pending ANDAs.)
After digging around a bit, we think we now have an answer as to why FDA did not grant 180-day exclusivity with rspect to the ‘148 and ‘096 reissue patents: FDA considers a reissue patent, which corrects an error in an issued patent (see 35 U.S.C. § 251), and its repective parent patent to be the same patent, such that there are not separate periods of 180-day exclusivity wth respect to both the parent and reissue patents. That is, it is an either/or proposition: either there is a 180-day exclusivity period associated with the parent patent, or a 180-day exclusivity period associated with the reissue patent, but not two exclusivity periods.
FDA’s policy with respect to the availability of a second round of 180-day exclusivity for “the same” patent – parent and reissue – appears to precede the Agency’s approval of ANDA No. 077302 for ADDERALL XR. Exactly when FDA decided this issue is unclear; however, we’ve been able to trace the policy back to the September 26, 2008 approval of Mylan’s ANDA No. 077858 for a generic version of ULTRACET (tramadol HCl and acetaminophen) Tablets, 37.5 mg/325 mg. In that case, Mylan appears to have been the first company to have submitted a Paragraph IV certification to U.S. Patent No. RE39,221 (“the ‘221 patent”), which is a reissue of U.S. Patent No. 5,336,691 (“the ‘691 patent”). Previously, on April 21, 2005, FDA approved Kali’s ANDA No. 076475 for generic ULTRACET Tablets, 37.5 mg/325 mg. Kali’s ANDA included a Paragraph IV certification to the ‘691 patent – the only patent listed in the Orange Book at that time for ULTRACET Tablets – and FDA granted Kali 180-day exclusivity with respect to that patent. FDA did not, however, grant Mylan 180-day exclusivity with respect to its Paragraph IV certification to the ‘221 reissue patent. Neither Actavis nor Mylan challenged FDA’s decision not to grant 180-day excluivity vis-à-vis the reissue patents.
The disposition of 180-day exclusivity for ULTRACET Tablets, 37.5 mg/325 mg, and the ‘691 and ‘221 patents may very well have been a case of first impression at FDA. We’re not aware of another, earlier case in which the issue of granting a second period of 180-day exclusivity involving a reissue patent arose. But the ULTRACET case does seem to represent a departure from earlier 180-day exclusivity decisions involving parent and reissue patents. Take, for example, FDA’s April 5, 2002 approval of Barr’s ANDA No. 075863 for KARIVA Tablets [Desogestrel/Ethinyl Estradiol and Ethinyl Estradiol Tablets, 0.15 mg/0.02 mg and 0.01 mg, respectively, (28-day regimen)], which is a generic version of MIRCETTE Tablets (28-day cycle). At the time of approval of ANDA No. 075863, two patents were listed in the Orange Book for MIRCETTE: U.S. Patent Nos. 4,921,843 (“the ‘843 patent”) and RE35,724 (“the ‘724 patent”). Barr’s ANDA included Paragraph IV certifications to both the ‘843 patent and the ‘724 patent, which is a reissue of the ‘843 patent, thereby qualifying the company for 180-day exclusivity on both patents. According to FDA’s ANDA approval letter:
[Barr] was the first ANDA applicant to submit a substantially complete ANDA containing Paragraph IV Certifications to the listed patents. Therefore, upon this approval, [Barr] is eligible for the remainder of the 180-day generic drug market exclusivity as provided for under the [Hatch-Waxman Amendments] in Section 505(j)(5)(B)(iv) of the Act. This 180-day exclusivity commenced on December 6, 2001, the date of the district court ruling, and will end 180 days thereafter.
Although the wording of the ANDA approval is not entirely clear, it certainly suggests that Barr’s 180-day exclusivity was based on its Paragraph IV certifications to both the the ‘843 and ‘724 patents, and not one or the other. That is, there was likely a separate 180-day exclusivity period for each patent, but those periods ran concurrently.
Although we won’t get into the merits of FDA’s decision that a reissue patent and its parent patent are “the same” patent for 180-day exclusivity purposes, the question that naturally arises is whether it matters now, or whether it is merely a footnote in the Hatch-Waxman history books – a vestigial remnant of a (nearly) bygone pre-MMA 180-day exclusivity era. The answer to that question seems to hing on the parenthetical “nearly” in the preceding sentence.
The FDA policy seems to only matter in the pre-MMA context, where 180-day exclusivity is patent-by-patent, thereby giving rise to the possibility of multiple rounds of 180-day exclusivity for the same drug product based on Paragraph IV certifications to different patents. There aren’t a lot of drug products remaining that are subject to the pre-MMA rules on 180-day exclusivity – maybe less than a handful. If, however, one of those remaining drugs involves a reissue patent and its parent patent and an ANDA landscape akin to the landscape for generic ADDERALL XR and ULTRACET, then the possibilty remains that FDA could be challenged if the Agency does not grant a second round of 180-day exclusivity. We have a suspicion that the issue is still alive for at least one pre-MMA drug.
For drug products subject to the post-MMA rules on 180-day exclusivity, FDA’s parent/reissue same patent policy does not seem to matter. Why? 180-day exclusivity post-MMA is drug product-by-drug product (with some patent-by-patent undertones), such that only a first applicant that certifies to any patent listed in the Orange Book for that drug product is eligible for exclusivity. Thus, the post-MMA statute does not give rise to multiple periods of 180-day exclusivity for the same drug product. That being said, insofar as FDA’s policy could be interpreted to mean that a reissue patent, although listed in the Orange Book, is not really a patent at all, one could imagine a complex (and perhaps outrageous) post-MMA scenario in which it might come into play.