Superseding 30-month Stay (Genzyme and Cobrek at the FDA)

The FDA recently granted NDA holder Genzyme’s petition for a superseding 30-month stay against approval of Cobrek’s generic version of Genzyme’s Hectorol drug.

In April 2000, the FDA approved Genzyme’s NDA for Hectorol formulated in ampules, and Genzyme submitted U.S. Patent No. 5,602,116 (“the ‘116 patent”) for Orange Book listing related to the Hectorol NDA. Cobrek, in filing an ANDA for Hectorol in October 2007, provided a paragraph IV certification regarding the ‘116 patent. Genzyme promptly initiated infringement litigation, triggering a 30-month stay against FDA approval of Cobrek’s generic Hectorol.

In December 2008, the FDA approved Genzyme’s supplemental NDA for an injectable version of Hectorol available in vials. Genzyme then listed both the ‘116 patent and U.S. Patent No. 7,148,211 (“the ‘211 patent”), regarding the vial form of Hectorol, in the Orange Book. Cobrek then submitted a paragraph IV certification regarding the ‘211 patent. Around this time, Cobrek also reformulated its product to reflect the changes to Genzyme’s formulation of Hectorol from ampule to vial. The FDA notified Cobrek that it required patent certifications regarding both the ‘211 and ‘116 patents, and Cobrek complied, providing the required notice to Genzyme. Genzyme again filed suit for infringement, this time asserting both the ‘211 and ‘116 patents.

After filing suit, Genzyme submitted a petition for a superseding 30-month stay. Cobrek opposed Genzyme’s request. In its reply, the FDA noted the language of the statute, which states that

If the applicant made a [paragraph IV] certification . . . approval shall be made effective immediately unless, before the expiration of 45 days after the date on which the notice [of a paragraph IV certification] is received, an action is brought for infringement of the patent that is the subject of the certification and for which information was submitted to the Secretary [for Orange Book listing] before the date on which the application (excluding an amendment or supplement to the application), which the Secretary later determines to be substantially complete, was submitted. If such an action is brought before the expiration of such days, the approval shall be made effective upon the expiration of the thirty-month period beginning on the date of the receipt of the notice [of a paragraph IV certification]. . . .
21 U.S.C. § 355(j)(5)(B)(iii) (emphasis added). Thus, for a 30-month stay to rely on a paragraph IV certification, the underlying patent information must have been submitted for Orange Book listing before the related ANDA was filed.[1] Additionally, any 30-month stay begins on the date that the NDA holder or patent owner receives notice of the paragraph IV certification. Because Genzyme submitted the ‘116 patent for Orange Book listing before Cobrek filed its ANDA, the FDA found that the ‘116 patent could be the basis for even a superseding 30-month stay and granted Genzyme’s request.

In the FDA’s decision, and in a 2003 guidance document that the decision cited in which the FDA provided guidelines concerning ANDAs and 30-month stays, the FDA has noted that superseding 30-month stays are sometimes possible. As in this case, a superseding 30-month stay is possible when the ANDA applicant re-files a paragraph IV certification for a patent for which it had filed a paragraph IV certification initially. The FDA also provided a hypothetical scenario in which an ANDA initially has a paragraph IV certification as to one patent and a paragraph III certification as to another and the applicant later changes the paragraph III certification to another paragraph IV certification. The ANDA applicant in such a case would provide the NDA holder or patent owner with notice of paragraph IV certifications on two separate occasions, from which two separate 30-month stays could potentially result. In both of these situations, the NDA holder or patent owner submitted the patent for listing in the Orange Book before the generic applicant filed for an ANDA, yet the generic applicant provided the NDA holder or patent owner with notice as to a paragraph IV certification on separate occasions.

Such situations contrast with cases in which an ANDA holder files a paragraph IV certification, then an NDA holder or patent owner submits Orange Book material for another relevant patent, and then the ANDA holder files another paragraph IV certification. The patent underlying the second paragraph IV certification in such a case would not be one “for which information was submitted to the Secretary . . . before the date on which the application . . . was submitted,” as required by the statute. The FDA decision regarding Hectorol notes that Congress added this clause to the statute in 2003 to prevent excessive delays in generic drug approval. Without this clause, an NDA holder could repeatedly add patents to its Orange Book listing to require further certifications from an ANDA applicant, giving the NDA holder an opportunity to incite a string of 30-month stays. The requirement that the NDA holder or patent owner submit Orange Book information prior to the ANDA filing for a 30-month stay makes the ANDA applicant more likely to be the party responsible for initiating any post-ANDA procedures that could result in multiple 30-month stays. [2]

In light of this decision, an NDA holder who receives multiple paragraph IV certification notices, which may embroil the NDA holder in multiple infringement lawsuits, has the chance to further combat the generic manufacturer with multiple 30-month stays. Likewise, ANDA filers should file later paragraph IV certifications with care. Submitting paragraph IV certifications on multiple occasions for a single ANDA can ultimately result in multiple 30-month stays if based on patents submitted for Orange Book listing before the ANDA filing.

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1 The FDA also noted that this aspect of the provision applied only to Orange Book listings submitted after August 18, 2003. However, because the ‘116 patent was submitted for Orange Book listing prior to both August 2003 and Cobrek’s ANDA filing and because the ‘211 patent was submitted for Orange Book listing after both August 2003 and Cobrek’s ANDA filing, the effect is the same: the ‘116 patent can be the basis for a 30-month stay in this case, while the ‘211 patent cannot. The FDA stated that, even if the 2003 provisions had applied to the ‘116 patent’s Orange Book listing, the result here would be the same.

2 While the FDA required Cobrek to make a second certification regarding the ‘116 patent in the Hectorol case, the FDA notes that Cobrek should have argued against that requirement at that time if it did not agree, rather than filing a second paragraph IV certification and providing notice to Genzyme regarding a second paragraph IV certification.