FDA revises forms for submission of patent information to the Orange Book: Federal Circuit decision in Novartis AG v. Lee alters patent term adjustment
Two recent developments will affect the listing of patent information with pharmaceutical products approved by the U.S. Food and Drug Administration (FDA). First, the FDA has revised the forms on which such information is submitted. The revised forms may alter the manner in which sponsors describe patent claims covering methods of using their FDA-approved drug products. Second, the Federal Circuit recently held that the U.S. Patent and Trademark Office (PTO) has incorrectly interpreted a statutory patent term adjustment under 35 USC 154 for certain patents whose prosecution included a request for continued examination. Although this decision is not limited to pharmaceutical patents, any changes to patent expiration dates for FDA-approved drug products must be promptly submitted to the FDA on the revised forms.
The FDA changes instructions on method of use information submitted with Orange Book-listed patents
As of November 2013, the FDA issued new versions of Form FDA 3542a (Patent Information Submitted With the Filing of an NDA, Amendment, or Supplement) and Form FDA 3542 (Patent Information Submitted Upon and After Approval of an NDA or Supplement). While there are no changes to the fields of the forms themselves, the FDA has revised the instructions on identifying labeling information regarding method of use claims. The agency requested public comment on the paperwork burden imposed by the forms, but did not explain the basis for its changes. See 78 FR 36193 (June 17, 2013); see also 78 FR 57164 (Sept. 17, 2013). The chart below describes one of the key revisions to both forms.
|Form FDA 3542a||Method of Use(4.2a)||Specify the part of the proposed drug labeling that is claimed by the patent.||Identify the precise words of the approval [sic] labeling that describe with specificity the patented method of use.|
|Form FDA 3542||Method of Use(4.2a)||Specify the part of the approved drug labeling that is claimed by the patent.||Identify the precise words of the approval labeling that describe with specificity the patented method of use.|
Both revised Form FDA 3542a and revised Form FDA 3542 have identical instructions on identifying labeling information regarding method of use claims, other than a spelling error.
By way of context, a sponsor that submits a new drug application (NDA), an amendment, or a supplement, must include information about certain patents. 21 USC 355(b)(1); 21 USC 355(c)(2); see 21 CFR 314.53. The sponsor must submit information about patents that claim the sponsor’s drug or a method of using the sponsor’s drug and for which a claim of patent infringement could reasonably be asserted against someone manufacturing or selling an unlicensed version of the drug. 21 USC 355(b)(1); 21 USC 355(c)(2); 21 CFR 314.53(b)(1). The FDA limits the submission of patent information to patents that claim the drug substance (active ingredient), the drug product (formulation and composition), or a method of using the drug. See 21 CFR 314.53(b)(1). When submitting this patent information prior to approval, sponsors use Form FDA 3542a; when submitting patent information post approval, sponsors use Form FDA 3542.
On the basis of the information provided in these forms, the FDA lists the patents in its publication titled, Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book). Among the information posted in a drug’s Orange Book listing is a “use code,” which is a description of the approved method of use or indication covered by the sponsor’s method of use patent. The brand manufacturer submits the use code to the FDA as part of Form 3542, and the FDA accepts the code without verifying its accuracy. In turn, generic manufacturers rely on the code to facilitate approval of generic drugs as soon as patents permit, and more importantly, to seek approval of drugs by proposing labeling that “carves out” any methods of use that are still under patent. See 21 CFR 314.94(a)(8)(iv).
The changes to the instructions are directed to how sponsors may submit information regarding method of use claims on both forms. In the new instructions, the agency is instructing sponsors to align the method of use patent claims with direct, verbatim text in the proposed or final drug labeling.
This change may be one attempt by the FDA to bring more order to the use code issues examined in Caraco Pharmaceutical Laboratories, Ltd. v. Novo Nordisk A/S, in which the Court decided that a generic manufacturer may “force correction of a use code that inaccurately describes the brand’s patent as covering a particular method of using the drug in question.” See Caraco Pharm. Lab. Ltd. v. Novo Nordisk A/S, 132 S. Ct. 1670, 1675 (2012). Whether the FDA will exercise greater scrutiny of patent information submitted for listing in the Orange Book remains to be seen.
Federal Circuit decision increases patent term adjustment for certain issued patents and pending applications
On 15 January 2014, in Novartis AG v. Lee, Nos. 2013-1160, -1179, 2014 WL 128577 (Fed. Cir. Jan. 15, 2014), the U.S. Court of Appeals for the Federal Circuit held that the PTO had been miscalculating patent term adjustment (PTA) for patents whose prosecution included a request for continued examination. This decision affects patents across many industries. For patents covering FDA-approved pharmaceutical products, companies should review their Orange Book-listed patents as soon as possible to determine if their terms are eligible to be increased.
As background, Congress provided for PTA to compensate for PTO delays that reduce a patent’s term. See Pub. L. No. 106-113, § 1000(a)(9), 113 Stat. 1501, 1536. One provision in the PTA statute is that the patent’s term will be adjusted one day for each day that the PTO fails to issue a patent within three years after the application’s filing or commencement date. See 35 USC 154(b)(1)(B). Under prior PTO practice, time between allowance to issuance would not count towards the PTO’s 3-year period, if the patent owner had requested continued examination. The Federal Circuit held that the PTO mistakenly excluded the time from allowance to issuance in these circumstances.
In light of the decision, pharmaceutical companies should review their listed patents to determine if they may be entitled to a later expiration date. If so, a revised expiration date must be promptly submitted to the FDA on the Form FDA 3542 described above. Moreover, in light of the change to the form, method of use information previously submitted to the agency, in section 4.2 of the form, may need to be revised to conform to the new instructions.
Importantly, submission of a revised expiration date does not affect the date the FDA considers the patent to have been submitted to the Orange Book for purposes of determining 30-month stays on approvability of generic drug applications. A 30-month stay is available where an innovator sponsor and/or patent owner timely sues following a generic applicant’s paragraph IV certification with regard to a patent that was listed with the FDA before submission of the generic application. 21 USC 355(j)(5)(B)(iii); see Draft Guidance, Listed Drugs, 30-Month Stays, and Approval of ANDAs and 505(b)(2) Applications Under Hatch-Waxman, as Amended by the Medicare Prescription Drug, Improvement and Modernization Act of 2003, Questions and Answers, at 8 (Oct. 2004). In other words, a “later-listed” patent will not give rise to a 30-month stay. However, the FDA considers a patent to have been listed on the first date that patent information is submitted with the approved NDA. The further submission of a new expiration date reflecting a corrected PTA under 35 USC 154 (or patent term extension under 35 USC 156) is immaterial to this analysis.
The FDA addressed this precise issue in its response to a citizen petition regarding a generic version of Roche’s Boniva (ibandronate sodium). FDA Petition Response regarding Boniva, Docket No. FDA-2010-P-0518 (Feb. 22, 2011). In that response, the agency emphasized that the operative question in a 30-month stay determination is whether the NDA holder had first submitted patent information prior to the submission of the abbreviated new drug application (ANDA):
The fact that Roche subsequently submitted updated patent information to reflect the patent term extension for the ‘814 patent after Orchid’s ANDA submission, does not change the analysis above or our determination that a 30-month stay is appropriate here.
Id. at 10.
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