In a non-precedential decision issued February 6, 2014, the Federal Circuit affirmed a district court decision that upheld the four Orange Book listed patents for Pfizer’s Lyrica® product. According to the court’s rules, the non-precedential designation of Pfizer Inc. v. Teva Pharmaceuticals USA, Inc. means that the panel determined that it did not add signi?cantly to the body of law, but future panels may still look to it for “guidance or persuasive reasoning.” As such, this decision upholding the Lyrica® patents illustrates the strength and breadth of patent protection that can be obtained for a new molecular entity.

The Patents At Issue

The patents at issue in the district court were U.S. Patent 6,197,819, U.S. Patent 5,563,175, U.S. Patent 6,001,876, and U.S. Reissue Patent 41,920 (a reissue of the ’876 patent.).  These patents are listed in the Orange Book for Pfizer’s Lyrica® product, and this litigation was brought under 35 USC 271(e)(2)(A) after the defendants filed Abbreviated New Drug Applications (ANDAs) seeking FDA approval to market generic versions of Lyrica®.

According to the Federal Circuit decision, only two Lyrica® patents were in play for the appeal, the ’819 patent and the RE ’920 patent. From these, the court focused on claim 2 of the ’819 patent:

2. 4-amino-3-(2-methylpropyl) butanoic acid, or a pharmaceutically acceptable salt thereof.

The prescribing information for Lyrica® identifies the active ingredient as Pregabalin and provides the chemical name

(S)-3-(aminomethyl)-5-methylhexanoic acid

which uses different nomenclature to identify the S-enantiomer of the compound recited in claim 2. The Federal Circuit also refers to the compound as “3-isobutylGABA.”

The district court upheld the claims against enablement, written description, and obviousness challenges. As summarized by the Federal Circuit, because the defendants had stipulated to infringement, the district court issued an injunction that enjoined the defendants “from commercially manufacturing, using, offering for sale, or selling their proposed products” prior to the December 30, 2018 expiration date of the ’819 patent.

The Federal Circuit Decision

The Federal Circuit decision was authored by Judge Prost, and joined by Chief Judge Rader and Judge Moore.

The Federal Circuit first addressed the district court’s construction of claim 2 as generically reciting 3-isobutylGABA rather than specifying a racemic mixture of enantiomers, as argued by the defendants.

The Federal Circuit found that specification supported the district court’s broader claim construction because the specification used the compound name generally, used the racemic designation in some instances, and used the enantiomeric designations in other instances.  Because the racemic designation was not used in claim 2, the Federal Circuit agreed that “it should not be so limited.” The court rejected the defendants’ arguments that the report of data for racemic mixtures warranted construing claim 2 as being limited to racemic mixtures.

The enablement challenge was based on the assertion that, in order to support the generic claim construction, the specification “must teach a skilled artisan how to prepare every conceivable mixture of 3-isobutylGABA’s enantiomers.” The Federal Circuit rejected this line of argument, noting:

  • “[T]here is no requirement that a specification must ‘disclose what is routine and well known in the art.’”
  • “[T]here is no dispute in the record that the co-inventors of the ’819 patent were the first to create and claim the chemical compound 3-isobutylGABA.
  • “It is also undisputed that the parent application discloses the method for synthesizing the compound and states that the compound’s ‘enantiomers may be prepared or isolated by methods already well known in the art.’”
  • “[T]he PTO Examiner … withdrew an enablement rejection … during prosecution of the patent.”

The Federal Circuit concluded:

Where a claim has been construed to cover a chemical compound, the specification is not deficient merely because it does not disclose how to prepare a particular form or mixture—among hundreds of possible permutations—of that compound. See In re Hogan, 559 F.2d 595, 606 (CCPA 1977) (noting that requiring such specific disclosures would “impose an impossible burden on inventors”).

The Federal Circuit characterized the written description challenge as similar to the enablement challenge, being based on an alleged failure of the specification to disclose the various enantiomeric mixtures encompassed by claim 2. The Federal Circuit rejected this line of argument, noting:

[W]ritten description does not require inventors, at the time of their application for a patent, to reduce to practice and be in physical possession of every species (e.g., the S-enantiomer of 3-isobutylGABA) of a genus (3-isobutylGABA) claim. For claims to a chemical compound, an application satisfies the written description requirement when it details “relevant identifying characteristics” such that the compound can be distinguished from other compounds. In re Wallach, 378 F.3d 1330, 1333, 1335 (Fed. Cir. 2004).

Because the specification ”disclosed the structure of 3-isobutylGABA as the preferred embodiment of the invention,” “set forth in vitro and in vivo data for the compound,” and “described a method of synthesizing the compound,” the description was “sufficient for persons of ordinary skill in the art to recognize that the inventor invented what is claimed.”

The obviousness challenge on appeal was based on the assertion that the district court failed to make the following factual findings:

  1. “Fish, Shashoua, and Colonge taught that 3-isopropylGABA and other homologous compounds may have anticonvulsant activity.”
  2. “[O]ne of ordinary skill in the art would have expected 3-isobutylGABA to have anticonvulsant activity due to its structural similarities to 3-isopropylGABA.”
  3. “[G]abapentin, a 3-alkylGABA compound in the prior art with demonstrated anticonvulsant efficacy, provided a motivation for persons skilled in the art to try other alkyl substituents at GABA’s 3-position.

The Federal Circuit assessed the obviousness challenge under its “lead compound” framework. The Federal Circuit agreed with the district court that the evidence did not establish that either 3-isopropylGABA or gabapentin would have been selected as a lead compounds for anticonvulsant drugs,  or that it would have been obvious to modify those compounds in the manner required to arrive at 3-isobutylGABA.

Thus, the Federal Circuit affirmed the district court’s judgments that the patents were not invalid.

Developing New Drugs 

New molecular entities may be the “gold standard” for new pharmaceutical products, but they also are the hardest to come by and may take the longest to develop. The FDA publishes annual lists of newly approved ”new molecular entities (NMEs)” which it describes as “active moieties that have not been approved by FDA previously, either as a single ingredient drug or as part of a combination product,” although some NMEs may be drugs that “contain active moieties that are closely related to active moieties in products that have previously been approved,” such as biological products. Twenty-seven NMEs were approved in 2013, 39 were approved in 2012, and 30 were approved in 2011. In contrast, the FDA approved almost 100 New Drug Applications and Biologics License Applications in 2013 alone.