In August 2021, the Court of Appeal for the Federal Circuit (CAFC), in a per curiam opinion, quietly decided one of the most important pharma cases in recent years in GlaxoSmithKline v Teva Pharmaceuticals USA (Fed Cir 2021).

The decision resulted in a $235 million infringement verdict for GSK. In addition, a dozen amicus curiae briefs were filed for consideration with the per curiam decision, from parties including both brand companies, generic drug companies and NPOs.

The decision in GSK v Teva effectively redefined the understanding of skinny label exceptions to infringement.

When a generic wants to enter the market with a drug covered by an Orange Book-listed patent, its Abbreviated New Drug Application (ANDA) is required to contain a certification as to any patent listed in the Orange Book that:

• Such patent has expired (a paragraph II certification);
• The date on which such patent will expire (a paragraph III certification); or
• That such patent is invalid, unenforceable, or will not be infringed by the manufacture, use, or sale of the new drug for which the application is submitted (a paragraph IV certification).

Also listed with each patent in the Orange Book are “use codes”. Patent use codes designate the use that is covered by the claims of a patent that is directed to an approved indication or use of a drug product. An exception to the required paragraph (II)-(IV) certification can occur when the patent that is listed only claims a method of use.

In this case, the ANDA applicant may omit the approved method of use from their generic drug label. In this case the generic company submits a “section VIII statement” that the listed patent does not claim a use for which the applicant seeks approval. The label under a section VIII statement is commonly referred to as a “skinny label”.

A significant shift

The Federal Circuit previously stated an ANDA infringement is “limited to an analysis of whether what the generic drug maker is requesting authorisation for in the ANDA would be an act of infringement if performed”. (Warner–Lambert v Apotex [2003]). The court held in Warner–Lambert, with regard to a section VIII statement, that “the request to make and sell a drug labelled with a permissible (non-infringing) use cannot reasonably be interpreted as an act of infringement (induced or otherwise) with respect to a patent on an unapproved use, as the ANDA does not induce anyone to perform the unapproved acts required to infringe”.

Thus, historically, a drug marketed under a skinny label has been viewed as being non-infringing of the patented method, which has been carved out from the label. However, the understanding that infringement of a patented method of treatment could be avoided by obtaining approval and marketing with a label based on a section VIII carve out statement was significantly revised under the recent GSK v Teva decision.

The approved GSK drug Coreg (carvedilol) was approved for three indications: mild-to-severe chronic heart failure hypertension (CHF), left ventricular dysfunction following myocardial infarction (post-MI LVD), and hypertension. Teva marketed a generic version of carvedilol under a skinny label, which listed only hypertension and post-MI LVD.

The GSK RE40,000 patent claimed: “A method of decreasing mortality caused by congestive heart failure … wherein the administering comprises administering to said patient daily maintenance dosages for a maintenance period to decrease a risk of mortality caused by congestive heart failure …”

The Orange Book listed the ‘000 patent with use code U-233, ie, “decreasing mortality caused by congestive heart failure”. Teva submitted a section VIII statement with its ANDA stating that the label for its generic carvedilol would not include an indication defined by use code U-233 for “decreasing mortality caused by congestive heart failure”.

Interpreting the label

However, press releases and marketing materials from Teva indicated that its generic carvedilol was for the treatment of heart failure and hypertension, was the “generic version of [GSK’s] cardiovascular agent Coreg”, and was an AB-rated generic equivalent [ie therapeutically equivalent] of Coreg.

GSK sued Teva for infringement of the ‘000 patent based on the sale of the generic drug under the skinny label. GSK argued that indication on the “skinny label” for treating post-MI LVD would induce infringement of the claims in the ‘000 patent to, “a method of decreasing mortality caused by congestive heart failure”. Thus, GSK argued that the label of Teva was not, in fact, a skinny label because it still instructed the claimed method of use of the ‘000 patent.

GSK’s expert testified that post-MI LVD “is intertwined with heart failure” and the expert of Teva acknowledged that a patient having post-MI LVD as described on Teva’s label would also be diagnosed as suffering from congestive heart failure, as construed by the district court.

Teva’s label explicitly stated that, “Carvedilol is indicated to reduce cardiovascular mortality” in post-MI LVD patients. Thus, it was asserted by GSK, that the post-MI LVD indication on Teva’s partial label satisfied the claimed feature of decreasing mortality caused by congestive heart failure.

The court considered the testimony of both experts and concluded that the “combination of Teva’s partial label, Dr McCullough’s [GSK expert] element-by-element testimony that the partial label explicitly instructs administering carvedilol for the claimed use of decreasing mortality caused by CHF, and Dr Zusman’s [Teva expert] admission that the post-MI LVD indication falls within the definition of congestive heart failure is substantial evidence that supports the jury’s finding”.

Teva also asserted that GSK only listed use code U-233 in the Orange Book and the patent claims should therefore be interpreted as being limited to the use defined by the use code. However, the CAFC noted that the FDA has clearly and unequivocally taken the position that reliance on Orange Book listings is in no way meant to replace an independent review of the relevant patents by a third party.