Following the Supreme Court’s decision in Caraco Pharm. Labs., Ltd. v. Novo Nordisk A/S, 566 U.S. 399, 132 S. Ct. 1670 (2012), much has been written about overly broad patent use codes and their potential to confuse FDA’s carve-out decisions for generic drugs. But what about overly narrow patent use codes? A decision from the Federal Circuit late last year, in Glaxosmithkline LLC v. Teva Pharm. USA, Inc., 2021 U.S. App. LEXIS 23173 (Fed. Cir. Aug. 5, 2021) (“GSK v. Teva”), suggests that narrow patent use codes can also be just as impactful.
In GSK v. Teva, an en banc panel of the Federal Circuit affirmed a jury’s $234 million verdict against Teva Pharmaceuticals USA, Inc. (“Teva”) for infringing a method of treatment patent owned by GlaxoSmithKline LLC and SmithKline Beecham (Cork) Ltd. (collectively, “GSK”) for GSK’s CoReg® (a/k/a carvedilol), in spite of a label carve-out.
In 2007, when Teva secured FDA approval to market carvedilol, GSK’s label for CoReg® included three approved indications:
- Hypertension
- Chronic heart failure (“CHF”)
- Left ventricular dysfunction (“LVD”)
GSK also owned U.S. Patent No. 5,760,069 (the “069 patent”), which was subsequently reissued as RE 40,000 to claim:
1. A method of decreasing mortality caused by congestive heart failure in a patient in need thereof which comprises administering a therapeutically acceptable amount of carvedilol in conjunction with one or more other therapeutic agents, said agents being selected from the group consisting of an angiotensin converting enzyme inhibitor (ACE), a diuretic, and digoxin, …
The Orange Book gives the following use code for RE 40,000:
Decreasing Mortality Caused By Congestive Heart Failure.
Given the express reference to CHF in RE 40,000, and the express reference to CHF in the use code, FDA allowed Teva to carve out the CHF indication from its label, and to market its carvedilol only for hypertension and LVD.
Unfortunately for Teva, GSK proved at trial that any patient with LVD will also be diagnosed as having CHF. Thus, when Teva marketed its products under a label that included patients with LVD, it was also marketing its products for patients with CHF, and thereby inducing infringement of RE 40,000. Hence the $234 million verdict.
The situation obviously caught Teva by surprise, but the lesson to be learned is quite simple: Never rely solely on a patent use code when evaluating patent infringement. Use codes are an internal tool developed by FDA to carry out its review of label carve-outs. As stated by the Federal Circuit:
the FDA has made clear that use codes in the Orange Book "are not meant to substitute for the [ANDA] applicant's review of the patent and the approved labeling."
Generics should undertake thorough reviews of their labels to ensure they do not encourage doctors to prescribe a medication for a patented use, regardless of the use code.
One further issue remains in the lawsuit. FDA’s form 3542, which is used by patent owners to list their patents in the Orange Book, required GSK in section 4.2a to "identify the use with specific reference to the approved labeling for the drug product." As Orange Book practitioners know, section 4.2a essentially informs FDA what sections of the label the patent owner believes must be carved out to avoid patent infringement.
However, GSK only listed its CHF indication in section 4.2a. GSK did not list the LVD indication in section 4.2a. As a result, FDA did not know that GSK took the position that a generic drug labeled for LVD could infringe RE 40,000. If Teva had requested a copy of the form 3542 from FDA under the Open Records Act, it also would not have known.
Teva argued on appeal that GSK’s failure to mention LVD in section 4.2a should create an estoppel that prevents GSK from suing Teva for patent infringement. The Federal Circuit declined to address the issue because it was unclear whether Teva had reviewed a copy of GSK’s form 3542, and reliance is an essential element of the doctrine of equitable estoppel. However, the Federal Circuit did remand the issue to the trial court judge for further consideration.
As of today, five months after the Federal Circuit decision, the trial court has not reopened the case to consider the issue of estoppel.
