March 1, 2021
The decision in GlaxoSmithKline LLC. V Teva Pharms. (976 F.3d 1347 (Fed. Cir. 2020) has caused panic in the generic industry because it has been interpreted as killing the “skinny label” approach to generic drug approval. A “skinny label” allows a generic company where there are multiple approved indications for a drug and some are protected by patent and others are not, to omit the patented indications from its label and avoid the need for a paragraph (iv) certification and 35 U.S.C. 217(e)(2) litigation. During the oral argument on February 23, 2021, on remand to the original panel, it became clear that the skinny label exception is not under attack although you wouldn’t know it from the Federal Circuit’s decision or the press reports.
The issue being litigated is whether Teva’s skinny label used from 2008 to 2011 avoids inducing infringement of GSK’s patent Re. 40,000 (Re ‘000). In 2011 Teva submitted a new label containing all three approved indications:
1.1 Heart Failure
COREG is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization [see Drug Interactions (7.4) and Clinical Studies (14.1)].
1.2 Left Ventricular Dysfunction Following Myocardial
COREG is indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of ≤40% (with or without symptomatic heart failure) [see Clinical Studies (14.2)].
COREG is indicated for the management of essential hypertension [see Clinical Studies (14.3, 14.4)] It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.
Before 2011 Teva’s label had omitted indication 1.1 Heart Failure. There is no dispute that that Re. ‘000 is not infringed by using Coreg® to treat hypertension, indication 1.3, nor is there any dispute that Teva’s label from 2008 to 2011 did not contain indication 1.1, chronic heart failure, which is admittedly claimed by Re ‘000. The issue was whether indication 1.2, Myocardial Infarction Left Ventricle Dysfunction (MILVD) induces infringement of claims 1 - 3 of Re. ‘000. On this point the jury had ruled in GSK’s favor, a decision reversed on JMOL and reinstated in the original appellate decision.
Re. ‘000 claim 1 reads:
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,
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, and said maintenance period is greater than six months.
At the February 23 oral argument Teva claimed that the indication required that the congestive heart failure be chronic arguing that GSK’s expert had looked to other portions of the label to support his opinion it covered non-chronic conditions. The weakness in that argument is that section 14.2 of the label referenced in 1.2 provided clinical results for patients “with or without symptoms of heart failure.” Also, the use code submitted in form FDA 3542 for listing Re. ‘000 in the Orange Book read:
Treatment Of Mild-To-Severe Heart Failure of Ischemic Or Cardiomyopathic Origin. Usually In Addition To Diuretics, ACE Inhibitor, And Digitalis To Increase Survival
Teva argued in its brief that GSK told the FDA that its method of use patents claimed treating chronic heart failure. However, the use code definitions provided by GSK did not use the term “chronic.”Thus, GSK is a conventional 35 U.S.C. 271(b) cause of action for inducement and does not implicate the “skinny label” provisions of Hatch-Waxman.