Two Pharma and Biotech Cases to Watch in 2022

Monty Python and the Holy Grail: “I’m Not Dead Yet.” Source: Youtube

As we enter the second month of 2022, the old saying, “If at first you don’t succeed, try, try again” and the famous line, “I’m not dead,” from Monty Python and the Holy Grail, come to mind to describe two issues we’ll be watching closely this year relating to litigation involving small and large molecule therapies.

In the first instance, Amgen recently petitioned the Supreme Court to review the Federal Circuit’s affirmance invalidating several patent claims based on the lack of enablement for genus claims. This case comes on the heels of the Supreme Court’s denial of cert. in Idenix Pharms. LLC v. Gilead Sci. Inc., 941 F.3d 1149 (Fed. Cir. 2019) on similar issues. Amgen now hopes for a better result.

Another case we’re watching concerns generics’ ability to seek Food and Drug Administration (FDA) approval for less than all of the indications for which the reference drug is approved—also known as a “skinny label.”  For all the hubbub over the opinion in GlaxoSmithKline LLC v. Teva Pharm. USA, Inc., 7 F.4th 1320 (Fed. Cir. 2021), the district court’s decision in Amarin Pharma, Inc. v. Hikma Pharms. USA Inc., No. CV20-1630-RGA-JLH, D.I. 97 (D.Del. January 4, 2022) shows that the skinny label may not be dead just yet.

Enablement of Genus Claims in the Biotechnology Sector

Last year, Amgen Inc. v. Sanofi-Aventis, 987 F.3d 1080 (Fed. Cir. 2021), revived the discussion around enablement of genus claims in the biotechnology sector, this time specifically relating to antibody claims with functional limitations. At the district court, a jury found that the claims were not invalid for lack of enablement, but Judge Andrews granted Sanofi’s JMOL, finding the claims at issue invalid. On appeal, the Federal Circuit discussed prior decisions on enablement of claims with functional limitations, finding that “[w]hat emerges from our case law is that the enablement inquiry for claims that include functional requirements can be particularly focused on the breadth of those requirements, especially where predictability and guidance fall short.” Amgen, 987 F.3d at 1086. The Federal Circuit stressed the importance of considering the quantity of experimentation, and the full scope of the claims. Id. As the panel stepped through the Wands factors for enablement, it affirmed the district court’s holding that Amgen’s asserted claims to a genus of antibodies were invalid for lack of enablement as a matter of law.

In November 2021, Amgen petitioned the Supreme Court for a writ of certiorari, presenting the following questions to the high court:

[1.] Whether enablement is “a question of fact to be determined by the jury,’ … or “ a question of law that [the court] review[s] without deference,” as the Federal Circuit holds.

[2.] Whether enablement is governed by the statutory requirement that the specification teach those skillied in the art to “make and use” the claimed invention … or whether it must instead enable those skilled in the art “to reach the full scope of claimed embodiments” without undue experimentation—i.e, to cumulatively identify and make all or nearly all embodiments of the invention without substantial “ time and effort,” ….

See Case No. 21-757, November 18, 2021.

Earlier last year, the Supreme Court denied certiorari in Idenix v. Gilead (No. 20-380, January 19, 2021), which presented similar issues and left in place a Federal Circuit decision that many patentees believe created a heightened enablement standard for genus claims. There, a divided Federal Circuit panel held invalid claims directed to methods of treating hepatitis C using a genus that covered “tens if not hundreds of thousands” of 2’-methyl-up nucleosides. In doing so, the majority focused on the undue experimentation factor to find that the specification “does not provide enough meaningful guidance or working examples, across the full scope of the claim, to allow a POSA to determine which 2’-methyl-up nucleosides would or would not be effective against HCV without extensive screening.”  941 F.3d at 1162.

In the wake of Idenix, branded pharmaceutical companies and trade organizations sounded the alarm over the death of genus claims for biotechnology inventions, whereas generic and biosimilar companies touted this result as a reaffirmation of the Court’s reasoning in Wyeth & Cordis Corp. v. Abbott Labs., 720 F.3d 1380 (Fed. 2013). As the law currently stands, genus claims that rely on functional or broad structural limitations to cover monoclonal antibodies (mAbs) can be invalid for lack of enablement where the specification does not provide further guidance.

Three amicus briefs have been filed in support of Amgen’s petition, and Sanofi’s response is currently due March 14, 2022. Based on the similarity of the questions presented to those that the Supreme Court declined to answer in Idenix v. Gilead, Amgen’s petition has a slim chance of success. Regardless, patent owners should be wary of asserting claims that characterize a mAb purely on its function.

Skinny Labels Aren’t Dead Yet

Another case we’ve been watching closely is Amarin’s litigation against Hikma and Health Net, concerning Hikma’s “skinny-label” generic of Amarin’s Vascepa® (icosapent ethyl). Amarin’s Vascepa® is FDA-approved for both the treatment of severe hypertriglyceridemia (the “SH indication”) and cardiovascular risk reduction (the “CV indication”), but only the CV indication is covered by Amarin’s patents. In November 2020, Hikma launched its FDA-approved generic product with the CV indication carved-out from its label (under 21 U.S.C. § 355(j)(2)(A)(viii)). Soon after, Amarin filed a patent infringement case in Delaware district court alleging that Hikma nonetheless induces infringement of its SH indication patents based. Case No. CV 20-1630-RGA-JLH.

Amarin’s infringement case was based on the Federal Circuit’s decisions in GSK v. Teva, which found that Teva induced infringement of GSK’s method-of-treatment patent despite having a skinny label that lacked the indication at issue. See Case No. 2018-1976 (opinion dated October 2, 2020, and re-hearing opinion dated August 5, 2021). In both decisions, the majority found Teva liable for induced infringement based on its label along with press releases and other marketing materials. However, in its re-hearing opinion, the majority addressed concerns from Teva and amici by stressing that its opinion was fact specific and did not change the law permitting generic drug companies to avoid induced infringement by carving indications out of their labels. Judge Prost again dissented, arguing the new opinion left concerns of significant risk and uncertainty for generic filers that carve out indications from their labels.

Hikma moved to dismiss Amarin’s complaint under Rule 12(b)(6). In opposition, Amarin argued that Hikma’s label teaches CV risk reduction because Hikma’s label includes a warning concerning side effects for patients with CV disease and because Hikma’s label does not affirmatively state not to use its product for the CV indication. In August 2021, Magistrate Judge Hall recommended denying Hikma’s motion, finding Amarin’s allegations plausible based on the lack of a factual record. Case No. CV 20-1630-RGA-JLH, D.I. 64 (D. Del. August 3, 2021).

Following the re-hearing opinion in GSK v. Teva, Judge Andrews rejected Amarin’s arguments and the Magistrate’s recommendation and granted Hikma’s motion to dismiss. In doing so, Judge Andrews focused on the following factors:  (i) the warning in Hikma’s label to patients with CV disease was not an instruction or encouragement, (ii) there is no precedent requiring Hikma to include an affirmative statement in its label to discourage the use of its product for the patented indication, and (iii) Hikma’s public statements about Vascepa® sales and that its product is a generic equivalent to Vascepa® did not rise to the level of inducing acts. Case No. CV 20-1630-RGA-JLH, D.I. 97 (D. Del. January 4, 2022).

However, Judge Andrews permitted Amarin’s case against Health Net (an insurance company that provides coverage for Vascepa® and Hikma’s generic product) to go forward. Amarin alleges that Health Net’s formulary placement of Hikma’s generic as being interchangeable with Vascepa® for all indications induces infringement of Amarin’s patents covering the CV indication.

We’ll be watching this case closely, as insurers are not typically implicated in Hatch-Waxman litigation. We also expect Amarin to appeal the dismissal of its case against Hikma, and it will be interesting to see whether the Federal Circuit adheres to the promise it made in its GSK v. Teva re-hearing opinion to conduct a fact-specific analysis in each case.