Federal Circuit Distinguishes Amgen in Reversal of Invalidation of Teva Headache Treatment Patents

The U.S. Court of Appeals for the Federal Circuit (CAFC) issued a precedential decision today in Teva Pharmaceuticals International GmbH v. Eli Lilly and Company, reversing the United States District Court for the District of Massachusetts’s grant of judgment as a matter of law (JMOL) of invalidity of Teva’s headache treatment patents. The district court found that the asserted claims were invalid for failing to satisfy both the written description and enablement requirements of 35 U.S.C. § 112, but the CAFC found the district court’s grant of JMOL improper on both counts. The opinion was authored by Judge Prost and joined by Judge Cunningham and District Judge Andrews.

The dispute centered on U.S. Patent Nos. 8,586,045, 9,884,907, and 9,884,908, which claim methods of using humanized anti-CGRP antagonist antibodies to treat headache. The patents describe CGRP as a protein found in humans, and that when it binds to receptors on certain cells, the cells expand and increase blood flow through blood vessels, a phenomenon associated with headache. Teva filed a lawsuit against Eli Lilly and Company in September 2018, alleging that Lilly indirectly infringed the patents via its Emgality product.

The jury returned a verdict for Teva, finding that Lilly willfully infringed the asserted claims and failed to prove invalidity under the written description or enablement doctrines, and awarded Teva damages. Lilly then moved for JMOL of invalidity on the grounds of written description and enablement, which the district court granted, and Teva appealed.

In addressing the written-description requirement, the CAFC explained that, for claims to a genus, adequate written description requires disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus. The CAFC noted that the patents make clear that their claimed invention is the use of anti-CGRP antagonist antibodies, or humanized versions thereof, to treat headache, not such antibodies themselves. Several prior cases were particularly instructive for the CAFC’s analysis, including Ajinomoto Co. v. ITC, In re Herschler, and In re Fuetterer, all of which involved claims pertaining to a well-known genus that was not, itself, the invention.

“A reasonable jury could have found that anti-CGRP antagonist antibodies themselves and methods of making them were well known, replete, or extensively described in the prior art— based on Lilly’s own statements” during previous Patent Trial and Appeal Board (PTAB) inter partes review (IPR) proceedings, said the CAFC. Furthermore, a reasonable jury could have found that humanization was “a well-established and routine procedure” by the priority date, again based on Lilly’s own statements in those proceedings. It was also undisputed that a skilled artisan would have understood from the specification that all humanized anti-CGRP antagonist antibodies treat headache.

Lilly distinguished the precedent by focusing on the requirement that the antibodies be humanized, noting that humanized versions of those antibodies were absent from the prior art altogether and that the specification disclosed only one humanized version. The CAFC found this focus on humanization unpersuasive, and said the specification disclosed several examples of murine anti-CGRP antagonist antibodies and prior-art methods of humanization. “As the jury could have seen it, murine versions —themselves well known, with several examples disclosed—were just a routine (and likewise disclosed) procedure away from being humanized.”

The CAFC also rejected Lilly’s argument that, because humanizing an anti-CGRP antagonist antibody requires knowing its amino acid sequence, and because no such sequences were disclosed, an adequate written description was lacking. Substantial evidence showed that a skilled artisan possessing an anti-CGRP antagonist antibody could determine its amino acid sequence through known sequencing techniques.

Moreover, Lilly argued that because its product differs structurally and functionally from the sole humanized anti-CGRP antagonist antibody disclosed in the specification, the written description must be inadequate. The CAFC rejected this argument as well, finding that a reasonable jury could have found that a skilled artisan reading the specification would have understood that anti-CGRP antagonist antibodies could bind to different regions of CGRP and still accomplish the claimed function of treating headache.

Turning to enablement, Lilly argued that the number of candidate antibodies for inclusion in this genus is very large and that the specification does not tell a skilled artisan how to determine in advance which ones will antagonize CGRP. Lilly contended that the inventors left to others the “research assignment” of screening and testing those candidates, which would have been “so time-consuming and expensive as to constitute undue experimentation.”

Even assuming in Lilly’s favor that 1) making all anti-CGRP antagonist antibodies would have required screening and testing a very large number of candidate antibodies, and 2) that the amount of time and expense required would have constituted undue experimentation, the Federal Circuit explained that the asserted claims are not like the claims in Amgen Inc. v. Sanofi, 987 F.3d 1080, 1084 (Fed. Cir. 2021) and Baxalta Inc. v. Genentech, Inc., 81 F.4th 1362, 1366 (Fed. Cir. 2023).  The claims “do not claim humanized anti-CGRP antagonist antibodies themselves; instead, they claim only the use of such antibodies for the different, limited purpose of treating headache,” said the opinion. If they did, the case would resemble Amgen, where “the claims were to the entire genus of antibodies that (1) bind to specific amino acid residues on the protein PCSK9 and (2) block PCSK9 from binding to certain receptors.”

Given “the ‘well-known status’ of anti-CGRP antagonist antibodies and the routine nature of humanization, the more relevant ‘research assignment’ in this case would have been determining which humanized anti-CGRP antagonist antibodies treat headache,” wrote the CAFC. Here, the specification disclosed that all such antibodies work for that purpose. The CAFC concluded that undertaking to find or make all of them would be “more akin to extra credit than a necessary research assignment left to others to complete.”

Ultimately, the CAFC reversed the district court’s JMOL and remanded the case for further proceedings consistent with the opinion.