By Kevin E. Noonan –

The Federal Circuit reversed a District Court grant of judgment as a matter of law (JMOL) that overturned a jury verdict that defendant Eli Lilly had not satisfied the clear-and-convincing-evidence standard in challenging on Section 112(a) grounds claims asserted by Teva Pharmaceuticals in Teva Pharmaceuticals International v. Eli Lilly & Co.  In addition to providing a “man bites dog” aspect to the case, the opinion also sets forth circumstances where an insufficient disclosure in a patent specification relating to components of the claimed invention can be supplemented by the knowledge of one having ordinary skill in the art.

The case arose in patent infringement (not ANDA) litigation between the parties over claims in U.S. Patent Nos. 8,586,045; 9,884,907; and 9,884,908, relating to the use as a headache treatment (Teva’s Anjovy, Eli Lilly’s Emgality) comprising antibodies immunologically specific for calcitonin gene-related peptide (CGRP), wherein this protein can cause or exacerbate headache when binding to certain cell surface receptors and increasing blood flow thereby.  The antibodies prevent such binding and thus reduce or eliminate headache.  Claim 30 of the ‘045 patent is set forth as representative:

A method for reducing incidence of or treating headache in a human, comprising administering to the human an effective amount of an anti-CGRP antagonist antibody, wherein said anti-CGRP antagonist antibody is a . . . humanized monoclonal antibody.

The parties had been involved in several inter partes review (IPR) proceedings that had resulted in invalidation of Teva’s claims directed to the antibodies themselves (U.S. Patent Nos. 9,340,614; 9,266,951; 9,890,210; 9,346,881; 9,890,211; and 8,597,649).  The evidence from those IPRs according to the opinion was that murine anti-GCRP antibodies “were well known in the art” and that the art was “replete with exemplary disclosures of anti-CGRP antagonist antibodies,” as were methods for producing these antibodies (which were “extensively described”).  The antibodies recited in both the antibody and headache patents being humanized, Lilly had asserted evidence in the IPRs that humanization (modifying murine antibodies to be sufficiently human-like antibodies and thereby avoid immunological rejection) was “was a well-established and routine procedure” at the time these patents were filed.  On the other hand, Eli Lilly was unsuccessful in establishing for the Board that claims for methods of treating headache using these antibodies were invalid in view of the prior art.

In the face of a jury verdict that Eli Lilly had not satisfied the clear and convincing evidence standard to invalidate the asserted claims on § 112(a) grounds, the District Court granted JMOL on Eli Lilly’s § 112(a) defenses because, even though the jury could have reasonably found that murine anti-CGRP antibodies were known in the art and that the skilled artisan would have known how to make such antibodies, humanize such antibodies, and use such humanized antibodies to treat headache, as a matter of law the claims were invalid for failure to satisfy both the written description and enablement requirements of 35 U.S.C. § 112(a).

The Federal Circuit reversed and remanded, in an opinion by Judge Prost joined by Judge Cunningham and the Honorable Richard G. Andrews, District Judge, U.S. District Court for the District of Delaware, sitting by designation.  On de novo review under First Circuit law, the panel found that the District Court’s JMOL grant was not supported by evidence that “so strongly and overwhelmingly” was in Eli Lilly’s favor that “a reasonable jury could not have returned the verdict” that the claims were not invalid, under Acevedo-Diaz v. Aponte, 1 F.3d 62, 66 (1st Cir. 1993).  The opinion first addressed written description issues.  The opinion recites the now-established standard that for a genus claim the specification must disclose a representative number of species or structural features in common between the members of the genus; in this case, it was the “reasonable number of species” prong of the test that was at issue.  But the opinion also cautions that “there are no ‘bright-line rules governing . . . the number of species that must be disclosed to describe a genus claim, as this number necessarily changes with each invention,’” citing Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc), which many will recognize as the culmination of the development of written description jurisprudence beginning with Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997).  For their analysis of the issues supporting the jury’s decision (and that the District Court erred in granting JMOL), the panel turned to Ajinomoto Co. v. International Trade Commission (Fed. Cir. 2019), which stands for the proposition that when assessing the disclosure a specification is “read in light of the background knowledge in the art” that can establish that the representative number of species requirement was satisfied.  The Court then cited In re Herschler, 591 F.2d 693, 695 (C.C.P.A. 1979), for similar rubrics, where the invention was the use of dimethylsulfoxide (DMSO) to facilitate transfer of steroid drugs through the skin.  The written description requirement was satisfied in that case because, although only one species of steroid drug was disclosed, the skilled worker would have recognized that “while steroids ‘as drugs’ might vary broadly in their physiological activity, steroids ‘as a class of compounds carried through a layer of skin by DMSO’ appeared on the record to be ‘quite similar’” in the capacity to be more effectively transferred through the skin by DMSO.

Applying this precedent, the panel understood the invention to be a method using “anti-CGRP antagonist antibodies, or humanized versions thereof, to treat headache—not such antibodies themselves,” and that distinction is the basis for their opinion.  This shifts the focus away from the issues arising in Ariad and, more recently, Amgen v. Sanofi because the invention is this use, not the antibodies per se.  In a footnote, the opinion mentions Judge Bryson’s conclusion, sitting by designation in Erfindergemeinschaft UroPep GbR v. Eli Lilly & Co., 276 F. Supp. 3d 629, 648 (E.D. Tex. 2017), that “when a genus is well understood in the art and not itself the invention but is instead a component of the claim, background knowledge may provide the necessary support for the claim” (emphasis in opinion).

The opinion states that the basis for reversing the District Court’s grant of JMOL is whether a reasonable jury could have come to its original conclusion (i.e., that Lilly had not established invalidity under the written description requirement by clear and convincing evidence), illustrating the changing criteria used by the Court.  What might have required express disclosure 20 years ago no longer does so, because of the development of additional knowledge in the art in the interim, wherein the inventor is entitled to include what the person of ordinary skill in the art would understand to supplement what is expressly disclosed.  This brings to mind the admonition that “a patent need not teach, and preferably omits, what is well known in the art,” in Hybritech Incorporated v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1384 (Fed. Cir. 1986), citing Lindemann Maschinenfabrik GmbH v. American Hoist and Derrick Co., 730 F.2d 1452, 1463 (Fed. Cir. 1984).

According to the panel, the prior art had disclosed several murine versions and prior-art methods of humanization against a backdrop of anti-CGRP antagonist antibodies (and methods of making them) being well known and humanization being routine.  This supplies what was not explicitly disclosed but does not have to be in view of what was known in the art.  “And, critically, a skilled artisan would have understood from the specification that all humanized anti-CGRP antagonist antibodies treat headache,” according to the opinion.  Treating headache was what was claimed (“[a] method for reducing incidence of or treating headache in a human”) and it is this claim against which the written description requirement was properly applied by the jury according to the Court.

The panel reviewed and dismissed as lacking Eli Lilly’s arguments to the contrary.  These include that humanized versions of the therapeutic antibodies (anti-CGRP antagonist antibodies) were not known in the art.  The panel rebutted this argument with the facts that murine versions of humanized versions of the therapeutic antibodies were known and the skilled artisan would understand methods for humanizing that were also known in the art.  This conclusion was supported by the Ariad decision, wherein a specification need not show an actual reduction to practice in order to satisfy the written-description requirement and that, at the time the application was filed amino acid sequencing of antibodies was routine.  Eli Lilly also cited Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir. 2004), for the principle that claims to methods of use require written description disclosure of what is used in the methods.  The Federal Circuit distinguished that opinion because in Rochester “the specification did not disclose any compounds usable in the claimed methods, nor was there any evidence that such compounds were known.”  The Court apparently recognized (without expressly stating so) that the Rochester claims were so-called “single means claims,” i.e., “methods of doing X using something that does X,” while in Ariad the claims were to “methods of doing X, and the claims ‘encompass[ed] the use of all substances’ that did X.”

The opinion then turns to Eli Lilly’s argument regarding the “structural or functional differences among the genus of humanized anti-CGRP antagonist antibodies” (there are three of them, although the anti-CGRP antagonist antibody disclosed in the specification bound only one of them).  In rejecting this argument, the opinion states 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,’” once again applying the written description standard to what was claimed, treating headache.  Lilly (also unsuccessfully) argued that, because its product differs structurally and functionally from the sole humanized anti-CGRP antagonist antibody disclosed in the specification, written description must be inadequate for a lack or “representativeness,” citing AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 1301 (Fed. Cir. 2014).  The Court rejects this argument because written description provides no “bright-line rules governing . . . the number of species that must be disclosed to describe a genus claim, as this number necessarily changes with each invention” and that:

[A] skilled artisan reading the specification would have understood that anti-CGRP antagonist antibodies were well known (and disclosed), that humanizing [antibodies] was routine (and disclosed), and that, insofar as treating headache is concerned, all humanized versions of such antibodies work [in the claimed method].

With regard to enablement, the panel asserted the standard that a disclosure must be “at least commensurate with the scope of the claims” under Amgen Inc. v. Sanofi, 987 F.3d 1080, 1084 (Fed. Cir. 2021), aff’d 598 U.S. 594 (2023).  Lilly makes the conventional breadth argument (unsuccessfully) regarding purportedly undue experimentation required to enable all anti-CGRP antagonist antibodies.  The Court concedes that if enablement required “screening and testing” the expected “very large number of candidate antibodies” to identify anti-CGRP antagonist antibodies, even if routine at the time the application was filed, it would constitute undue experimentation under Idenix Pharms. LLC v. Gilead Scis. Inc., 941 F.3d 1149, 1163 (Fed. Cir. 2019).  But the opinion distinguishes this required scope of enablement based on differences between composition claims and methods of using compositions not otherwise claimed, stating that “[t]he asserted claims here are unlike the claims in Amgen and Baxalta [Inc. v. Genentech, Inc., 81 F.4th 1362, 1366 (Fed. Cir. 2023)], however, because they 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.”  Here, “[i]n light of 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” according to the opinion.

Finally the Court distinguishes the situation in this case over that in Idenix because in that case there was no evidence that all the undisclosed species had the claimed structure, whereas in this case “it is undisputed that a reasonable jury could have found that all humanized anti-CGRP antagonist antibodies treat headache, thereby obviating any extensive screening to determine which ones do.”                                                                                      

As with all cases regarding sufficiency of disclosure, the outcome relied heavily on the facts.  To the extent that this decision provides any strategic recommendations it was the focus in the claims regarding methods for treating a specific ailment (headache) using known antibodies (anti-CGRP antagonist antibodies) to a known antigen (CGRP) or antibodies that could be produced using known methods (humanization), all in view of the understanding of the skilled artisan.  Also important was the capacity of all anti-CGRP antagonist antibodies to achieve the headache-relieving effect.  This case brings to mind opportunities for using (however counterintuitively) acknowledgment of what is known in the art (which Eli Lilly did not do in pursuit of claims to anti-CGRP antagonist antibodies lost in IPR) to provide sufficient support for what is not (using the anti-CGRP antagonist antibodies for treating headache).

* Eli Lilly was likely precluded by the provisions of 35 U.S.C. § 315(e)(2) from asserting these defenses at trial due to the PTAB and Federal Circuit’s determinations to the contrary in the IPRs.

Teva Pharmaceuticals International v. Eli Lilly & Co. (Fed. Cir. 2026)
Panel: Circuit Judges Prost and Cunningham and District Judge Andrews
Opinion by Circuit Judge Prost