. . . trial testimony established that “there are a ‘mind-bogglingly large’ number of antibodies that could potentially fit within the scope” of the patent claims but “the actual number is not ‘knowable. . . .’”
In Teva Pharm. Int’l GmbH v. Eli Lilly & Co., No. 18-cv-12029 (D. Mass. Sep. 26, 2023), the United States District Court for the District of Massachusetts set aside the jury’s $176 million verdict of patent infringement in plaintiff Teva’s favor by granting defendant Elli Lilly’s post-trial Rule 50(b) motion for judgment as a matter of law. The court ruled that Teva’s asserted patent claims were invalid because the patents lacked a written description of the invention commensurate with the claims’ scope and failed to enable the full scope of the claimed inventions.
The three asserted Teva patents, U.S. Patent Nos. 8,586,045; 9,884,907; and 9,884,908, each share a common specification and have claims directed to methods for treating headaches that involve blocking the binding function of a headache inducing protein called “calcitonin gene-related peptide (“CGRP protein”). The claimed methods involve administering effective dosage amounts of humanized anti-CGRP antibodies that bind to and block the CGRP proteins’ headache inducing activity by pre-occupying its binding sites at specific complementary determining regions (“CDR”), thereby inactivating the proteins’ disease-causing function. A “humanized” antibody is an animal antibody adapted in the laboratory for compatibility with the human immune system.
The trial testimony established that “there are a ‘mind-bogglingly large’ number of antibodies that could potentially fit within the scope” of the patent claims but “the actual number is not ‘knowable.’” Opinion at 15 (emphasis in original). Such functionally compatible antibodies have amino acid sequences that form structural shapes matching the target CDR of the CGRP proteins in a manner that facilitates their binding. At trial, however, Teva’s expert conceded that an antibody’s potential CGRP binding properties cannot be predicted by its amino acid sequences but instead must be assessed through a series of in vitro an in vivo testing. Id. at 15-16. The parties’ experts appeared to agree that as of the patents’ priority date, the process of “humanizing” any antibody candidate could require “many months” of work and cost “maybe half a million dollars.” Id. at 16.
The court began its written description analysis by noting that the Patent Act requires each patent to “contain a written description of the invention.” Id. at 17 (quoting 35 U.S.C. § 112). The court explained that a patent’s written description is viewed from the perspective of a person of ordinary skill in the art and thereby “incorporates the knowledge in the prior art” as a supplement to the patent’s written description. Id. at 18-19. In practice, the scope of a patent’s claimed subject matter must not exceed the scope of the patent’s written description of the invention.
In cases such as this one, where the patents claim a broad genus of antibodies using functional language, the written description must provide either “a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 18 (quoting AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1299 (Fed. Cir. 2014)); see also Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1335 (Fed. Cir. 2021). The court therefore reviewed the trial record regarding (1) the scope of Teva’s asserted patent claims, (2) the number of species of the invention disclosed in the patents’ specification, and (3) the disclosure of common structural features of the claimed antibodies that identify a particular antibody as a member of the claimed genus.
Regarding the scope of the patent claims, the court determined that “even viewing the evidence in the light most favorable to the verdict, the Asserted Claims are broad,” generally covering methods of using humanized anti-CGRP antibodies to treat headaches. Id. at 20. In the court’s view, the breadth of the claims was underscored by their “lack of structural limitations” and lack of an identification of “any narrower amino acid sequence or structure of antibodies possessing those functions.” Id. at 20-21. The court noted that the claims’ breadth requires a written description of the invention commensurate with their broad scope that either discloses “sufficient representative species” or identifies common structural antibody features related to the claimed functions that would enable a person of ordinary skill in the art to recognize an antibody’s membership in the claimed genus. Id. at 21-22.
In the court’s view, a reasonable jury could have found only that the patents’ common specification disclosed no more than one representative species—a humanized anti-CGRP antibody referred to in the patents as the “G1” antibody. Id. at 24. Although the patents disclosed up to 84 variants of the G1 antibody, none of the variants were full-length antibodies with antagonist activity against CGRP protein. Id. The court further concluded that the alternative murine antibodies disclosed in the patents “are not representative species” of the invention because none of the murine antibodies had been humanized. Id. at 25-26. The court noted that in other situations, the disclosure of a single species provided adequate written description support where the patent specification additionally demonstrated a known correlation between the claimed function and the structure of the single embodiment of the invention disclosed in the patent. Id. at 33-34 (citing Invitrogen Corp. v. Clontech Lab'ys, Inc., 429 F.3d 1052, 1073-74 (Fed. Cir. 2005)).
Here, however, the court pointed to undisputed evidence that Teva’s patents were the first to disclose the method of using humanized anti-CGRP antibodies to treat headaches. The prior art knowledge, therefore, did little to supplement an understanding of the single G1 antibody’s structural relationship with the claimed functions. Id. at 37-38. The court further relied on Teva’s apparent concession that identification of additional embodiments “would depend entirely on testing,” leading the court to conclude that the patent’s specification, at most, presented “‘only a research plan, leaving it to others to explore the unknown contours of the claimed genus.’” Id. at 38 (quoting Abbvie, 759 F.3d at 1300).
In reaching that conclusion, the court rejected Teva’s suggestion that the patents, in fact, did disclose common structural features such as the antibodies’ Y-shaped structure and complementarity with CGRP. Id. at 40. The court noted that all full-length antibodies have a “Y-shaped structure” and that the asserted “complementarity with CGRP” merely begs the question unanswered by the patents, i.e., which amino acid sequences or other structural features of an antibody provide the necessary complementarity with CGRP? Id. at 41. For these and other related reasons, the court determined that even when viewing the evidence in the light most favorable to the verdict, no reasonably jury could find that Teva’s patents provide an adequate written description of the invention.
Turning to the issue of enablement, the court recited the Patent Act’s requirement that each patent must “teach the public how ‘to practice the full scope of the claimed invention.’” Id. at 41-42 (quoting 35 U.S.C. § 112). The court acknowledged that this enablement requirement presumes the relevant knowledge and skill in the art and permissively requires only that the patent’s disclosure teach an ordinary person of skill in the art how to practice the invention “without undue experimentation.” Id. (citing Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080, 1084 (Fed. Cir. 2021); In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988) (undue experimentation factors)).
The court, however, recognized that the extent of the required enabling disclosure depends on the scope of the patent’s claims. In other words, “‘the more a party claims, the broader the monopoly it demands, the more it must enable.’” Id. at 45 (quoting Amgen v. Sanofi, 598 U.S. 594, 613 (2023)). The court’s enablement analysis, therefore, largely paralleled its written description analysis, beginning with a review of the patents’ claim scope which includes “the entire functionally-defined genus of humanized anti-CGRP antagonistic antibodies.” Id. at 46. In contrast to that broad claim scope, the patents’ “specification disclosed only one covered antibody”—the G1 antibody. Id. Moreover, because the patents failed to disclose any common amino acid sequences or other structures relevant to the claimed functions, a person of ordinary skill in the art “could not predict whether any [potential candidate] antibody would satisfy the claims.” Id. A person of ordinary skill in the art, therefore, attempting to make one of the claimed antibodies would be resigned to a “trial and error” process of identifying, making, and testing candidate antibodies which Teva conceded could “take months and cost at least tens of thousands of dollars per antibody.” Id. at 46-47.
The court did not expressly reject Teva’s contention that making, testing, and humanizing antibodies according to the in vitro and in vivo assays disclosed in the patents’ specification could be described as “routine” work. The court, however, found that Teva’s patents did little more than other invalidated patents which “disclosed ‘only a starting point for further iterative research in an unpredictable and poorly understood field.’” Id. at 47 (quoting Wyeth & Cordis Corp. v. Abbot Lab'ys, 720 F.3d 1380, 1385 (Fed. Cir. 2013)). The court explained that “even if the jury concluded that the state of the art was generally predictable in the sense that anti-CGRP antagonist antibodies would treat headache, that does not change the fact that, . . . each potential antibody would have to be synthesized and screened for effectiveness.” Id. 48-49.
In other words, although the synthesis and screening work might be routine, there was no guidance in the patent for identifying or making antibodies with specific amino acid sequences or other structures that perform the claimed functions. At most, the patents disclosed a new research objective—finding antibodies that antagonize CGRP protein—while providing only in vitro and in vivo assays to aid researchers in their quest to find such antibodies among a “‘mind-bogglingly large’ number of antibodies that could potentially fit within the scope” of the claims. Id. at 15. The court therefore determined that based on these facts, a reasonable jury could only find that the full scope of the patents’ claims is not enabled by their disclosure and therefore ruled as a matter of law that the claims are invalid.
This case and the several cases recited by the court in its decision present cautionary precedent to patent drafters in the biological arts, especially in pioneering subject matter involving complex living systems that resist full comprehension. Where the patent claims describe the claimed subject matter by reference to its function, this precedent signals the safer course of describing common structural features relevant to the claimed function. The precedent, however, sympathizes with those situations in which such structural description may not be feasible and allows for the alternative disclosure of representative species of the claimed genus, which should be as numerous and diverse as practicable. Whatever constraints may be faced in drafting the patent’s specification, care should be taken that the scope of the claims, at least a narrowed set of dependent claims, is faithful to the scope of the patent’s written description.
* * *
As a pathfinder in global disputes resolution, YMF Law Tokyo leverages three decades of experience in complex cross-border litigation in representing Japanese clients before U.S. courts and assisting U.S., European, and other clients located outside of Japan in coordinating local investigations and disputes in Japan with Japanese counsel. If we can be of assistance, please use the contact inquiry form at https://ja.ymf-law.com or email directly to york.faulkner@ymf-law.com.