New York Law Journal: The 'Amgen v. Sanofi' Enablement Battle and Best Practices in Light of the Federal Circuit's 112(a) Opinion on Broad, Functional Genus Claims
The U.S. Supreme Court will soon decide a petition for writ of certiorari filed by Amgen in its longstanding patent suit against Sanofi concerning cholesterol-lowering monoclonal antibody therapy. Amgen specifically seeks rulings from the Supreme Court on the issue of enablement, as codified in 35 U.S.C. §112(a). The petition comes after years of litigation between Amgen, the maker of the anti-cholesterol drug Repata, and Sanofi, the maker of a competitor drug Praluent. Amgen’s asserted patent claims have twice been found valid by juries, but repeatedly held to be invalid for lack of enablement by the District Court of Delaware and the U.S. Court of Appeals for the Federal Circuit.
35 U.S.C. §112(a) requires that a patent’s specification must contain “a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same.”
Amgen’s petition asks the Supreme Court to consider the following two questions:
(1) Whether enablement is “a question of fact to be determined by the jury” as the Supreme Court held in Wood v. Underhill, 46 U.S. (5 How.) 1, 4 (1846), or “a question of law that [the court] review[s] without deference,” as held by the Federal Circuit;
(2) Whether enablement is governed by the statutory requirement that the specification teach those skilled in the art to “make and use” the claimed invention, 35 U.S.C. §112, 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.’”
Elevated levels of low-density lipoprotein (LDL) cholesterol, colloquially known as the “bad” cholesterol, contributes to heart disease. The body regulates LDL levels through LDL receptors on the outside of cells, which act to remove LDL cholesterol from the blood. An enzyme called PCSK9 binds to these LDL receptors, causing them to degrade. This decreases the number of LDL receptors, which in turn increases circulating LDL levels.
The two related patents-in-suit, U.S. Patent Nos. 8,829,165 and 8,859,741, are directed to a genus of monoclonal antibodies that bind and block PCSK9 so that LDL receptors do not degrade and can continue to regulate the amount of LDL cholesterol in the bloodstream. The two patents share a common specification that discloses amino acid sequences for twenty-six different antibodies, including the antibody referred to as 21B12, which Amgen markets and sells as Repatha. The specification discloses the structures of both 21B12 as well as the antibody known as 31H4, and illustrates specifically where the two antibodies bind to PCSK9. The patent claims cover more than those two particular antibodies, however, and instead cover a genus of antibodies in functional terms by describing how the antibodies act, as opposed to their structure. Specifically, the claims cover all antibodies that bind to certain amino acids on PCSK9 and block its binding to receptors. Claim 1, illustrative of the ‘165 patent, is reproduced here: “An isolated monoclonal antibody, wherein, when bound to PCSK9, the monoclonal antibody binds to at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.”
Prior to the issuance of the patents-in-suit, Amgen was granted U.S. Patent No. 8,030,457, which covered just the particular amino acid sequence of 21B12. Sanofi holds a patent on a different antibody that can also bind to PCSK9. Both patents claimed the particular antibodies by their amino acid sequence, as opposed to how they functioned. It was only later that Amgen was granted additional patents to the broader genus claims, asserting them against Sanofi within a matter of days.
At the trial court in the District of Delaware, Amgen brought an action against Sanofi for patent infringement. Sanofi stipulated to infringement and asserted invalidity defenses under 35 U.S.C. §112. A first jury found the claims were enabled under §112, but the District Court subsequently granted Sanofi’s JMOL, holding that the claims of Amgen’s asserted patents were invalid for lack of enablement. On appeal, the Federal Circuit vacated the District Court’s invalidity holding and remanded for a new trial. After a second trial, a jury again found the claims were enabled. Again, the District Court overturned the jury’s verdict on JMOL on enablement grounds. Amgen appealed to the Federal Circuit for a second time, and a panel consisting of J. Prost, Lourie, and Hughes affirmed, holding that the claims required undue experimentation to obtain antibodies within the scope of claims and were thus invalid for lack of enablement. On November 18, 2021, Amgen filed a Petition for a writ of certiorari. While cert has not yet been granted, the Supreme Court recently sought a view of the case by the federal government requesting that the U.S. Solicitor General file a brief in the case.
Is Enablement a Question of Law or Fact?
The first question Amgen propounds is “whether enablement is a question of law or fact”—an issue not briefed by the parties below. Amgen questions the Federal Circuit’s statement in its opinion that “[w]hether a claim satisfies the enablement requirement of 35 U.S.C. §112 is a question of law.” Amgen v. Sanofi, Aventisub, 987 F.3d 1080, 1084 (Fed. Cir. 2021). Amgen asserts in its petition that by making enablement a question of law, the Federal Circuit “licenses courts to substitute their judgments, sub silentio, on disputed issues that ‘it was the right of the jury to determine.’” Brief for Petitioner, Amgen v. Sanofi, (petition for cert. filed Nov. 18, 2021) (No. 21- 757), 2021 WL 5506421, at *20. Amgen argues that the Supreme Court already answered the question in Wood v. Underhill, 46 U.S. 1, 4 (1846) when that court determined that enablement was “a question of fact to be determined by the jury.” Id. at 6.
In its opposition to Amgen’s petition, Sanofi asserts that the Federal Circuit has long held that patent validity is a “question of law with underlying factual questions” and that courts have always retained the right to make rulings on issues, including purely factual issues, based on an insufficient evidentiary showing. Brief for Respondent, Amgen v. Sanofi, (petition for cert. filed Nov. 18, 2021) (No. 21-757), 2022 WL 811154, at *18-19. Sanofi’s opposition argues that Wood explicitly stated that “when the specification of a new composition of matter gives only the names of the substances which are to be mixed together, without stating any relative proportion, undoubtedly it would be the duty of the court to declare the patent … void.” Id. at *22. Sanofi also argues that the issue is not proper for cert because the question was not briefed in the lower courts. Id. at *24-25.
The Enablement Standard for Functional Genus Claims
Amgen’s second question concerns the standard for enablement of functional genus claims. In finding that the claims were not enabled, the Federal Circuit had summarized various prior decisions on enablement of functional claims. It then applied the Wands factors to determine whether a person of ordinary skill in the art would be able to practice the claimed invention without “undue experimentation.” Amgen, 987 F.3d at 1084. The Wands factors are: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. Id.
The Federal Circuit first focused on the broad, functional nature of the claims, noting that this poses “high hurdles in fulfilling the enablement requirement.” Id. at 1087. The court stated that “it is important to consider the quantity of experimentation that would be required to make and use, not only the limited number of embodiments that the patent discloses, but also the full scope of the claim.” Id. at 1086. The opinion emphasized the significant delta between Amgen’s broad claims and the disclosed examples in the specification, and the ‘‘substantial time and effort” that would be required to obtain embodiments outside the scope of the disclosed examples and guidance. Id. The opinion also noted that the invention was in an “unpredictable field of science with respect to satisfying the full scope of the functional limitations” and that because the scope of the claims encompassed “millions of candidates claimed with respect to multiple specific functions,” a person of skill would need to “first generate and then screen each candidate antibody” to determine whether it meets the functional claim limitations. Id. at 1087- 88.
Amgen took issue with the Federal Circuit’s emphasis that the specification must enable the “full scope of the claim.” Brief for Petitioner at *11-13. In its petition, Amgen argues that the Federal Circuit had “rewritten the substantive enablement standard” for genus claims by invalidating genus claims if “substantial time and effort” would be required, rather than simply whether persons of art could “make and use” the invention per the plain language of §112. Id. at *12. Amgen states that this “new” enablement standard “defies test, precedent, and policy.” Id. at *25. Amgen’s petition asserts that precedent requires the party challenging validity to prove “‘concrete identification of at least some embodiment’ that cannot be made without undue experimentation,” which Sanofi had not done. Id. at *28.
Amgen does not dispute the broad nature of its genus claims, but rather the sufficiency of its patents’ disclosure, arguing that the patents-in-suit were a “rich handbook,” providing a “wealth of information” about the claimed antibodies.” Id. at *8. Amgen notes that the specification disclosed the amino acid sequence of 26 of these antibodies and that persons of art “can also follow the patents’ step-by-step “roadmap,” which teaches artisans to generate antibodies across the scope of the claims using “routine and well-known” techniques, including “‘immunizing mice,’ specifically tailored to produce the claimed antibodies” and “can use ‘automated high throughput techniques’ to select antibodies within the claims “ ‘quickly, efficiently, and cheaply.’” Id. at *32- 33.
In opposition, Sanofi asserts that the statutory requirement is clear that a “patentee has not fulfilled the statutory requirement—or its end of the bargain—if the patent describes how to make and use only part of the invention,” and that Amgen never disputed that enablement requires making and using the “full scope” of the claimed invention when these were given as jury instructions in the district court cases. Brief for Respondent at *30-31. Sanofi argues that Amgen’s genus claims cover “‘a vast scope of possible antibodies,’ reaching ‘millions’ if not ‘an astronomically large number’” and emphasized that Amgen’s own witnesses were “unable even to estimate the number of antibodies within the claims scope” but testified that “following the patents’ teaching would generate ‘millions and millions of antibodies.’” Id. at *8. Sanofi’s opposition also argues that a skilled person would have to test “every single antibody generated by Amgen’s disclosed methods to determine whether it had the necessary functional properties.” Id.
While the Federal Circuit’s “full scope of the claim” standard as applied to functional claims is not entirely new, its opinion did not reconcile this standard with precedent establishing that claim coverage of some inoperative embodiments would not necessarily invalidate a claim. See Wyeth & Cordis v. Abbott Labs., 720 F.3d 1380, 1384 (Fed. Cir. 2013); Idenix Pharms. v. Gilead Scis., 941 F.3d 1149, 1154 (Fed. Cir. 2019); Crown Operations Int’l, Ltd. v. Solutia, 289 F.3d 1367, 1380 (Fed. Cir. 2002). Further, because neither Sanofi nor the Federal Circuit identified a particular embodiment that was not enabled, the Federal Circuit’s decision may, effectively, shift the burden of proving enablement to the patent holder by requiring the owner to show that the full breadth of the claims are enabled.
The Federal Circuit’s opinion and a potential Supreme Court affirmance may have far-reaching implications, and it appears, at least for now, that broad functional genus claims will be scrutinized, and patent draftsmen and patent holders asserting such claims should beware of enablement challenges. And, only time will tell how “devastating” the effect on innovation will be, as Amgen’s petition warns. Brief for Petitioner at *3, 25. In the meantime, patent prosecutors should heed the Wands factors when drafting specifications and claims and close attention should be paid to those factors that are in their control, such as the amount of direction and embodiments given in the specification. Further, subgenus claims and species claims should always be included, just in case the broader genus claim is invalidated. Litigants should expect that enablement of broad, functional, genus claims will be challenged. So, proofs of enablement should be gathered and developed early in the litigation, and expert witnesses chosen carefully, especially because tensions may arise between issues related to enablement and other invalidity theories, particularly obviousness.
The Supreme Court will hopefully establish clear precedent sooner rather than later, especially since the question goes to the very heart of the quid pro quo bargain that the American patent system is based upon—that in exchange for a full disclosure of an invention to the public, the inventor is granted an exclusive right to that invention for a set period of time. The Supreme Court has often disagreed with the Federal Circuit—we shall see if this is yet another of those disagreements.
Reprinted with permission from the June 1, 2022 issue of the New York Law Journal. © 2022. ALM Media Properties, LLC. Further duplication without permission is prohibited. All rights reserved.