IP Law Daily, PATENT—U.S.: High Court affirms Federal Circuit’s narrow enablement approach, (May 18, 2023)

By Cheryl Beise, J.D.

Claims of two Amgen patents covering a genus of cholesterol-lowering antibodies called for undue experimentation.

In a unanimous opinion authored by Justice Gorsuch, the U.S. Supreme Court has affirmed a Federal Circuit decision finding that certain claims of two Amgen patents reciting a broad genus of antibody compounds for reducing low-density lipoprotein cholesterol (LDL-C), or bad cholesterol, are invalid for lack of enablement. The High Court agreed that Amgen failed to enable all that it has claimed, even allowing for a reasonable degree of experimentation. The approaches recited in the claims for identifying the claimed antibodies merely described Amgen’s trial-and-error method for finding functional antibodies or called for undue experimentation, given the state of the art. “These two approaches amount to little more than two research assignments,” the Court said (Amgen Inc. v. Sanofi, May 18, 2023, Gorsuch, N.).

This case involves the validity of inventions directed to monoclonal antibodies that help reduce low-density lipoprotein cholesterol (LDL-C), or bad cholesterol. These antibodies inhibit the operation of a naturally occurring protein known as PCSK9, which degrades LDL receptors and contributes to high cholesterol levels. Amgen’s markets a PCSK9-inhibiting drug under the name Repatha and Sanofi markets one under the name Praluent. In 2011, Amgen obtained a patent for the antibody employed in its drug, and Sanofi received one covering the antibody used in its drug. Each patent describes the relevant antibody by its unique amino acid sequence.

The dispute in this case concerns two additional patents Amgen obtained in 2014 relating back to the 2011 patent: U.S. Patent Nos. 8,829,165 (the ’165 patent) and 8,859,741 (the ’741 patent), both titled “Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9).” The patents disclose 26 example antibodies, characterized by amino-acid sequences that perform two functions: binding to specific amino acid residues on PCSK9 and blocking PCSK9 from binding to LDL receptors. The patents further describe two methods—a step-by-step “roadmap” and a “conservative substitution” that could be used to make additional antibodies (beyond the 26 examples) that perform the binding-and-blocking functions described in the claims. The “roadmap” directs scientists to: (1) generate a range of antibodies in the lab; (2) test those antibodies to determine whether any bind to PCSK9; (3) test those antibodies that bind to PCSK9 to determine whether any bind to the sweet spot as described in the claims; and (4) test those antibodies that bind to the sweet spot as described in the claims to determine whether any block PCSK9 from binding to LDL receptors. The “conservative substitution” technique requires scientists to: (1) start with an antibody known to perform the described functions; (2) replace select amino acids in the antibody with other amino acids known to have similar properties; and (3) test the resulting antibody to see if it also performs the described functions.

Litigation history. In 2014, Amgen Inc., Amgen Manufacturing, Ltd., and Amgen USA, Inc. (collectively, Amgen) sued Sanofi, Aventisub LLC, Regeneron Pharmaceuticals Inc., and Sanofi-Aventis U.S. LLC (collectively, Sanofi) for infringement of several patents, including the ’165 patent and the ’741 patent. Amgen and Sanofi stipulated to infringement of selected claims, including claims 19 and 29 of the ’165 patent and claim 7 of the ’741 patent, and tried issues of validity to a jury in March 2016. The jury determined that the patents were not shown to be invalid for lack of enablement and written description. The Federal Circuit affirmed in part and reversed in part, concluding that the district court erred in its evidentiary rulings and jury instructions regarding Sanofi’s written description and enablement defenses. The case was remanded for a new trial on the issue of written description and enablement.

Following remand, the jury again found that Sanofi failed to prove that the asserted claims were invalid for lack of written description and enablement. The district court, however, granted Sanofi’s motion for judgment as a matter of law for lack of enablement but denied the motion for lack of written description. On February 11, 2021, the Federal Circuit affirmed, agreeing that the patent claims are not enabled because they require undue experimentation. The Federal Circuit later denied Amgen’s petition for en banc rehearing. The Federal Circuit found that the methods the Amgen patents outlined for generating additional antibodies failed to provide significant guidance or direction to a person of ordinary skill in the art for the full scope of the claims. The evidence showed that the scope of the claims encompasses millions of candidates claimed with respect to multiple specific functions, and that it would be necessary to first generate and then screen each candidate antibody to determine whether it meets the double-function claim limitations. Because the claims would require undue experimentation, or a trial-and-error process of discovery, they were invalid for lack of enablement.

Amgen’s petition for certiorari presented two questions, but the Supreme Court agreed only to consider one: 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.’” Amgen’s unreviewed question had asked whether enablement is “a question of fact to be determined by the jury.”

Enablement. Under the Patent Act’s enablement provision, 35 U.S.C. § 112(a), 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 make and use the [invention].” To prove that a claim is invalid for lack of enablement, a challenger must show by clear and convincing evidence that a person of ordinary skill in the art would not be able to practice the claimed invention without undue experimentation. The purpose of the enablement requirement is to ensure that the public is told how to carry out the invention, i.e., to make and use it.

The Supreme Court noted that while Congress has revised the patent laws over time, it has left the “enablement” obligation largely intact. The Court then reviewed its own jurisprudence addressing enablement, including Wood v. Underhill, 5 How. 1 (1846); O’Reilly v. Morse, 15 How. 62 (1854); The Incandescent Lamp Patent, 159 U. S. 465 (1895); Minerals Separation, Ltd. v. Hyde, 242 U. S. 261 (1916); and Holland Furniture Co. v. Perkins Glue Co., 277 U.S. 245 (1928). These early cases reinforced the principle that the specification must enable the full scope of the invention as defined by its claims. “The more one claims, the more one must enable,” the Court said. “If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class.”

“That is not to say a specification always must describe with particularity how to make and use every single embodiment within a claimed class,” the Court added. The Court noted that in some cases, disclosing a general quality may reliably enable a person skilled in the art to make and use all of what is claimed, not merely a subset. The Court also observed that a specification is not necessarily inadequate just because a skilled artist must engage in some measure of adaptation or testing. The amount of experimentation that is reasonable depends on the nature of the invention and the underlying art, the Court explained.

Scope of Amgen’s patents. Turning to claims 19 and 29 of the ’165 patent and claim 7 of the ’741 patent, the Supreme Court agreed with the Federal Circuit that Amgen failed to enable all that it claimed, even allowing for a reasonable degree of experimentation. Like the patents found invalid in Morse, Incandescent Lamp, and Holland Furniture, Amgen’s patents seek “to monopolize an entire class of things defined by their function—every antibody that both binds to particular areas of the sweet spot of PCSK9 and blocks PCSK9 from binding to LDL receptor,” the Court determined. “Much as Morse sought to claim all telegraphic forms of communication, Sawyer and Man sought to claim all fibrous and textile materials for incandescence, and Perkins sought to claim all starch glues that work as well as animal glue for wood veneering, Amgen seeks to claim ‘sovereignty over [an] entire kingdom’ of antibodies,” the Court said, citing Incandescent Lamp, 159 U.S., at 476.

Amgen argued that its broad claims are enabled because scientists can make and use every undisclosed but functional antibody if they simply follow the company’s “roadmap” or its proposal for “conservative substitution.” The Court disagreed. “These two approaches amount to little more than two research assignments,” the Court said. The roadmap “merely describes step-by-step Amgen’s own trial-and-error method for finding functional antibodies—calling on scientists to create a wide range of candidate antibodies and then screen each to see which happen to bind to PCSK9 in the right place and block it from binding to LDL receptors.” The conservative substitution “requires scientists to make substitutions to the amino acid sequences of antibodies known to work and then test the resulting antibodies to see if they do too—an uncertain prospect given the state of the art.”

Amgen also contended the Federal Circuit erred by conflating the question whether an invention is enabled with the question of how much time it takes a person skilled in the art to make every embodiment within a broad claim. While the Court agreed that “enablement is not measured against the cumulative time and effort it takes to make every embodiment within a claim,” it did not appear the Federal Circuit thought otherwise. The Federal Circuit found Amgen offers persons skilled in the art little more than advice to engage in “trial and error.”

Amgen next argued that the Federal Circuit erroneously “raise[d] the bar” for enablement of claims that encompass an entire “genus” of embodiments defined by their function. The Court agreed with Amgen that there is one statutory enablement standard, but the Court did not find the Federal Circuit to have thought differently. Instead, the Federal Circuit recognized only that the more a party claims for itself the more it must enable.

Lastly, Amgen contended that affirming the Federal Circuit’s decision in this case would risk “destroy[ing] incentives for breakthrough inventions.” The Court declined to address this argument, noting that it is up to Congress “to strike the balance between incentivizing inventors and ensuring the public receives the full benefit of their innovations.” In enacting Section 112, Congress has determined that “if an inventor claims a lot, but enables only a little, the public does not receive its benefit of the bargain,” the Court said.

Practitioner commentary. Vincent K. Shier, Ph.D., a partner in the Intellectual Property Practice Group in Haynes Boone’s Washington, D.C. office, said in a statement to IP Law Daily that the Court’s opinion today appears to be consistent with the trend over the past decade which has increasingly focused on limiting claim scope.

While the Court agreed with Amgen that functional/genus claims should not be held to a stricter standard of enablement, in Shier’s view, the practical effect of the decision will be that the genus claims of any scope and regardless of technology will now be harder to obtain and even harder to defend. “Although the subject matter at issue in Sanofi was monoclonal antibodies, in this decision, SCOTUS gave a clear indication that this arguably heightened standard of enablement should and will be applied across all areas of technology,” Shier observed. “Indeed, many patents currently in force are now very susceptible to invalidity attacks based on enablement.”

According to Shier, the decision has left many questions unanswered. “For example, if 26 species and a ‘roadmap’ for identifying more members of the claimed genus is not enough, what would be? Is all ‘trial-and-error’ experimentation necessarily undue experimentation? If the ‘trial-and-error’ experimentation is nonetheless routine, is it still undue experimentation? What is the impact of inoperable embodiments?”

As a result of this uncertainty, Shier predicts that innovators will likely need to pursue a larger number of patents of narrower scope. “However, on a day when the USPTO is holding a public hearing on its proposal of patent fee increases which would make it substantially more expensive for stakeholders to exploit the full scope of their invention (e.g., new surcharge on continuation applications) this is not very welcomed news in many sectors,” Shier said.

Christopher Cowles, an intellectual property partner in Withers’ Boston Office, opined that today’s decision “confirms the Court's hostility to Amgen's assertion that Amgen's identification of a ‘sweet spot’ in the naturally-occurring PCSK9 protein entitled Amgen to monopoly protection of the full scope of all antibodies encompassed by the composition-of-matter claims of Amgen's '165 (US Patent No. 8,829,165) and '741 (US Patent No. 8,859,741) patents.”

Hearkening back to oral argument, Cowles observed that Amgen’s counsel was in the unenviable position of attempting to support Amgen's enablement of all such claimed antibodies. In contrast, according to Cowles, “Sanofi counsel’s characterization of both the law (enablement requires that a skilled artisan would be able to make and use the claimed invention, without reliance upon undue experimentation) and the science (notably referring to an expert Declaration penned by Sir Gregory Winter) respectively undermined Amgen's assertions regarding the predictability of the genus of antibodies claimed, thereby highlighting the lack of enablement of Amgen’s disputed claims.”

In Cowles’s view, the ultimate impact of the Court’s ruling today “should be one of harmonizing USPTO patentability standards in the antibody therapeutic space with literally all other areas of biologic therapeutics—including nucleic acids therapeutics—in a long-overdue acknowledgement of the unpredictability of development of safe and effective biologics in all such areas of research and development.”

The case is No. 21-757.

Attorneys: Jeffrey Alan Lamken (Mololamken LLP) for Amgen Inc., Amgen Manufacturing, Ltd. and Amgen USA, Inc. Paul D. Clement (Clement & Murphy, PLLC) for Sanofi, Aventisub LLC, Regeneron Pharmaceuticals, Inc. and Sanofi-Aventis U.S. LLC. Vincent K. Shier (Hayes and Boone, LLP). Christopher Cowles (Withers).

Companies: Amgen Inc.; Amgen Manufacturing, Ltd.; Amgen USA, Inc.; Sanofi; Aventisub LLC; Regeneron Pharmaceuticals, Inc.; Sanofi-Aventis U.S. LLC

Cases: Patent FedCirNews