In Amgen Inc. v. Sanofi,1 the Federal Circuit held that the use of broad functional claim language raises the bar for enablement. Specifically, the court held that defining an antibody based on binding to a certain protein rather than describing the amino acid sequences was considered functional and required more information to meet the enablement requirement. The court held that the enablement requirement was not satisfied because the claims encompassed a broad genus of antibodies having no identifiable common structural features.
Amgen Inc. owned U.S. Patent 8,829,165 (the ’165 patent) and U.S. Patent 8,859,741 (the ’741 patent). The ’165 and ’741 patents related to antibodies that bind to the proprotein convertase subtilisin/kexin type 9 (PCSK9) and lower low-density lipoprotein (LDL) cholesterol levels by blocking PCSK9 from binding to LDL receptors (LDLRs). Elevated LDL cholesterol is associated with heart disease. The patent specification described amino acid sequences for 26 antibodies, including the antibody (identified as “21B12”) with the basic designation of evolocumab, sold by Amgen as Repatha®. The specification described three-dimensional structures for the antibody called 21B12 and described where that antibody bonded to PCSK9. The ’165 and ’741 patents claimed antibodies that bonded to 15 amino acids (i.e., “residues”) of the PCSK9 protein and blocked PCSK9 from binding to LDLRs.2
The ’165 patent claims recited:
1. 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.
19. The isolated monoclonal antibody of claim 1 wherein the isolated monoclonal antibody binds to at least two of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of PCSK9 listed in SEQ ID NO: 3.
29. A pharmaceutical composition comprising an isolated monoclonal antibody, wherein the isolated monoclonal antibody binds to at least two of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of PCSK9 listed in SEQ ID NO: 3, and blocks the binding of PCSK9 to LDLR by at least 80%.3
The ’741 patent claims recited:
1. An isolated monoclonal antibody that binds to PCSK9, wherein the isolated monoclonal antibody binds an epitope on PCSK9 comprising at least one of residues 237 or 238 of SEQ ID NO: 3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.
2. The isolated monoclonal antibody of claim 1, wherein the isolated monoclonal antibody is a neutralizing antibody.
7. The isolated monoclonal antibody of claim 2, wherein the epitope is a functional epitope.4
The claimed antibodies were “defined by their function: binding to a combinations [sic] of sites (residues) on the PCSK9 protein, in a range from one residue to all of them; and blocking the PCSK9/LDLR interaction.”5
The district court held that the ’165 and ’741 patent claims were invalid for lack of enablement. Amgen appealed, and the Federal Circuit affirmed.
35 U.S.C. Section 112 provides that a patent specification must “enable any person skilled in the art … to make and use” the claimed invention.6 The Federal Circuit noted that the specification must provide details with respect to the scope of the claims.
“To prove that a claim is invalid for lack of enablement, a challenger must show … that a person of ordinary skill in the art would not be able to practice the claimed invention without ‘undue experimentation.’”7 “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.”8 These factual considerations are known as the “Wands factors” and include the following:
(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.9
The court acknowledged that even though the specification is not required to “describe how to make and use every possible variant of the claimed invention, when a range is claimed, there must be reasonable enablement of the scope of the range.”10
On appeal, Amgen argued that the claims were enabled because there was no undue experimentation needed to obtain antibodies wholly within the breadth of the claims. Amgen argued that it presented expert testimony demonstrating a person of skill in the art could make all antibodies within the claim scope by using anchor antibodies and conventional screening methods or by making amino acid replacements in the 26 examples described in the specification. Sanofi countered that the Wands factors indicated that the claims were not enabled because there were millions of antibody possibilities within the scope of the claims, the specification did not provide an adequate description and undue experimentation was required.11
The Federal Circuit explained:
[T]he enablement inquiry for claims that include functional requirements can be particularly focused on the breadth of those requirements, especially where predictability and guidance fall short. In particular, 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.12
The court reasoned that “[w]hile functional claim limitations are not necessarily precluded in claims that meet the enablement requirement, such limitations pose high hurdles in fulfilling the enablement requirement for claims with broad functional language.”13The court noted that each of the claims recited:
a composition claim defined, not by structure, but by meeting functional limitations … [and] that the specification here did not enable preparation of the full scope of these double-function claims without undue experimentation. … The binding limitation is itself enough here to require undue experimentation.14
With respect to the specific Wands factors, the court concurred with the district court that the claim language was too broad, and it was clear that the claims were:
far broader in functional diversity than the disclosed examples. … Further, the use of broad functional claim limitations raises the bar for enablement, a bar that the district court found was not met.15
The court also noted that the invention was unpredictable in connection with fulfilling the full breadth of the functional claim limitations. For example, Amgen’s expert witness acknowledged that converting an antibody’s amino acid sequence into a known three-dimensional structure was currently not possible. The court reasoned that there was only evidence that a small subgroup of the antibodies could be generated reliably. The court acknowledged that while the specification provided some description, including data regarding specific embodiments, there was not sufficient guidance besides the limited working examples.16
The Federal Circuit therefore agreed with the district court that the necessary experimentation would require significant time and energy. It explained:
We do not hold that the effort required to exhaust a genus is dispositive. It is appropriate, however, to look at the amount of effort needed to obtain embodiments outside the scope of the disclosed examples and guidance. The functional limitations here are broad, the disclosed examples and guidance are narrow, and no reasonable jury could conclude under these facts that anything but “substantial time and effort” would be required to reach the full scope of claimed embodiments.17
The court consequently determined that, considering the Wands factors, undue experimentation would be needed to enable the complete scope of the claims. Specifically, the claim scope covered millions of antibody candidates with numerous functions, and the court determined that it would be essential to first produce and then review each antibody candidate to assess whether it satisfied the double-function recited in the claims.18
Therefore, the court affirmed the district court’s holding that the claims were invalid for lack of enablement.19
In Amgen v. Sanofi, the Federal Circuit held that describing antibody-related inventions using functional language based on what they bind to does not satisfy the enablement requirement under 35 U.S.C. Section 112. The court held that it would have taken “undue experimentation” to identify the hundreds of millions of other antibodies that bind to a protein called PCSK9 for Amgen’s antibody cholesterol drug Repatha.
The court has raised the bar for inventions that utilize functional language in their patent specification. Patent applicants would be well advised to provide a variety of examples to accompany the functional description in order to enhance their chances of satisfying the enablement requirement. In addition, including a variety of independent and dependent claims directed to what is believed to be the more valuable aspects of the invention is also recommended. The dependent claims can be used to recite narrower features of the invention, including structural features that complement the functional language in the claims.
1 Amgen Inc. v. Sanofi, 987 F.3d 1080, 2021 USPQ2d 169, 2021 WL 501114 (Fed. Cir. 2021).
2 Id., 987 F.3d at 1083.
3 Id., 987 F.3d at 1083 (quoting U.S. Patent No. 8,829,165 col. 427 l. 47–col. 430 l. 23).
4 Id., 987 F.3d at 1083 (quoting U.S. Patent No. 8,859,741 col. 427 ll. 36–57).
5 Id., 987 F.3d at 1083.
6 Id., 987 F.3d at 1084 (quoting 35 U.S.C. § 112(a)).
7 Id., 987 F.3d at 1084 (quoting Alcon Research Ltd. v. Barr Labs Inc., 745 F.3d 1180, 1188, 110 USPQ2d 1008, 1014 (Fed. Cir. 2014); In re Wands, 858 F.2d 731, 736–37, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)).
8 Id., 987 F.3d at 1084 (quoting In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)).
9 Id., 987 F.3d at 1084 (quoting In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)).
10 Id., 987 F.3d at 1085 (quoting McRO, Inc. v. Bandai Namco Games Am. Inc., 959 F.3d 1091, 1100, 2020 USPQ2d 10550, at *8 (Fed. Cir. 2020).
11 Id., 987 F.3d at 1085.
12 Id., 987 F.3d at 1086.
13 Id., 987 F.3d at 1087 (citing Wyeth & Cordis Corp. v. Abbott Labs, 720 F.3d 1380, 1384, 107 USPQ2d 1273, 1275 (Fed. Cir. 2013) (finding that practicing the full scope of the claims would require excessive experimentation); Enzo Life Scis. Inc. v. Roche Molecular Sys. Inc., 928 F.3d 1340, 1345 (Fed. Cir. 2019) (finding that the specification failed to teach whether the many embodiments would be both hybridizable and detectable upon hybridization); Idenix Pharms. LLC v. Gilead Scis. Inc., 941 F.3d 1149, 1155–56, 2019 USPQ2d 415844, at *2–3 (Fed. Cir. 2019) (finding that the broad functional limitation of having efficacy against hepatitis C virus increased the number of nucleoside candidates that would need to be screened)).
14 Id., 987 F.3d at 1087.
15 Id., 987 F.3d at 1087.
16 Id., 987 F.3d at 1087–88.
17 Id., 987 F.3d at 1088.
18 Id., 987 F.3d at 1088.
19 Id., 987 F.3d at 1088.