In a precedential opinion in Amgen Inc. et al. v. Sanofi, Aventisub LLC, et al., No. 20-1074 (Fed. Cir. 2021) issued on February 11, 2021, the Federal Circuit affirmed the decision of the United States District Court for the District of Delaware granting JMOL that Amgen’s Repatha® patents (U.S. Patent Nos. 8,829,165 and 8,859,741) were invalid for lack of enablement. The district court’s grant of JMOL overturned a jury verdict finding Amgen’s claims were not invalid for lack of enablement.
The claims at issue cover a genus of monoclonal antibodies that bind a certain epitope of PCSK9 and block binding of PCSK9 to the LDL receptor. The Federal Circuit ultimately concluded that practicing the full scope of the claims would require undue experimentation given the breadth of the functional claim limitations, the limited guidance and examples provided in the specification, and the unpredictability of antibody generation.
The Federal Circuit applied the Wands factors in its analysis, stating that Wands “did not proclaim that all broad claims to antibodies are necessarily enabled.” The Court found the facts were more akin to those in Wyeth, Enzo, and Idenix, in which the claims at issue—drawn to small molecules, rather than antibodies—had both structural and functional limitations, and in which the specifications failed to teach whether the many embodiments of the broad claims would exhibit the required functionality.[i]
Summarizing the body of enablement law, the Court stated “[w]hat emerges from our case law is that the 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.” While the Court stated that its holding is not that “the effort required to exhaust a genus is dispositive,” it held that “[i]t is appropriate … to look at the amount of effort needed to obtain embodiments outside the scope of the disclosed examples and guidance.” Thus, while a claim that includes functional language may be enabled, broad functional limitations create “high hurdles” for fulfilling the enablement requirement.
According to the Court, Amgen’s patent disclosures failed to satisfy this heightened bar. As the Court reasoned, making the full scope of the claimed embodiments in the Repatha patents would require “substantial time and effort.” The only ways to discover the undisclosed claimed embodiments would be either through trial and error (i.e., making structural modifications to the disclosed antibodies and then screening the new antibodies for the desired binding and blocking properties), or by discovering the antibodies de novo according to the randomization-and-screening “roadmap” described in the specification. The Federal Circuit agreed with the district court that the small subset of examples of antibodies provided in the specification did not provide sufficient guidance as to how to obtain the full range of working embodiments within the claims.
The Federal Circuit’s conclusion here was not unexpected, especially after the panel judges made clear during the oral arguments held in December that Amgen faced an “uphill battle” in defending the validity of their antibody genus claims. But how does this decision impact the biologics market and the future of antibody claims? Significantly.
First, it’s now open season not only on antibody patents, but also on patents covering a large genus of molecules in general, particularly those reciting functional limitations. Armed with this decision, patent challengers may now more easily invalidate antibody claims through post-grant review or ex parte reexamination, as well as during litigation. A search of USPTO records reveals that there may be nearly 25,000 patents granted in the past 20 years that claim antibodies based on the functions of “binding” or “blocking” susceptible to invalidation for lack of enablement.[ii] And at least some of those patents may cover highly profitable drugs with significant market share or be currently blocking or deterring market entry of other molecules into the pharmaceutical market. In fact, of the top ten global best-selling drugs forecasted for 2021, five are antibody drugs or antibody fragment drugs, with tens of billions of dollars in annual sales.[iii] By putting broad functionally defined patent claims at serious jeopardy, competing companies may be able to enter the market with molecules that will emerge from under the shadow of such claims.
Second, while the Federal Circuit’s opinion does not provide guidance as to how patent owners should claim a novel genus of antibodies, the decision strongly suggests that purely functional language likely will not suffice. Patent drafters seeking to claim an antibody genus using functional limitations will need to pay close attention to the requisite analysis to enable one of ordinary skill in the art to make and use the claimed scope, e.g., by disclosing sufficient structural features and limitations, a substantial number of examples of antibodies that fall within the genus relative to the genus as a whole, and a crystal clear roadmap that can be used to identify antibodies within the scope of the claim without undue experimentation. Whenever possible, patent drafters should primarily focus on structural claiming as the first line of defense, e.g., by drafting claims reciting specific complementary determining region (CDR) sequences, or perhaps a high percentage of identity to a specific disclosed amino acid sequence. Functional claiming may still have value as a second line of defense in patent claims, particularly if the drafter carefully considers the breadth of the claims, provides a sufficient amount of direction and guidance, and provides a number of specific working examples demonstrating that species spanning the full scope of the claims achieve the claimed function.
Notably, this decision diverges from European practice, where broad patents to antibodies against a new epitope are the norm, and follow-on applications claiming particular sequences are often rejected as lacking inventive step over the broad patent’s functional disclosures.
Given the cascading repercussions of this decision, Amgen will likely file a petition for writ of certiorari. It will be interesting to see if a petition is granted in this case, particularly after the Supreme Court refused in January 2021 to consider whether a genus claim is not enabled “as a matter of law” if it encompasses a large number of compounds in Idenix.[iv]
[i] See Wyeth & Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380, 1385–86 (Fed. Cir. 2013); Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., 928 F.3d 1340, 1345–48 (Fed. Cir. 2019), cert. denied 140 S.Ct. 2634 (2020); Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149, 1160–63, 1165 (Fed. Cir. 2019), cert. denied 2021 WL 161021 (Jan. 19, 2021).
[ii] Based on PTO Patent Full-Text and Image Database searches (http://patft.uspto.gov/netahtml/PTO/search-adv.htm) conducted on February 23, 2021 using the query: ACLM/antibody AND (ACLM/bind$ OR ACLM/block$) AND ISD/20000223->20210223.
[iv] 941 F.3d 1149, 1160–63, 1165 (Fed. Cir. 2019), cert. denied 2021 WL 161021 (Jan. 19, 2021).