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Articles and IP News

Are Biopharma Genus Patent Claims Dead?

December 8, 2020

A recent Supreme Court petition for certiorari alleges that genus claims are no longer viable under the Federal Circuit’s recent application of enablement and written description law.1 The petition has huge ramifications not only for its filer, Idenix, which seeks to reinstate a $2.5 billion patent damages award, but for the biopharma industry, which frequently relies on genus claims to protect inventions.2

Idenix filed its petition after a split Federal Circuit panel upheld a patent invalidity judgment in its long running dispute over whether Idenix’s patent is infringed by Gilead’s highly successful SOVALDI (sofosbuvir) hepatitis C (“HCV”) treatment.3 At the district court level, Judge Stark had overturned a jury verdict in Idenix’s favor by granting JMOL of patent invalidity for lack of enablement.4 The Federal Circuit not only upheld the district court’s non-enablement judgment, it held that the Idenix patent was also invalid for lack of written description.5 In its petition, Idenix argues that the Federal Circuit improperly applied “bright line” rules that effectively kill genus patent claims and disincentivize research, a position joined by a number of amici, including industry heavyweights GSK and Amgen.6 Whether the Supreme Court grants the petition, and if so, how it rules, will have consequences not only for the protection of small molecules, like the ones at issue in the Idenix case, but also biologics, such as antibodies, which are also often protected by genus claims.

Biopharma research typically yields a large group of chemically related compounds believed to be active against a particular condition or disease. Because of our first-to-file patent system, companies are pressured into filing a patent application early on in their research before a particular drug candidate is selected for further investigation in the clinic. They often do so by filing patent claims covering a large genus of compounds, as Idenix did in a bid to protect the nucleoside compounds it alleges it discovered for treating HCV. Without the ability to protect such research through broad genus claims, Idenix argues, third parties may unfairly piggyback off of the innovator’s work by pursuing a substantially similar compound, thus diminishing the incentives for research and the sharing of discoveries with the world. On the flip side, others would contend that permitting too broad of a genus patent claim unduly prevents others from pursuing research in the same field as the innovator. Where the line is drawn could significantly affect the future of drug research.

District Court Proceedings

Claim 1 of the Idenix patent reads:

A method for the treatment of a hepatitis C virus infection, comprising administering an effective amount of a purine or pyrimidine β-D-2′-methyl Ribofuranosyl nucleoside or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.7

At Idenix’s urging, the district court construed the preamble (italicized above) as a narrowing functional limitation such that for a compound to infringe, it must have activity against HCV.8 The court further construed the claimed structural limitation “β-D-2′-methyl-ribofuranosyl nucleoside” broadly to require a methyl group in the 2′ up position and nearly any non-hydrogen substituent at the 2′ down and 3′ down positions.9 Gilead, whose accused 2′-methyl-up sofosbuvir compound has a fluorine substituent at the 2′ down position, stipulated to infringement of the claim as so construed.10 Gilead instead argued that Idenix’s patent – which discloses fluorine substituents at other positions, but not at the 2′ down position – is invalid for lack of enablement and written description. The jury found for Idenix, and awarded it over $2.5 billion in damages. However, the district court overturned the jury’s verdict, granting JMOL of patent invalidity for lack of enablement.11

The Federal Circuit’s Decision

According to the Federal Circuit, the key enablement question on appeal was whether a person of ordinary skill in the art (“POSA”) would know, without undue experimentation, which of the potentially billions of 2′-methyl-up nucleosides within the claimed structural genus would be effective for treating HCV.12 In a 2:1 decision authored by Chief Judge Prost, the court concluded the Idenix claim is not enabled,13 for among the following reasons:

  • Based on various formulae in the patent specification, the structural genus of the claim literally encompasses at least “many, many thousands” of candidate compounds.14
  • Even accounting for the high level of skill in the art, the quantity of experimentation to determine which 2′-methyl-up nucleosides have efficacy against HCV is “very high”.15
  • The court rejected Idenix’s argument that a POSA would have focused instead on a “significantly smaller” subset of candidate compounds to test – those likely to inhibit the NS5B polymerase – because NS5B inhibition is not part of the claim and the patent discloses other ways to treat HCV.16
  • Idenix conceded that screening would still be required, and even although synthesis of an individual compound was “largely routine”, the art was “unpredictable” and Idenix’s patent fails to provide “meaningful guidance” as to which 2′-methyl-up nucleosides are effective against HCV.17
  • The breadth of the Idenix patent claim leaves a POSA searching for a “needle in a haystack” to determine which of the “large number” of 2′-methyl-up nucleosides falls into the “small” group of candidates that effectively treats HCV.18

Weighing each of the enablement factors, the court held as a matter of law that the Idenix patent is invalid for lack of enablement.19

The Federal Circuit went on to address the district court’s denial of JMOL on the issue of written description.20 The key issue there was whether the patent demonstrated that the inventor was in possession of those claimed 2′-methyl-up nucleosides that fall within the boundaries of the claim, but that were not encompassed by explicit formulas or examples disclosed in the specification.21 Ultimately, the Federal Circuit held that the Idenix patent is also invalid for lack of written description,22 noting the following reasons:

  • The Idenix patent fails to sufficiently disclose 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.”23
  • While the specification provided eighteen “principal embodiments” by disclosing “position-by-position” formulae of compounds that may treat HCV,24 the specification provides no indication, other than generic language, “that any nucleosides outside of those disclosed in its formulas could be effective to treat HCV—much less any indication as to which of those undisclosed nucleosides would be effective.”25
  • The specification provides no method of distinguishing effective from ineffective compounds outside of the disclosed formulae.26
  • The court rejected Idenix’s argument that it had provided “abundant traditional blazemarks for the claims—working examples, formulas, data, synthesis routes, and the target” because Idenix’s lists or examples state that they are effective nucleosides but do not explain what makes them effective or why, thus depriving the POSA of “meaningful guidance” as to which compounds beyond the examples and formulae would provide the same result.27
  • While written description does not require a “nucleotide-by nucleotide” recitation of the entire genus, the absence of 2′-fluoro down nucleosides in the specification was “conspicuous” particularly in light of the disclosure of fluorine as a possible substituent at other positions on the nucleosides.28

In light of the foregoing, the court held as a matter of law that the Idenix patent is invalid for lack of written description.29 In her dissent, Judge Newman opined the court erred in finding that the “specific narrow claims” of the Idenix patent were invalid because “[t]he large number of unclaimed chemical variants in the specification are not described, not synthesized, and not tested for antiviral activity”. Judge Newman stated she would have decided the appeal instead on the ground that the claims, correctly construed, are valid and not infringed.30

Idenix’s Cert. Petition

Idenix’s petition presents two “related” questions:

1. Whether, as the Federal Circuit has held, a genus claim is not enabled “as a matter of law” if it encompasses a large number of compounds—or whether, as this Court has recognized, enablement is a context-specific jury question; and

2. Whether, as the Federal Circuit has held, § 112(a) contains a separate “possession” requirement—or whether, as the statute provides, § 112(a) sets forth a single substantive requirement of “a written description of the invention” sufficient “to enable any person skilled in the art … to make and use the same.”31

As to the first question, Idenix argues in its petition that the Federal Circuit’s adverse enablement ruling is problematic because it is numbers-based.32 In particular, Idenix contends that “the Federal Circuit adopted a bright-line rule whereby genus claims are not enabled if they cover ‘too many’ compounds.”33 According to Idenix, this begs the question: “how ‘many, many’ is too ‘many, many’?”34 Idenix contends that “pharmaceuticals and biologics have numerous possible chemical variants, many of which share the same basic properties.”35 Thus, “[i]t is often ‘impossible’ to identify each one that will share that property in advance; ‘trial and error experiments’ cannot be ‘[a]void[ed].’”36 Idenix argues that if the applicant claims the whole “class that shares a specific structure and exhibits a particular property, she runs headlong into the Federal Circuit’s numerosity prohibition: Her patent may cover too many possible embodiments to be enabled. . . . But if [the applicant] claims only specific compounds, competitors can freeride on her key insight by creating a slightly different variant.”37

As to the second question, Idenix contends that the Federal Circuit’s written description “possession” test is “indeterminate”, “sows confusion”, and “impedes innovation”.38 Specifically, Idenix argues that Section 112 does not contain a separate “possession” requirement at all, and that all that is required is a description sufficient to enable making and using the invention.39 Idenix further posits that the written description test puts applicants in a conundrum because if they list too many examples in the specification in an effort to meet the “representative number of species” requirement, they run “the risk of suggesting that embodiments not specifically mentioned in the specification were purposefully omitted.”40

Conclusion

The Idenix petition raises questions that go to the heart of the proper scope of patent protection for the discovery of a new class of potentially-active compounds. When is a genus claim too large? How many species in the genus must be exemplified? How much extrapolation is permissible from the species that are specifically disclosed in the specification? How do you show “possession” in this context beyond enablement? While these are important questions, the chances of the Supreme Court granting Idenix’s petition, at first blush, would appear low. As one noted commentator has described it, the Supreme Court has “a seeming institutional reticence against deciding questions presented regarding Section 112(a).”41 But with the changed make-up of the court, and the heightened public awareness of the importance of drug research, it remains to be seen whether the Supreme Court will decide it is time to review the written description and enablement requirements in the context of biopharma patent claiming.

1See Petition for Writ of Certiorari, Idenix Pharm. LLC v. Gilead Scis. Inc., No. 2018-1691, (Fed. Cir.).
2See id.
3Idenix Pharm. LLC v. Gilead Scis. Inc., 941 F.3d 1149, 1164 (Fed. Cir. 2019).
4Idenix Pharm. LLC v. Gilead Scis., Inc., 2018 WL 922125, at *25 (D. Del. Feb. 16, 2018).
5Idenix, 941 F.3d. at 1165.
6Petition for Writ of Certiorari, 14, Idenix Pharm. LLC v. Gilead Scis. Inc., No. 2018-1691, (Fed. Cir.).
7U.S. Patent Number 7,608,597, col. 142, ll. 63–67.
8Idenix, 2018 WL 922125 at *11.
9Id.
10Id. at *1.
11Id. at *25.
12Idenix, 941 F.3d at 1155.
13Id. at 1165.
14Id. 1t 1157.
15Id. at 1156-57.
16Id. at 1157.
17Id. at 1160-61.
18Id.at 1162.
19Id. at 1165.
20Id. at 1163.
21Id.
22Id. at 1164.
23Id. (quoting Ariad Pharm., Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010)).
24See generally U.S. Patent Number 7,608,597, col. 5 l. 29–col. 13 l. 42.
25Idenix, 941 F.3d at 1164 (citing U.S. Patent No. 7,608,597, col. 15 l. 51–col. 16 l. 10) (emphasis in original).
26Id.
27Id.
28Id. at 1165.
29Id.
30Id. at 1165.
31Petition for Writ of Certiorari, Idenix Pharm. LLC v. Gilead Scis. Inc., No. 2018-1691, (Fed. Cir.).
32Id.
33Petition for Writ of Certiorari, 15, Idenix Pharm. LLC v. Gilead Scis. Inc., No. 2018-1691, (Fed. Cir.).
34Id. (emphasis in original).
35Id.
36Id. (citation omitted).
37Id. (citation omitted).
38Id.
39Id.
40Id.
41Kevin E. Noonan, Supreme Court Denies Certiorari in Actavis Laboratories v. Nalproprion Pharmaceuticals, Patent Docs (May 31, 2020), https://www.patentdocs.org/2020/05/.