PTAB Year in Review – PTAB Trends in 2024: Challenges to Genus Claims

In the biotechnology and chemical spaces, genus claims are often sought by patent applicants to protect not only a specific product of interest, but also as a means to protect against others making related products that incorporate the advance over the prior art made by the applicant. In 2024, the Patent Trial and Appeal Board (PTAB) issued several decisions in the biotechnology and chemical space where the written description and enablement requirements came into play in proceedings involving challenges to genus claims. As these patentability requirements are seemingly become stricter for biotechnological and chemical inventions, and the Supreme Court has recently weighed in with respect to enablement, it is worth assessing how the PTAB handled analysis of written description and enablement requirements in the biotechnology and chemical spaces in 2024.

Lack of Enablement for Sequence Identity Claims Having a Functional Element

As the Federal Circuit has recognized, generic claims reciting functional elements make such claims especially susceptible for attack by written description and enable-ment.¹ In Inari Agriculture, Inc. v. Pioneer Hi-Bred International, Inc., claims challenged in a post-grant review (PGR) were directed to a transgenic plant comprising a recombinant polynucleotide encoding an enzyme having dual-substrate activity, wherein the enzyme comprised (1)  amino acids having at least 85% sequence identity to a specific sequence and (2) a specific amino acid motif with specific spacing between fixed amino acid sequences in the motif.²

At institution, the Board found that it was more likely than not that at least one challenged claim of the challenged patent lacked written description and enablement.³ That finding by the Board also involved a decision that the challenged patent was PGR-eligible because the challenged patent’s pre-AIA priority application was also found to not provide written description and enablement support.⁴

In its Final Written Decision, the Board reaffirmed its findings with respect to lack of enablement in the priority application. In doing so, the Board stepped through the Wands factors and pointed to the Supreme Court’s finding in Amgen v. Sanofi that analyzing enablement of genus claims involves determining if there is a common quality running through the genus that gives it a peculiar fitness for the claimed function.⁵

In short, the Board’s analysis found that based on the claimed sequence’s length and the requirement for it having at least 85% sequence identity to the recited sequence, the claim encompassed up to 2.4 x 10¹⁰⁶ candidate species, whereas the specification disclosed two exemplary sequences.⁶ The Board also found that it would not have been predictable which of the possible species encompassed by the claims would have the claimed dual-enzyme activity and which would not.⁷ Additionally, the Board determined that (1) there was a lack of guidance and working examples in the specification that would indicate which of the candidate species would meet the claimed function, (2) a skilled artisan would not know from the art which amino acids could tolerate changes, and (3) unpredictability between in vitro and in vivo function would require making and testing each variant for its activity.⁸

Lastly, aiding in the Board’s final determination of a lack of enablement were experiments performed by the patent owner previous to the filing of the PGR and submitted during the proceeding. Those experiments showed that having the claimed amino acid motif, claimed amino acid spacing, and claimed sequence identity did not constitute (1) a structure-function correlation sufficient enough to predict function; or (2) a common quality running through the genus.⁹

In view of the above, the Board concluded that “[w]hile it may have been possible for a skilled artisan to make certain polypeptides” with the claimed function “using the guidance provided in the [s]pecification and the methods known by an ordinarily skilled artisan, practicing the full scope of the claimed polypeptides would fall outside routine experimentation.”¹⁰

This case is particularly instructive because many patent applicants seeking protection for a protein of interest typically include sequence identity claims as a standard practice. Such sequence identity claims tied to a functional element should be assessed on both the petitioner’s and patent owner’s sides for the claimed genus’s size, any unpredictability that would require making and testing each variant for whether it meets the claimed function, how sufficiently the claims are supported by a structure-function correlation or a representative number or species in the specification, and what was the knowledge in the art at the time of filing. This case also reaffirms that post-Amgen weighing the Wands factors remains an instructive tool in assessing enablement support.

A Single Working Example Not Sufficient to Support Broad Functional Claim

In Forte Biosciences, Inc. v. University of Massachusetts,¹¹ the Board found a lack of written description and enablement upon analogizing the facts at issue with those in Juno v. Kite¹² and Amgen. The Board determined that the challenged claims were “directed broadly to a method of treating vitiligo by administering an inhibitor of IL-15 or the IL-15 receptor in a therapeutically affective amount,” which was “a functional description, requiring that the administered compound be both an inhibitor of IL-15 or IL-15 receptor and therapeutically effective.”¹³

Regarding written description, the patent owner sought to frame the inquiry as to whether or not the challenged patent demonstrated possession of the claimed method of treating vitiligo with an IL-15 or IL-15 receptor inhibitor and not whether the inventors were in possession of the entire genus of IL-15 and IL-15 receptor inhibitors capable of functioning in the claimed method.¹⁴ The Board disagreed that the analysis should be solely focused on the claimed method, but should also focus on the genus of inhibitors because the claimed method could not be practiced with-out them.¹⁵

The Board then analyzed the scope of the claimed genus and found it to be broad, encompassing at least small molecules, antibodies, nucleic acids, and peptides.¹⁶ Yet, the specification only provided one working example, an antibody, and the art demonstrated unpredictability in which IL-15 and IL-15 receptor inhibitors would be effective.¹⁷ Based on that, the Board likened the facts to Juno. There, the claims encompassed any single-chain antibody fragment (“scFv”) capable of binding a target antigen and the specification only disclosed two exemplary scFvs in working examples. That led to a finding of a lack of written description because a skilled artisan would not have found the two disclosed examples sufficiently representative of the entire genus.¹⁸ Applying that in Forte, the Board found a lack of written description. It determined that given the unpredictability in the art a skilled artisan would not have found the single working example using an antibody sufficiently representative of the different possible inhibitor types disclosed in the specification and the hundreds of known IL-15/IL-15 receptor inhibitors.¹⁹ It also found a lack of structure-function correlation in the specification and the art given that the candidate species encompassed by the claims were not all a readily identifiable class, did not all target the same biological pathways, did not have any common structural features, and did not always function as inhibitors.²⁰

Turning to enablement, the Board found the facts in Forte similar to those in Amgen.²¹ The Board found that, as in Amgen where the claims encompassed the entire genus of antibodies capable of binding specific residues of their target and blocking its function and the specification provided a limited number of exemplary antibodies, the claims in Forte encompassed the entire genus of IL-15/IL-15 receptor inhibitors capable of treating vitiligo and only one working example.²² Pointing again to the unpredictability as to which inhibitors would and would not function to treat vitiligo, the Board determined that a skilled artisan would have to painstakingly test every candidate compound to determine if it met the claimed function.²³ The Board thus found a lack of enablement. In doing so, it rejected the patent owner’s argument that the claims being to a method absolved it of the need to disclose information about what inhibitors met the claimed function.²⁴

The Board’s decision in Forte provides another example of how broad functional claims can be particularly susceptible to written description and enablement challenges, whether they are directed to a product or a method. This decision also demonstrates how cases such as Juno and Amgen remain instructive when lodging and defending against § 112(a) challenges, as well as how extrinsic evidence of unpredictability and inoperability can be utilized.

Blaze Marks Would Not Have Directed a Skilled Artisan to Envisage a Claimed Subgenus

It is well-established that “the hallmark of written description is disclosure.”²⁵ For genus claims, the Federal Circuit has held that sufficient disclosure can be established by showing that a specification discloses a representative number of species or features common to the claimed genus, such that a skilled artisan would be able to visualize or recognize the members of the genus.²⁶

Throughout the years, the Federal Circuit has established different ways of determining whether a patent specification discloses either or those two factors sufficiently enough to support a genus claim: (1) searching for a precise definition, such as by structure, formula, chemical name, physical properties, or other properties sufficient to distinguish the species of the genus from others; (2) looking for structure-function correlations in the specification and/or known in the art when analyzing functional claims; (3) analogizing a claimed genus to a plot of land and seeing how much of that plot of land the species disclosed in a specification cover; and (4) looking for blaze marks that direct a skilled artisan to the claimed subject matter.²⁷

In Daiichi Sankyo, Inc. v. Seagen Inc., the Board analyzed the challenged claims in a PGR using a “blaze marks” analysis and found a lack of written description in both the patent and its priority applications.²⁸ There, the challenged claims were directed to an antibody-drug conjugate (“ADC”) having a certain chemical formula comprising a “tetrapeptide” subunit and a “drug moiety.”²⁹

To make the patent PGR-eligible, the petitioner challenged patent’s priority claim. At issue was a “W_w” element in the claims that required that the ADC comprises a tetrapeptide made up of four amino acids selected from combinations of glycine and phenylalanine (“gly/phe”), as well other requirements.³⁰ The petitioner argued that the W_w element encompasses 81 different species, none of which were specifically identified in the patent’s priority applications, whose disclosure embodied over 47 million species.³¹ The petitioner further stated that there were no blaze marks in the specifications of the priority applications that would have pointed a skilled artisan to the claimed gly/phe tetrapeptides, rather one would have been directed to a different subgenus.³² In response, the patent owner pointed to three other tetrapeptides that had different combinations of amino acids, other than gly/phe, disclosed in the priority applications, which the patent owner asserted would have guided a skilled artisan to the claimed gly/phe tetrapeptides.³³

Upon analysis of the parties’ arguments, the Board found that the preponderance of the evidence showed that the priority applications lacked the requisite descriptive support for the W_w element. Applying a “blaze marks” analysis, the Board stated that the disclosure of the priority applications would not “allow a person of ordinary skill in the art to inherently, necessarily, or immediately envisage a tetra-peptide with only glycine or phenylalanine as the amino acids.”³⁴ The Board, therefore, concluded that “the requisite description” for the claimed W_w element was “lacking in the priority applications as it is an ‘undifferentiated description. . . [that] failed to provide sufficient ‘blaze marks’ to guide a reader through the forest of disclosed possibilities toward the claimed compound, which resided among the myriad others that also could have been made.’”³⁵

The Board also found that, while the claimed gly/phe tetra-peptides might have been obvious in view of the other specifically disclosed tetrapeptides, “a description that merely renders the invention obvious does not satisfy the written description argument.”³⁶ And because the challenged patent’s specification also suffered from the same lack of blaze marks as the priority applications, the Board found that the challenged claims lacked written description support in the challenged patent as well.

The petitioner in Daiichi also challenged the challenged patent’s written description support for the “drug moiety” element. The petitioner took the position that the challenged patent’s specification failed to disclose a representative number of species or common structural features of drug moieties for use in the claimed ADC.³⁷ The Board disagreed, finding the facts similar to those in Capon v. Eshhar, because the art was “aware of a number of chemotherapeutic drug compounds and the use of antibody-drug conjugates.”³⁸ The specification also disclosed a large number of drugs, incorporated by reference numerous references describing ADCs, and the structures of chemotherapeutic agents were known in the art.³⁹ The Board also found the facts different from those in Juno because the claims were focused on the particular linker selected, rather than the drug, and the specification-at-issue disclosed “dozens of different known chemotherapeutic agents in multiple different classes that would have been expected to kill cancer cells.”⁴⁰ The Board, therefore, found the “drug moiety” element sufficiently supported in the challenged patent.

The decision in Daiichi demonstrates how claims to a specific subgenus or species can be susceptible to written description challenges when a skilled artisan would not have been directed to selection of the claimed subgenus or species by a patent’s specification. The Daiichi decision also demonstrates how different facts can lead to different conclusions on written description. Unlike in Forte, where Juno was found applicable, here the claims did not recite any functional elements and the claimed “drug moiety” genus was well established. Thus, Daiichi shows how the outcome of a case can depend on how the written description issue is framed.

Future Considerations

In a world post-Amgen’s role in analyzing enablement and with increasingly tighter written description requirements being imposed on biotechnology and chemical patents, an array of possible invalidity §112 attacks and defenses become available for challenging and defending genus claims in the biotechnology and chemical spaces at the PTAB: assessing whether or not the challenged patent has disclosed a clear structure-function relationship for functional claims, demonstrating a lack of or presence of sufficient representative species, the presence or absence of blaze marks directing a skilled artisan to the claimed genus, the presence or absence of a sufficient number of working examples, and/or showing a lack of or presence of a common quality running through the genus that gives it a peculiar fitness for its particular purpose.

Also of note, the above decisions all involved PGRs, where challenges to written description and enablement are typically top-of-mind because PGR-eligible patents can be challenged under the provisions of § 112(a). Nonetheless, these decisions can also be instructive for inter partes reviews (IPRs), where unpatentability challenges are limited to grounds based on prior art patents and printed publications. Indeed, as discussed above, petitioners made use of written description and enablement arguments to attack the priority claim of the challenged claims. Such § 112-based priority attacks are also available in IPRs and can be a useful tool for bringing challenges based on intervening prior art.

[1] See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349 (Fed. Cir. 2010) (discussing written description); Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080 (Fed. Cir. 2021) (discussing enablement).
[2] Inari Agric., Inc. v. Pioneer Hi-Bred Int’l, Inc., PGR2023-00022, Paper 50, at *4−5 (PTAB Oct. 10, 2024).
[3] Id. at *6.
[4] Id.
[5] Id. at *13−33 (citing In re Wands, 858 F.2d 731 (Fed. Cir. 1988); Amgen Inc. v. Sanofi, 143 S.Ct. 1243 (2023)).
[6] Id. at *13.
[7] Id. at *19−21.
[8] Id. at *22−29.
[9] Id. at *20, 30−32.
[10] Id. at *32 (the Board found that it did not need to reach the issue of written description
given that it found a lack of enablement).
[11] Forte Biosciences, Inc. v. Univ. of Mass., PGR2023-00014, Paper 45 (PTAB June 24, 2024).
[12] Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330 (Fed. Cir. 2021).
[13] Forte at *16.
[14] Id.
[15] Id. at *16−*17 (citing Univ. of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 925−26 (Fed. Cir. 2004)).
[16] Id. at *17.
[17] Id. at *17−*20.
[18] Juno, 10 F.4th at 1338−39.
[19] Forte at *20.
[20] Id. at *21−*22.
[21] Id. at *29−31.
[22] Id. at *30.
[23] Id. at *31−*33.
[24] Id. at *36−*37.
[25] Ariad, 598 F.3d at 1351.
[26] Id. at 1350.
[27] Id.; AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300 (Fed. Cir. 2014); Idenix Pharm. LLC v. Gilead Sci., 1149, 1164 (Fed. Cir. 2019) (citing In re Ruschig, 379 F.2d 990, 994−95 (CCPA 1967)).
[28] Daiichi Sankyo, Inc. v. Seagen Inc., PGR2021-00030, Paper 57 (PTAB Jan. 16, 2024).
[29] Id. at *8.
[30] Id. at *15.
[31] Id.
[32] Id. at 16.
[33] Id. at 18.
[34] Id. at 25.
[35] Id. at *28 (quoting Novozymes A/S v. Dupont Nutrition Biosciences APS, 723 F.3d 1336, 1349 (Fed. Cir. 2013)).
[36] Id. at *29 (cleaned up).
[37] Id. at 31.
[38] Id. (citing Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005)).
[39] Id. at 37−38.
[40] Id. at 38−39.

This article appeared in the 2024 PTAB Year in Review: Analysis & Trends report.