During the week of April 29–May 3, 2019, the Patent Trial and Appeal Board (“Board”) issued one decision in TC 1600—a final written decision in a post-grant review (“PGR”):
Grünenthal GmbH v. Antecip Bioventures II LLC, PGR2018-00001
Claims 1–2 were previously disclaimed. See PGR2018-00001, Paper 48 (Final Written Decision) at 3. Remaining claims 3–30 broadly embraced zoledronic acid in a salt or acid form, with or without the addition of one or more bioavailability-enhancing ingredients. See id. at 11. More specifically, the independent claims recited an oral pharmaceutical dosage form comprising forms of zoledronic acid and other components, including specific bioavailability percentages of zoledronic acid of about 1.2–4% in humans (claim 23), and a method for treating arthritis in humans comprising orally administering a zoledronic acid salt or acid dosage form and other components, also including specific bioavailability percentages of zoledronic acid of about 1.1–4% (claim 3). See id. at 5–7.
Petitioner Grünenthal GmbH asserted multiple grounds of unpatentability, including § 112(a) lack of enablement (claims 3–30), § 112(b) indefiniteness (claim 15), § 102 anticipation (claim 23), and multiple grounds of § 103 obviousness (claims 3–30). Id. at 7–8. However, the Board considered only § 112(a) lack of enablement of claims 3–30 before finding the claims unpatentable, and it declined to reach other grounds. Id. at 20–21. Specifically, under the Wands factors, the Board assessed whether the ’268 patent’s specification taught an ordinarily skilled artisan how to make and use any dosage form having zoledronic acid bioavailability within the claimed ranges:
- Wands factor one—the nature of the invention, level of skill in the art, and unpredictability of the art: Pharmaceutical formulations is an unpredictable field and bioavailability may be influenced by multiple factors. See id. at 11–12.
- Wands factor two—the state of the prior art: At least 22 forms of zoledronic acid and its salts were known before the priority date, were expected to have different properties, and were generally known to have poor bioavailability. An ordinarily skilled artisan would have believed that all zoledronic acid forms, as claimed, could not achieve a bioavailability above 1% without an enhancer. See id. at 12–13.
- Wands factor three—the breadth of the claims, lack of guidance, and absence of working examples: Claims 3–30 use the transitional phrase “comprising” and are “broad” claims, yet the specification disclosed (1) no examples of zoledronic acid dosage forms, (2) no bioavailability-enhancing ingredients that may be added to improve zoledronic acid’s bioavailability to at least 1.1%, and (3) no pharmacokinetic data identifying bioavailability of 1.1–4%. at 13–14. While the specification disclosed that the disodium salt form “may be more bioavailable,” the claims were not so limited. Id. at 14. Furthermore, the specification contained hypothetical bioavailability ranges without any “actual data obtained from any dosage form, or any other information explaining how to make a dosage form having a bioavailability that falls within the claimed ranges.” Id. at 14–15. In fact, the Patent Owner’s witness likened a belief that certain zoledronic acid salt forms might have bioavailability to within the range of 1.1% without enhancers to a “belie[f] in ‘fairies.’” Id. at 14.
- Wands factor four—the quantity of experimentation required: Patent Owner relied on a public reference, arguably within the skilled artisan’s knowledge, relating to bioavailability of a specific zoledronic acid salt form. The Board noted the reference’s failure to address bioavailability in humans (it addressed only beagle dogs), but ultimately focused on the need for enablement to be found in the specification, not in the knowledge of one skilled in the art. See id. at 15–17 (citing in part Genentech Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997)).
Ultimately, the Board found that 1) the field was unpredictable, 2) the claims were broad, 3) the specification lacked any “guideposts that would have illuminated a path toward even one dosage form that has a bioavailability that falls within the scope of any claim,” and 4) the level of experimentation required to determine whether even one dosage form falls within the scope of the claimed bioavailability ranges was far in excess of routine experimentation. See id. at 17–20. The Board thus found claims 3–30 unpatentable for lack of enablement.