Zoledronic acid - USA

Decision on PGR: Apr 29, 2019

AIA Review	Filing Date	Institution Date	Petitioner	US Patent	Respondent	FINAL WRITTEN DECISION
PGR2018-00001	10/10/2017	05/01/2018	Grunenthal GmbH	9,539,268	Antecip Bioventures II LLC	Claims 3–30 are unpatentable

US 9,539,268 (Antecip Bioventures II LLC) – Non OB

1. A method of treating arthritis comprising orally administering a dosage form to a mammal in need thereof, wherein the dosage form comprises: ##STR00022## (Ion B) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or ##STR00023## (Ion C) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; wherein each A is independently an acidic functional group; wherein, if present, the bioavailability of Compound A in the dosage form is from about 1.1% to about 4%.

3. A method of treating arthritis comprising orally administering a dosage form to a human being suffering from arthritis, wherein the dosage form comprises: a) zoledronic acid in a salt or an acid form; or b) one of the following: 1) zoledronic acid in a salt or an acid form and ##STR00024## (Ion 1) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or 2) zoledronic acid in a salt or an acid form and ##STR00025## (Ion 2) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or 3) zoledronic acid in a salt or an acid form and a combination of Ion 1 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w, and Ion 2 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; wherein the dosage form is free of therapeutically active agents that are not zoledronic acid in a salt or an acid form, Ion 1 in a salt form, or Ion 2 in a salt form; wherein any amount in % w/w is based upon the total weight of zoledronic acid in a salt or an acid form, Ion 1, Ion 2, and any corresponding counter ions; and wherein the bioavailability of zoledronic acid in the dosage form is about 1.1% to about 4%.

23. A pharmaceutical dosage form for oral administration comprising: a) zoledronic acid in a salt form; or b) one of the following: 1) zoledronic acid in a salt or an acid form and ##STR00026## (Ion 1) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; 2) zoledronic acid in a salt or an acid form and ##STR00027## (Ion 2) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or 3) zoledronic acid in a salt or an acid form and a combination of Ion 1 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w, and Ion 2 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; wherein the dosage form is free of therapeutically active agents that are not zoledronic acid in a salt or an acid form, Ion 1 in a salt form, or Ion 2 in a salt form; wherein any amount in % w/w is based upon the total weight of zoledronic acid in a salt or an acid form, Ion 1, Ion 2, and any corresponding counter ions; and wherein the bioavailability of zoledronic acid in the dosage form is about 1.2% to about 4% in a human being.

PTAB decision:

Petitioner asserted various grounds such as 35 U.S.C. § 112(a) (lack of enablement), 35 U.S.C. § 112(b) (indefiniteness), 35 U.S.C. § 102 (anticipation) & 35 U.S.C. § 103 (obviousness) in its petition.

PTAB in summary with respect to “enablement” held that the specification includes no disclosure that explains how one may reliably distinguish dosage forms that fall within the scope of the claims from those that do not––short of preparing the forms and testing their bioavailability. The only example provided in the specification of the ’268 patent demonstrates the synthesis of compounds 1 and 2; it contains no guidance for selecting forms of zoledronic acid having the requisite bioavailability. The art of pharmaceutical dosage formulation is unpredictable.  Where an ordinarily skilled artisan would have understood that unmodified zoledronic acid has an oral bioavailability of less than 1%, that artisan could not have been expected to resolve, without any guidance, how to arrive at a dosage form having a bioavailability of 3% or 4%, without engaging in undue experimentation. Therefore, Petitioner has demonstrated by a preponderance of the evidence that claims 3–30 are unpatentable for lack of enablement under 35 U.S.C. § 112(a).

PTAB thus declined to reach other grounds of unpatentability asserted in the petition.