Cabazitaxel - USA

On Aug 14, 2019, Federal Circuit affirmed-in-part & vacated-in-part district court’s decision regarding Jevtana® compound & method of use patent.

This appeal concerns Sanofi’s patent US  5,847,170 & US 8,927,592. The US’ 170 patent claims cabazitaxel compound & US’ 592 patent claims method of treatment of prostate cancer with cabazitaxel. Defendants (Fresenius, Dr Reddy’s lab, Sandoz, Accord, Apotex, Actavis & Mylan) filed ANDA with USFDA to market generic version of Jevtana®. Sanofi sued defendants under Hatch-Waxman regulation for infringement.While the litigation was pending some defendants challenged US’592 in PTAB. After oral hearing PTAB found claim 1-5 & 7-30 invalid as obvious. PTAB also denied Sanofi’s motion to amend the claims. Sanofi then disclaimed claims 7, 11, 14–16, 26 and informed the district court accordingly. But district court still ruled that disclaimed are invalid. Sanofi appealed because as per them there was no case or controversy as claims were cancelled. Defendants cross-appealed & took position that there was case or controversy & district court did not err. Defendants also appealed district court’s decision which found claims 1-2 of US’170 valid.

a. Appeal regarding case or controversy - 

On appeal, Sanofi argues that after it disclaimed the particular claims, there was no longer a case or controversy regarding those claims, and the district court thus lacked authority to invalidate them. Defendants responded that there may still have been a case or controversy over the disclaimed claims depending on the merits of their potential future issue or claim preclusion defense, which Defendants could raise if Sanofi succeeds in amending claims of the ’592 patent & then asserts the amended claims against Defendants.

Federal Circuit said that Article III empowers federal courts to adjudicate only “Cases” and “Controversies.” To satisfy the case or controversy requirement in the declaratory judgment context, the parties’ dispute must be “‘real and substantial” rather than mere hypothetical state of facts. Further, “an actual controversy must be extant at all stages of review, not merely at the time the complaint is filed. When Sanofi disclaimed the disclaimed claims, it “effectively eliminated those claims from the . . . patent,” Vectra Fitness, Inc. v. TNWK Corp., 162 F.3d 1379, 1383 (Fed. Cir. 1998), leaving the ’592 patent “as though the disclaimed claim(s) had ‘never existed,’” Genetics Inst., LLC v. Novartis Vaccines & Diagnostics, Inc., 655 F.3d 1291, 1299 (Fed. Cir. 2011). Defendants here point to no such concrete and realistic threat created by the effectively nonexistent disclaimed claims. Therefore, Defendants’ reliance on Teva [Teva Pharmaceuticals USA, Inc. v. Novartis Pharmaceuticals Corp., 482 F.3d 1330 (Fed. Cir. 2007)] is misplaced.

Defendants further alleged that if court vacates the district court’s judgment of invalidity of the disclaimed claims, then Defendants will lose the possible benefit of an issue preclusion defense based on that judgment should Sanofi obtain amended claims and assert them against Defendants. Federal Circuit, however, concluded that this alleged injury did not provide a case or controversy at the time of the court’s judgment. Because the relevance of the disclaimed claims to a possible issue preclusion defense was merely speculative. Second, even assuming that Defendants’ stake in the district court’s judgment concerning the disclaimed claims was sufficiently imminent, they have not established that the judgment pertaining to those claims is material to a possible future suit. Defendants have not shown the existence of a case or controversy over the disclaimed claims at the time the district court entered judgment. The district court thus lacked authority & therefore Federal Circuit vacated court’s judgment with respect to disclaimed claims.

b. Appeal regarding validity of claims 1 & 2 of US’170 –

                                                [Fig: https://ejhp.bmj.com/content/22/5/260]

Defendants’ cross-appealed from the district court’s judgment that cabazitaxel, claimed in claims 1 and 2 of the ’170 patent, would not have been obvious over docetaxel, which has been determined to be the lead compound and, in effect here, the closest prior art.  Defendants argued at the district court that a skilled artisan would have been motivated to increase the lipophilicity of docetaxel to interfere with a protein called Pgp to thwart drug resistance & therefore, would have made replacement at C7 & C10 position with methoxy group. Sanofi responded that Defendants’ obviousness theory was hindsight-driven and that the district court did not err in rejecting it.

Federal Circuit said that district court made no error as in finding that prior art references, Hait and Lampidis would not have provided a reason to make docetaxel more lipophilic. Because, these references not contemplate taxanes, they investigated compounds that are structurally very different from taxanes. Even assuming there was some general motivation to make docetaxel more lipophilic to combat drug resistance, the district court also did not clearly err in finding that Defendants failed to establish a motivation to do so by specifically making simultaneous methoxy substitutions at C7 and C10. Taxane researchers investigated substitutions at many positions (C2, C3′, C7, C9, and C10), and the voluminous references in this case support that finding. Despite the apparent interest in taxane analogs, not a single reference relied on by Defendants made simultaneous substitutions of any kind at C7 and C10. And of the references that made individual methoxy substitutions at C7 or C10, none tested those taxane analogs against drug resistant cell lines or taught that the analogs would overcome drug resistance. Defendants reference-specific arguments are emblematic of hindsight reasoning.

Thus, Federal Circuit agreed with Sanofi that the district court correctly concluded that claims 1 and 2 of the ’170 patent would not have been obvious over docetaxel.