One of the casualties of the Leahy-Smith America Invents Act in 2012 was 35 U.S.C. § 145, which had provided recourse to U.S. District Courts for U.S. patent applicants disgruntled with a determination of unpatentability before the U.S. Patent and Trademark Office, but was abrogated by the AIA. This avenue had as one advantage the ability to present new evidence and to have that evidence evaluated by the Court. While providing an alternative outlet, the outcome was not always to the applicant's benefit; an example of a negative outcome arose recently in ImmunoGen, Inc. v. Hirshfeld, an appeal to the Federal Circuit from a decision against the applicant by the District Court (because after all, recourse to the District Court does not guarantee an outcome different from that before the PTO).
The case arose over ImmunoGen's U.S. Application No. 14/509,809, directed to administration of mirvetuximab (an immunoconjugate between an antibody and an anticancer drug) for treating ovarian and peritoneal cancer cells that overexpress Folate Receptor 1 ("FOLR1"). A disadvantage arising from mirvetuximab administration was a severe ocular side-effect that could compromise sight in patients receiving the treatment. ImmunoGen determined that if the dose was adjusted to 6mg/kg of the patient's adjusted ideal body weight (as set forth below) these side effects could be avoided. The claims of the '809 application were directed to these adjusted administration methods; Claim 1 is representative:
1. A method for treating a human patient having an FOLR1-expressing ovarian cancer or cancer of the peritoneum comprising administering to the patient an immunoconjugate which binds to FOLR1 polypeptide,
wherein the immunoconjugate comprises an antibody or antigen-binding fragment thereof that comprises the variable light chain (VL) complementarity determining region (CDR)-1, VL CDR-2, VL CDR-3, variable heavy chain (VH) CDR-1, VH CDR-2, and VH CDR-3 of SEQ ID NOs: 6-9, 11, and 12, respectively, and a maytansinoid, and
wherein the immunoconjugate is administered at a dose of 6 milligrams (mg) per kilogram (kg) of adjusted ideal body weight (AIBW) of the patient.
As disclosed in the specification, the adjusted ideal body weight (or "AIBW") was defined as "a size descriptor that accounts for sex, total body weight, and height." A related value used to calculate AIBW is "ideal body weight" ("IBW"), which is "a size descriptor that is unrelated to total body weight," as it is "an estimate of weight corrected for sex and height, and optionally frame size." These measurements are disclosed in Green and Duffull, 2004, British Journal of Clinical Pharmacology 58: 119-33, incorporated by reference in the specification, wherein ImmunoGen disclosed exemplary formulae for each of AIBW and IBW for men and women:
AIBW = IBW + 0.4(Actual weight in kg – IBW)
IBW (male) = 0.9H – 88
IBW (female) = 0.9H – 92
The PTO rejected the claims for obviousness and obviousness-type double patenting and ImmunoGen appealed to the U.S. District Court for the Eastern District of Virginia. That Court granted summary judgment against ImmunoGen for being "fatally indefinite and fatally obvious" as a matter of law. This appeal followed.
The Federal Circuit vacated the District Court's grant of summary judgment against ImmunoGen and remanded, in an opinion by Judge Clevenger joined by Judges Newman and Stoll. Prior to the Court's legal analysis, the opinion notes that "the district court resolved numerous factual disputes against non-movant ImmunoGen," which the opinion characterized as "an error that is fatal to its ultimate ruling." In the opinion the panel explicates its reasoning as follows. Both indefiniteness and obviousness are questions of law and thus amenable to summary judgment determinations; how a Court comes to decisions on these questions is governed by regional Circuit law but have in common that questions of fact should be decided in favor of the non-movant (here, ImmunoGen). In the District Court action, the USPTO asserted (not improperly) for the first time indefiniteness as a ground for denying a patent to ImmunoGen. The basis for this decision was that the specification described its formula for determining AIBW as "exemplary" which the District Court held as a matter of law made the value capable of being calculated in multiple ways, "leav[ing] a skilled artisan to wonder or to guess whether the formula provided is the only one covered by the '809 Application." This situation was compounded in the Court's view by the definition of IBW as correcting for "sex and height, and optionally frame size" (emphasis in opinion). The District Court refused to consider an express example in the specification as well as expert testimony for the question of whether the skilled artisan would be able to understand the scope and meaning of the AIBW parameter.
The Federal Circuit disagreed, finding the specification replete with intrinsic disclosure that would inform the skilled worker on the meaning of the measurement. These included:
(1) the claims and specification are drawn to a specific dosing regimen for a specific immunoconjugate, which is significant in light of expert testimony that the correction factor used to calculate AIBW is drug-specific; (2) Example 4 describes dosing mirvetuximab in accordance with the claimed method and uses the same AIBW and IBW formulas disclosed in the definitions section; and (3) during the prosecution of the '809 Application, the USPTO never disputed the definiteness, or gave any indication it failed to understand the meaning, of the now-allegedly indefinite term.
The Federal Circuit also credited extrinsic evidence presented by both parties' experts as well as the Green reference. According to the panel, "[w]hen we view this evidence in the light most favorable to ImmunoGen—as we must in our review—we conclude that there are still disputed questions of material fact and summary judgment is therefore inappropriate."
Turning to the District Court's grant of summary judgment on obviousness, the Federal Circuit opined that "the district court improperly resolved a number of factual findings against ImmunoGen." These included the determination that "ocular toxicity was a known negative effect of [immunoconjugates] like [ImmunoGen's]," about which the panel recognized there was conflicting expert testimony. In addition, on this question ImmunoGen presented contrary evidence, including that "(1) ocular toxicity is not well-understood; (2) immunoconjugates have unique pharmacokinetic characteristics, making it difficult to generalize pharmacological effects; (3) it was not known that mirvetuximab would cause ocular toxicity; and (4) published results for Phase 1 testing of mirvetuximab reported no study drug-related serious adverse events or dose-limiting toxicity." In addition, the District Court credited statements in published PCT applications, Nos. WO 2011/106528 and WO 2012/135675 that mirvetuximab dosing could be "easily determined" in the face of expert testimony to the contrary. Finally, the District Court found that changing the dose as disclosed in the '809 specification did not "significantly change the dose for patients who are not significantly overweight or underweight," despite evidence in the '809 application and Phase 1 clinical trials leading to the opposite conclusion. The District Court's finding that there were no undisputed questions of material fact in view of this evidence was error according to the Federal Circuit, which "repeats across its other factual findings, including those relating to motivation to combine, reasonable expectation of success, and secondary considerations." Accordingly, the Federal Circuit remanded the case to the District Court "for proceedings consistent with [their] opinion."
ImmunoGen, Inc. v. Hirshfeld (Fed. Cir. 2022)
Panel: Circuit Judges Newman, Clevenger, and Stoll
Opinion by Circuit Judge Clevenger
