Federal Circuit Cautions Against Rigid Approach to Prosecution History Estoppel in Fourth Appeal from ALIMTA® Litigations

On August 9, 2019, the United States Court of Appeals for the Federal Circuit, in Eli Lilly & Co. v. Hospira, Inc., Nos. 2018-2126, 2127, 2128, reversed in-part and affirmed in-part a district court’s determination of infringement.  The Federal Circuit reversed the district court’s finding of literal infringement but ultimately affirmed judgments of infringement based on the doctrine of equivalents.

Eli Lilly and Company (“Lilly”) is the owner of U.S. Patent No. 7,772,209 (“the ’209 patent”), which includes claims directed to a method of administering a chemotherapy drug, pemetrexed disodium, a type of antifolate.  The claimed method includes a pretreatment regime of vitamin B12 and folic acid, and is marketed by Lilly under the trade name ALIMTA®.  Both Hospira, Inc. (“Hospira”) and Dr. Reddy’s Laboratories, Ltd. and Dr. Reddy’s Laboratories, Inc. (collectively “DRL”) submitted New Drug Applications (“NDAs”) under § 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(b)(2), seeking to market a generic version of ALIMTA® with an alternative pemetrexed salt.  Lilly asserted the ’209 patent in separate actions against the NDA applicants in the United States District Court for the Southern District of Indiana. 

In the DRL case, the district court construed the phrase “administration of pemetrexed disodium” to mean “liquid administration of pemetrexed disodium,” which “is accomplished by dissolving the solid compound pemetrexed disodium into solution.”  On summary judgment, the district court denied DRL’s theory of noninfringement, holding that prosecution history estoppel did not bar Lilly from asserting that DRL’s proposed pemetrexed salt compound would infringe through the doctrine of equivalents.  The district court also rejected DRL’s argument that Lilly had dedicated DRL’s proposed pemetrexed salt compound to the public under the disclosure-dedication rule.  Following a bench trial, the district court applied the insubstantial differences test to hold that DRL’s proposed product was equivalent to the claimed composition in the ’209 patent.

Hospira also litigated the doctrine of equivalents.  However, Lilly asserted literal infringement because Hospira’s proposed label allows for the reconstitution of its pemetrexed salt in saline.  The district court granted Lilly’s motion for summary judgment for both literal infringement and infringement under the doctrine of equivalents.

On appeal, Hospira argued that the district court incorrectly ruled that its proposed pemetrexed product would literally infringe the claims of the ’209 patent.  And both Hospira and DRL argued that the district court erred in finding that Lilly was not estopped from bringing its doctrine of equivalents claim based on its actions during prosecution of the ’209 patent’s parent application.  DRL also argued that the district court erred in finding that its proposed product was equivalent to the claims of the ’209 patent.

The Federal Circuit agreed with Hospira that the district court’s holding of literal infringement was clearly erroneous in light of the construction of “administration of pemetrexed disodium.”  Specifically, the district court had erred in holding that this method step would be literally met when Hospira’s proposed product is dissolved in saline before administration, reasoning that once a pemetrexed salt is dissolved into solution, the salt’s crystalline structure dissolves and that specific pemetrexed salt no longer exists due to the dissociation of the individual ions.  The Court concluded that simply because pemetrexed and sodium ions might co-exist in a solution together does not mean that that the solution is literally pemetrexed disodium.  Because Hospira’s proposed product would not practice the step of “administration of pemetrexed disodium,” the Federal Circuit reversed the district court’s judgment on literal infringement.

Turning to infringement under the doctrine of equivalents, the Federal Circuit affirmed, holding that the district court correctly determined that equivalents were not surrendered by narrowing the claims during prosecution.  In the parent application of the ’209 patent, Lilly had initially sought broader claims.  Independent claims 2 and 5 of the parent application originally referred to “an antifolate” and not a specific pemetrexed salt.  In response to these claims being rejected as anticipated and obvious, Lilly amended both claims to narrow “antifolate” to “pemetrexed disodium” and canceled a dependent claim limited to pemetrexed disodium.  The examiner eventually withdrew both rejections, and the application issued as U.S. Patent No. 7,053,065, and the ’209 patent later issued from a continuation application.

Defending the district court’s application of the doctrine of equivalents, Lilly argued that its amendment narrowing “an antifolate” to “pemetrexed disodium” was merely a tangential change in relation to DRL and Hospira’s proposed product and that the tangential relation exception should apply.  DRL and Hospira emphasized that the tangential relation is very narrow and DRL further contended that an applicant’s remorse at ceding more claim scope than necessary is not a valid reason for the tangential exception to apply.  The Court cautioned against such a rigid reading of the case law, concluding that Lilly had narrowed the claims to avoid a different antifolate, and that the particular salt to which pemetrexed is complexed was only “tenuously” related to the reason for the narrowing amendment. 

The Federal Circuit also rejected DRL and Hospira’s argument that Lilly needed to prove that it could not have drafted a claim that literally encompassed their proposed pemetrexed salt, finding such argument unsupported and excessive.  Noting that the doctrine is fact specific, the Federal Circuit reaffirmed that whether an amendment only tangentially relates must be determined within the framework of the patented invention and the patent’s prosecution history.  In view of the prosecution history, the Court reasoned that “it is unlikely that a competitor would have been ‘justified in assuming that if he [made an equivalent pemetrexed salt], he would not infringe [the ’209 patent].’”

Finally, the Federal Circuit ruled that the disclosure-dedication rule did not bar Lilly from asserting infringement under the doctrine of equivalents.  Because the ’209 patent does not disclose methods of treatment using DRL and Hospira’s proposed pemetrexed salt, Lilly could not have dedicated a method using that particular salt to the public.

On the merits, the Federal Circuit applied the insubstantial differences test for doctrine of equivalents.  The Federal Circuit stated that in biochemical cases, structural or pharmacological characteristics are particularly germane when examining relevant differences under the insubstantial difference test.  Although DRL focused on chemical differences between its proposed pemetrexed salt to pemetrexed disodium, e.g., pH, buffering capacity, or solubility, in arguing that its method of administration was substantially different than the ’209 patent, the Federal Circuit noted that DRL’s method of treatment contained the same concentration of pemetrexed anion, the clinically relevant molecule, immediately before administration.  Therefore, the Federal Circuit concluded that the district court did not err in finding that DRL and Hospira’s proposed products infringed claims of the ’209 patent.

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