IP Law Daily Proposed chemotherapy treatment methods infringed Alimta patent under doctrine of equivalents
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Friday, August 9, 2019

Proposed chemotherapy treatment methods infringed Alimta patent under doctrine of equivalents

By Thomas Long, J.D.

A ruling that Hospira’s proposed drug literally infringed Eli Lilly’s patent was reversed, but Hospira’s and Dr. Reddy’s use of pemetrexed ditromethamine was not substantially different from Lilly’s patented use of pemetrexed disodium.

The federal district court in Indianapolis erroneously found that pharmaceutical company Hospira literally infringed an Eli Lilly and Co. patent for a method of administering a chemotherapy drug, pemetrexed disodium, with vitamins, in light of the district court’s claim construction of "administration of pemetrexed disodium," when the Hospira product used a different salt of pemetrexed, the U.S. Court of Appeals for the Federal Circuit has decided. However, the Federal Circuit affirmed the lower court’s decision that Hospira’s planned pemetrexed product infringed the patent under the doctrine of equivalents, as well as a decision in a separate infringement action in the same district that a competing product planned by Dr. Reddy’s Laboratories, Inc. and Dr. Reddy’s Laboratories, Ltd. (collectively, "Dr. Reddy’s") also infringed under the doctrine of equivalents. The Federal Circuit affirmed the district court findings that Lilly did not surrender claim scope during prosecution of its patent and did not dedicate use of the defendants’ salt to the public, and that it was not precluded from contending that the defendants’ use of pemetrexed ditromethamine would infringe under an equivalents theory (Eli Lilly and Co. v. Hospira, Inc., August 9, 2019, Lourie, A.).

Lilly markets the compound pemetrexed in the form of a disodium salt as Alimta®, for use both alone and in combination with other active agents to treat certain types of non-small cell lung cancer and mesothelioma. The defendants sought Food and Drug Administration approval to make and market competing pemetrexed products. Lilly asserted that the defendants’ submissions of New Drug Applications (NDA) pursuant to 21 U.S.C. §355(b)(2) infringed Lilly’s U.S. Patent 7,772,209 ("the ’209 patent") under 35 U.S.C. §271(e)(2). The ’209 patent provides for a method of using the compound pemetrexed disodium that mitigates the toxicity associated with pemetrexed treatment, using the vitamin pretreatment regimen of vitamin B12 and folic acid. Although Hospira and Dr. Reddy’s NDAs relied on Lilly’s clinical data for pemetrexed disodium, their proposed products used a different pemetrexed salt, pemetrexed ditromethamine.

In the Dr. Reddy’s case, the district court construed the patent’s phrase "administration of pemetrexed disodium" to mean "liquid administration of pemetrexed disodium," which "is accomplished by dissolving the solid compound pemetrexed disodium into solution." In the Hospira case, Lilly also asserted infringement under the doctrine of equivalents, but Lilly also asserted literal infringement because Hospira’s proposed product label allows reconstitution of its pemetrexed ditromethamine salt in saline. The court determined on summary judgment that the label for Dr. Reddy’s infringed the ’209 patent under the doctrine of equivalents. After the decision in the Dr. Reddy’s case was issued, Hospira conceded, contingent upon its right to appeal, that its product would infringe under the claim construction of "administration of pemetrexed disodium" set forth in that opinion and that its doctrine of equivalents arguments were likewise foreclosed. The district court determined on summary judgment that Hospira’s NDA product literally infringed the ’209 patent and also infringed under the doctrine of equivalents. The district court entered orders under 35 U.S.C. § 271(e)(4)(A) prohibiting FDA approval of the products at issue until the expiration of the ’209 patent. Both defendants appealed.

Arguments on appeal. Hospira requested reversal of the district court’s finding that its submission of an NDA for its pemetrexed product literally infringed the claims of the ’209 patent. Dr. Reddy’s and Hospira both argued that the district court erred as a matter of law by refusing to apply prosecution history estoppel to bar Lilly’s doctrine of equivalents claim, and Dr. Reddy’s also contended that the disclosure-dedication rule precluded Lilly’s equivalents claim. Finally, Dr. Reddy’s disputed the district court’s finding that administration of pemetrexed ditromethamine is equivalent to the claim element "administration of pemetrexed disodium."

Literal infringement. According to Hospira, it cannot literally infringe the claims of the ’209 patent because intravenous administration of pemetrexed ditromethamine dissolved in saline—a solution which contains pemetrexed and chloride anions alongside sodium and tromethamine cations—is not "administration of pemetrexed disodium." The Federal Circuit agreed, holding that it was clearly erroneous for the district court to hold that the "administration of pemetrexed disodium" step was met because Hospira’s pemetrexed ditromethamine product will be dissolved in saline before administration. "A solution of pemetrexed and chloride anions and tromethamine and sodium cations cannot be deemed pemetrexed disodium simply because some assortment of the ions in the solution consists of pemetrexed and two sodium cations," the court said. The court concluded that to literally practice the "administration of pemetrexed disodium" step under the district court’s claim construction, the pemetrexed disodium salt must be itself administered. Therefore, the district court’s finding of literal infringement was reversed.

Doctrine of equivalents. The Federal Circuit noted that while it was settled that a patentee is entitled to invoke to some extent the doctrine of equivalents in all cases, courts had placed important limitations on a patentee’s ability to assert infringement under an equivalents theory. These limitations included prosecution history estoppel, the disclosure-dedication rule, and the principle that substantial differences between the accused product and the patented invention will foreclose a finding of infringement.

Prosecution history estoppel. Prosecution history estoppel arises when a patent applicant narrows the scope of claims during prosecution for a reason substantially relating to patentability, thereby surrendering claim scope. The primary dispute here was whether Lilly rebutted the presumption of prosecution history estoppel that attached to a narrowing amendment it made to the application that resulted in the ’209 patent. In order to overcome an anticipation rejection by the USPTO’s patent examiner, Lilly had amended the claims to narrow the original reference to "antifolate" to "pemetrexed disodium" and cancelled its dependent claim limited to pemetrexed disodium. The district court held that prosecution history estoppel did not bar Lilly from asserting that Dr. Reddy’s proposed pemetrexed ditromethamine product would infringe through the doctrine of equivalents because the reason for Lilly’s amendment was to distinguish other antifolates and was therefore only tangential to pemetrexed ditromethamine. The Federal Circuit agreed with the district court, reasoning that the particular type of salt to which pemetrexed is complexed related only tenuously to the reason for the narrowing amendment, which was to avoid anticipation by prior art. The appellate court said that the prosecution history strongly indicated that the reason for the amendment was not to cede other, functionally identical, pemetrexed salts. The argument that Lilly must prove that it could not have drafted a claim that literally encompassed pemetrexed ditromethamine was rejected as excessive and contrary to precedent.

Disclosure-dedication rule. Under the disclosure-dedication rule, subject matter disclosed by a patentee, but not claimed, is considered dedicated to the public. The district court rejected Dr. Reddy’s argument that Lilly dedicated pemetrexed ditromethamine to the public under the disclosure-dedication rule through its reference to a prior art patent’s antifolate compounds because the prior art was not incorporated by reference into the ’209 patent. The district court also concluded that, in any event, Lilly’s reference disclosed pemetrexed ditromethamine only within a genus of thousands of compounds, which did not constitute the requisite disclosure of an identifiable alternative under Federal Circuit precedent. The Federal Circuit held that the disclosure-dedication rule was inapplicable to this case because the ’209 patent did not disclose methods of treatment using pemetrexed ditromethamine, and, therefore, Lilly could not have dedicated this method to the public.

Merits of equivalents claim. A component in an accused product or process may be equivalent to a claim element if the two are insubstantially different with respect to the role played by the element in the context of the specific patent claim, the court explained. Dr. Reddy’s argued that the district court erred in finding that its proposed pemetrexed ditromethamine product will be administered in an insubstantially different way from the claimed method. The Federal Circuit found no clear error in the district court’s findings that the chemical differences between sodium and tromethamine were clinically irrelevant because each undisputedly lacked therapeutic activity. Dr. Reddy’s product would accomplish an identical aim to the patented invention, furnishing the same amount of pemetrexed to active sites in the body, in exactly the same way, by diluting a pemetrexed salt in an aqueous solution for intravenous administration. Therefore, the court held that both cases were "eminently suitable for application of the doctrine of equivalents," and that neither prosecution history estoppel nor the disclosure-dedication rule barred Lilly from asserting infringement through equivalence.

This case is No. 2018-2126, 2018-2127, and 2018-2128.

Attorneys: Adam Lawrence Perlman (Williams & Connolly LLP) for Eli Lilly and Co. Bradford Peter Lyerla (Jenner & Block LLP) for Hospira, Inc. John C. O'Quinn (Kirkland & Ellis LLP) for Dr. Reddy’s Laboratories, Inc., and Dr. Reddy’s Laboratories, Ltd.

Companies: Eli Lilly and Co.; Hospira, Inc.; Dr. Reddy’s Laboratories, Inc.; Dr. Reddy’s Laboratories, Ltd.

MainStory: TopStory Patent FedCirNews

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