On August 9, 2019, the Federal Circuit issued an opinion in Eli Lilly and Co. v. Hospira, Inc. that addresses the “tangential” exception to prosecution history estoppel. The Federal Circuit affirmed the district court’s finding of infringement under the doctrine of equivalents because a narrowing amendment made during prosecution was only tangentially related to the equivalents in the accused products.

 

Hospira and Dr. Reddy’s (collectively, appellants) filed new drug applications (NDAs) to market pemetrexed ditromethamine. Eli Lilly alleged that submission of those NDAs infringed Eli Lilly’s U.S. Patent 7,772,209 under the Hatch-Waxman Act. 

 

The ‘209 patent claims an improved method of treatment with antifolates,¹ particularly pemetrexed disodium, where a methylmalonic acid lowering agent² and folic acid are administered before administration of pemetrexed disodium. 

 

Representative claim 12 of the ‘209 patent reads:

 

12. An improved method for administering pemetrexed disodium to a patient in need of chemo-therapeutic treatment, wherein the improvement comprises:

 

a) administration of between about 350 μg and about 1000 μg of folic acid prior to the first administration of pemetrexed disodium;

 

b) administration of about 500 μg to about 1500 μg of vitamin B12, prior to the first administration of pemetrexed disodium; and

 

c) administration of pemetrexed disodium.

 

(Emphasis added).

 

The issue before the Federal Circuit was whether the use of a different salt form of pemetrexed (pemetrexed ditromethamine) in appellants’ NDA products was equivalent to the pemetrexed disodium in the ‘209 patent claims.

 

The ‘209 patent claims priority to an application that issued as U.S. Patent No. 7,053,065. As filed, the application for the ‘065 patent included claims 2 and 5 to methods of administering antifolates with a methylmalonic acid lowering agent, with or without folic acid:

 

2. A method of reducing the toxicity associated with the administration of an antifolate to a mammal comprising

administering to said mammal an effective amount of said antifolate in combination with a methylmalonic acid lowering agent.

5. A method of reducing the toxicity associated with the administration of an antifolate to a mammal comprising

administering to said mammal an effective amount of said antifolate in combination with a methylmalonic acid lowering agent and FBP [folic binding protein] binding agent [folic acid is an FBP binding agent].

 

During prosecution, claim 2 was rejected as anticipated by Arsenyan, which taught treating mouse tumors with methotrexate (an antifolate) and methylcobalamin (a vitamin B12 derivative that reduces methylmalonic acid), and claim 5 was rejected as obvious over Ohmori (which taught co-administration of vitamin B12 and folic acid) and John (which taught that toxicities often accompanied administration of pemetrexed disodium). 

 

In response to the rejections, Eli Lilly amended claims 2 and 5 by narrowing “antifolate” to “pemetrexed disodium,” arguing, with respect to claim 2, that Arsenyan does not disclose pemetrexed disodium, and with respect to claim 5, that John does not suggest co-administration with vitamin B12 or folate, and Ohmori does not “teach the use of [vitamin B12] to reduce toxicities associated with an antifolate.” The Patent Office then withdrew its rejections. 

 

If an accused product falls squarely within the language of a patent claim, infringement is said to be literal. But if the accused product lacks even a single claim element, the claim is not literally infringed. However, infringement may still be found under the doctrine of equivalents, a doctrine that prevents an accused infringer from avoiding infringement by changing only insubstantial details of a claimed invention while retaining their essential functionality. See Sage Products, Inc. v. Devon Industries, 126 F.3d 1420, 1424 (Fed. Cir. 1997).

 

One limitation on the doctrine of equivalents is prosecution history estoppel. “Prosecution history estoppel applies as part of an infringement analysis to prevent a patentee from using the doctrine of equivalents to recapture subject matter surrendered from the literal scope of a claim during prosecution.” Trading Techs. Int'l, Inc. v. Open E Cry, LLC, 728 F.3d 1309, 1322 (Fed. Cir. 2013).

 

The surrender of subject matter by amendment during patent prosecution creates a presumption that the surrendered subject matter cannot be recaptured under the doctrine of equivalents. See, e.g., AquaTex Indus. v. Techniche Solutions, 479 F.3d 1320, 1325 (Fed. Cir. 2007). The patentee can rebut that presumption by showing that the amendment was unrelated to patentability.³ Id. 

 

Appellants argued that Eli Lilly’s amendment of the claim term “antifolate” to “pemetrexed disodium” during prosecution of the ‘065 patent estopped Eli Lilly from arguing that appellants’ pemetrexed ditromethamine was equivalent to the pemetrexed disodium claimed in the ‘209 patent.⁴  

 

Eli Lilly did not dispute that the amendment was both narrowing and made for a substantial reason relating to patentability. Rather, Eli Lilly argued that the amendment bore no more than a tangential relationship to the equivalent (i.e., pemetrexed ditromethamine) in question. 

 

The Federal Circuit rejected appellants’ argument that prosecution history estoppel should apply because during prosecution, Eli Lilly failed to explain why it did not pursue an amendment that would have literally encompassed pemetrexed ditromethamine, finding that “[t]he reason for Lilly’s amendment, as the district court concluded, was to narrow original claim 2 to avoid Arsenyan, which only discloses treatments using methotrexate,” and therefore “the particular type of salt to which pemetrexed is complexed relates only tenuously to the reason for the narrowing amendment.” The Federal Circuit explained that the prosecution of claim 5 supported its finding:

 

the art cited against original claim 5 and its dependent claims in the obviousness ground of rejection was replete with information about pemetrexed disodium; John disclosed clinical trials using pemetrexed disodium, reporting both its efficacy and its toxic side effects. … The prosecution record implies that Lilly’s amendment, inartful though it might have been, was prudential in nature and did not need or intend to cede other pemetrexed salts.

 

The Federal Circuit also distinguished precedent that held “an applicant’s remorse at ceding more claim scope than necessary is not a reason for the tangential exception to apply.” While the Federal Circuit acknowledged that Appellants’ argument is “generally true … where the tangential exception is invoked, [the reason for the amendment] cannot be determined without reference to the context in which it was made, including the prior art that might have given rise to the amendment in the first place.” The Federal Circuit also 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]” (internal quotations and citation omitted). 

 

The Federal Circuit also distinguished precedent that held “where the reason for the amendment and the equivalent in question both relate to the same claim element, the tangential exception does not apply.” Acknowledging that that argument is also often true, and that usually “an amendment that narrows an existing claim element evinces an intention to relinquish that claim scope,” the Federal Circuit held that “the rest of the prosecution history, and the ’209 patent itself, show that it is implausible that the reason for Lilly’s amendment was to surrender other pemetrexed salts.” 

 

While a narrowing amendment made in response to a prior art rejection will typically result in prosecution history estoppel, the Federal Circuit’s Eli Lilly decision highlights the importance of carefully analyzing the file history to determine the reason for the narrowing amendment. If the reason was only tangential to the equivalent at issue, estoppel will not apply.