ViiV Healthcare UK Ltd. v. Lupin Ltd.

Case Name: ViiV Healthcare UK Ltd. v. Lupin Ltd., C.A. 11-576-RGA (consol.), 2013 U.S. Dist. LEXIS 176790 (D. Del. Dec. 17, 2013) (Andrews, J.) (ANDA product did not infringe asserted claims because it used abacavir in a salt form, not abacavir in its free base or pure form; invention is not obvious because there was very little about anti-HIV therapy that could be described as predictable at the time of the invention.)

Drug Product and Patent(s)-in-Suit: Trizivir® (abacavir sulfate/lamivudine/zidovudine); U.S. Patent No. 6,417,191 (“the ’191 patent”)

Nature of the Case and Issue(s) Presented: ViiV asserts that independent claim 45 recites abacavir, AZT, and 3TC, and Lupin’s generic tablet capsule product will infringe dependent claim 47, which claims a tablet capsule unit dosage form comprising those compounds. In response, Lupin argues that claim 47 is limited to the chemical formulation of “abacavir free base,” i.e., pure abacavir. Lupin argues that its generic product does not contain “abacavir free base,” but rather uses “abacavir sulfate,” a salt form of abacavir. According to Lupin, the salt form of abacavir has a chemical structure that differs from pure abacavir, and the salt form’s chemical structure is not encompassed by claim 47. Defendants also asserted that the ’191 patent is invalid as obvious. Lupin individually asserted that the ’191 patent is invalid due to lack of enablement and utility. The court held a bench trial and found that: (i) defendants failed to prove any of their invalidity defenses by clear and convincing evidence; and (ii) ViiV failed to prove that Lupin’s generic drug product infringes the asserted claims of the ’191 patent.

Why Defendants Prevailed: The court found that Lupin’s proposed ANDA product will not infringe, literally or under the doctrine of equivalents, the asserted claims of the ’191 patent. Lupin’s ANDA product will use abacavir sulfate, not abacavir in its free base or pure form. Each ANDA section proffered by ViiV identifies the active ingredient as “abacavir sulfate.” The proposed ANDA labeling expressly defines the active ingredient as the sulfate or salt form. Although ViiV argued that abacavir is “in” abacavir sulfate, the court found that the sulfate form comes into being only after a reaction between abacavir free base and sulfuric acid in isopropyl alcohol, and the resulting salt product has a changed molecular weight and forms new molecular bonds. Therefore, it is chemically distinct from abacavir free base or pure abacavir. The court held that Lupin’s ANDA does not contain abacavir free base as recited in claim 45.

As for the method claims, all of the asserted claims recited the limitation, “the treatment or prevention of the symptoms or effects of an HIV infection.” The parties disputed whether treatment or prevention of the HIV infection itself falls within the scope of “symptoms or effects.” Lupin argued that the plain meaning of “symptoms or effects” of HIV is limited to opportunistic infections or conditions and not to the HIV infection itself. Because its generic drug product is intended to treat HIV infection, not the symptoms or effects of an infection, Lupin argued it does not indirectly infringe the claims. ViiV disagreed and argued that Lupin’s ANDA product is aimed at halting replication of HIV, which is an effect of infection, and it therefore infringed that limitation. The court found that defendants’ products met the limitation of treating “symptoms or effects” of an HIV infection even though the products only acted on the HIV virus and not the actual symptoms or effects related to HIV infection. But the methods claims included the abacavir free base limitation, and therefore, for the same reasons the formulation claim was not infringed, the method claims were not infringed.

Concerning obviousness, Teva asserted that the combination of abacavir and 3TC was obvious because: (i) a skilled artisan would have been motivated to combine complementary and potent nucleoside reverse transcriptase inhibitors (“NRTIs”) to treat early-stage HIV, with a reasonable expectation that such a combination would suppress HIV reproduction and delay or prevent the development of resistant strains of the virus; and (ii) a skilled artisan would have been particularly motivated to replace AZT in the AZT/3TC combination with the NRTI abacavir, yet it avoided the toxicity problems associated with AZT while still complementing 3TC. Lupin argued that a skilled artisan would have been motivated to build upon the success of AZT/3TC by adding a third potent and low-toxicity drug to the therapeutic regimen. ViiV argued that combination therapy was unpredictable, the sizeable universe of potentially useful drugs was inconsistent with an obviousness finding, problems of cross-resistance overrode considerations of potency and would have discouraged a skilled artisan from combining abacavir and 3TC, and it made no sense to alter AZT/3TC by substituting abacavir for AZT, as AZT/3TC was the only known combination that worked. The court agreed with ViiV and found that at the time of the invention, there would have been too many possible combinations that a skilled artisan would not have been necessarily motivated to combine the three drugs claimed in the ’191 patent. Moreover, it was not settled at the time of the invention whether the cross resistance of the three drugs would have taught away from the patented combination.

Concerning secondary considerations of non-obviousness, the Court found that at the time of the invention in 1995, there were “monumental” efforts to discover drugs treatments for HIV infection, most of which failed. This favored ViiV. But the court rejected ViiV’s assertion of industry praise and commercial success. ViiV had numerous blocking patents that would have prevented others from competing in the market.

Finally, the court rejected defendants’ argument that the patent claims were not enabled because the specification failed to teach how to treat all mammals. The claims were limited to “infected animals,” and the specification consistently referred to “infected animals.” As only humans and possibly primates could be infected with HIV, the specification did not need to teach how to treat all mammals, just those that could be infected with HIV.