Eli Lilly and Company today got hammered by a jury in the U.S. District Court of Massachusetts in Boston in a decision in the case of Ariad Pharmaceuticals et al. v. Eli Lilly and Company. The Jury handed down a verdict that U.S. Patent No. 6,410,516, owned by Harvard, the Massachusetts Institute of Technology, and the Whitehead Institute and licensed to Ariad Pharmaceuticals, is valid and infringed by Lilly’s sale of Evista® and Xigris®.

The ‘516 patent, awarded after 16 years of prosecution in the USPTO, presents 203 separate claims covering methods of treating disease by regulating a family of molecules known as NF-kB, a biological trigger believed to play a role in a wide range of illnesses from cancer to osteoporosis to bacterial infections.

The ‘516 patent claims methods based on the discovery of a naturally-occurring biological pathway, the NF-kappaB pathway. While Ariad contends that the patent covers all means for modulating the NF-kappaB pathway, Lilly’s contention is that it discovered the drugs in question, Evista and Xigris and disclosed their medicinal properties years before the patentees’ scientists made their discovery.

In June 2002, Lilly was sued by Ariad, MIT, Whitehead and Harvard in the U.S. District Court of Massachusetts alleging that sales of two of Lilly’s products, Evista and Xigris, were inducing the infringement of their patent and seeking royalties on past and future sales of these products. The jury awarded the plaintiffs approximately $65 million in back royalties and a 2.3 percent royalty on future U.S. sales of Evista and Xigris until the patent’s expiration in 2019.

Regarding Evista, the jury found that the drug infringed claims 80 and 95:

80. [A method for modifying effects of external influences on a eukaryotic cell, which external influences induce NF-kappaB-mediated intracellular signaling, the method comprising altering NF-kappaB activity in the cells such that NF-kappaB-mediated effects of external influences are modified … wherein NF-kappaB activity in the cell is reduced] wherein reducing NF-kappaB activity comprises reducing binding of NF-kappaB to NF-kappaB recognition sites on genes which are transcriptionally regulated by NF-kappaB.

95. [A method for reducing, in eukaryotic cells, the level of expression of genes which are activated by extracellular influences which induce NF-kappaB-mediated intracellular signaling, the method comprising reducing NF-kappaB activity in the cells such that expression of said genes is reduced] carried out on human cells.

1(a) Does a patient who takes Evista in accordance with the product label for prevention and/or treatment of osteoporosis infringe claim 80 and/or claim 95 of the ‘516 patent? Yes.

1(b) Did defendant Eli Lilly induce infringement of claim 80 and/or claim 95 by selling or causing a third party to sell Evista to such patients? Yes.

1(c) Did defendant Eli Lilly contributorily infringe claim 80 and/or claim 95 by selling or causing a third party to sell Evista? Yes.

Regarding Evista, the jury found that the drug infringed claims 144 and 145:

144. [A method for reducing bacterial lipopolysaccharide-induced expression of cytokines in mammalian cells, which method comprises reducing NF-kappaB activity in the cells so as to reduce bacterial lipopolysaccharide-induced expression of said cytokines in the cells], wherein reducing NF-kappaB activity comprises reducing binding of NF-kappaB to NF-kappaB recognition sites on genes which are transcriptionally regulated by NF-kappaB.

145. [A method for reducing bacterial lipopolysaccharide-induced expression of cytokines in mammalian cells, which method comprises reducing NF-kappaB activity in the cells so as to reduce bacterial lipopolysaccharide-induced expression of said cytokines in the cells], carried out on human cells.

2(a) Does a patient who takes Xigris in accordance with the product label for treatment of severe sepsis infringe claim 144 and/or claim 145? Yes.

2(b) Did defendant Eli Lilly induce infringement of claim 144 and/or claim 145 of the ‘516 patent by selling or causing a third party to sell Xigris? Yes.

2(c) Did defendant Eli Lilly contributorily infringe claim 144 and/or claim 145 by selling or causing a third party to sell Xigris? Yes.

This decision appears to go against long-standing patent practice in that one cannot get a patent that would remove known materials from the public. In addition, it has always been the case that one may patent a drug without knowing how it works. If this decision were allowed to stand, many drugs could eventually be found to infringe patents that were issued long after the drugs themselves were discovered.

This also begs the question of if a researcher discovers a drug without ever knowing the drug acts on a patented pathway or before the pathway is understood, does that constitute infringement? If the drug was acting on the pathway before the pathway was discovered, does the existence of the drug invalidate the patent on the pathway by rendering it not “new”? This could also give rise to an ever-increasing number of conflicting patents. Because NF-kB can activate so many genes, more than 150, it is implicated in many diseases.

A separate bench trial with the U.S. District Court of Massachusetts will be held on Lilly’s contention that the patent is unenforceable and will also consider the patent’s improper coverage of natural processes. In June 2005, the U.S. Patent and Trademark Office commenced a reexamination of the patent (Reexam. C.N. 90/007,828). The reexamination is currently in progress although the USPTO has not issued any substantive action.

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