[Ip-health] Can a Known Drug Infringe a Later Issued Patent on the Pathway of Action? A Jury Says Yes.

[James Love]

In this somewhat dated report, Patent Baristas discuss a case where a
Harvard/MIT patent, which was awarded after 16 years of prosecution,
involving 203 separate claims for methods based on a naturally-
occurring biological pathway, was used against drugs already in the
market, despite the fact that the discovery of the drugs and their
medicinal properties were known and disclosed years before the new
patented "invention."  From the PB note:

* 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.

I raise this because it provides an illustration of a practice that
countries might want to address pro-actively, in guidelines for
patents on medicines.   For example, by indicating that new patents
could not remove known uses of known materials from use, or some
other rule.  This type of litigation is expensive, and jury verdicts
in patent cases are notoriously random.  Jamie

http://patentbaristas.com/archives/cat_ip_litigation.php

May 04, 2006
Can a Known Drug Infringe a Later Issued Patent on the Pathway of
Action? A Jury Says Yes.

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 (tm) and Xigris (tm).

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 =91516 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 =91516 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.

---------------------------------
James Love, CPTech / www.cptech.org / mailto:james.love@cptech.org /
tel. +1.202.332.2670 / mobile +1.202.361.3040

"If everyone thinks the same: No one thinks."  Bill Walton"