By Andrew Williams —

When
assessing the validity of a patent, you cannot ignore the dependent
claims.  That was the main takeaway from
the recent Federal Circuit case, Research Foundation of State University of New York v. Mylan Pharmaceuticals
Inc.  In that case, the lower court
had invalidated all of the asserted claims of two particular patents as
inherently anticipated in view of several prior art references.  However, three of these claims were dependent
claims, and they all had the same additional limitation — "wherein the
tetracycline compound has substantially no anti-microbial activity in said
mammal system."  The lower court did not
address this limitation, so the Federal Circuit vacated the finding of
invalidity of these three claims and remanded for a determination whether the
identified prior art references also contained this limitation.  The Court did not, however, fault the lower
court for overlooking this limitation, but instead placed the blame squarely on
the patent-asserting parties for failing to highlight this issue in the
post-trial papers.  The result was
somewhat academic, in part because the Plaintiffs also asserted a
later-expiring patent that had been found by the lower court to be valid and
infringed by Mylan.  The Federal Circuit
affirmed the remainder of the lower court's findings, with the result being
that the FDA will not be able to approve Mylan's ANDA until the expiration of
the infringed patent, which currently will occur on December 19, 2027.

The
Federal Circuit opinion did not contain much more detail than the above
paragraph.  In fact, without that one
issue, this case most likely would have been a Rule 36 affirmance.  Therefore, for the benefit of the readers of
this blog, we will provide some context for this case.  The drug at issue is doxycycline, which is
sold by Galderma Laboratories, L.P. under the brand name Oracea® for the
treatment of acne rosacea.  There were
five patents that cover Oracea® that were asserted in this case:  the "Ashley Patents," U.S. Patent Nos. 7,211,267 and 7,232,572; the "Amin Patents,"
U.S. Patent Nos. 5,789,395 and 5,919,775; and the "Chang Patent," U.S. Patent
No. 7,749,532.

In
October 2008, Mylan submitted ANDA No. 90-855 to market a generic version of
this drug.  Because doxycycline was an
old antibiotic, it was not entitled to most of the benefits of the Hatch-Waxman
scheme at the time of this ANDA filing.  However, Congress subsequently revised the statute, paving the way for
the Orange Book listing of the Ashley and Amin patents.  Nevertheless, the FDA made a determination
that these "later-listed" antibiotic patents were not entitled to a 30-month
stay.  Because the stay was not
available, Galderma requested a preliminary injunction, which the United States
District Court for the District of Delaware granted on June 28, 2010.  The FDA then approved Mylan's product on July
1, and the Chang patent issued on July 6, 2010.  In an effort to invalidate the Chang patent, Mylan filed a declaratory
judgment action, and the two cases were subsequently combined.

After
a trial on the merits, the lower court found that the Ashley patents were not
infringed by Mylan because Galderma failed to prove that Mylan's ANDA product
contained an amount of doxycycline that does not significantly inhibit the
growth of microorganisms.  This outcome
was based in part on the construction of two claim terms:  "a sub-antibacterial
amount," which was held to mean "an amount that does not significantly inhibit
the growth of microorganisms, e.g.,
bacteria," and "an amount that . . . has substantially no antibiotic activity,"
which was held to mean "an amount that is effective to treat the papules and
pustules of rosacea but does not significantly inhibit the growth of
microorganisms, e.g., bacteria."  The District Court also determined that the word "amount" applies to all parts of the human body.  Therefore, the Court concluded, because there
are approximately 100,000,00,000,000 bacterial cells in the human body, it
would be almost impossible for Galderma to prove infringement of a claim that
required no significant inhibition of any of these microorganisms.  Moreover, Mylan had introduced in vivo studies that showed that the administration
of its ANDA product significantly inhibited the growth of the bacteria in the
oral cavity.  As a result, the District Court held
that the claims of the Ashley patents were not infringed.  Mylan did not, however, prove that these same
claims were invalid.

With
respect to the Amin patents, which were the two patents that were the subject
of the Federal Circuit opinion, the Court also found that Galderma failed to
prove that the asserted claims were infringed.  Galderma had failed to prove that Mylan's ANDA product would inhibit the
production of endogenously produced Nitric Oxide ("NO"), or inhibit the
expression of inducible Nitric Oxide synthase ("iNOS").  In addition to the non-infringement finding,
the lower court found that the asserted claims were inherently anticipated by
several prior art references.  Claim 1 of
the '395 patent was representative:

1.  A method for inhibiting nitric oxide production in a mammal system,
comprising providing to the mammalian system an amount of a tetracycline
compound sufficient to cause a decrease in the amount of nitric oxide produced
endogenously by the mammalian-system.

The
cited art did not expressly teach that the prior art use of doxycycline
inhibited NO production or iNOS expression, but the District Court found these to be
inherent properties of these references.  Half of these references taught the use of lower dosages of doxycycline,
but the lower court only reviewed the higher dosage references to conclude that
they all inherently anticipate all of the claimed methods.  However, as indicated above, because the
dependent limitation, which required that the compound also have no
anti-microbial activity, was not addressed, the validity finding of these
dependent claims was in error.  The
Federal Circuit stopped short of reversing this finding, but instead remanded
for a determination of not only the teaching of the lower-dosage references,
but an analysis of whether any of the references inherently disclosed the lack
of anti-microbial activity.

Finally,
the lower court did find that the later issued Chang patent was valid and
infringed.  However, because the Chang
patent was not Orange Book listed, the District Court held a separate hearing regarding remedies
on February 17, 2012.  The Court
subsequently granted a permanent injunction pursuant to 35 U.S.C. § 283 for
many of the same reasons that it had previously granted the preliminary
injunction.  It also held that Galderma
was entitled to relief under 35 U.S.C. § 271(e)(4)(A), which prevents the FDA
from approving an ANDA product prior to the expiration of the patent at
issue.  Mylan had questioned whether such a
remedy under this section was appropriate because the patent was not listed in
the Orange Book.  The District Court pointed out,
however, that the Federal Circuit recently addressed the issue whether Section
271(e)(2) was available to non-Orange Book listed patents that cover an ANDA
product, concluding that it is the filing of an ANDA that infringes a patent
that provides jurisdiction, regardless of whether that patent is listed in the
Orange Book.  See AstraZeneca Pharmacetuticals LP v. Apotex Corp., 669 F.3d 1370
(Fed. Cir. 2012).  By extension, the
lower court held that the Hatch-Waxman remedy of Section 271(e)(4) is also be
available to a patent holder, regardless of whether the patent at issue is
Orange Book listed.

The
final matter addressed by the lower court was the disposition of the bond that
Galderma posted upon entry of the preliminary injunction.  Mylan pointed out that the FDA approved its
ANDA product on July 1, 2010, but the Chang patent did not issue until July 6,
2010.  Therefore, Mylan contended,
because the District Court found that Mylan's ANDA product did not infringe either the
Ashley or Amin patents, it was entitled to be compensated for the time between
these few days.  The lower court
disagreed, in part because Mylan had not presented its "winning" argument
regarding the in vivo data until
trial, and therefore to a certain extent was to blame for the harm it suffered.

In
the end, the remand to determine the validity of the Amin patents was somewhat
academic, in part because Mylan was found not to infringe the Amin patents
anyway.  However, Galderma and its
co-plaintiffs have filed suit against several other ANDA filers seeking to
market generic versions of this drug.  Therefore, because it is possible that one or more of these ANDA products
will be found to infringe the Amin patents, the validity of the dependent claim
may turn out to be relevant after all.

Research
Foundation of State University of New York v. Mylan Pharmaceuticals Inc. (Fed.
Cir. 2013)
Nonprecedential
disposition
Panel:
Circuit Judges Newman, Reyna, and Taranto
Per
curiam opinion