By
Andrew Williams —

Last
week, the Federal Circuit partially overturned the U.S. District Court for the
District of Delaware's decision in Santarus,
Inc. v. Par Pharmaceutical, Inc., thereby allowing Santarus to keep Par's
generic version of Zegerid® off the market until the expiration of the Orange
Book-listed patents.  Judge Newman
provided a separate opinion, also finding that Santarus should have been
successful, but disagreeing with the majority per curiam opinion on the issues of what is required for written
description of a negative claim limitation, whether the subject matter in a
parent patent can serve as prior art to a chain of continuation-in-part
applications, and whether a claimed invention can be considered obvious in view
of overwhelming evidence of unexpected results and skepticism in the field.

The
technology at issue in this case involved specialized formulations of
benzimidazole proton pump inhibitors ("PPIs"), such as omeprazole or
lansoprazole.  This class of compounds is
able to inhibit gastric acid secretion to prevent and treat stomach
acid-related diseases and disorders.  Even though these PPIs block stomach acid production, they are extremely
sensitive to this same acid.  Therefore,
the prior art FDA-approved formulations included an enteric coating to protect
the active ingredient.  Dr. Phillips, at
the University of Missouri, figured out how to formulate these drugs without
the enteric coating by including a buffering agent that allowed the PPIs to be
directly absorbed from the stomach into the blood stream.  This had numerous advantages, including rapid
and consistent bioavailability, increased effectiveness, and ease of
administration (thereby assisting patient compliance).  Dr. Phillips filed a first provisional on
January 4, 1996, to which the first patent, U.S. Patent No.
5,840,737 ("the '737 patent"), claimed priority.  All of the patents at issue in this case were
either continuations or continuations-in-part in a chain that stretched back to
the '737 patent.  The patents-in-suit
included U.S. Patent Nos. 6,489,346 ("the '346 patent"), 6,645,988 ("the
'988 patent"), 6,699,885 ("the '885 patent"), 6,780,882 ("the
'882 patent"), and 7,399,772 ("the '772 patent").

The
present action was initiated after Par filed an ANDA to market the same
formulation as the Zegerid® PPI.  In
response to Santarus' claims of infringement of selected claims of the
patents-in-suit, Par alleged that it did not infringe, and asserted that the
claims at issue were unenforceable, as well as invalid for either a lack of
written description or as being obvious over the prior art.  The Delaware Court found that the claims were
infringed, and that they were not unenforceable, but that some of the claims of
the '772 patent were invalid as failing the written description requirement,
and that all claims were invalid as obvious.  Both parties appealed the rulings adverse to it, but Par did not
challenge the finding of infringement.

Inequitable
Conduct

As
an initial matter, the Federal Circuit affirmed the lower court's finding that
the applicant did not commit inequitable conduct.  Par had alleged that Dr. Phillips had
intentionally withheld information during the prosecution of the parent
application, and only submitted it during the prosecution of subsequent
applications.  Dr. Phillips claimed that
he was not aware that he needed to submit information related to the
experimental administration to patients.  In addition, once the University's patent counsel became aware of the
information, he submitted it in an Information Disclosure Statement.  The lower court found that Dr. Phillips's
explanation "strained credibility," but that there was insufficient
evidence to establish by clear and convincing evidence that there was an
affirmative intent to deceive.  On
appeal, Par stressed the "strained credibility" comment, but the
entire panel agreed that the lower court's decision was in accord with Therasense.  This determination is good news for
pharmaceutical companies that in-license technology from Universities.  With a different outcome, entire patent
portfolios could have been jeopardized based solely on the misconceptions of
inventors who are not always aware of the intricacies of patent law.

Written
Description

The next issue related to the adequacy of disclosure involving certain claims of
the '772 patent that had the negative limitation "wherein the composition
contains no sucralfate."  This
limitation was apparently added during the prosecution of the application, citing
to the specification's highlighting that sucralfate and other compounds have certain
disadvantages.  The lower court,
majority, and concurrence all took different views of what is required to
support a negative limitation.  On the
one hand, the District Court held that the negative limitation could only be
added if the specification demonstrated that sucralfate was
contraindicated.  The lower court
concluded that, because the Phillips' composition was only described as
advantageous in the specification, the negative limitation could not satisfy
the written description requirement.  The
majority took a more lenient approach, pointing out that "[n]egative claim
limitations are adequately supported when the specification describes a reason to
exclude the relevant limitation."  Because those skilled in the art would
understand that the disadvantages of including sucralfate could be avoided by
the Phillips formulation, the written description was satisfied.  Furthermore, because the originally filed
application contained the same disclosure related to sucralfate, these claims
were entitled to claim priority back to the '737 patent (which is an important
consideration for the obviousness analysis).

Judge
Newman agreed that the negative limitation had adequate written description
support, and that these claims were entitled to the priority claim, but she
complained that the majority opinion unnecessarily created a new requirement
that a specification "describe a reason" for a claim limitation.  In justifying her criticism, she pointed out
that applicants routinely amend claims during prosecution in response to prior
art cited by the Patent Office.  Moreover, she pointed out that data may be generated during the
application process that may necessitate claim amendments that were not necessarily
appreciated when the application was filed.  By requiring a reason in the specification for a negative limitation,
she warned, a patent applicant may no longer be able to sufficiently narrow an
application to get around the prior art.  Ultimately, she concluded, the Court's new requirement adds uncertainty,
which will be to the detriment of commerce.

Obviousness
– '737 patent as prior art

The
more interesting issue relating to sufficiency of disclosure involved the use
of the ultimate parent, the '737 patent, as prior art against a subset of the
asserted claims.  The patents at issue
were all continuations and continuations-in-part that reached back to the '737
patent.  The District Court had made a
priority determination for all of the claims, and because it determined that a
subset of the claims could not claim priority to the '737 patent, that patent
could be cited as prior art.  Interestingly,
except for the sucralfate claims mentioned above, Santarus did not challenge
the lower court's priority determination as to any of the claims.

The
Federal Circuit overturned the obviousness determination with regard to the
sucralfate negative limitation claims.  However, because the '737 patent disclosed all of the limitations of the
other asserted claims, the Court upheld the obviousness determination.  The dissent pointed out that the problem with
this decision was that, if the '737 patent did, in fact, contain all of these limitations,
why were these patents unable to claim priority back to the same
disclosure.  In fact, Judge Newman
appears to take the position that subject matter common to a patent and a
priority document can never be used to invalidate a patent claim.

Santarus
had made three arguments as to why the '737 patent failed to disclose the
claimed subject matter.  In the first two
arguments, it alleged that the '737 patent failed to disclose non-enteric
coated PPIs and buffer within the claimed ratios, and failed to disclose that
the buffering agent be sodium bicarbonate "in an amount from about 1000 mg
to about 2000 mg."  For both of
these arguments, the majority went to great effort to point out how these
ratios or ranges overlap ranges disclosed in the '737 patent.  However, the majority opinion did not explain
why one skilled in the art would have selected the particular claimed range, or
would have had any expectation that such a range would work.  Presumably, therefore, the overlap was so
great that such a determination was unnecessary.  If this was the case, though, it is unclear
why the '737 patent did not anticipate the claims at issue rather than just
render them obvious.  Santarus' final
argument was that the '737 patent did not recite the specific blood serum
concentrations of PPI that were recited in some of the claims.  The Court pointed out that such
concentrations were inherent properties of the '737 patent, and therefore their
inclusion in the claim could not otherwise make an invalid claim valid.  Again, the problem is that the Court was
undertaking an obviousness determination, and as such, inherency should not be
a factor.  Instead, the analysis should
focus on why one skilled in the art would have selected the particular
concentrations to arrive at the claimed blood serum concentrations.  Of course, if the '737 patent "anticipated"
the claims, than it is unquestionable that one could not simply claim the
inherent properties of carrying out the disclosure.

Judge
Newman appears to have a valid point that the subject matter of the '737 patent
should not be used as prior art against the claims at issue, especially in view
of the fact that the obviousness determination was in view of only the single
reference, and that reference appears to anticipate the claims more than render
them obvious.  Of course, if the '737
patent "anticipated" the claims at issue, then it must have supported
the claims in the first place.  As
unsatisfactory as it is, the answer probably lies in the fact that Santarus did
not challenge the lower court's priority determination.  It would be very interesting to see if the
majority opinion would have been different would Santarus have done so.

Obviousness
– '737 patent not prior art

Finally,
the lower court had held that the remaining asserted claims were invalid as
obvious in view of two references, Pilbrant and Lammers.  The majority overturned this determination
with regard to conventional oral dosage forms, such as tablets, capsules, or
granules with non-enteric coated PPIs, because it found that Pilbrant taught
away from formulating omeprazole according to the claims with regard to these
forms.  However, the majority did not
accept Santarus' assertion that Pilbrant taught away from all non-enteric
coated omeprazole formulations.  As a result, the Court upheld the obviousness
determination with regard to these claims.

The
dissent, again, would have overturned the invalidity determination with regard
to all of the claims.  As Judge Newman
pointed out, the majority opinion failed to take into account the entirety of
the Pilbrant teaching.  Apparently, when
read properly, Pilbrant actually taught away from using omeprazole without the
enteric coating.  Moreover, according to
Judge Newman, the majority erred by only focusing on these two references, and
failed to take into account the state of the art, in which every patent or
publication stated that PPI must be enteric coated.  In fact, there was apparently much skepticism
in the art that the Phillips formulation would even work.  As such, Judge Newman accused the majority of
using hindsight reasoning.  Finally,
Zegerid® had sales of over $100 million in 2008, demonstrating commercial
success, which the dissent pointed out can be highly probative of the
non-obviousness.

Santarus, Inc. v. Par
Pharmaceutical, Inc. (Fed. Cir. 2012)
Panel: Chief Judge Rader and Circuit Judges Newman and Moore
Opinion for the court Per Curiam; opinion concurring in part and dissenting in part by Circuit Judge Newman