[Ip-health] Pfizer v. Apotex (IP Frontline)

[Tahir Amin]

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Pfizer v. Apotex (IP Frontline)

Harold Wegner <http://www.ipfrontline.com/aboutsource.asp?editorid=3D195>
date: Tuesday, May 22, 2007

Today in *Pfizer, Inc. v. Apotex, Inc.*, __ F.3d __ (Fed. Cir. 2007)(en
banc)(order), *panel proceedings*, 480 F.3d 1348 (2007)(Michel, C.J.), the
court refused to grant rehearing en banc in one of the most controversial
chemical patent opinions in the history of the court in conflict with, *int=
er
alia*, the leading case, *In re Papesch*, 315 F.2d 381 (CCPA 1963).

Excerpts from the individual dissents of the three members of the court in
dissent from the denial of rehearing en banc are set forth below; the full
order including the dissents is attached.

The majority panel opinion was on behalf of two members of the court; the
third member concurred in the result only.

*NEWMAN, Circuit Judge, dissenting from the denial of rehearing en banc.*

=85 [I]t was intended and expected that [the Federal Circuit] would provide
uniform national law in all of the fields assigned to our exclusive
jurisdiction; not only in patent law. Our cases are rarely factually simple=
,
and when there arise apparently divergent panel statements of the law and
its application, the responsibility for en banc review looms large. The goa=
l
of judging is "full, equal and exact" enforcement of the law. See Roscoe
Pound, The Etiquette of Justice, 3 Proceedings Neb. St. Bar Assn. 231 (1909=
)
("full, equal and exact enforcement of substantive law is the end" of the
judicial process). Through the system of en banc review, courts can remedy
panel lapses, if indeed this decision represents such a lapse, or uniformly
adopt panel advances in the law, if indeed this decision represents such an
advance. =85

*LOURIE, Circuit Judge, dissenting from the denial of rehearing en banc.*

=85 At bottom, I consider that the decision of the panel was incorrect. But=
,
we do not rehear appeals simply because a non-panel member disagrees with
its result. See Amgen Inc. v. Hoechst Marion Roussel, Inc., 469 F.3d 1039,
1043 (Fed. Cir. 2006) (Lourie, J., concurring) ("I do not believe that ever=
y
error by a panel is enbancable. A panel is entitled to err without the full
court descending upon it."). Federal Rule of Appellate Procedure 35(a)
provides that "[a]n en banc hearing or rehearing is not favored and
ordinarily will not be ordered unless: (1) en banc consideration is
necessary to secure or maintain uniformity of the court's decisions; or (2)
the proceeding involves a question of exceptional importance." Our Internal
Operating Procedures ("IOPs") state that "[a]mong the reasons for en banc
actions are: (1) necessity of securing or maintaining uniformity of
decision; (2) involvement of a question of exceptional importance; (3)
necessity of overruling a prior holding of this or a predecessor court
expressed in an opinion having precedential status; or (4) the initiation,
continuation, or resolution of a conflict with another circuit." IOP 13(2).

However, consistent with those established criteria for taking a case en
banc, I consider that the panel erred in its legal determinations, and that
those errors will confuse the law relating to rebuttal of a prima facie cas=
e
of obviousness of a chemical compound. Thus, an en banc hearing is warrante=
d
in this case in order to maintain uniformity of the court's decisions and
because it presents questions of exceptional importance.

The panel reversed the district court's decision that claims relating to
amlodipine besylate (the active ingredient in the hypertension drug
Norvasc(r)) were valid and nonobvious after a bench trial. Pfizer, Inc. v.
Apotex, Inc., 480 F.3d 1348 (Fed. Cir. 2007). In my view, several legal
errors were made in this decision, and improper deference was given to
fact-findings of the district court.

First, the panel failed to defer to fact-findings made by the district cour=
t
that were not clearly erroneous regarding the unexpected properties of
amlodipine besylate. Evidence in the record, including trial testimony of
experts and Pfizer scientists, internal research and development documents,
and a scientific article, supported the district court's finding that "the
besylate salt clearly and unexpectedly exhibited a superior combination of
properties when compared to what was suggested in the preferred
preparation." District Court Oral Op. Tr. at 23:13-15; see Pet. for Reh'g e=
n
banc at 5-6. The panel disregarded that express finding of fact, holding
that "Pfizer has simply failed to prove that the results are unexpected."
Pfizer, 480 F.3d at 1371. Moreover, relying on the testimony of both
parties' experts, the district court found that there was no reasonable
expectation of success with regard to using the besylate salt form of
amlodipine. District Court Oral Op. Tr. at 23:1-9. However, rather than giv=
e
deference to the district court's fact-findings, the panel substituted its
own finding that a reasonable expectation of success existed in the art. Se=
e
Pfizer, 480 F.3d at 1361, 1364-65 ("The record also satisfies us that,
contrary to the district court's finding, a reasonable fact-finder could
only conclude that the skilled artisan would have had a reasonable
expectation of success with the besylate salt form of amlodipine."). Much
public discussion has occurred, and even judicial comments in opinions, tha=
t
we should defer to district court judges concerning certain aspects of clai=
m
construction, which we have held is a matter of law. Be that as it may, it
is undisputed that we must defer to fact-findings by a district court,
unless they are clearly erroneous, and I do not believe that they were here=
.


In addition, the panel improperly placed greater importance on the
therapeutic value of a claimed compound over the value of its physical
properties. The panel concluded that the improvement of the invention, whic=
h
related to drug formulation, viz., increased stability and decreased
stickiness, was "insufficient" to meet the standards of patentability. Id.
at 1368 (emphases added) ("[W]e hold that the optimization of the acid
addition salt formulation for an active pharmaceutical ingredient would hav=
e
been obvious where as here the acid addition salt formulation has no effect
on the therapeutic effectiveness of the active ingredient and the prior art
heavily suggests the particular anion used to form the salt."). I read that
conclusion as improperly requiring a compound to possess a specific type of
improvement over the prior art=97in this case, improved therapeutic
properties=97to be patentable, negating other important properties, a
conclusion that is not compelled by our case law and not sound. Any useful
and unexpected property should be eligible to overcome a prima facie
obviousness determination. See In re Papesch, 315 F.2d 381, 391 (CCPA 1963)
("From the standpoint of patent law, a compound and all of its properties
are inseparable; they are one and the same thing. . . . There is no basis i=
n
law for ignoring any property in making such a comparison.").

Third, the panel also found that the invention was the result of routine
experimentation, and therefore was not patentable. See Pfizer, 480 F.3d at
1367 (emphases added) (stating that the "type of experiments used by
Pfizer's scientists to verify the physicochemical characteristics of each
salt are not equivalent to the trial and error procedures often employed to
discover a new compound where the prior art gave no motivation or suggestio=
n
to make the new compound nor a reasonable expectation of success"). That
conclusion conflicts with the statutory requirement that "[p]atentability
shall not be negatived by the manner in which the invention was made." 35
U.S.C. =A7 103(a). Moreover, the conclusion contradicts the district court'=
s
supported findings that the results were unexpected, and that the
experiments led to showing the totality of the properties of the invention,
see Papesch, 315 F.2d 381, which makes the compound nonobvious, not merely
to the verification of results.

In addition, holding an inventor's expectations of success against the
objective unexpectedness of the properties of the compound unfairly suggest=
s
that an inventor should try only that which he doubts will work. See Pfizer=
,
480 F.3d at 1371 ("Dr. Wells' testimony reflects the fact that he believed
that amlodipine besylate would solve the problems of amlodipine maleate.").
Inventors generally are optimistic about what they choose to experiment
with, but that does not necessarily suggest obviousness.

These issues are of exceptional importance. Chemical and pharmaceutical
compounds often can be found to be prima facie obvious, as they are based o=
n
prior work that could reasonably suggest them, see KSR Int'l Co. v. Telefle=
x
Inc., --- S.Ct. ---, 2007 WL 1237837 (Apr. 30, 2007), but commercialization
of such compounds may depend on their possession of unexpected properties.
Such properties may be biological or physical. A failure to recognize all
such properties that may be relevant to the value of such a compound may
doom the compound to being poured down the drain rather than becoming an
important therapeutic. The general public, innovative companies, and,
ultimately, generic companies, depend upon faithful adherence to this
principle. In addition, our cases hold that unexpected properties make for
non-obviousness, see Papesch, 315 F.2d 381, and this decision disdains such
properties if they are not biological. That is a conflict with our preceden=
t
that needs resolution.

Not least, the question of deference to district courts, at least on fact
issues, needs reaffirming. We must not shy away from reversing fact-finding=
s
that truly are clearly erroneous, as we do encounter them from time to time=
,
but this case does not present them.

*RADER, Circuit Judge, dissenting from the denial of rehearing en banc.*

=85 In this case, the trial court made the factual determination that the
besylate salt form of amlodipine had unexpected superior properties over th=
e
closest prior art. Accordingly, the underlying patent ('303) was valid and
nonobvious. Three separate district courts held trials involving the '303
patent. Indeed, each of those three different district court judges came to
the same factual conclusion regarding the nonobviousness of amlodipine
besylate. Because the factual determinations in the case below were not
clearly erroneous, this court should have deferred to the district court's
factual findings.

As the testimony indicated, the properties of new pharmaceutical salt forms
are entirely unpredictable. Even the Berge reference on which the panel
relied clearly states: "Unfortunately there is no reliable way of predictin=
g
the influence of a particular salt species on the behavior of the parent
compound." The district court agreed and made the factual determination tha=
t
the superior properties of amlodipine besylate over the prior art (increase=
d
stability and decreased stickiness) were indeed unexpected =96 a finding th=
at
deserved deference.

Furthermore 'obvious to try' jurisprudence has a very limited application i=
n
cases of this nature. With unpredictable pharmaceutical inventions, this
court more wisely employs a reasonable expectation of success analysis. In
this case, salt selection is unpredictable, thus rebutting, as most other
courts found, any reasonable expectation of success. Although the panel
gives "lip service" to the principle that 'obvious to try' does not work in
this field, it nonetheless appears to be the basis for its decision in this
case. In addition, the panel discerned a reasonable expectation of success
by giving undue emphasis to the inventor's subjective hopes for the outcome
of his experiments.

The panel also mistakenly determined that the superior properties of the
besylate did not overcome a prima facie case of obviousness because they
showed no superior therapeutic value=97the maleate salt form of amlodipine
worked just as well as the besylate form in clinical trials. Therapeutic
value, however, is just one property of a pharmaceutical. Other properties,
such as solubility, stability, hygroscopicity, and processability, must als=
o
play a role in the analysis of advantages. The superior properties of the
besylate salt form of amlodipine, overcame the stability and stickiness
problems that existed with the maleate salt form and created a superior
formulation. Although the maleate salt form was also therapeutically
effective, the besylate form was still a significant improvement because it
overcame the stability and processing problems that could have prevented
successful commercial marketing.

The panel also found that amlodipine besylate was not patentable since it
was made by a routine testing or a "well known problem solving strategy."
This clearly violates the statutory mandate that "patentability shall not b=
e
negatived by manner in which the invention was made." 35 U.S.C. 103(a). Man=
y
if not most pharmaceutical inventions are discovered through a routine
screening protocol or through an established trial and error process.
Pharmaceutical inventions discovered by these routine screening methods
include not only new formulations and salt forms, but also include the
active pharmaceutical compounds themselves. Thus, this decision calls into
question countless pharmaceutical patents, which in turn could have a
profoundly negative effect on investments into the design and development o=
f
new life-saving pharmaceuticals. =85