United States Court of Appeals for the Federal Circuit
2008-1480, -1481
ASTRAZENECA PHARMACEUTICALS LP and ASTRAZENECA UK LIMITED,
Plaintiffs-Appellees,
v.
TEVA PHARMACEUTICALS USA, INC.
and TEVA PHARMACEUTICAL INDUSTRIES, LTD.,
Defendants-Appellants,
and
SANDOZ, INC.,
Defendant-Appellant.
Henry J. Renk, Fitzpatrick Cella, Harper & Scinto, of New York, New York, argued for
plaintiffs-appellees. With him on the brief were Bruce C. Haas; Charles E. Lipsey, Finnegan,
Henderson, Farabow Garrett & Dunner, LLP, of Reston, Virginia, and Thomas A. Stevens,
AstraZeneca Pharmaceuticals LP, of Wilmington, Delaware.
Ira J. Levy, Goodwin Proctor LLP, of New York, New York, argued for defendants-
appellants Teva Pharmaceuticals USA, Inc., et al. With him on the brief were Henry C.
Dinger, Daryl L. Wiesen and John T. Bennett, of Boston, Massachusetts.
Douglass C. Hochstetler, Schiff Hardin LLP, of Chicago, Illinois, argued for defendant-
appellant Sandoz, Inc. With him on the brief were Jason G. Harp; and Beth D. Jacob, of New
York, New York.
Appealed from: United States District Court for the District of New Jersey
Judge Joel A. Pisano
United States Court of Appeals for the Federal Circuit
2008-1480,-1481
ASTRAZENECA PHARMACEUTICALS LP and ASTRAZENECA UK LIMITED,
Plaintiffs-Appellees,
v.
TEVA PHARMACEUTICALS USA, INC.
and TEVA PHARMACEUTICAL INDUSTRIES, LTD.,
Defendants-Appellants,
and
SANDOZ, INC.,
Defendant-Appellant.
Appeal from the United States District Court for the District of New Jersey in consolidated
Case Nos. 05-CV-5333, 06-CV-1528, 07-CV-1632, and 07-CV-3001, Judge Joel A. Pisano.
___________________________
DECIDED: September 25, 2009
___________________________
Before NEWMAN, RADER, and PROST Circuit Judges.
NEWMAN, Circuit Judge.
Teva Pharmaceuticals USA, Inc., Teva Pharmaceutical Industries, Ltd., and Sandoz,
Inc. appeal from the grant, by the United States District Court for the District of New Jersey,
of AstraZeneca Pharmaceuticals LP and AstraZeneca UK Limited’s motion for summary
judgment of no inequitable conduct. 1 The district court ruled that the Appellants had not
presented evidence sufficient for a reasonable jury to find that, in prosecution of the subject
patent application in the Patent and Trademark Office (“PTO”), AstraZeneca made a
misrepresentation of material fact or an omission of material fact, with intent to deceive or
mislead the patent examiner into granting the patent. We affirm the district court’s ruling.
BACKGROUND
AstraZeneca is the assignee of United States Patent No. 4,879,288 (“the ’288
patent”) which claims the antipsychotic drug quetiapine, having the following structural
formula:
AstraZeneca markets quetiapine under the brand name “SEROQUEL®.” The ’288
patent explains that this product is an “atypical” antipsychotic drug, which means that,
unlike “typical” antipsychotics, it does not produce involuntary body movements including
torsion spasms, muscle spasms and dystonia of the face, neck, or back with protrusion of
1
AstraZeneca Pharm. LP v. Teva Pharm. USA, 567 F. Supp. 2d 683 (D.N.J.
2008).
2008-1480,-1481 2
the tongue, and tonic spasms of the limbs (dyskinesias). Such undesirable side effects
were not unusual for antipsychotic drugs. An earlier atypical antipsychotic drug, clozapine,
had become available in the 1970s, but it was withdrawn from the market after it was
discovered to cause a potentially deadly reduction in white blood cell count known as
agranulocytosis. The AstraZeneca product quetiapine was approved by the FDA in 1997.
The ’288 patent expires on September 26, 2011.
Teva and Sandoz each filed abbreviated new drug applications (“ANDAs”) for
approval to sell their production of quetiapine under 21 U.S.C. §355(j), certifying under
“paragraph IV” that the ’288 patent is invalid and/or not infringed. Paragraph IV
certifications are, by statute, an act of technical patent infringement designed to permit
litigation of patent issues for products subject to federal regulatory approval. 35 U.S.C.
§271(e)(2)(A). In accordance with the statutory procedures, AstraZeneca filed infringement
suits against Teva and Sandoz; the suits were consolidated in the District Court for the
District of New Jersey. See 21 U.S.C. §355(j)(5)(B)(iii).
The district court granted summary judgment that there was no inequitable conduct
in prosecution of the ’288 patent application. That is the only issue of this appeal.
DISCUSSION
The grant of summary judgment receives plenary review on appeal. Innogenetics,
N.V. v. Abbott Labs., 512 F.3d 1363, 1378 (Fed. Cir. 2008). “Although the premises of
inequitable conduct require findings based on all the evidence, a procedure that may
preclude summary determination, a motion for summary judgment may be granted when,
drawing all reasonable factual inferences in favor of the non-movant, the evidence is such
that the non-movant can not prevail.” ATD Corp. v. Lydall, Inc., 159 F.3d 534, 547 (Fed.
2008-1480,-1481 3
Cir. 1998) (citation omitted). On appellate review, we accordingly consider the evidence
and all reasonable factual inferences, in light of the applicable law and the burdens and
standards of proof. Id. at 540.
The issue presented in this case relates to the extent to which the patent applicant,
having fully disclosed the relevant prior art and having provided comparative data to the
satisfaction of the patent examiner, must also present any additional unpublished
information in the applicant’s possession concerning other less structurally similar
compounds, and must also synthesize additional compounds for comparative testing. The
district court reviewed the evidence in the dual contexts of the materiality of any withheld or
omitted information, and whether deceptive intent had been established. These are the
essential factual underpinnings of the charge of inequitable conduct, and both materiality
and deceptive intent must be established by clear and convincing evidence. See
Kingsdown Medical Consultants, Ltd. v. Hollister Inc., 863 F.2d 867, 872 (Fed. Cir. 1988)
(en banc) (both materiality and deceptive intent must be shown). Intent to deceive cannot
be inferred from a high degree of materiality alone, but must be separately proved to
establish unenforceability due to inequitable conduct. Id. at 876; see Star Scientific, Inc. v.
R.J. Reynolds Tobacco Co., 537 F.3d 1357, 1366 (Fed. Cir. 2008) (“[T]he fact that
information later found material was not disclosed cannot, by itself, satisfy the deceptive
intent element of inequitable conduct.”).
If both materiality and deceptive intent are established, the court shall balance these
findings, with cognizance of the underlying facts, and determine whether, in the specific
case, there was inequitable conduct in the prosecution of the patent application. Star
Scientific, 537 F.3d at 1365. Upon determining that there was inequitable conduct in
2008-1480,-1481 4
obtaining the patent, the district court may in its discretion declare the patent permanently
unenforceable. Kingsdown, 863 F.2d at 876.
The Prior Art
The references on which the Appellants base their argument of withholding
comparative data were all before the PTO. After filing of the ’288 patent application, before
the examiner’s first Office Action, AstraZeneca filed an Information Disclosure Statement
(“IDS”) listing several references including those described below, and stated: “Enclosed
herewith . . . is a list of references believed to be relevant to the subject matter of the
invention[.]” The relevant compounds in these references are Compound 21076, described
in the German-language publication Research Disclosure (1980) (“Research Disclosure”);
Compound 24028, described in U.S. Patent No. 3,539,573 to Schmutz et al. (“Schmutz II”);
Perlapine, described in U.S. Patent No. 3,389,139 to Schmutz et al. (“Schmutz I”); and
Fluperlapine, described in U.S. Patent No. 4,308,207 to Hunziker et al. (“Hunziker”). These
four compounds have the structural formulae shown below:
2008-1480,-1481 5
AstraZeneca had internal test data for these four compounds as well as for many other
compounds; data that were generated in the course of the research leading to quetiapine.
This internal information was not included in its IDS—that is the main basis of the
Appellants’ inequitable conduct argument, for they argue that AstraZeneca’s data showed
that some prior art compounds potentially exhibited atypical antipsychotic activity, and that
this information should have been reported to the patent examiner.
The examiner, in the first Office Action, cited several references showing compounds
of close structural similarity to quetiapine. The examiner cited Schmutz II as the primary
reference, in view of U.S. Patent No. 4,097,597 to Horrom (“Horrom”), which was another
reference included in AstraZeneca’s IDS, and other combinations of secondary references.
In particular, the examiner identified a compound described in Schmutz II to which the
2008-1480,-1481 6
parties refer as “Schmutz X,” and a compound described in Horrom. These structures are
as follows:
During the prosecution the applicant and the examiner discussed the prior art
compounds, for it was not disputed that the structural differences were small among these
various compounds. The examiner based the rejection on structural similarity alone, and
the applicant in response pressed the unpredictability of the critical physiological property of
atypicality, and that the prior art provided no reason to make the particular compound
quetiapine for the purpose of obtaining atypical antipsychotic properties. AstraZeneca
pointed to the long-felt need for such a drug, because the use of clozapine was severely
limited and no suitable replacement was available in the United States.
The examiner persisted in the rejection, stating that in accordance with the law of
obviousness as to the claimed structure it is not necessary that the prior art described or
suggested that a specific structure would impart a specific property, if in fact the prior art
product had the desired property. The examiner stated that in order to overcome the
structural obviousness rejection AstraZeneca must provide proof that the prior art
compounds:
2008-1480,-1481 7
do not necessarily or inherently possess the characteristics of the claimed
product. . . . In other words, once a condition of prima facie structural
obviousness has been made out, it must be overcome by a side-to-side
comparison with the closest art compound(s). In this case, one would test
both the prior art species ([Horrom compound] and [Schmutz X]) and the
claimed specie for their ability to avoid e.g. tardive dyskinesia (or whatever
undesirable side effect applicant wishes to focus on).
PTO Paper No. 10, December 2, 1988. The examiner referred to the IDS and stated:
[T]he cited references are noted. None disclose [sic] compounds closer than
the species already discussed.
Id.
In response to the examiner’s position, AstraZeneca submitted the Declaration of
one of the inventors, Dr. Migler, with data for the Horrom compound and a Schmutz
compound. The prosecuting attorney explained that AstraZeneca did not have psychotic
test data for Schmutz X, and that such data would be “very expensive to generate now,”
and as a substitute AstraZeneca offered pre-existing internal data for Schmutz B, which the
inventors believed was closer structurally than Schmutz X because the hydroxyethyl side-
chain of Schmutz B is more similar to quetiapine’s side-chain than is the ethyl side-chain of
Schmutz X. These structures are:
Dr. Migler’s declaration contained psychotic test data showing that the Horrom
compound’s antipsychotic properties were “typical.” The declaration also contained
2008-1480,-1481 8
psychotic test data for Schmutz B, and showed that it too was “typical.” Dr. Migler also
included test data for another compound described in Schmutz II that the parties call
Schmutz A, which differs from quetiapine in that Schmutz A’s left benzene ring is
substituted with chlorine (whereas quetiapine’s left ring is unsubstituted), and Schmutz A's
side chain is methyl (as compared to quetiapine's hydroxyethoxyethyl). The test data
showed that Schmutz A was inactive for antipsychotic activity; AstraZeneca explained that
in light of this inactivity no test for atypical side-effects was conducted for Schmutz A.
The Appellants’ inequitable conduct arguments before the district court, and again
before this court, focus on the fact that AstraZeneca did not submit to the PTO its internal
test data for perlapine, fluperlapine, compound 21076, and compound 24028, shown supra.
The Appellants state that it was a material withholding to provide test data only for the
compounds on which the examiner relied, stating that AstraZeneca’s internal test data
showed that compounds other than quetiapine possessed potential atypical antipsychotic
activity. Thus, the Appellants argued that the Migler Declaration was deliberately
misleading.
The district court found that AstraZeneca properly addressed the closest prior art, in
response to the examiner’s specific requests, and that the premises of the factual
allegations of material withholding with deceptive intent had not been shown sufficiently to
avoid the grant of summary judgment, citing that inequitable conduct in patent prosecution
requires proof by clear and convincing evidence of both (1) an affirmative misrepresentation
of material fact, a failure to disclose material information, or submission of false material
information, and (2) an intent to deceive the examiner by such material falsity.
2008-1480,-1481 9
AstraZeneca, 567 F. Supp. 2d at 691 (citing Cargill, Inc. v. Canbra Foods, Ltd., 476 F.3d
1359, 1364 (Fed. Cir. 2007)).
Materiality
Several standards for establishing the fact of materiality in connection with patent
prosecution have been proposed. See, e.g., Litton Indus. Products, Inc. v. Solid State
Systems Corp., 755 F.2d 158, 166 n.19 (Fed. Cir. 1985) (identifying “four tests: (1)
objective ‘but for’; (2) subjective ‘but for’; (3) ‘but it may have been’; (4) PTO Rule 1.56(a),
i.e., whether there is a substantial likelihood that a reasonable examiner would have
considered the omitted reference or false information important in deciding whether to allow
the application to issue as a patent.”) While a uniform standard has not been rigorously
applied in the courts, the fourth test of whether a reasonable examiner would have
considered the information important in deciding whether to grant the patent, even when
the omitted information does not negate patentability, is most often employed. See, e.g.,
Upjohn Co. v. Mova Pharm. Corp., 225 F.3d 1306, 1312 (Fed. Cir. 2000). “However, a
reference need not be provided to the examiner if it is merely cumulative to or less material
than other references before the examiner.” Id.
Appellants contend that AstraZeneca misrepresented that the atypical properties of
quetiapine were unexpected, stating that AstraZeneca presented internal test data about
similar compounds that were typical while omitting internal test data about similar
compounds that were potentially atypical. AstraZeneca states that it properly focused on
the prior art compounds that were structurally closest to quetiapine and that its internal test
data show that these closest compounds were not atypical. AstraZeneca states that this is
the comparison requested by the examiner, and the comparison most directly in line with
2008-1480,-1481 10
the applicable law. AstraZeneca states that it never represented to the examiner that
quetiapine’s atypical properties made it completely unique among structurally similar
compounds, and points out that in its IDS AstraZeneca identified the references describing
the compounds that the Appellants here assert are potentially atypical antipsychotics, i.e.,
perlapine, fluperlapine, compound 24028, and compound 21076.
No relevant reference is asserted to have been withheld. Various references stated
that certain prior art compounds were known to be atypical antipsychotics, such as
clozapine and fluperlapine. For example, the cited Hunziker reference identifies
fluperlapine as a “non-classical neuroleptic” (i.e., antipsychotic) “like clozapine.” 2 U.S.
Patent No. 4,308,207 col.3 ll.5-9. AstraZeneca points out that since the Hunziker reference
describes fluperlapine as having atypical properties, AstraZeneca’s internal test data on
whether fluperlapine is atypical is, at most, cumulative information.
With all of the references before him, the Examiner made a prima facie obviousness
rejection based on the structural similarity between quetiapine and the two prior art
compounds that he identified as structurally closest to quetiapine; that is, Schmutz X and
the Horrom Compound. As we have discussed, AstraZeneca responded that it had test
data for the Horrom Compound, but that it did not have test data for Schmutz X, and
provided test data for Schmutz B; AstraZeneca told the examiner that the test data on
Schmutz X would be “very expensive to generate now” and that Schmutz B was actually
2
AstraZeneca requests that we take judicial notice that Sandoz, in a document
filed in a separate proceeding before the United States District Court for the District of New
Jersey, acknowledged that the Hunziker patent describes fluperlapine as an atypical
antipsychotic. AstraZeneca Pharm. LP v. Sandoz, Inc., Civil Action No. 09-CV-870 (JAP)
(TJB) (D.N.J. 2009). We take judicial notice of this statement, which merely confirms an
uncontested fact, as Sandoz’s brief already states “Hunziker described fluperlapine as
being a non-classical antipsychotic like clozapine.”
2008-1480,-1481 11
structurally closer to quetiapine than Schmutz X. Appellants charge that both of these
statements to the examiner are material misrepresentations. AstraZeneca replies that both
statements are accurate and true.
First, the Appellants argue that AstraZeneca falsely stated that generating test data
on Schmutz X would be “very expensive.” Appellants contend that expense was mere
pretext, asserted because AstraZeneca believed that Schmutz X was atypical based on the
structural similarity between Schmutz X and Compound 24028, which AstraZeneca knew to
have potential atypical properties. Appellants do not assert that AstraZeneca had data for
Schmutz X and withheld it; nor do they argue that Schmutz X is in fact atypical, and no data
are presented to this effect. Instead the Appellants seem to argue that because of the
structural similarity between Schmutz X and Compound 24028, Schmutz X could be
atypical, and thus should have been synthesized and its antipsychotic properties tested.
The Appellants’ position appears to be that AstraZeneca’s failure to do so was a material
withholding or omission, with deceptive intent.
Although there may be situations in which the failure to conduct specific tests of
specific compounds can be criticized, in this case there was no evidence that the
information gleaned, if such tests had been conducted, would have been material to
patentability. It was not disputed that it was unpredictable whether a given compound
would exhibit atypical antipsychotic properties. The record demonstrates that structural
similarity is not a predictor of whether antipsychotic behavior would be typical or atypical.
As AstraZeneca points out, the properties of these structurally similar compounds vary
significantly with minor structural changes. 3 The Appellants made no showing as to
3
During the course of this litigation, the district court collaterally estopped Teva
2008-1480,-1481 12
whether the structural similarity between Schmutz X and Compound 24028 would establish
whether Schmutz X would have atypical properties. In the context of the knowledge in this
field, as reflected in the various references, AstraZeneca’s provision of its existing test data
for Schmutz B, instead of preparing and testing Schmutz X, cannot constitute a material
misrepresentation. The district court correctly so held.
The Appellants also argue that AstraZeneca should have submitted to the examiner
its existing test data for Compound 24028 because Compound 24028 and Schmutz B are
“equally close“ to quetiapine. The Appellants state that the data should have been
submitted although not identified or requested by the examiner.
To ascertain what is “equally close,” in identifying the structurally closest prior art,
the compounds are viewed as they would be perceived by persons experienced in the
particular field of science. Precedent suggests that as a starting point it is useful to
ascertain the common elements of the claimed invention and the prior art. See In re
Merchant, 575 F.2d 865, 868 (CCPA 1978) (determining the common elements). Thus the
Appellants point out that Compound 24028, Schmutz B, and quetiapine differ only in their
respective side chains. That is correct. However, AstraZeneca is also correct in pointing
out that Schmutz B’s hydroxyethyl side chain is structurally closer to quetiapine’s
hydroxyethoxyethyl side chain, both in length of the chain and in the hydroxyl end group,
than is Compound 24028’s methyl side chain, as shown below:
from challenging the unpredictability of atypical antipsychotic properties because Teva had
agreed to be bound by the decision of the district court in Eli Lilly & Co. v. Zenith Goldline
Pharms., Inc., 364 F. Supp. 2d 820, 831 ¶14 (S.D. Ind. 2005), which involved many of the
same issues regarding the development of an atypical antipsychotic. See AstraZeneca
Pharm. LP v. Teva Pharm. USA, Civil Action No. 05-CV-05333 (JAP) (TJB), Order Granting
Motion for Summary Judgment Based on Collateral Estoppel (D.N.J. Oct. 12, 2007).
2008-1480,-1481 13
The patent examiner did not dispute AstraZeneca’s scientific position, and accepted the
proffered data on Schmutz B as the closest prior art. Accordingly, AstraZeneca’s
substitution of Schmutz B in place of Schmutz X was not a material misrepresentation, and
the non-provision of the data on Compound 24028, which is structurally less similar to
quetiapine, was not a material omission.
The appellants also argue that AstraZeneca’s submission of its internal test data of
Schmutz B along with its internal test data of Schmutz A was an implied misrepresentation
because it omitted other internal test data of potentially atypical compounds including
fluperlapine, perlapine, Compound 21076, and Compound 24028. We agree with the
district court that the Migler declaration, which was directed to the closest prior art
compounds, was not an implied misrepresentation. AstraZeneca has not asserted that no
prior art compound is atypical. Rather, AstraZeneca demonstrated, as the examiner
required, that the structurally closest prior art compounds did not possess the same
properties as quetiapine. The prosecuting attorney explained that Schmutz A was on the
same list of antipsychotics as Schmutz X. A reasonable examiner would not have
understood the Migler declaration as stating that no prior art product had the atypical
property shown by quetiapine, for it was known that other atypical antipsychotics existed,
2008-1480,-1481 14
including fluperlapine and clozapine. A reasonable examiner would understand
AstraZeneca’s statements to refer to the closest prior art compounds, not all prior art
compounds. AstraZeneca’s inclusion of the Schmutz A data is not an “implied”
misrepresentation.
We conclude, as did the district court, that the evidence cannot support a finding that
AstraZeneca misrepresented or omitted material information.
Deceptive Intent
Intent to deceive is an independent element of inequitable conduct, and must be
independently established by clear and convincing evidence. Star Scientific, 537 F.3d at
1365; Cargill, 476 F.3d at 1364; see Molins PLC v. Textron, Inc., 48 F.3d 1172, 1181 (Fed.
Cir. 1995) (“[C]lear and convincing evidence must prove that an applicant had the specific
intent to accomplish an act that the applicant ought not to have performed, viz., misleading
or deceiving the PTO. In a case involving nondisclosure of information, clear and
convincing evidence must show that the applicant made a deliberate decision to withhold a
known material reference.”); Allen Organ Co. v. Kimball Int’l, Inc., 839 F.2d 1556, 1567
(Fed. Cir. 1988) (“[m]ateriality does not presume intent, which is a separate and essential
component of inequitable conduct”).
Appellants state that they have shown a “high degree of materiality,” and that they
therefore need a proportionally lesser showing of intent to deceive to establish the requisite
threshold level of intent. That is incorrect. Evidence of mistake or negligence, even gross
negligence, is not sufficient to support inequitable conduct in patent prosecution.
Kingsdown, 863 F.2d at 876. To establish the requisite deceptive intent, “the involved
conduct, viewed in light of all the evidence, including evidence indicative of good faith, must
2008-1480,-1481 15
indicate sufficient culpability to require a finding of intent to deceive.” Id. While the court
must, as the final step, weigh and balance the findings of materiality and intent, this
presupposes that a threshold level of both of these elements has already been established
by clear and convincing evidence. See Manville Sales Corp. v. Paramount Systems, Inc.,
917 F.2d 544, 551 (Fed. Cir. 1990) (“Inequitable conduct requires proof by clear and
convincing evidence. A threshold showing of both materiality and intent to mislead or
deceive must be first established, and then those fact-findings are balanced to make the
determination whether ‘the scales tilt to a conclusion that inequitable conduct occurred.’”).
The only evidence of intent offered by the Appellants is AstraZeneca’s internal
knowledge of certain compounds of this structural class that were atypical, without including
this information in the IDS. The Appellants argue that it is irrelevant that the omitted
compounds are not the closest structural analogs, and irrelevant that the patent examiner
asked for comparative data for other, closer compounds. The Appellants offer no evidence
or suggestion of deceptive intent, other than the fact that this information was not provided.
The law is clear that “inequitable conduct requires not intent to withhold, but rather intent to
deceive. Intent to deceive cannot be inferred simply from the decision to withhold
[information] where the reasons given for the withholding are plausible.” Dayco Products,
Inc. v. Total Containment, Inc., 329 F.3d 1358, 1367 (Fed. Cir. 2003). As argued by
Appellants, an applicant would not know how much of its research effort must be filed with
the PTO, although of no interest to the examiner, or run the risk of accusation of
wrongdoing no matter where the line is drawn.
As we have discussed, the omitted test data were not material because the
compounds were not the structurally closest compounds, whereas AstraZeneca and the
2008-1480,-1481 16
examiner focused on the structurally closest compounds. Although the Appellants argue
that this is an inadequate reason, no evidence of bad faith has been proffered concerning
the omission of data for the less similar compounds, AstraZeneca presented plausible
reasons for its presentation of arguments and data during the prosecution, and although
the Appellants dispute AstraZeneca’s reasoning, intentional withholding for the purpose of
deceiving the examiner is unsupported by evidence sufficient to avert summary judgment.
We reach the same conclusion as did the district court, that the Appellants have not
provided evidence sufficient to establish the threshold facts of material withholding with the
intent to deceive. The grant of summary judgment of no inequitable conduct is affirmed.
COSTS
Each party shall bear its own costs.
AFFIRMED.
2008-1480,-1481 17