Aventis Pharma S.A. v. Hospira, Inc. , 675 F.3d 1324 ( 2012 )

United States Court of Appeals
for the Federal Circuit
__________________________
AVENTIS PHARMA S.A. AND
SANOFI-AVENTIS U.S., LLC,
Plaintiffs-Appellants,
v.
HOSPIRA, INC.,
Defendant-Appellee,
and
APOTEX INC. AND APOTEX CORP.,
Defendants-Appellees.
__________________________
2011-1018
__________________________
Appeal from the United States District Court for the
District of Delaware in consolidated case nos. 07-CV-0721
and 08-CV-0496, Chief Judge Gregory M. Sleet.
__________________________
Decided: April 9, 2012
__________________________
GEORGE F. PAPPAS, Covington & Burling, LLP, of
Washington, DC, argued for plaintiffs-appellants Aventis
Pharma S.A., et al.. With him on the brief were
CHRISTOPHER N. SIPES, KEVIN B. COLLINS, MICHAEL N.
KENNEDY, and ROGER A. FORD.
AVENTIS PHARMA v. HOSPIRA 2
JAMES F. HURST, Winston & Strawn, LLP, of Chicago,
Illinois, argued for defendant-appellee, Hospira, Inc.
With him on the brief was IMRON T. ALY. Of counsel on
the brief were STEFFEN N. JOHNSON, GEOFFREY P. EATON,
and JACOB R. LOSHIN, of Washington, DC. Of counsel was
ANDREW NICHOLS.
RICHARD T. RUZICH, Duane Morris LLP, of Washing-
ton, DC, argued for defendants-appellees, Apotex Inc., et
al. With him on the brief were ARTHUR M. DRESNER,
KERRY B. MCTIGUE, KRISTINA CAGGIANO and MATTHEW C.
MOUSLEY. Of counsel on the brief was SHASHANK
UPADHYE, Apotex, Inc., of Toronto, Ontario, Canada.
__________________________
Before LINN, DYK, and PROST, Circuit Judges.
PROST, Circuit Judge.
Aventis Pharma S.A. and Sanofi-Aventis U.S., L.LC.
(collectively “Sanofi”) filed suit against Hospira, Inc.
(“Hospira”) and Apotex Inc. and Apotex Corp. (collectively
“Apotex”) under 35 U.S.C. § 271(e) for infringement of
U.S. Patent Nos. 5,750,561 (“’561 patent”) and 5,714,512
(“’512 patent”). After a bench trial, the district court
found, inter alia, that claim 5 of the ’561 patent and claim
7 of the ’512 patent were invalid for obviousness under 35
U.S.C. § 103, that claim 7 of the ’512 patent was not
infringed, and that both the ’561 and ’512 patents were
unenforceable for inequitable conduct. Sanofi has ap-
pealed. For the reasons set forth below, we affirm.
3 AVENTIS PHARMA v. HOSPIRA
I. BACKGROUND
The ’561 and ’512 patents are pharmaceutical patents
related to the administration of the chemotherapy cancer
drug docetaxel, which is marketed under the brand-name
Taxotere. The patents are assigned to Aventis Pharma
S.A., and Sanofi-Aventis U.S., L.L.C. is the holder of the
New Drug Application for Taxotere. Docetaxel is a suc-
cessor to the cancer drug paclitaxel, marketed as Taxol,
and the composition for docetaxel was covered by now-
expired U.S. Patent No. 4,814,470 (“’470 patent”). Both
docetaxel and paclitaxel belong to the class of compounds
known as taxanes.
Taxanes are administered through an intravenous in-
fusion, accomplished by slowly delivering the drug in a
diluted aqueous solution called a “perfusion.” Taxanes,
however, have low solubility in water and tend to precipi-
tate, i.e., form solid clumps, and come out of solution. To
delay precipitation, taxanes are mixed with additives like
surfactants and ethanol; these additives stabilize the
perfusion and delay the amount of time before precipita-
tion occurs. The taxane is combined with the additives to
form a “stock solution” which is then mixed into an in-
jectable aqueous solution, such as saline, to form a perfu-
sion.
In the prior art, the surfactant Cremophor was used
with taxanes to form the stock solution, but it was known
to trigger serious allergic reactions, including anaphylac-
tic shock. ’561 patent col.1 ll.59-63; ’512 patent col.2 ll.31-
35. The ’561 and ’512 patents relate to using surfactants
other than Cremophor with docetaxel and decreasing the
amount of ethanol to reduce alcohol intoxication and
anaphylactic effects in patients. After Hospira and Apo-
tex applied for Federal Drug Administration (“FDA”)
AVENTIS PHARMA v. HOSPIRA 4
approval to market generic versions of Taxotere, Sanofi
filed suit against them for infringement of the ’561 and
’512 patents. Only claim 5 of the ’561 patent and claim 7
of the ’512 patent are at issue on appeal.
The ’561 patent is titled “Compositions containing
taxane derivatives” and describes taxane compositions,
including a perfusion that avoids anaphylactic and alcohol
intoxication manifestations. Claim 5 of the ’561 patent
recites:
5. A perfusion, which contains approximately 1
mg/ml or less of compound of formula as defined
in claim 1, and which contains less than 35 ml/l of
ethanol and less than 35 ml/l of polysorbate,
wherein said perfusion is capable of being injected
without anaphylactic or alcohol intoxication mani-
festations being associated therewith.
The ’512 patent is titled “New compositions contain-
ing taxane derivatives,” and discloses taxane compositions
with reduced ethanol. Claim 7 depends from claims 1 and
6. As corrected by a Certificate of Correction, those
claims recite:
1. A composition comprising a compound of the
formula
5 AVENTIS PHARMA v. HOSPIRA
in which Ar is unsubstituted phenyl, R7 is phenyl
or tert butoxy, R6 is hydrogen, R5 is acetyloxy or
hydroxy, R3 and R4 taken together form an oxo
radical, R1 is hydroxy and R2 is hydrogen, said
composition being dissolved in a surfactant se-
lected from polysorbate, polyoxyethylated vegeta-
ble oil, and polyethoxylated castor oil, said
composition being essentially free or free of etha-
nol.
6. The composition of claim 1, wherein R5 is hy-
droxy and R7 is tert butoxy.
7. The composition of claim 6, wherein said sur-
factant is polysorbate.
After a bench trial, the court found that claim 7 of the
’512 patent was invalid as obvious and not infringed by
Hospira or Apotex. With respect to claim 5 of the ’561
patent, the court found that Hospira and Apotex did
infringe but concluded that the claim was obvious. The
court also determined that the ’512 and ’561 patents were
unenforceable for inequitable conduct.
II. DISCUSSION
On appeal, Sanofi challenges the district court’s con-
struction of two claim terms: “perfusion” in claim 5 of the
’561 patent and “essentially free or free of ethanol” in
claim 7 of the ’512 patent. Based on the district court’s
constructions, Sanofi argues that the court erred in find-
ing that both claims were invalid for obviousness under
35 U.S.C. § 103 and that Apotex’s and Hospira’s accused
products did not infringe claim 7 of the ’512 patent.
Additionally, Sanofi contends that the court erred in
finding that the ’561 and ’512 patents were unenforceable
AVENTIS PHARMA v. HOSPIRA 6
for inequitable conduct. We have jurisdiction under 28
U.S.C. § 1295(a)(1).
A. Claim 5 of the ’561 Patent
Claim construction is a question of law reviewed de
novo. Cybor Corp. v. FAS Techs., 138 F.3d 1448, 1454-55
(Fed. Cir. 1998) (en banc). Claim terms generally are
construed in accordance with the ordinary and customary
meaning they would have to one of ordinary skill in the
art in light of the specification and the prosecution his-
tory. Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed.
Cir. 2005) (en banc).
Before the district court, the parties initially agreed to
construe “perfusion” in claim 5 of the ’561 patent as “a
solution suitable for infusion into patients including at
least active pharmaceutical ingredient and an aqueous
infusion fluid such as physiological saline or glucose.”
Aventis Pharma S.A. v. Hospira, Inc., 743 F. Supp. 2d
305, 332 (D. Del. 2010). The parties, however, later
realized that they did not agree on the meaning of the
phrase “suitable for infusion into patients” in their pro-
posed construction, leading Sanofi to ask the district court
to require that the claimed “perfusion” also be effective for
treatment, safe, and stable (i.e., not precipitate) for at
least eight hours. The court declined to impose these
additional limitations and instead construed “perfusion”
to mean “an injectable solution containing the active
pharmaceutical ingredient and an aqueous infusion fluid.”
Id. at 333. On appeal, Sanofi argues that the district
court erred in not construing “perfusion” to include these
additional efficacy, safety, and stability limitations.
We can easily dispose of Sanofi’s first two limitations.
Neither the claims, the specification, nor the prosecution
7 AVENTIS PHARMA v. HOSPIRA
history suggest that the claimed perfusion must satisfy
certain safety or efficacy standards. We previously have
refused to impose such limitations when not required by
the language of the claims or the specification, see Mitsu-
bishi Chem. Corp. v. Barr Labs., Inc., 435 F. App’x 927,
934-35 (Fed. Cir. 2011); Iovate Health Scis., Inc. v. Bio-
Engineered Supplements & Nutrition, Inc., 586 F.3d 1376,
1382 (Fed. Cir. 2009), and decline to do so here.
Regarding Sanofi’s eight-hour stability limitation,
Sanofi does not contend that “perfusion,” as that term is
normally understood in the art, includes such a limita-
tion. Instead, Sanofi argues that based on how the term
is used in the context of the ’561 patent, the claimed
“perfusion” must demonstrate at least eight hours of
stability. See Oral Argument 3:05-3:10, available at
http://www.cafc.uscourts.gov/oral-argument-recordings/
2011-1018/all. This court recently reiterated the strin-
gent standard for narrowing a claim term beyond its plain
and ordinary meaning in Thorner v. Sony Computer
Entertainment America L.L.C., 669 F.3d 1362 (Fed. Cir.
2012). There, we explained that we will only interpret a
claim term more narrowly than its ordinary meaning
under two circumstances: “1) when a patentee sets out a
definition and acts as [its] own lexicographer, or 2) when
the patentee disavows the full scope of a claim term either
in the specification or during prosecution.” Id. at 1365.
“To act as its own lexicographer, a patentee must
‘clearly set forth a definition of the disputed claim term’
other than its plain and ordinary meaning.” Id. (quoting
CCS Fitness, Inc. v. Brunswick Corp., 288 F.3d 1359, 1366
(Fed. Cir. 2002)). In other words, “the patentee must
‘clearly express an intent’ to redefine the term.” Id. This
clear expression need not be in haec verba but may be
inferred from clear limiting descriptions of the invention
AVENTIS PHARMA v. HOSPIRA 8
in the specification or prosecution history. Similarly, to
disavow claim scope, “[t]he patentee may demonstrate
intent to deviate from the ordinary and accustomed
meaning of a claim term by including in the specification
expressions of manifest exclusion or restriction, repre-
senting a clear disavowal of claim scope.” Id. at 1366(quoting Teleflex, Inc. v. Ficosa N. Am. Corp., 299 F.3d
1313, 1325 (Fed. Cir. 2002)). Moreover, “[i]t is . . . not
enough that the only embodiments, or all of the embodi-
ments, contain a particular limitation” to limit a claim
term beyond its ordinary meaning. Id. Here, because
neither exception applies, the district court correctly did
not include an eight-hour stability limitation in its con-
struction of “perfusion.”
We begin our analysis with the language of the
claims. Phillips, 415 F.3d at 1312. Claim 5 requires that
the “perfusion” be “capable of being injected without
anaphylactic or alcohol intoxication manifestations,” but
contains no limitations with respect to the claimed perfu-
sion’s stability. Had the patentee similarly intended to
require that the “perfusion” display a certain duration of
stability, it could have included such a limitation in the
claim but notably did not. By expressly identifying the
specific characteristics of the “perfusion,” i.e., that it is
not associated with “anaphylactic or alcohol intoxication
manifestations,” the plain language of claim 5 indicates
that the term has its ordinary meaning subject only to
those specifically enumerated limitations.
This interpretation of “perfusion” also is consistent
with the teachings of the specification. Although the
specification does refer to perfusions with a stability of at
least eight hours, see ’561 patent col.2 ll.43-45 (“The new
perfusions [referring to examples in the specification] are
stable from a physical standpoint, that is to say no pre-
9 AVENTIS PHARMA v. HOSPIRA
cipitation phenomenon is seen to appear within approxi-
mately 8 hours.”), and the disclosed examples of perfu-
sions have stabilities exceeding eight hours, see id. at
col.2 l.59-col.3 l.26, these general descriptions of the
characteristics of embodiments do not suffice to limit the
claims. See Thorner, 669 F.3d at 1366 (“It is likewise not
enough that the only embodiments, or all of the embodi-
ments, contain a particular limitation.”). Indeed, the
specification expressly instructs that the disclosed exam-
ples “are not to be considered as limiting the invention.”
’561 patent col.2 ll.53-54. Moreover, in contrast to the
specification’s discussion of anaphylactic and alcohol
intoxication manifestations, nothing in the specification
indicates that a minimum stability of eight hours is an
essential feature of the claimed perfusion or an advantage
of the perfusion over the prior art. See Liebel-Flarsheim
Co. v. Medrad, Inc., 358 F.3d 898, 906-09 (Fed. Cir. 2004)
(distinguishing cases where the court narrowly construed
an otherwise broad claim term).
Nor does the prosecution history evidence a clear and
unmistakable disavowal of claim scope. The prosecution
history can offer insight into the meaning of a particular
claim term, but the “[c]laim language and the specifica-
tion generally carry greater weight.” HTC Corp. v. IPCom
GmbH & Co., 667 F.3d 1270, 1276 (Fed. Cir. 2012). Here,
the patentee’s observation during prosecution that the
perfusions in the Tarr reference demonstrated signs of
precipitation after four hours and thirty minutes neither
indicates that the claimed perfusion has a special defini-
tion nor clearly and unmistakably manifests the pat-
entee’s intention to limit claim 5 to perfusions that are
stable for at least eight hours. The Tarr reference was
not directed to the two-solvent solution of claim 5 but to a
prior art three-solvent solution; the argument was that
AVENTIS PHARMA v. HOSPIRA 10
the presence of the third solvent materially affected the
characteristics of the claimed composition.
Lastly, we reject Sanofi’s argument that the district
court improperly relied on extrinsic evidence in the form
of expert testimony in construing this claim term. Ac-
cording to Sanofi, because the intrinsic evidence alone
dictates the proper construction of perfusion, any extrin-
sic evidence is irrelevant. A district court, however, has
the discretion to take expert testimony into account in
determining the ordinary meaning of a claim term to one
skilled in the art. Phillips, 415 F.3d at 1319 (“[B]ecause
extrinsic evidence can help educate the court regarding
the field of the invention and can help the court deter-
mine what a person of ordinary skill in the art would
understand claim terms to mean, it is permissible for the
district court in its sound discretion to admit and use
such evidence.”). Here, the district court heard testimony
from both sides’ experts, including testimony from San-
ofi’s expert, Dr. Howard Burris, which was consistent
with the intrinsic evidence and supports the conclusion
that the ordinary meaning of a perfusion does not include
the stability limitation proposed by Sanofi. Consequently,
the district court did not err in relying on extrinsic evi-
dence in construing this claim term.
In sum, we conclude that the patentee did not narrow
the ordinary meaning of “perfusion” in claim 5 of the ’561
patent by either acting as its own lexicographer or dis-
claiming claim scope and therefore agree with the district
court that a “perfusion” is simply “an injectable solution
containing the active pharmaceutical ingredient and an
aqueous infusion fluid.”
Having affirmed the court’s claim construction, we
next address the district court’s conclusion that claim 5
11 AVENTIS PHARMA v. HOSPIRA
was invalid as obvious under 35 U.S.C. § 103. A patent is
invalid for obviousness “if the differences between the
subject matter sought to be patented and the prior art are
such that the subject matter as a whole would have been
obvious at the time the invention was made to a person
having ordinary skill in the art to which said subject
matter pertains.” 35 U.S.C. § 103(a). “Obviousness is a
question of law based on underlying findings of fact.” In
re Kubin, 561 F.3d 1351, 1355 (Fed. Cir. 2009). These
underlying factual inquiries are (1) the scope and content
of the prior art; (2) the differences between the prior art
and the claims at issue; (3) the level of ordinary skill in
the art; and (4) any relevant secondary considerations,
such as commercial success, long felt but unsolved needs,
and the failure of others. KSR Int’l Co. v. Teleflex Inc.,
550 U.S. 398, 406 (2007) (citing Graham v. John Deere
Co., 383 U.S. 1, 17-18 (1966)). On appeal from a bench
trial, we review the district court’s legal determination
that an invention is obvious de novo and the court’s
underlying factual determinations for clear error. Eli
Lilly & Co. v. Teva Pharms. USA, Inc., 619 F.3d 1329,
1336 (Fed. Cir. 2010).
The district court found that claim 5 was obvious in
light of the prior art, including the Guéritte-Voegelein
reference (“GV reference”) and the Dictionnaire Vidal
(“Vidal reference”). During oral argument, Sanofi’s
counsel confirmed that under the district court’s construc-
tion of “perfusion,” Sanofi did not dispute that claim 5
was obvious based on the prior art. Oral Argument 22:23-
22:45. Because we have affirmed the district court’s
construction of “perfusion,” we also affirm the district
court’s judgment that claim 5 of the ’561 patent is invalid
under 35 U.S.C. § 103.
AVENTIS PHARMA v. HOSPIRA 12
B. Claim 7 of the ’512 patent
Sanofi argues that the district court erred in constru-
ing the claim term “essentially free or free of ethanol” in
claim 7 of the ’512 patent as meaning that the claimed
perfusion contains “the same amount of ethanol as a stock
solution with no more than 5% ethanol by volume.”
Aventis, 743 F. Supp. 2d at 359. We need not resolve this
issue, however, because its resolution does not require
reversal of the district court’s obviousness determination.
Claim 7 of the ’512 patent claims a “composition,”
which the parties agree can be either a stock solution or a
perfusion. With respect to stock solutions, the parties
also agree that the phrase “essentially free or free of
ethanol” in claim 7 means “no more than 5% ethanol by
volume.” Id. Relying on this construction, the district
court found that claim 7 was obvious, noting that the “the
specification and claims of the prior art ’470 Patent[,] . . .
disclose and contemplate both ethanol-containing and
essentially ethanol-free stock solutions . . . .” Id. at 337
n.15 (emphasis added). Sanofi has not addressed the
district court’s obviousness finding with respect to stock
solutions in its opening brief. To the extent that Sanofi’s
conclusory statement in its reply that there is not “art in
the record of polysorbate stock solutions containing less
than 5% ethanol,” amounts to a challenge to the invalidity
finding, that argument is waived. Advanced Magnetic
Closures, Inc. v. Rome Fastener Corp., 607 F.3d 817, 833
(Fed. Cir. 2010) (“This court has consistently held that a
party waives an argument not raised in its opening
brief.”). Thus, regardless of whether the court correctly
construed “essentially free or free of ethanol” as it relates
to perfusions, the district court’s unchallenged finding
that the claimed stock solutions were obvious in light of
the prior art also renders the “composition” in claim 7
13 AVENTIS PHARMA v. HOSPIRA
obvious. See Titanium Metals Corp. v. Banner, 778 F.2d
775, 782 (Fed. Cir. 1985) (“It is . . . an elementary princi-
ple of patent law that when, as by a recitation of ranges or
otherwise, a claim covers several compositions, the claim
is ‘anticipated’ if one of them is in the prior art.”). We
accordingly affirm the district court’s judgment that claim
7 of the ’512 patent is invalid under 35 U.S.C. § 103.
C. Inequitable Conduct
Sanofi also appeals the district court’s determination
that both the ’512 and ’561 patents are unenforceable for
inequitable conduct. As an initial matter, Sanofi contends
that the district court abused its discretion in allowing
Hospira and Apotex to amend their pleadings after the
scheduling order deadline to add allegations related to
inequitable conduct without first finding that Hospira and
Apotex had established “good cause” as required by Fed-
eral Rule of Civil Procedure 16(b)(4). We review a district
court’s granting of a motion to amend pleadings under the
law of the regional circuit. Creative Compounds, L.L.C. v.
Starmark Labs., 651 F.3d 1303, 1309 (Fed. Cir. 2011). In
the Third Circuit, such decisions are reviewed for an
abuse of discretion. Race Tires Am., Inc. v. Hoosier Rac-
ing Tire Corp., 614 F.3d 57, 73 (3d Cir. 2010). Under Rule
16(b)(4), a scheduling order “may be modified only for
good cause and with the judge’s consent.” Fed. R. Civ. P.
16(b)(4).
Here, the parties do not dispute that the scheduling
order—and consequently Rule 16(b)(4)’s “good cause”
requirement—apply to Hospira’s amendment. With
respect to Apotex’s amendment, however, both Apotex
and Hospira argue that Apotex was never subject to the
scheduling order and therefore did not need to demon-
strate good cause to amend its pleadings. Assuming
AVENTIS PHARMA v. HOSPIRA 14
without deciding that the deadlines in the scheduling
order covered both Apotex and Hospira, we cannot say
that the district court abused its discretion in allowing
the amendments. Hospira timely asserted a claim for
inequitable conduct in its original counterclaims but,
shortly after deposing named-inventor Jean-Louis Fabre,
moved to amend its allegations after the scheduling order
deadline to specifically identify the withheld Vidal and
GV references. The district court granted the motion,
finding that “the timing of Hospira’s motion [did] not
appear to have been the product of bad faith” and that
Sanofi would not be unduly prejudiced by the amendment.
Apotex then filed a motion to amend its counterclaims to
add a claim of inequitable conduct, which the district
court also granted. Given the circumstances of this case,
including the temporal proximity of the amendments to
inventor Fabre’s deposition, there was good cause for the
amendments, and the district court did not abuse its
discretion in allowing them. Consequently, we turn to the
merits.
The district court found that the Vidal and GV refer-
ences were material to patentability and that inventor
Fabre intentionally withheld them with the intent to
deceive the U.S. Patent and Trademark Office (“PTO”).
Based on these findings, the court concluded that the ’512
and ’561 patents were unenforceable for inequitable
conduct. Sanofi argues that we should reverse the court’s
inequitable conduct judgment because Fabre explained
why he did not disclose these references to the PTO and,
thus, the court’s finding that he acted with the intent to
deceive was not the single most reasonable inference that
could be drawn from the evidence. Additionally, Sanofi
contends that these references were not material to
patentability because they were duplicative of references
that were before the PTO. In response, Apotex and
15 AVENTIS PHARMA v. HOSPIRA
Hospira argue that the district court’s intent findings are
supported by both the evidence and the court’s credibility
determinations. Regarding materiality, they maintain
that the district court properly applied the but-for mate-
riality analysis in concluding that the references were
material to patentability. We agree with Apotex and
Hospira.
In reviewing the district court’s inequitable conduct
determination, we review the court’s underlying factual
findings for clear error and its ultimate decision as to
inequitable conduct for an abuse of discretion. Star
Scientific, Inc. v. R.J. Reynolds Tobacco Co., 537 F.3d
1357, 1365 (Fed. Cir. 2008). To prevail on an inequitable
conduct defense, a defendant must establish both the
materiality of the withheld reference and the applicant’s
intent to deceive the PTO. Therasense, Inc. v. Becton,
Dickinson & Co., 649 F.3d 1276, 1290 (Fed. Cir. 2011) (en
banc). In Therasense, this court rejected the “sliding
scale” approach to proving inequitable conduct “where a
weak showing of intent may be found sufficient based on a
strong showing of materiality, and vice versa.” Id. In-
stead, we instructed that “[i]ntent and materiality are
separate requirements.” Id. Additionally, we held that
but-for materiality is the standard for evaluating the
materiality prong of the analysis unless there is affirma-
tive egregious misconduct. Id. at 1292. In this case,
although the district court did not have the benefit of our
Therasense opinion when it rendered its inequitable
conduct decision, the court nevertheless found that the
withheld references were but-for material to patentability
and made distinct intent and materiality findings rather
than employing the now-abrogated sliding scale approach.
Consequently, as set forth below, we conclude that the
court’s inequitable conduct determination withstands
even the more rigorous standard adopted in Therasense.
AVENTIS PHARMA v. HOSPIRA 16
1. Materiality
A prior art reference “is but-for material if the PTO
would not have allowed a claim had it been aware of the
undisclosed prior art.” Therasense, 649 F.3d at 1291.
Unlike the clear and convincing evidence standard for
invalidating a patent in the district court under 35 U.S.C.
§§ 102 and 103, the standard for establishing but-for
materiality in the inequitable conduct context only re-
quires a preponderance of the evidence, “giv[ing] claims
their broadest reasonable construction.” Id. at 1291-92.
As a result, when a “claim is properly invalidated in
district court based on the deliberately withheld refer-
ence, then that reference is necessarily material” for
purposes of the inequitable conduct inquiry. Id. at 1292.
On the other hand, even if the withheld reference is not
sufficient to invalidate the claim in district court, “the
reference may be material if it would have blocked patent
issuance under the PTO’s different evidentiary stan-
dards.” Id.Here, we have affirmed the district court’s finding
that the ’561 and ’512 patents were invalid based on, inter
alia, the withheld GV and Vidal references. Because such
references are necessarily material to patentability, the
district court did not err in finding that the materiality
requirement was established.
2. Intent
To satisfy the intent requirement, “the accused in-
fringer must prove by clear and convincing evidence that
the applicant knew of the reference, knew that it was
material, and made a deliberate decision to withhold it.”
Id. In Therasense, we confirmed that inequitable conduct
requires clear and convincing evidence of a specific intent
17 AVENTIS PHARMA v. HOSPIRA
to deceive the PTO and that “the specific intent to deceive
must be ‘the single most reasonable inference able to be
drawn from the evidence.’” Id. (quoting Star Scientific,
537 F.3d at 1366). “This court reviews the district court’s
factual findings regarding what reasonable inferences
may be drawn from the evidence for clear error.” Id. at
1291. In this case, the district court heard extensive
testimony from inventor Fabre regarding both the Vidal
and GV references, and the court’s finding that Fabre
acted with a specific intent to deceive the PTO in with-
holding those references is not clearly erroneous.
The Vidal reference discloses Sandoz’s experience us-
ing polysorbate 80 as a surfactant with the cancer drug
etoposide. During the trial, Fabre testified that he did
not cite the Vidal reference to the PTO because the eto-
poside-type experiments he and his co-inventors per-
formed with doxcetaxel resulted in perfusions that did not
demonstrate eight hours of stability. According to Fabre,
he believed that these experiments were failures and that
he therefore did not need to disclose the Vidal reference to
the PTO. Sanofi argues that based on this testimony the
district court erred in finding that Fabre had the specific
intent to deceive the PTO because that finding was not
the single most reasonable inference that could be drawn.
We disagree.
The district court considered Fabre’s explanation for
withholding the Vidal reference and expressly rejected it
based on both the evidence presented and the finding that
Fabre lacked credibility. Specifically, the district court
relied on Fabre’s testimony that he learned of replacing
Cremophor with polysorbate 80 from the Vidal reference
and that the Sandoz experience disclosed in the reference
was one of the “main factors that shaped [his] thinking”
in choosing polysorbate 80 and led him to believe that
AVENTIS PHARMA v. HOSPIRA 18
replacing Cremophor with polysorbate 80 would avoid
anaphylactic manifestations. Aventis, 743 F. Supp. 2d at
351-53. This testimony also was consistent with a Sanofi
internal memorandum acknowledging the side effects
associated with Cremophor and noting that Sandoz had
used polysorbate 80 (i.e., “TWEEN”) instead of Cremophor
in its etoposide product. Id. at 351; J.A. 5666.
In making its intent finding, the district court also
emphasized that in Fabre and his co-inventors’ submis-
sions to the PTO, they cited the Rowinsky reference,
which identified the “problem” the inventors were trying
to solve—i.e., the anaphylactic reactions associated with
Cremophor—but did not cite the Vidal reference, which
revealed the “solution”—i.e., the switch from Cremophor
to polysorbate 80. Aventis, 743 F. Supp. 2d at 352. The
court found that “[t]here simply is no justification for
telling the [PTO] about the prior art disclosing the prob-
lem [Fabre] examined while concealing key prior art
disclosing the solution he chose.” Id. at 353.
Finally, in addressing Fabre’s excuse that he withheld
the Vidal reference because the etoposide-type experi-
ments he and his co-inventors performed were failures,
the court found that Fabre’s testimony was not credible.
The court determined that during Fabre’s direct examina-
tion he did not address all of the etoposide-type experi-
ments that he and his colleagues had undertaken but
rather only reviewed those experiments that demon-
strated low stability and thus supported Fabre’s excuse
for not disclosing the reference. The remaining experi-
ments discussed during Fabre’s cross-examination, how-
ever, displayed stabilities ranging from five hours and
forty minutes to over thirty hours. Id. at 352-53; J.A.
5566-69. Fabre attempted to downplay the significance of
these experiments by stating that they were not “eto-
19 AVENTIS PHARMA v. HOSPIRA
poside-type formulations.” But the district court found
that Fabre’s testimony was contrary to the titles of the
Sanofi documents detailing those experiments and lacked
credibility: “The court does not find credible Fabre’s
witness-stand assertion, twenty years after the docu-
ments were prepared, that the contemporaneous descrip-
tion of these formulations as ‘etoposide-type’ did not
reflect how Sanofi’s researchers actually viewed the
formulations.” Aventis, 743 F. Supp. 2d at 353. Based on
the evidence and his assessment of Fabre’s testimony, the
court found that Fabre “knew that the Vidal reference
and the other etoposide prior art were relevant to the
patentability of his alleged invention, but nonetheless
chose not to disclose it to the patent office.” Id. From this
finding, the court concluded that Fabre acted with the
intent to deceive the PTO when he withheld the Vidal
reference. Id.In light of the evidence before the district court sup-
porting the finding of a specific intent to deceive, coupled
with the deference we must afford to the district court’s
credibility determinations, we cannot conclude that the
court’s finding that Fabre withheld the Vidal reference
with the specific intent to deceive the PTO was clearly
erroneous.
We reach the same conclusion with respect to the GV
reference. The GV reference describes the relationship
between the structure and activity of various analogues of
paclitaxel including docetaxel and names one of Fabre’s
colleagues as an author. Specifically relevant to the
patentability of the patents at issue, the reference states:
“Moreover Taxotere (13a) showed a better solubility in
excipient system (polysorbate 80/ethanol, 1:1) . . . .” J.A.
5631. Fabre testified that he did not cite the GV refer-
ence to the PTO because he only read a March 1990 draft
AVENTIS PHARMA v. HOSPIRA 20
of the reference which did not include this sentence
disclosing the polysorbate 80/docetaxel formulation.
Again, the district court found that this testimony
was not credible and relied on the other evidence pre-
sented during the trial in finding that Fabre withheld the
reference with the specific intent to deceive the PTO. The
court explained that Fabre was the project leader of
Sanofi’s Taxotere development, had to approve the GV
reference for publication, and had testified that he re-
viewed the article “with some care to make sure that it
was a proper article for the company to be publishing.”
Id. at 353-54. The court further highlighted Fabre’s
testimony that in March 1992, he was dissatisfied with
the clinical brochure for Taxotere because it did not list
the GV reference and affirmatively took steps to ensure
that the reference was identified. Six months later,
however, when Fabre signed his patent declaration, he
failed to disclose the reference to the PTO. Id. at 353.
Relying on this evidence, the district court found that
Fabre “‘reviewed . . . with some care’ the final version of
the GV reference prior to signing the patent declaration,
was aware of the reference’s materiality to the prosecu-
tion of his patents, and purposefully decided not to dis-
close it despite this knowledge.” Id. at 354. Thus,
contrary to Sanofi’s contention, in concluding that Fabre
acted with a specific intent to deceive the PTO, the dis-
trict court did not rely solely on its finding that Fabre was
not credible but instead viewed Fabre’s testimony in light
of the other evidence to reach its intent conclusion. Based
on the evidence presented, this finding was not clearly
erroneous.
Relying on these materiality and intent findings, the
district court found the patents were unenforceable due to
inequitable conduct. Id. at 354. Based on the district
21 AVENTIS PHARMA v. HOSPIRA
court’s thorough discussion of its factual findings and its
well-reasoned analysis that is consistent with Therasense,
this determination was not an abuse of discretion. We
accordingly affirm.
III. CONCLUSION
We have considered Sanofi’s additional arguments for
reversing the district court’s decision and conclude that
they similarly lack merit. Consequently, for the reasons
set forth above, the district court’s judgment that claim 5
of the ’561 patent and claim 7 of the ’512 patent are
invalid for obviousness and that the ’561 and ’512 patents
are unenforceable for inequitable conduct is affirmed.
AFFIRMED