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 Washington, 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 appealed. 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 successor to the cancer drug paclitaxel, marketed as Taxol, 

and the composition for docetaxel was covered by nowexpired 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 infusion, accomplished by slowly delivering the drug in a 

diluted aqueous solution called a “perfusion.” Taxanes, 

however, have low solubility in water and tend to precipitate, 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 precipitation occurs. The taxane is combined with the additives to 

form a “stock solution” which is then mixed into an injectable aqueous solution, such as saline, to form a perfusion. 

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 anaphylactic 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 Apotex 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 manifestations being associated therewith. 

The ’512 patent is titled “New compositions containing 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 selected from polysorbate, polyoxyethylated vegetable oil, and polyethoxylated castor oil, said 

composition being essentially free or free of ethanol. 

6. The composition of claim 1, wherein R5 is hydroxy and R7 is tert butoxy. 

7. The composition of claim 6, wherein said surfactant 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 construction 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 finding 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 history. 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 proposed 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 Mitsubishi Chem. Corp. v. Barr Labs., Inc., 435 F. App’x 927, 

934-35 (Fed. Cir. 2011); Iovate Health Scis., Inc. v. BioEngineered 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 limitation. 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 stringent 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, representing 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 embodiments, 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 construction 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 perfusion’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 approximately 8 hours.”), and the disclosed examples of perfusions 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 embodiments, contain a particular limitation.”). Indeed, the 

specification expressly instructs that the disclosed examples “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 specification 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 definition nor clearly and unmistakably manifests the patentee’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. According to Sanofi, because the intrinsic evidence alone 

dictates the proper construction of perfusion, any extrinsic 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 determine 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 Sanofi’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 evidence 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 disclaiming 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 construction 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 construing 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 principle 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 Federal 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 Racing 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 demonstrate 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 references 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 materiality 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. Instead, 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 affirmative 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 requires 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 reference, 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 standards.” 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 infringer 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 withholding those references is not clearly erroneous. 

The Vidal reference discloses Sandoz’s experience using 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 etoposide-type experiments he and his co-inventors performed 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’ submissions 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 problem [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 experiments 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 examination he did not address all of the etoposide-type experiments that he and his colleagues had undertaken but 

rather only reviewed those experiments that demonstrated low stability and thus supported Fabre’s excuse 

for not disclosing the reference. The remaining experiments discussed during Fabre’s cross-examination, however, 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 documents were prepared, that the contemporaneous description 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 supporting 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 reference 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 presented 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 reviewed 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 prosecution of his patents, and purposefully decided not to disclose 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 district 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