Aventis Pharma s.a. v. Amphastar Pharmaceuticals, Inc. ( 2006 )

NOTE: Pursuant to Fed. Cir. R. 47.6, this disposition
is not citable as precedent. It is a public record.
United States Court of Appeals for the Federal Circuit
05-1513
AVENTIS PHARMA S.A. and AVENTIS PHARMACEUTICALS INC.,
Plaintiffs-Appellants,
v.
AMPHASTAR PHARMACEUTICALS, INC.,
Defendant-Appellee,
and
TEVA PHARMACEUTICALS USA, INC.,
Defendant-Appellee.
__________________________
DECIDED: April 10, 2006
__________________________
Before RADER, SCHALL, and PROST, Circuit Judges.
PROST, Circuit Judge.
Aventis Pharma S.A. and Aventis Pharmaceuticals, Inc., (collectively, “Aventis”)
appeal from decisions of the United States District Court for the Central District of
California granting summary judgment in favor of Amphastar Pharmaceuticals, Inc.,
(“Amphastar”) and Teva Pharmaceuticals USA, Inc., (“Teva”) (jointly “appellees”)
holding unenforceable United States Patent No. 5,389,618 (“the ’618 patent”), Aventis
Pharma S.A. v. Amphastar Pharm., 390 F. Supp. 2d 936 (C.D. Cal. 2005) (“Aventis
Opinion”), and United States Reissue Patent No. 38,743 (“the ’743 reissue patent”),
Aventis Pharma S.A. v. Amphastar Pharm., 390 F. Supp. 2d 952 (C.D. Cal. 2005).
Although there are no genuine issues of material fact with respect to materiality,
because genuine issues of material fact remain as to intent, we reverse the district
court’s grant of summary judgment of inequitable conduct and remand for further
proceedings consistent with this opinion.
BACKGROUND
The ’618 patent and the ’743 reissue patent disclose and claim mixtures of low
molecular weight herapin (“LMWH”) used to prevent blood clots. During prosecution of
the application leading to the ’618 patent and the ’743 reissue patent, Aventis compared
the half-life of a product allegedly covered by the ’618 patent (Example 6 of the ’618
patent or “Debrie LMWH”) at a 40 mg dose to the half-life of a prior art product (“EP
40,144 LMWH” or “Mardiguian LMWH”) at a 60 mg dose. Aventis made these
comparisons to the Patent and Trademark Office (“PTO”) in the patent application, in
several office action responses, and in two declarations by a French scientist named Dr.
Andre Uzan to show an unexpected and significantly better half-life of Debrie LMWH
when compared to EP 40,144 LMWH. Aventis did not, however, expressly disclose the
dosages at which the half-life comparisons were made, and specifically, that the EP
40,144 LMWH data was for a 60 mg dose.
The ’618 patent and the ’743 reissue patent purportedly cover drug compositions
called Lovenox® that are approved by the Food and Drug Administration (“FDA”).
Amphastar and Teva filed Abbreviated New Drug Applications (“ANDAs”) with the FDA
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to obtain approval to market generic versions of Lovenox®. In response, Aventis, the
owners of the ’618 patent and the ’743 reissue patent, filed a patent infringement suit
against Amphastar and Teva in the United States District Court for the Central District of
California.
The district court granted a motion for summary judgment of unenforceability due
to inequitable conduct submitted by Amphastar. Without holding a hearing, the court
concluded that Aventis’s repeated representations of patentability based on the
purported improved half-life of Debrie LMWH were material. The court faulted Aventis
for comparing data based on different doses to show an improved half-life, when a
comparison of available data using the same doses actually showed that there was little
if any difference between the half-lives of the prior art and the purported invention. The
court rejected Aventis’s argument that Dr. Uzan’s first declaration can reasonably be
interpreted as meaning that the disclosed half-life data was based on different dosages,
calling the argument “specious.”
Regarding intent, the court rejected Aventis’s argument that the use of the 40 mg
Debrie LMWH data, as opposed to the 60 mg Debrie LMWH data, was reasonable. The
court stated that the question is not whether use of the 40 mg data was reasonable, but
whether there was an omission of material fact, particularly in light of the fact that the
same study showed that the 60 mg Debrie LMWH data and the 60 mg EP 40,144
LMWH data was much closer than the 40 mg Debrie LMWH data and the 60 mg EP
40,144 LMWH data. Based on these circumstances, the court found that the facts
support a strong inference of intent. The court then weighed materiality and intent. It
found weighty uncontroverted evidence sufficient to establish materiality and intent to
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deceive, and further stated that Aventis submitted just a scintilla of evidence in
opposition. It therefore granted summary judgment of unenforceability due to
inequitable conduct.1
Aventis timely appealed. We have jurisdiction under 28 U.S.C. § 1295(a)(1).
DISCUSSION
A. Standards of Review
We review a district court’s grant of summary judgment under the law of the
applicable regional circuit. CollegeNet Inc. v. ApplyYourself Inc., 418 F.3d 1225, 1230
(Fed. Cir. 2005). In the Ninth Circuit, a grant of summary judgment is reviewed de
novo. Leonel v. Am. Airlines, Inc., 400 F.3d 702, 708 (9th Cir. 2005). “We must
determine ‘whether, viewing the evidence in the light most favorable to the nonmoving
party, there are any genuine issues of material fact and whether the district court
correctly applied the relevant substantive law.’” Id. (quoting Lopez v. Smith, 203 F.3d
1122, 1131 (9th Cir. 2000) (en banc)).
This court recently stated the standards for finding inequitable conduct as
follows:
1
Aventis filed the reissue application that led to the ’743 reissue patent
before filing suit against Amphastar and Teva. During prosecution of the reissue
application, Aventis informed the examiner that it was not relying on any statement or
argument based on Example 6 made during prosecution of the application leading to
the ’618 patent. The ’743 reissue patent issued, and therefore Aventis surrendered the
’618 patent by operation of law, the day before the district court granted Amphastar’s
summary judgment motion with respect to the ’618 patent. After granting summary
judgment on the ’618 patent, the court applied the holding of Hoffman-La Roche Inc. v.
Lemmon Co., 906 F.2d 684, 688-89 (Fed. Cir. 1990) (inequitable conduct in original
patent renders any reissue patent unenforceable), to enter summary judgment of
unenforceability against the ’743 reissue patent. Aventis Pharma, 390 F. Supp. 2d at
954-55.
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Applicants for patents have a duty to prosecute patents in the PTO with
candor and good faith, including a duty to disclose information known to
the applicants to be material to patentability. A breach of this duty may
constitute inequitable conduct, which can arise from an affirmative
misrepresentation of a material fact, failure to disclose material
information, or submission of false material information, coupled with an
intent to deceive or mislead the PTO. A party asserting that a patent is
unenforceable due to inequitable conduct must prove materiality and
intent by clear and convincing evidence. Once threshold findings of
materiality and intent are established, the trial court must weigh them to
determine whether the equities warrant a conclusion that inequitable
conduct occurred. This requires a careful balancing: when the
misrepresentation or withheld information is highly material, a lesser
quantum of proof is needed to establish the requisite intent. In contrast,
the less material the information, the greater the proof must be.
Purdue Pharma L.P. v. Endo Pharm., Inc., 438 F.3d 1123, 1128-29 (Fed. Cir. 2006)
(citations omitted).
B. Materiality
We first consider whether there is any issue of material fact that the applicant for
the ’618 patent failed to disclose material facts to the PTO. The threshold showing of
materiality required to proceed to the “balancing” portion of the inequitable conduct
inquiry can be met by showing a reasonable examiner would have considered such
information important in deciding whether to allow the application. Digital Control, Inc.
v. Charles Mach. Works, 437 F.3d 1309, 1316 (Fed. Cir. 2006).
The district court first determined that “Amphastar, by clear and convincing
evidence, has met its initial burden of identifying for the court those portions of the
materials on file that it believes demonstrates the absence of any genuine issue of
material fact with respect to Aventis’s failure to disclose material information.” Aventis
Opinion, 390 F. Supp. 2d at 946. We agree that based on Aventis’s undisputed
omissions, Amphastar met its initial burden of showing that Aventis failed to disclose
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material information. Aventis never disclosed during prosecution that it derived the half-
life data for the EP 40,144 LMWH at a 60 mg dose. The half-life comparisons were
highly material to patentability. In multiple office actions, the examiner rejected claims
for the Debrie compounds based on the EP 40,144 patent. Each time, Aventis
distinguished the Debrie compounds based on their “significant” increase in half-life over
the EP 40,144 compounds without providing any information regarding the dosage at
which the data for either compound was obtained. In its final office action, Aventis
provided three tables of test data: 1) Debrie LMWHs labeled as obtained at 40 mg; 2)
Debrie LMWH labeled as obtained at 60 mg; and 3) EP 40,144 LMWH without a label
as to its dosage. The failure to disclose that the EP 40,144 data was obtained at 60 mg
denied the examiner an opportunity to determine whether the differences in half-lives
between the Debrie and EP 40,144 compounds were significant. Therefore, an
omission that would have revealed that the difference in half-lives was actually much
smaller was material to patentability. A comparison made at the same dosage, 60 mg,
would have yielded a much smaller difference in half-life. Given the centrality of the
differences in half-lives to patentability, by failing to disclose the dosage of the 60 mg
compound or to disclose that the difference in half-lives at the same dosage was
actually lower, Aventis failed to disclose material information to the PTO.
The district court then found that Aventis failed to establish any facts showing a
genuine issue of material fact that a material omission was made in prosecution of the
’618 patent. Id. at 946.
On appeal, Aventis argues that it has raised material facts regarding materiality
of the omission. Aventis contends that if the dose information was material, the
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examiner would have requested it because 1) she was presented with half-life data that
enabled her to compare various doses, and 2) she had a motivation to compare them.
Aventis argues that the examiner would have been so motivated because Dr. Uzan did
inform the examiner that the dosage comparison was done at different dosages, Dr.
Uzan never expressly represented that he was comparing half-life at the same dose,
those of skill in the art frequently compared half-lives at different doses and so the
examiner should have assumed this here, and because the specification teaches that
the half-life of the claimed products are independent of dose. We reject these
arguments.
In support of its argument that Dr. Uzan did inform the examiner that the dosage
comparison was done at different dosages, Aventis points to language in Dr. Uzan’s
March 29, 1993 declaration, stating:
the claimed formulations had a plasma half life longer than 4 1/2 hours in
45% of the cases in contrast to Mardiguan [sic] who achieved such a half
life in only 17% of the cases. This represents an increase in 250% in the
half life and is very significant because it enables the same effect to be
achieved with lower dosages.
(J.A. 1894) (emphasis added). Dr. Uzan explained at his deposition that he believes
that the second sentence “say[s] that the comparison is a comparison between two
doses of which one is lower than the other.” (J.A. 2119-20.) Aventis’s rebuttal expert
claimed the statement “reasonably conveys that at a lower dose of the [Debrie] product,
a higher percentage of subjects exhibited a half-life longer than 4 1/2 hours.” (J.A.
1010.) Aventis maintains that the court erred in dismissing this interpretation of the
sentence as “specious,” and argues that, at a minimum, the testimony is subject to
reasonable debate.
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Although Dr. Uzan may have had some doubt as to the meaning of his
statement, we find there is no reasonable debate as to what it stated to the patent
office. A reasonable examiner would understand the statement only to allege a benefit
of the claimed invention, not as a disclosure that different dosages were being
compared. Aventis’s own statements incorporating Dr. Uzan’s declaration support this
conclusion. For example, in one office action, Aventis stated:
[T]he half life obtained for the claimed preparation was 4.36 +- 1.07 hours
whereas that for Mardiguian was 3.33 +- 0.2 hours. This is approximately
a 30% difference in results and is significant in that it means that the
claimed preparations can be administered in significantly lower doses.
(J.A. 1933) (emphasis added); (see also J.A. 1885-86 (referencing Dr. Uzan’s
statement)). It is not plausible to read these statements as indicating to the examiner
that the data for the Debrie LMWH was obtained for a lower dose than the Mardiguian
LMWH. They tell the examiner that the longer half-life of the claimed invention is a
benefit. We therefore agree with the district court that there is no genuine issue of
material fact that Dr. Uzan did not disclose in this statement that the comparison was
made using data from different doses.2
Second, although Aventis did not expressly represent that the half-life
comparison was at the same dosage, it repeatedly compared the 40 mg Debrie LMWH
table’s data with the unlabelled EP 40,144 data. By making the comparison at different
dosages without disclosing that this was so, Aventis led the examiner away from any
2
If, as Aventis argues, Dr. Uzan did actually believe he was disclosing a
comparison of different doses, in part because he is a native French speaker, this may
go to his intent, as discussed further below.
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questions about dosage or any motivation to question the dosage for the EP 40,144
data.
In addition, we reject Aventis’s argument that the examiner would be motivated to
compare half-lives at different dosages, as this was common practice. In each of the
prior art references Aventis cites as showing comparisons at different dosages, the
differences in dosages was expressly disclosed. In addition, although a comparison of
preferred therapeutic doses may be the norm, there is no evidence that the examiner
was ever made aware that the preferred therapeutic dose for the Debrie compound was
40 mg. Therefore, though it may at times be reasonable to compare half-lives for
different dosages would not have motivated the examiner to compare the unlabelled 60
mg EP 40,144 data with the 60 mg Debrie data, when the comparison provided used
the 40 mg Debrie data.
Finally, we reject Aventis’s position that the examiner would be motivated to
compare different dosages because the specification stated that the claimed
compounds were dose independent. Indeed, if the examiner truly credited the fact that
the Debrie LMWHs are dose independent, the examiner would have had no reason to
compare the EP 40,144 data with different doses of the Debrie data because the Debrie
data at different doses would be the same. In addition, the examiner could not have
been aware of whether the EP 40,144 data was for a particular dose or for some
combination of dosages, such that a comparison would be irrelevant.
In summary, it was insufficient to merely submit the underlying data to the
examiner and later argue that the examiner could have requested the EP 40,144
dosage information to make additional comparisons. The withholding of the EP 40,144
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dosage information prevented the examiner from considering information important in
deciding whether to allow the application, and was therefore a failure to disclose
material information to the PTO. Digital Control, 437 F.3d at 1314.
C. Intent to Deceive the PTO
Even if an omission is found to be material, the omission must also be found to
have been made with the intent to deceive. “Materiality does not presume intent, which
is a separate and essential component of inequitable conduct.” GFI, Inc. v. Franklin,
Corp., 265 F.3d 1268, 1274 (Fed. Cir. 2001) (quoting Manville Sales Corp. v.
Paramount Sys., Inc., 917 F.2d 544, 552 (Fed. Cir. 1990)). To find an intent to deceive,
“the involved conduct, viewed in light of all the evidence, including evidence of good
faith, must indicate sufficient culpability to require a finding of intent to deceive.”
Paragon Podiatry Lab., Inc. v. KLM Labs., Inc., 984 F.2d 1182, 1189 (Fed. Cir. 1993)
(quoting Kingsdown Med. Consultants Ltd. v. Hollister, Inc., 863 F.2d 867, 876 (Fed.
Cir. 1988) (en banc)). “Intent need not be shown by direct evidence, but may be
inferred from the totality of the evidence.” Digital Control, 437 F.3d at 1319. However,
“[i]n the summary judgment context, all inferences must be made in favor of the
nonmovant; thus, it is often improper to determine at summary judgment that a patentee
made intentional misstatements or omissions to the PTO.” Id. at 1317. On summary
judgment, to create a genuine issue of material fact, Aventis was required to state
specific facts supporting a plausible justification or excuse for its failure to disclose
material information. Paragon Podiatry, 984 F.2d at 1191.
Here, the district court did not find direct evidence of intent to deceive, but found
that the “facts and circumstances surrounding the failure to disclose the dose differential
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. . . supports a strong inference of intent by Aventis to deceive the PTO.” Aventis
Opinion, 390 F. Supp. 2d at 951-52. Aventis contends that the district court erred in
finding an intent to deceive on summary judgment by denying Dr. Uzan an opportunity
to testify in person, ignoring evidence negating intent, misconstruing deposition
testimony, and drawing factual inferences adverse to Aventis. Because Aventis has
met its burden of setting forth a plausible justification for its failure to disclose material
information, deciding all inferences in favor of Aventis, we hold that the district court
erred in finding intent to deceive on summary judgment.
For example, the district court found it irrelevant whether comparison at different
doses was reasonable. Id. at 951. On appeal, Teva also advocates this position,
arguing that the relevant inquiry is whether there was an intent to deceive in failing to
disclose the 60 mg dosage amount of the prior art product. We disagree. The
reasonableness of the comparison between different dosages is relevant to determining
whether the failure to disclose that the comparison was made using 60 mg EP 40,144
data was made with an intent to deceive. Because there exist genuine issues of
material fact as to the reasonableness of the comparisons made by Aventis,3 we must
draw an inference for purposes of summary judgment that it was reasonable to compare
the 40 mg Debrie half-life with the 60 mg EP 40,144 half-life. Accepting that inference,
the district court was required to determine whether Aventis still intended to deceive by
withholding the dosages at which the comparisons were made.
3
For example, Aventis argues the comparison was reasonable because: 1)
it reflects the preferred dosage level for therapeutic reasons; 2) the 60 mg dosage level
was not preferred because it caused bleeding in some patients; and 3) the 40 mg
dosage level was more reliable because it had been confirmed in a separate study.
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Aventis maintains that Dr. Uzan had a reasonable belief that he informed the
examiner that his half-life comparison was made at different doses and that he could not
have intended to deceive because he disclosed the data based on 60 mg. Aventis
further explains that Dr. Uzan had no reason to make a prospective statement about
what would be possible using a lower dose based on a comparison at the same dose,
because he could and did directly make that point by comparing the 60 mg EP 40,144
LMWH data against the 40 mg Debrie LMWH data. Aventis also points out that the
district court did not even reference, let alone draw reasonable inferences from the fact
that Dr. Uzan submitted the half-life data for 60 mg of Debrie LMWH, which would allow
the examiner to compare the data from equal doses.
Although the district court did not reference all of Aventis’s arguments, it
ultimately concluded that the facts supported a strong inference of intent to deceive.
The district court’s inference was reasonable—by failing to disclose that the EP 40,144
data was at a 60 mg dose, Aventis may have been painting the rosiest picture possible
as to the half-life improvement of its claimed compounds in an attempt to deceive the
examiner.4 Appellees contend that this is only reasonable inference to draw from the
facts presented.
However, there is another reasonable inference—namely, as Aventis argues, if
the comparison between different doses was reasonable, the failure to disclose may
have been due purely to inadvertence. Based on the facts presented by Aventis, these
are not “insupportable, [or] specious . . . explanations or excuses.” Paragon Podiatry,
4
Even the disclosure of the 60 mg Debrie data might ultimately militate a
finding of intent to deceive because it implies that Dr. Uzan was aware that the 60 mg
data was relevant to the comparison, but did not specifically tell the examiner why.
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984 F.2d at 1190. Neither are Aventis’s contentions merely “[c]onclusory allegations
and attorney arguments.” Ferring v. Barr, 437 F.3d 1181, 1193 (Fed. Cir. 2006).
Aventis presents declarations from the inventor, the declarant, and an expert witness
stating facts supporting a “plausible justification” for its material omission. Paragon
Podiatry, 984 F.2d at 1191. Therefore, a finding of intent was inappropriate on
summary judgment.
CONCLUSION
While we agree with the district court with regard to its finding of materiality on
summary judgment, there remain genuine issues of material fact regarding Aventis’s
intent to deceive the PTO. Therefore, we reverse the district court’s decisions granting
summary judgment of unenforceability of the ’618 patent and ’743 reissue patent and
remand for further proceedings consistent with this opinion.
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