CASRIP Newsletter - Summer 2008, Volume 15, Issue 2
Strong Inference of Intent to Deceive PTO Supported by Materiality of Disclosure: Aventis Pharma S.A. v. Amphastar Pharmaceuticals, Inc.
by Sheri Wardwell 
In Aventis Pharma S.A. v. Amphastar Pharmaceuticals, Inc., the Federal Circuit demonstrated its willingness to infer the element of intent to commit inequitable conduct when there is a failure to disclose a highly material fact to the United States Patent and Trademark Office (PTO) examiner during the prosecution of a patent.  The Federal Circuit affirmed that patents held by Aventis Pharma S.A. (Aventis) were unenforceable when Aventis was found to have intentionally deceived the PTO examiner by failing to disclose the dosage of a prior art product in a comparison with the claimed compound that was highly material to issuance of the patent. 
A. Patent Prosecution Background
Aventis owns U.S. Patent No. 5,389,618 (“the ‘618 patent”) and the reissue patent, U.S. Patent No. RE 38,743 (“the ‘743 patent”), for a composition of low molecular weight heparinic polysaccharides marketed as Lovenox(r)(Clexane(r) in Europe) to prevent and treat thromboses.  The original claim for the ‘618 patent was rejected under 35 U.S.C. §§ 102(b)/103 for prior art references, including European Patent 40,144 (“EP ‘144”).  The examiner did not consider the claim to unequivocally demonstrate an “unexpected or unobvious property not demonstrated by the prior art products.” 
Aventis amended the claim and refuted the anticipation rejection, under 35 U.S.C. § 102(b), by distinguishing differences in the physical properties of the claimed compound and EP ‘144. Aventis argued that differences in physical properties indicate differences in the structural composition of the compounds, which would indicate that the claimed compound is not inherent to EP ‘144.  In example 6, Aventis provided plasma half-life data obtained from Dr. Uzan, a non-inventor, to demonstrate that the half life of the patented compound at 40mg was longer when compared to the EP ‘144 compound. In a declaration, Dr. Uzan stated the difference “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.” Dr. Uzan concluded in his declaration that “the formulations of [EP ‘144] are clearly outside the scope of the present invention.”  Aventis refuted the obviousness rejection, under 35 U.S.C. § 103, asserting the properties of the claimed compound were not exhibited by the EP ‘144 compound and, therefore, EP ‘144 would not suggest to one of skill in the art the properties of the claimed compound. 
The claim was again rejected in a third office action, under 35 U.S.C § 103, because there was not sufficient evidence to demonstrate the existence of a compositional structure in the claimed compound not inherent to EP ‘144. In response, a second declaration from Dr. Uzan was submitted that included tables of raw data of the plasma half-life of the claimed compound and EP ‘144. Dr. Uzan reported the half-life of the claimed compound, from Table X, to be 4.36 ± 1.07 at 40mg and the half-life of EP ‘144, from Table III, to be 3.33 ±0.2. Table III did not indicate a dosage for EP ‘144. He asserted that the difference between the half-life values of the two compounds was statistically significant. Aventis claimed the difference in half-life values tends to show a difference in structure and properties between the two compounds. Only after submission of the second Dr. Uzan declaration was the application approved.
B. Procedural History
Amphastar Pharmaceuticals, Inc. (Amphastar) challenged the Aventis patents to market a generic version of Lovenox(r).  Aventis responded with a suit for infringement of the ‘618 patent. Amphastar filed a motion for summary judgment claiming that ‘618 is unenforceable because of Dr. Uzan’s inequitable conduct in failing to disclose that the comparison of half-life values was made at different doses of the claimed compound and the EP ‘144 compound. The district court granted Amphastar’s motion for summary judgment finding the dosage to be material to the patent application and “a strong inference of intent to deceive because it could find no credible explanation for comparing half-lives at different doses and because comparisons at the same dose showed little difference in half-life.”
On appeal, the Federal Circuit held that while dosage in comparing half-life values is material to patentability, the district court must determine whether Aventis intended to deceive the examiner.  The Federal Circuit added that the “reasonableness of the comparison at different doses is relevant to determine whether there was an intent to deceive in withholding the dosage.” 
On remand, the district court held a bench trial finding that Dr. Uzan’s failure to disclose the dosage was intentional because the defendants provided clear and convincing evidence that Aventis knew the dosage was not being disclosed, knew the dosage was material to securing a patent, and was unable to provide a reasonable explanation for comparing different doses or omitting the dosage value.  The district court determined that but for the failure to disclose the dosage of EP ‘144, the patent application would not have issued and, therefore, the ‘618 patent is unenforceable because of inequitable conduct. 
A. The District Court Did Not Abuse Its Discretion in Finding Inequitable Conduct
Inequitable conduct analysis requires first, determining whether the applicant intended to mislead by omitting material information  and second, weighing the intent and the materiality of the information to determine whether the behavior is sufficiently culpable to find a patent unenforceable.  The Federal Circuit agreed with the district court that the primary issue surrounding the rejection of the ‘618 patent, at least before the third office action, was whether the composition of the claimed compound were inherent to the EP ‘144 compound.  The Federal Circuit rejected Aventis’ contention that the half-life data was admitted to answer only the obviousness rejection, under 35 U.S.C § 103, finding that the half-life data was used in the patent prosecution to refute both anticipation and obviousness.  Because a comparison of the half-lives of the claimed compound and the EP ‘144 compound at the same dosages was required to demonstrate that the composition of the claimed compound was not inherent to the EP ‘144 compound,  the dosage of EP ‘144 was material to refute anticipation under 35 U.S.C § 102(b).  The heavy reliance on the half-life data makes the dosage value of EP’ 144 highly material to the ‘618 patent prosecution.
The Federal Circuit stressed that the more material the information is to the prosecution of the patent the lower the burden of demonstrating intent to find inequitable conduct.  The failure to disclose the highly material dosage value of EP ‘144 indicates intent to deceive the examiner.  The Federal Circuit found the district court did not abuse its discretion when it found that the presumption of intent supported by sufficient evidence that Aventis intentionally provided misleading data by omitting the dosage value. The possible justifications posited by Aventis did not convince the Federal Circuit that the omission was inadvertent,  or that comparison of different doses was the scientific standard,  or that Dr. Uzan’s declarations were sufficient to convey to the examiner that the comparisons were performed at different doses. 
Deference was given to the weight the district court placed on the materiality of the evidence and the strong inference of intent in finding sufficient culpability on the part of Aventis to deceive the PTO.  The Federal Circuit found no error with the decision to hold the ‘618 patent unenforceable because of inequitable conduct. 
B. Limiting the Defense of Inequitable Conduct
Judge Rader, in his dissent, suggests that the defense of inequitable conduct should be reserved for extreme cases of fraud and deception and not a knee-jerk response to a suit for patent infringment.  Judge Rader argues that the rule from Kingsdown Med. Consultants, Ltd. V. Hollister, Inc. should be followed, where culpable conduct must be supported by clear and convincing evidence of intent to deceive in order to make a patent unenforceable.  In effect, Judge Rader avers that the Federal Circuit decision neglects the rule from Kingsdown by relying on the materiality of the omission to infer intent rather than clear evidence of intent.  While it is common to use inequitable conduct as a defensive strategy, it is rarely successful and often results in driving up the cost of litigation and encouraging applicants to overload PTO examiners with data so as not to be seen as omitting material information.  Because of this inefficiency, inequitable conduct is considered a plague on infringement suits. 
C. Scope of Standard for Identifying Inequitable Conduct as a Defense
Limiting the use of the defense of inequitable conduct by requiring clear and convincing evidence may allow court and counsel to focus on the merits of the patent rather than explorations of misconduct. However, a clear and convincing evidence standard may be inherently underinclusive in identifying all inequitable conduct that exists. If the purpose of the inequitable conduct is to deter intentional deception before the PTO, then all such individuals should be punished to prevent further inequitable conduct in the future. While adopting broader standard then clear and convincing evidence would capture more inequitable conduct, determining culpability is difficult and a broad rule risks mistaking innocent behavior for inequitable conduct. One must question whether it is worse to mistakenly not enforce a patent or to enforce a patent procured by inequitable means. In the present case, the Federal Circuit chose a broader rule for capturing all potential inequitable conduct while cautioning abuse of inequitable conduct as a defense.
The Federal Circuit highlights the important issue of inequitable conduct in the pharmaceutical industry and the resulting tug-of-war between generic drug manufacturers and patent holders. It should be no surprise that inequitable conduct is a contentious topic fueled by the pressure from the millions of dollars at stake in securing patent rights and the relative ease in taking advantage of the PTO’s reliance on the good faith of applicants. While patent holders fear that entire patents will be lost for relatively minor acts of misconduct, generic drug manufacturers believe that the large pharmaceutical companies are cheating their way to patents for financial success. 
The tension has not gone unnoticed by Congress. The House has already passed the Patent Reform Act of 2007 (Act),  which is currently stalled in the Senate pending language on damages for infringement suits,  that would make it more difficult to use the defense of inequitable conduct to decrease litigation and patent transaction costs.  If the legislation were to pass into law, cases like the present may be decided differently. The Act would require that the element of intent be found by clear and convincing evidence, as Judge Rader proposes, and could not, as the present case demonstrates, be inferred from the materiality of the omission. 
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1 Sheri Wardwell is a J.D. candidate at the University of Washington School of Law.
2 Aventis Pharma S.A. v. Amphastar Pharmaceuticals, Inc., 525 F.3d 1334 (Fed.Cir.2008).
4 Id. at 1337.
5 Id. at 1338.
7 Id. at 1339.
8 Id. at 1338.
10 Id. at 1339.
11 Id. at 1339-40 (Dr. Uzan also relied on the differences in the ratio of various polysaccharide MW weight averages and number of average molecular weight, but the examiner continued to reject this data as demonstrative of the claimed compound’s different composition because EP’144 generally described mixtures of polysaccharides having MWs not patentably distinct from the claimed compound).
12 Id. at 1339.
13 Id. at 1340 (in the third office action the examiner rejects the claim for the reasons of record in the second office action, which stated that “any properties would be inherent in the prior art compounds because they have the same structure as the claimed compounds”).
14 Id. at 1340.
19 Id. at 1340 (Amphastar filed an Abbreviated New Drug Application with FDA for approval and included a certification to challenge the Aventis ‘618 patent).
20 Aventis Pharma S.A. v. Amphastar Pharmaceuticals, Inc., 390 F.Supp.2d 936 (C.D.Cal. 2005).
21 Aventis Pharma S.A., 525 F.3d at 1341.
22 Aventis Pharma S.A., 390 F.Supp.2d at 951-952.
23 Aventis Pharma S.A., 525 F.3d at 1342.
24 Id. (citing Aventis Pharma S.A. v. Amphastar Pharmaceuticals, Inc., 176 Fed.Appx 117, 122-23 (Fed. Cir. 2006)).
25 Aventis Pharma S.A. v. Amphastar Pharmaceuticals, Inc., 475 F.Supp.2d 970, 993 (C.D.Cal. 2005).
26 Id. at 994.
27 Impax Labs., Inc. v. Aventis Pharms. Inc., 468 F.3d 1366, 1374 (Fed.Cir. 2006).
28 Aventis Pharma S.A., 475 F.Supp.2d at 976.
29 Aventis Pharma S.A., 525 F.3d at 1347.
30 Id. at 1346.
31 Id. at 1348 (Aventis conceded that to compare half-lives in order to show a compositional difference between the compounds the dosages of the compounds must be the same).
33 Id. at 1344.
34 Id. at 1346.
35 Id. at 1349.
36 Id. at 1348.
37 Id. at 1348-49.
38 Id. at 1349.
39 Id. at 1349.
41 Id. at 1350 (citing Kingsdown Med. Consultants, Ltd. V. Hollister, Inc., 863 F.2d 867 (Fed.Cir. 1988)).
43 Reuters, New BIO Study Concludes Patent 'Reform' Legislation Would Impose Significant Costs on Patents, http://www.reuters.com/article/pressRelease/idUS229846Feb-2008խ듓촶, (last visited Jul 9, 2008).
44 Aventis Pharma S.A., 525 F.3d at 1340.
45 Dan Slater, Patent’s ‘Inequitable Conduct Doctrine’: Death Penalty for Minor Conduct? http://blogs.wsj.com/law/2008/04/30/patents-inequitable-conduct-doctrine-death-penalty-for-minor-conduct/trackback/, (last visited Jul 9, 2008).
46 GovTrack.us. H.R. 1908--110th Congress (2007): Patent Reform Act of 2007, GovTrack.us (database of federal legislation), http://www.govtrack.us/congress/bill.xpd?bill=h110-1908, (last visited Jul 9, 2008).
47 Carlos M. Gutierrez, Get Moving on Patent Reform Measure Stalled in Senate http://www.siliconvalley.com/ci_9223962?IADID=Search-www.siliconvalley.com-www.siliconvalley.com, (last visited Jul 9, 2008).
48 Robert Pear, Patent Law Battle a Boon to Lobbyists, N.Y. Times, http://www.nytimes.com/2008/04/30/business/30patent.html?ref=health, (last visited Jul 9, 2008).
49 Patent Reform Act of 2007, H.R. 1908, 110th Cong. §12 (2007).
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