In Aventis Pharma S.A.v. Amphastar Pharmaceuticals, Inc., No. 2007-1280 (Fed. Cir. May 14, 2008), Aventis Pharma S.A. and Aventis Pharmaceuticals, Inc. (collectively, “Aventis”) appealed the District Court for the Central District of California’s finding of inequitable conduct and holding of unenforceability of Aventis’ Patent No. RE 38,743 (the ‘743 patent) and Patent No. 5,389,618 (the ‘618 patent). The Federal Circuit affirmed.
The ‘734 patent and ‘618 patent are directed to the composition of low molecular weight heparins (“LMWHs”). These LMWHs comprise the drug Lovenox® (marketed as Clexane® in Europe), which helps to prevent blood clotting, while minimizing the chance of hemorrhage, especially in high-risk surgery.
In the first office action, the patent examiner rejected the claims under 35 U.S.C. §§ 102(b)/103 over several references, including European Patent 40,144 (EP ‘144), stating that each of the prior art references teaches sulfated heparinic admixtures within the molecular weight (MW) range of the claims and is considered to be inherently the same as the claimed admixtures. The examiner noted the fact that the PTO does not have testing facilities, so it is the responsibility of the Applicant to convincingly demonstrate that the claimed product provides an unexpected or unobvious property, different from prior art products.
Aventis then offered an example to the specification, supporting its assertion that the claimed LMWHs exhibit a significantly longer half-life than formulations prepared in accordance with EP ‘144, and because it is well established that compounds are inseparable from their properties, the evidence of a difference in a property (here, half-life), serves as evidence of a difference in structure. Nonetheless, the examiner issued a second office action maintaining the rejection citing the same reasons from the first office action. She reiterated that any properties would be inherent in the prior art compounds because they have the same structure as the claimed compounds.
Aventis amended its claim and submitted a declaration from Dr. Uzan, who distinguished the claimed formulations from the formulations in EP ‘144. Upon the third office action, the examiner withdrew several 102/103 rejections over other prior art references but continued to reject the claims over EP ‘144 for the reasons already in the record. Aventis argued in its response that EP ‘144 does not suggest compounds containing polysaccharides of the claimed MW in the claimed proportions and that the examiner improperly relied on inherency to reject the claimed compounds over EP ‘144. Aventis also averred that the claimed compounds had been shown to differ from the compounds of EP ‘144 in both structure and property based on Dr. Uzan’s declarations about the difference in half-lives. At this point, the ‘618 patent was allowed.
Amphastar Pharmaceuticals, Inc. (“Amphastar”) and Teva Pharmaceuticals USA, Inc. (“Teva”) each filed an Abbreviated New Drug Application with the FDA to obtain approval to generic market versions of Lovenox®, and in so doing, challenged Aventis’ ‘743 and ‘618 patents. Aventis sued Amphastar and Teva in the District Court for the Central District of California for infringement of the ‘618 patent. Amphastar filed a motion for summary judgment on its affirmative defense and counterclaim that the ‘618 patent is unenforceable due to inequitable conduct.
First, the District Court found that the Aventis’ representation of the improved half-life of the patented compound as compared to the EP ‘144 compound was material to patentability as the examiner ultimately allowed the ‘618 application after the final representation that the difference in mean half-life was statistically significant. Second, the court found a strong inference of intent to deceive because it found no credible explanation for comparing half-lives at different doses, and comparisons at the same dose showed little difference in half-life. Upon weighing the evidence of materiality and intent, the District Court granted summary judgment against Aventis and held the ‘618 patent unenforceable.
On appeal, Aventis argued that the District Court erred in finding materiality because if the dose information were material to patentability, the examiner would have requested it because: (1) she was presented with half-life data that enable her to compare various doses, (2) Dr. Uzan informed the examiner that the half-life comparison was done at different doses, (3) those of skill in the art frequently compare half-lives at different doses, and (4) half-life is independent of dose. Aventis Pharma S.A. v. Amphastar Pharms., Inc., 176 Fed. Appx. 117, 120 (Fed. Cir. 2006). To support its first two reasons, Aventis relied on the statement in the Dr. Uzan’s declaration that “[t]his 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’s testimony that he believed this to mean “that the comparison is a comparison between two doses of which one is lower that the other, id. at 120-21; Dr. Uzan’s submission of the half-life data for the claimed compound at 60 mg as well as 40 mg, id. at 123. The court did not accept Aventis’ reasons and concluded that the withholding of the EP ‘144 dosage information prevented the examiner from considering information important to patentability and constituted a failure to disclose material information. Id. at 122. However, this court also reversed the grant of summary judgment of unenforceability of the ‘618 patent and ‘743 patent and remanded to the District Court for determination of whether there was intent to deceive. Id. at 12. It noted, in particular, that the reasonableness of the comparison at different doses is relevant to determining whether there was an intent to deceive in withholding the dosage of the EP ‘144 composition. Id. at 122-23.
Following remand, the District Court held a bench trial on the issue of intent. The court again considered the explanations offered by Aventis for Dr. Uzan’s failure to disclose the dose of the EP ‘144 composition in its half-life comparisons and was not persuaded that he presented the half-life comparisons to show only a difference in property and not also a difference in composition. Aventis Pharma S.A. v. Amphastar Pharms., Inc., 475 F. Supp. 2d 970, 975 (C.D. Cal. 2007). The court determined that but for Dr. Uzan’s intentional omissions, the probability was high that the ‘618 patent would not have issued, and it held the ‘618 patent and the ‘743 patent unenforceable due to inequitable conduct. Id. at 994.
Its second time on appeal, Aventis offered a new justification, alleging that Dr. Uzan’s half-life comparisons were intended to show a difference in properties in response to the obviousness rejection under 35 U.S.C. § 103, not to demonstrate a compositional difference to address the anticipation rejection under 35 U.S.C. § 102, as the District Court concluded. Aventis bases this on the premise that while a half-life comparison must be done using equivalent doses to establish a compositional difference, a half-life comparison may be done using different doses if the purpose is to establish a difference in property. In fact, Aventis argues, that it is more appropriate to use the “clinically relevant dose” of each compound to demonstrate a difference in property.
With respect to materiality, Aventis contends that the District Court made two clearly erroneous findings of fact: (1) that the central question relating to patentability was compositional differences, and (2) that the purpose of Dr. Uzan’s half-life comparisons was to show compositional differences. Aventis contended that anticipation was the only rejection of record, even though there was an obviousness rejection present throughout prosecution and that the District Court erred in concluding that the “issue of obviousness necessarily folds into, and is subsumed, by inherency.” Aventis III, 475 F. Supp. 2d at 982 n.10. Although the District Court incorrectly suggested in a footnote that obviousness is subsumed by inherency, the Federal Circuit sees this merely as recognition by the court that the notion of inherency was part and parcel of the examiner’s rejections. Id. at 979. Furthermore, several statements in the opinion clearly indicate that the court was aware of the obviousness rejection. Id. at 980. The Federal Circuit does not find clear error in the District Court’s ultimate decision, recognizing the court’s understanding that the PTO did not have the facilities to test the products and that Aventis did not provide evidence of a difference in property to show a compositional difference. Second, the Federal Circuit does not agree with Aventis that the District Court clearly erred in its determination that the half-life comparisons were, at least in part, intended to show compositional differences because Dr. Uzan’s example and all of the evidence directed at the EP ‘144 reference appears without distinction between the § 102 and § 103 aspects of the rejection. Therefore, the District Court properly found that the half-life comparisons were intended to address both the anticipation and obviousness rejections, and the failure to disclose the dosage information evidenced intent to deceive.
Aventis further urges that the examiner clearly withdrew the § 102 rejection based on the MW distribution data, and the half-life data in the second Uzan declaration was intended only to overcome the § 103 rejection. Therefore, it avers that the anticipation rejection was not still pending at the time of the third office action. The Federal Circuit notes, however, that although the court may have erred in concluding that the anticipation rejection was still pending in the third office action, that conclusion was not critical to the court’s ultimate determination that there was intent to deceive, based on evidence prior to the third office action. Therefore, the District Court did not clearly err in determining that the half-life comparisons were, in part, intended to show compositional differences to address the anticipation rejection under 35 U.S.C. § 102 and, thus, rejecting Aventis’ argument that they were intended only to show differences in property, such that dosage was immaterial.
Aventis then argued that the District Court clearly erred in excluding evidence that comparison of half-lives at different doses was the standard practice in the LMWH field. The Federal Circuit finds no abuse of discretion by the court’s exclusion of the evidence because evidence of industry practice of clinically-relevant doses would only be pertinent if there was a finding that the half-life comparisons were used to address obviousness and not anticipation because Aventis has conceded that half-life comparisons must be at the same dose to show compositional differences. Further, the court noted that neither the claims nor the specification were limited to prevention of deep venous thrombosis in high-risk surgical patients and that the patented composition could be used at several different doses for several different indications.
The District Court heard Dr. Uzan’s testimony that he did not have deceptive intent and considered this along with all the other relevant evidence, yet the court determined that it did not outweigh the cumulative evidence evincing an intent to deceive. Therefore, it maintained that the District Court did not err in concluding that the other evidence outweighed Dr. Uzan’s testimony.
Lastly, the Federal Circuit upheld the District Court’s finding that Dr. Uzan failed to disclose the dosage information because in the least, the information was provided in a very misleading way. Dr. Uzan’s failure to disclose the information was also not found purely due to inadvertence. Unlike any of the inadvertent omissions made in prosecution, there is sufficient evidence of concealment to warrant a determination that the dose information was intentionally withheld.
Judge Rader dissented because he did not find that the record showed clear and convincing evidence of intent to deceive the PTO. Specifically, Judge Radar pointed out that the inequitable conduct claim is used too frequently and improperly. Even if Dr. Uzan was negligent, this does not show culpable intent to deceive based on Kingsdown Med. Consultants, Ltd. V. Hollister, Inc., 863 F.2d 867, 876 (Fed. Cir. 1988) (en banc). Rader also pointed out that Dr. Uzan, a world-class scientist, would not likely risk his reputation and tarnish his career for a single example in the prosecution of a patent for an invention in which he was not even involved. Also, Dr. Uzan’s candor in revealing the error himself and correcting it before it resulted in an issued patent was inconsistent with deceptive intent.
Significance to Patent Applicants
Aventis represents a continuation of the Federal Circuit’s recent trend to ignore, for purposes of inequitable conduct, any need for intent in determining fraud on the patent office. Instead, as noted by the dissent, the Federal Circuit focuses almost exclusively on materiality, thereby encouraging frivolous inequitable conduct charges. Aventis also provides a cautionary note about the need for declarations to be as precise as possible since any error in the declaration could result in a charge of inequitable conduct. Specifically, the Federal Circuit is holding that declarations are inevitably material to the Examiner such that, even without intent to deceive, any error in the declaration amounts effectively to inequitable conduct by the patentee. As such, Aventis serves as notice to inventors to carefully review a declaration presenting facts to an Examiner to ensure that the facts in the declaration are both technically accurate and not misleading as to the outstanding rejections for which the facts are being presented.