By Donald Zuhn --
Earlier this month, the Federal Circuit in a 2-1 decision affirmed the determination by the District Court for the Central District of California that U.S. Patent Nos. RE 38,743 and 5,389,618, which are owned by Plaintiffs-Appellees Aventis Pharma S.A. and Aventis Pharmaceuticals, Inc. (Aventis), are unenforceable for inequitable conduct. In affirming the District Court's determination of unenforceability, the Federal Circuit concluded that the lower court did not abuse its discretion in finding that Aventis intended to deceive the U.S. Patent and Trademark Office while procuring the '743 and '618 patents.
The '743 and '618 patents are directed to a composition comprising low molecular weight heparins (LMWHs), which Aventis markets as Lovenox® in the U.S. and as Clexane® in Europe, and which is used to prevent blood clotting while minimizing the possibility of hemorrhaging, especially during high-risk surgery. The '743 patent is a reissue of the '618 patent.
During prosecution of the '618 patent, the examiner rejected the claims as being anticipated and/or obvious in view of European Patent No. 0 040 144, asserting that the '144 patent teaches a LMWH composition that falls within the molecular weight range recited in the claims and which is considered to be inherently the same as the claimed LMWH composition. In attempting to overcome the rejection, Aventis pointed to Example 6 of the specification, which states that a 40 mg dose of the claimed composition has a half-life of more than 4.5 hours in 45% of cases and an unspecified dose of the composition of the '144 patent has a half-life of more than 4.5 hours in only 17% of cases. Aventis argued that because compounds are inseparable from their properties, the evidence of a difference in a property (i.e., half-life) is evidence of a difference in structure, and thus the compositions were not inherently the same.
In a second Office action, the examiner maintained the 102 and 103 rejections for reasons of record, and noted again that the Patent Office did not have facilities for testing and comparing products that appear to be identical or nearly identical, such as the claimed and prior art LMWH compositions. Aventis responded by amending the claims and submitting a declaration from Dr. Andre Uzan, an Aventis chemist (but non-inventor) who had helped with the preparation of Example 6. The Uzan Declaration reiterated the results of Example 6, described the specific composition of claimed heparin admixture (in support of the claim amendments), and concluded that the LMWH composition of the '144 patent was "clearly outside the scope of the present invention."
In a third Office action, the examiner withdrew the 102 rejection but maintained the 103 rejection, stating that Aventis had failed to show a statistically significant difference between the half-life of the claimed LMWH composition and the half-life of the prior art ('144 patent) LMWH composition. Aventis responded by submitting a second declaration from Dr. Uzan, which provided results showing a statistically significant difference between a 40 mg dose of the claimed composition and an unspecified dose of the prior art composition. In response to Aventis' submission, the examiner allowed the '618 patent.
Seeking approval to market a generic version of Aventis' LMWH composition, Defendants-Appellees Amphastar Pharmaceuticals, Inc. and Teva Pharmaceuticals USA, Inc. each filed an Abbreviated New Drug Application (ANDA) with the FDA. Aventis responded by filing an infringement suit against each ANDA filer in the District Court for the Central District of California.
In Aventis I, Amphastar filed a motion for summary judgment of unenforceability, asserting that Dr. Uzan had engaged in inequitable conduct for failing to disclose that different doses of the claimed and prior art compositions had been used to generate the results disclosed in Example 6 and the second Uzan Declaration (Dr. Uzan had used a 60 mg dose of the prior art composition). The District Court granted Amphastar's motion, finding that Aventis' representation that the claimed composition had a better half-life than the prior art composition was material to patentability, and further, that there was a strong inference of intent to deceive since there was "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 affirmed the finding of materiality, but remanded on the issue of intent to deceive. In particular, the Federal Circuit determined that the reasonableness of using different doses to compare the compositions was relevant to determining whether there was an intent to deceive (Aventis had argued that those of ordinary skill in the art frequently compare half-lives at different doses).
In Aventis III, the District Court rejected Aventis' arguments for failing to disclose the dose of the prior art composition. In particular, Aventis had asserted that it was customary to compare the half-lives of different drugs at their clinically relevant doses, the comparison of drugs at different doses was reasonable because half-lives are dose independent, and the failure to disclose the dose of the prior art composition was the result of inadvertence. The District Court rejected each of these arguments, and with respect to the inadvertence argument, specifically determined that "it was not credible that a scientist with Dr. Uzan’s qualifications could have committed, and failed to correct during a lengthy prosecution, such an egregious error."
In the instant appeal, Aventis first argued that the failure to disclose the dose of the prior art composition was permissible since the half-life compositions were intended to show a difference in properties (to overcome the 103 rejection) and not a difference in composition (to overcome the 102 rejection). This new argument was premised on the fact that the latter situation requires equivalent doses and the former permits different doses. The Federal Circuit, however, rejected Aventis' argument, finding that the District Court did not clearly err in determining that the half-life comparisons were intended to show compositional differences to address the 102 rejection.
Aventis next renewed its argument that it was customary to compare the half-lives of different drugs at their clinically relevant (and thus, different) doses. The Federal Circuit also rejected this argument, finding that evidence of the industry practice of using clinically-relevant doses would only be relevant if the half-life comparisons were being used to address an obviousness rejection, and not an anticipation rejection. The Federal Circuit also rejected Aventis' remaining arguments (including inadvertence), affirming the District Court's finding of inequitable conduct and holding of unenforceability of the '743 and '618 patents.
Judge Rader, writing in dissent, noted that "my reading of our case law restricts a finding of inequitable conduct to only the most extreme cases of fraud and deception," and stated that "[t]o my eyes, this record does not show clear and convincing evidence of intent to deceive the United States Patent and Trademark Office." Judge Rader (at left) found the instant case to be distinguishable from Nilssen v. Osram Sylvania, Inc., 504 F.3d 1223 (Fed. Cir. 2007) – where an improper claim of small entity status led to a finding of inequitable conduct – or General Electro. Music Corp. v. Samick Music Corp., 19 F.3d 1405 (Fed. Cir. 1994) – where the patentee filed a petition to make special with a declaration that falsely stated that a thorough search of the prior art had been conducted.
Despite acknowledging that "[w]ithout question, Dr. Uzan should have disclosed the dosage of the ['144 patent] LMWH in example 6," and further, that "Dr. Uzan ought to have disclosed to the USPTO that he compared the 60 mg dose of the prior art ['144 patent] LMWH to the 40 mg dose of the [claimed] LMWH in the declaration he submitted on March 29, 1993 [i.e., the first Uzan Declaration]," Judge Rader found that Dr. Uzan's argument for not disclosing the dose "has merit." In particular, Dr. Uzan had testified that the different dose "did not come to his mind."
In support of Dr. Uzan's testimony, Judge Rader noted that:
the absence of a dosage in [Example 6] is blatantly obvious. Surely if Dr. Uzan had intended to deceive the USPTO, he would not have made this omission so conspicuous. Moreover, I find it difficult to fathom that a scientist of Dr. Uzan's caliber and reputation would engage in such deception. . . . This world-class scientist would hardly risk his reputation and tarnish his brilliant career for a single example in the prosecution of a patent for an invention in which he was not even involved.
Judge Rader also noted that Dr. Uzan had revealed and corrected the error himself by submitting all of the underlying data to the Patent Office with his second declaration before the '618 patent had issued, and that "[t]his candor is inconsistent with deceptive intent." Moreover, because the '743 patent issued with all of the original independent claims, but without Example 6 (which was deleted during reissue proceedings), Judge Rader observed that "[t]he half-life data were apparently not even necessary for patentability."
Aventis Pharma S.A. v. Amphastar Pharmaceuticals (Fed. Cir. 2008)
Panel: Circuit Judges Rader, Prost, and Moore
Opinion by Circuit Judge Prost; dissenting opinion by Circuit Judge Rader
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