In AstraZeneca Pharmaceuticals LP v. Teva Pharmaceuticals USA, issued September 25, 2009, the Federal Circuit upheld the District Court's finding of no inequitable conduct in the prosecution of US Patent No. 4,879,288 ("the '288 patent"). The '288 patent has survived what Federal Circuit judges call a "plague" on US patents—allegations of inequitable conduct (wrongdoing) which may be easily pled, but not easily dismissed.
In the present case, Teva alleged that AstraZeneca misled the Examiner during prosecution of the '288 patent by disclosing data only on prior art compounds that would help but not hinder prosecution. The Federal Circuit found that AstraZeneca's submission of data relating to closest prior-art compounds satisfied its duties to the USPTO during prosecution. AstraZeneca's selective submission and omission of data relating to other structurally-similar compounds was not inequitable conduct in procuring the '288 patent.
As inequitable conduct was the only issue on appeal, Teva Pharmaceuticals issued a press release on September 25, 2009, stating it expects to market quetiapine compositions after the expiration of the '288 patent. The '288 patent covers AstraZeneca's antipsychotic drug "Seroquel" (active ingredient: quetiapine), having 2008 sales in excess of $4.4 billion.
Summary of the case
AstraZeneca alleged infringement of the '288 patent by generic drug makers Teva Pharmaceuticals and Sandoz, Inc. (collectively, "Teva"), in response to the generic companies' ANDA filings for approval to sell generic quetiapine compositions in the United States. AstraZeneca moved for summary judgment against Teva's assertions that the '288 patent was unenforceable due to inequitable conduct; the District Court found for AstraZeneca, and Teva appealed to the Federal Circuit.
The '288 patent discloses that antipsychotic drugs typically cause undesired, involuntary movements, and that quetiapine is atypical in that it causes fewer and less intense involuntary movements (see, e.g., US Patent No. 4,879,288 column 1 lines 41-68 and Example 9). Claim 1 of the '288 patent is directed to a compound having the chemical structure of quetiapine, a dibenzothiazepine having a piperazine ring N-substituted with –CH2CH2OCH2CH2OH. During prosecution of the '288 patent, the Examiner rejected claims to quetiapine as obvious in view of two prior-art compounds the Examiner identified as the structurally-closest prior art – "Schmutz X" and "Horrom" – where Schmutz X was N-substituted with –CH2CH3, and Horrom was a chlorinated diazepine. The Examiner required submission of data comparing atypical properties of quetiapine with Schmutz X and Horrom to overcome the rejection.
In response, AstraZeneca submitted a declaration with already-existing internal data comparing quetiapine with Horrom, noting that quetiapine caused atypical side effects and Horrom did not. The declaration also advised that internal data was not readily available regarding Schmutz X, and that generating such data would be very expensive. However, the declaration submitted that prior-art compound Schmutz B (N-substituted with –CH2CH2OH) was structurally closer to quetiapine (–CH2CH2OCH2CH2OH) than Schmutz X (–CH2CH3), and provided data to show that quetiapine caused atypical side effects and Schmutz B did not. The declaration also volunteered that another compound, Schmutz A (a chlorinated compound having an N-substituted –CH3 group on the piperazine ring), did not provide antipsychotic effects, emphasizing that structurally-similar compounds did not necessarily provide the same pharmacological results. The Examiner accepted the substitution of Schmutz B for Schmutz X as the closest prior art and allowed claims to quetiapine to issue to grant.
To prove inequitable conduct, a challenger must show a patent applicant (1) misrepresented material information (2) with an intent to deceive the USPTO. Teva alleged that AstraZeneca misrepresented material information because the substitution of Schmutz B for Schmutz X, the omission of data relating to other structurally-similar compounds, and the selective submission of data regarding Schmutz A were meant to lead the Examiner away from data AstraZeneca knew would be or could be damaging to its quetiapine application.
In considering the issue, the Federal Circuit decided that Schmutz B was, in fact, structurally more similar to quetiapine than Schmutz X, and that a reasonable examiner would have accepted AstraZeneca's substitution of Schmutz B for Schmutz X as the structurally-closest prior art. AstraZeneca's omission of data relating to other structurally-similar compounds and selective disclosure of information relating to Schmutz A were therefore not material misrepresentations because the Examiner and applicant reasonably identified and focused on the closest prior art, and found that structural similarities or differences were not determinative of typical or atypical side effects. The Court also noted that Teva did not show that AstraZeneca had data for Schmutz X and withheld it, and that Teva did not present its own evidence that Schmutz X is an atypical antipsychotic agent; whether these circumstances would have altered the Court's opinion is not clear from the record.
Teva also alleged AstraZeneca intended to deceive the Examiner during prosecution of the '288 patent by not preparing and submitting data on Schmutz X and other compounds, and by submitting information on Schmutz A. The Federal Circuit held that an intent to withhold data on structurally similar compounds is not an intent to deceive, particularly where plausible reasons are given for withholding information:
an applicant would not know how much of its research must be filed with the PTO, although of no interest to the Examiner, or run the risk of wrongdoing no matter where the line is drawn.
Overall, AstraZeneca's disclosure of comparative information regarding the structurally-closest prior-art compounds was enough to satisfy duties imposed by the USPTO on a patent applicant. AstraZeneca's selective submission and omission of data relating to other structurally-similar compounds was not seen as materially misrepresenting information to, or intending to deceive, the USPTO examiner.
Vol. 53, June 2010