Eli Lilly patent for atomoxetine for use in treating ADHD invalid for lack of utility

Novopharm Ltd. v. Eli Lilly and Company 2010 FC 915

Novopharm Limited (now known as Teva Canada Limited but hereafter referred to as Novopharm) sought a declaration under s. 60(1) of the Patent Act, R.S.C. 1985, c. P-4 that Eli Lilly and Company’s (Lilly’s) Canadian Patent No. 2,209,735 (the ‘735 Patent) was invalid and void. The ‘735 Patent claimed the use of the medicine atomoxetine for treating attention deficit hyperactivity disorder (ADHD) in three of its manifestations among all age groups (children, adolescents and adults). The ‘735 Patent did not claim the compound atomoxetine but only its use to treat ADHD.

In its Statement of Claim, Novopharm asserted that each of the 16 claims of the ‘735 Patent were invalid on the grounds of obviousness, anticipation, inutility, and incomplete disclosure concerning the selection of atomoxetine from an earlier genus patent.  Lilly’s Statement of Defence asserted the validity of the ‘735 Patent and argued that the invention was neither obvious nor anticipated by the prior art, that the ‘735 Patent was not a selection patent but rather claimed a new and inventive use for atomoxetine, and that Lilly had established the utility of atomoxetine by virtue of studies that had been conducted. In the alternative, although denying that any issue of sound prediction of utility arose, Lilly asserted that “there was a factual basis for the alleged predictions” and that “there was an articulable and sound line of reasoning from which the desired result could be inferred”.

The Federal Court considered each of the grounds raised in the Statement of Claim, as well as the applicable standard of proof, and ultimately found the ‘735 Patent to be invalid on the basis of lack of utility. The Court granted a declaration of invalidity under s. 60(1) of the Patent Act, and declared that Novopharm was not required to address the ‘735 Patent for the purposes of the Patented Medicines (Notice of Compliance) Regulations (SOR/93-133).

Background

Atomoxetine was originally studied by Lilly as early as 1979 for use as an antidepressant, however this research was terminated in 1991 due to an inability to establish efficacy. Considering its uneventful use in depression research and its known profile as a selective norepinephrine reuptake inhibitor (NRI), atomoxetine was soon proposed for use as an ADHD medication. By 1994, Lilly and the Massachusetts General Hospital had agreed to co-sponsor a clinical trial of atomoxetine as a treatment for ADHD (the MGH Study).

At trial, testimony was received from three experts on behalf of Novopharm and one on behalf of Lilly. In arriving at its decision, the Court noted that Lilly was unable to secure the voluntary attendance of any witness with direct knowledge of the MGH Study which constituted Lilly’s evidence of utility. As such, the Court was required to assess the evidence on the basis of incomplete information contained in the study report.

Standard of Proof, Obviousness, Anticipation and Selection Patents

Although Lilly attempted to rely on the Supreme Court decision in Apotex Inc. v. Wellcome Foundation Ltd., 2002 SCC 77, 21 C.P.R. (4th) 499 (“AZT”) in support of the argument that the decision of the Patent Commissioner to approve the ‘735 Patent should be entitled to a degree of deference, the Court disagreed.  Novopharm had the onus of establishing invalidity on the usual balance of probabilities standard.

With respect to the question of obviousness, the point of particular evidentiary controversy was whether, in 1995, it was obvious that atomoxetine ought to work to treat ADHD based on the established efficacy of several medications with arguably similar selectivity profiles.  After a thorough consideration of the prior art, as well as the evidence presented by the various experts, the Court, in dismissing Novopharm’s argument, stated, “My own review of the prior art evidence indicates that the profiles of the drugs that worked to treat ADHD were simply too diverse, and their mechanism of presumed action within the highly complex neurological systems involved were too uncertain to draw any firm conclusion about the efficacy of atomoxetine.”

With respect to anticipation, one prior art patent simply referred to some of its claimed compounds (none of which were atomoxetine) as NRIs, while another referred to atomoxetine as an NRI, but only to treat depression.  These prior art patents clearly failed to anticipate the ‘735 Patent as the use of atomoxetine to treat ADHD was not disclosed in either patent.  Novopharm further argued that two oral conversations that fell outside the one year grace period anticipated disclosure of the invention.  The Court dismissed Novopharm’s allegation, however, on the basis that the first such conversation was not corroborated, while the second conversation was confidential in nature.

As for the argument that the ‘735 Patent was an invalid selection patent, the fact that atomoxetine was claimed in a prior patent did not render the ‘735 Patent a selection.  The ‘735 Patent claimed a new use for atomoxetine and did not attempt to reclaim the compound itself. As a result, there was no requirement that Lilly disclose any special advantage that atomoxetine enjoyed over compounds claimed in the prior patent.  It was sufficient to assert an inventive new use without any additional disclosure requirements.

Utility, Sound Prediction and Disclosure

Utility is not established on the basis of a mere hypothesis, an unproven idea or sheer speculation, even if later established.  Lilly argued that it need only show that atomoxetine had a mere “scintilla of utility” to uphold the patent.  The Court noted, however, that “the requirement of utility would be met if, at the Canadian filing date of the ’735 Patent, there was sufficient evidence that atomoxetine was clinically useful in treating some patients with ADHD or, alternatively, that such efficacy could be soundly predicted.” 

The judge ultimately accepted the evidence of Novopharm’s experts going to the significant limitations of the MGH Study relied upon by Lilly. The study’s most critical shortcomings were related to its small sample size, the potential for imperfect patient blinding, and the limited study duration. The Court found that the study’s reported results failed to demonstrate the clinical utility of atomoxetine to treat ADHD in adults or children. The results of the study were promising but only preliminary.  Utility therefore had not been demonstrated.

With respect to the question of sound prediction, Lilly made the highly strained argument that the statement in the ’735 Patent that atomoxetine is useful to treat ADHD is sufficient disclosure because “by stating that the compound works, the patentee is also telling the world why it works”.  In a case involving a claimed sound prediction of utility, however, it is beyond debate that an additional disclosure obligation arises.  This obligation is met by disclosing in the patent both the factual data on which the prediction is based and the line of reasoning followed to enable the prediction to be made.  This requirement to disclose the basis of the prediction in the patent specification is said to be the quid pro quo the patentee offers in exchange for the patent monopoly.  The ‘735 Patent failed for want of disclosure because some reference to the findings in the MGH Study that atomoxetine was useful in the treatment of ADHD was required to be set out in the patent.  The invention in the ‘735 Patent therefore was also not soundly predicted.  As a result, the Court concluded that the ‘735 Patent was invalid for lack of utility.
 

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