Lilly Icos LLC v. Pfizer Ltd

Factual and Procedural Background

The Plaintiff, Lilly ICOS LLC ("Lilly"), initiated an action seeking to invalidate and revoke European Patent (UK) 702,555 ("the Patent") registered in the name of Company B. The Patent concerns the medical use of certain chemical compounds for treating male erectile dysfunction ("MED"), notably including sildenafil citrate, the active ingredient in the drug known commercially as Viagra. Company B asserts that the commercial success of Viagra evidences the inventiveness of the Patent. Lilly, developing its own anti-impotence drug, contends that the Patent is invalid on grounds of anticipation by prior art, obviousness, insufficiency, and added matter.

The Patent claims a second medical use of compounds, including sildenafil citrate, for the treatment of MED. The Patent specification describes the anatomical, physiological, and chemical background relevant to erection and the role of cyclic guanosine monophosphate phosphodiesterases (cGMP PDEs) and their inhibitors. The Patent includes claims directed to specific chemical formulas as well as broader claims directed to any cGMP PDE inhibitor for the oral treatment of MED.

The parties disputed the proper construction of key claims, particularly claims 10 and 11, which are broader and concern the use of cGMP PDE inhibitors generally. The Plaintiff challenged the Patent’s validity primarily on obviousness, relying on prior publications and a PhD thesis, while also raising anticipation and other grounds. The Defendant defended the Patent on the basis of its inventiveness and claim construction.

Legal Issues Presented

1. Whether the Patent claims, particularly claims 10 and 11, should be construed as requiring selectivity and potency of cGMP PDE inhibition, or whether they cover any cGMP PDE inhibitor effective in treating MED.
2. Whether the Patent is invalid for obviousness in light of prior art publications and thesis, specifically the Rajfer paper, the Murray review article, and the Bush PhD thesis.
3. Whether the Patent is anticipated by the prior art, notably the Korenman publication.
4. The impact of claim construction on the validity challenges, including the requirement of efficacy and causation for treatment claims.

Arguments of the Parties

Appellant's Arguments (Lilly)

• The Patent claims should be construed broadly to cover any compound inhibiting cGMP PDEs, without requiring selectivity or potency.
• The Patent is obvious over prior art, particularly the Rajfer paper elucidating the nitric oxide pathway and the role of cGMP PDE inhibitors in penile smooth muscle relaxation.
• The Murray review article further strengthens obviousness by highlighting PDE VA inhibitors and their potential therapeutic uses including impotence.
• The Bush PhD thesis also supports obviousness by recommending clinical development of specific cGMP PDE inhibitors for impotence treatment.
• The Korenman publication anticipates the Patent by disclosing use of pentoxifylline, a cGMP PDE inhibitor, for treating impotence.

Appellee's Arguments (Company B)

• The claims require selectivity and potency in cGMP PDE inhibition, restricting their scope.
• Effective treatment must be attributable to the identified compounds alone, excluding placebo effects or combined treatments unless the compound contributes substantially.
• The Patent is not obvious as the prior art does not directly or clearly suggest the use of cGMP PDE inhibitors orally for MED.
• Concerns about oral administration and potential side effects would deter the skilled person from trying oral PDE inhibitors.
• The Korenman publication does not demonstrate efficacy or selective PDE inhibition sufficient to anticipate the Patent.

Table of Precedents Cited

Court's Reasoning and Analysis

The court undertook a detailed construction of the Patent claims, particularly claims 10 and 11, concluding that these claims cover the use of any cGMP PDE inhibitor effective in treating MED, without requiring selectivity or potency of inhibition. The court rejected the Defendant's arguments that selectivity and causation of efficacy by PDE inhibition were claim requirements, noting that the specification did not impose such limitations or provide guidance on selectivity thresholds.

On obviousness, the court applied the Windsurfing framework, identifying the inventive concept as the use of cGMP PDE inhibitors for the treatment of MED, including oral administration. The court considered the skilled addressee as a team with expertise in pharmacology, medicinal chemistry, and urology, possessing common general knowledge as of June 1993.

The court analyzed the key prior art:

• Rajfer paper: Established the role of nitric oxide and cGMP in penile erection and demonstrated that selective cGMP PDE inhibitors (e.g., zaprinast) enhanced relaxation of human corpus cavernosum smooth muscle in vitro. The court found this teaching would have encouraged the skilled person to try PDE inhibitors for MED treatment.
• Murray article: Reviewed PDE isoenzymes, highlighting PDE VA (PDEV) inhibitors' tissue specificity and therapeutic potential, including for impotence. The court found this paper would have further encouraged the skilled person to pursue PDE inhibitors, including oral administration.
• Bush thesis: Supported the physiological basis for PDE inhibitors in treating impotence, recommending clinical development of specific cGMP PDE inhibitors. The court considered this thesis as reinforcing the obviousness case.

Regarding oral administration, the court rejected arguments that concerns about side effects or systemic effects would deter the skilled person from trying oral PDE inhibitors. Evidence showed that oral administration was the preferred route, with known PDE inhibitors already tested orally without significant adverse effects.

On anticipation, the court found the Korenman publication insufficient to anticipate the Patent because it did not demonstrate efficacy of pentoxifylline as a PDE inhibitor in treating MED. The court emphasized that efficacy is a requirement for anticipation and found the evidence did not establish such efficacy.

Overall, the court concluded that the Patent claims were invalid for obviousness in light of the prior art, particularly Rajfer, Murray, and Bush.

Holding and Implications

The Patent is held invalid for obviousness.

The court ruled that the prior art rendered the claimed invention obvious to a person skilled in the art as of the priority date. Consequently, the Patent cannot be maintained. The direct effect is that Lilly is not restrained by the Patent in developing and marketing its anti-impotence drug. No new precedent was established, and the decision primarily applies the existing legal principles on patent construction, obviousness, and anticipation to the facts of this case.