Eli Lilly & Co. v. Perrigo Co.

Two of plaintiff’s patents relating to the formulation and application of axillary transdermal testosterone were invalid while a third patent was valid and infringed by one of the joint defendants.

October 25, 2016

GENERICally Speaking

Case Name: Eli Lilly & Co. v. Perrigo Co., Case No. 1:13-cv-00851-SEB-DKL (S.D. Ind. Aug. 22, 2016) 

Drug Product and Patent(s)-in-Suit: Axiron® (testosterone metered transdermal solution); U.S. Patents Nos. 8,071,075 (“the ’075 patent”), 8,435,944 (“the ’944 patent”), and 8,807,861 (“the ’861 patent”)

Nature of the Case and Issue(s) Presented: Eli Lilly is the exclusive licensee of the patents-in-suit and the holder of an approved new drug application for the manufacture and sale of a testosterone solution applied to the skin, commercially known as Axiron. Axiron is applied to the axilla or armpit region of the body.

The patents-in-suit teach a formula for a transdermal testosterone drug (the ’057 patent), applied to the axilla (the ’944 patent) using an applicator with a deformable double-wall structure (the ’861 patent). Eli Lilly brought suit against defendants after each of them filed an ANDA seeking FDA approval to make and sell a generic transdermal testosterone product. After a bench trial, the court concluded that the ’057 and ’944 patents were invalid, and thus not infringed. The court also found that the applicator manufactured by Actavis, Perrigo, and Lupin would not infringe the ’861 patent, but that the applicator manufactured by Amneal would infringe the ’861 patent.

Why Defendants Prevailed: The court determined that the ’057 patent was invalid on both written description and enablement grounds. The ’057 patent included an element requiring the presence of an octyl salicylate penetration enhancer in an amount of 10-10000% by weight of testosterone. Thus, the scope of the claim contemplated a formulation having 100 times more octyl salicylate by weight than testosterone. The specification did not include any example of a formulation’s approaching this amount of octyl salicylate. Further, the specification indicated that testosterone is most effectively delivered by using less penetration enhancer than testosterone. For this reason, a person of ordinary skill, having read the specification, would not understand that the inventors possessed a 10000% penetration enhancer formulation. Accordingly, the patent was invalid for lack of written description. For the same reasons, the ’057 patent was also invalid for a lack of enablement. In addition, a person of ordinary skill would be required to perform an undue amount of experimentation to determine whether a 10000% penetration enhancer formulation would actually work as an effective treatment.

The ’944 patent was also invalid, but on obviousness grounds. The relevant claim of the ’944 patent required each of the following elements: (i) a pharmaceutically effective amount of testosterone; (ii) one or more lower alkyl alcohols selected from a group consisting of ethanol, isopropanol, and mixtures thereof, wherein the combined volume of the lower alkyl alcohol(s) is more than 80% (v/v) of the composition; (iii) the penetration enhancer octisalate in an amount of from 0.01% to 15% (w/v); (iv) the viscosity modulating agent polyvinyl pyrrolidone present in an amount from 1% to 3% (w/v) of the composition, in an amount effective to increase the viscosity of the composition to within the range of from greater than the viscosity of water to less than 300 centipoise; and (v) optionally, water, wherein the composition is applied in an amount effective to achieve a testosterone blood level in the subject of at least 200 ng/dL.” A single prior-art reference, the ’725 publication, taught each of the above elements. The claim also required that the formulation be applied to “at least one axilla of the subject, without occlusion by a patch device.” While the ’725 publication did not teach this “axilla” limitation, another prior art reference, the ’268 publication, explicitly listed the armpit as a site for transdermal delivery of drugs, including testosterone. This point was also bolstered by additional references’ teaching the application of a transdermal drug to the non-hairy portion of the axilla. Thus, in combination, one of ordinary skill would conclude that the claims of the ’944 patent were obvious.

Finally, the court found that the applicators manufactured by Actavis, Perrigo, and Lupin did not infringe the ’861 patent, but that the applicator manufactured by Amneal did infringe. In each case, the dispute focused on the ’861 patent’s requirement that the applicator contain a deformable double wall. Actavis’s and Perrigo’s applicators consisted of only a single wall, and thus did not meet the double wall element of the claims. The court rejected the testimony of Eli Lilly’s expert that the silicone wall structures of Actavis’s and Perrigo’s applicators would double over when applied with sufficient pressure to the axilla. Eli Lilly’s expert’s findings were flawed because the testing did not simulate the manner in which the applicators were actually used. In the first set of testing, the expert simply manipulated that applicator, and did not use it on his axilla or with a liquid matching the viscosity of the testosterone solution. In the second set of testing, the expert tested the applicators on his axilla at his home, using a cranberry juice/rubbing alcohol combination. Although the expert could not remember the ratio used to create this mixture, it did not have the same viscosity as the testosterone solution or a placebo. Since the force required to “double over” the wall was necessary to prevent the solution’s leaking, this was an important consideration. Further, in both tests, the expert did not record the testing, either by using video or by taking contemporaneous notes. The court accordingly discounted his testing. Actavis and Perrigo, on the other hand, presented video evidence of the applicator in use which showed the wall did not deform. Thus, Actavis and Perrigo did not infringe the patent. Lupin’s applicator also did not infringe the ’861 patent because its wall was made of polypropylene, a rigid plastic. When pressure is applied to the applicator, the wall retracts into the base of the applicator, allowing the base to contact the axilla. When the pressure is removed, the wall springs back out of the base and into place. Thus, the applicator wall does not deform, as required by the patent. Finally, Amneal stipulated that its applicator met every limitation, save one. Rather than having two walls mounted onto the base, the Amneal applicator’s wall was connected to the base only once, but folded over to form a double wall. If the double-wall limitation were to require both walls to connect to the base, Amneal would not infringe. The court concluded that the claims did not require any such limitation. Although one preferred embodiment referred to an attached lower edge of the wall, the claims were not limited only to the preferred embodiment. Further, there was no disclaimer during the prosecution process. Finally, a dependent claim explicitly required the lower edge of the wall be attached to the support. Based on claim differentiation, the court concluded that no such requirement existed in the independent claim.

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