Ivermectin – USA

On Aug 21, 2019, Delaware court found Galderma’s method of treating rosacea patent invalid for anticipation.

Galderma sued Teva under Hatch-Waxman act for infringement of several patents listed in orange book for Soolantra® cream. Court held bench trial from June 10 to 12, 2019, focusing essentially on 3 patents; US 9,089,587, US 9,233,117, and US 9,233,118. Teva argued that asserted claims of these patents are invalid for lack of written description, anticipation, and obviousness. Broadly these patents are directed to methods of treating papulopustular rosacea. All of the asserted claims require (1) topically administering, (2) once daily, (3) to a skin area affected by the inflammatory lesions of rosacea, ( 4) a pharmaceutical composition comprising 1 % by weight ivermectin and a pharmaceutically acceptable carrier.

Anticipation:

Teva argues that the asserted claims are invalid as anticipated by either the McDaniel patent or the Manetta patent. McDaniel claims an invention relating to "a method for treatment of rosacea (acne rosacea) in humans employing orally-administered or topically-applied ivermectin." explicitly discloses an embodiment using topical ivermectin:

“Ivermectin is formulated into a cosmetically-acceptable topical lotion, cream, or gel and applied to skin affected by rosacea. Because of the well-known barrier effect the skin presents to the penetration of topical medications, such a route of treatment with ivermectin would be anticipated to require once or twice-daily applications for as long as four weeks to achieve sufficient follicle penetration and effective miticidal activity. A topical formulation that could achieve this effect would contain about 1-5% ivermectin”.

Thus, court said that McDaniel discloses every element of the claimed treatment method, ie. "topically administering",  "once daily", "to a skin area affected by the inflammatory lesions of papulopustular rosacea"  and  "a pharmaceutical composition comprising about 1 % by weight ivermectin and a pharmaceutically acceptable carrier".

Galderma argued that McDaniel fails to disclose (1) the use of topical ivermectin for the purpose of treating inflammatory lesions of papulopustular rosacea and (2) the use of 1 % ivermectin once daily.

With respect to first point, Galderma argued that McDaniel fails to disclose the use of ivermectin to treat inflammatory lesions because it discloses a method that "elicit lesion formation" and co-administers ivermectin with "conventional anti-rosacea medications." But court disagreed & said that any increase in lesion formation is temporary. Regardless, lesion formation is a measure of efficacy and is irrelevant to whether McDaniel discloses the steps of the treatment method. With respect to second point, Galderma argued that McDaniel's disclosure of "about 1-5% ivermectin" is not "sufficiently specific" to anticipate the asserted claims and is not connected to the once-daily dosing frequency. Court again disagreed & said that, although McDaniel discloses a genus of 1-5% ivermectin, there is no evidence that 1-5% is a particularly broad range for the purposes of the claimed treatment method. Galderma has made no allegation of criticality or provided any evidence demonstrating any difference across the range. There is thus no "considerable difference" between the 1 % ivermectin limitation and the 1-5% ivermectin range in McDaniel. Also, McDaniel ties the use of 1 % ivermectin to a once-daily dosage. McDaniel provides a clear reason to connect the disclosure of 1 % ivermectin with once-daily applications as it explicitly teaches the use of both elements together.

Court further said that, aside from the treatment method, the only remaining limitations are those relating to efficacy. "Under the principles of inherency, if the prior art necessarily functions in accordance with, or includes, the claimed limitations, it anticipates." [MEHL/Biophile Int'! Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999)]. Galderma argued that McDaniel's treatment of rosacea generally is insufficient for anticipation because it will not necessarily result in treatment of inflammatory lesions of papulopustular rosacea. But court said that, the issue is not whether McDaniel's formulation if applied would inherently treat inflammatory lesions of papulopustular rosacea, but whether McDaniel discloses the application of the formulation to inflammatory lesions of papulopustular rosacea. And court found that it does.

Court further said that, the only remaining issue is whether McDaniel also discloses using the same ivermectin formulation as in the asserted claims. The parties have stipulated, "Manetta enables McDaniel in 2012 as to the formulation." Thus, as of 2012, before the critical dates of the asserted claims, a person of ordinary skill in the art would have been able to practice McDaniel's disclosed treatment method with Manetta's formulation without undue experimentation. The Manetta formulation is the formulation for Galderma's product, Soolantra. Galderma argued that Teva has failed to meet its burden on anticipation because it must show that all 1 % ivermectin formulations disclosed in McDaniel would necessarily achieve the claimed efficacies. But court said that, it is well established that "[f]or a prior-art reference to be enabling, it need not enable the claim in its entirety, but instead the reference need only enable a single embodiment of the claim."

Court held that the asserted claims consist of the same steps described in McDaniel and are directed to the same use-treating inflammatory lesions of papulopustular rosacea. "Using the same composition claimed by [Galderma] in the same manner claimed by [Galderma] naturally results in the same claimed skin benefits." Therefore, the claimed efficacies are nothing more than "the natural result flowing from the explicit disclosure" of the claimed treatment method. As such, those efficacies are inherent to and anticipated by McDaniel's disclosure of the claimed treatment method.

Court thus did not address other invalidity arguments as each of the asserted claims found invalid for anticipation.