Doxycycline – USA

On Mar 25, 2020, Federal Circuit affirmed-in part infringement of Chang patents & revesed-in part district court’s decision of Ashley II Patents.

In March 2016, Plaintiffs Galderma filed suit against Defendants Amneal as defendants sought to bring to market a generic version of Plaintiffs’ Oracea® Capsules, a once-daily 40 milligram administration of doxycycline for the treatment of the papules and pustules of acne rosacea. Plaintiffs alleged infringement of U.S. Patent Nos. 8,206,740 (“Chang ’740 patent”); 8,394,405 (“Chang ’405 patent”); 8,470,364 (“Chang ’364 patent”); 7,749,532 (“Chang ’532 patent”) (collectively, the “Chang patents”); 7,211,267 (“Ashley ’267 patent”); 7,232,572 (“Ashley ’572 patent”); (collectively, the “Ashley I patents”); 8,603,506 (“Ashley ’506 patent”); and 9,241,946 (“Ashley ’946 patent”) (collectively, the “Ashley II patents”). The Chang and Ashley patents are generally directed to low-dose doxycycline formulations for the treatment of the papules and pustules of acne rosacea. Specifically, the Chang patents describe “pharmaceutical composition[s] of doxycycline that contain[] an immediate release (IR) component of the drug and a delayed release (DR) component of the drug, which are combined into one dosage unit for once-daily dosing.” The asserted claims of the Ashley patents generally cover methods of treating acne or rosacea by oral administration of a low daily dose doxycycline. Following bench trial District court found infringement of Chang patents & Ashley II patents & non-infringement of Ashley I patent. You can read the summary “reported here” on this blog.

Chang patents:

Claim 1 of the ’740 patent is illustrative:

1. An oral pharmaceutical composition of doxycycline, which at a once-daily dosage will give steady state blood levels of doxycycline of a minimum of 0.1 μg/ml and a maximum of 1.0 μg/ml, the composition consisting of (i) an immediate release (IR) portion comprising 30 mg doxycycline; (ii) a delayed release (DR) portion comprising 10 mg doxycycline; and optionally, (iii) one or more pharmaceutically acceptable excipients.

During appeal, Amneal argued that Galderma’s arguments during the ’740 inter partes review proceedings clearly and unmistakably surrendered subject matter and therefore preclude a finding that Amneal’s products infringe the Chang patents under the doctrine of equivalents. Federal Circuit said that “statements made by a patent owner during an IPR proceeding can be considered during claim construction and relied upon to support a finding of prosecution disclaimer” so long as the statements are “both clear and unmistakable.” [Aylus Networks, Inc. v. Apple Inc., 856 F.3d 1353, 1361–62 (Fed. Cir. 2017)]. Federal Ciruit said that what Galderma argued  with respect to “delayed release” construction during IPR was rejected by board. Board clearly put the public on notice that the meaning of delayed release with respect to the Chang Patents is not limited to formulations requiring that there be no substantial release in the stomach. Accordingly, Federal Ciruit saw no error in the district court’s conclusion that Galderma was not precluded by these statements from asserting the doctrine of equivalents.

Now turning to the merits, Federal Circuit said that Amneal’s product is manufactured by layering doxycycline such that doxycycline releases at various intervals. Because a portion is prevented from releasing immediately, such later-releasing portion of doxycycline occurs “at a time other than immediately following oral administration” as construed by District court with respect to term “delayed release”. Therefore, this later-releasing portion, “in combination with [the DR portion of doxycycline], is insubstantially different from the 10 mg DR portion claimed in Chang.” Thus, district court did not clearly err in finding infringement under the doctrine of equivalents with respect to the Chang Patents.

The Ashley II patents:

Claim 15 of the ’506 patent is illustrative:

15. A method for treating papules and pustules of rosacea in a human in need thereof, the method comprising administering orally to said human doxycycline, or a pharmaceutically acceptable salt thereof, in an amount of 40 mg per day, wherein the amount results in no reduction of skin microflora during a six-month treatment, without administering a bisphosphonate compound.

The district court construed “wherein the amount results in no reduction of skin microflora during a six-month treatment” as “wherein the amount results in no reduction of skin microflora vis-à-vis a placebo control during a sixmonth treatment, with microbiological sampling at baseline and month six.” It found that Amneal’s product infringes the asserted claims of the Ashley II Patents under the doctrine of equivalents.

Amneal argued that allegations of infringement under the doctrine of equivalents require “particularized testimony and linking argument as to the ‘insubstantiality of the differences’ between the claimed invention and the accused . . . process, or with respect to the function, way, result test . . . evidence must be presented on a limitation-by-limitation basis.” Amneal said that argument presented by Galderma was related to the “sub-antibacterial amount” limitation of the Ashley I patents and the record does not support that it “applies equally to the overlapping subject matter of the ‘skin microflora’ terms” here. Galderma did not present particularized testimony and linking argument as to the reduction in skin microflora term. Rather, it presented testimony with respect to the “sub-antibacterial amount” limitation of the Ashley I patents and, now attempting to link it to the “skin microflora”. Because the record wholly lacked the requisite particularized testimony required to find infringement under the doctrine of equivalents, Federal Circuit reversed the district court’s judgment.