Doxycycline – USA

On Aug 27, 2018, District court of Delaware issued opinion (redacted) & held that Galderma patents are valid & infringed by Amneal pharmaceuticals in Hatch-Waxman litigation.

In March 2016, Plaintiffs Galderma filed suit against Defendants Amneal under the Hatch-Waxman Act, 35 U.S.C. § 271(e). 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”); 8,603,506 (“Ashley ’506 patent”); and 9,241,946 (“Ashley ’946 patent”) (collectively, the “Ashley 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. In February 2018, the Court held a five-day bench trial.

Infringement of the Chang Patents

Galderma asserted that Amneal’s ANDA product infringes claim 1 of the Chang ’532 patent, claim 1 of the Chang ’740 patent, claims 1 and 3 of the Chang ’405 patent, and claims 1 and 2 of the Chang ’364 patent (the “asserted claims of the Chang patents”) under the doctrine of equivalents. During trial, Amneal contended that Galderma cannot assert infringement under the doctrine of equivalents because: (1) Galderma’s theory would vitiate the claims, (2) Galderma surrendered equivalents to the 10 mg DR portion during prosecution, and (3) Galderma disclaimed in prosecution formulations that release in the stomach. The Court however, disagreed.

Court after hearing both parties said that nothing in the Court’s construction of “delayed release” limits the way in which that delay is created. Thus, it does not matter whether the delay is caused by an enteric coating or some other barrier, so long as release does not occur until “a time other than immediately following oral administration.” Amneal’s ANDA contain two equivalent excipients as a DR portions in which release is delayed until sometime well after “immediately following oral administration.” Accordingly, the Court concluded that Galderma has proven, by a preponderance of the evidence, that Amneal’s two excipients DR portion are insubstantially different or performs the same function in the same way to achieve the same result from the 10 mg DR portion claimed in Chang. Thus, Amneal infringes claim 1 of the Chang ’740 patent, claims 1 and 3 of the Chang ’405 patent, and claims 1 and 2 of the Chang ’364 patent. With respect to ‘532 patent, Galderma has failed to prove that Amneal’s ANDA product infringes claim 1 of the Chang ’532 patent. Claim 1 has an additional limitation missing from the asserted claims of the other Chang patents: the “the DR portion is in the form of pellets” and is “coated with at least one enteric polymer.” Galderma has not demonstrated that enteric polymers, which prevent release in the stomach, would be considered interchangeable with Amneal’s polymer. Nor has Galderma offered evidence proving that Amneal’s ANDA works in the same way as an enteric polymer to delay release.

Infringement of the Ashley Patents

Galderma contended that Amneal’s ANDA product infringes claim 30 of the Ashley ’267 patent and claims 14, 15, 23, 24, and 26 of the Ashley ’572 patent (the “asserted claims of the Ashley I patents”), as well as claims 3, 4, 5, 15, and 16 of the Ashley ’506 patent and claims 13, 14, 15, and 16 of the Ashley ’946 patent (the “asserted claims of the Ashley II patents”), “at least” under the doctrine of equivalents. Amneal responded that Galderma is collaterally estopped from asserting the Ashley I patents and, anyway, Amneal’s ANDA product does not infringe any of the asserted claims of the Ashley patents, literally or under the doctrine of equivalents. Court agreed with Amneal that Galderma is collaterally estopped from asserting the Ashley I patents. With respect to the Ashley II patents, Court held that Galderma has proven by a preponderance of the evidence that Amneal’s ANDA product infringes the asserted claims under the doctrine of equivalents.

Amneal contended that Galderma is collaterally estopped from asserting the Ashley I patents based on the Court’s finding in Mylan that 40 mg doxycycline administered once-daily does not meet the “sub-antibacterial amount” limitation of the Ashley I patents. In Mylan, the Court decided that a 40 mg once-daily administration of doxycycline does significantly inhibit the growth of microorganisms and, therefore, fails to meet the sub-antibacterial limitation of the Ashley I patents. Collateral estoppel applies even if Galderma here presented new evidence that was not before the Court in Mylan. The Court decided the issue of infringement in Mylan following a trial at which Galderma had a full and fair opportunity to present any evidence of infringement it wished. Any new evidence Galderma offers now in support of its doctrine of equivalents infringement theory was neither controlling nor otherwise essential to the Court’s finding of non-infringement in Mylan. Thus, the Court found that Galderma is collaterally estopped from asserting infringement of the Ashley I patents, literally or under the doctrine of equivalents.

Galderma alleges Amneal’s ANDA product infringes the asserted claims of the Ashley II patents “at least” under the doctrine of equivalents. The only limitation in dispute is “wherein the amount [of doxycycline] results in no reduction of skin microflora during a six-month treatment” (the “skin microflora limitation”). The Court construed this term to mean an amount that “results in no reduction of skin microflora vis-à-vis a placebo control during a six-month treatment, with microbiological sampling at baseline and month six.” While Galderma has not proven Amneal’s ANDA product literally meets this limitation, Galderma has proven, by a preponderance of the evidence, that Amneal’s ANDA product infringes the asserted claims of the Ashley II patents under the doctrine of equivalents. Court also held that Galderma has also proven that Amneal’s efforts to persuade doctors and patients to use Amneal’s ANDA product in a manner consistent with Amneal’s Label make Amneal liable for indirectly infringing the asserted claims of the Ashley II patents, by both inducing and contributing to direct infringement by third parties.

Validity of the Ashley Patent:

Amneal contends that: (1) all of the asserted claims of the Ashley patents are invalid for lack of enablement; (2) all of the asserted claims of the Ashley patents are invalid for lack of written description; (3) claim 30 of the Ashley ’267 patent, claim 15 of the Ashley ’506 patent, and claim 13 of the Ashley ’946 patent are invalid as anticipated by Dr. Feldman’s and/or his patient’s use of Periostat® to treat rosacea; (4) claims 3, 4, 5, and 16 of the Ashley ’506 patent, claims 14, 15, and 16 of the Ashley ’946 patent, and all of the asserted claims of the Ashley ’572 patent are obvious in view of Dr. Feldman and/or his patient’s use of Periostat®; and (5) the asserted claims of the Ashley I patents are indefinite in view of the “sub-antibacterial amount” terms. Court however held that, Amneal has failed to meet its burden to prove by clear and convincing evidence that any of the asserted claims are invalid.

CONCLUSION:

Galderma has proven by a preponderance of the evidence that Amneal infringes claim 1 of the Chang ’740 patent; claims 1 and 3 of the Chang ’405 patent; claims 1 and 2 of the Chang ’364 patent; claims 3, 4, 5, 15, and 16 of the Ashley ’506 patent; and claims 13, 14, 15, and 16 of the Ashley ’946 patent. Galderma has not proven Amneal infringes claim 1 of the Chang ’532 patent; claim 30 of the Ashley ’267 patent; or claims 14, 15, 23, 24, and 26 of the Ashley ’572 patent. Amneal has failed to meet its burden to prove by clear and convincing evidence that any of the asserted claims are invalid.