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.

Efinaconazole – USA

On Mar. 13, 2020, Federal Circuit reversed PTAB’s claim construction & thus vacated final written decision and remanded matter back to the PTAB.

Acrux filed inter partes review (IPR) of all claims (1-2) of U.S. Patent No. 7,214,506. US’506 patent claims methods for topically treating fungal infections in human nails. Board issued claim construction & ultimately determined that all claims of the ’506 patent are unpatentable for obviousness. During IPR, Kaken proposed that the phrase “treating a subject having onychomycosis” means “treating the infection at least where it primarily resides in the keratinized nail plate and underlying nail bed.”  Board rejected Kaken’s construction as too narrow, concluding that “the express definition of onychomycosis includes superficial mycosis, which in turn is expressly defined as a disease that lies in the skin or visible mucosa.” Accordingly, the Board concluded, “treating onychomycosis” includes treating “superficial mycosis that involves disease of the skin or visible mucosa.” Applying that construction, the Board determined that a skilled artisan would have been motivated to combine the cited references and thus the claims are obvious.

During appeal, Kaken challenges the Board’s construction of “treating a subject having onychomycosis.” According to Kaken, the Board’s construction ignores the ’506 patent’s core innovation—“a topical treatment that can easily penetrate the tough keratin in the nail plate”. Federal Circuit said that the Board drew an unwarranted inference from the broad definition in specification. As a matter of ordinary meaning, a statement that a particular disease invades the body would not imply that it can invade any part of the body. So too, when the specification says that “onychomycosis” is a disease involving invasion of the “nail,” it does not compel the conclusion that the disease can invade any part of the defined “nail.”

Moreover, other parts of the specification, which explain that an effective topical treatment would need to penetrate the nail plate, support Kaken’s construction. The ’506 patent briefly describes topical treatments known in the prior art. It notes that those treatments were largely ineffective because they “could not sufficiently permeate the thick keratin in the nail plate.” Accordingly, the ’506 patent explains, an effective topical treatment must have “good permeability, good retention capacity and conservation of high activity in the nail plate.” Also, the prosecution history—which includes, specifically, statements made by Kaken to overcome a rejection and the examiner’s statements explaining withdrawal of the rejection based on those statements—provides decisive support for limiting the claim phrase at issue to a plate-penetrating treatment of an infection inside or under the nail plate. The Board relied on its erroneous claim construction throughout its consideration of facts that were part of its obviousness analysis. Thus, federal Circuit vacated the Board’s decision & remanded matter back to the board for reconsideration.

Linagliptin – USA

On Mar. 16, 2020, Federal Circuit reversed in-part & affirmed in-part district court’s decision in a case involving DPP-IV inhibitors such as linagliptin.

Boehringer (Plaintiff) sued Mylan & Aurobindo (Defendants) in district court over U.S. Patent Nos. 8,853,156, 9,173,859 and 8,673,927, which relate to the treatment of type 2 diabetes mellitus. District court issued judgment on the pleadings under Federal Rule of Civil Procedure 12(c) & held that claims 10-17, 24 and 25 of the ’156 patent are directed to ineligible subject matter under 35 U.S.C. § 101. The district court also held that claims 1, 14, 15, 20, and 21 of the ’859 patent and claims 7, 9, 15, 17, 19, 25, and 26 of the ’927 patent are invalid for obviousness-type double patenting in light of the claims of US 8,178,541, and invalid as obvious in view of US 2004/0097510. Boehringer appealed.

35 U.S.C. § 101 (ineligibility):

Independent claim 1 of US’156:

   1.   A method of treating and/or preventing metabolic diseases in a patient for whom metformin therapy is inappropriate due to at least one contraindication against metformin comprising orally administering to the patient a DPP-IV inhibitor wherein the contraindication is selected from the group consisting of: renal disease, renal impairment or renal dysfunction, unstable or acute congestive heart failure, acute or chronic metabolic acidosis, and hereditary galactose intolerance.

   10.  The method according to claim 1 wherein the metabolic disorder is type 2 diabetes mellitus and wherein the contraindication is renal disease, renal impairment or renal dysfunction, and wherein said DPP-4 inhibitor is used for said patient in the same dose as for a patient with normal renal function.

Defendants argued that the claims are directed to the natural law that “certain DPP-IV inhibitors (including linagliptin) are metabolized by the liver rather than the kidney.” Boehringer argued that the claims are directed to a “method of treating a specific disease ([type 2 diabetes mellitus]) for specific patients (with renal impairment) using a specific compound (linagliptin) at specific doses (same dose in patients with renal impairment as in patients with normal renal function) to achieve a specific outcome.” Federal Circuit citing “Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals International Ltd., 887 F.3d 1117 (Fed. Cir. 2018)”, held that the claims are directed to a particular method of treatment under step one and are therefore patent eligible. The claims of the ’156 patent are directed to a method of treating type 2 diabetes mellitus using a DPP-IV inhibitor, such as linagliptin. That certain DPP-IV inhibitors (including linagliptin) are metabolized by the liver rather than the kidney, does not make the claim ‘directed to’ that natural ability. Thus, claims are directed to a method of treatment at step one, as patent eligible and therefore need not reach step two.

Obviousness-type double patenting (ODTP) & 35 U.S.C. § 103 (Obviousness):

The claims at issue of both patents (US’859 & US’927) relate to the treatment of type 2 diabetes mellitus with linagliptin in 2.5 or 5 mg doses. US 8,178,541 (earlier expiring patent) was cited for ODTP & US 2004/0097510 was cited for obviousness. Federal Circuit sided with district court which found that the claimed invention’s doses of linagliptin in 2.5 mg and 5 mg fall within the ’510 publications disclosed range of 1–100 mg, thus there is a presumption of obviousness. Court also said that the person of ordinary skill in the art would have obtained the claimed dosages through routine experimentation. Based on the evidences & testimony it can be concluded that dose-ranging studies are common & are required for FDA approval. Dr. Grass testified that dose ranging studies are “conducted starting with a low dose, and sequentially moving through increasing doses.” Based on these facts & evidences, Federal Circuit affirmed district court & found asserted claims of the ’859 and ’927 patents invalid for obviousness and obviousness-type double patenting.

Infliximab – USA

On Mar. 05, 2020, Federal Circuit (Rule 36 judgment) upheld a Massachusetts court’s decision that Celltrion’s biosimilar Inflectra (infliximab-dyyb) does not infringe Janssen’s patent.

The main patent at issues was U.S. Patent No. 7,598,083, which claims cell culture media compositions used to produce infliximab. Janssen does not allege literal infringement of the '083 patent. Rather, Janssen argues only that Celltrion's accused media infringe claim 1 under the doctrine of equivalents. Celltrion denied the allegations and moved for summary judgment of non-infringement on the grounds that Janssen's asserted scope of equivalents would ensnare the prior art. District Court Judge Mark Wolf in his 104-page ruling held that the “defendants are entitled to summary judgment of non-infringement of the '083 patent because Janssen has not produced sufficient evidence to prove that the scope of equivalents would not ensnare the prior art.” In essence, the court found that no reasonable factfinder could conclude that the hypothetical claims that Janssen relies upon to avoid ensnarement would have been patentable because they were obvious rather than inventive. You can read the summary “reported here” on this blog.