Vilanterol / Umeclidinium – USA

 

On Nov. 19, 2020, Federal Circuit affirmed judgment of infringement & damages against Glaxo.

Plaintiff (Vectura Ltd) filed suit in 2016 against defendant (Glaxo) for alleged infringement of US 8,303,991 patent. The ’991 patent concerns the production of “composite active particles” for use in pulmonary administration, such as in dry-powder inhalers. The composite active particles described in the patent consist of additive material (magnesium stearate) that is adhered to particles of active ingredient. The additive particles promote the dispersion and delivery of the active ingredient into the lungs when the inhaler is activated. The specification discloses “milling method” to produce composite active particles.

In the district court, Vectura alleged infringement by GSK’s Ellipta-brand inhalers: the Breo, Anoro, and Incruse devices. Each of the accused inhalers features one or more “blisters,” which are sealed receptacles containing a single active ingredient, an excipient, and, optionally, additive material. The blisters use magnesium stearate as the additive material and lactose as the excipient. GSK uses multi-step mixing process. GSK first mixes the lactose excipient with magnesium stearate in the absence of the active ingredient. After a de-lumping step, GSK then mixes the lactose particles with the active ingredient. In that step, small particles of the active ingredient are deposited onto the larger lactose particles.

The issue here is claim construction of two disputed terms: 1) “composite active particles” and 2) “promotes the dispersion of the composite active particles”.

With respect to first claim construction, GSK’s proposed construction of that term included a process limitation requiring that the composite active particles be “formed by milling . . .But district court rejected that argument & construed the term to mean “[a] single particulate entit[y/ies] made up of a particle of active material to which one or more particles of additive material are fixed such that the active and additive particles do not separate in the airstream.”  During appeal Glaxo challenged the said construction & said that the court should have construed that term to require that the composite particles be produced by the “high energy milling” process referred to in the specification. GKS argued this based on support in the specification & based on prosecution history. During prosecution Vectura said that wet-mixing processes disclosed in prior art were different from the “aggressive milling procedure” recited in the application. For this reason, GSK argued, the applicants clearly disclaimed mixing processes other than high-energy milling, confirming that the term “composite active particles” should be construed to include a process limitation.

Federal Circuit, however, denied the arguments & said that although the ’991 patent contains a few statements suggesting that its high-energy milling is required, those statements are outweighed by the numerous statements indicating that high-energy milling is merely a preferred process. Moreover, the fact that the ’991 patent criticizes other methods is not dispositive. Therefore, the specification of the ’991 patent does not make its milling method an essential part of apparatus claim 1. With respect to prosecution response, Federal Circuit said that the statement did not purport to add a process limitation to the apparatus claim. Instead, that statement merely sought to demonstrate that Prior art’s coated particles were necessarily different from the applicants’ coated particles because it used a process that could not possibly produce “particulate additive matter on the surface of [a] particle of active material,” as required by the applicants’ claim. Applicant distinguished prior art based on the unique structure of the claimed composite particles, not the disclosed milling method.

With respect to second claim construction, Parties agreed that Vectura needed to prove that the use of magnesium stearate in the accused inhalers improves the dispersion of the active ingredient compared to identical products in which only the lactose excipient is coated with magnesium stearate. GSK argued that there was no substantial evidence of infringement as to that limitation because Vectura staked its case on a defective scientific test (referred to as “Study 2). Federal Circuit, however, said that the principal flaw in GSK’s argument is that Vectura did not rely solely on Study 2 to prove that the accused inhalers satisfy the dispersion limitation. Vectura introduced other evidence on dispersion as well. Vectura’s witnesses testified that coating active ingredient particles with magnesium stearate helps overcome the tendency of the particles to stick together and therefore increases the dispersion of the particles in the lungs. Evidence of tests conducted on coated and uncoated active-ingredient particles showed that coating the active particles substantially increased the dispersion of the active-ingredient particles and thus the amount of the active ingredient that could be delivered deep into the lungs. Tests run on GSK’s products showed that the particles of vilanterol and umeclidinium were consistently associated with magnesium stearate.

Federal Circuit thus affirmed the infringement & also damages awarded by the Jury.

Epinephrine – USA

On Nov. 23, 2020, Federal Circuit affirmed district court & held that Hospira’s ANDA infringes composition limitations.

Background of the case:

The plaintiffs (Par) own US 9,119,876 and US 9,295,657, which claim particular compositions containing epinephrine. These patents cover Par’s marketed product, Adrenalin®. Hospira filed ANDA seeking permission to manufacture and market a generic version of Par’s Adrenalin®, 1 mg/mL, product. Par sued Hospira for patent infringement based on ’876 and ’657 patents. District court found in favor of Par & held Hospira’s ANDA infringing certain limitations of asserted claims.

The ’876 and ’657 patents share same specification. Claim 1 of the ’876 patent is representative:

1. A composition comprising:

in the range of about 0.5 to 1.5 mg/mL of epinephrine and/or salts thereof, in the range of about 6 to 8 mg/mL of a tonicity regulating agent, in the range of about 2.8 to 3.8 mg/mL of a pH raising agent, in the range of about 0.1 to 1.1 mg/mL of an antioxidant, in the range of about 0.001 to 0.010 mL/mL of a pH lowering agent, and in the range of about 0.01 to 0.4 mg/mL of a transition metal complexing agent, wherein the antioxidant comprises sodium bisulfite and/or sodium metabisulfite.

Relevant here, the issues related to limitations of tonicity agent, pH lowering agent & transition metal complexing agent.

Federal Circuit analysis:

With respect to “about 6 to 8 mg/mL of a tonicity regulating agent” limitation, Hospira argued that its ANDA contains concentration of 9 mg/mL of sodium chloride & thus not falling into the claim limitation. However, during claim construction parties agreed in the district court that the term “about” had its “plain and ordinary meaning; i.e., approximately.” Hospira did not propose any further narrowing construction.  Federal Circuit said that the evidence supported a finding that “about 8” encompasses 9, considering the purpose of the upper limit. The court credited Dr. Elder’s testimony on this point, which focused on the technological facts, the importance of the purpose of the limitation, and the limitation’s noncriticality. Dr. Elder explained the purpose of both ends of the claim range—to avoid hypertonicity of the solution (which would lead to cell shrinkage) and to avoid hypotonicity of the solution (which would lead to cell swelling) and thereby achieve isotonicity, which is the stated goal of Hospira’s inclusion of sodium chloride. And he explained why it was clear that a “physiologically acceptable” concentration would include concentrations as high as 9 mg/mL, there being nothing critical to the exact numbers in the claimed range given the purposes of the upper and lower limits. Thus, Federal Circuit find no clear error with the district court’s finding on this matter.

With respect to “about 0.01 to 0.4 mg/mL of a transition metal complexing agent” limitation, Hospira argued that district court’s analysis should have focused entirely on the characteristics of the composition that Hospira was likely to sell, not on what compositions the ANDA, if approved, would allow Hospira to market. Federal Circuit disagreed & said that the district court did not commit clear error in finding that citric acid acts as a transition metal complexing agent in Hospira’s ANDA product. Hospira represented to the FDA that its citric acid buffer has a “chelating effect” allowing it to complex with transition metals. Moreover, Hospira’s experts acknowledged at trial that citric acid has “chelating properties” and therefore could bind with elemental impurities in its product.  As it is a Hatch-Waxman suit, statements made in the ANDA to gain approval can be used to find infringement. And if ANDA is silent on those statements then it is the product that the generic company is likely to sell that guides the infringement analysis. But, here, Hospira made these statements & thus it is the ANDA that governs infringement analysis & not the product which would likely to sell.  

With respect to “about 0.001 to 0.010 mL/mL of a pH lowering agent” limitation, Hospira argued that the trial court improperly accepted Par’s counting not just hydrochloric acid but also citric acid as a pH lowering agent. Hospira contends that citric acid—specifically, the citric acid that remains after subtracting the amount that serves as a transition metal complexing agent—cannot be a pH lowering agent because it is already included in the buffer system that counts toward meeting the claim limitation requiring a certain amount of pH raising agent. Federal Circuit however said that Hospira has not made and preserved a claim-construction argument that, an acid, i.e., a pH lowering agent, cannot also be part of an agent that overall serves to raise pH. Indeed, the passages of the specification of the ’876 and ’657 patents that discuss a “buffer system” made up of an acid and a base, at least strongly suggest the opposite. Federal circuit thus rejected Hospira’s argument that citric acid molecules must be allocated between the pH raising agent limitation and the pH lower agent limitation.

Efinaconazole - USA

On Nov. 05, 2020 Federal Circuit affirmed-in-part district court’s interpretation of proper venue in Hatch-Waxman cases.

Mylan (Mylan Pharmaceuticals Inc. (MPI)/ Mylan Laboratories Ltd.(MLL)/ Mylan Inc.) in Jun.2018 filed ANDA with  USFDA to market generic version of Jublia®. Plaintiff (Valeant pharma / Dow pharma) on Sep 26, 2018 filed suit in New Jersey district court. The next day, Valeant filed an essentially identical protective suit against Mylan in the Northern District of West Virginia. In Jan. 2019, Mylan moved to dismiss Valeant’s New Jersey District Court complaint against MPI and Mylan Inc. for improper venue pursuant to Federal Rule of Civil Procedure 12(b)(3). Mylan argued that venue was improper under § 1400(b) because no Mylan defendant resides in New Jersey, the only alleged act of infringement—submission of the ANDA—did not occur in New Jersey, and the Mylan defendants do not have regular and established places of business in New Jersey. In response, Valeant argued that it is unduly narrow to limit “an act of infringement” under § 1400(b) to the act of submitting the ANDA. Valeant contended that “the Court must consider Mylan’s planned, future acts.” In August 2019, the district court granted Mylan’s motion to dismiss the complaint against all defendants based on improper venue. Valeant appealed.

Federal Circuit said that under Hatch-Waxman cases, it is an act of infringement to submit an ANDA (artificial infringement). Federal Circuit further said that the question in this appeal, therefore, is whether the act of infringement identified in § 1400(b) occurs only when and where an ANDA-filer submits its ANDA to the FDA or occurs wherever future distribution of the generic is contemplated. Court said that they are bound by the decision of Supreme Court in “TC Heartland”. Court said that both parties agreed that § 1400(b) requires a past act of infringement.  Specifically, “has committed acts of infringement,” a present perfect phrase, counsels that the acts accused of infringement must have already occurred.  However, in Hatch-Waxman cases no actual infringement occurs. Therefore, it is the submission of the ANDA, and only the submission, that constitutes an act of infringement in this context.  Since, MPI has not submitted ANDA from New Jersey, it not a proper venue for this case. Proper venue would be West Virginia from where MPI submitted an ANDA, as district court correctly found. Distribution of product in future has no relevance here. Therefore, it does not matter if future sell would occur in New Jersey. Venue is proper only in those districts that are sufficiently related to the ANDA submission—in those districts where acts occurred that would suffice to categorize those taking them as a “submitter” under § 271(e).

Federal Circuit reversed with respect to the entity, MLL. Court said that as this is a foreign entity, it is subject to venue in any judicial district, including the District of New Jersey. Whether MLL can be held answerable to claims of infringement in this case turns on whether MLL’s involvement in the submission of the ANDA is sufficient for it to be considered a “submitter,” and thus, amenable to suit. The district court’s conclusion dismissing the complaint as to all defendants after only evaluating Mylan’s venue argument is, therefore, incongruous. Federal Circuit, thus, reversed the district court’s venue-based dismissal of MLL and remanded for further consideration.

Dapagliflozin – India

Brief background of the case is like this. Plaintiff, Astrazeneca filed suit against number of generic companies for launching generic dapagliflozin (DAPA) product in India. Two patents-in-suit are IN 205147 (Genus patent - expired on Oct 02, 2020) & IN 235625 (specific patent – expires on May 15, 2023). Defendants filed counterclaim alleging invalidity of IN’625 patent based on IN’147 patent. Astrazeneca then asked for interim injunction.  Both Plaintiff & Defendants (Alkem & Intas) filed their respective briefs.

Court said that the issue at this stage of preliminary injunction is whether defendants have raised a credible challenge to IN 625? Actual validity issued would be tried at trial stage. The challenge to the species patent i.e. IN 625 is, broadly, laid on the grounds such as lack of novelty in view of prior claiming, lack of novelty due to prior publication, lack of inventive step, failure of the plaintiffs to make full and fair disclosure as required under Section 8 of the Act. Court said that the fact that both in the pleadings and in the documents, there is a definitive assertion that DAPA is covered in the genus patents granted in India. Plaintiff said that DAPA is covered but it is not disclosed in genus patent. Plaintiff further argued that coverage does not necessarily include disclosure which is founded on the Markush claim/group. But court said that the fact that the plaintiffs have taken out an infringement action both for IN 147 and IN 625 is a sufficient clue, at least at this juncture, that DAPA is claimed in both suit patents. Therefore, the defendants submission that IN 625 should be revoked on account of prior claiming under the provisions of Section 64(1)(a) of the Act has substance, at least at this stage.

With respect to anticipated by what was published or publicly known, court said that while counsel for the defendants, based on the affidavit of Mr. Martin, did try to convey that a person skilled in the art could iterate the claims and arrive at 8 molecules based on prior publication and not hindsight, this is an aspect which would be required to be tested in a trial. Therefore, on this score, the defendants' defence, at this stage, in my opinion, does not inject vulnerability.

With respect to inventive step, court said that there is no clue in IN 625 of an unknown technical effect on its priority date. Plaintiff tried to persuade the court with post filing evidences. But court said that post priority date evidence can only be taken into account to confirm the existence of technical effect which is found embedded in the specification of IN 625 and is capable of being understood by a skilled person having common general knowledge and not to rely upon the same to establish its effect for the first time. The plaintiffs have not been able to demonstrate, at least at this stage, the existence of such technical effect in the specifications.

With respect to Section 8 requirement, court said that in the instant actions, specific details were sought by the Indian Patent Office concerning search and examination report. What was submitted by the plaintiffs to the Indian Patent Office via the letter dated 10.01.2005 were the corresponding US patents and not the examination reports. It is also not denied by the plaintiffs that their response of 19.08.2002, whereby, the validity period of US 117 was voluntarily aligned with the US genus patent i.e. US 126 was not placed before the Indian Patent Office. The submission advanced on behalf of the plaintiffs that the terminal disclaimer is an obviation and not an admission of obviousness is not an answer to the provisions of Section 8(2) of the Act which is mandatory.

With respect to other injunctive factors such as balance of convenience, irreparable harm & public interest, court found these in favor of defendants. Court thus denied injunction but asked defendants to place on record the details, quantum, and value of drug manufactured and sold. The defendants via their affidavits will also undertake to pay damages as and when called upon to do so by the Court.