DCT

1:18-cv-00193

AstraZeneca Ab v. Mylan Pharma Inc

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Key Events
Amended Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00203, N.D. W. Va., 07/17/2020
  • Venue Allegations: Venue is alleged to be proper based on Defendant Mylan Pharmaceuticals Inc.'s residence and regular place of business within the district, and on tortious acts of patent infringement committed within the district by all Defendants, with Defendants 3M and Kindeva having also consented to venue.
  • Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA for proposed generic versions of the Symbicort® inhaler constitutes an act of infringement of four patents related to stable pharmaceutical compositions for inhalation.
  • Technical Context: The technology concerns formulations for pressurized metered-dose inhalers (pMDIs) that combine formoterol (a long-acting beta-agonist) and budesonide (a corticosteroid) for the treatment of respiratory diseases such as asthma and COPD.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' filing of ANDA No. 211699 and their subsequent issuance of Paragraph IV certification letters. These letters notified the Plaintiff that Defendants seek FDA approval to market generic products prior to the expiration of the patents-in-suit, alleging the patents are invalid, unenforceable, or will not be infringed. The patents-in-suit constitute a patent family, with each subsequent patent being a continuation of the application that led to the prior one, creating an overlapping and evolving scope of protection.

Case Timeline

Date Event
2002-02-01 Earliest Priority Date for all Patents-in-Suit
2006-07-21 FDA approves New Drug Application for Symbicort
2010-07-20 U.S. Patent No. 7,759,328 Issues
2012-03-27 U.S. Patent No. 8,143,239 Issues
2013-11-05 U.S. Patent No. 8,575,137 Issues
2018-06-26 FDA Form 356h for ANDA No. 211699 submitted by 3M
2018-08-15 FDA sends Paragraph IV Acknowledgment Letter to 3M
2018-08-17 3M transfers interest in ANDA No. 211699 to Mylan
2018-08-30 Mylan sends Notice Letter for ’328, ’239, ’137 patents
2019-01-01 U.S. Patent No. 10,166,247 Issues
2019-10-11 Mylan sends Second Notice Letter for ’247 patent
2020-05-01 3M divests drug delivery business to Kindeva
2020-07-17 Fourth Amended Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 7,759,328 - “Composition for Inhalation,” issued July 20, 2010

The Invention Explained

  • Problem Addressed: The patent addresses the technical challenge of ensuring the physical "stability" of a pharmaceutical product containing a mixture of compounds for administration via a pressurized metered-dose inhaler (pMDI) (’328 Patent, col. 1:12-24). Specifically, it seeks to prevent the active drug particles from agglomerating or settling in the hydrofluoroalkane (HFA) propellant, which could lead to inconsistent and inaccurate dosing.
  • The Patented Solution: The invention is a specific formulation that solves the stability problem by combining the two active ingredients, formoterol and budesonide, with two key excipients: polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) (’328 Patent, col. 1:25-29). This particular combination of ingredients, within defined concentrations, is described as exhibiting "excellent physical suspension stability" in an HFA 227 propellant (’328 Patent, col. 1:25-29).
  • Technical Importance: This formulation enabled the reliable delivery of a combination therapy for respiratory disease from a convenient pMDI device, a widely used format for respiratory medications.

Key Claims at a Glance

The complaint does not identify specific asserted claims. Independent claim 1 is representative of the invention:

  • A pharmaceutical composition comprising formoterol fumarate dihydrate, budesonide, 1,1,1,2,3,3,3-heptafluoropropane (HFA227), PVP K25 (polyvinyl pyrrolidone with a nominal K-value of 25), and PEG-1000 (polyethylene glycol with an average molecular weight of 1,000),
  • wherein the formoterol fumarate dihydrate is present at a concentration of 0.09 mg/ml,
  • the budesonide is present at a concentration in the range of 1 mg/ml to 8 mg/ml,
  • the PVP K25 is present at a concentration of 0.001% w/w,
  • and the PEG-1000 is present at a concentration of 0.3% w/w.

U.S. Patent No. 8,143,239 - “Composition for Inhalation,” issued March 27, 2012

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the ’328 Patent, this patent addresses the same fundamental problem of maintaining a stable suspension of formoterol and budesonide particles in a pMDI formulation (’239 Patent, col. 1:15-30).
  • The Patented Solution: The solution is again based on the combination of formoterol, budesonide, HFA 227, PVP, and PEG (’239 Patent, Abstract). However, the claims of the ’239 Patent are directed to the physical inhaler device containing the suspension and define different concentration ranges for the PVP and PEG excipients compared to the ’328 Patent, while adding a limitation on the dosage delivered per actuation.
  • Technical Importance: The invention provides an alternative proprietary scope for the stable combination drug formulation, focusing on the inhaler system as a whole and the dosage it delivers.

Key Claims at a Glance

The complaint does not identify specific asserted claims. Independent claim 1 is representative:

  • A pressurized metered dose inhaler containing a suspension composition comprising formoterol fumarate dihydrate in the form of particles; budesonide in the form of particles; 1,1,1,2,3,3,3-heptafluoropropane (HFA227); polyvinyl pyrrolidone (PVP); and polyethylene glycol (PEG),
  • wherein the budesonide is present in the composition at a concentration in the range of 1 mg/ml to 8 mg/ml,
  • the PVP is present at a concentration in the range of 0.001% to 0.01% w/w,
  • and the PEG is present at a concentration in the range of 0.05 to 0.5% w/w,
  • and wherein an actuation of the inhaler delivers 4.5 µg formoterol fumarate dihydrate and 40 to 320 µg budesonide.

U.S. Patent No. 8,575,137 - “Composition for Inhalation,” issued November 5, 2013

Technology Synopsis

This patent, a continuation from the same family, also describes a stable pharmaceutical suspension for pMDIs to treat respiratory disorders like asthma and COPD (’137 Patent, col. 1:11-19). It addresses the technical problem of maintaining the physical stability of formoterol and budesonide in an HFA propellant by using a specific formulation containing polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) as excipients (’137 Patent, col. 1:24-34).

Asserted Claims

The complaint makes general allegations of infringement; independent claim 1 is representative.

Accused Features

The complaint alleges that the Defendants' ANDA products, as generic versions of Symbicort®, will contain a formulation of formoterol, budesonide, HFA, PVP, and PEG that infringes the patent (Compl. ¶¶17, 102-105).

U.S. Patent No. 10,166,247 - “Composition for Inhalation,” issued January 1, 2019

Technology Synopsis

As the most recent patent in the asserted family, this patent also claims a stable pMDI formulation for formoterol and budesonide (’247 Patent, Abstract). The invention provides a solution to the problem of suspension instability in HFA propellants by employing a composition that includes the excipients polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) at defined concentrations (’247 Patent, col. 1:30-38).

Asserted Claims

The complaint makes general allegations of infringement; independent claim 1 is representative.

Accused Features

Defendants' ANDA products are accused of infringing by comprising a stable pharmaceutical suspension of formoterol, budesonide, HFA227, PVP, and PEG (Compl. ¶¶19, 119-122).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the generic drug products described in Abbreviated New Drug Application (ANDA) No. 211699, referred to as "Mylan's ANDA Products" (Compl. ¶¶1, 21).

Functionality and Market Context

  • The products are generic versions of AstraZeneca's Symbicort®, an inhalation aerosol delivered via a pressurized metered-dose inhaler ("inhaler") (Compl. ¶¶1, 10).
  • They are formulated to deliver two active ingredients, budesonide and formoterol fumarate dihydrate, for the treatment of asthma and chronic obstructive pulmonary disease (COPD) (Compl. ¶10).
  • The ANDA seeks approval for two dosage forms: 80 mcg budesonide/4.5 mcg formoterol and 160 mcg budesonide/4.5 mcg formoterol (Compl. ¶¶10, 21).
  • The complaint alleges that to be approved as a generic equivalent, the ANDA products must necessarily contain the same active ingredients and excipients as the patented formulations, including HFA227, polyvinyl pyrrolidone (PVP), and polyethylene glycol (PEG) (Compl. ¶¶13, 15, 17, 19). The filing of the ANDA is an act of infringement under 35 U.S.C. § 271(e)(2) intended to secure FDA approval for commercial sale prior to the expiration of the patents-in-suit (Compl. ¶1).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain explicit claim charts. The infringement theory, standard in ANDA litigation, is that the defendants' generic product, to be bioequivalent to the branded Symbicort® product, will necessarily meet the limitations of the asserted claims.

’328 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition comprising formoterol fumarate dihydrate, budesonide, 1,1,1,2,3,3,3-heptafluoropropane (HFA227), PVP K25... and PEG-1000... The Mylan ANDA Products are alleged to be generic versions of Symbicort®, which is formulated with these same active ingredients, propellant, and excipients. ¶¶13, 21, 71 col. 1:30-38
wherein the formoterol fumarate dihydrate is present at a concentration of 0.09 mg/ml The ANDA product is alleged to match the formulation of Symbicort®, which the patent describes as having this concentration of formoterol. ¶¶13, 70 col. 3:20-24
the budesonide is present at a concentration in the range of 1 mg/ml to 8 mg/ml The ANDA product is alleged to contain budesonide within this claimed concentration range to achieve bioequivalence with Symbicort's approved dosages. ¶¶13, 70 col. 3:24-28
the PVP K25 is present at a concentration of 0.001% w/w The ANDA product is alleged to contain PVP K25 at this specific concentration, which the patent teaches is preferred for achieving suspension stability. ¶¶13, 70 col. 1:40
and the PEG-1000 is present at a concentration of 0.3% w/w The ANDA product is alleged to contain PEG-1000 at this specific concentration, which the patent teaches is preferred for stability and valve performance. ¶¶13, 70 col. 1:42-43

’239 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pressurized metered dose inhaler containing a suspension composition comprising formoterol fumarate dihydrate... budesonide... HFA227; polyvinyl pyrrolidone (PVP); and polyethylene glycol (PEG) The Mylan ANDA Products are pressurized metered-dose inhalers alleged to contain a suspension with these components. ¶¶15, 21, 88 col. 1:19-23
wherein the budesonide is present... at a concentration in the range of 1 mg/ml to 8 mg/ml The ANDA product is alleged to contain budesonide within this concentration range to match the dosages of the branded product. ¶¶15, 87 col. 3:24-28
the PVP is present at a concentration in the range of 0.001% to 0.01% w/w The infringement allegation suggests the ANDA product's formulation will meet this claimed range for the PVP excipient. ¶¶15, 87 col. 1:31-38
and the PEG is present at a concentration in the range of 0.05 to 0.5% w/w The infringement allegation suggests the ANDA product's formulation will meet this claimed range for the PEG excipient. ¶¶15, 87 col. 1:31-38
and wherein an actuation of the inhaler delivers 4.5 µg formoterol fumarate dihydrate and 40 to 320 µg budesonide. The Mylan ANDA Products are explicitly alleged to be available in 80/4.5 mcg and 160/4.5 mcg dosages, falling within this claimed delivery range. ¶¶10, 15, 21, 87 col. 1:45-48

Identified Points of Contention

  • Technical Questions: A primary question will be factual: Does the specific formulation detailed in Defendants' confidential ANDA submission literally meet every concentration and component limitation of the asserted claims? The dispute may focus on whether the excipients used (e.g., PVP, PEG) and their concentrations in the Mylan product are identical to those claimed, or if Defendants have designed a formulation that avoids the literal claim scope.
  • Scope Questions: The complaint alleges Defendants have asserted non-infringement (Compl. ¶26). This raises the question of whether Defendants' formulation includes additional or different components that could be argued to place it outside the scope of claims reciting "comprising," or if the concentrations used fall outside the claimed ranges. The availability of the doctrine of equivalents to capture formulations with insubstantially different concentrations may become a central legal issue.

V. Key Claim Terms for Construction

The Term: "a concentration of 0.001% w/w" (from ’328 Patent, claim 1) and similar definite numerical limitations.

Context and Importance

This term is a precise numerical value, not a range. Its construction is critical because any deviation in the accused product, however small, could support a literal non-infringement defense. Practitioners may focus on this term because the patent's specification discusses experiments across a range of concentrations, but the claim was granted with this exact value, suggesting a potential surrender of broader scope.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: A plaintiff may argue that while the literal scope is precise, the specification shows that the invention's stabilizing principle works across a range of concentrations (e.g., ’328 Patent, col. 2:23-25 showing tests from 0.0001% to 0.05%), supporting an argument that a formulation with an insubstantially different concentration infringes under the doctrine of equivalents.
  • Evidence for a Narrower Interpretation: A defendant will likely argue that the term must be given its plain and ordinary meaning: exactly 0.001%. The specification explicitly states that "Preferably the PVP is present in an amount of 0.001% w/w" (’328 Patent, col. 1:40), which a defendant could argue was a deliberate choice to limit the claim to the preferred embodiment, distinguishing it from the broader ranges tested.

The Term: "comprising"

Context and Importance

This transitional phrase defines whether the claims are "open" (permitting additional, unlisted elements) or "closed." In formulation cases, this is critical because a generic product may contain additional stabilizers or excipients not listed in the patent. The central question is whether the presence of such additional components allows the accused product to escape infringement.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: "Comprising" is a bedrock term in patent law and is consistently interpreted as open-ended, meaning "including but not limited to." The claims use this standard term without any language to suggest a more restrictive meaning.
  • Evidence for a Narrower Interpretation: A defendant may argue that the specification implicitly limits the scope. The statement that "certain HFA formulations comprising formoterol and budesonide together with polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) exhibit excellent physical suspension stability" (’328 Patent, col. 1:25-29) could be used to argue that the invention consists essentially of these components, and the addition of other ingredients that materially affect stability would place a formulation outside the claim's scope.

VI. Other Allegations

Indirect Infringement

The complaint alleges induced infringement, stating that upon approval, Defendants will market their ANDA products with a product label and insert containing instructions for administration (Compl. ¶¶72, 89, 106, 123). The allegation is that by instructing health care professionals and patients to use the product in its intended manner, Defendants will knowingly encourage and induce direct infringement of the patented compositions and methods.

Willful Infringement

The complaint alleges that Defendants had "actual and constructive notice" of the patents before filing their ANDA and have "no reasonable basis" for their assertions of non-infringement and invalidity (Compl. ¶¶73, 90, 107, 124). While not using the word "willful," the complaint alleges the case is "exceptional" and seeks attorneys' fees under 35 U.S.C. § 285, which are the pleadings necessary to support a later claim for enhanced damages based on willful infringement (Compl. ¶¶74, 91, 108, 124).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A core issue will be one of compositional identity: Does the precise formulation contained in Defendants' confidential ANDA—specifically the identity and concentration of its excipients—fall within the literal scope of the numerical values and ranges defined in the asserted claims, or has it been successfully "designed around" the patents?
  • A second central question will be one of patent validity: In light of the extensive prosecution history of this patent family, can Defendants meet their burden of proving by clear and convincing evidence that the claimed formulations were obvious over prior art methods for stabilizing pMDI suspensions?
  • Finally, the case may turn on a question of infringement scope: If literal infringement is not found, will the doctrine of equivalents be available to Plaintiffs to capture a formulation with only insubstantially different excipient concentrations, or will the patents' prosecution history be found to have limited the scope of enforceable equivalents?