DCT

1:18-cv-00193

AstraZeneca Ab v. Mylan Pharma Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00203, N.D. W. Va., 11/12/2019
  • Venue Allegations: Venue is alleged to be proper as to Mylan because it resides and has a regular and established place of business in the district. Venue is alleged to be proper as to 3M because it has consented to venue in West Virginia for the purposes of this litigation.
  • Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market generic versions of the Symbicort® inhaler constitutes an act of infringement of four patents directed to pharmaceutical compositions for inhalation.
  • Technical Context: The technology concerns stable suspension formulations containing the active ingredients budesonide (a corticosteroid) and formoterol (a long-acting beta-agonist) in a hydrofluoroalkane (HFA) propellant for use in pressurized metered-dose inhalers (pMDIs) to treat asthma and COPD.
  • Key Procedural History: This action arises under the Hatch-Waxman Act and was initiated after Defendants filed ANDA No. 211699 seeking FDA approval for generic versions of Symbicort®. The complaint states that Defendants provided Plaintiffs with notice letters including Paragraph IV certifications, which asserted that the patents-in-suit are invalid, unenforceable, and/or would not be infringed by the proposed generic products. This filing is a Third Amended Complaint.

Case Timeline

Date Event
2002-02-01 Earliest Priority Date for all Patents-in-Suit ('328, '239, '137, '247)
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 Defendant 3M submits FDA Form 356h for the ANDA
2018-08-15 FDA sends Paragraph IV Acknowledgment Letter to 3M
2018-08-17 3M allegedly transfers interests in ANDA to Mylan
2018-08-30 Mylan sends First Notice Letter regarding '328, '239, and '137 patents
2019-01-01 U.S. Patent No. 10,166,247 issues
2019-10-11 Mylan sends Second Notice Letter regarding '247 patent
2019-11-12 Third Amended Complaint is 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 identifies stability as one of the most important factors in developing a therapeutically useful pharmaceutical product, particularly for combination drugs like formoterol and budesonide delivered via pressurized metered-dose inhalers (pMDIs), which can require specific excipients ('328 Patent, col. 1:12-24).
  • The Patented Solution: The invention is a specific pharmaceutical composition that claims to achieve "excellent physical suspension stability" by combining the active ingredients formoterol and budesonide with a specific propellant (HFA 227) and two excipients, polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG), at precisely defined concentrations ('328 Patent, Abstract; col. 1:29-36).
  • Technical Importance: The claimed formulation provided a stable liquid suspension for delivering a combination therapy from a pMDI, offering a different delivery mechanism from the existing dry powder inhaler for the same combination of drugs ('328 Patent, col. 1:17-24).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims, with independent claim 1 being central ('328 Patent, Claim 1).
  • Essential elements of independent claim 1 include:
    • A pharmaceutical composition comprising: formoterol fumarate dihydrate, budesonide, 1,1,1,2,3,3,3-heptafluoropropane (HFA227), PVP K25, and PEG-1000.
    • 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.
    • The PEG-1000 is present at a concentration of 0.3% w/w.
  • The complaint’s general infringement allegation suggests a reservation of the right to assert dependent claims (Compl. ¶62).

U.S. Patent No. 8,143,239 - "Composition for Inhalation," Issued March 27, 2012

The Invention Explained

  • Problem Addressed: Like its parent patent, the '239 Patent addresses the technical challenge of ensuring the stability of combination drug formulations intended for pMDI delivery ('239 Patent, col. 1:20-25).
  • The Patented Solution: This invention claims a complete drug delivery system: a pressurized metered-dose inhaler that contains a suspension composition. The composition includes formoterol, budesonide, HFA227, PVP, and PEG. The claims recite specific concentration ranges for the components within the inhaler and specify the exact dosage of the active ingredients delivered upon a single actuation ('239 Patent, Abstract; col. 2:40-52).
  • Technical Importance: This patent extends protection from the formulation itself to the final, patient-facing product—the inhaler device loaded with the stable formulation and characterized by the dose it delivers.

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims, with independent claim 1 being representative ('239 Patent, Claim 1).
  • Essential elements of independent claim 1 include:
    • A pressurized metered dose inhaler containing a suspension composition comprising: formoterol fumarate dihydrate (as particles), budesonide (as particles), HFA227, PVP, and PEG.
    • The budesonide is present 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.
    • The PEG is present at a concentration in the range of 0.05 to 0.5% w/w.
    • An actuation of the inhaler delivers 4.5 µg of formoterol fumarate dihydrate and 40 to 320 µg of budesonide.
  • The complaint’s phrasing implies the right to assert dependent claims is reserved (Compl. ¶79).

U.S. Patent No. 8,575,137 - "Composition for Inhalation," Issued November 5, 2013

Technology Synopsis

Continuing the inventive line, the '137 Patent claims a pharmaceutical suspension composition for inhalation comprising formoterol, budesonide, HFA227, PVP, and PEG. The patent recites specific concentration ranges for these components, which are essential for achieving the desired physical stability for pMDI delivery ('137 Patent, Abstract; col. 2:42-53).

Asserted Claims

The complaint alleges infringement of one or more claims of the '137 patent (Compl. ¶96). The patent includes independent claims 1 and 9.

Accused Features

The complaint alleges that Mylan's ANDA Products, which are generic versions of Symbicort, are pharmaceutical suspension compositions that meet the limitations of the '137 patent’s claims (Compl. ¶¶15, 19, 94).

U.S. Patent No. 10,166,247 - "Composition for Inhalation," Issued January 1, 2019

Technology Synopsis

The '247 Patent claims a stable pharmaceutical suspension composition comprising formoterol, budesonide (or an epimer thereof), HFA227, PVP, and PEG. This patent explicitly introduces the functional limitation of "stable" into the claim itself and defines specific concentration ranges for the components required to achieve this stability ('247 Patent, Abstract; Claim 1).

Asserted Claims

The complaint alleges infringement of one or more claims of the '247 patent (Compl. ¶113). The patent includes independent claim 1.

Accused Features

The complaint alleges that Mylan's ANDA Products are stable pharmaceutical suspension compositions that contain the claimed ingredients at the claimed concentrations, thereby infringing the '247 patent (Compl. ¶¶17, 19, 111).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants' generic versions of Symbicort®, described as "Budesonide and Formoterol Fumarate Dihydrate Inhalation Aerosol" in two dosage forms: 80 mcg/4.5 mcg and 160 mcg/4.5 mcg ("Mylan's ANDA Products") (Compl. ¶¶8, 19).

Functionality and Market Context

The products are pressurized metered-dose inhalers intended for treating asthma and chronic obstructive pulmonary disease (COPD) (Compl. ¶8). The lawsuit was triggered by Defendants' filing of Abbreviated New Drug Application (ANDA) No. 211699, which seeks FDA approval to market these generic products before the expiration of the patents-in-suit (Compl. ¶19). Symbicort® is identified as a prescription drug sold and distributed by Plaintiff AstraZeneca (Compl. ¶¶8, 10).

Visual Evidence

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain claim charts or detailed technical specifications of the accused products. The infringement allegations are based on the premise that the product detailed in ANDA No. 211699 will, if approved and marketed, 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... Mylan's ANDA Products are alleged to be compositions containing these five specific ingredients. ¶11, ¶19, ¶60 col. 7:16-21
...formoterol fumarate dihydrate is present at a concentration of 0.09 mg/ml... The ANDA Products are alleged to contain formoterol at this precise concentration. ¶11, ¶19, ¶60 col. 7:21-22
...budesonide is present at a concentration in the range of 1 mg/ml to 8 mg/ml... The ANDA Products are alleged to contain budesonide at a concentration within this range. ¶11, ¶19, ¶60 col. 7:23-24
...PVP K25 is present at a concentration of 0.001% w/w... The ANDA Products are alleged to contain PVP K25 at this precise concentration. ¶11, ¶19, ¶60 col. 7:25-26
...PEG-1000 is present at a concentration of 0.3% w/w. The ANDA Products are alleged to contain PEG-1000 at this precise concentration. ¶11, ¶19, ¶60 col. 7:27-28

'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)... Mylan's ANDA Products are alleged to be pMDIs containing a suspension with these components. ¶13, ¶19, ¶77 col. 8:51-56
...budesonide is present...at a concentration in the range of 1 mg/ml to 8 mg/ml... The formulation in the ANDA Products is alleged to contain budesonide within this concentration range. ¶13, ¶19, ¶77 col. 8:57-58
...PVP is present at a concentration in the range of 0.001% to 0.01% w/w... The formulation in the ANDA Products is alleged to contain PVP within this concentration range. ¶13, ¶19, ¶77 col. 8:59-60
...an actuation of the inhaler delivers 4.5 µg formoterol fumarate dihydrate and 40 to 320 µg budesonide. As generic versions of Symbicort, the ANDA Products are alleged to deliver these dosages per actuation. ¶8, ¶13, ¶19 col. 8:63-65

Identified Points of Contention

  • Scope Questions: The primary point of contention will be factual: does the precise formulation disclosed in the confidential ANDA fall within the specific concentration values and ranges claimed in the patents? The '328 patent, for example, claims exact percentages for PVP and PEG, leaving no room for deviation in a literal infringement analysis. The later patents claim ranges, raising the question of whether Mylan’s formulation falls inside or outside those boundaries.
  • Technical Questions: The complaint does not provide sufficient detail for analysis of specific technical questions. The central technical question for the court will be a comparison of the ANDA formulation against the claim limitations. For the '247 patent, a key question may be whether the ANDA product meets the patent’s definition of a "stable" composition.

V. Key Claim Terms for Construction

The Term: "a concentration of 0.001% w/w" (from '328 Patent, Claim 1)

  • Context and Importance: This term's construction is critical because it is a precise value, not a range. Practitioners may focus on this term because any measurable deviation in the accused product's formulation, however small, would likely defeat a claim of literal infringement. The case for infringement of this claim may depend entirely on whether the ANDA product contains exactly this amount of PVP K25.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent itself provides no evidence for an interpretation broader than the exact value. A party might argue for a broader interpretation under the doctrine of equivalents, but the claim language itself is precise.
    • Evidence for a Narrower Interpretation: The claim language recites the exact value "0.001% w/w." The specification reinforces the centrality of this value, stating in its experimental section that formulations with 0.001% w/w PVP "gave the best suspension stability overall" and were the "most stable" in tests ('328 Patent, col. 5:23-24, 44-46). This suggests the patentee considered this specific concentration to be a critical and deliberate choice.

The Term: "stable" (from '247 Patent, Claim 1)

  • Context and Importance: This term introduces a functional characteristic into the composition claim. Practitioners may focus on this term because its meaning is not explicitly defined by a numerical value in the claim itself. The dispute will likely center on what standard of stability is required and whether the defendants' product meets that standard.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party could argue that "stable" should be given its plain and ordinary meaning to a person of skill in the art of pharmaceutical formulation, which might encompass any product meeting regulatory requirements for shelf life and dose consistency.
    • Evidence for a Narrower Interpretation: The patent specification provides extensive data from OSCAR and Turbiscan tests and states that certain formulations "were stable for up to 12 months at 25° C./60% RH" ('247 Patent, col. 8:32-33). A party could argue that these examples act as a lexicographical definition, limiting the scope of "stable" to compositions that achieve the level of performance documented in the patent's own experiments.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement, stating that upon approval, Defendants will market their ANDA products with labels and inserts that will instruct both healthcare professionals and end-users to administer the product in a manner that directly infringes the patent claims (Compl. ¶¶ 64, 81, 98, 115).
  • Willful Infringement: The complaint alleges willful infringement based on Defendants having pre-suit knowledge of the patents, as evidenced by their Paragraph IV certifications asserting invalidity and/or non-infringement. It is alleged that Defendants had no reasonable basis for these assertions (Compl. ¶¶ 65-66, 82-83, 99-100, 116).

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

  • A core issue will be one of compositional identity: Will discovery of the confidential ANDA filing reveal that Defendants’ proposed generic product contains every ingredient at the exact concentrations (for the '328 patent) or within the specified ranges (for the other patents) as required by the asserted claims? The outcome of the literal infringement analysis hinges on this factual comparison.
  • A key legal and technical question will be one of claim scope: For the '247 patent, what is the proper construction of the term "stable"? Will the court define it broadly according to its ordinary meaning in the art, or will it be limited to the specific stability performance data and test results disclosed in the patent's specification?
  • A final question will concern the doctrine of equivalents: If Defendants' product is found to have a formulation that deviates slightly from the literal claim language, will Plaintiffs be able to establish infringement under the doctrine of equivalents? This will depend on whether the deviations are insubstantial and whether the patent's prosecution history limits the application of the doctrine.