DCT

3:18-cv-16399

AstraZeneca Pharma LP v. Alkem Laboratories Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:18-cv-16399, D.N.J., 11/21/2018
  • Venue Allegations: Venue is alleged to be proper because the defendant is a foreign corporation not resident in the United States.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the COPD drug DALIRESP® constitutes an act of infringement of three patents directed to high-purity compositions of the active ingredient, roflumilast.
  • Technical Context: The technology concerns pharmaceutical process chemistry, specifically methods for manufacturing an active pharmaceutical ingredient (roflumilast) that achieve a high level of purity and minimize a specific, difficult-to-remove impurity.
  • Key Procedural History: This is a Hatch-Waxman action initiated in response to Defendant's Paragraph IV certification. The complaint discloses that the patents-in-suit have been the subject of previous, settled litigation against other generic pharmaceutical manufacturers, suggesting a history of enforcement for this patent portfolio.

Case Timeline

Date Event
2003-03-10 Priority Date for '206, '064, and '142 Patents
2011-02-28 FDA approval of DALIRESP® (NDA No. 022522)
2013-09-17 U.S. Patent No. 8,536,206 Issued
2013-12-10 U.S. Patent No. 8,604,064 Issued
2013-12-31 U.S. Patent No. 8,618,142 Issued
2016-04-29 AstraZeneca AB received ownership of the DALIRESP® NDA
2018-08-28 Date on or before which Alkem submitted ANDA No. 212490
2018-10-09 Alkem sent Paragraph IV Notice Letter to Plaintiffs
2018-11-21 Complaint Filed

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

U.S. Patent No. 8,536,206 - "PROCESS FOR THE PREPARATION OF ROFLUMILAST", Issued September 17, 2013

The Invention Explained

  • Problem Addressed: The patent describes that prior art processes for preparing the drug roflumilast were unsuitable for industrial-scale manufacturing because they resulted in significant levels (over 3% by weight) of a specific by-product, N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-hydroxybenzamide, which could not be effectively removed through standard purification techniques like recrystallization (’206 Patent, col. 2:20-32).
  • The Patented Solution: The invention is a process for preparing roflumilast that "surprisingly" avoids the formation of the problematic by-product. This is achieved by reacting an activated derivative of a benzoic acid precursor with a significant excess of the anion of 4-amino-3,5-dichloropyridine, a counterintuitive step that substantially averts by-product formation and yields high-purity roflumilast (’206 Patent, Abstract; col. 2:33-40). The resulting claims are not for the process itself, but for methods of treating diseases using the high-purity roflumilast produced by such a process.
  • Technical Importance: This process enables the large-scale manufacture of roflumilast with a purity of at least 99% and containing less than 0.1% of the key impurity, which is critical for producing a safe and effective pharmaceutical active ingredient suitable for regulatory approval (’206 Patent, col. 4:30-34, 4:46-51).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" without specification (Compl. ¶39). The asserted independent claims are likely method of treatment claims defined by the purity of the administered roflumilast, such as independent claim 6.
  • Independent Claim 6 recites:
    • A method for the treatment of chronic obstructive pulmonary disease,
    • comprising: administering to a patient suffering from chronic obstructive pulmonary disease,
    • a therapeutically effective amount of roflumilast having a purity of greater than or equal to 99% by weight,
    • and N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-hydroxybenzamide present (relative to roflumilast) in an amount greater than zero and less than 0.1% by weight.
  • The complaint reserves the right to assert other claims, including dependent claims (Compl. ¶39).

U.S. Patent No. 8,604,064 - "PROCESS FOR THE PREPARATION OF ROFLUMILAST", Issued December 10, 2013

The Invention Explained

  • Problem Addressed: As a continuation of the same application leading to the '206 Patent, this patent addresses the identical technical problem: the need for an industrial-scale process to produce roflumilast free from significant levels of the 4-hydroxybenzamide impurity (’064 Patent, col. 2:25-35).
  • The Patented Solution: The patent discloses the same solution as the ’206 Patent, which involves using an excess of one reactant to suppress impurity formation and thereby achieve high product purity (’064 Patent, col. 2:36-45). The claims in this patent are directed to methods of treatment for a broader set of airway disorders and to the compositions themselves, defined by the specific purity profile.
  • Technical Importance: The technical importance is identical to that of the ’206 Patent: enabling the manufacture of roflumilast at a purity level suitable for pharmaceutical use (’064 Patent, col. 4:51-54).

Key Claims at a Glance

  • The complaint generally asserts infringement of "one or more claims" (Compl. ¶50). A representative independent claim is Claim 1.
  • Independent Claim 1 recites:
    • A method for the treatment of an acute or chronic airway disorder
    • comprising: administering to a patient suffering from an acute or chronic airway disorder, a therapeutically effective amount of
    • roflumilast having a purity of greater than or equal to 99% by weight,
    • and N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-hydroxybenzamide present (relative to roflumilast) in an amount greater than zero and less than 0.1% by weight.
  • The complaint reserves the right to assert other claims (Compl. ¶50).

U.S. Patent No. 8,618,142 - "PROCESS FOR THE PREPARATION OF ROFLUMILAST", Issued December 31, 2013

  • Technology Synopsis: This patent is a member of the same family as the '206 and '064 patents and is directed to the same core technology. It solves the problem of producing high-purity roflumilast by disclosing a process that minimizes a key impurity. The patent claims compositions and pharmaceutical dosage forms of roflumilast that are defined by this specific purity profile, namely ≥99% purity and an impurity level of less than 0.1% (’142 Patent, Abstract; col. 8:20-26).
  • Asserted Claims: The complaint generally asserts "one or more claims" (Compl. ¶61). The patent includes independent claims to compositions (Claim 1), pharmaceutical compositions (Claim 4), dosage forms (Claim 7), and specific tablets (Claim 17).
  • Accused Features: The complaint alleges that Alkem's generic roflumilast tablets, as described in its ANDA, will necessarily be manufactured to a purity level that meets the limitations of the asserted claims (Compl. ¶¶60-61).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendant Alkem's generic roflumilast 500 mcg tablets, as described in its Abbreviated New Drug Application (ANDA) No. 212490 filed with the FDA (Compl. ¶¶31, 37).

Functionality and Market Context

The product is a generic version of Plaintiffs' branded drug, DALIRESP®, and is intended to be bioequivalent (Compl. ¶31). The proposed labeling for Alkem's product indicates its use for treating severe Chronic Obstructive Pulmonary Disease (COPD), the same indication as DALIRESP® (Compl. ¶32). The filing of the ANDA with a Paragraph IV certification, seeking to market a generic version prior to the expiration of the patents-in-suit, constitutes the act of infringement under 35 U.S.C. § 271(e)(2) that triggered this lawsuit (Compl. ¶¶33-34, 43).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint. The infringement theory is based on the chemical composition of the accused product, which is not depicted visually.

'206 Patent Infringement Allegations

Claim Element (from Independent Claim 6) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for the treatment of chronic obstructive pulmonary disease... Alkem's proposed labeling for its ANDA product specifies its use as a treatment to reduce the risk of COPD exacerbation. ¶32 col. 7:21-27
comprising: administering to a patient suffering from chronic obstructive pulmonary disease... The complaint alleges that if Alkem's ANDA is approved, the product will be administered to patients for the treatment of COPD. ¶39 col. 7:21-27
a therapeutically effective amount of roflumilast having a purity of greater than or equal to 99% by weight, The complaint alleges that the manufacture, use, or sale of Alkem's product would infringe, which requires that the roflumilast active ingredient meets this purity level. ¶38 col. 8:6-8
and N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-hydroxybenzamide present (relative to roflumilast) in an amount greater than zero and less than 0.1% by weight. The infringement allegation requires that Alkem's product, as a result of its manufacturing process, contains this specific impurity within the claimed range. ¶38 col. 8:6-8

'064 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for the treatment of an acute or chronic airway disorder... Alkem's product is indicated for the treatment of COPD, which is a chronic airway disorder. ¶¶32, 50 col. 7:40-45
comprising administering to a patient suffering from an acute or chronic airway disorder... The complaint alleges that if its ANDA is approved, Alkem's product will be administered to patients for this purpose. ¶50 col. 7:40-45
a therapeutically effective amount of roflumilast having a purity of greater than or equal to 99% by weight, The complaint alleges that the manufacture of Alkem's product would infringe, which necessitates that the active ingredient meets this purity threshold. ¶49 col. 8:46-48
and N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-hydroxybenzamide present (relative to roflumilast) in an amount greater than zero and less than 0.1% by weight. The infringement allegation requires that Alkem's product contains this specific impurity within the claimed range. ¶49 col. 8:46-52

Identified Points of Contention

  • Evidentiary Question: The central issue for infringement will be factual and evidentiary. Does the roflumilast active pharmaceutical ingredient in Alkem's ANDA batch actually meet the specific purity and impurity profiles recited in the claims (i.e., ≥99% purity and <0.1% of the specified hydroxybenzamide impurity)? The complaint alleges this on information and belief, but the case will depend on chemical analysis produced during discovery.
  • Legal Question (Validity): Alkem’s non-infringement and/or invalidity defense may question the patentability of claims defined by a purity profile. A key question for the court could be whether the claimed purity profile is itself novel and non-obvious over prior art roflumilast, or if the claims are impermissibly attempting to patent a known product by way of a new process.

V. Key Claim Terms for Construction

The claims are defined by numerical thresholds, which typically do not require extensive construction. However, the nature of the claims raises strategic questions around the central defining limitation.

The Term

"roflumilast having a purity of greater than or equal to 99% by weight"

Context and Importance

This limitation, along with the corresponding impurity limit, forms the entire basis of the patents' alleged novelty and is the central point of the infringement allegation. The dispute will turn on whether Alkem's product meets this quantitative standard. Practitioners may focus on this term to frame validity challenges, questioning whether this purity level was inherently present in prior art roflumilast, even if not explicitly measured or disclosed.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: A party could argue that the plain language of the claim defines the invention by its resulting characteristics (the purity profile), regardless of the process used to achieve it. The claim language itself contains no process limitations, suggesting any roflumilast meeting the purity standard infringes (’206 Patent, col. 8:6-8).
  • Evidence for a Narrower Interpretation: A party could argue the term's patentable weight is inextricably linked to the novel process described in the specification. The patent repeatedly emphasizes that it was the "surprising" discovery of a specific process (using an excess of the amine anion) that enabled this purity level, which prior art processes could not achieve (’206 Patent, col. 2:33-50). This context may be used to argue that the patentability of the product-by-process style claim rests on the novelty of that underlying process.

VI. Other Allegations

Indirect Infringement

The complaint alleges active inducement of infringement against all three patents. The factual basis is that Alkem, with knowledge of the patents, intends to sell its generic product with labeling that will inevitably instruct and encourage physicians and patients to administer the drug in a manner that directly infringes the patented methods of treatment (Compl. ¶¶ 39-40, 50-51, 61-62).

Willful Infringement

While the complaint does not use the word "willful," it alleges that this is an "exceptional case" and seeks attorneys' fees under 35 U.S.C. § 285 (Compl. ¶¶ 44, 55, 66). This allegation is based on Alkem's alleged knowledge of the patents, evidenced by its Paragraph IV certification and notice letter sent to Plaintiffs on October 9, 2018, prior to the filing of the lawsuit (Compl. ¶33).

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

The resolution of this case will likely depend on the answers to two central questions:

  • A core issue will be one of evidentiary fact: does the chemical composition of Alkem's generic roflumilast, as specified in its ANDA, actually meet the quantitative purity (≥99%) and impurity (<0.1%) thresholds defined in the asserted claims? The case's outcome on infringement hinges on this yet-to-be-seen technical evidence.
  • A second key issue will be one of claim validity: are the asserted claims, which define the invention by a specific purity profile, patentably distinct from prior art roflumilast? The court may need to decide whether the claims are valid based on the novelty of the purity profile itself, or if they are impermissible attempts to claim a known product through a new manufacturing process.