DCT

1:21-cv-01760

Novartis Pharma Corp v. Hetero USA Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:21-cv-01760, D. Del., 12/16/2021
  • Venue Allegations: Venue is asserted based on Defendant Hetero USA Inc.’s incorporation in Delaware and on the status of the other defendants as foreign entities who may be sued in any judicial district. The complaint also notes an agreement between the parties to litigate patent actions concerning the at-issue ANDA in the District of Delaware.
  • Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff’s ENTRESTO® (sacubitril/valsartan) tablets constitutes an act of infringement of a patent covering a specific dosage regimen for the drug.
  • Technical Context: The technology concerns a specific method for administering a combination drug therapy (sacubitril/valsartan) used to treat chronic heart failure, a condition with significant mortality and morbidity.
  • Key Procedural History: This lawsuit was initiated under the Hatch-Waxman Act following Defendants’ submission of ANDA No. 213668 to the FDA, which included a Paragraph IV certification against the patent-in-suit. This certification asserts that the patent is invalid, unenforceable, or will not be infringed by the proposed generic product. The complaint was filed within the 45-day window triggered by Novartis’s receipt of Defendants’ notice letter, which may statutorily stay FDA approval of the generic for up to 30 months.

Case Timeline

Date Event
2015-05-11 ’667 Patent Priority Date
2021-07-13 ’667 Patent Issue Date
2021-11-01 Defendants send Notice Letter to Plaintiff regarding ANDA filing
2021-12-16 Complaint Filing Date

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

U.S. Patent No. 11,058,667 - Sacubitril-Valsartan Dosage Regimen for Treating Heart Failure

The Invention Explained

  • Problem Addressed: The patent addresses the clinical challenge of safely initiating treatment with LCZ696 (sacubitril/valsartan), a potent combination therapy for chronic heart failure. The background notes that prior studies provided "limited information on how the physician should initiate the LCZ696 therapy in clinical practice, in particular for those patients who are currently on the low dose of ACEIs or ARBs, or ACEI/ARB-naïve patients" (’667 Patent, col. 3:28-33).
  • The Patented Solution: The patent discloses a specific multi-step dosage "up-titration" regimen designed to solve this problem. The method involves starting patients on a low twice-daily dose (e.g., 50 mg), increasing it to an intermediate dose (e.g., 100 mg) after several weeks, and finally increasing it again to a target therapeutic dose (e.g., 200 mg) (’667 Patent, Abstract; col. 4:16-32). This gradual increase over a period of approximately 6 weeks is designed to allow patients to safely acclimate to the drug and reach the effective target dose (’667 Patent, col. 3:55-65).
  • Technical Importance: The claimed regimen provides a standardized, clinically-tested protocol intended to improve safety and tolerability (e.g., mitigating risks of hypotension and renal dysfunction) when initiating this novel heart failure therapy in a vulnerable patient population (’667 Patent, col. 5:45-49).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" without specifying which ones, but provides language that tracks independent claim 1 (Compl. ¶29, 39).
  • Essential elements of independent claim 1 include:
    • A regimen for treating chronic heart failure with reduced ejection fraction.
    • Administering a twice-daily target dose of 200 mg of sacubitril and valsartan in a 1:1 molar ratio.
    • Reaching that target dose after a specific titration process.
    • The titration begins with a twice-daily starting dose of 50 mg for about 3 to 4 weeks.
    • This is followed by a twice-daily dose of 100 mg for about 3 to 4 weeks.
    • The regimen is for a human patient who is either not taking, or is taking a "low dose" of, an ACE inhibitor or ARB before starting the treatment.
  • The complaint does not explicitly reserve the right to assert dependent claims, but the general allegation of infringing "one or more claims" leaves this possibility open (Compl. ¶38).

III. The Accused Instrumentality

Product Identification

Defendants’ generic sacubitril/valsartan tablets in 24 mg/26 mg, 49 mg/51 mg, and 97 mg/103 mg dosages, for which approval is sought in ANDA No. 213668 ("Hetero ANDA Products") (Compl. ¶1, 9).

Functionality and Market Context

  • The Hetero ANDA Products are generic versions of Novartis’s branded drug, ENTRESTO®, and are intended to be therapeutically equivalent (Compl. ¶1). The core of the infringement allegation is not the composition of the tablets themselves, but the instructions for their use that will be included in the product's labeling upon FDA approval (Compl. ¶38-39).
  • The complaint alleges that these instructions will direct physicians and patients to practice the patented dosage regimen for treating chronic heart failure with reduced ejection fraction (Compl. ¶39). The product is positioned to compete directly with ENTRESTO® in the significant market for heart failure treatments (Compl. ¶1).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that the use of the Hetero ANDA Products, in accordance with the instructions that will be provided on their label, will directly infringe the ’667 Patent, and that Defendants will induce and contribute to that infringement (Compl. ¶38-40).

’667 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A regimen for treating chronic heart failure with reduced ejection fraction, which comprises administering to a human patient in need thereof a twice-daily target dose of 200 mg of sacubitril or a pharmaceutically acceptable salt thereof with valsartan or a pharmaceutically acceptable salt thereof... Defendants' product is intended to be labeled for use in a regimen for treating chronic heart failure with reduced ejection fraction, including administration of a 200 mg target dose. ¶29, 39 col. 4:16-21
wherein the twice daily target dose 200 mg is reached after a titration with a twice daily starting dose of 50 mg of sacubitril...and valsartan...for from about 3 weeks to about 4 weeks, The proposed product label allegedly contains instructions to reach the target dose via a titration that begins with a twice-daily 50 mg starting dose. ¶29, 39 col. 4:22-26
followed by a twice daily dose of 100 mg of sacubitril...and valsartan...for from about 3 weeks to about 4 weeks, followed by the twice daily target dose of 200 mg thereafter; The proposed product label allegedly instructs a subsequent titration step using a twice-daily 100 mg dose before reaching the 200 mg target dose. ¶29, 39 col. 4:26-30
and wherein: (i) the twice daily starting dose of 50 mg is for use in a human patient neither taking an angiotensin-converting enzyme (ACE) inhibitor nor taking an angiotensin II receptor blocker (ARB) before initiating treatment...or (ii) the twice daily starting dose of 50 mg is for use in a human patient taking a low dose of an...ACE inhibitor or...ARB before initiating treatment... The proposed product label allegedly instructs initiating the regimen in patients who are not on, or are on a low dose of, a prior ACE inhibitor or ARB. ¶29, 39 col. 4:30-32; col. 21:1-17

Identified Points of Contention

  • Scope Questions: A central question will be whether Defendants’ proposed product label requires administration according to the specific multi-step titration schedule of claim 1, or if it allows for physician discretion that could result in a non-infringing administration schedule. The scope of "about 3 weeks to about 4 weeks" for each titration step may be disputed.
  • Technical Questions: The dispute will likely focus on the content of the proposed label. What evidence does the complaint provide that the label will contain instructions that map directly onto every element of the claim, including the specific patient population defined as being on a "low dose" of a prior ACE inhibitor/ARB?

V. Key Claim Terms for Construction

"a regimen for treating chronic heart failure with reduced ejection fraction"

  • Context and Importance: This preamble language defines the specific medical context of the invention. Practitioners may focus on this term because if the Defendants’ proposed label includes multiple approved uses, the infringement analysis may depend on whether this specific use is instructed in a manner that meets the claim limitations.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent repeatedly describes the invention in the general context of treating "heart failure" or "chronic heart failure" (’667 Patent, col. 3:1-5; col. 4:16-17).
    • Evidence for a Narrower Interpretation: The claim language itself, along with the detailed description of the TITRATION clinical trial, specifically targets patients with "systolic dysfunction" and a "reduced left ventricular ejection fraction (LVEF) of ≤35%" (’667 Patent, col. 6:9-11; col. 16:44-46), suggesting the regimen is intended for this specific sub-population of heart failure patients.

"low dose"

  • Context and Importance: This term is critical for defining the patient population to whom the titration regimen applies. The infringement analysis for patients already on related therapies will hinge on whether their prior dosage qualifies as "low."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The term itself could be argued to encompass a range of dosages that a clinician would consider low in practice, not limited to a specific numerical cutoff.
    • Evidence for a Narrower Interpretation: The patent specification explicitly provides a quantitative definition, stating that a lower dose "is equivalent to <10 mg of enalapril per day" (’667 Patent, col. 5:42-44). Dependent claim 7 further recites that the low dose "is equivalent to a dose of ≤10 mg of enalapril per day" (’667 Patent, col. 21:13-17), providing strong evidence for a narrow, numerically-defined construction.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges both induced and contributory infringement.
    • Inducement is alleged on the basis that Defendants, with knowledge of the ’667 Patent, will market the Hetero ANDA Products with labeling that instructs and encourages physicians and patients to perform the patented method of administration (Compl. ¶39). Defendants' knowledge is established by their Paragraph IV certification and notice letter (Compl. ¶9).
    • Contributory infringement is alleged on the grounds that the Hetero ANDA Products are "especially made or especially adapted for use in infringing" the patent and are "not suitable for substantial non-infringing use" (Compl. ¶40-41).

Willful Infringement

  • The complaint does not use the word "willful" but requests a declaration that the case is "exceptional" pursuant to 35 U.S.C. § 285 and seeks an award of attorney's fees (Compl. ¶51). The basis for this allegation is Defendants’ alleged knowledge of the patent at the time of their ANDA filing and their subsequent actions to seek FDA approval for a product whose labeled use will allegedly infringe (Compl. ¶9, 39).

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

  • A core issue will be one of instructional equivalence: Does the language in Hetero's proposed product label, which is central to the inducement claim, map precisely onto the specific, multi-step titration sequence and patient population criteria required by Claim 1? Any deviation or allowance for clinical discretion in the label could form the basis of a non-infringement defense.
  • A key question will be one of claim scope and definition: The case will likely turn on the construction of key claim terms, particularly whether the definition of a "low dose" of a prior therapy is limited to the specific quantitative equivalent of enalapril mentioned in the patent's specification and dependent claims.