Novartis v. Alkem Laboratories Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Novartis Pharmaceuticals Corporation (Delaware)
  • Defendant: Alkem Laboratories Ltd. (India); S&B Pharma, Inc. (Delaware)
  • Plaintiff’s Counsel: McCarter & English, LLP; Venable LLP
• Case Identification: 1:22-cv-00032, D. Del., 01/07/2022
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant S&B Pharma, Inc. is a Delaware corporation, and Defendant Alkem Laboratories Ltd. is a foreign entity that has allegedly agreed to litigate this patent action in this district.
• Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff's ENTRESTO® (sacubitril/valsartan) tablets constitutes an act of infringement of a patent covering a specific dosage and titration regimen for treating heart failure.
• Technical Context: The technology at issue is a method-of-use patent for a pharmaceutical therapy that combines an angiotensin receptor inhibitor (valsartan) with a neprilysin inhibitor (sacubitril) to treat chronic heart failure with reduced ejection fraction.
• Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following a November 23, 2021 notice letter from Alkem to Novartis, which contained a Paragraph IV certification against the patent-in-suit for ANDA No. 213764. The complaint asserts the patent-in-suit is listed in the FDA's "Orange Book" for ENTRESTO®.

Case Timeline

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

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

• Patent Identification: U.S. Patent No. 11,058,667, "Sacubitril-Valsartan Dosage Regimen for Treating Heart Failure," issued July 13, 2021. (Compl. ¶22; ’667 Patent, p. 1).

The Invention Explained

• Problem Addressed: The patent addresses the need for a safe and effective dosing protocol for initiating treatment with the combination drug LCZ696 (sacubitril/valsartan). Prior clinical trials provided "limited information on how the physician should initiate the LCZ696 therapy in clinical practice," particularly for patients who were either new to such therapies or were previously on low doses of existing drugs like ACE inhibitors or ARBs. (’667 Patent, col. 2:27-33).
• The Patented Solution: The patent discloses a specific multi-step dosage regimen that begins with a low dose of sacubitril/valsartan and gradually increases, or "titrates," the dose upwards over several weeks to a final target maintenance dose. (’667 Patent, col. 3:1-9). This up-titration schedule is designed to allow the target dose to be "safely reached in the large majority of the patients" by managing potential side effects like hypotension and renal dysfunction. (’667 Patent, col. 2:51-54, 5:45-49).
• Technical Importance: The regimen provides a standardized, clinically-tested method to safely administer a novel heart failure drug, improving the likelihood that patients, especially those sensitive to such medications, can achieve and maintain the therapeutically effective target dose. (’667 Patent, col. 2:55-68).

Key Claims at a Glance

• The complaint alleges infringement of "one or more claims," with language closely tracking independent claim 1. (Compl. ¶¶24, 33-34).
• 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/valsartan (corresponding to 97 mg sacubitril/103 mg valsartan).
  • Reaching the target dose via a specific titration schedule: a starting dose of 50 mg (24 mg/26 mg) for "about 3 weeks to about 4 weeks," followed by an intermediate dose of 100 mg (49 mg/51 mg) for "about 3 weeks to about 4 weeks."
  • The regimen is specified for a patient who is either not taking an ACE inhibitor/ARB or is taking a "low dose" of an ACE inhibitor/ARB before starting the regimen.
• The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are the "Alkem ANDA Products," identified as proposed generic sacubitril/valsartan tablets in 24 mg/26 mg, 49 mg/51 mg, and 97 mg/103 mg strengths, corresponding to Novartis's ENTRESTO® tablets. (Compl. ¶¶1, 7).

Functionality and Market Context

• The infringement allegation centers on the proposed use of the Alkem ANDA Products, not merely their composition. The complaint alleges that upon approval, the labeling for Defendants' products "must contain instructions for practicing a regimen for the treatment of chronic heart failure" that will direct physicians and patients to use the tablets in a manner that directly infringes the patented method. (Compl. ¶¶33-34). The product is intended to be a lower-cost generic alternative to ENTRESTO®, which is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure. (Compl. ¶25).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’667 Patent Infringement Allegations

• Identified Points of Contention:
  • Scope Questions: The core dispute will likely concern whether the exact language of the Defendants' proposed product label, once finalized, falls within the scope of the claim limitations. The case will turn on a direct comparison of the label's instructions to the claim's requirements for dose amounts, titration timing, and patient populations.
  • Technical Questions: A key question for the court will be one of "instructional identity": Does the language in the proposed label "instruct" or "encourage" the specific multi-step regimen of Claim 1? A label that provides physicians with discretion or offers alternative titration schedules may raise questions about whether it directs infringement of the specific claimed method.

V. Key Claim Terms for Construction

• The Term: "a low dose of an angiotensin-converting enzyme (ACE) inhibitor or a low dose of an angiotensin II receptor blocker (ARB)"

• Context and Importance: This term defines a key patient sub-population to which the patented regimen applies. The definition of "low dose" is critical for determining the scope of infringement, as it distinguishes this group from patients on higher doses of prior therapies, who may follow a different titration path. Practitioners may focus on this term because the patent's supporting clinical study explicitly stratified patients based on this criterion.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The term is not explicitly defined within independent claim 1, which could support an argument for applying its plain and ordinary meaning as understood by a person of ordinary skill in the art.
  • Evidence for a Narrower Interpretation: The specification, in describing the clinical trial that underpins the invention, provides a specific definition for the "Low RAAS stratum" as patients receiving "≤10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs." (’667 Patent, col. 17:15-18). Furthermore, dependent claim 14 explicitly defines "low dose" as "equivalent to the dose of <10 mg of enalapril per day." (’667 Patent, col. 22:13-16). This provides strong intrinsic evidence for a specific, quantitative limit.

• The Term: "for from about 3 weeks to about 4 weeks"

• Context and Importance: This phrase dictates the duration of the initial and intermediate steps of the titration regimen. The scope of "about" will be central to determining whether a label with slightly different timing instructions is infringing.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The use of "about" and a range ("from 3... to 4") suggests the patentee intended to claim a flexible timeframe, not a rigid, fixed duration for each step.
  • Evidence for a Narrower Interpretation: Dependent claim 2 recites a more specific duration of "for about 3 weeks" for the first titration step and "for about 3 weeks" for the second. (’667 Patent, col. 21:18-23). This may be used to argue that "about 3 weeks" is the preferred embodiment and that the range in the independent claim should not be construed to cover substantially shorter or longer periods. The clinical trial design figure also depicts specific time intervals between dose escalations, which could be used to cabin the meaning of "about." (’667 Patent, FIG. 1).

VI. Other Allegations

• Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b). The factual basis is the allegation that Defendants' product labeling, if approved, "will actively encourage, recommend, or promote this infringement with knowledge of the ’667 patent" and with the intent that medical providers and patients will follow the infringing instructions. (Compl. ¶34).
• Willful Infringement: The complaint does not use the term "willful infringement" but does seek a declaration that the case is "exceptional" pursuant to 35 U.S.C. § 285, which would permit an award of attorney's fees. (Compl. ¶46). The alleged basis for knowledge is, at minimum, the pre-suit notice letter sent by Alkem to Novartis. (Compl. ¶7).

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

• A core issue will be one of instructional infringement: Will the final, FDA-approved product label for Defendants’ generic tablets contain language that directs, encourages, or requires medical professionals and patients to follow the specific, multi-step titration regimen recited in the asserted claims, or will it allow for non-infringing uses?
• A key legal question will be one of claim construction: How will the court define the scope of claim terms such as "low dose" and the durational requirement "for from about 3 weeks to about 4 weeks"? The resolution of these terms will be critical in mapping the language of the accused label onto the patent claims.