Novartis Pharma Corp v. HEC Pharm Co Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Novartis Pharmaceuticals Corporation (Delaware)
  • Defendant: Apotex Inc., et al. (Various)
  • Plaintiff’s Counsel: McCarter & English, LLP; Gibson, Dunn & Crutcher LLP
• Case Identification: 1:20-cv-00133, D. Del., 01/28/2020
• Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because each Defendant is, inter alia, incorporated in Delaware, has a regular and established place of business in the district, has committed acts of infringement in the district, and has previously litigated in the district.
• Core Dispute: Plaintiff alleges that Defendants' Abbreviated New Drug Applications (ANDAs) to market generic versions of Plaintiff's multiple sclerosis drug GILENYA® constitute an act of infringement of a patent covering a specific method for administering the drug.
• Technical Context: The technology concerns a therapeutic method for the drug fingolimod that includes specific pre-treatment screening and vaccination steps to improve the drug's safety profile by mitigating the risk of viral infection.
• Key Procedural History: The patent-in-suit was issued on the same day the complaint was filed. The complaint notes that this suit follows extensive, ongoing litigation between the same parties over a related patent (U.S. Patent No. 9,187,405) covering the same drug product, in which the court granted a preliminary injunction against several defendants.

Case Timeline

Date	Event
2009-09-29	U.S. Patent No. 10,543,179 Priority Date
2016-01-22	Apotex and Strides ANDA Notice Letters Sent to Plaintiff
2020-01-28	U.S. Patent No. 10,543,179 Issued
2020-01-28	Complaint Filed

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

• Patent Identification: U.S. Patent No. 10,543,179, "Dosage Regimen of an S1P Receptor Modulator," issued January 28, 2020.

The Invention Explained

• Problem Addressed: The administration of S1P receptor modulators like fingolimod, while effective for treating autoimmune diseases like multiple sclerosis (MS), can induce adverse events, including a transient reduction in heart rate and increased risk of infections (U.S. Patent No. 10,543,179, col. 4:4-14). The patent describes a "significant unmet need for effective new therapies in MS, which limit or reduce the possible adverse events or side effects" (ʼ179 Patent, col. 4:29-34).
• The Patented Solution: The patent discloses a method of treatment designed to improve the safety profile of fingolimod. The method involves specific actions a healthcare provider would take before and during administration of the drug. Specifically, the invention requires testing a patient for a history of varicella zoster virus (VZV, the virus that causes chickenpox) and vaccinating the patient if they are determined to be at risk of infection, prior to administering a 0.5 mg daily oral dose of fingolimod (ʼ179 Patent, Abstract; col. 8:59-64).
• Technical Importance: This regimen allows for the safe administration of an effective therapy by prospectively identifying and mitigating a specific infection risk associated with the drug's mechanism of action, thereby improving the drug's overall risk/benefit profile and patient compliance (ʼ179 Patent, col. 4:48-50, 18:1-6).

Key Claims at a Glance

• The complaint asserts at least independent claim 1 (Compl. ¶140).
• The essential elements of independent claim 1 are:
  • A method for treating relapsing remitting multiple sclerosis in a patient.
  • Identifying a patient at risk of contracting infection caused by varicella zoster virus by testing the patient for a history of infection.
  • Vaccinating the patient at risk.
  • Administering orally fingolimod (or a salt thereof) at a daily dosage of 0.5 mg.
• The complaint does not explicitly reserve the right to assert dependent claims, but the infringement counts refer to "one or more claims of the '179 patent" (Compl. ¶138).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the generic fingolimod 0.5 mg capsules for which each Defendant has filed an ANDA with the U.S. Food and Drug Administration (FDA) (Compl. ¶1).

Functionality and Market Context

The Defendants' ANDA products are intended to be generic versions of Novartis's GILENYA® capsules (Compl. ¶1). As such, they contain the same active ingredient (fingolimod), are administered orally in the same dosage form and strength (0.5 mg capsules), and are intended to be bioequivalent (Compl. ¶136). The complaint alleges that upon approval, the Defendants' products will be marketed for the treatment of relapsing forms of MS with a proposed product label that will be "substantially identical to the GILENYA® label" (Compl. ¶140, ¶149).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

Claim Chart Summary

The complaint alleges that the Defendants' proposed product labels will induce infringement of the '179 patent by instructing physicians and patients to perform the claimed method.

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method for treating relapsing remitting multiple sclerosis... comprising:	The proposed label for the ANDA products will recommend a "0.5 mg orally once-daily" dosage "for the treatment of relapsing forms of multiple sclerosis (MS), to include . . . relapsing-remitting disease."	¶140, ¶149	col. 24:7-9
(a) identifying a patient at risk of contracting infection caused by varicella zoster virus by testing said patient for a history of infection caused by varicella zoster virus,	The proposed label instructs physicians to "[t]est patients for antibodies to varicella zoster virus (VZV) before initiating" treatment.	¶140, ¶149	col. 24:10-14
(b) vaccinating the patient at risk of contracting infection caused by varicella zoster virus, and	The proposed label states that "VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with" the drug.	¶140, ¶149	col. 24:15-16
(c) administering orally fingolimod or a pharmaceutically acceptable salt thereof to said patient at a daily dosage of 0.5 mg...	The proposed label recommends a dosing regimen of "0.5 mg orally once-daily."	¶140, ¶149	col. 24:17-19

Identified Points of Contention

• Scope Questions: A central issue may be whether the language on the Defendants' proposed labels is sufficient to induce infringement of the method claim. Specifically, the analysis may focus on whether a label that "recommends" vaccination for a subset of patients (antibody-negative ones) meets the affirmative claim limitation of "vaccinating the patient."
• Technical Questions: The infringement allegation relies on the theory that physicians, guided by the proposed label, will perform all steps of the claimed method. This raises the evidentiary question of whether the label's instructions make the performance of the complete, multi-step method inevitable for a class of patients, or if a physician could reasonably follow parts of the label (e.g., testing and prescribing) without performing other parts (e.g., vaccinating), thereby avoiding direct infringement.

V. Key Claim Terms for Construction

• The Term: "vaccinating the patient"
• Context and Importance: This term recites an affirmative, active step in the claimed method. The infringement case is based on inducement, and the complaint alleges the accused product label "recommends" this action. The construction of this term is critical because the outcome may depend on whether a "recommendation" on a label is legally sufficient to induce the "vaccinating" step. Practitioners may focus on this term because it represents the potential weak link in the chain of induced infringement.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent's overall objective is to provide a safer dosage regimen. One might argue that the term should be read in light of this purpose, where causing a vaccination to occur (e.g., via a strong recommendation that becomes the standard of care) is encompassed by the term.
  • Evidence for a Narrower Interpretation: The plain language of the claim uses an active verb, "vaccinating," which suggests a direct physical action. The specification describes this step as a direct consequence of a negative serology test: "In case the searched serology is negative, the patient may be vaccinated, e.g. against varicella zoster virus" (ʼ179 Patent, col. 8:62-64). This could support a narrower reading that requires the actual administration of a vaccine, not merely its recommendation.

VI. Other Allegations

• Indirect Infringement: The complaint's primary theory is active inducement of infringement under 35 U.S.C. § 271(b). It alleges that each Defendant, by seeking approval for its ANDA product with a proposed label that instructs users on the patented method, intends to cause physicians and patients to infringe the '179 patent (Compl. ¶143, ¶145, ¶152). The complaint also alleges the ANDA product is not suitable for any substantial non-infringing use, supporting a claim for contributory infringement under § 271(c) (Compl. ¶144, ¶153).
• Willful Infringement: The complaint alleges that upon approval of their ANDAs, Defendants "will have actual knowledge of the '179 patent and will actively induce infringement," and will do so "immediately and imminently upon final approval" (Compl. ¶143, ¶152). This forms the basis for a claim of post-grant, post-filing willful infringement.

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

• A central issue will be one of inducement: Can a product label that "recommends" a medical procedure (vaccination) for a specific patient sub-population be sufficient evidence of the specific intent required to prove inducement of a method claim that recites the affirmative performance of that procedure?
• A related question will be one of claim scope and divided infringement: Does the claim language require that a single actor perform or direct all the steps of the claimed method, and if so, does the generic label's set of instructions and recommendations compel such a unified performance by a treating physician, or does it leave open a commercially significant, non-infringing use where a physician might test but not vaccinate?