DCT

3:22-cv-05830

Neurocrine Biosciences Inc v. Zydus Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:22-cv-05830, D.N.J., 09/30/2022
  • Venue Allegations: Plaintiff alleges venue is proper based on Defendant Zydus Pharmaceuticals being incorporated in New Jersey, Defendant Zydus Healthcare having its principal place of business in New Jersey, and Defendants Zydus Worldwide and Zydus Lifesciences being alien corporations that may be sued in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's INGREZZA® product constitutes infringement of a patent related to high-dosage valbenazine formulations.
  • Technical Context: The technology concerns pharmaceutical compositions that enable high-dose formulations of the drug valbenazine, used for treating neurological disorders like tardive dyskinesia, to be manufactured in reasonably sized capsules for oral administration.
  • Key Procedural History: This lawsuit is the fourth wave of litigation initiated by Neurocrine against Zydus concerning the same ANDA. The complaint follows three previous sets of lawsuits targeting different patents listed in the FDA's Orange Book for INGREZZA®, each filed in response to a separate Paragraph IV notice letter from Zydus. The prior suits, originally filed in both New Jersey and Delaware, were consolidated in the District of Delaware. This action concerns a newly issued patent and a fourth notice letter.

Case Timeline

Date Event
2017-04-11 FDA approves Neurocrine's New Drug Application (NDA) for INGREZZA®
2017-09-21 U.S. Patent No. 11,311,532 Priority Date
2021-06-15 Zydus sends First Paragraph IV Notice Letter to Neurocrine
2021-07-30 Neurocrine files "First Suits" against Zydus on other patents
2021-09-16 Zydus sends Second Paragraph IV Notice Letter to Neurocrine
2021-10-29 Neurocrine files "Second Suits" against Zydus on other patents
2022-02-18 Zydus sends Third Paragraph IV Notice Letter to Neurocrine
2022-04-01 Neurocrine files "Third Suits" against Zydus on other patents
2022-04-26 U.S. Patent No. 11,311,532 Issues
2022-08-17 Zydus sends Fourth Paragraph IV Notice Letter to Neurocrine
2022-09-30 Complaint Filed

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

U.S. Patent No. 11,311,532 - "High Dosage Valbenazine Formulation and Compositions, Methods, and Kits Related Thereto"

  • Issued: April 26, 2022

The Invention Explained

  • Problem Addressed: The patent describes a technical challenge in creating high-dose capsules of valbenazine. The high molecular weight of the active ingredient's ditosylate salt form makes it difficult to create a powder blend with the necessary flow properties for manufacturing, particularly at drug loading levels above 30% (’532 Patent, col. 1:60-col. 2:2). This can prevent the formulation of higher doses in capsules small enough for patients to swallow easily, a concern highlighted by FDA guidance (’532 Patent, col. 2:4-33).
  • The Patented Solution: The patent discloses a specific solid pharmaceutical composition that overcomes these manufacturing hurdles. The solution is a formulation combining valbenazine ditosylate with a particular set of excipients—including silicified microcrystalline cellulose, isomalt, and hydroxypropyl methylcellulose—that together create a blend with suitable properties for encapsulation at high drug loads (’532 Patent, Abstract; col. 12:55-65). A process flow diagram illustrates the manufacturing steps, including blending, roller compaction, and encapsulation, designed to ensure dose uniformity (’532 Patent, Fig. 1).
  • Technical Importance: This formulation enables the production of higher-strength valbenazine capsules (e.g., 80 mg) in a standard size, potentially improving patient compliance and convenience for chronic therapy (’532 Patent, col. 12:2-4).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim of the '532 patent (Compl. ¶52, ¶54). Independent claim 1 is representative of the core composition claims.
  • Independent Claim 1:
    • A solid pharmaceutical composition comprising:
    • A ditosylate salt of valbenazine;
    • at least one water-insoluble filler;
    • at least one water-soluble diluent;
    • at least one binder;
    • at least one disintegrant;
    • at least one lubricant; and
    • wherein the ditosylate salt is present at a level of at least 30% by weight of the solid pharmaceutical composition.
  • The complaint does not specify any asserted dependent claims but alleges infringement of "one or more claims" (’532 Patent, col. 24:36-col. 25:5; Compl. ¶54).

III. The Accused Instrumentality

Product Identification

  • The accused products are Zydus's proposed generic Valbenazine Capsules in 40 mg, 60 mg, and 80 mg dosage forms (Compl. ¶1, ¶44).

Functionality and Market Context

  • The complaint alleges that Zydus has filed ANDA No. 216137 seeking FDA approval to market these capsules, which are described as "generic versions" of Neurocrine's INGREZZA® Capsules (Compl. ¶44). The complaint further alleges that Zydus's generic products are represented to the FDA as "pharmaceutically and therapeutically equivalent" to INGREZZA® (Compl. ¶50). INGREZZA® is approved for the treatment of tardive dyskinesia (Compl. ¶38).

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or specific, element-by-element infringement allegations. The infringement theory is statutory under the Hatch-Waxman Act, where the submission of an ANDA for a product covered by a valid patent is an act of infringement (Compl. ¶52). The central allegation is that the product formulation described in Zydus's confidential ANDA will, if manufactured and sold, meet all the limitations of at least one claim of the '532 patent (Compl. ¶54). The allegation that Zydus's product is "pharmaceutically and therapeutically equivalent" to INGREZZA® supports the inference that its composition is substantially similar to the patented formulation (Compl. ¶50).

No probative visual evidence provided in complaint.

  • Identified Points of Contention:
    • Factual Question: The primary factual dispute will concern the precise composition of Zydus's proposed generic product as detailed in its ANDA. The key question is whether that formulation contains each of the functionally-defined excipients (e.g., a "water-insoluble filler," a "binder") and the minimum drug load (e.g., "at least 30% by weight") required by the asserted patent claims.
    • Scope Questions: A central legal dispute may arise over the proper interpretation of the functional categories of excipients. For example, a question may be whether a single ingredient in Zydus's formulation that performs multiple functions (e.g., as both a filler and a binder) can satisfy two distinct claim limitations.

V. Key Claim Terms for Construction

"solid pharmaceutical composition"

  • Context and Importance: This term, appearing in the preamble of claim 1, could be a focal point of claim construction. Its definition is critical because the patent's background heavily emphasizes that prior art high-dose formulations "were not manufacturable" and could not be successfully encapsulated. Practitioners may focus on this term to determine if it implicitly requires certain physical properties (e.g., flowability, density, compressibility) necessary to solve the patent's stated problem.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The term could be given its plain and ordinary meaning: any solid mixture of the recited ingredients, regardless of its bulk physical properties.
    • Evidence for a Narrower Interpretation: The specification suggests that not all solid mixtures are within the scope of the invention. Example 2 describes a prior art formulation that failed because it was "not possible to compress enough powder into a compact that would fit into a Size 0 capsule shell" (’532 Patent, col. 24:10-13). This may support an argument that a "solid pharmaceutical composition" must possess the manufacturability characteristics that the patent purports to provide.

"at least one water-insoluble filler"

  • Context and Importance: This is one of several functionally-defined excipient limitations in claim 1. Its construction is important because the infringement analysis will depend on whether an ingredient in Zydus's product falls within this category. The outcome could determine whether the claim is infringed.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides a general description of the class, stating the term refers to inert substances added to increase the bulk of the formulation (’532 Patent, col. 21:20-29). This supports an interpretation based purely on the function of an ingredient in the accused product.
    • Evidence for a Narrower Interpretation: Dependent claim 6 and the preferred embodiment in Example 1 both identify "microcrystalline cellulose" as the water-insoluble filler (’532 Patent, col. 25:6-8; Table 2). This could be used to argue that the term should be limited to the specific types of fillers disclosed as being successful, or those with very similar properties.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Zydus will induce infringement by providing a proposed package insert that will instruct healthcare professionals and patients to use the generic product in a manner that directly infringes the patent's method claims (Compl. ¶55, ¶57).
  • Willful Infringement: The complaint does not use the term "willful infringement." However, it alleges Zydus has "actual knowledge" of the '532 patent, citing Zydus's Fourth Notice Letter as evidence (Compl. ¶51). The prayer for relief also seeks a finding that this is an "exceptional case" warranting an award of attorney fees, a remedy often associated with findings of willful infringement (Compl. p. 13, ¶F).

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

  • A central evidentiary question will be one of compositional identity: does the specific formulation of Zydus's proposed generic product, as confidentially described in its ANDA, contain every ingredient type and meet the drug load percentage required by an asserted claim of the '532 patent?
  • A key legal question will be one of claim scope: will the court construe the functional terms for excipients (e.g., "binder," "filler") broadly based on their general purpose, or more narrowly by linking them to the specific embodiments and physical properties the patent describes as essential for solving the technical problem of manufacturing high-dose capsules?
  • A critical issue for the defense will be validity: can Zydus establish by clear and convincing evidence that the claimed combination of well-known pharmaceutical excipients was obvious to a person of ordinary skill in the art seeking to create a high-dosage form of valbenazine?