DCT

2:24-cv-00036

Nivagen Inc v. Sun Pharma Industries Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:24-cv-00036, E.D. Tex., 01/23/2024
  • Venue Allegations: Plaintiff alleges venue is proper in the Eastern District of Texas based on Defendants' maintenance of regular and established places of business in the district, employment of sales personnel in Texas, advertisement for positions located in Dallas, and participation in the Texas Medicare rebate program.
  • Core Dispute: Plaintiff alleges that Defendants’ phenobarbital sodium drug product, Sezaby, infringes patents related to storage-stable lyophilized pharmaceutical compositions and the methods for producing them.
  • Technical Context: The technology relates to pharmaceutical formulations for phenobarbital, an anti-convulsant, focusing on creating a stable, injectable powder (lyophilized) form that avoids the use of organic solvents and minimizes the formation of toxic degradation products.
  • Key Procedural History: The complaint alleges that one or more Defendants anonymously filed a Third Party Submission with ten prior art references during the prosecution of the application leading to the ’598 Patent. It further alleges that the application for the ’598 Patent was cited by the USPTO against a patent application owned by Defendant SPARC, putting Defendants on notice of the technology.

Case Timeline

Date Event
2019-09-20 Priority Date for ’598 and ’076 Patents
2021-08-31 Anonymous Third Party Submission filed in ’598 Patent prosecution
2022-08-09 U.S. Patent No. 11,406,598 Issues
2022-11-17 Accused Product "Sezaby" Receives FDA Approval
2023-07-24 Defendants File Citizen Petition with FDA
2024-01-23 U.S. Patent No. 11,878,076 Issues
2024-01-23 Complaint Filed

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

U.S. Patent No. 11,406,598 - Lyophilized Compositions of Phenobarbital Sodium Salt

  • Issued: August 9, 2022

The Invention Explained

  • Problem Addressed: The patent's background section describes the instability of Phenobarbital Sodium in aqueous solutions, where it readily hydrolyzes to form toxic degradation products, including phenylethylacetylurea (PEAU). It notes that existing liquid formulations often use organic solvents like alcohol, which are undesirable for administration, particularly to newborns. (’598 Patent, col. 1:44-2:33).
  • The Patented Solution: The invention is a specific multi-step method for producing a storage-stable, high-purity, amorphous lyophilized (freeze-dried) powder of Phenobarbital Sodium. The method involves dissolving the drug in water, controlling the pH to a specific range (9.2-10.2), and then subjecting the solution to a precise lyophilization protocol with distinct freezing, primary drying, and secondary drying steps under controlled temperature and vacuum conditions. (’598 Patent, Abstract; col. 10:2-46). This process is designed to yield a stable powder that minimizes impurity formation upon reconstitution. (’598 Patent, col. 3:1-12).
  • Technical Importance: The claimed method aims to produce a pure, stable, injectable form of phenobarbital free from organic solvents, which could enhance its safety profile for vulnerable patient populations. (’598 Patent, col. 2:20-24).

Key Claims at a Glance

  • The complaint asserts at least independent Claim 1 (Compl. ¶62).
  • The essential elements of Claim 1 include:
    • A method of producing a storage-stable form of lyophilized amorphous phenobarbital sodium composition.
    • Adding phenobarbital sodium to water to form a solution with a pH between 9.2 and 10.2, where the solution does not contain an organic solvent.
    • Lyophilizing the solution under a protocol comprising a freezing step, a primary drying step, and a secondary drying step.
    • The freezing step comprises freezing to a temperature of about -50° C. without applying a vacuum.
    • The primary drying step comprises applying a vacuum (50-75 mTorr) at a temperature between about -50° C. and 0° C. for at least 1,000 minutes.
    • The secondary drying step comprises applying a vacuum (50-75 mTorr) at a temperature between about 25° C. and 50° C. for at least 200 minutes.
    • The resulting lyophilized product has an initial moisture content of ≤ 1.5%.
    • The resulting product, upon storage over 3 months, forms no more than 0.2% PEAU when reconstituted.
  • The complaint reserves the right to assert additional claims (Compl. ¶57).

U.S. Patent No. 11,878,076 - Lyophilized Compositions of Phenobarbital Sodium Salt

  • Issued: January 23, 2024

The Invention Explained

  • Problem Addressed: As a continuation of the application for the ’598 Patent, the ’076 patent addresses the same problem of instability and impurity formation in Phenobarbital Sodium formulations. (’076 Patent, col. 1:41-2:42).
  • The Patented Solution: Rather than claiming the manufacturing method, this patent claims the resulting product: a storage-stable pharmaceutical product in a single-use vial. The claims define the product by its key characteristics, including the dose of phenobarbital sodium, its sterile and lyophilized form, its high purity (≥98%), and its stability over time (forming minimal PEAU after storage). (’076 Patent, Abstract; col. 59:26-60:21).
  • Technical Importance: The invention provides a finished drug product with defined characteristics of purity and stability, offering a reliable and potentially safer alternative to traditional liquid formulations. (’076 Patent, col. 2:17-24).

Key Claims at a Glance

  • The complaint asserts at least independent Claims 1 and 7 (Compl. ¶¶23, 71).
  • The essential elements of Claim 1 include:
    • A storage stable pharmaceutical product.
    • Comprising a single use dose vial.
    • And a composition comprising a 65 mg, 100 mg, 130 mg, or 200 mg dose of phenobarbital sodium in the vial.
    • Wherein the composition is sterile and lyophilized.
    • And wherein the composition comprises no less than 98% phenobarbital sodium.
  • The essential elements of Claim 7 include all elements of Claim 1 and add a functional property:
    • The composition has the property that when stored at room temperature for 6 months and then reconstituted with 10 mL of an aqueous solution, the reconstituted composition contains no more than 0.1% PEAU.
  • The complaint reserves the right to assert additional claims, including dependent claims 16 and 17 which specify a 100 mg dose (Compl. ¶¶24, 25, 57).

III. The Accused Instrumentality

Product Identification

  • The accused product is Defendants' "Sezaby" (phenobarbital sodium) for injection, for intravenous use (Compl. ¶¶39, 42).

Functionality and Market Context

  • Sezaby is supplied as a "sterile white to off white lyophilized powder in a 10 mL tubular glass vial" for reconstitution (Compl. ¶44). The product label, excerpted in the complaint, states that each single-dose vial contains 100 mg of phenobarbital sodium (Compl. ¶43). The label also specifies that upon reconstitution, the pH range is 9.20-10.00 and that the product "does not contain benzyl alcohol or propylene glycol" (Compl. ¶44). The complaint provides a screenshot from the Sezaby label showing its dosage and form (Compl. p. 17, Sec. 3). The label identifies Defendant Sun Pharmaceutical Medicare Ltd. as the manufacturer and Defendant Sun Pharmaceutical Industries, Inc. as the distributor (Compl. ¶46).

IV. Analysis of Infringement Allegations

11,406,598 Infringement Allegations

The complaint alleges that Defendants infringe the method claims of the ’598 Patent by manufacturing the Sezaby product (Compl. ¶¶48, 61).

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
adding phenobarbital sodium to water to form a phenobarbital sodium solution having a pH of between 9.2 and 10.2, wherein the phenobarbital sodium solution does not contain an organic solvent... The accused Sezaby product label states that its pH range is 9.20-10.00 and that it "does not contain benzyl alcohol or propylene glycol," which the complaint alleges fulfills this limitation (Compl. ¶44). ¶44 col. 33:12-18
lyophilizing the phenobarbital sodium solution in a container under a protocol comprising a freezing step, a primary drying step, and a secondary drying step... The Sezaby label describes the product as a "lyophilized powder" (Compl. ¶43). The complaint alleges on information and belief that Defendants manufacture Sezaby using a process that meets the claimed lyophilization steps (Compl. ¶48). The screenshot of the Sezaby label identifies it as a lyophilized powder for injection (Compl. p. 17, Sec. 11). ¶¶43, 48 col. 33:19-24
wherein the freezing step comprises freezing...to a temperature of about −50° C. without application of vacuum... The complaint alleges on information and belief that Defendants' manufacturing process for Sezaby includes the claimed freezing step (Compl. ¶48). No direct evidence of the specific manufacturing parameters is provided. ¶48 col. 33:25-28
wherein the primary drying step comprises application of vacuum...at a temperature of between about −50° C. and about 0° C. for at duration of at least 1,000 minutes... The complaint alleges on information and belief that Defendants' manufacturing process for Sezaby includes the claimed primary drying step (Compl. ¶48). No direct evidence of the specific manufacturing parameters is provided. ¶48 col. 33:29-34
wherein the secondary drying step comprises application of vacuum...at a temperature of between about 25° C. and about 50° C. for at duration of at least 200 minutes... The complaint alleges on information and belief that Defendants' manufacturing process for Sezaby includes the claimed secondary drying step (Compl. ¶48). No direct evidence of the specific manufacturing parameters is provided. ¶48 col. 33:35-40
wherein the lyophilized amorphous phenobarbital sodium forms, upon storage over 3 months, no more than 0.2% phenylethylacetylurea (PEAU) when reconstituted in an aqueous solution. The complaint alleges on information and belief that the Sezaby product, upon reconstitution, will contain no more than 0.1% PEAU, which would satisfy the claim's requirement of no more than 0.2% PEAU (Compl. ¶47). ¶47 col. 33:44-48

11,878,076 Infringement Allegations

The complaint alleges that the Sezaby product itself infringes the product claims of the ’076 Patent (Compl. ¶¶47, 70-71).

Claim Element (from Independent Claim 7) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical product, comprising: a single use dose vial... The accused Sezaby product label states it is supplied in a "single-dose vial for reconstitution" (Compl. ¶43). The complaint includes a screenshot from the Sezaby label showing its packaging as "One 100 mg single-dose vial" (Compl. p. 18, Sec. 16.1). ¶¶43, 45 col. 59:65-66
and a composition comprising a 65 mg dose, a 100 mg dose, a 130 mg dose, or a 200 mg dose of phenobarbital sodium, in the single use dose vial... The Sezaby product label states that "Each single-dose vial contains 100 mg of phenobarbital sodium" (Compl. ¶44). This corresponds to one of the doses enumerated in the claim. ¶44 col. 59:67-col. 60:2
wherein the composition is sterile and lyophilized... The Sezaby product label describes it as "sterile white to off white lyophilized powder" (Compl. ¶44). ¶44 col. 60:3-4
wherein the composition comprises no less than 98% phenobarbital sodium... The complaint alleges on information and belief that the Sezaby product will contain no less than 98% phenobarbital sodium (Compl. ¶47). ¶47 col. 60:5-6
and wherein the composition has the property that when the composition is stored at room temperature for 6 months and then reconstituted...the reconstituted composition contains no more than 0.1% phenylethylacetylurea (PEAU). The complaint alleges on information and belief that the Sezaby product, upon reconstitution after storage, will contain no more than 0.1% PEAU (Compl. ¶47). ¶47 col. 60:7-14
  • Identified Points of Contention:
    • Evidentiary Questions (’598 Patent): For the method claims of the ’598 patent, the complaint provides no direct evidence of Defendants' actual manufacturing process. The allegations regarding the specific temperature, pressure, and duration parameters of the lyophilization steps are based on "information and belief." A central issue will be what evidence can be obtained through discovery to demonstrate that Defendants' manufacturing method for Sezaby practices each claimed step.
    • Technical Questions (’076 Patent): For the product claims of the ’076 patent, the infringement allegations for purity (≥98%) and stability (≤0.1% PEAU after 6 months) are also made on "information and belief." The case may turn on the results of analytical testing of the accused Sezaby product to determine if it meets these claimed performance and composition characteristics.

V. Key Claim Terms for Construction

  • The Term: "lyophilized amorphous phenobarbital sodium composition" (’598 Patent, Claim 1)

  • Context and Importance: The distinction between "amorphous" and "crystalline" forms is a central theme of the patent. Practitioners may focus on this term because the patent presents the stability of an amorphous formulation as a surprising and unexpected result, contrary to the conventional wisdom that crystalline forms are more stable. The definition of "amorphous" will be critical to determining the scope of the method claim.

    • Evidence for a Broader Interpretation: The specification broadly defines the invention as an "amorphous lyophilized Phenobarbital Sodium with high stability and purity" (’598 Patent, col. 2:40-42) and suggests the amorphous percentage can range from 20% to 100% (’598 Patent, col. 2:62-66), which could support a construction that does not require a completely non-crystalline structure.
    • Evidence for a Narrower Interpretation: The patent provides X-ray powder diffraction (XRPD) data in Figures 5B and 5C as exemplary of the invention, which show a classic amorphous halo pattern without sharp crystalline peaks. A defendant could argue that "amorphous" should be construed to mean a composition exhibiting such an XRPD pattern, potentially excluding products that are only partially amorphous. (’598 Patent, col. 8:49-54).

  • The Term: "storage stable" (’076 Patent, Claim 1)

  • Context and Importance: This term is the preamble of Claim 1 and is given specific functional meaning in other claims, such as Claim 7, which requires that the product form "no more than 0.1% phenylethylacetylurea (PEAU)" after six months of storage at room temperature. The interpretation of what constitutes "storage stable" will directly impact the infringement analysis.

    • Evidence for a Broader Interpretation: A plaintiff may argue that "storage stable" is a general descriptor and that infringement of Claim 1 does not require meeting the specific stability metrics of dependent claims, but rather a general improvement over the prior art's unstable liquid formulations.
    • Evidence for a Narrower Interpretation: A defendant may argue that the term must be defined by the specific stability data and properties disclosed in the patent. The specification repeatedly links stability to the minimal formation of degradation products like PEAU over time under specific conditions. (’076 Patent, col. 3:26-44). Claim 7 explicitly ties the term to a specific functional outcome (≤0.1% PEAU), which a court may use to define the term's scope for all claims.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges Defendants induced infringement by marketing Sezaby to healthcare practitioners and distributing materials with instructions on how to use the product, which would constitute direct infringement by the end-users (Compl. ¶¶63, 72). It also alleges contributory infringement by providing material parts of the invention not suitable for substantial non-infringing use (Compl. ¶¶64, 73).
  • Willful Infringement: The complaint makes detailed allegations of willful infringement based on pre-suit knowledge. It alleges that Defendants (or their agents) anonymously filed a Third Party Submission against the application for the ’598 Patent on August 31, 2021 (Compl. ¶¶27, 65). To support this, the complaint provides a screenshot from the USPTO website showing that the attorney who filed the submission also represents Defendant SPIL on its own patent matters (Compl. p. 13). The complaint further alleges notice because the application for the ’598 Patent was cited by the USPTO against a patent application owned by Defendant SPARC (Compl. ¶¶51-52, 65).

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

  • A core issue will be one of evidentiary proof for the manufacturing method: Can Plaintiff produce evidence through discovery demonstrating that Defendants’ confidential process for manufacturing Sezaby practices the specific temperature, vacuum, and duration parameters required by the method claims of the ’598 Patent? The complaint's reliance on "information and belief" for these elements makes this a central battleground.
  • A second key question will be one of product performance and composition: Does the commercial Sezaby product meet the quantitative purity (≥98% phenobarbital sodium) and long-term stability (≤0.1% PEAU after 6 months) limitations of the ’076 Patent's product claims? The outcome will likely depend on expert testimony and the results of independent laboratory testing.
  • A third major question relates to willfulness and enhanced damages: The complaint presents specific, documented allegations of Defendants' pre-suit knowledge via their alleged anonymous participation in the patent’s prosecution. A crucial issue for the court will be whether these facts are proven and, if so, whether Defendants' subsequent alleged infringement constitutes the type of egregious conduct that warrants enhanced damages.