DCT

3:20-cv-14933

TherapeuticsMD Inc v. Amneal Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:20-cv-14933, D.N.J., 10/23/2020
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendants have their principal places of business in Bridgewater, New Jersey, and conduct continuous business in the state, including the development and preparation of generic drug applications.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff’s BIJUVA® drug product constitutes an act of infringement of a patent covering combination hormone replacement formulations.
  • Technical Context: The technology relates to oral pharmaceutical formulations for hormone replacement therapy (HRT) that combine bio-identical estradiol and progesterone to treat symptoms of menopause.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 214293 to the FDA. Plaintiff received a Paragraph IV Notice Letter from Defendants regarding a family of related patents no earlier than March 17, 2020. The patent-in-suit was issued on October 20, 2020, and this complaint was filed three days later.

Case Timeline

Date Event
2012-06-18 ’740 Patent Priority Date
2020-03-17 Plaintiff received Defendants' first Paragraph IV Notice Letter (no earlier than)
2020-07-17 Plaintiff received Defendants' second Paragraph IV Notice Letter (no earlier than)
2020-10-20 ’740 Patent Issue Date
2020-10-23 Complaint Filing Date

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

U.S. Patent No. 10,806,740 - "Natural Combination Hormone Replacement Formulations and Therapies"

  • Patent Identification: U.S. Patent No. 10,806,740, "Natural Combination Hormone Replacement Formulations and Therapies", issued October 20, 2020.

The Invention Explained

  • Problem Addressed: The patent's background section notes the lack of an FDA-approved product that combines bio-identical estradiol and bio-identical progesterone for hormone replacement therapy (HRT) (’740 Patent, col. 1:30-39). Existing therapies often used estrogens derived from non-human sources (e.g., mare's urine) or synthetic progestins, which differ chemically from the hormones naturally produced in the human body (’740 Patent, col. 2:1-10).
  • The Patented Solution: The invention provides a pharmaceutical formulation for co-administering bio-identical estradiol and progesterone in a single oral dosage form. The formulation uses a medium chain oil (such as a C6-C12 fatty acid ester) as a carrier that solubilizes the estradiol while keeping the progesterone in a suspended state (’740 Patent, Abstract; col. 2:40-47). This approach is designed to deliver a "natural" HRT option in a stable and effective combination product.
  • Technical Importance: The formulation provides a commercially viable method for combining two chemically distinct and naturally occurring hormones into a single oral dose, addressing an unmet need in the HRT market for bio-identical combination therapies (’740 Patent, col. 1:30-39).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’740 Patent (Compl. ¶35). Independent claim 1 is representative.
  • Essential elements of independent claim 1 include:
    • A pharmaceutical formulation for administering estradiol and progesterone.
    • The formulation contains 17β-estradiol, with at least about 80% being solubilized.
    • The formulation contains suspended progesterone.
    • It includes a solubilizing agent comprising a medium chain oil (predominantly esters of C6 to C12 fatty acids).
    • It includes a surfactant (lauroyl macrogol-32 glycerides or similar) present from 0.01 wt % to 10 wt %, where the oil-to-surfactant ratio is 8:1 or greater.
    • When administered to a female subject, the formulation produces specific pharmacokinetic (PK) profiles for either progesterone or estradiol.
  • The complaint does not explicitly reserve the right to assert dependent claims, but the general allegation of infringing "one or more claims" preserves this option.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendants’ proposed generic version of TherapeuticsMD Inc’s BIJUVA® drug product, which is the subject of ANDA No. 214293 ("Amneal's Proposed Product") (Compl. ¶1).

Functionality and Market Context

  • Amneal’s Proposed Product is identified as a 1 mg/100 mg estradiol/progesterone capsule (Compl. ¶26).
  • The proposed product label will indicate its use for treating moderate to severe vasomotor symptoms due to menopause in women with a uterus, directly mirroring the indication for the branded BIJUVA® product (Compl. ¶¶7, 28). The filing of the ANDA is an explicit attempt to enter the market with a generic equivalent before the expiration of the ’740 Patent (Compl. ¶1).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint provides a notice pleading of infringement, as is common in ANDA litigation, without a detailed element-by-element analysis. The infringement theory is that because Amneal's Proposed Product is a generic copy of BIJUVA®, it will necessarily meet the limitations of the patent claims covering the BIJUVA® formulation.

’740 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical formulation for administering estradiol and progesterone to a female subject in need thereof... Amneal's Proposed Product is a capsule containing 1 mg of estradiol and 100 mg of progesterone for treating menopausal symptoms. ¶¶1, 26, 28 col. 2:40-44
comprising: 17β-estradiol, wherein at least about 80% of the estradiol in the formulation is solubilized; Amneal's Proposed Product, as a bioequivalent generic, is alleged to contain solubilized 17β-estradiol in its formulation. ¶¶8, 35 col. 4:51-53
suspended progesterone; Amneal's Proposed Product is alleged to contain progesterone in a suspended, rather than fully dissolved, state. ¶¶8, 35 col. 2:45-46
a solubilizing agent comprising a medium chain oil ... wherein the fatty acid esters are predominantly esters of C6 to C12 fatty acids; Amneal's Proposed Product is alleged to use a medium chain oil as a carrier, consistent with the formulation of the reference drug product. ¶¶8, 35 col. 8:65-9:14
a surfactant comprising at least one of lauroyl macrogol-32 glycerides ... wherein the surfactant is present in the formulation in an amount from 0.01 wt % to 10 wt % and the ratio of the medium chain oil to the surfactant is 8:1 or greater; Amneal's Proposed Product is alleged to contain a surfactant within the claimed chemical class, concentration, and ratio relative to the oil. ¶¶8, 35 col. 15:46-col. 16:2
and wherein when administered to a female subject, the formulation produces: (a) one or more progesterone-related pharmacokinetic parameters...or (b) one or more estradiol-related pharmacokinetic parameters... As part of its ANDA, Amneal's Proposed Product must demonstrate bioequivalence, which requires it to produce pharmacokinetic profiles that allegedly fall within the claimed ranges. ¶¶1, 35 col. 4:14-34
  • Identified Points of Contention:
    • Scope Questions: A central dispute may be whether the term "suspended progesterone," which is not explicitly defined with particle size limitations in the claim, should be interpreted more narrowly in light of the specification's repeated focus on "micronized progesterone" (’740 Patent, col. 8:22; FIG. 4). Another question is how the "at least about 80%... solubilized" estradiol limitation is to be measured and proven.
    • Technical Questions: A key evidentiary question will be whether Amneal’s formulation factually meets the compositional and ratio limitations of claim 1, particularly the specific class of surfactant and the required oil-to-surfactant ratio of 8:1 or greater. Further, the court will have to determine if the pharmacokinetic data submitted in Amneal’s ANDA demonstrates that its product will, upon administration, produce the specific AUC and Cmax values required by the final "wherein" clauses of the claim.

V. Key Claim Terms for Construction

  • The Term: "suspended progesterone"

  • Context and Importance: The physical state of the progesterone is a core element of the claimed formulation, distinguishing it from the "solubilized" estradiol. Whether this term is construed broadly (i.e., simply not dissolved) or narrowly (i.e., implying specific characteristics of the suspension) will be critical to the infringement analysis.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: Claim 1 uses the general term "suspended progesterone" without any modifiers related to particle size or method of suspension, which may support a construction that covers any formulation where the progesterone is not fully dissolved in the oil carrier (’740 Patent, col. 45:39).
    • Evidence for a Narrower Interpretation: The specification repeatedly describes the progesterone as "micronized" and provides detailed particle size data (’740 Patent, col. 11:35-43). The patent also contrasts "suspended" with "partially solubilized" and "fully solubilized" progesterone formulations, suggesting "suspended" implies a specific state that may be linked to the micronized embodiments described as preferred (’740 Patent, col. 10:20-25).

  • The Term: "wherein when administered to a female subject, the formulation produces..." [specific pharmacokinetic parameters]

  • Context and Importance: This "wherein" clause defines the invention by its functional results (pharmacokinetic performance) rather than solely by its structure. The entire infringement case could depend on whether Amneal's product is shown to produce these precise PK outcomes, making the interpretation of these ranges and the conditions under which they are measured paramount.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party might argue that if a product meets the structural limitations of the claim, infringement of the PK limitations should be presumed, especially in an ANDA context where bioequivalence is the goal. The patent presents these PK values as an inherent property of the claimed formulation (’740 Patent, col. 4:14-34).
    • Evidence for a Narrower Interpretation: A party could argue this is a strict, limiting clause that must be proven independently of the structural elements. The patent dedicates significant space to PK data from clinical studies (e.g., ’740 Patent, Tables 29-35), suggesting these values are not merely descriptive but are essential, defining features of the invention that must be strictly met by an accused product.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement, stating that upon approval, Amneal will "intentionally encourage acts of direct infringement" with knowledge of the patent (Compl. ¶38). This is likely based on the proposed product labeling that will instruct physicians and patients to use the product in an infringing manner. The complaint also alleges contributory infringement, asserting the product is especially adapted for an infringing use and has no substantial non-infringing use (Compl. ¶39).
  • Willful Infringement: The complaint does not include a specific count for willful infringement. However, it does allege the case is "exceptional" and seeks an award of attorneys' fees pursuant to 35 U.S.C. § 285 (Compl. ¶42).

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

  • A core issue will be one of claim construction and scope: can the term "suspended progesterone" in the claims be limited by the specification's extensive discussion of "micronized progesterone," or will it be given its plain and ordinary meaning? The resolution of this question will directly impact the scope of the patent and the evidence required to prove infringement.
  • A second key issue will be one of evidentiary proof for functional limitations: will infringement be determined primarily by comparing the chemical composition of Amneal's product to the claim elements, or will the case turn on a detailed battle of experts over whether Amneal's product, when administered, is proven to generate the specific pharmacokinetic (PK) profiles recited in the claims?