DCT

2:20-cv-17496

TherapeuticsMD Inc v. Teva Pharma USA Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:20-cv-17496, D.N.J., 11/30/2020
  • Venue Allegations: Venue is alleged in the District of New Jersey based on Defendant Teva USA maintaining a principal place of business in Parsippany, New Jersey, and conducting business within the district.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's Imvexxy® product constitutes an act of infringement of two patents related to estradiol pharmaceutical compositions.
  • Technical Context: The technology concerns low-dose, solubilized estradiol formulations for vaginal inserts, designed to treat symptoms of vulvovaginal atrophy associated with menopause.
  • Key Procedural History: The complaint notes that this lawsuit follows three prior, consolidated patent infringement actions between the parties concerning other patents listed in the FDA's Orange Book for the same Imvexxy® product. The complaint states that as of its filing, Defendants had not yet sent a formal notice letter containing a paragraph IV certification for the two patents-in-suit, but alleges that Defendants will submit such certifications to obtain FDA approval.

Case Timeline

Date Event
2012-12-21 Priority Date for ’697 and ’487 Patents
2018-05-29 FDA Approval Date for Plaintiff's Imvexxy® product
2020-10-20 U.S. Patent No. 10,806,697 Issues
2020-11-17 U.S. Patent No. 10,835,487 Issues
2020-11-30 Complaint Filing Date

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

No probative visual evidence provided in complaint.

U.S. Patent No. 10,806,697 - "Vaginal Inserted Estradiol Pharmaceutical Compositions and Methods"

  • Patent Identification: U.S. Patent No. 10,806,697, titled "Vaginal Inserted Estradiol Pharmaceutical Compositions and Methods," issued October 20, 2020 (’697 Patent).

The Invention Explained

  • Problem Addressed: The patent describes that existing estrogen treatments for vulvovaginal atrophy (VVA) present challenges for patient compliance, stemming from issues with the particular form of treatment ('697 Patent, col. 2:5-9).
  • The Patented Solution: The invention is a soft gel vaginal pharmaceutical composition containing solubilized estradiol, which aims to mitigate limitations of other vaginal estradiol forms ('697 Patent, col. 2:10-15). The formulation is designed to ease administration, improve insertion safety, and minimize vaginal discharge by using a solubilizing agent, such as a medium chain oil, to dissolve the estradiol within a soft gelatin capsule ('697 Patent, col. 2:15-21, 2:30-34, Fig. 2).
  • Technical Importance: This approach seeks to provide a more effective and patient-friendly dosage form for local treatment of VVA, thereby potentially improving patient adherence to therapy ('697 Patent, col. 2:15-21).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims without specifying which claims are asserted (Compl. ¶54). Independent claims 1, 9, and 20 are representative composition claims. Claim 9 is analyzed below as it corresponds to one of the dosages of the accused product.
  • Essential elements of Independent Claim 9:
    • An encapsulated liquid pharmaceutical formulation
    • Comprising about 10 µg of 17β-estradiol uniformly dispersed in a solubilizing agent comprising a medium chain oil
    • The medium chain oil comprises at least one C6-C12 fatty acid or a glycol, monoglyceride, diglyceride, or triglyceride ester thereof
    • The formulation is a liquid at room temperature with a specific viscosity range and excludes certain hydrophilic gel-forming bioadhesive agents
    • Administration of the formulation provides specific pharmacokinetic (PK) outcomes, namely a corrected geometric mean peak plasma concentration (Cmax) and area under the curve (AUC) for 17β-estradiol within defined ranges
    • The formulation is encapsulated in a capsule
    • 17β-estradiol is the only active hormone in the formulation
  • The complaint does not explicitly reserve the right to assert dependent claims but makes a general allegation against the patent.

U.S. Patent No. 10,835,487 - "Vaginal Inserted Estradiol Pharmaceutical Compositions and Methods"

  • Patent Identification: U.S. Patent No. 10,835,487, titled "Vaginal Inserted Estradiol Pharmaceutical Compositions and Methods," issued November 17, 2020 (’487 Patent).

The Invention Explained

  • Problem Addressed: As with the ’697 Patent, the background addresses patient compliance issues associated with existing forms of estrogen treatment for VVA (’487 Patent, col. 2:5-9).
  • The Patented Solution: The patent describes a method of treating VVA by administering an intravaginal softgel insert containing estradiol solubilized in a liquid solvent system (’487 Patent, col. 2:10-15, col. 58:8-23). The solvent system is specifically defined as a 9:1 ratio of a C6-C14 fatty acid ester of glycerol to a particular nonionic surfactant, which is intended to produce a specific pharmacokinetic profile upon administration (’487 Patent, col. 58:12-23).
  • Technical Importance: This method claims a specific formulation ratio and resulting PK profile to provide localized treatment for VVA symptoms, aiming to enhance efficacy and patient experience (’487 Patent, col. 2:15-21).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims without specifying which claims are asserted (Compl. ¶69). Independent claim 1 is a representative method claim.
  • Essential elements of Independent Claim 1:
    • A method of treating a female patient with a symptom of VVA
    • The method comprises administering an intravaginal softgel insert
    • The insert comprises 10 mcg of 17β-estradiol as the only active hormone
    • The insert also comprises a liquid solvent system with a specific viscosity, consisting of a 9:1 w/w ratio of (i) C6-C14 fatty acid mono-, di-, or triesters of glycerol to (ii) a nonionic surfactant (PEG-6 stearate, PEG-32 stearate, and ethylene glycol palmitostearate)
    • Administration achieves a specific PK profile (Cmax or AUC) for 17β-estradiol
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • Defendants' proposed generic "Estradiol Vaginal Insert 4 mcg and 10 mcg" product, for which Defendants filed ANDA No. 214137 (Compl. ¶¶18, 51).

Functionality and Market Context

  • The accused product is a generic version of Plaintiff's Imvexxy® and is indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy due to menopause (Compl. ¶¶34, 50).
  • The proposed prescribing information states the product is administered intravaginally (Compl. ¶35). The formulation is alleged to contain inactive ingredients including "medium chain triglycerides, polyethylene glycol, polyethylene glycol stearates," among others (Compl. ¶36).
  • The complaint alleges that Defendant Teva is the "leading generic pharmaceutical company in the United States" and that the ANDA filing is part of its generic products pipeline (Compl. ¶¶6, 8).

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or detailed infringement contentions. The analysis below is based on the complaint's description of the accused ANDA product.

’697 Patent Infringement Allegations

Claim Element (from Independent Claim 9) - Alleged Infringing Functionality - Complaint Citation Patent Citation
An encapsulated liquid pharmaceutical formulation - The accused product is described as a vaginal insert, which is a form of encapsulated formulation (Compl. ¶51).
comprising about 10 µg of 17β-estradiol - The accused product is an Estradiol Vaginal Insert supplied in a 10 mcg dosage (Compl. ¶51). - ¶51 col. 55:20-21
uniformly dispersed in a solubilizing agent comprising a medium chain oil, wherein the medium chain oil comprises at least one C6-C12 fatty acid or a... triglyceride ester thereof The accused product's proposed inactive ingredients include "medium chain triglycerides" (Compl. ¶36), which falls within the patent's description of the claimed solubilizing agent ('697 Patent, col. 10:1-3). ¶36 col. 9:1-12
wherein after a single administration... provides... a corrected geometric mean peak plasma concentration (Cmax) of 17β-estradiol of about 12 pg/ml to about 18 pg/ml; and a corrected geometric mean area under the curve (AUC)0-24 of 17β-estradiol of about 42 pg*hr/ml to about 63 pg*hr/ml The complaint does not provide sufficient detail for analysis of this element. Infringement is alleged on the basis that the ANDA product is a generic equivalent of the patented Imvexxy® product (Compl. ¶50). ¶54 col. 55:30-36
wherein 17β-estradiol is the only active hormone in the encapsulated pharmaceutical formulation - Estradiol is the active ingredient in the accused ANDA product (Compl. ¶18). The complaint does not allege the presence of any other active hormones. - ¶18 col. 55:40-42
  • Identified Points of Contention:
    • Evidentiary Questions: A primary question will be whether Plaintiff can produce evidence that Defendant’s ANDA product meets the specific pharmacokinetic (PK) limitations for Cmax and AUC recited in the claim. The complaint makes a conclusory allegation of infringement but provides no data regarding the PK profile of the accused product.
    • Scope Questions: The construction of the term "about 10 µg" will be relevant. While it appears to read directly on the 10 mcg accused product, its scope will be a question for the court, particularly if there are manufacturing variances.

’487 Patent Infringement Allegations

Claim Element (from Independent Claim 1) - Alleged Infringing Functionality - Complaint Citation Patent Citation
A method of treating a female patient with a symptom of vulvovaginal atrophy, the method comprising administering... an intravaginal softgel insert The proposed prescribing information for the accused product indicates it for treatment of dyspareunia, a symptom of VVA, and instructs for intravaginal administration (Compl. ¶¶34-35). This suggests inducement of the claimed method. ¶¶34-35 col. 58:8-11
the insert comprising: a. 10 mcg of 17β-estradiol, the estradiol being the only active pharmaceutical ingredient - The accused product is available in a 10 mcg dosage, and estradiol is its sole active ingredient (Compl. ¶¶18, 51). - ¶¶18, 51 col. 58:12-14
b. a liquid solvent system... consisting of a 9:1 w/w ratio of (i) one or more C6 to C14 fatty acid mono-, di-, or triesters of glycerol to (ii) a nonionic surfactant consisting of PEG-6 stearate, PEG-32 stearate, and ethylene glycol palmitostearate The complaint does not provide sufficient detail for analysis of this element. It lists "medium chain triglycerides" and "polyethylene glycol stearates" as inactive ingredients but does not specify their ratios (Compl. ¶36). ¶36 col. 58:15-23
wherein after a single administration... the patient achieves at least one of: i. a peak plasma concentration (Cmax)... or ii. a mean area under the curve (AUC)... - The a complaint does not provide sufficient detail for analysis of this element. - ¶69 col. 58:24-32
  • Identified Points of Contention:
    • Technical Questions: A central factual dispute will be whether the formulation of the accused ANDA product meets the highly specific "9:1 w/w ratio" of a glyceride component to a nonionic surfactant component as required by the claim. The complaint's list of inactive ingredients suggests the presence of these types of components but provides no information on their proportions.
    • Evidentiary Questions: As with the ’697 Patent, a key evidentiary question is whether the accused product, when administered according to its label, will achieve the specific PK outcomes recited in the claim.

V. Key Claim Terms for Construction

  • The Term: "a liquid solvent system... consisting of a 9:1 w/w ratio of (i)... glycerol to (ii)... nonionic surfactant" (’487 Patent, Claim 1)
  • Context and Importance: This term is critical because "consisting of" is a closed-ended transition phrase, meaning the solvent system cannot include other components. Practitioners may focus on this term because the infringement analysis will turn on whether Defendant's formulation, which lists numerous inactive ingredients (Compl. ¶36), can be found to have a solvent system containing only the two specified component types in the claimed 9:1 ratio.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent frequently uses the open-ended term "comprising" in other claims and throughout the specification, suggesting that the drafters' choice of the more restrictive "consisting of" in this specific claim was intentional and should be given its narrow meaning.
    • Evidence for a Narrower Interpretation: The plain meaning of "consisting of" strongly supports a narrow interpretation that excludes any other components from the "liquid solvent system." The specification distinguishes between the "solubilizing agent" and other excipients like lubricants or antioxidants, which may support an argument that these other ingredients in the accused product are not part of the claimed "solvent system" itself (’487 Patent, col. 18:31-65).
  • The Term: "a corrected geometric mean peak plasma concentration (Cmax)" and "a corrected geometric mean area under the curve (AUC)" (’697 Patent, Claim 9)
  • Context and Importance: These pharmacokinetic parameters define the patented invention by its clinical result rather than solely by its physical composition. The definition of these terms, including the method for "correcting" the geometric mean (e.g., for baseline levels), will be central to determining whether the accused product infringes.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The detailed description describes multiple clinical studies and presents PK data in various formats, including arithmetic and geometric means, and notes that measurements can be baseline-adjusted (’697 Patent, col. 27:50-28:28, Tables 29-40). A party might argue that any scientifically reasonable method of correction demonstrated in the patent falls within the claim scope.
    • Evidence for a Narrower Interpretation: A party might argue that the term should be limited to the specific statistical methods and correction protocols used to generate the data explicitly presented in the patent's examples that correspond to the claimed PK ranges (’697 Patent, col. 35:1-36:47).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will induce infringement by offering for sale and selling the ANDA product with proposed prescribing information that will instruct physicians and patients to administer the drug in a manner that infringes the asserted method claims (Compl. ¶¶34-35, 70).
  • Willful Infringement: The complaint's prayer for relief seeks a declaration of willful infringement and enhanced damages (Compl. Prayer for Relief ¶¶ G, N). However, the body of the complaint does not allege specific facts to support pre-suit knowledge of the patents-in-suit, noting that the patents issued less than two months before the complaint was filed and that Defendants had not yet sent a paragraph IV certification notice (Compl. ¶¶38, 41, 44).

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

  • A core issue will be one of evidentiary proof: can the Plaintiff demonstrate, likely through expert testimony and analysis of the ANDA filing, that the Defendant's proposed generic product will necessarily meet the specific pharmacokinetic (PK) parameters for Cmax and AUC that are recited as claim limitations in both asserted patents? The complaint itself is silent on this dispositive technical point.
  • A key question of claim scope will be whether the specific formulation of the accused product falls within the narrow limitations of the asserted claims. For the ’487 patent, this centers on the "consisting of a 9:1 w/w ratio" language, which presents a significant hurdle if the accused product contains other components in its solvent system or uses a different ratio.
  • A central procedural question relates to the timing of the lawsuit. By filing suit before receiving a paragraph IV notice letter for the patents-in-suit, the Plaintiff has initiated a declaratory judgment action based on an anticipated, rather than actual, act of infringement under the Hatch-Waxman Act, which may raise jurisdictional questions for the court to resolve.