DCT
2:20-cv-03485
TherapeuticsMD Inc v. Teva Pharma USA Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: TherapeuticsMD, Inc. (Nevada)
- Defendant: Teva Pharmaceuticals USA, Inc. (Delaware) and Teva Pharmaceutical Industries Limited (Israel)
- Plaintiff’s Counsel: Saul Ewing Arnstein & Lehr LLP
- Case Identification: 2:20-cv-03485, D.N.J., 04/01/2020
- Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant Teva USA maintains a principal place of business in Parsippany, New Jersey, and has engaged in business and acts of alleged infringement within the district.
- Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's Imvexxy® (estradiol vaginal inserts) constitutes an act of infringement of five U.S. patents covering the drug's composition and methods of use.
- Technical Context: The technology relates to low-dose, solubilized estradiol formulations in a soft gelatin capsule for treating symptoms of vulvar and vaginal atrophy (VVA) associated with menopause.
- Key Procedural History: The litigation was triggered by a February 18, 2020 notice letter from Teva USA to TherapeuticsMD, informing the latter of Teva's ANDA No. 214137 filing with the FDA, which included Paragraph IV certifications asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by Teva's proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2012-12-21 | Priority Date for ’091, ’382, and ’072 Patents |
| 2015-11-10 | U.S. Patent No. 9,180,091 Issued |
| 2016-03-22 | U.S. Patent No. 9,289,382 Issued |
| 2016-06-10 | Priority Date for ’630 and ’708 Patents |
| 2018-05-29 | Plaintiff's Imvexxy® approved under NDA No. 208564 |
| 2019-04-16 | U.S. Patent No. 10,258,630 Issued |
| 2019-09-03 | U.S. Patent No. 10,398,708 Issued |
| 2019-11-12 | U.S. Patent No. 10,471,072 Issued |
| 2020-02-18 | Defendant Teva USA sends Paragraph IV Notice Letter |
| 2020-04-01 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,180,091 - "Soluble Estradiol Capsule for Vaginal Insertion," Issued November 10, 2015
The Invention Explained
- Problem Addressed: The patent describes issues with prior art treatments for VVA, noting that vaginal creams and gels can be messy and wear off, while compressed tablets may not fully dissolve, and the reusable applicators for both can cause discomfort and present hygienic concerns (’091 Patent, col. 1:44-65).
- The Patented Solution: The invention is a soft gelatin capsule containing estradiol that is fully or substantially solubilized in a lipophilic agent, such as a medium chain oil. This formulation is designed to be inserted vaginally, where the capsule dissolves and releases the solubilized drug for local absorption, aiming to improve patient comfort and compliance (’091 Patent, col. 2:1-12; Abstract).
- Technical Importance: The invention provides a unit-dose, applicator-optional formulation for low-dose, localized hormone therapy that avoids the perceived drawbacks of creams and non-dissolving tablets (Compl. ¶24).
Key Claims at a Glance
- The complaint asserts infringement of one or more unspecified claims (Compl. ¶71). Independent claim 1 is a representative composition claim:
- A vaginal suppository comprising: a) a therapeutically effective amount of estradiol; and b) a solubilizing agent, wherein the solubilizing agent comprises at least one C6-C12 fatty acid or a glycol, monoglyceride, diglyceride, or triglyceride ester thereof;
- wherein estradiol is the only active hormone in the vaginal suppository; and
- wherein the vaginal suppository does not include a hydrophilic gel-forming bioadhesive agent in the solubilizing agent.
U.S. Patent No. 9,289,382 - "Vaginal Inserted Estradiol Pharmaceutical Compositions and Methods," Issued March 22, 2016
The Invention Explained
- Problem Addressed: The patent addresses the need for an effective and convenient method of treating moderate to severe dyspareunia (painful intercourse), a symptom of VVA, while minimizing the problems associated with prior treatments (’382 Patent, col. 1:19-25).
- The Patented Solution: The invention is a method of treatment that involves intravaginally administering a soft gelatin capsule containing a specific liquid pharmaceutical composition. The composition includes a low dose of estradiol (4 µg to 25 µg) and an excipient that increases its viscosity, allowing the formulation to spread over and be absorbed by the vaginal tissue (’382 Patent, Abstract; col. 2:41-52).
- Technical Importance: This patent claims the specific method of using such a formulation to achieve a clinical outcome, potentially protecting not just the product's composition but also its approved regimen for treating dyspareunia (Compl. ¶34).
Key Claims at a Glance
- The complaint asserts infringement of one or more unspecified claims (Compl. ¶88). Independent claim 1 is a representative method of treatment claim:
- A method for treating moderate to severe dyspareunia in a human subject, the method comprising: intravaginally administering estradiol to the subject by inserting a soft gelatin capsule... into the vagina;
- wherein the composition comprises about 4 µg to about 25 µg of estradiol and an excipient that increases the viscosity of the composition;
- wherein the composition has a viscosity from about 50 cP to about 1000 cP at 25° C.; and
- wherein upon insertion into the vaginal tissue, the composition spreads over the vaginal tissue and the estradiol is absorbed by the vaginal tissue.
U.S. Patent No. 10,258,630 - "Vaginal Inserted Estradiol Pharmaceutical Compositions and Methods," Issued April 16, 2019
- Technology Synopsis: This patent claims methods for treating moderate to severe dyspareunia by administering a softgel capsule containing a specified liquid composition of estradiol. The claims focus on achieving specific clinical outcomes, such as an increase in the percentage of vaginal superficial cells and a decrease in vaginal pH within two to six weeks of administration (’630 Patent, col. 137:30-138:8).
- Asserted Claims: The complaint asserts infringement of one or more unspecified claims (Compl. ¶104). Independent claim 1 is representative.
- Accused Features: Defendants' ANDA Product and its proposed method of use for treating dyspareunia are alleged to infringe (Compl. ¶97, ¶102).
U.S. Patent No. 10,398,708 - "Vaginal Inserted Estradiol Pharmaceutical Compositions and Methods," Issued September 3, 2019
- Technology Synopsis: This patent is directed to methods of treating moderate to severe dyspareunia by administering a liquid pharmaceutical composition containing estradiol. The claims specify the composition's viscosity and the dosing regimen (once daily for two weeks and twice weekly thereafter) (’708 Patent, col. 137:30-138:9).
- Asserted Claims: The complaint asserts infringement of one or more unspecified claims (Compl. ¶120). Independent claim 1 is representative.
- Accused Features: Defendants' ANDA Product and its proposed dosing regimen for treating dyspareunia are alleged to infringe (Compl. ¶113, ¶118).
U.S. Patent No. 10,471,072 - "Vaginal Inserted Estradiol Pharmaceutical Compositions and Methods," Issued November 12, 2019
- Technology Synopsis: This patent claims methods for treating vulvovaginal atrophy by inserting a soft gelatin capsule containing a liquid estradiol composition into the lower third of the vagina. The invention is described as providing a treatment that is locally absorbed (’072 Patent, col. 1:63-67; Abstract).
- Asserted Claims: The complaint asserts infringement of one or more unspecified claims (Compl. ¶136). Independent claim 1 is representative.
- Accused Features: Defendants' ANDA Product and its proposed method of administration for treating VVA symptoms are alleged to infringe (Compl. ¶129, ¶134).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Defendants' proposed "Estradiol Vaginal Insert, 4 mcg and 10 mcg," for which Teva submitted ANDA No. 214137 to the FDA (Compl. ¶17, ¶64).
Functionality and Market Context
- The complaint alleges, based on Defendants' proposed prescribing information, that the ANDA Product is intended for the "treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause" (Compl. ¶31, ¶34). The proposed instructions allegedly direct administration "intravaginally" with an initial daily dosage for two weeks, followed by twice-weekly administration (Compl. ¶32). The complaint also lists the inactive ingredients allegedly contained in the ANDA Product, which include "medium chain triglycerides" (Compl. ¶33).
- The ANDA Product is a generic version of Plaintiff’s FDA-approved product, Imvexxy®, and seeks to enter the market for treatments for symptoms of menopause (Compl. ¶63).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
U.S. Patent No. 9,180,091 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a vaginal suppository comprising: a) a therapeutically effective amount of estradiol | Defendants' ANDA Product is an estradiol vaginal insert offered in 4 mcg and 10 mcg dosages for treating VVA. | ¶64; ¶31 | col. 2:1-3 |
| b) a solubilizing agent, wherein the solubilizing agent comprises at least one C6-C12 fatty acid or a glycol, monoglyceride, diglyceride, or triglyceride ester thereof | The proposed prescribing information for Defendants' ANDA Product lists "medium chain triglycerides" as an inactive ingredient. | ¶33 | col. 3:55-63 |
| wherein estradiol is the only active hormone in the vaginal suppository | Estradiol is the sole active pharmaceutical ingredient identified in the allegations regarding Defendants' ANDA product. | ¶31; ¶64 | col. 15:19-22 |
| wherein the vaginal suppository does not include a hydrophilic gel-forming bioadhesive agent in the solubilizing agent | The list of inactive ingredients alleged for Defendants' ANDA product does not contain a hydrophilic gel-forming bioadhesive agent. | ¶33 | col. 15:23-26 |
U.S. Patent No. 9,289,382 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating moderate to severe dyspareunia in a human subject | The proposed prescribing information for Defendants' ANDA Product states it is for the "treatment of moderate to severe dyspareunia." | ¶31 | col. 1:19-25 |
| comprising: intravaginally administering estradiol to the subject by inserting a soft gelatin capsule... into the vagina | The proposed prescribing information instructs users to administer the product "intravaginally; insert with the smaller end up for a depth of about two inches into the vaginal canal." | ¶32 | col. 56:7-13 |
| wherein the composition comprises about 4 µg to about 25 µg of estradiol | Defendants' ANDA Product is formulated in 4 mcg and 10 mcg dosages. | ¶64 | col. 55:61-63 |
| and an excipient that increases the viscosity of the composition, wherein the composition has a viscosity from about 50 cP to about 1000 cP at 25° C. | Infringement is alleged based on the ANDA Product being a generic copy of Plaintiff's Imvexxy®, which embodies the patented invention. | ¶63; ¶80 | col. 55:64-67 |
| wherein upon insertion into the vaginal tissue, the composition spreads over the vaginal tissue and the estradiol is absorbed by the vaginal tissue | Infringement is alleged based on the ANDA Product being a generic copy of Plaintiff's Imvexxy® and its proposed bioequivalence. | ¶63; ¶80 | col. 56:11-13 |
Identified Points of Contention
- Scope Questions: A potential point of contention regarding the '091 patent is whether the term "solubilizing agent" as defined in the patent encompasses the specific combination of inactive ingredients used in Defendants' ANDA Product (Compl. ¶33).
- Technical Questions: For the '382 patent and the other method patents, a central question may be whether use of the ANDA Product according to its proposed label necessarily results in the claimed physical properties (e.g., viscosity) and clinical outcomes. The complaint's allegations are based on the ANDA product being a generic copy, which raises the evidentiary question of how direct infringement of these method limitations will be proven.
V. Key Claim Terms for Construction
The Term: "solubilizing agent" (’091 Patent, Claim 1)
- Context and Importance: This term is foundational to the composition claims. The infringement analysis will depend on whether the specific formulation of Defendants' ANDA product, which allegedly includes "medium chain triglycerides" among other excipients (Compl. ¶33), falls within the scope of this term as construed by the court.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a broad definition, stating the term "refers to an agent or combination of agents that solubilize an active pharmaceutical ingredient" and provides a long, non-exhaustive list of examples, including "medium chain fatty acid esters of glycerol" (’091 Patent, col. 3:55-67).
- Evidence for a Narrower Interpretation: The patent emphasizes that the invention is a "soluble estradiol capsule" and describes specific formulations in its examples that achieve this result (’091 Patent, col. 8:5-25). A party might argue that a "solubilizing agent" must be one that achieves the specific degree of solubilization described in the patent's preferred embodiments.
The Term: "wherein the composition spreads over the vaginal tissue and the estradiol is absorbed by the vaginal tissue" (’382 Patent, Claim 1)
- Context and Importance: This functional language is a key limitation of the asserted method claims. Practitioners may focus on this term because infringement will require a showing that this specific result necessarily occurs when the accused product is used as instructed.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent's detailed description states that the liquid compositions "are more readily absorbed in the vaginal tissue, and also are dispersed over a larger surface area of the vaginal tissue" compared to prior art (’382 Patent, col. 11:59-63), which could support a broad interpretation of any spreading and absorption.
- Evidence for a Narrower Interpretation: The specification includes extensive clinical data and pharmacokinetic profiles that characterize the absorption and effects of the patented invention (’382 Patent, col. 35-58). A party could argue that this claim language should be limited to require the specific spreading and absorption characteristics demonstrated in those studies.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendants will induce infringement by marketing and selling the ANDA Product with proposed labeling that instructs physicians and patients to administer the drug in a manner that directly infringes the method-of-treatment claims (Compl. ¶72, ¶89, ¶105, ¶121, ¶137).
- Willful Infringement: The complaint does not contain a separate count for willful infringement, but the prayer for relief for each of the five patents requests a declaration that Defendants' infringement is "willful" and an award of enhanced damages (Compl., Prayer for Relief ¶G, N, U, BB, II). The basis for this allegation appears to be Defendants' knowledge of the patents-in-suit via their listing in the FDA's Orange Book and the subsequent filing of an ANDA with a Paragraph IV certification.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim construction: can the term "solubilizing agent," as used in the composition patents, be construed to read on the specific combination of inactive ingredients allegedly contained in Defendants' proposed generic product? The outcome of this question will be critical for the infringement analysis of the composition claims.
- A key evidentiary question will be one of inevitable function: for the asserted method-of-treatment claims, what evidence will demonstrate that administering Defendants' product according to its proposed label will necessarily and inevitably result in the specific physical properties (e.g., viscosity, spreading) and clinical outcomes (e.g., treating dyspareunia) recited in the claims?