DCT
1:18-cv-00699
Noven Pharma Inc v. Amneal Pharma LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Noven Pharmaceuticals, Inc. (Delaware)
- Defendant: Amneal Pharmaceuticals LLC (Delaware)
- Plaintiff’s Counsel: Ashby & Geddes; Foley & Lardner LLP
- Case Identification: 1:18-cv-00699, D. Del., 05/08/2018
- Venue Allegations: Venue is alleged to be proper in the District of Delaware based on Defendant Amneal Pharmaceuticals LLC being a Delaware corporation. The complaint further notes Amneal has previously submitted to the jurisdiction of the court in other patent matters.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic estradiol transdermal system constitutes an act of infringement of three patents covering Plaintiff's branded Minivelle® product.
- Technical Context: The technology involves transdermal drug delivery systems, specifically adhesive patches formulated to deliver the hormone estradiol through the skin for treating symptoms associated with menopause.
- Key Procedural History: This is a Hatch-Waxman action initiated in response to Defendant’s ANDA No. 211396 filing, which included a Paragraph IV certification alleging the patents-in-suit are invalid or not infringed. Plaintiff received the Paragraph IV notice letter on or about March 26, 2018, and filed this complaint within the statutory 45-day period, triggering an automatic 30-month stay of FDA approval for the generic product.
Case Timeline
| Date | Event |
|---|---|
| 2008-07-10 | Earliest Priority Date ('’900, '’310, '’419 Patents) |
| 2012-10-29 | FDA Approval of Noven's Minivelle® (NDA No. 203752) |
| 2014-09-23 | FDA Approval of additional Minivelle® dosage strength |
| 2017-08-08 | U.S. Patent No. 9,724,310 Issued |
| 2017-08-15 | U.S. Patent No. 9,730,900 Issued |
| 2017-12-05 | U.S. Patent No. 9,833,419 Issued |
| 2018-03-26 | Noven receives Amneal's Paragraph IV notice letter |
| 2018-05-08 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,730,900 - Transdermal Estrogen Device and Delivery (Issued Aug. 15, 2017)
The Invention Explained
- Problem Addressed: The patent describes a need for smaller transdermal drug delivery systems that do not sacrifice therapeutic efficacy (Compl. ¶28; '900 Patent, col. 1:11-21). Patients generally prefer smaller patches for aesthetic and comfort reasons, but developing a smaller patch that can still deliver the required daily dose of a drug like estrogen is a significant technical challenge (’900 Patent, col. 2:1-9).
- The Patented Solution: The invention is a "monolithic" (single-layer) transdermal patch with a specific formulation that includes a blend of acrylic and silicone adhesives with soluble PVP (’900 Patent, col. 2:10-25). The key insight is that increasing the "coat weight"—the amount of the drug-polymer matrix per unit of surface area—unexpectedly increases the drug "flux," or the rate of delivery through the skin. This allows for a smaller, more concentrated patch to deliver a therapeutic dose comparable to larger, existing patches (’900 Patent, col. 4:56-66).
- Technical Importance: The technology enabled the development of smaller, more patient-friendly estradiol patches that could achieve the same therapeutic delivery rates as larger, less convenient predecessors (’900 Patent, col. 4:56-66).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶43).
- Claim 1 is a method claim with the following essential elements:
- A method for administering estradiol, comprising applying to the skin or mucosa of a subject a monolithic transdermal drug delivery system.
- The system consists of a backing layer and a single adhesive polymer matrix layer.
- The polymer matrix comprises estradiol as the only drug.
- The polymer matrix has a coat weight of "greater than about 10 mg/cm²".
- The polymer matrix includes "greater than 0.156 mg/cm² estradiol".
- The system achieves an estradiol flux "of from about 0.0125 to about 0.05 mg/cm²/day".
- The complaint also alleges infringement of one or more unspecified claims of the patent (Compl. ¶58).
U.S. Patent No. 9,724,310 - Transdermal Estrogen Device and Delivery (Issued Aug. 8, 2017)
The Invention Explained
- Problem Addressed: The patent addresses the same technical problem as the ’900 patent: the need for smaller, more efficient transdermal patches for delivering estrogen (’310 Patent, col. 1:11-21, col. 2:1-9).
- The Patented Solution: The solution is identical to that of the ’900 patent, involving a monolithic patch with a high coat weight and specific polymer formulation to achieve a higher drug flux, thereby enabling a smaller patch size for a given therapeutic dose (’310 Patent, Abstract; col. 4:50-60).
- Technical Importance: As with the ’900 patent, this approach advanced the field by allowing for smaller, more comfortable transdermal systems without compromising the drug delivery rate (’310 Patent, col. 4:50-60).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶43).
- Claim 1 is a system claim with the following essential elements:
- A monolithic transdermal drug delivery system for estradiol, consisting of a backing layer, a single adhesive polymer matrix layer, and an optional release liner.
- The polymer matrix layer comprises estradiol as the only drug.
- The polymer matrix layer has a coat weight of "greater than about 10 mg/cm²".
- The polymer matrix includes "greater than 0.156 mg/cm² estradiol".
- The system achieves an estradiol flux "of from about 0.0125 to about 0.05 mg/cm²/day".
- The complaint suggests that additional, unspecified claims may also be asserted (Compl. ¶70).
Multi-Patent Capsule: U.S. Patent No. 9,833,419
- Patent Identification: U.S. Patent No. 9,833,419, "Transdermal Estrogen Device and Delivery," issued December 5, 2017.
- Technology Synopsis: This patent, part of the same family as the ’900 and ’310 patents, discloses a transdermal system for delivering estrogen that solves the problem of creating smaller, more patient-friendly patches. The invention achieves this through a monolithic patch design with a specific polymer matrix and a higher-than-conventional coat weight, which results in an increased drug delivery rate per unit area (’419 Patent, col. 1:11-21, col. 4:55-65).
- Asserted Claims: At least independent claim 1 (Compl. ¶43).
- Accused Features: The complaint accuses Amneal's proposed generic estradiol transdermal system, as described in its ANDA No. 211396, of infringing the patent (Compl. ¶¶39-40, 76).
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is Defendant Amneal's proposed generic "Estradiol Transdermal System," which is the subject of ANDA No. 211396 ("Amneal's ANDA Product") (Compl. ¶5).
- Functionality and Market Context: Amneal's ANDA Product is a generic version of Noven's Minivelle® product, a transdermal patch for hormone replacement therapy (Compl. ¶5). It is intended for the treatment of moderate to severe vasomotor symptoms (e.g., "hot flashes") and for the prevention of post-menopausal osteoporosis (Compl. ¶25). The complaint alleges that the proposed labeling for Amneal's product is "substantially the same" as the approved labeling for Minivelle® and that it will be administered in the same manner (Compl. ¶¶48-49). The filing of the ANDA itself, seeking FDA approval to market this generic product prior to the expiration of the patents-in-suit, is the statutory act of infringement alleged in the complaint (Compl. ¶42).
IV. Analysis of Infringement Allegations
The complaint alleges that Amneal's ANDA Product, being a generic copy of Noven's Minivelle®, will necessarily meet the limitations of the asserted claims. The patents’ specifications include a graph illustrating the increased estradiol flux of the invention (’900 Patent, FIG. 1). The complaint alleges that the accused ANDA product will achieve a flux rate falling within the patented ranges (Compl. ¶¶50, 64).
'900 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for administering estradiol, comprising applying to the skin or mucosa of a subject in need thereof a monolithic transdermal drug delivery system... | The proposed product labeling for Amneal's ANDA Product will instruct medical personnel and patients to apply the system to the skin. | ¶54 | col. 16:48-50 |
| ...consisting of (i) a backing layer and (ii) a single adhesive polymer matrix layer... | Amneal's ANDA Product is alleged to be a monolithic system with a single adhesive polymer matrix layer and a backing layer, consistent with its status as a generic of Minivelle®. | ¶47, ¶50 | col. 6:40-54 |
| ...comprising an adhesive polymer matrix comprising estradiol as the only drug... | The ANDA Product is an estradiol transdermal system and is alleged to contain estradiol as the sole drug active ingredient. | ¶28, ¶47 | col. 15:52-54 |
| ...wherein the polymer matrix has a coat weight of greater than about 10 mg/cm²... | The ANDA Product is alleged to have the same formulation as Minivelle®, which embodies a coat weight greater than 10 mg/cm². | ¶28, ¶47 | col. 15:55-57 |
| ...and includes greater than 0.156 mg/cm² estradiol... | Amneal's product is alleged to meet this concentration threshold, based on it being a generic copy of the commercial product. | ¶28, ¶47 | col. 15:57-59 |
| ...and the system achieves an estradiol flux of from about 0.0125 to about 0.05 mg/cm²/day... | The ANDA Product is alleged to deliver estradiol at a rate that falls within the claimed flux range. | ¶28, ¶47 | col. 16:1-3 |
'310 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A monolithic transdermal drug delivery system for estradiol, consisting of (i) a backing layer, (ii) a single adhesive polymer matrix layer... | Amneal's ANDA Product is alleged to be a monolithic system that consists of these structural components. | ¶33, ¶64 | col. 6:40-54 |
| ...wherein the single adhesive polymer matrix layer comprises an adhesive polymer matrix comprising estradiol as the only drug... | The ANDA Product's polymer matrix is alleged to contain only estradiol as the active drug. | ¶33, ¶64 | col. 15:47-49 |
| ...wherein the adhesive polymer matrix layer has a coat weight of greater than about 10 mg/cm²... | The ANDA Product is alleged to be manufactured with a coat weight meeting this limitation. | ¶33, ¶64 | col. 15:50-52 |
| ...and includes greater than 0.156 mg/cm² estradiol... | The ANDA Product is alleged to be formulated with an estradiol concentration meeting this limitation. | ¶33, ¶64 | col. 15:52-54 |
| ...and the system achieves an estradiol flux of from about 0.0125 to about 0.05 mg/cm²/day... | The ANDA Product is alleged to provide a drug delivery rate that falls within this specified range. | ¶33, ¶64 | col. 15:54-57 |
- Identified Points of Contention:
- Scope Questions: A central issue may be the interpretation of the word "about" as it modifies the quantitative limitations for coat weight, estradiol concentration, and flux. The scope of "about" will determine whether minor variations in Amneal's formulation fall inside or outside the claims. Another question could relate to the term "monolithic" if Amneal's product contains any structural element that could be argued to function as a distinct layer or rate-controlling membrane.
- Technical Questions: The primary technical dispute will be factual: what are the actual physical and performance characteristics of Amneal's ANDA Product? The complaint's allegations are based on the premise that the ANDA product is a copy of Minivelle®. The case will depend on evidence from the confidential ANDA filing and expert testing to determine if Amneal's product specification for coat weight, drug concentration, and resulting flux literally meets the claimed ranges.
No probative visual evidence provided in complaint.
V. Key Claim Terms for Construction
The Term: "coat weight of greater than about 10 mg/cm²"
Context and Importance: This limitation is the technical core of the asserted invention. The patents teach that, contrary to conventional expectations, increasing the coat weight above a certain threshold increases the drug flux, enabling a smaller patch. Infringement will directly depend on whether Amneal's product meets this quantitative threshold, and how the term "about" is construed.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of "about" indicates the patentee did not intend 10 mg/cm² to be a strict, absolute cutoff (’310 Patent, col. 15:51). The specification also provides examples of embodiments with coat weights of 12.5 mg/cm² and 15 mg/cm², both of which are significantly greater than 10, suggesting the term is not limited to values just above 10 (’310 Patent, col. 15:20-22).
- Evidence for a Narrower Interpretation: A party might argue that "about" should be interpreted narrowly in the context of the specific examples provided. The patent contrasts the invention with prior art like Vivelle-Dot®, which has a specific coat weight, and a defendant could argue "about 10 mg/cm²" should be construed as only a slight, insignificant variation from 10 mg/cm².
The Term: "monolithic"
Context and Importance: This term defines the fundamental structure of the claimed patch. The infringement analysis depends on whether the accused product has a "single adhesive polymer matrix layer" without other rate-controlling structures.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a definition, stating a monolithic system "comprises a single polymer matrix layer comprising a pressure-sensitive adhesive or bioadhesive with drug dissolved or dispersed therein, and no rate-controlling membrane" (’310 Patent, col. 6:50-54). This provides a clear, functional definition that could encompass various formulations.
- Evidence for a Narrower Interpretation: The detailed description primarily focuses on a specific blend of an acrylic adhesive, a silicone adhesive, and soluble PVP (’310 Patent, col. 2:16-19). A defendant could argue that the term "monolithic" should be limited to the types of single-layer structures actually described and enabled in the specification, potentially excluding different polymer blends or structures that might have functionally distinct domains within a single layer.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement, stating that Amneal intends for its product to be used in an infringing manner and that its proposed product labeling will actively instruct medical personnel and patients to perform the steps of the asserted method claims (Compl. ¶¶53-55). It also pleads contributory infringement, alleging Amneal's product is a material part of the invention with no substantial non-infringing use (Compl. ¶¶57, 59).
- Willful Infringement: Willfulness is alleged based on Amneal's pre-suit knowledge of the patents, as evidenced by its Paragraph IV certification (Compl. ¶61). The complaint asserts that Amneal "acted without a reasonable basis for a good faith belief that it would not be liable for infringing" the patents-in-suit (Compl. ¶¶61, 73, 85).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim construction and scope: how broadly will the court interpret the term "about" as applied to the critical numerical limitations for coat weight and drug flux? The outcome of the infringement analysis will likely depend on whether the precise specifications of Amneal's product, as detailed in its confidential ANDA, are found to fall within the patent's claimed ranges.
- The central evidentiary question will be one of technical fact: what are the actual physical characteristics of Amneal's proposed generic product? As the complaint's allegations are premised on the ANDA product being a bioequivalent copy of Minivelle®, the case will turn on a factual comparison between the product described in the ANDA and the limitations recited in the asserted claims.