DCT
1:25-cv-01330
Novartis Pharma Corp v. Apotex Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Novartis Pharmaceuticals Corporation (Delaware)
- Defendant: Apotex Inc. (Canada) and Apotex Corp. (Delaware)
- Plaintiff’s Counsel: McCarter & English, LLP
- Case Identification: 1:25-cv-01330, D. Del., 10/30/2025
- Venue Allegations: Venue is alleged to be proper as Defendant Apotex Corp. is a Delaware corporation, and Defendant Apotex Inc. is a Canadian corporation subject to personal jurisdiction in the district.
- Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) seeking to market a generic version of the cancer drug Mekinist® constitutes an act of infringement of four patents related to pharmaceutical compositions of trametinib dimethyl sulfoxide.
- Technical Context: The technology concerns specific formulations for an oral anticancer medication designed to ensure chemical stability, consistent bioavailability, and a desirable therapeutic profile.
- Key Procedural History: This litigation was initiated under the Hatch-Waxman Act following a September 17, 2025 notice letter from Apotex to Novartis. In the letter, Apotex stated it had filed ANDA No. 220471 with a Paragraph IV certification, asserting that the patents-in-suit are invalid and/or will not be infringed by its proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2010-12-20 | Priority Date for '304, '706, '941, '021 Patents |
| 2013-11-12 | '304 Patent Issued |
| 2015-10-13 | '706 Patent Issued |
| 2016-03-01 | '941 Patent Issued |
| 2016-07-26 | '021 Patent Issued |
| 2025-09-17 | Apotex sends Notice Letter to Novartis |
| 2025-10-30 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,580,304 - "Pharmaceutical Composition," issued November 12, 2013
The Invention Explained
- Problem Addressed: The patent describes challenges in formulating the active pharmaceutical ingredient trametinib dimethyl sulfoxide solvate (referred to as "Compound A"). These challenges include the compound's tendency to undergo "desolvation"—reverting to a less soluble, unsolvated form ("Compound B")—especially when exposed to moisture during manufacturing, which can lead to inconsistent drug exposure and poor pharmacodynamic properties (ʼ304 Patent, col. 5:23-29, col. 6:54-59). The compound is also described as suffering from photo-instability ('304 Patent, col. 6:1-6).
- The Patented Solution: The patent discloses a solid oral tablet formulation designed to maintain the stability and bioavailability of Compound A. The solution involves formulating the tablet with excipients that are "substantially free of water" to prevent desolvation, thereby ensuring the amount of the less soluble "unsolvated drug" does not exceed a specified threshold ('304 Patent, Abstract; col. 5:45-51). The use of specific film coatings is also described as a way to improve the compound's photo-stability ('304 Patent, col. 6:26-34).
- Technical Importance: This formulation approach enables the creation of a stable, commercially viable oral dosage form for a potent anticancer compound, which is critical for ensuring consistent and safe delivery of the intended therapeutic dose ('304 Patent, col. 5:30-34).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claim 8 (Compl. ¶43).
- Essential elements of independent claim 1 include:
- A pharmaceutical tablet comprising a specific amount of trametinib dimethyl sulfoxide solvate.
- The tablet contains from about 25% to about 89% by weight of one or more excipients.
- The excipients are "substantially free of water."
- The amount of "unsolvated drug" in the tablet does not exceed about 20%.
- The complaint reserves the right to assert additional claims (Compl. ¶50).
U.S. Patent No. 9,155,706 - "Pharmaceutical Composition," issued October 13, 2015
The Invention Explained
- Problem Addressed: The patent addresses the issue of "poor exposure and absorption" of Compound A when administered in vivo, a common problem for pharmaceutically active compounds with low solubility ('706 Patent, col. 5:4-5, col. 5:23-26).
- The Patented Solution: The invention claims a pharmaceutical formulation where the active ingredient is "micronized," meaning its particles are processed to be significantly smaller than their natural state ('706 Patent, col. 35:67-36:3). By reducing the particle size to a specified diameter (e.g., 30 microns or less), the formulation achieves an "acceptable exposure/absorption profile" ('706 Patent, col. 5:6-14). This is because smaller particles have a larger relative surface area, which can increase the dissolution rate and subsequent absorption of a poorly soluble drug.
- Technical Importance: Micronization is a key technique for improving the bioavailability of poorly water-soluble drugs, allowing for effective oral administration and more predictable therapeutic outcomes ('706 Patent, col. 38:64-67).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 8 and 16 (Compl. ¶68).
- Essential elements of independent claim 1 include:
- A pharmaceutical tablet comprising a specific amount of trametinib dimethyl sulfoxide solvate.
- At least 50% of the drug particles have a "particle size of 30 micron or less."
- The complaint reserves the right to assert additional claims (Compl. ¶74).
U.S. Patent No. 9,271,941 - "Pharmaceutical Composition," issued March 1, 2016
Technology Synopsis
This patent claims a pharmaceutical tablet formulation for trametinib dimethyl sulfoxide solvate that combines several features disclosed in the parent patents to ensure stability and bioavailability. The invention addresses the technical challenges of desolvation and poor absorption by requiring a specific combination of: a high percentage of excipients (25% to 89%) that are substantially free of water, and a drug particle size of 30 microns or less for at least 50% of the particles (Compl. ¶87; '941 Patent, Abstract).
Asserted Claims
Independent claim 1 and dependent claim 8 are asserted (Compl. ¶91).
Accused Features
The complaint alleges that Apotex's ANDA Product is a tablet containing the claimed drug that meets the limitations on excipient percentage, water content, and drug particle size (Compl. ¶¶ 92-94).
U.S. Patent No. 9,399,021 - "Pharmaceutical Composition," issued July 26, 2016
Technology Synopsis
This patent focuses on the physical properties of the active drug substance to solve the problem of inconsistent drug exposure. The invention covers a pharmaceutical tablet of trametinib dimethyl sulfoxide solvate where the drug particles are explicitly required to be "micronized" and/or meet a particle size limitation where at least 50% of the particles are 30 microns or less (Compl. ¶110; '021 Patent, Abstract). This is intended to improve the dissolution rate and bioavailability of the poorly soluble compound.
Asserted Claims
Independent claim 1 and dependent claims 8 and 17 are asserted (Compl. ¶115).
Accused Features
Apotex's ANDA Product is alleged to contain drug particles that are "micronized" and meet the claimed particle size distribution (Compl. ¶¶ 117-118).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is "Apotex's ANDA Product," identified as a generic version of Mekinist® (trametinib dimethyl sulfoxide) tablets in 0.5 mg and 2 mg dosages, for which Apotex submitted ANDA No. 220471 to the FDA (Compl. ¶¶ 2-3).
Functionality and Market Context
The product is an anticancer medication indicated for the treatment of certain types of melanoma (Compl. ¶33). The complaint alleges, upon information and belief, that Apotex’s ANDA Product is a pharmaceutical tablet containing trametinib dimethyl sulfoxide solvate formulated in a manner that corresponds to the specific limitations of the asserted patents (Compl. ¶¶ 44-47, 69-71, 92-94, 116-118). The complaint states that the ANDA product is not yet publicly available (Compl. ¶35).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
8,580,304 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate... | Apotex's ANDA Product is a pharmaceutical tablet that contains trametinib dimethyl sulfoxide solvate. | ¶44 | col. 5:10-16 |
| b) the tablet contains from about 25% to about 89% by weight of one or more excipients, where the excipients are substantially free of water; | Apotex's ANDA Product contains from about 25% to about 89% by weight of one or more excipients that are substantially free of water. | ¶45 | col. 22:60-65 |
| and c) the amount of unsolvated drug does not exceed about 20%. | The amount of unsolvated drug in Apotex's ANDA Product does not exceed about 20%. | ¶46 | col. 6:54-64 |
- Identified Points of Contention:
- Scope Questions: The infringement analysis may focus on the construction of terms of degree. A potential question is how the term "about," used in the context of both the excipient percentage ("about 25% to about 89%") and the unsolvated drug limit ("about 20%"), will be interpreted by the court. Similarly, the scope of "substantially free of water" may be contested.
- Technical Questions: As the complaint’s allegations are made "on information and belief," the central technical question is evidentiary. What proof will emerge from discovery of Apotex's confidential ANDA regarding the precise weight percentage of excipients, the actual water content in those excipients and the final product, and the measured amount of desolvated drug under various conditions?
9,155,706 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate... | Apotex's ANDA Product is a pharmaceutical tablet that contains trametinib dimethyl sulfoxide solvate. | ¶69 | col. 5:10-16 |
| b) at least 50% of the drug particles have a particle size of 30 micron or less. | At least 50% of the drug particles in Apotex's ANDA Product have a particle size of 30 microns or less. | ¶70 | col. 5:6-14 |
- Identified Points of Contention:
- Scope Questions: A primary question for claim construction may be how "particle size" is to be measured. The parties may dispute the appropriate analytical technique (e.g., laser diffraction, microscopy), the sample preparation method, and whether the measurement applies to the raw drug substance or the particles as they exist within the final compressed tablet.
- Technical Questions: The infringement determination will depend entirely on the factual results of testing Apotex's product. What evidence does the complaint provide, beyond "information and belief," that the particle size distribution in the ANDA Product actually meets the "at least 50%... 30 micron or less" limitation?
V. Key Claim Terms for Construction
The Term: "substantially free of water" ('304 Patent, Claim 1)
- Context and Importance: This term is critical for the non-obviousness and infringement arguments for the patents focused on formulation stability. Its definition will determine whether Apotex's choice of excipients and manufacturing process falls within the scope of the claims. Practitioners may focus on this term because it is a term of degree whose boundaries are not explicitly defined in the claim itself.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification states that "it is contemplated that the excipient could contain minor amounts of water," suggesting the term does not require absolute dryness ('304 Patent, col. 22:60-62).
- Evidence for a Narrower Interpretation: The specification provides specific, narrowing examples of what "minor amounts" could mean: "for example: about 5% by weight or less, suitably about 2.5% by weight of less, suitably about 1% by weight of less" ('304 Patent, col. 22:62-65). A party could argue these examples limit the reasonable scope of the term.
The Term: "particle size" ('706 Patent, Claim 1)
- Context and Importance: The infringement analysis for the '706, '941, and '021 patents hinges on this term. The outcome of the case for these patents will depend on how particle size is measured and whether the accused product meets the claimed metric. Practitioners may focus on this term because the method of measurement can yield different results and is often a point of contention in pharmaceutical patent cases.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim language itself—"a particle size of 30 micron or less"—is facially broad and does not specify a measurement technique. A patentee may argue it covers any standard industry method that would have been understood by a person of ordinary skill in the art at the time.
- Evidence for a Narrower Interpretation: The patent specification describes a "suitable particle size distribution" with more specific metrics (e.g., X50: 1.0-4.2 µm) and a particular analytical method for determining DMSO content which may inform testing protocols ('706 Patent, col. 36:8-12, Table 11). A defendant might argue that these details implicitly limit how "particle size" should be understood and measured for the purposes of the claims.
VI. Other Allegations
- Indirect Infringement: The complaint alleges active inducement of infringement for all four patents-in-suit. The allegations state that Apotex plans and intends for its ANDA Product to be used in an infringing manner, and that its proposed product labeling will instruct and encourage physicians and patients to administer the infringing tablets, thereby inducing infringement by others (e.g., Compl. ¶¶ 51-52, 75-76). Apotex's alleged knowledge of the patents is based on their listing in the FDA's Orange Book and the statutory requirements of the ANDA filing process (Compl. ¶¶ 40, 52).
- Willful Infringement: While not pleaded as a separate count, the complaint alleges that Apotex had knowledge of the patents-in-suit and, despite this knowledge, has "continued to assert its intent to manufacture, offer for sale, sell, distribute, and/or import" its ANDA product (e.g., Compl. ¶53). The prayer for relief requests a finding that this is an "exceptional case" warranting an award of attorneys' fees pursuant to 35 U.S.C. § 285 (Compl. p. 23, ¶e).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: as the specific formulation of the accused product is detailed in a confidential ANDA filing, the case will likely turn on whether post-discovery factual evidence confirms that Apotex's proposed generic product meets the specific quantitative limitations of the claims related to excipient content, water levels, desolvation rates, and drug particle size distribution.
- A key legal issue will be one of definitional scope: the construction of claim terms of degree, particularly "substantially free of water" and "about," will be critical. The court's interpretation of these terms will set the boundaries for infringement and may determine whether Apotex's formulation, even if chemically similar, is legally equivalent to the patented invention.
- An underlying technical question will be one of measurement methodology: for claims involving "particle size," the case may involve a dispute over the appropriate analytical techniques and standards for measuring this property within a finished drug product, which could lead to conflicting expert testimony on the ultimate question of infringement.