DCT
1:22-cv-00228
Exelixis Inc v. MSN Laboratories Pvt Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Exelixis, Inc. (Delaware)
- Defendant: MSN Laboratories Private Limited (India) and MSN Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:22-cv-00228, D. Del., 02/23/2022
- Venue Allegations: Venue is alleged to be proper as to MSN Pharmaceuticals, Inc. because it is a Delaware corporation and as to MSN Laboratories Private Limited because it is not a resident of the United States and may be sued in any judicial district.
- Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the cancer drug CABOMETYX® constitutes an act of infringement of three patents covering crystalline malate salt forms of the active ingredient cabozantinib.
- Technical Context: The dispute centers on the specific solid-state chemical form of an active pharmaceutical ingredient, a critical aspect of drug formulation that affects stability, manufacturing, and bioavailability.
- Key Procedural History: The complaint states this is the third lawsuit Plaintiff has filed against Defendants concerning the same ANDA, with prior actions asserting different patents. Defendants are alleged to have sent a Paragraph IV notice letter on January 10, 2022, asserting that the patents-in-suit are invalid, unenforceable, and/or would not be infringed by the proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2009-01-16 | Priority Date for ’439, ’440, and ’015 Patents |
| 2016-01-01 | FDA approval for CABOMETYX® (year only provided) |
| 2019-10-29 | Plaintiff commenced first litigation against Defendant on ANDA No. 213878 |
| 2020-05-11 | Plaintiff commenced second litigation against Defendant on ANDA No. 213878 |
| 2021-08-17 | U.S. Patent No. 11,091,439 Issued |
| 2021-08-17 | U.S. Patent No. 11,091,440 Issued |
| 2021-08-24 | U.S. Patent No. 11,098,015 Issued |
| 2022-01-10 | Defendant's Paragraph IV Notice Letter sent |
| 2022-02-23 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,091,439 - Malate Salt of N-(4-{[6,7-BIS(METHYLOXY) QUINOLIN-4-YL]OXY}PHENYL)-N'-(4-FLUOROPHENYL)CYCLOPROPANE-1,1-DICARBOXAMIDE, AND CRYSTALLINE FORMS THEROF FOR THE TREATMENT OF CANCER
The Invention Explained
- Problem Addressed: The patent acknowledges a known chemical compound, N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (the active ingredient in cabozantinib), as a potent kinase inhibitor for cancer treatment. However, the patent notes that for a compound to be a viable drug, a suitable physical form is required that has desirable properties relating to "processing, manufacturing, storage stability, and/or usefulness as a drug" (’439 Patent, col. 3:19-25).
- The Patented Solution: The patent discloses malate salts of the active ingredient and, more specifically, crystalline and amorphous forms of those salts (’439 Patent, Abstract). These salt forms are described as having suitable properties for use in a pharmaceutical composition, with the patent providing detailed characterization data for two distinct crystalline polymorphs, designated Form N-1 and Form N-2 (’439 Patent, col. 4:33-47; Figs. 1, 8).
- Technical Importance: The creation of a stable, manufacturable, and bioavailable solid salt form is a critical and non-obvious step in transforming a promising active pharmaceutical ingredient into a commercially viable drug product.
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 3 and 4 (Compl. ¶30).
- Independent Claim 1 elements:
- N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide, malate salt,
- wherein said salt is crystalline.
U.S. Patent No. 11,091,440 - Malate Salt of N-(4-{[6,7-BIS(METHYLOXY) QUINOLIN-4-YL]OXY}PHENYL)-N'-(4-FLUOROPHENYL)CYCLOPROPANE-1,1-DICARBOXAMIDE, AND CRYSTALLINE FORMS THEREOF FOR THE TREATMENT OF CANCER
The Invention Explained
- Problem Addressed: The ’440 Patent shares a nearly identical specification with the ’439 Patent and addresses the same technical problem: the need for a pharmaceutically suitable form of the cabozantinib active ingredient (’440 Patent, col. 3:19-25).
- The Patented Solution: The invention claims a pharmaceutical composition that includes the crystalline malate salt of the active ingredient combined with a pharmaceutically acceptable excipient (’440 Patent, Abstract, claim 1). This shifts the focus from the compound itself to the formulated drug product ready for administration to a patient.
- Technical Importance: Patenting a finished pharmaceutical formulation provides a distinct layer of protection beyond the active ingredient itself, covering the drug product as it is actually manufactured and sold.
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claim 3 (Compl. ¶39).
- Independent Claim 1 elements:
- A pharmaceutical composition comprising the N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide, malate salt,
- wherein said salt is crystalline; and
- a pharmaceutically acceptable excipient.
U.S. Patent No. 11,098,015 - Malate Salt of N-(4-{[6,7-BIS(METHYLOXY) QUINOLIN-4-YL]OXY}PHENYL)-N'-(4-FLUOROPHENYL)CYCLOPROPANE-1,1-DICARBOXAMIDE, AND CRYSTALLINE FORMS THEREOF FOR THE TREATMENT OF CANCER
Technology Synopsis
The ’015 Patent addresses the same underlying need for a stable, crystalline salt form of cabozantinib. The invention claimed is a method of using this specific crystalline salt form to treat cancer in a subject (’015 Patent, claim 1).
Asserted Claims
Independent claim 1 and dependent claim 2 are asserted (Compl. ¶48).
Accused Features
The complaint alleges that Defendants' proposed generic product, when used in accordance with its proposed labeling for the treatment of cancer, will infringe the patented method (Compl. ¶¶50-51).
III. The Accused Instrumentality
Product Identification
The "MSN ANDA Product," identified as a generic version of CABOMETYX® (cabozantinib (S)-Malate Tablets) in 20 mg, 40 mg, and 60 mg dosage strengths, for which Defendants have submitted ANDA No. 213878 to the FDA (Compl. ¶¶1, 22).
Functionality and Market Context
The MSN ANDA Product is a tyrosine kinase inhibitor intended for oral administration for the treatment of certain cancers, including kidney, liver, and thyroid cancer (Compl. ¶19). The complaint alleges that by submitting the ANDA, Defendants have represented to the FDA that their product has the same active ingredient, dosage forms, and strengths as CABOMETYX® and is bioequivalent (Compl. ¶23). The filing of the ANDA itself, seeking approval to market this product prior to patent expiry, constitutes the statutory act of infringement under the Hatch-Waxman Act (Compl. ¶30).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not contain a claim chart exhibit. The following summary is based on the narrative allegations.
'439 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide, malate salt... | The MSN ANDA Product contains cabozantinib (S)-malate, which is the same active ingredient as CABOMETYX®. | ¶23 | col. 5:27-44 |
| ...wherein said salt is crystalline. | The complaint alleges that Defendants' submission of ANDA No. 213878 constituted an act of infringement of the asserted claims, which require a crystalline salt. | ¶30 | col. 8:26-32 |
'440 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising the N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide, malate salt, wherein said salt is crystalline... | The MSN ANDA Product is a pharmaceutical composition in tablet form containing cabozantinib (S)-malate, which the complaint alleges will infringe the claims requiring a crystalline salt. | ¶¶22, 23, 39 | col. 14:49-54 |
| ...and a pharmaceutically acceptable excipient. | The MSN ANDA Product is formulated as tablets for oral administration, which necessarily include pharmaceutically acceptable excipients. | ¶22 | col. 15:4-10 |
Identified Points of Contention
- Evidentiary Question: The complaint does not present direct evidence, such as X-ray powder diffraction (XRPD) data, confirming the solid-state form of the active ingredient in Defendants' proposed product. A central question for discovery and trial will be what evidence the ANDA contains regarding the polymorphic form of the cabozantinib malate and whether that form is "crystalline."
- Scope Question: A potential point of contention may be the scope of the term "crystalline." The patents disclose two specific polymorphs, Form N-1 and Form N-2 (’439 Patent, Figs. 1, 8). The infringement analysis may turn on whether Defendants' product contains a crystalline form that falls outside the specific embodiments disclosed but is still within the broader scope of the claims.
- Strategic Question: The complaint alleges that Defendants' Paragraph IV notice letter did not contest infringement of the asserted claims of the '439, '440, and '015 patents, instead focusing on invalidity and unenforceability (Compl. ¶¶29, 38, 47). This raises the question of whether non-infringement will be a primary defense in the litigation or if the case will center primarily on Defendants' invalidity and unenforceability arguments.
V. Key Claim Terms for Construction
- The Term: "crystalline"
- Context and Importance: This term is the central technical limitation in the asserted independent claims of the '439 and '440 patents. Whether Defendants' product meets this limitation will be a dispositive issue for infringement. If the active ingredient in the MSN ANDA Product is amorphous, it may not infringe these claims.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patents do not provide an explicit definition of "crystalline." A party could argue it should be given its ordinary meaning in pharmaceutical science, referring generally to a solid material whose constituents are arranged in a highly ordered microscopic structure. The claims are not drafted to be limited to a specific polymorph.
- Evidence for a Narrower Interpretation: The specifications provide extensive, detailed characterization for two specific crystalline polymorphs, "Form N-1" and "Form N-2," including specific XRPD and solid-state NMR spectral peaks (’439 Patent, col. 8:46-67; col. 9:7-21). A party might argue that the scope of "crystalline" should be understood in the context of these detailed examples, although the lack of explicit limiting language in the claims may counter this argument.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement and contributory infringement for all three asserted patents (Compl. ¶¶31, 40, 49-52). With respect to the '015 method-of-use patent, the complaint specifically alleges that Defendants will induce infringement by encouraging healthcare providers and patients to use the MSN ANDA Product in accordance with its proposed labeling for the treatment of cancer (Compl. ¶51).
- Willful Infringement: The complaint alleges that Defendants acted without a reasonable basis for believing they would not be liable for infringement, based on their knowledge of the patents as evidenced by the submission of their Paragraph IV certification (Compl. ¶¶25, 35, 44, 55). Plaintiff characterizes the case as "exceptional" (Compl. ¶35).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of evidentiary proof: What is the actual solid-state form of the cabozantinib malate active ingredient in the product described in MSN’s ANDA? The case will likely depend on scientific evidence, such as diffraction and spectroscopy data produced during discovery, to determine if the accused product meets the "crystalline" limitation of the claims.
- A key strategic question will be the focus of the defense: Given the complaint’s allegation that MSN’s Paragraph IV letter did not contest infringement, the case may center on MSN’s asserted defenses of invalidity and unenforceability. The strength and nature of these unpleaded defenses will be critical to the litigation's trajectory.
- A central question of claim scope will be the definition of "crystalline": Will the term be construed broadly to encompass any ordered solid form of the malate salt, or will its interpretation be influenced by the specific N-1 and N-2 polymorphs extensively characterized in the patent specifications?