DCT
1:20-cv-00633
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; Wilmer Cutler Pickering Hale and Dorr LLP
- Case Identification: 1:20-cv-00633, D. Del., 05/11/2020
- Venue Allegations: Venue is alleged to be proper for MSN Pharmaceuticals, Inc. as it is a Delaware corporation. For MSN Laboratories Private Limited, an Indian corporation, venue is alleged to be proper on the basis that 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 two U.S. patents.
- Technical Context: The technology involves chemical compounds known as tyrosine kinase inhibitors, specifically cabozantinib, used in targeted cancer therapies.
- Key Procedural History: The complaint notes this is the second lawsuit Exelixis has filed against MSN concerning this ANDA. A prior suit, filed in October 2019, involves a different patent (U.S. Patent No. 8,877,776). The current action arises from MSN’s Paragraph IV certification alleging that the two patents-in-suit are invalid and/or would not be infringed.
Case Timeline
| Date | Event |
|---|---|
| 2004-06-04 | Earliest Priority Date for '473 and '284 Patents |
| 2009-08-25 | '473 Patent Issue Date |
| 2013-07-30 | '284 Patent Issue Date |
| 2016-01-01 | CABOMETYX® (cabozantinib) FDA Approval Year |
| 2019-10-29 | Exelixis commences first litigation against MSN regarding ANDA No. 213878 |
| 2020-05-04 | Date of MSN's Paragraph IV Notice Letter |
| 2020-05-11 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,579,473 - "C-Met Modulators and Methods of Use", issued August 25, 2009
The Invention Explained
- Problem Addressed: The patent identifies a need for improved therapeutic agents for treating cancer ('473 Patent, col. 2:38-42). It highlights that the activity of protein kinases—enzymes that regulate cellular pathways controlling growth and proliferation—is frequently abnormal in cancer cells. Specifically, it notes that the c-Met receptor tyrosine kinase is an attractive target for developing small-molecule anti-cancer drugs due to its role in tumor growth ('473 Patent, col. 2:42-67).
- The Patented Solution: The invention provides a class of chemical compounds, including specific quinolines and quinazolines, designed to modulate (primarily inhibit) the activity of kinases like c-Met ('473 Patent, Abstract). By inhibiting these specific enzymes, the compounds aim to disrupt the cellular signaling that drives cancer progression, thereby treating diseases associated with unregulated cellular activity ('473 Patent, col. 6:21-26).
- Technical Importance: The invention describes targeted therapies that aim to inhibit specific molecular pathways involved in cancer, representing a more precise approach than conventional, non-specific chemotherapies ('473 Patent, col. 2:56-62).
Key Claims at a Glance
- The complaint asserts claims 1-7 (Compl. ¶29). The lead independent claim is Claim 1.
- Independent Claim 1 recites:
- A compound according to the chemical structure of formula XIVa, or a pharmaceutically acceptable salt thereof.
- Wherein the substituent Q is C(H).
- Wherein the substituent R³⁰ is halo.
- Wherein the substituent R⁵⁰ is halo.
- Wherein the substituent R²⁰ is an unsubstituted C₁₋₄alkyl group.
U.S. Patent No. 8,497,284 - "C-Met Modulators and Methods of Use", issued July 30, 2013
The Invention Explained
- Problem Addressed: Similar to its parent '473 patent, the '284 Patent addresses the need for improved cancer treatments by targeting the abnormal activity of protein kinases like c-Met, which are implicated in cell proliferation and survival ('284 Patent, col. 2:32-53).
- The Patented Solution: Rather than claiming a broad class of compounds, this patent claims specific methods of using a particular compound—N-(4-{[6,7-bis(methoxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (cabozantinib)—to treat various cancers ('284 Patent, col. 403:20-404:20). The invention is the application of this specific chemical entity for a therapeutic purpose.
- Technical Importance: The patent links a specific chemical compound to a defined therapeutic utility, claiming the right to use that compound to treat cancers such as kidney, liver, breast, and colon cancer, thereby providing the basis for its use as an approved pharmaceutical product ('284 Patent, col. 404:7-20).
Key Claims at a Glance
- The complaint asserts claims 1-2, 8, 12, 18, 22, and 23 (Compl. ¶38). The lead independent claims are 1, 22, and 23.
- Independent Claim 1 recites:
- A method of treating a disease or disorder, wherein the disease or disorder is cancer.
- The method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound with the specific chemical structure of cabozantinib, or a pharmaceutically acceptable salt thereof.
- Independent Claim 22 recites:
- A method of treating a disease or disorder by administering a therapeutically effective amount of cabozantinib (or a salt thereof) or a composition containing it.
- Wherein the disease or disorder is specified as liver cancer, pancreatic cancer, gastrointestinal cancer, fallopian tube cancer, hematologic cancer, or skin cancer.
- Independent Claim 23 recites:
- A method of treating a disease or disorder by administering a therapeutically effective amount of cabozantinib (or a salt thereof) or a composition containing it.
- Wherein the disease or disorder is specified as kidney cancer, breast cancer, or colon cancer.
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is 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 MSN submitted ANDA No. 213878 to the FDA (Compl. ¶¶1, 21).
- Functionality and Market Context: The complaint alleges that by filing its ANDA, MSN has represented to the FDA that its generic product has the same active ingredient, dosage forms, and strengths as CABOMETYX®, and that it is bioequivalent to CABOMETYX® (Compl. ¶22). CABOMETYX® is a tyrosine kinase inhibitor approved for treating advanced renal cell carcinoma and hepatocellular carcinoma (Compl. ¶19). The filing of the ANDA is the statutory act of infringement alleged in the complaint, which seeks to prevent MSN from launching its generic product before the expiration of the patents-in-suit (Compl. ¶¶1, 29, 38).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
'473 Patent Infringement Allegations
The complaint alleges that infringement is not contested by MSN, only validity (Compl. ¶28). The infringement theory is based on the statutory act of filing an ANDA for a drug containing the patented compound.
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A compound according to formula XIVa... or a pharmaceutically acceptable salt thereof... | The MSN ANDA Product is alleged to contain cabozantinib, which is a compound that falls within the scope of formula XIVa, or a pharmaceutically acceptable salt thereof. | ¶¶22, 29 | col. 411:10-23 |
| wherein... Q is C(H); R³⁰ is halo; R⁵⁰ is halo; and R²⁰ is an unsubstituted C₁₋₄alkyl group | The specific chemical structure of the active ingredient cabozantinib in the MSN ANDA Product is alleged to satisfy these substituent requirements of the claimed formula. | ¶¶22, 29 | col. 411:24-27 |
'284 Patent Infringement Allegations
The complaint alleges that infringement of the asserted claims is not contested, only validity (Compl. ¶37). The infringement theory is based on inducement, whereby MSN's proposed label for its ANDA product will instruct medical professionals and patients to use the drug for the patented methods.
| Claim Element (from Independent Claim 23) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating a disease or disorder... wherein the disease or disorder is kidney cancer... | MSN's proposed label for its ANDA Product will allegedly instruct users to administer the product for the treatment of kidney cancer, an approved indication for CABOMETYX®. | ¶¶19, 41 | col. 406:17-20 |
| comprising administering to a mammal in need of the treatment a therapeutically effective amount... | MSN's proposed product is formulated in 20, 40, and 60 mg tablets, which are alleged to be therapeutically effective amounts, and the proposed label will instruct their administration. | ¶¶21, 41 | col. 406:10-12 |
| ...of a compound having the following structure: [cabozantinib structure] or a pharmaceutically acceptable salt thereof... | The active ingredient in the MSN ANDA Product is alleged to be the cabozantinib compound recited in the claim, or a pharmaceutically acceptable salt thereof. | ¶22 | col. 405:15-30 |
Identified Points of Contention
- Validity vs. Infringement: The complaint repeatedly states that MSN's notice letter did not contest infringement of the asserted claims, but instead challenged their validity (Compl. ¶¶28, 37). This suggests the primary legal battle may center on invalidity defenses (e.g., obviousness or lack of enablement) rather than claim construction or non-infringement.
- Scope Questions (Label Carve-Out): The complaint notes that MSN's notice letter states the indication for "hepatocellular carcinoma (HCC) who have been previously treated with sorafenib will be carved out of MSN's proposed label" (Compl. ¶23). This raises the question of whether this "carve-out" is sufficient to avoid inducing infringement of method claims directed to treating liver cancer, such as asserted claim 22 of the '284 Patent. The court may need to decide if selling the drug for one infringing use (e.g., kidney cancer) can still lead to liability for inducement of another, "carved-out" infringing use.
V. Key Claim Terms for Construction
- '473 Patent: The complaint does not provide sufficient detail for analysis of key claim terms. The central dispute, as framed by the complaint, appears to be validity, not the interpretation of specific terms in the chemical structure claim (Compl. ¶28).
- '284 Patent:
- The Term: "therapeutically effective amount" (from claims 1, 22, 23).
- Context and Importance: This term is fundamental to the asserted method-of-use claims, defining the dosage that constitutes an infringing act. In an ANDA case, its meaning is critical because infringement is tied to the instructions on the proposed generic label. Practitioners may focus on this term to determine if the dosages in MSN's ANDA (20, 40, and 60 mg tablets) meet the claimed requirement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a broad, functional definition: "the amount of the compound...that will elicit the biological or medical response of a...human that is being sought by the researcher...or medical doctor" ('284 Patent, col. 259:12-18). This supports an interpretation not tied to a specific numerical dose, but to achieving a therapeutic effect.
- Evidence for a Narrower Interpretation: A party could potentially argue the term should be limited by the dosage ranges discussed in the patent's examples or the specification, which mentions a range of "about 0.1 to about 1000 mg, per kg of body weight per day" ('284 Patent, col. 264:25-27). However, the breadth of this exemplary range may make a narrowing argument difficult.
VI. Other Allegations
- Indirect Infringement: For the '284 Patent, the core allegation is indirect infringement. The complaint pleads active inducement under 35 U.S.C. § 271(b), alleging that MSN's proposed product labeling will intentionally encourage and instruct healthcare providers and patients to perform the patented methods of treatment (Compl. ¶41). It also pleads contributory infringement under § 271(c), alleging the MSN ANDA Product is a material part of the invention, not a staple article of commerce, and is especially made for an infringing use (Compl. ¶42).
- Willful Infringement: The complaint alleges that MSN acted "without a reasonable basis for believing that they would not be liable" for infringement, thereby making this an "exceptional case" warranting enhanced damages (Compl. ¶¶34, 45). This allegation is based on MSN's alleged pre-suit knowledge of the patents, as evidenced by its Paragraph IV certification and the associated notice letter sent to Exelixis (Compl. ¶¶21, 24).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of patent validity: Given the complaint’s assertion that MSN does not contest infringement of the asserted claims, the case will likely turn on whether MSN can prove by clear and convincing evidence that the '473 compound patent and '284 method-of-use patent are invalid on grounds such as obviousness, anticipation, or lack of written description.
- A key secondary issue will be one of induced infringement liability: Can MSN's "carve-out" of the hepatocellular carcinoma indication from its proposed drug label successfully avoid a finding of induced infringement for claims covering that use, or will the marketing of the drug for its remaining approved indication (renal cell carcinoma) be found to inevitably or intentionally encourage off-label use for the carved-out indication?