DCT
2:23-cv-03959
Janssen Pharmaceutica NV v. Natco Pharma Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Janssen Pharmaceutica NV (Belgium); Janssen Biotech, Inc. (Pennsylvania); Astex Therapeutics Ltd. (England and Wales)
- Defendant: Natco Pharma Ltd. (India)
- Plaintiff’s Counsel: Robinson Miller LLC; Sidley Austin LLP
- Case Identification: 2:23-cv-03959, D.N.J., 07/25/2023
- Venue Allegations: Plaintiffs allege venue is proper because Defendant is a foreign corporation subject to personal jurisdiction in the district, has continuous and systematic contacts with New Jersey, and has previously consented to venue in the district in similar patent actions based on Abbreviated New Drug Application (ANDA) filings.
- Core Dispute: Plaintiffs allege that Defendant's submission of an ANDA to the FDA seeking approval to market a generic version of the cancer drug BALVERSA® (erdafitinib) infringes two patents covering the drug's chemical composition and its method of use.
- Technical Context: The technology lies in the field of targeted oncology therapeutics, specifically focusing on small-molecule inhibitors of the Fibroblast Growth Factor Receptor (FGFR) kinase pathway for the treatment of certain types of urothelial carcinoma.
- Key Procedural History: This is a patent infringement action filed under the Hatch-Waxman Act, triggered by Defendant’s filing of ANDA No. 218578 with a Paragraph IV certification, asserting that Plaintiffs' patents are invalid and/or not infringed. Both patents-in-suit are listed in the FDA's Orange Book as covering BALVERSA®. Subsequent to the complaint's filing, the assignee of the ’106 Patent filed a disclaimer for claims 6-11, 13, 18, and 20-23. An ex parte reexamination of the ’106 Patent was also concluded, with a certificate issued on July 12, 2024, confirming the patentability of the remaining asserted independent claim 1 and other asserted claims.
Case Timeline
| Date | Event |
|---|---|
| 2014-03-26 | ’971 Patent Priority Date |
| 2017-02-06 | ’106 Patent Priority Date |
| 2018-02-27 | ’971 Patent Issue Date |
| 2021-08-03 | ’106 Patent Issue Date |
| 2022-12-13 | Disclaimer of certain claims of the ’106 Patent |
| 2023-01-10 | ’106 Patent Certificate of Correction (adding inventor) |
| 2023-06-12 | Defendant sends notice letter regarding ANDA filing |
| 2023-07-25 | Complaint Filing Date |
| 2024-07-12 | Ex Parte Reexamination Certificate issued for ’106 Patent |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,902,714, "Quinoxaline Derivatives Useful as FGFR Kinase Modulators" (Issued Feb. 27, 2018)
The Invention Explained
- Problem Addressed: The patent addresses the need for new therapeutic compounds to treat diseases driven by the fibroblast growth factor (FGF) family of protein tyrosine kinase receptors, which are implicated in various cancers through functions like cell differentiation and angiogenesis (’971 Patent, col. 19:1-24).
- The Patented Solution: The invention provides a new class of quinoxaline derivative compounds, defined by a core chemical structure, that are designed to modulate or inhibit FGFR kinase activity (’971 Patent, col. 1:11-21; col. 1:44-53). Compound 1, identified as erdafitinib, is a specific embodiment of this invention (’971 Patent, col. 45:6-19).
- Technical Importance: The invention provides a novel composition of matter for targeted cancer therapy, offering a new chemical tool to inhibit the FGFR signaling pathway, which is known to be dysregulated in many tumor types, including bladder, breast, and lung cancer (’971 Patent, col. 25:1-10).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 2–3, 5–6, 8–13, 15, 17–18, and 21–22 (Compl. ¶40).
- Independent Claim 1 is a composition of matter claim defining a genus of quinoxaline derivatives with the following essential structural features:
- A core quinoxaline structure.
- A substituted pyrazole group attached to the quinoxaline core.
- A substituted diazepine or piperazine ring fused to the quinoxaline core.
- Specific substituent groups (R1, R2a, R2b, R2c, R3, R4) at defined positions on the chemical scaffold.
- The complaint reserves the right to assert additional claims (Compl. ¶40).
U.S. Patent No. 11,077,106, "Cancer Treatment" (Issued Aug. 3, 2021)
The Invention Explained
- Problem Addressed: The patent recognizes that while erdafitinib is an effective cancer treatment, its use can lead to on-target toxicities, such as elevated serum phosphate levels (hyperphosphatemia), which can limit the drug's therapeutic potential (’106 Patent, col. 1:12-16, col. 4:21-26).
- The Patented Solution: The patent discloses a specific method of administering erdafitinib to maximize its efficacy while managing toxicity. The method involves starting with a specific daily dose (8 mg), monitoring the patient's serum phosphate levels during the first treatment cycle, and then either increasing the dose (to 9 mg), maintaining the dose, or temporarily interrupting treatment based on whether the phosphate level is below, within, or above a predefined target range (’106 Patent, col. 5:6-20; col. 18:1-18).
- Technical Importance: This patent claims a personalized dosing strategy that aims to optimize the therapeutic window of an FGFR inhibitor by using a pharmacodynamic marker (serum phosphate) to guide dose adjustments, a key step in refining targeted cancer therapies (’106 Patent, col. 4:20-29).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 2-5, 12, 14-17, and 19 (Compl. ¶54).
- Independent Claim 1 is a method of treatment claim for urothelial cancer with an FGFR genomic alteration, comprising the steps of:
- a) administering 8 mg of erdafitinib daily on a continuous basis.
- b) measuring the subject's serum phosphate levels on a treatment day during the first cycle.
- c-1) administering 9 mg daily if the phosphate level is <5.5 mg/dL.
- c-2) continuing to administer 8 mg daily if the phosphate level is between 5.5 and <7 mg/dL.
- c-3) temporarily interrupting the treatment if the phosphate level is ≥7 mg/dL.
- The complaint reserves the right to assert additional claims (Compl. ¶54).
III. The Accused Instrumentality
Product Identification
- Defendant's proposed generic erdafitinib oral tablets (3 mg, 4 mg, and 5 mg), as described in ANDA No. 218578 (the "ANDA Product") (Compl. ¶29).
Functionality and Market Context
- The ANDA Product contains erdafitinib, an inhibitor of FGFR kinases, as its active ingredient (Compl. ¶32). By filing the ANDA, Defendant represents that its product is a generic copy of BALVERSA® and is bioequivalent (Compl. ¶32).
- The complaint alleges that upon FDA approval, the ANDA Product will be marketed for the same FDA-approved indication as BALVERSA®: the treatment of adult patients with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 or FGFR2 genetic alterations (Compl. ¶¶19, 34).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
’971 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| [The full chemical structure as defined by Claim 1, which encompasses erdafitinib] | The active pharmaceutical ingredient in Natco's ANDA Product is erdafitinib, which the complaint alleges is a compound covered by one or more claims of the ’971 Patent. | ¶32, ¶40 | col. 7:55-8:18 |
- Identified Points of Contention:
- Scope Questions: In an ANDA case involving a composition of matter, the primary infringement question is whether the generic drug's active ingredient is the claimed compound. The complaint alleges that Natco's ANDA Product contains the same active ingredient as BALVERSA®, which is erdafitinib (Compl. ¶32). A potential, though less common, dispute could arise over whether the specific salt or polymorphic form used in the generic falls within the scope of the claim term "a pharmaceutically acceptable salt thereof or the solvates thereof." The complaint does not provide sufficient detail for analysis of this specific element.
’106 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a) administering to a subject in need thereof, 8 mg of erdafitinib daily on a continuous basis; | The complaint alleges that Natco's proposed product labeling will instruct medical professionals and patients to administer the ANDA Product for its approved indication, which will involve an 8 mg daily starting dose. | ¶43-¶44, ¶57 | col. 5:6-14 |
| b) measuring the serum phosphate levels of the subject on a treatment day during the first cycle of erdafitinib treatment; | The proposed labeling for Natco's ANDA Product will allegedly direct the monitoring of serum phosphate levels to manage the drug’s effects. | ¶43-¶44, ¶58 | col. 5:30-34 |
| c-1) when the serum phosphate levels are <5.5 mg/dL, erdafitinib is administered in an amount of 9 mg daily, on a continuous basis; or | The proposed labeling will allegedly instruct dose up-titration to 9 mg daily if a patient's serum phosphate levels are below the target range. | ¶43-¶44, ¶58 | col. 8:39-42 |
| c-2) when the serum phosphate levels range from and including 5.5 mg/dL to <7 mg/dL, erdafitinib is further administered in an amount of 8 mg daily...; or | The proposed labeling will allegedly instruct physicians to maintain the 8 mg daily dose if a patient's serum phosphate levels are within the target range. | ¶43-¶44, ¶58 | col. 8:42-44 |
| c-3) when the serum phosphate levels are ≥7 mg/dL, the erdafitinib treatment is interrupted temporarily. | The proposed labeling will allegedly instruct physicians to temporarily interrupt treatment if a patient's serum phosphate levels exceed the target range. | ¶43-¶44, ¶58 | col. 8:44-51 |
- Identified Points of Contention:
- Technical Questions: A key question for induced infringement is whether the instructions in the ANDA Product's proposed label will necessarily direct users to perform each and every step of the claimed method. The court will need to compare the proposed label against each limitation of the asserted claims.
- Scope Questions: Do the instructions on the proposed label align with the claim limitations? For instance, does the label's recommended timing for phosphate measurement fall within the scope of "on a treatment day during the first cycle," or does it specify a different schedule that might avoid infringement?
V. Key Claim Terms for Construction
’106 Patent
The Term: "a treatment day during the first cycle of erdafitinib treatment"
Context and Importance: The timing of the serum phosphate measurement is a critical step that triggers the subsequent dose adjustments. The definition of this term is central to the infringement analysis, as Natco may argue its proposed label instructs measurement on a timeline outside the claimed scope, or that the term is indefinite.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The plain language of the claim does not specify a particular day, only that the measurement occurs on "a treatment day" within the first cycle. This could support an interpretation covering measurement on any day during that period (’106 Patent, col. 18:1-5).
- Evidence for a Narrower Interpretation: The specification repeatedly highlights day 14 as a key time point for assessment. The detailed description states that up-titration decisions are measured "in particular on day 14±2 days" (’106 Patent, col. 7:51-54). A defendant may argue this context limits the claim scope to measurements performed on or around day 14.
The Term: "interrupted temporarily"
Context and Importance: The precise meaning of this term is crucial for determining infringement of claim 1(c-3). Practitioners may focus on this term because the conditions for both stopping and, importantly, restarting treatment define the boundaries of the claimed method.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim language itself does not specify the conditions for restarting therapy, only that the interruption is "temporary." This could be argued to cover any non-permanent cessation of the drug in response to elevated phosphate levels.
- Evidence for a Narrower Interpretation: Dependent claim 6 explicitly adds the limitation that the interruption continues "until serum phosphate levels are <5.5 mg/dL." Further, Table 3 in the specification details a specific re-start protocol (’106 Patent, col. 24:1-38). A party could argue that "interrupted temporarily" must be read to include the subsequent re-start conditions described in the patent, potentially narrowing its scope.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Natco will induce infringement of the ’106 patent because its proposed product labeling will instruct medical professionals to administer the ANDA Product in accordance with the patented method (Compl. ¶¶ 46, 58). The complaint also pleads contributory infringement, alleging the ANDA Product is not suitable for substantial non-infringing use and is especially adapted for infringing the patents (Compl. ¶¶ 47, 61).
- Willful Infringement: Plaintiffs allege that Natco had knowledge of the patents-in-suit at least as of its ANDA submission date, which included a Paragraph IV certification against those patents (Compl. ¶¶ 48, 62). The complaint further alleges that Natco "acted without a reasonable basis for believing that it would not be liable for infringing" the patents, which forms the basis for a claim of willful infringement (Compl. ¶¶ 49, 63).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of induced infringement: Will Natco's proposed product label, once finalized, be found to encourage, recommend, or promote that medical professionals perform each and every step of the dosing and monitoring regimen claimed in the ’106 patent, thereby establishing the requisite intent for inducement?
- The dispute may also turn on claim construction: Can the method steps of the ’106 patent, such as monitoring on "a treatment day during the first cycle" and "interrupted temporarily," be interpreted broadly based on their plain meaning, or will the court limit their scope to the specific embodiments and timelines detailed in the patent's specification (e.g., monitoring on day 14)?
- A key evidentiary question will concern invalidity: While the complaint focuses on infringement, Natco’s Paragraph IV certification asserts the patents are invalid (Compl. ¶31). The litigation will likely center on whether the claimed erdafitinib compound in the ’714 patent or the specific dose-adjustment method in the ’106 patent would have been obvious to a person of ordinary skill in the art at the time of the inventions.