DCT

1:23-cv-01193

Taiho Pharmaceutical Co Ltd v. Eugia Pharma Specialities Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-01193, D. Del., 10/20/2023
  • Venue Allegations: Plaintiff alleges venue is proper based on Defendants' business activities in Delaware, intent to market and sell the accused product in the state, and the fact that Defendants have previously submitted to the jurisdiction of the court in other matters.
  • Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff's Lonsurf® cancer treatment constitutes infringement of a patent covering methods of treating cancer by administering Lonsurf® in combination with certain therapeutic antibodies.
  • Technical Context: The technology involves combination cancer therapies, which seek to improve patient outcomes by pairing different types of drugs, in this case, a cytotoxic chemotherapy agent with a targeted antibody therapy.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff's receipt of a Paragraph IV notice letter from Defendants concerning ANDA No. 213893. The notice letter asserted that Defendants' proposed generic product would not infringe the patent-in-suit. The complaint also notes the existence of related litigation between the parties in the same district concerning the same ANDA.

Case Timeline

Date Event
2013-09-06 '537 Patent Priority Date
2015-09-22 FDA Approval of Lonsurf® NDA No. 207981
2018-04-17 '537 Patent Issue Date
2023-09-08 Plaintiff received Defendants' Paragraph IV notice letter
2023-10-20 Complaint Filing Date

II. Technology and Patent(s)-in-Suit Analysis

  • Patent Identification: U.S. Patent No. 9,943,537, "Antitumor Agent And Antitumor Effect Enhancer," issued April 17, 2018. (Compl. ¶50).

The Invention Explained

  • Problem Addressed: The patent describes the separate clinical use of a combination drug (trifluridine/tipiracil, or "FTD/TPI") and molecularly targeted antibody therapies (anti-VEGF or anti-EGFR antibodies). It notes that a combination therapy using these two classes of drugs was not previously known and aims to provide a novel cancer treatment method with both excellent antitumor effect and fewer adverse effects. (Compl., Ex. B, ’537 Patent, col. 2:28-33, 62-67).
  • The Patented Solution: The invention is a method of treatment wherein the FTD/TPI combination drug is administered "in combination" with an anti-VEGF or anti-EGFR antibody. The patent asserts that this concomitant use "remarkably enhances the antitumor effect" of the antibody therapy while also suppressing adverse effects, a surprising result given that combination therapies often increase side effects. (Compl., Ex. B, ’537 Patent, col. 2:36-41, col. 12:30-38).
  • Technical Importance: The invention proposed a therapeutic synergy between two different classes of oncology drugs, suggesting a path to more effective and tolerable cancer treatment regimens. (Compl., Ex. B, ’537 Patent, col. 4:50-53).

Key Claims at a Glance

  • The complaint asserts independent claims 1, 6, 7, and 8. (Compl. ¶¶ 52-53). Claim 1 is the most frequently cited.
  • The essential elements of independent claim 1 are:
    • A method for treating a cancer, comprising:
    • administering to a subject in need thereof 17 to 115% of a recommended daily dose of a combination drug comprising trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5, and
    • 11 to 100% of a recommended daily dose of an antibody selected from the group consisting of bevacizumab, cetuximab, and panitumumab,
    • in combination.
  • The complaint notes that the remaining claims are dependent claims directed to methods of treating cancer with a combination drug. (Compl. ¶53).

III. The Accused Instrumentality

Product Identification

  • Defendants' proposed generic trifluridine and tipiracil tablets, for which approval is sought under ANDA No. 213893 ("Eugia's ANDA Product"). (Compl. ¶¶ 8, 56).

Functionality and Market Context

  • The accused instrumentality is a generic version of Plaintiff's Lonsurf® product, intended for the same indications, which include treatment of metastatic colorectal cancer and metastatic gastric cancer. (Compl. ¶¶ 49, 64). The infringement action is based on the submission of the ANDA itself, which seeks FDA approval to market the generic product for these uses. (Compl. ¶59). The central allegation is that the proposed product labeling for the generic drug will be "substantially the same" as the approved labeling for Lonsurf® and will instruct medical personnel to use the drug in a manner that infringes the ’537 Patent. (Compl. ¶¶ 65, 73). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'537 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating a cancer, comprising: administering to a subject in need thereof 17 to 115% of a recommended daily dose of a combination drug comprising trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5, The proposed labeling for Eugia's ANDA Product will allegedly instruct medical personnel to treat cancer by administering the generic drug, which contains trifluridine and tipiracil hydrochloride at the specified molar ratio and within the claimed dosage range. ¶¶ 69-70 col. 18:48-55
and 11 to 100% of a recommended daily dose of an antibody selected from the group consisting of bevacizumab, cetuximab, and panitumumab, The proposed labeling will allegedly instruct for the product's use with an antibody such as bevacizumab, consistent with the approved Lonsurf® label, and within the claimed dosage range. ¶¶ 49, 65, 69-70 col. 18:56-62
in combination. The proposed labeling will allegedly instruct medical personnel to administer the ANDA product and the antibody together as a combination therapy. ¶¶ 69-70 col. 18:63

Identified Points of Contention

  • Scope Questions: A primary issue for the court will be whether the specific instructions in Defendants' proposed product label meet every limitation of the asserted claims. The dispute may center on whether the label requires or merely permits administration in an infringing manner, raising the question of whether substantial non-infringing uses for the generic product, as labeled, exist.
  • Technical Questions: The analysis will likely focus on comparing the dosage and administration schedule information in the proposed label against the specific numerical ranges recited in the claims (e.g., "17 to 115%" and "11 to 100%"). What evidence will show that the instructions on the proposed label for Eugia's ANDA Product will result in administration that falls within these specific claimed percentage ranges of the "recommended daily dose"?

V. Key Claim Terms for Construction

The Term: "in combination"

  • Context and Importance: The definition of this term is critical for determining what constitutes an infringing act of administration. Practitioners may focus on this term because its scope will dictate whether the method requires simultaneous administration, a specific sequence of administration, or allows for a more flexible therapeutic regimen where the two drugs are used concurrently over a course of treatment.
  • Intrinsic Evidence for a Broader Interpretation: The patent specification describes the administration as occurring "within a certain period," which may support an interpretation that does not require simultaneous delivery. ('537 Patent, col. 6:14-16).
  • Intrinsic Evidence for a Narrower Interpretation: The detailed examples in the patent describe specific, overlapping administration schedules (e.g., FTD/TPI administered daily for a period, with the antibody administered twice a week during that same period), which could be argued to limit the term to contemporaneous use. ('537 Patent, col. 10:11-16).

The Term: "recommended daily dose"

  • Context and Importance: Infringement hinges on whether the dosages instructed on the proposed label fall within the percentages of the "recommended daily dose" recited in the claims. The definition of this baseline "dose" is therefore essential to the infringement analysis.
  • Intrinsic Evidence for a Broader Interpretation: The patent calculates dosages relative to the "recommending dose (RD)" for a given drug in human or animal models, suggesting the term refers to a standard, clinically recognized dosage as would be understood by a person skilled in the art. ('537 Patent, col. 14:50-54).
  • Intrinsic Evidence for a Narrower Interpretation: An argument could be made that the term is tied to the specific doses described in the patent's own examples, or that it is indefinite if it relies on an external, unstated standard that may change over time.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b), asserting that Defendants know of the patent and that their proposed product labeling will specifically instruct and encourage medical professionals to perform the patented method of treatment, thereby infringing the claims. (Compl. ¶¶ 72, 73, 76).
  • Willful Infringement: The complaint alleges that Defendants were aware of the ’537 Patent as early as its issue date and acted "without reasonable basis for a good faith belief that it would not be liable for infringing," which forms the basis for a willfulness claim based on pre-suit knowledge. (Compl. ¶¶ 80, 101).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A core issue will be one of label-based inducement: Will the final, FDA-approved label for Eugia's ANDA product contain instructions that affirmatively direct physicians and patients to administer the generic drug in combination with a claimed antibody, in a manner that satisfies all limitations of a valid claim of the '537 patent?
  • A key question will be one of definitional precision: Can the dosage instructions on the proposed generic label be proven to fall within the specific percentage ranges of the "recommended daily dose" as that term is construed by the court, and does the nature of the co-administration instructions fall within the scope of the term "in combination"?